Abstract and case study poster sessions will be conducted during the 2022 College of American Pathologists Annual Meeting (CAP22), which is scheduled for October 8–11 at the Hyatt Regency New Orleans Hotel. The poster sessions will occur in the Exhibit Hall located in the Elite Hall. Specific dates and times for each poster session are listed below; “poster focus” times are dedicated poster-viewing periods. Also shown before each poster session are the subject areas that will be presented.

Noon–3:00 PM; Poster Focus, Noon–1:00 PM
Gastrointestinal and Liver Pathology; Hematopathology; Head, Neck, and Oral Pathology
Incidence of Epstein-Barr Virus Infection in Patients Diagnosed With Gastric Adenocarcinoma at Westchester Medical Center

(Poster No. 1)

Elayna M. Shanker, BS1 ([email protected]); Gautam Vanga, MBBS2; Sravanthi Lavu, MBBS2; Lakshmisree A. Vemulakonda, MBBS2; Sabrina Kohanzad, BS1; Marcelo F. Cassini, MD, PhD.2 1Department of Pathology, New York Medical College, Valhalla; Department of Pathology, Westchester Medical Center, Valhalla, New York.

Context: Gastric cancer, a leading cause of cancer mortality, is associated with pathogens including Helicobacter pylori and Epstein-Barr virus (EBV). The geographic distribution and incidence of EBV-associated gastric cancer was described by The Cancer Genome Atlas (TCGA). In their 2014 study, which classified major subtypes of gastric cancer, EBV was associated with 9% of total gastric cancers. In this study, we identified the incidence of EBV-positive cases in patients diagnosed with gastric adenocarcinoma at our hospital and compared the results with TCGA data.

Design: We collected retrospective data, using the Softpath System, from patients diagnosed with “gastric adenocarcinoma” between January 2010 and December 2019. Using immunohistochemical staining, we identified tumors infected by EBV and compared the results with TCGA data, using a Student t test.

Results: Our data revealed 114 cases of gastric adenocarcinoma with samples from upper endoscopic biopsy and gastric resections. Based on the necessary sample size, 43 cases of gastric adenocarcinoma were randomized for immunohistochemical staining for EBV. We found 9 EBV-positive (Figure 1.1) and 34 EBV-negative cases. The incidence of EBV positivity at our hospital was 21%, compared with 9% from the TCGA database (~2.4 times higher).

Conclusions: The incidence of EBV-positive gastric adenocarcinoma at our hospital is significantly higher when compared with the TCGA database. This may be due to environmental exposures, variation in local diet, or perhaps higher EBV incidence in this area. Additionally, small sample size or immunohistochemical staining (rather than genome sequencing) may explain this disparity. Further epidemiologic studies are needed to identify possible geographic differences accounting for this change in EBV positivity.

Stercoral Colitis and Perforation in a Setting of Chronic Heroin Abuse

(Poster No. 2)

Steven H. Adams, MD ([email protected]); Jela Bandovic, MD. Department of Pathology, Stony Brook University Hospital, Stony Brook, New York.

Stercoral colitis, from the Latin stercus (feces), refers to inflammation of a colon segment by fecal impaction. Severe impaction leads to distention, increased pressure, and resultant necrosis and perforation of the intestinal wall. The commonly reported site of ischemia and necrosis is the antimesenteric side of the sigmoid colon. Cases occur in the settings of chronic constipation in the elderly, psychiatric disorders, and pharmacologic treatment with anticholinergic, opioid, or nonsteroidal anti-inflammatory drugs. Only a handful of stercoral colitis cases have been attributed to chronic heroin addiction. A 30-year-old man with a history of chronic constipation and polysubstance abuse (heroin, opioids, cocaine, and marijuana) was admitted for acute abdominal pain. CT showed perforation of the colon with pneumoperitoneum. Surgical exploration revealed feculent peritonitis, with a very large fecal impaction of the sigmoid—distended to 10 cm in diameter, with perforation of the sigmoid at the descending/sigmoid-colon junction. A colonic segment sent to pathology, 38 cm in length, revealed a 2.5 × 2-cm antimesenteric sigmoidal perforation (Figure 1.2, A). The opened specimen contained multiple fecalomas (compacted and hardened fecal matter) (Figure 1.2, B). Histologic sections showed markedly thickened muscularis propria (Figure 1.2, C) and acute fibrinopurulent serositis, with the colonic mucosa around the perforation site showing ischemic changes (Figure 1.2, D). Given the clinical history of chronic constipation and luminal impacted fecal material, the findings were compatible with stercoral colitis, complicated with perforation and peritonitis. The clinical history of heroin and opioid abuse was a likely contributing factor to the patient's constipation and fecal impaction.

How Diagnostic Is “Undiagnostic”: A Review of Benign and Nondiagnostic Fine-Needle Aspirates of Pancreatic Lesions

(Poster No. 3)

Danielle R. Petty, DO1 ([email protected]); Omer A. Hassan, MD2; Wencheng Li, MD.2 1Department of Pathology, University of Florida, Gainesville; 2Department of Pathology, Wake Forest Baptist Medical Center, Winston Salem, North Carolina.

Context: Fine-needle aspiration (FNA) is used to diagnose pancreatic lesions. If initial results are “no malignancy” or “nondiagnostic” and clinical suspicion remains high, rebiopsy is performed. The purpose of this study was to evaluate the negative predictive value (NPV) of the diagnoses “no malignancy” and/or “nondiagnostic” for solid pancreatic lesions to provide data to aid in decision-making.

Design: One hundred ten pancreatic FNAs from 2015 to 2017 with diagnoses of “nondiagnostic” or “no malignancy” were identified. Patients without follow-up or those who died of unknown or unrelated causes were excluded, leaving 98 cases. Thirty-five had radiographically solid lesions.

Results: Fourteen FNA adequacy statements were “suboptimal” or “unsatisfactory,” and consequently all were categorized as “nondiagnostic.” Of these, 7 were eventually diagnosed with cancer, 86% (6) of which were neuroendocrine tumors. Twenty-one cases were “satisfactory,” although 7 were categorized as “nondiagnostic.” Six of the nondiagnostic cases were eventually diagnosed with cancer, 5 of which were ductal adenocarcinomas and 1 of which was neuroendocrine. Fourteen cases were diagnosed as “no malignancy”—71% representing true negatives. Four patients (29%) with this diagnosis were eventually diagnosed with cancer (3 ductal adenocarcinomas and 1 mucinous cystic neoplasm) (Figure 1.3).

Conclusions: “Satisfactory” cases with a diagnosis of “no malignancy” had an NPV of 71%. Between 57.1% (unsatisfactory samples) and 86% (satisfactory samples) of “nondiagnostic” biopsies were proven to be malignant. “Unsatisfactory” samples were disproportionately neuroendocrine tumors (86%), which suggests that neuroendocrine lesions may be more difficult to sample.

Accessory Spleen Presenting as Gastric Fundic Lesion

(Poster No. 4)

Fnu Raja, MD ([email protected]); Rania Rayes Danan, MD; Amer Khiyami, MD. Department of Pathology, MetroHealth Medical Center, Cleveland, Ohio.

An accessory spleen (AS) is a small nodule of splenic tissue located separately from the main body of the spleen and is found in approximately 15% of the population. The physiologic function is similar to that of the normal spleen, and it is usually located in the splenic hilum and tail of the pancreas. We describe a rare case of AS that presented as a gastric fundic mass in a middle-aged woman with a history of breast cancer and hysterectomy for a benign condition. She presented with fatigue and was found to have iron-deficiency anemia. On further workup, endoscopy revealed a submucosal gastric fundic lesion with nonneoplastic overlying mucosa. Follow-up radial endoscopic ultrasonography for the lesion revealed a uniform, oval-like lesion measuring 2.0 × 1.5 cm. Full-thickness resection was performed, and tissue was sent for histology. Microscopically, a polypoid gastric mucosa was remarkable for active gastritis, ulceration, pit abscesses, and chronic lymphoplasmacytic inflammation (Figure 1.4, A and B). No dysplasia or intestinal metaplasia was seen. Submucosa was significant for AS tissue extending to the deep tissue (Figure 1.4, C and D). Helicobacter pylori immunohistochemistry was negative. Patients with gastric AS are usually asymptomatic; complications include rupture, hemorrhage, and torsion. ASs are usually discovered incidentally and can be mistaken for neoplastic growth. In a clinical case necessitating a therapeutic splenectomy, it is necessary to remove AS tissue as well to resolve symptoms. We must be aware of possible ASs in the stomach. Histology and immunohistochemistry stains can guide our diagnosis.

Association of Isolated Colitis With Nonsteroidal Anti-Inflammatory Drug Usage

(Poster No. 5)

Ashbita Pokharel, MBBS ([email protected]); Wei Li, MD, PhD. Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, Michigan.

Context: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been known to produce various clinical gastrointestinal side effects and histopathologic changes. It has been reported that NSAID usage is associated with isolated colitis in the periappendiceal orifice region. This study aimed to further evaluate the clinicopathologic features of 16 patients with isolated colitis limited to the cecum or periappendiceal orifice region.

Design: A retrospective review was performed on biopsy specimens from 16 patients with histologically proven colitis (focal active colitis with no chronicity) limited to the cecum or periappendiceal orifice. No significant pathologic changes in the terminal ileum or other parts of the colon were identified in cases studied. Patients with a history of colorectal tumor or inflammatory bowel diseases were excluded from the study. Relevant clinical history, follow-up studies, and endoscopic findings were evaluated.

Results: Erosion, ulceration, and erythema were the main endoscopic findings in the cases studied. Among 16 cases, 9 (56%) had a history of routine NSAID usage. Among these 8 patients, 7 demonstrated resolution of pathologic abnormality after cessation of the drugs following repeated colonoscopy. Seven patients (44%) had nonroutine NSAID usage. After follow-up examination, none of the patients had infectious disease of the gastrointestinal tract or inflammatory bowel disease.

Conclusions: Our results confirm previously reported findings of a strong association of isolated colitis in the cecum or periappendiceal orifice region with NSAIDs. Our data support the conclusion that pathologic changes of isolated colitis are reversible after the cessation of NSAIDs.

Segmental Cholangiectasia: A Diagnostic Pitfall for Radiologists

(Poster No. 6)

Recep Nigdelioglu, MD ([email protected]); Zong-Ming Eric Chen, MD, PhD. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Segmental cholangiectasia is a rare disease that appears to result from recurrent attacks of obstructive cholangitis and shares similar histologic features with recurrent pyogenic cholangitis, which is more common in Asian populations. The etiology is unclear. However, the role of Escherichia coli in promoting bile precipitation through its bacterial β-glucuronidase activity is widely accepted. Radiologically, segmental cholangiectasia can present as a mass or a biliary stricture, suggesting a cholangiocarcinoma or a cystic biliary neoplasm, which can be a big pitfall. We present a case of a 43-year-old man with abdominal pain and intermittent fevers during the past 2 years. MRI showed a gallbladder mass with accompanying left hepatic atrophy suggesting a cholangiocarcinoma. A liver resection and cholecystectomy were performed. The gross pathologic examination of the gallbladder showed hemorrhagic sludgy material with no mass lesion in the liver or gallbladder. Sections of the liver showed hilar parenchymal atrophy, bile duct dilation (Figure 1.6, A), prominent periductal fibrosis (Figure 1.6, B), active and chronic inflammation with plasma cells, and focal intraductal cholelithiasis (Figure 1.6, C). The gallbladder showed chronic inflammation and prominent reactive lymphoid follicles, consistent with follicular cholecystitis (Figure 1.6, D). There was no epithelial dysplasia or malignancy. The IgG4/IgG index in plasma cells was less than 5%. Overall, the presence of intraductal cholelithiasis, ductal ectasia, and parenchymal atrophy was most consistent with segmental cholangiectasia (recurrent pyogenic cholangitis) of the liver. In conclusion, segmental cholangiectasia can be a clinical pitfall and should be considered by pathologists in the appropriate clinical context.

Clinicopathologic Features of Benign Vascular Lesions of the Gastrointestinal Tract: A Single-Institution Experience

(Poster No. 7)

Cansu Karakas, MD ([email protected]); Aaron R. Huber, DO; Diana Agostini-Vulaj, DO. Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York.

Context: Various types of benign vascular lesions (BVLs) occur in the gastrointestinal (GI) tract. We sought to further evaluate and clinicopathologically characterize these entities.

Design: We searched our pathology archives from 2009 to 2021 for patients with BVLs. Clinicopathologic data were collected.

Results: There were 28 patients (46% women, 54% men) with a median age of 65 years (range, 35–81 years). Sites included the colon (n = 26), with the ascending colon being most common (n = 13); small bowel (n = 1); and stomach (n = 1). Patients presented for screening colonoscopy (n = 15), GI bleeding (n = 9), or nonspecific GI symptoms (n = 5). Endoscopically, polyps were most common (15 of 28, 54%), with size range 0.2–3.0 cm (median, 0.4 cm). Histologically, 18 (64%) were hemangiomas (Figure 1.7, A); 5 (18%) arteriovenous malformations (Figure 1.7, B); 2 (7%) portal colopathies; and 1 (3.5%) each hemangiolymphangioma, lymphangioma, and florid vascular proliferation. Fifteen (53%) involved mucosa, 5 (18%) submucosa, 6 (21%) both, and 2 (7%) were transmural. Erosion/ulceration was observed in 2 (7%). Concurrent lesions included 12 (43%) adenomas, 5 (18%) hyperplastic polyps, and 1 (3.5%) each leiomyoma, lipoma, and colon adenocarcinoma. Furthermore, 23 (82%) had additional comorbidities, with cardiovascular disease being most common (7, 25%). Only 2 had subsequent/recurrent BVLs (1 year and 6 months after initial diagnosis).

Conclusions: BVLs occur in elderly patients and are most commonly identified as small polyps on screening colonoscopy; however, a significant number may have GI bleeding. These entities can be further refined into a specific diagnosis with histologic examination, although this can be difficult with small biopsies. In our cohort, BVLs were most commonly reclassified as hemangiomas.

Lymphoglandular Complexes Are Likely Diagnostic Pitfalls for Risk-Stratifying Colonic Adenomatous Polyps

(Poster No. 8)

Cherry Pun, MD1 ([email protected]); Hala Faragalla, MD, MSc2; Jeffrey Mosko, MD, MSc3; Catherine Streutker, MD, MSc.2 1Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada; 2Department of Laboratory Medicine and 3Division of Gastroenterology, Unity Health, Toronto, Ontario, Canada.

Context: Lymphoglandular complexes (LGCs) are present in the gastrointestinal tract where lymphoid aggregates reside beneath the overlying epithelium. They are known to cause defects in the muscularis mucosae and can traverse into the submucosa (SM). This can pose a diagnostic challenge when adenomatous polyps of the colon involve the LGC, mimicking SM invasion. Our study aimed to assess the frequency of these lesions and associated clinical outcomes.

Design: We searched our laboratory information system at St Michael's Hospital in Toronto, Canada, for polypectomies performed between 2000 and 2021 showing LGC involvement by adenomatous epithelium. Histopathologic characteristics and clinical outcomes were reviewed.

Results: Twelve polypectomies were identified, with a median patient age of 65 years (Table). Nine polyps were interpreted as focally invasive and 3 without invasion. All lesions showed involvement of LGCs. Features supporting pseudoinvasion included rounded architecture with continuous involvement of overlying epithelium, presence of lamina propria, and absence of desmoplasia or high-grade dysplasia. Invasive lesions were typically focal and only superficially invasive. Features supporting invasion included complex architecture, luminal necrosis, desmoplasia, and adjacent high-grade dysplasia. Patients with adenomas were placed on surveillance. Three of 9 patients with invasive polyps underwent resection and had pT1N0 disease. All patients were alive without disease at follow-up.

Conclusions: Considering the good outcome in our invasive cases with follow-up, submucosal “invasion” via an LGC likely does not represent the same biology as true invasion into the SM. Pathologists and clinicians should be aware of this rare diagnostic pitfall and consider polypectomy as curative when no other high-risk features are identified.

Low-Grade Mucinous Carcinoma Peritonei Metastatic to an Axillary Lymph Node

(Poster No. 9)

Karina M. Bach, MD ([email protected]); Amila Orucevic, MD, PhD; Lisa D. Duncan, MD. Department of Pathology, University of Tennessee Medical Center, Knoxville.

Mucinous carcinoma peritonei, also termed pseudomyxoma peritonei, is the peritoneal spread of a ruptured mucinous neoplasm, most often of appendiceal origin. Filling of the abdominal cavity can cause secondary complications such as gelatinous ascites as well as adhesions and compression, leading to malfunction of any abdominal organ. Current treatment guidelines include cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). We present a case of a 53-year-old man with low-grade mucinous carcinoma peritonei diagnosed in July 2020. He underwent cytoreductive surgery but was not able to receive HIPEC or continue adjuvant chemotherapy owing to various medical issues and complications. The initial surgery revealed extensive tumor involvement of multiple organs, including the colon, liver, and spleen. Three of 12 nodes were positive at that time. In October 2021, surveillance imaging showed a right axillary mass and multiple abdominal masses. Palliative cytoreductive surgery and HIPEC were performed with an uncomplicated postoperative course. However, axillary dissection was subsequently done owing to consistent enlargement of an axillary node. Of 8 lymph nodes in level 1, one was positive for low-grade mucinous carcinoma, measuring up to 4 cm with extranodal extension. This is the first reported case of primary appendiceal mucinous carcinoma with metastasis to the axilla. This atypical presentation of a mucinous carcinoma with lack of high-grade component associated with aggressive spread may provide insight to further characterize the paradoxical behavior of this rare tumor.

Intraductal Tubulopapillary Neoplasms of Pancreas With Potentially Targetable Fusions: Report of a New Partner of FGFR2 and Novel STARD3NL::BRAF Fusion

(Poster No. 10)

Irena Manukyan, MD, PhD1 ([email protected]); Susan Hsiao, MD, PhD1; Ladan Fazlollahi, MD, MPH2; Helen Remotti, MD2; Mahesh M. Mansukhani, MD.1 Departments of 1Personalized Genomic Medicine and 2Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York.

Context: Intraductal tubulopapillary neoplasm (ITPN) is rare and genetically distinct from intraductal papillary mucinous neoplasm and ductal adenocarcinoma. We present cytohistologic correlation with molecular characterization of ITPNs diagnosed at our institution.

Design: A review of the Columbia University Anatomic Pathology database from 2016 through 2021 identified 3 patients diagnosed with ITPN. Tumor DNA was subjected to targeted sequencing using the Illumina HiSeq platform, with a hybrid-capture targeting 467 genes, including introns of 72 genes (“CCCP”). Targeted cDNA sequencing with a 16-gene custom anchored multiplex polymerase chain reaction (PCR) panel was used for fusion transcript detection.

Results:KRAS G12V and TP53 variants were detected in the first case, with multifocal invasive carcinoma in both ITPN and the invasive component, indicating the same cellular origin. FGFR2::INA fusion was found in the second case, where fine-needle aspiration (Figure 1.10, A) showed cytologically bland neoplastic cells with elongated nuclei and scant cytoplasm with no intracytoplasmic mucin. On pancreatectomy (Figure 1.10, B), the neoplasm was occupying the main pancreatic duct. Histologic diagnosis was confirmed as ITPN with no invasion (Figure 1.10, C). STARD3NL::BRAF fusion was detected in a third case with a microscopic focus of invasion.

Conclusions: Differentiation of ITPN from other pancreatic neoplasms is crucial given the known favorable prognosis and high frequency—and diversity—of potentially targetable fusions in ITPN. If invasion occurs, characterization of the specific fusion can direct enrollment in basket trials or off-label use of therapy approved for other histologic tumor types (eg, MEK or FGFR2 inhibitors) in the above cases should they have recurred or metastasized.

Incidental Acinar Cystic Transformation of the Pancreas in a Patient With High-Grade Ovarian Serous Carcinoma

(Poster No. 11)

Recep Nigdelioglu, MD ([email protected]); Clarissa E. Jordan, MD; Benjamin J. Van Treeck, MD; Saba Yasir, MBBS. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Acinar cystic transformation of the pancreas is a rare, newly recognized nonneoplastic lesion. This cystic transformation is characterized by unilocular or multilocular cysts lined by benign-appearing acinar and ductal epithelium. The etiology is unknown, and, unlike cystic precursors of pancreatic ductal adenocarcinoma, alterations in KRAS, GNAS, or TP53 have not been reported. We report an incidental acinar cystic transformation of the pancreas in a patient with high-grade ovarian serous carcinoma. The patient was a 46-year-old woman with a history of papillary thyroid carcinoma status post thyroidectomy and bilateral ovarian masses on neoadjuvant chemotherapy whose CT showed a small cystic lesion in the pancreatic tail. The radiologic impression was a pancreatic cyst or metastatic disease. She underwent extensive surgery, including total hysterectomy and bilateral salpingooophorectomy, tumor debulking, and distal pancreatectomy. Bilateral ovaries, fallopian tubes, and omental nodules showed high-grade serous carcinoma with minimal therapeutic response (Figure 1.11, A). Gross examination of the pancreas showed 2 cysts ranging from 1.1 to 1.3 cm (Figure 1.11, B). Histologic sections showed these cystic lesions were lined by 1–2 cell layers of epithelium (Figure 1.11, C), with acinar differentiation supported by trypsin stain (Figure 1.11, D), and an underlying hyalinized wall that was negative for ER. The patient was referred to genetic counseling. In conclusion, acinar cystic transformation of the pancreas is a nonneoplastic lesion, and its distinction from neoplastic mimickers, such as pancreatic intraductal tubulopapillary neoplasm or an intraductal spread of acinar cell carcinoma, might be critical for pathologists.

Multiple Hepatocellular Adenomas in an Adult Female Childhood Cancer Survivor: A Clinical Association to Remember

(Poster No. 12)

Saba Shafi, MD1 ([email protected]); Denise Gamble, DO1; Martha Yearsley, MD1; Jordan Cloyd, MD2; Michael Wellner, MD3; Wei Chen, MD, PhD.1 Departments of 1Pathology and Laboratory Medicine, 2Surgical Oncology, and 3Hepatology, The Ohio State University Wexner Medical Center, Columbus.

Childhood cancer survivors are at risk for certain acquired conditions after treatment, but without known causative germline alterations. Therapy-associated hepatic hemochromatosis and colonic polyposis are well known; however, hepatocellular adenomas (HCAs) are not well documented beside a series of 12 cases (PMID: 27781382). We report an additional such case to increase awareness of HCAs in the setting of childhood cancer survivors. A 34-year-old woman presented with multiple liver masses on imaging noted during workup for cardiac valve regurgitation. Her history revealed childhood acute myeloid leukemia at 6 months and again at 2.5 years, with total body radiation, chemotherapy, and bone marrow transplant. She had been on hormone replacement therapy for 10+ years up to the detection of liver masses. Biopsy of a right liver mass revealed a well-differentiated hepatocellular lesion consistent with HCA. A subsequent liver resection was performed. Resection showed multiple HCAs, ranging from 2.3 to 8.5 cm. Immunostains (Figure 1.12, A through D) demonstrated the tumor to be focally positive for glutamine synthetase, serum amyloid A, and CRP, while negative for glypican 3. A β-catenin stain was negative for nuclear staining. Liver fatty acid–binding protein showed normal staining. Reticulin stains showed patchy mild disruption of reticulin fibers only. Here we present a rare case of multiple HCAs NOS in a woman with a history of childhood acute myeloid leukemia. To the best of our knowledge, this is the 13th such case reported in the English literature and highlights the predilection for development of HCAs after prolonged hormone replacement therapy in these hypogonadal patients post childhood cancer therapy.

Comparative Analysis of Microsatellite Instability Testing in Gastrointestinal and Pancreatic Specimens by Mismatch Repair Protein Immunohistochemistry and a New, Rapid, Highly Automated Polymerase Chain Reaction Platform

(Poster No. 13)

Priscilla Quach, DO ([email protected]); Ameer Hamza, MD. Department of Pathology, University of Kansas Medical Center, Kansas City.

Context: Recent studies have demonstrated a promising response to checkpoint inhibition in microsatellite-instability (MSI) cancers. Therefore, the utility of different techniques, including immunohistochemical (IHC) analysis of mismatch repair (MMR) proteins, polymerase chain reaction (PCR)–based MSI analysis, and even next-generation sequencing–based detection of MMR-D, has increased considerably. We analyzed a relatively new, highly automated, and rapid PCR-based platform in comparison with MMR testing by IHC.

Design: MMR-IHC and MSI-PCR were ordered concurrently. Data including patient age and sex, tumor location, type of specimen (biopsy versus resection), MMR-IHC and MSI-PCR results, turnaround time, and processing cost were collected.

Results: Data were collected for 44 patients. Mean patient age was 70.1 years ± 12.1. Twenty patients were female, 24 were male. MMR-IHC was intact in 39 (88.6%), and 5 (11.4%) had MMR-IHC loss. Of the 5 cases with loss of MMR protein expression, 4 were MSI and 1 was microsatellite stable by PCR. Figure 1.13 demonstrates results segregated by different sites. Mean turnaround times for IHC and PCR reporting were 1.05 and 1.63 days, respectively. The processing cost for the MMR-IHC panel was $160, and the cost for MSI-PCR was $240.

Conclusions: Establishing the MSI status in cancer is more critical than ever. Newer PCR-based highly automated technology provides an alternative method of MSI detection that has high concordance with more conventional IHC testing, especially in the tubular gastrointestinal tract, and has a rapid turnaround time with minimal tech and pathologist time. However, the operating cost is higher, and the specific gene mutation is not identified, unlike with MMR testing by IHC.

Anal Squamous Cell Carcinoma as the Initial Presentation of Human Immunodeficiency Virus Infection

(Poster No. 14)

Saman S. Karimi, MD, MS ([email protected]); Maria F. Gonzalez, MD. Department of Pathology, University of Illinois at Chicago.

Human immunodeficiency virus (HIV) is a well-established risk factor for the development of certain types of malignancies. The incidence of anal squamous cell carcinoma is 30 times higher in HIV patients than in the general population and is currently on the rise. We report a case of a 61-year-old man with a chief complaint of several months of lower left abdominal pain, worsening rectal pain, constipation, and anemia who presented to the emergency department with a 1-month history of hematochezia. Digital rectal examination revealed a noncircumferential, firm, nodular, and indurated anal mass with fistula formation, located at the posterior rectal wall. MRI of the pelvis demonstrated an annular stenosing anal mass measuring 7.5 × 3.5 × 2.5 cm and a left posterior-lateral anal fistula with perianal abscess. Flexible sigmoidoscopy was performed, revealing a large, fungating, ulcerated anal mass with extension to the proximal rectum with fistula formation that was biopsied and sent to pathology for histopathologic evaluation. Microscopic examination revealed an invasive, well-differentiated squamous cell carcinoma arising from a background of condyloma acuminatum with high-grade anal intraepithelial neoplasia (Figure 1.14, A and B). The clinicians were alerted, with recommendation to test for underlying immunodeficiency. Fifth-generation HIV antigen-antibody results were reactive, and confirmatory testing demonstrated HIV-1 infection, with an absolute CD4 count of 301 cells/μL. High-risk HPV infection, a known risk factor for the development of anal squamous cell carcinoma, is detected in 30%–90% of HIV patients. Therefore, HIV infection status is an important consideration in patients presenting with squamous cell carcinoma of the anus.

Schwann Cell Hamartomatous Proliferation of Gallbladder: More Ubiquitous Than Originally Perceived

(Poster No. 15)

Claudia Rojas, MD ([email protected]); Alicia Hirzel, MD. Department of Pathology, Memorial Health System/Joe DiMaggio Children's Hospital, Miramar, Florida.

Benign nerve sheath tumors are commonly seen as superficial cutaneous or soft tissue compartment lesions. They are relatively uncommon in the gastrointestinal tract and present as polypoid masses, histologically typified as schwannomas, ganglioneuromas, and perineuriomas. Mucosal Schwann cell hamartoma is a benign neural lesion characterized by pure Schwann cell proliferation with no known syndromic association. Immunohistochemistry may be necessary to differentiate Schwann cell hamartoma of the gallbladder from other mimics. We present 2 cases of Schwann cell hamartomas of the gallbladder. Patient 1 was a 16-year-old adolescent boy with a history of abdominal pain lasting 3 months, exacerbated by fatty foods. Ultrasonography revealed sludge and gallstones with a slight thickening of the gallbladder and no evidence of choledocholithiasis. Sections showed subacute and chronic cholecystitis with cholelithiasis. Areas of bland spindle cells in the lamina propria were noted. The spindle cells (Figure 1.15, A) were diffusely positive for SOX10 and S100 (Figure 1.15, B). Patient 2 was a 29-year-old woman with colicky right upper quadrant pain radiating to the back and right shoulder. She underwent cholecystectomy. Sections showed chronic cholecystitis, cholesterolosis, and wavy lamina propria spindle cells (Figure 1.15, C) positive for S100 (Figure 1.15, D) and SOX10 and negative for EMA, neurofilament, and CD34. No mitoses or atypia were observed. The histomorphology and immunoprofile in both cases were reminiscent of mucosal Schwann cell hamartoma described in the colorectal mucosa, consistent with Schwann cell hamartoma–like lesion. Schwann cell hamartoma–like lesions of the gallbladder have been recently seen in up to 4% of examined cases. More studies are needed to establish the significance of this lesion.

Granulomatous Lymphangitis as a First Manifestation of Crohn Disease in a Pediatric Patient

(Poster No. 16)

Claudia Rojas, MD ([email protected]); Alicia Hirzel, MD. Department of Pathology, Memorial Health System/Joe DiMaggio Children's Hospital, Miramar, Florida.

Crohn disease is an inflammatory bowel disease with an array of extraintestinal involvement. Genital edema in children is a rare entity that is usually idiopathic and self-limiting. We report a case of a 9-year-old boy with a history of multiple allergies but no history of gastrointestinal complaints. The patient had recently returned from India when he began to experience intermittent penile skin swelling. He was treated with antibiotics, antihistamines, and steroids, with temporary resolution of the symptoms. Owing to the recent travel history, filariasis was the presumptive diagnosis. He underwent circumcision, and the foreskin showed considerable dermal edema with perilymphatic and intralymphatic necrotizing and nonnecrotizing granulomas (Figure 1.16, A and B). GMS, AFB, and FITE stains were negative, and PCR microbiology was also negative. An immunohistochemical stain for CD31 (Figure 1.16, C) highlighted the endothelium, and CD68 immunostain (Figure 1.16, D) was positive for CD6. No parasites were identified. The possibility of Crohn disease was raised, and molecular testing with Prometheus IBD sgi Diagnostic was performed and showed a pattern consistent with inflammatory bowel disease, Crohn disease type. Granulomatous lymphangitis is a rare condition that presents with genital edema and should be considered in the differential diagnosis of chronic idiopathic genital edema, particularly in younger individuals. This condition can predate Crohn disease by many years. Further clinical workup, including additional laboratory studies and close follow-up for coexisting or subsequent development of Crohn disease, is vital for early diagnosis in these patients.

Myeloid Sarcoma: Rare and Often Misdiagnosed

(Poster No. 17)

Claudia Rojas, MD ([email protected]); Alicia Hirzel, MD. Department of Pathology, Memorial Health System/Joe DiMaggio Children's Hospital, Miramar, Florida.

Myeloid sarcoma is a pathologic diagnosis for an extramedullary proliferation of blasts of 1 or more of the myeloid lineages that disrupts the normal architecture of the tissue in which it is found. It is a rare condition, most often associated with acute myeloid leukemia (AML), although in some rare cases it may present in nonleukemic patients. It should therefore be considered in the differential diagnosis of any atypical cellular infiltrate. It may occur at any site, leading to varied clinical presentations. We present a case of myeloid sarcoma with diffuse involvement of the gastrointestinal tract. The patient was an 88-year-old woman with a history of myelodysplasia who presented with nausea, vomiting, and diarrhea. Colonoscopy revealed mild erythema along different sections of the colon, including the ascending and sigmoid colon, suggestive of mild colitis. No other findings were noted. Histologic sections showed fragments of colonic mucosa with an abnormal lamina propria infiltrate, focally permeating between the layers of the intestinal wall, forming sheets (Figure 1.17, A). The neoplastic cells were positive for CD117 (Figure 1.17, B), CD34, and muramidase (lysozyme) and negative for cyclin D1, CD138, CD56, CD20, CD5, κ, λ, tryptase, CD68, CD3, CD34, and myeloperoxidase. The Ki-67 proliferative index was approximately 30%. Follow-up with bone marrow and flow cytometry revealed AML with myelodysplasia-related changes. Diagnosis of myeloid sarcoma is challenging and relies on a high index of suspicion as well as radiologic, histologic, immunophenotypic, and molecular analyses, which are also essential for risk stratification and treatment planning.

An Unusual Rectal Smooth Muscle Tumor Arising From the Muscularis Mucosa

(Poster No. 18)

Megan Gage, DO ([email protected]); David R. Martin, MD; Joshua A. Hanson, MD. Department of Pathology, University of New Mexico, Albuquerque.

Malignant smooth muscle tumors (SMTs) rarely arise in the rectal muscularis propria (MP), but primary rectal muscularis mucosa (MM) leiomyosarcoma has not been documented. A comprehensive study suggests that there is malignant potential in intramural colorectal SMTs with ≥3 mitoses/5 mm2. A second study including 88 colorectal MM SMTs failed to identify any malignant tumors, despite rare lesions showing cytologic atypia but minimal mitoses. We present a case of an atypical rectal MM SMT (0.5 cm; Figure 1.18, A) identified as a polyp on screening colonoscopy in a 70-year-old woman. It was desmin positive (Figure 1.18, B) and demonstrated significant cytologic atypia (Figure 1.18, C), with a mitotic count of 7/5 mm2 (including an atypical mitosis; Figure 1.18, D), meeting criteria for malignancy as defined for MP SMTs. The case was sent to several experts, whose opinions varied from “leiomyosarcoma” to “atypical SMT.” This is the first documented case of a rectal MM SMT meeting malignant criteria for MP tumors. The patient is free from recurrence/metastatic disease 9 months post polypectomy. Given the cytologic atypia and numerous mitoses, we believe a diagnosis of benign leiomyoma is inadequate. However, because malignancy is not yet reported in MM SMTs, a diagnosis of leiomyosarcoma is also inappropriate. Accordingly, we propose the classification of atypical SMT of uncertain malignant potential for lesions arising from MM that show concerning morphologic features. Complete endoscopic resection with periodic close follow-up is recommended until more is known about the behavior of these uncommon MM SMTs.

Colitis as a Form of Presentation of Eosinophilic Granulomatosis With Polyangiitis: A Case Report and a Diagnostic Challenge

(Poster No. 19)

Ahmad M. Alkashash, MD ([email protected]); Jingmei Lin, MD, PhD. Department of Pathology, Indiana University, Indianapolis.

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a disease of systemic vasculitis. Presentation as vasculitis in the gastrointestinal (GI) tract is rare. We present a case of EGPA with colonic involvement as the initial presentation. A 61-year-old man developed profuse watery diarrhea shortly after cholecystectomy in an outside hospital that was thought to be due to Clostridioides difficile colitis. He received multiple courses of medications, but these failed. Upon his being admitted to our institution, results of repeated GI PCR panel, stool culture, and C difficile algorithm all were negative. Colonoscopy showed patchy erythematous and decreased vascular mucosa (Figure 1.19, A). Biopsy showed eosinophilic necrotizing granulomatous vasculitis (Figure 1.19, B through D). Leukocytosis was detected with 47% of eosinophils. Bone marrow examination excluded a malignant process. A full ova/parasites panel was all negative. Transthoracic echocardiography showed depressed ejection fraction (35%). Cardiac MRI demonstrated patchy mid-epicardial enhancement, mild active inflammation, and scar. p-ANCAs were negative, but both myeloperoxidase (25) and proteinase 3 (186) were positive. After an extensive workup, the patient was found to meet the criteria for EGPA. He started therapy with cyclophosphamide, as recommended by the American College of Rheumatology 2021 Guidelines. The diagnosis of EGPA in the GI tract requires high clinical suspicion because symptoms can vary from nonspecific to a severe surgical abdomen. p-ANCAs are positive in 50%–65% of EGPA patients and thus were not surprising to be negative in our patient. Awareness of GI involvement by EGPA is important to prompt proper diagnosis and management.

CD68, CK7, and HepPar1 Expression in Oncocytic Pancreatic Neuroendocrine Tumors and Intraductal Oncocytic Papillary Neoplasms

(Poster No. 20)

David McKenzie, MD ([email protected]); Cynthia Guy, MD; Chanjuan Shi, MD, PhD. Department of Pathology, Duke University Medical Center, Durham, North Carolina.

Context: The DNAJB1-PRKACA oncofusion gene reported in most fibrolamellar carcinomas (FCs) has also been shown to be present in some oncocytic pancreaticobiliary neoplasms, including intraductal oncocytic papillary neoplasms (IOPNs) and intraductal papillary mucinous neoplasms (IPMNs) with mixed oncocytic features (IPMN-MOFs). Given that FC is immunoreactive with CD68, CK7, and HepPar1, we sought to investigate this immunoprofile in oncocytic pancreatic lesions.

Design: Since 2008, a total of 10 cases of IOPN (n = 3) and IPMN-MOF (n = 7) have been identified. Six oncocytic pancreatic neuroendocrine tumors (PanNETs) were also included. Cases were stained with CD68, CK7, and HepPar1. The staining pattern was characterized as focal, patchy, or diffuse, and intensity was characterized as weak, moderate, or strong.

Results: Of the total cases (n = 16), diffuse immunoreactivity for CD68 was seen in only 1, with focal or patchy staining in 8 and the remaining negative (Table). Most cases of IOPN and IPMN-MOF showed at least focal CD68 positivity (7 of 10). Notably, the positivity was more common in the duct-lining cells than in solid portions. Immunostaining for CK7 was strongly positive in 2 of 3 IOPN and 6 of 7 IPMN-MOF cases. HepPar1 was strong and diffusely positive in 3 of 3 IOPN and 3 of 7 IPMN-MOF cases. Some oncocytic PanNETs were positive for these markers, but less frequently.

Conclusions: Most IOPNs/IPMN-MOFs strongly express CK7 and HepPar1, and CD68 immunostaining is typically negative or weak and focal. CD68 is, therefore, more specific for FC. In addition, presence of HepPar1 expression in most oncocytic pancreatic lesions is indicative of its nonspecificity, which further supports the utilization of multiple hepatocellular carcinoma markers.

Different MUC1, MUC2, and CDX2 Expression in Mucinous, Micropapillary, and Diffuse Foci of Ampulla of Vater Carcinoma

(Poster No. 21)

HaiJuan Gao, MD ([email protected]); Cary Johnson, MD; Robert Edwards, MD; Vishal Chandan, MD; Xiaodong Li, MD. Department of Pathology, University of California Irvine, Orange.

Context: Ampulla of Vater carcinoma (AVC) is a well-known tumor with a heterogeneous immunoprofile that is different from similar histologic subtypes of colonic or pancreatic adenocarcinoma.

Design: A total of 105 AVC cases of Whipple resections from 2001 to 2019 were retrospectively reviewed. The cases with presurgical therapy were excluded to avoid chemotherapeutic-associated morphologic changes. One representative section of tumor with specific variant component was chosen for immunohistochemistry using a panel of antibodies: MUC1, MUC2, and CDX2.

Results: Six of 105 cases (5.7%) were mucinous adenocarcinoma (with >50% stromal mucin deposition). Three cases (2.9%) had less than 50% mucin. All mucinous areas were positive for MUC2 and CDX2; 6 also showed positivity for MUC1. The adjacent nonmucinous areas were negative for MUC2 in 5 of 6 cases and showed variable stains for MUC1 and CDX2. Six cases (5.7%) had foci of micropapillary pattern (10%–80%), all of them positive for MUC1, only 1 positive for CDX2, and none positive for MUC2. The adjacent nonmicropapillary area showed a similar immunoprofile. Twelve cases (11.4%) showed a diffuse pattern characterized by solid or infiltrating single cells; these foci were positive for MUC1 (12 of 12) and CDX2 (10 of 12), with only 1 case positive for MUC2. The adjacent nondiffuse areas showed a similar immunoprofile except in 1 case.

Conclusions: Mucinous component is different from micropapillary and diffuse patterns in AVC: they show a different immunoprofile to adjacent tumor. In addition, these mucinous foci are positive for MUC2, which is usually negative in adjacent nonmucinous area.

Leiomyosarcoma of the Colon: An Aggressive Tumor With Pitfalls in Diagnosis

(Poster No. 22)

Mary C. Bailey, MD ([email protected]); Peyman Dinarvand, MD. Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas.

Leiomyosarcoma (LMS) is a malignant mesenchymal neoplasm with cells that demonstrate smooth muscle differentiation. While it can occur in almost any part of the body, it is most commonly found in the abdomen, retroperitoneum, and uterus. However, LMS is rarely found in the gastrointestinal tract. We present the case of a middle-aged man with a history of diverticulitis complicated by perforation who subsequently underwent surgery. An incidental 8.3-cm mass was found in the sigmoid colon. Microscopic examination of this mass demonstrated a high-grade spindle cell neoplasm with perpendicularly oriented fascicles of spindle cells and brightly eosinophilic cytoplasm (Figure 1.22, A). There was abundant cellular atypia, frequent mitoses, and necrosis. The tumor cells stained positively for caldesmon, desmin (Figure 1.22, B), SMA (Figure 1.22, C), and CAM 5.2 (Figure 1.22, D). They were negative for CD117, DOG1, HMB-45, S100, β-catenin, STAT6, ALK1, and pankeratin. MDM2 FISH was performed to rule out dedifferentiated liposarcoma and showed no amplification. Positivity for CAM 5.2 is a pitfall in the diagnosis of LMS that can mislead the pathologist into considering an epithelial malignancy. This case report aims to discuss the features of LMS appearing in this rare location, the main differential diagnoses, and this tumor's immunostaining profile to help guide the pathologist to the correct diagnosis. A comprehensive panel of appropriate immunostains paired with thorough familiarity of pitfalls, such as CAM 5.2 positivity, is important in reaching the correct diagnosis for patients with this rare entity.

Pleomorphic Liposarcoma of Small Bowel

(Poster No. 23)

Anup Jnawali, MD ([email protected]); Mohammad Al-Attar, MD; Michelle Yang, MD. Department of Pathology, University of Massachusetts Memorial Medical Center, Worcester.

Pleomorphic liposarcoma (PLS) is a rare subtype of liposarcoma accounting for <5% of all liposarcomas of soft tissue. PLS arising in the gastrointestinal tract (GI) is rare, with only a handful of cases reported in the English-language literature. We report a case of a 71-year-old woman with a history of rectal adenocarcinoma, presenting with small-bowel obstruction and found to have a mass in the jejunum. The patient underwent small-bowel resection. Gross examination revealed a 7.8 × 6.9 × 2.2-cm exophytic, soft, tan mass (Figure 1.23, A) with a hemorrhagic and necrotic cut surface. Microscopic evaluation revealed heterogeneous epithelioid malignant cells (Figure 1.23, B), some with intracytoplasmic clear/fatty droplets and rarely scalloping the nucleus, suggestive of lipoblasts (Figure 1.23, C), and others with numerous intracytoplasmic eosinophilic globules highlighted by PAS/diastase stain. Scattered multinucleated giant cells were also present. The mitotic count was high (~80/10 high-power fields), including bizarre mitotic figures, and the Ki-67 proliferation index was approximately 60%. Immunohistochemical studies demonstrated that the malignant cells were negative for CD117, DOG1, SMA, desmin, MyoD1, ERG1, CD34, CD31, pancytokeratin AE1/3, CK-OSCAR, EMA, CAM 5.2, SOX10, melan-A, and S100. INI1 was retained. β-Catenin showed membranous staining. P53 showed mutant phenotype (Figure 1.23, D). Fluorescence in situ hybridization was negative for MDM2 amplification and DDIT3 rearrangement. The morphologic and immunohistochemical features favored a diagnosis of PLS. Pleomorphic liposarcomas are aggressive sarcomas exhibiting local recurrence and a metastatic rate of 30%–50%; thus, recognition of this rare entity in the GI tract is important for treatment.

Rectosigmoid Colon Yolk Sac Tumor in the Absence of Testicular Involvement: A Potentially Novel Primary Site

(Poster No. 24)

Matthew G. Charles, BA ([email protected]); Ian A. Taylor-Cho, BA; Avani Pendse, MBBS, PhD. Department of Pathology, Duke University School of Medicine, Durham, North Carolina.

Yolk sac tumor (YST) is an aggressive gonadal germ cell tumor sometimes occurring in extragonadal sites, including the mediastinum and retroperitoneum. To our knowledge, pure primary colonic YST has not been reported in the English-language literature. We present a case of rectosigmoid colon YST with liver metastases without a demonstrable testicular primary. A 53-year-old man presented with abdominal pain and a rectosigmoid colon mass on imaging with likely liver metastases. Endoscopic biopsy revealed an adenocarcinoma with CDX2 positivity (without definite in situ lesion), yet the resection specimen did not show typical colorectal adenocarcinoma morphology. H&E-stained sections showed tumor with solid areas, anastomosing glands, and perivascular glomeruloid structures (Figure 1.24, A and B). Immunohistochemistry showed tumor cells positive for SALL4, glypican-3, CDX2 (Figure 1.24, C), and AFP (Figure 1.24, D). This was concordant with an AFP level of 14 000 ng/mL, confirming the diagnosis of YST. The patient had no testicular symptoms, and subsequent imaging was negative for testicular, mediastinal, and retroperitoneal pathology. Our case may represent an as-yet-unreported primary colonic YST. Other equally rare considerations are colonic metastasis from an occult (testicular) primary or mixed tumor with an unsampled colonic adenocarcinoma component. CDX2 staining, routinely used to confirm intestinal differentiation/origin, is reported to be positive in YST. CDX2 positivity in the initial small biopsy specimen could have led to a diagnosis of colonic adenocarcinoma. Thus, our case highlights the importance of clinical and laboratory correlation (elevated AFP) with specific morphologic clues (absence of in situ lesion) to reach an accurate diagnosis when the morphology is not “classic” and/or specimen size is limited.

ABCB4 Mutation and MDR3 Deficiency: A Diagnostic Consideration for Cholestatic Liver Diseases in Adults

(Poster No. 25)

Yipeng A. Geng, MD, PhD ([email protected]); Irene Riahi, MD; Bita Naini, MD. Department of Pathology, University of California, Los Angeles.

MDR3 deficiency is a rare cholestatic liver disorder caused by mutations in the ABCB4 gene. It includes several entities with a wide spectrum of clinical presentation. While usually considered in neonatal cholestasis, MDR3 deficiency is often an overlooked diagnosis in adults. We present the case of a 29-year-old woman with a history of intermittently elevated ALT, AST, and ALP since her first pregnancy in 2010. She reported no history of medication/supplement use. Viral serologies were negative. She underwent a liver biopsy at an outside hospital and was given a presumed diagnosis of an autoimmune hepatitis/primary biliary cholangitis (AIH/PBC) overlap syndrome, despite negative autoimmune serologic studies. She was treated with steroids without improvement and was referred to our institution. Review of histology demonstrated bile duct injury and focal bile duct loss. There was mild to moderate lymphoplasmacytic portal inflammation with mild interface activity, but no significant hepatitis to suggest AIH. Because of the patient's history of cholestatic liver disease during pregnancy and similar complications during pregnancy in her mother, the specimen was submitted for molecular testing, which revealed a mutation in ABCB4 (c.2869C>T, p.R957X). This nonsense mutation introduced a premature stop codon, resulting in a nonfunctional protein. The heterozygosity of this mutation explained the late onset and relatively mild clinical manifestation in this patient. In conclusion, MDR3 deficiency needs to be included as a diagnostic consideration in cholestatic liver diseases of not only infants but also adults. ABCB4 gene mutation analysis will help establish the diagnosis and avoid unnecessary treatment.

Clinicopathologic Features of Peutz-Jeghers Polyps Compared to Other Hamartomatous Polyps

(Poster No. 26)

Mark Ettel, MD ([email protected]); Xiaoyan Liao, MD, PhD. Department of Pathology, University of Rochester Medical Center, Rochester, New York.

Context: Peutz-Jeghers (PJ) syndrome is characterized by STK11 gene mutation, gastrointestinal polyposis, mucocutaneous pigmentation, and increased cancer risk. PJ polyps (PJPs) have fronds of lamina propria, cystically dilated glands, and arborizing smooth muscle. However, other hamartomatous polyps can mimic PJP. We compared cases of PJP to similar non-PJ polyp (NPJP) cases.

Design: Clinicopathologic features in patients with PJP from 2006 to 2021 were compared to controls with NPJP. Statistics were performed by using the t test and Fisher exact test.

Results: We identified 10 PJ syndrome patients with a mean age of 37 years (range, 9–68 years) and 36 PJP specimens. The 10 control patients had a mean age of 50 years (range, 13–80 years) and 11 NPJP specimens. There were no age or sex differences. Three PJP patients and 2 control patients had a history of malignancy. PJ specimens were more likely to have small bowel polyps (23 of 36 [64%] versus 1 of 11 [9%], P = .002); there was no difference in stomach or colon involvement. PJP specimens more often had multiple polyps (33 of 36 [92%] versus 7 of 11 [64%], P = .04). There was no difference in dysplasia or polyp size. Non-PJ cases were more likely than PJ cases to have histologic prolapse (0 of 25 [0%] versus 2 of 7 [29%], P = .04). Gastric PJPs were more likely to have foveolar hyperplasia (9 of 9 [100%] versus 1 of 3 [33%], P = .045). Upon follow-up, all NPJP patients were alive; 1 PJ patient died of urothelial carcinoma.

Conclusions: We showed that patients with PJP and NPJP can be differentiated by polyp location and presence of multiple polyps, but other features, including patient age, dysplasia, and history of malignancy, may overlap.

Liver Histopathology in Early-Onset Colorectal Cancer Patients: A Case Series

(Poster No. 27)

Saryn Doucette, MD; Mara L. Fernández-Santiago, MD ([email protected]); Kelly Simarski, AS. Department of Pathology, Medical College of Wisconsin, Milwaukee.

Context: Known risk factors for colorectal cancer (CRC) do not entirely explain the increasing incidence of early-onset (age below 50 years) CRC. There may be a unique set of risk factors not yet identified. Nonalcoholic fatty liver disease (NAFLD) has been linked to CRC but not specifically studied in patients younger than 50 years. To study this, we retrospectively evaluated the histopathology in hepatectomies from patients with early-onset CRC.

Design: A search of our pathology database from 2011–2021 identified hepatectomies for metastatic CRC in 21 early-onset CRC patients. Clinical and demographic data were obtained. Liver histopathology was evaluated on H&E, trichrome, reticulin, iron, and PAS/diastase stains.

Results: There were 8 men (38%) and 13 women (62%), including 3 Black, 2 Hispanic, and 16 White patients. The median age was 44 years (IQR, 41–47.5 years). Eleven patients had a family history of CRC but no documented hereditary syndrome. Steatosis was seen in 16 patients (76%): 2 severe (>66% fat), 4 moderate (>33%–66% fat), 6 mild (5%–33% fat), and 4 minimal (<5% fat), whereas 5 patients had no steatosis (see Table with clinical characteristics). Mild portal fibrosis was seen in 1 patient; 3 had mild sinusoidal fibrosis; 1 showed venous outflow obstruction; and 1 showed lymphocytic cholangitis.

Conclusions: Steatosis was the most common liver histopathologic abnormality in our pilot study of 21 early-onset CRC patients. Future studies will include evaluation of steatosis in patients with different stages of CRC to further explore the link between NAFLD and CRC. Histopathologic evaluation of nonneoplastic liver in hepatectomy specimens may identify clinically significant treatable conditions such as NAFLD.

Chronic Intestinal Pseudo-Obstruction Secondary to Diffuse Paraneoplastic Gastrointestinal Extramedullary Hematopoiesis Mimicking Crohn Disease: Report of a Rare Case

(Poster No. 28)

Kusum L. Sharma, MBBS1 ([email protected]); Ravi B. Singh, MBBS2; Xiaofei Zhang, MD, PhD.1 1Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and Clinics, Madison; 2Department of Medicine, SUNY Upstate Medical University, Syracuse, New York.

In hematopoietic disorders such as myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPNs), extramedullary hematopoiesis (EMH) occurs commonly in the spleen, liver, kidneys, and adrenal glands. Gastrointestinal tract involvement is uncommon and often focal. We report a case of a 65-year-old man with MDS/MPN with diffuse intestinal EMH causing chronic intestinal pseudo-obstruction (CIP), clinically mimicking Crohn disease, who underwent total colectomy for chronic megacolon. Initially, he developed an episode of adynamic ileus following hip surgery. Later, he had an episode of progressive gastroenteritis with dilated distal small bowel and proximal colon. CT angiography at that time did not reveal any pathology, and prior colonoscopy was normal. Further, he had multiple episodes of abdominal bloating with marked intestinal dilatation requiring decompression and thus was diagnosed with CIP with chronic megacolon. He was later diagnosed with MDS/MPN and received decitabine therapy. He continued to have pseudo-obstructive symptoms, and subsequent colonoscopy revealed focal inflammation in the transverse colon. Biopsy revealed focal active colitis. Owing to an unknown etiology and the recurrent nature of his disease, total abdominal colectomy was performed. Grossly dilated colon revealed deep fissures and mucosal cobblestoning. Microscopically, there was diffuse EMH with atypical megakaryocytes in the colon, ileum, appendix, and regional lymph nodes. Other findings were multifocal ulceration, transmural inflammation, neuromuscular hypertrophy, pyloric metaplasia, and architectural distortion. Extensive intestinal EMH may cause enteric ganglionic neuropathy and result in intestinal pseudo-obstruction. Thus, in patients with pseudo-obstructive symptoms and clinicopathologic features of inflammatory bowel disease, EMH secondary to a hematopoietic disorder should be considered as a differential.

Immune Checkpoint Inhibitor Therapy–Induced Collagenous Colitis: A Rare Adverse Outcome

(Poster No. 29)

Maria Kamal, MD1 ([email protected]); Mahum Nadeem, MD2; Elizabeth Gillies, MD.1 Departments of 1Pathology and 2Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City.

The failure of the immune system to recognize and eliminate malignant cells is the cornerstone of the pathogenesis of various malignancies. In 2011, with the approval of the first immune checkpoint inhibitor (ICI), cancer management was revolutionized. Nivolumab is an ICI with a distinct profile of gastrointestinal adverse events. Inflammatory bowel disease–like colitis is often associated with its use, and microscopic colitis is the least reported. Per our extensive literature search, only 4 cases of collagenous colitis due to ICI therapy have been reported to date. Here we add another interesting case to this brief list. A 75-year-old woman with small-cell lung carcinoma was started on immunotherapy with nivolumab/ipilimumab. Within a year of receiving treatment, she underwent colonoscopy for bothersome symptoms of chronic watery diarrhea and was diagnosed with immune-mediated colitis on histopathology. Colon biopsy at that time showed mildly active colitis and neutrophilic cryptitis with a negative infectious workup. She initially showed a good response to steroids, and her immunotherapy was held. However, her symptoms recurred when nivolumab was restarted after a year. Repeated colonoscopy and infectious workup were again normal. Colon biopsy this time revealed thickened subepithelial collagen and intraepithelial lymphocytes consistent with collagenous colitis (Figure 1.29). She was treated with steroids and intravenous fluids and discharged home. Our case highlights the importance of histopathologic examination in patients receiving ICI therapy with a normal colonoscopy. Collagenous colitis is an important differential in these cases. Histologic diagnosis and timely identification can guide clinicians for early targeted management.

Large Mucinous Cystic Neoplasm of Mesocolon in Association With Adenocarcinoma of Duodenum in an Elderly Man: A Rare Incidental Entity in a Male, Posing a Diagnostic Challenge

(Poster No. 30)

Prachi, MD ([email protected]); Hema M. Aiyer, MD. Department of Anatomic Pathology and Laboratory Medicine, Dharamshila Narayana Superspecialty Hospital, New Delhi, India.

Mucinous cystic neoplasms of the mesocolon are rare intra-abdominal lesions in the spectrum of mesenteric cysts, with an extremely rare incidence in male patients. To date, only 1 case has been reported in a 5-year-old boy and was designated as benign. These neoplasms commonly arise from the ovaries or from extraovarian sites like the pancreas, liver, and appendix. A 66-year-old man presented with vomiting and abdominal distention and was diagnosed with duodenal adenocarcinoma on upper gastrointestinal biopsy. Contrast-enhanced CT and MRI revealed abrupt luminal narrowing and wall thickening of D2, with a multiloculated septate cystic lesion close to the duodenal stricture that was diagnosed as cystic lymphangioma (Figure 1.30, A). The patient underwent Whipple resection with right hemicolectomy. Grossly, the mesentery adherent to the duodenum and colon showed a multilocular thin-walled cyst measuring 14 × 6.5 × 5.0 cm, filled with mucinous fluid (Figure 1.30, B). Microscopically, the cyst wall showed mucin-secreting epithelium of the intestinal type, with focal stratification, cribriform appearance, absence of ovarian-like stroma, and no evidence of malignancy (Figure 1.30, C). IHC showed positivity for CK7 and CK20, and benign mucinous cystic neoplasm of the mesocolon was diagnosed (Figure 1.30, D). The patient showed no recurrence on 2 years of follow-up. These rare tumors in males have unclear pathogenesis and pose diagnostic challenges preoperatively. They lack specific symptoms, biochemical markers, and radiologic findings. Given their malignant potential, they form differentials for all mesenteric cysts. Complete surgical excision is the mainstay of the treatment, followed by comprehensive microscopic evaluation for definitive diagnosis.

Unusual Presentation of Intraductal Papillary Mucinous Neoplasm With Marked Colonization/Fistulization of the Duodenal Mucosa and Common Bile Duct in an 81-Year-Old Man

(Poster No. 31)

Regina Reed, MD ([email protected]); George Sneed, DO. Department of Pathology, University of Tennessee Medical Center, Knoxville.

Intraductal papillary mucinous neoplasm (IPMN) is a benign mucin-producing neoplasm of the pancreas that arises in the main duct and/or branch ducts of the pancreas; however, about 40% of IPMNs are associated with invasive carcinoma. We report an unusual case of IPMN in an 81-year-old man that colonized/fistulized into the common bile duct (CBD) and duodenal mucosa. The patient initially presented with a dilated pancreatic duct and biliary obstruction. Imaging and endoscopic findings were most consistent with an IPMN, and the patient underwent a Whipple procedure. The Whipple specimen grossly demonstrated a multicystic mucinous lesion spanning 8 cm that was associated with the pancreatic duct (blue arrow in Figure 1.31, B) within the head and neck of the pancreas and extended into the CBD (yellow arrow in Figure 1.31, B) and protruded through the ampulla. There were also 2 villous lesions (arrows in Figure 1.31, C) located on the duodenal mucosa, 2.5 cm proximal to the ampulla. Microscopically, this process was diagnosed as IPMN, gastric foveolar type, with areas of high-grade dysplasia. The IPMN extended from the dilated pancreatic duct into the CBD (Figure 1.31, A) and prominently colonized surrounding smaller pancreatic branching ducts and, through excessive pressure, colonized submucosal duodenal ducts and formed a fistula to the duodenal mucosal surface (Figure 1.31, D). Despite the extensive colonization/fistulization of the IPMN, there was no invasion identified; hence, the prognosis was favorable. This case highlights that IPMN can present extensively with fistulization and colonization to neighboring organs and structures without being malignant or invasive.

Clinicopathologic and Molecular Analysis of Colorectal Carcinomas With Neuroendocrine Differentiation

(Poster No. 32)

Nazire E. Albayrak, MD ([email protected]); Bella L. Liu, MD; Alexandros D. Polydorides, MD; Stephen Ward, MD. Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai/The Mount Sinai Hospital, New York, New York.

Context: The World Health Organization subdivides colorectal neuroendocrine neoplasms into well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas (NECs), and mixed neuroendocrine–nonneuroendocrine neoplasms, including mixed adenoneuroendocrine carcinomas (MANECs). When the neuroendocrine component represents less than 30%, it is termed as adenocarcinoma with neuroendocrine differentiation (ANED). Colorectal cancer data sets reveal that molecular profiling of carcinomas with neuroendocrine differentiation is limited to 63 NECs and 3 MANECs.

Design: Fifty-seven cases of colorectal carcinoma with a range of neuroendocrine differentiation (19 ANEDs, 16 MANECs, and 22 NECs) were compared with 100 controls of adenocarcinoma without neuroendocrine differentiation along demographics, mutational profiles, histopathologic grade and stage, tumor size, and location. Well-differentiated neuroendocrine tumors of any grade were excluded.

Results: Colorectal carcinomas with neuroendocrine differentiation presented at an earlier age (median, 59 versus 65 years; P = .04) in a similar sex distribution. Compared with adenocarcinomas of the same tumor size (median, 4 cm) and location, poorly differentiated carcinomas with neuroendocrine differentiation showed more frequent lymph node (P < .001) and distant (P < .001) metastases and hence were associated with more advanced disease stage (ie, stage III/IV: 89% versus 40%; P < .001) at the time of diagnosis. Pearson correlation confirmed that frequency of BRAF mutations was correlated positively (r =.969) with neuroendocrine differentiation (31% NECs, 23% MANECs, and 6% ANEDs versus 3% conventional adenocarcinomas; P = .03). Furthermore, dysregulation of the RB1/p16 pathway was exclusively identified in NEC (13%) and MANEC (25%) groups.

Conclusions: In summary, poorly differentiated colorectal carcinomas with neuroendocrine differentiation display aggressive behavior. Yet, they are more likely to harbor certain mutations such as BRAF p.V600E, which is of therapeutic value.

Benign Epithelial Vascular Emboli and Bile Embolism in the Gallbladder of a COVID-19–Positive Patient With Subacute Calculous Cholecystitis

(Poster No. 33)

Christopher Q. Miller, MD1 ([email protected]); Hector Mesa, MD1; Sidney D. Bruce, MD2; Nikolay Popnikolov, MD1; Nishi Dave, MD.1 Departments of 1Pathology and 2General Surgery, Indiana University, Indianapolis.

Lymphovascular invasion is a hallmark of the neoplastic process, but the presence of benign epithelium in vessels has been reported in various tissues. Several mechanisms have been suggested as causes of such epithelial displacement, including surgical manipulation, increased mucosal friability, and inflammation. Here we report a case of benign epithelial vascular emboli in a gallbladder with cholecystitis. A 29-year-old man presented with acute calculous cholecystitis. The surgery was delayed for several weeks owing to his COVID-19 infection. Histologic examination of his cholecystectomy specimen revealed subacute cholecystitis and widespread vascular epithelial emboli with associated fibrin deposition and bile embolism (Figure 1.33, A through D). The epithelial emboli were localized in small veins and arterioles with D2-40/CD31+/CD34+ endothelium. The displaced epithelium showed benign cytologic features. It had a wild-type p53 expression pattern and a Ki-67 labeling index of <1%, supporting a benign process. No evidence of neoplasia could be found within the specimen. The presence of fibrin adherent to the epithelium and bile emboli was consistent with an in vivo process. Persistent inflammation, mucosal ulceration, and protracted surgical manipulation secondary to adhesive disease are favored to be the underlying causes of these histologic findings. Although we presumed an uneventful outcome, clinical follow-up was suggested owing to this unusual finding. To our knowledge, the displacement of benign epithelium has not been previously reported in the gallbladder. Pathologists should be aware of this rare phenomenon and spend extra effort to prove the benign nature of this process. The role of COVID-19 infection is uncertain.

Malignant Gastrointestinal Neuroectodermal Tumor Arising in the Extrahepatic Bile Ducts: A Rare Neoplasm in an Unusual Anatomic Location

(Poster No. 34)

Christopher Q. Miller, MD1 ([email protected]); Omer Saeed, MBBS1; Ahmad Al-Hader, MD2; Gail H. Vance, MD3; Chen Zhang, MD, PhD.1 Departments of 1Pathology, 2Hematology/Oncology, and 3Medical and Molecular Genetics, Indiana University, Indianapolis.

Malignant gastrointestinal neuroectodermal tumor (GNET), also referred to as clear cell sarcoma–like tumor of the gastrointestinal tract, is a rare aggressive neoplasm with fewer than 100 cases reported in the literature. Most cases are reported to arise in the tubular gastrointestinal tract. We report a unique case of GNET arising in the extrahepatic bile ducts. The patient was a 34-year-old woman who presented with painless jaundice and diarrhea several months after undergoing cholecystectomy for biliary dyskinesia. CT and endoscopic studies revealed a mass arising from the peripheral 4B bile ducts, involving the left hepatic duct and hepatic duct bifurcation. Evaluation of bile duct brushings resulted in the diagnosis of a malignant epithelioid neoplasm initially favored to represent melanoma. Partial hepatectomy with resection of the extrahepatic bile ducts was performed. Histologic examination of the lesion showed a malignant spindled and epithelioid neoplasm, extensively involving the wall of the extrahepatic bile ducts and invading the hepatic parenchyma (Figure 1.34, A through D). The neoplastic cells were strongly positive for S100 and SOX10. Immunohistochemical stains for various cytokeratins and melanoma markers were negative. Fluorescence in situ hybridization testing with EWSR1 break-apart probes showed rearrangement of the EWSR1 gene region. The immunohistochemical and molecular findings were consistent with a diagnosis of GNET arising in the extrahepatic bile ducts. The patient was followed up by active surveillance, with no evidence of local recurrence or distant metastasis, and is presently at 13 months status post resection.

Duodenal Metastasis as the Sole Recurrence of Regressive Sinonasal Melanoma in a Young African American Patient: A Rare Case Report

(Poster No. 35)

Khaled S. Mohamed, MD ([email protected]); Reeba Omman, MD. Department of Pathology, University of Florida College of Medicine-Jacksonville.

Malignant melanoma (MM) of the gastrointestinal (GI) tract is rare. MMs of the GI tract are metastatic and rarely primary. A total of 2.5% of cases are from a regressed melanoma of unknown primary origin. During autopsy, 50%–60% of cutaneous MMs have GI metastasis, and only 2% are diagnosed antemortem. Sinonasal MM represents <1% of all melanomas. In addition, duodenal melanoma accounts for 12% of GI MMs. The prognosis is worse in African Americans, with a higher rate of metastasis. A 37-year-old African American man had left-nostril MM after resection, radiation, and immunotherapy. After 4 years, PET scanning showed a 4.8-cm mass in the right abdomen with an SUV of 4.2. Endoscopic biopsy of a mass in the duodenum revealed melanoma. Despite treatment, PET displayed an enlarging mass with an SUV of 7.6. The patient experienced GI bleeding and weight loss and eventually underwent resection. The duodenum revealed a 6-cm mass (Figure 1.35, A) attached to the wall with necrosis and hemorrhage on serial sectioning. Histology revealed dense submucosal and muscularis externa involvement (Figure 1.35, B) of malignant spindle cells with prominent nucleoli, nuclear inclusions, and melanin pigmentation (Figure 1.35, C). The spindle cells were positive for SOX10 (Figure 1.35, D), melan-A, and S100, supportive of MM. The submitted lymph nodes were negative for metastatic melanoma. Given the patient's history, a metastatic duodenal MM was favored. Metastatic MM of the GI tract is rare and spreads often from lower extremities. The overall prognosis is poor. Early detection and surgery extend the mean survival to 48 months.

The Concordance Between Wide-Area Transepithelial Sampling With Computer-Assisted 3-Dimensional Analysis (WATS-3D) and Standard Endoscopic Biopsy in the Detection of Esophageal Dysplasia and Barrett Esophagus

(Poster No. 36)

Zarrin Hossein-Zadeh, MD ([email protected]); Chaohui Lisa Zhao, MD, PhD; Iman Hanna, MD; Solomon Turunbedu, MD; Gerasimos Karalis, MD. Department of Pathology, New York University, Langone-Long Island, Mineola.

Context: Barrett esophagus (BE) is a premalignant condition that develops as a consequence of chronic gastroesophageal reflux disease and which, if left untreated, can lead to dysplasia and neoplasia. The most common endoscopic surveillance method is traditional forceps biopsy. This technique has low sensitivity and often leaves most of the mucosa unsampled. Recently, the use of wide-area transepithelial sampling with computer-assisted 3-dimensional analysis (WATS-3D) has received much attention. The aim of this research was to add to our experience of WATS-3D by comparing it with traditional forceps biopsy.

Design: A retrospective observational study was performed. All existing GI biopsy cases diagnosed with WATS-3D were identified from our institutional database from 2019 to 2021. All the existing slides of the biopsy cases were reviewed. Univariate analysis was performed for statistical testing.

Results: A total of 109 cases were included in this study, with 85 males and 24 females. The average age of patients with BE was 63.1 ± 11.3 years. In 59 BE cases diagnosed with traditional forceps biopsy, 49 were classified as no dysplasia, 3 were indefinite for dysplasia, 6 were low-grade dysplasia, and 1 was high-grade dysplasia. In 72 cases diagnosed by WATS-3D, 64 were classified as no dysplasia, 7 were indefinite for dysplasia, and 1 was high-grade dysplasia (Figure 1.36, A through D). There was a significant difference between the 2 methods (P < .01).

Conclusions: Compared with traditional forceps biopsy, WATS-3D was more sensitive in finding intestinal metaplasia. However, WATS-3D tended to classify low-grade dysplasia as indefinite for dysplasia.

Epstein-Barr Virus–Associated Gastritis in a Patient With Polycythemia Vera on Ruxolitinib

(Poster No. 37)

Bianca Puello Yocum, MD1 ([email protected]); Jennifer Maratt, MD2; Hector Mesa, MD1; Nikolay Popnikolov, MD.1 Departments of 1Pathology and Laboratory Medicine and 2Gastroenterology, Indiana University, Indianapolis.

Epstein-Barr virus (EBV) is acquired early in life as asymptomatic or symptomatic infectious mononucleosis (IM) and remains latent in a few B cells in most individuals. Pathologic EBV reactivation affects immunosuppressed individuals and manifests as IM-like syndromes, polyclonal lymphoproliferative disorders, EBV-related lymphomas, or EBV-related carcinomas. EBV-associated gastritis (EBV-AG) is an underrecognized and very rarely reported entity. A 65-year-old woman with polycythemia vera treated with ruxolitinib presented with fatigue, fever, arthralgia, and worsening abdominal pain. Workup revealed high EBV viremia (EBV q.PCR, 75 103 IU/mL), increased liver enzymes, and acalculous cholecystitis. A liver biopsy showed chronic, mildly active hepatitis with negative EBV encoding region in situ hybridization (EBER-ISH), which was favored to be drug induced because it resolved spontaneously. She developed melena, and an upper esophagogastroduodenoscopy (EGD) revealed 1 gastric ulcer. Histologic examination showed ulcerated mucosa with prominent lymphoid infiltrate consisting predominantly of small lymphocytes and plasma cells. Classic lymphoepithelial lesions or atypical populations were not observed. Immunostaining for Helicobacter pylori was negative, and CD3, CD20, κ, and λ immunostains showed marked predominance of T over B cells and polyclonal plasma cells. EBER-ISH demonstrated numerous scattered EBV-positive cells (Figure 1.37, A through D), and a diagnosis of EBV-AG was made. She received 1 week of antiviral therapy, and follow-up EGD at 1 month showed a healing ulcer. After 2 months, new gastric ulcers and persistent viremia (EBV q.PCR, 5609 IU/mL) were identified. Numerous reports of symptomatic and asymptomatic EBV reactivation syndromes after ruxolitinib therapy are emerging. Reported mechanisms include impaired immunosurveillance due to severe reduction in T-lymphocyte subsets.

Mesenteric Rosai-Dorfman Disease in Cowden Syndrome With IgG4-Positive Infiltrate and Rare KRAS Mutation Suggesting Neoplasia

(Poster No. 38)

Benjamin Gertsen, MD1 ([email protected]); Tom C. DeRoche, MD2; Aaron R. Huber, DO.1 1Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York; 2Department of Pathology and Laboratory Medicine, Kaiser Permanente Airport Way Regional Laboratory, Portland, Oregon.

Rosai-Dorfman disease (RDD) is characterized by large S100-positive histiocytes exhibiting emperipolesis. The disease most commonly affects lymph nodes but may occur in extranodal sites, where there is often fibrosis with less pronounced emperipolesis. Prior theories of the pathogenesis of RDD have included infection or abnormal immune response. Recently some RDD cases have been found to harbor KRAS, NRAS, or MAP2K1 mutations, suggesting that a subset of RDD may represent neoplasms. IgG4-positive plasma cell infiltration has been described in RDD, and there is a questionable association with IgG4-related disease (IgG4RD). A 52-year-old man with Cowden syndrome who presented with hematochezia was found to have a mesenteric mass on imaging. The 6.5-cm ileal mesenteric mass and adjacent serosal deposits showed sheets of histiocytes in a background of lymphoplasmacytic inflammation and sclerosing fibrosis. Lesional histiocytes exhibited enlarged nuclei and voluminous cytoplasm with emperipolesis; they expressed S100 and CD68. Forty IgG4-positive plasma cells were seen per high-power field, with an IgG4:IgG ratio of 35% (Figure 1.38, A through D). Serum IgG4 was normal, and there were no clinical or imaging features of IgG4RD. KRAS (A146P) and PTEN (S170I) mutations were detected in tumor tissue. This report highlights the possibility of dense IgG4-positive plasma cell infiltration in RDD, which may cause morphologic overlap with IgG4RD given the fibrosis associated with extranodal RDD. The KRAS mutation further supports the contention that a subset of RDD cases represents neoplasms; additionally, to our knowledge, this KRAS variant in RDD is rare and has been reported only once previously.

An Institutional Review of Histology Protocol for Hirschsprung Disease

(Poster No. 39)

Nashwan Jabbour, MD ([email protected]); Nuha Shaker, MD; Nathan Shelman, MD; Shadi Qasem, MD. Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington.

Context: Hirschsprung disease is a congenital condition of intestinal innervation. Pathology laboratories have variable sectioning and staining protocols for these specimens. We aim to review our institutional experience in the processing of biopsies for Hirschsprung disease.

Design: Biopsy specimens were collected during 5 years (2015–2020). Twenty levels were obtained from each biopsy; 10 intervening levels were stained with hematoxylin-eosin (H&E), and 2 levels were stained for calretinin. Two teams reviewed the slides independently and recorded their findings.

Results: One hundred three biopsy specimens were obtained from 101 patients ranging in age from 1 day to 9 weeks (61 male and 2 female patients). Eighty cases (78%) were positive for ganglion cells and 23 cases (22%) were negative. Among the positive cases, the teams were able to find ganglion cells within the first 5 H&E levels in 72 cases (90%), and on the first calretinin stain level in 78 cases (98%). The teams were concordant on 98 cases (95%) and were able to identify ganglion cells within the same level, or 1 level away from each other, in all but 1 case (99%) (Figure 1.39).

Conclusions: Our findings support the current practice of obtaining multiple levels, and we confirm that calretinin is a helpful auxiliary stain in challenging cases. In our experience, ganglion cells can be identified in the first few H&E levels and the first level stained with calretinin. A tiered approach may be more practical and economic in the workup of biopsies for Hirschsprung disease.

Ovarian Granulosa Cell Tumor Initially Presenting as a Giant Liver Mass Radiologically Mimicking Primary Cystic Cholangiocarcinoma

(Poster No. 40)

Xia Qian, MD, PhD1 ([email protected]); Jinping Lai, MD, PhD.2 1Department of Pathology, Mount Sinai Hospital, New York, New York; 2Department of Pathology and Laboratory Medicine, Kaiser Permanente Sacramento Medical Center, Sacramento, California.

Ovarian granulosa cell tumor is a rare type of malignant sex-cord stromal tumor, with adult and juvenile types. The tumor initially presents as a giant liver mass; clinically mimicking primary cholangiocarcinoma is exceedingly rare. We report such a case of a 66-year-old woman who presented with right upper quadrant pain. Her past medical history was unremarkable except for a remote hysterectomy for a benign disease. Abdominal magnetic resonance imaging showed an 18.1-cm solid and cystic liver mass (Figure 1.40, A; T, T2 axial), and a subsequent fused positron emission tomography/computed tomography confirmed the solid and cystic mass with hypermetabolic activity (Figure 1.40, B; T) concerning for liver cystadenoma and associated cystadenocarcinoma/cholangiocarcinoma. A fine-needle core biopsy of the liver mass showed coffee-bean–shaped tumor cells (Figure 1.40, C). The tumor cells were positive for inhibin (Figure 1.40, D; left), Foxl2 (Figure 1.40, D; right), WT-1, SF1, vimentin, ER, and SMA. They were negative for AE1/AE3, CAM 5.2, EMA, glypican-3, HepPar1, arginase, CD34, desmin, CD10, CK7, CK20, synaptophysin, chromogranin, S100, HMB-45, CDX2, TTF1, and Pax8. A 2.5-cm ill-defined right ovarian mass was found through re-review of the imaging findings. The histologic features and immunoprofile supported a metastatic sex-cord stromal tumor favoring granulosa cell tumor, adult type, of the right ovary. Strata next-generation sequencing test was performed on the liver biopsy and Foxl2 p.C134W (NM_023067.3: c.402 C>G) mutation was present, consistent with granulosa cell tumor. After multidisciplinary tumor board discussion owing to inoperable disease, the patient underwent chemotherapy with clinical improvement.

“Quadruple-Negative” NTRK-Rearranged Gastrointestinal Stromal Tumor of the Esophagus

(Poster No. 41)

Bindu Challa, MD ([email protected]); Daniel Jones, MD, PhD; Ashwini Esnakula, MD, MS. Department of Pathology, The Ohio State University Wexner Medical Center, Columbus.

Gastrointestinal stromal tumors (GISTs) that are KIT/PDGFRA/BRAF mutation–negative and SDH-proficient can be regarded as “quadruple negative” GISTs. A rare molecular alteration in such cases included NTRK rearrangement, with 2 previously reported cases involving the large and small bowel. We present a case of quadruple-negative GIST with ETV6::NTRK3 fusion presenting in the esophagus in a 34-year-old woman with dysphagia. Endoscopy revealed a large, fungating mass in the mid-esophagus, and biopsies were nondiagnostic. The patient subsequently underwent esophagogastrectomy. Gross examination showed a 6.1-cm tan-white, nodular ulcerated mass (Figure 1.41, A). Histologic examination showed a multinodular myxoid lesion centered in the submucosa and extending into muscularis propria and mucosa. The lesion was composed of low-grade spindled to epithelioid cells with cytoplasmic vacuolization and rare intranuclear inclusions in a background of myxoid stroma (Figure 1.41, B and C) with prominent inflammatory response. Mitoses were rare (1/5 mm2), and tumor necrosis was not identified. On immunohistochemistry, lesional cells were diffusely positive for DOG-1 (Figure 1.41, D) and CD34 with scattered positivity for CD117, MDM2, and TLE1. The tumor was negative for S100, desmin, HMB-45, SMA, MUC4, STAT6, ALK-1, P63, EMA, CD31, and cytokeratins. Based on diffuse expression for DOG-1, the tumor was classified as a GIST. Next-generation sequencing (NGS) on tumor DNA with intron tiling of common oncogenes revealed a typical ETV6::NTRK3 gene fusion with results confirmed by NGS-based RNA sequencing (ETV6e5-NTRK3e14). The patient remained disease-free at 10-month follow-up. This case adds to the expanding spectrum of tumors with NTRK rearrangement that have proven to be therapeutically targetable with TRK inhibitors.

SF-1 Immunostain Outperforms ER and PR in the Diagnosis of Mucinous Cystic Neoplasm of the Pancreas

(Poster No. 42)

Niyati T. Desai, MBBS, MD ([email protected]); Matthias Szabolcs, MD; Helen E. Remotti, MD; Stephen M. Lagana, MD; Huaibin M. Ko, MD. Departments of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York.

Context: Mucinous cystic neoplasms (MCNs) are thick-walled mucinous cysts occurring almost exclusively in the pancreas of middle-aged women. Key histologic features include an inner mucinous epithelial layer and ovarian-type stroma. Immunostains for estrogen receptor (ER) and progesterone receptor (PR) are used in the diagnosis of MCN and help differentiate MCN from intraductal papillary mucinous neoplasm (IPMN). According to the World Health Organization, 30% are ER+ while 60%–90% are PR+. Here, we evaluate SF-1 immunostaining as a diagnostic and differentiating marker of MCN.

Design: Seventeen cases of MCN and 18 cases of IPMN were identified. SF-1 immunostaining was performed. Nuclear positivity for SF-1 in spindled stroma was scored by 2 pathologists. Both extent (% positive cells: 0, ≤5%; 1+, 6%–25%; 2+, 26%–50%; 3+, 51%–75%; and 4+, 76%–100%) and intensity (negative [0], weak [1+, visible at 20×], moderate [2+, visible at 10×], or strong [3+, visible at 4×]) were evaluated.

Results: SF-1 was positive in all 17 MCN cases; most were strongly and diffusely positive (14 of 17, 82.4%). SF-1 staining was specific for ovarian stroma (nuclear) without positivity in tumor epithelium or surrounding pancreas. Conversely, SF-1 was negative in all cases of IPMN. In contrast, ER and PR staining was commonly “weak” or “focal” (Table).

Conclusions: SF-1 immunostain is a robust marker of ovarian stroma in MCN, distinguishes between MCN and IPMN, and is positive in MCN when ER or PR stains are weak/negative. In conclusion, SF-1 is an underused but useful marker for MCN.

Recurrent Colonic Adenocarcinoma Exhibiting Mucosal Colonization and Mimicking a Second Primary With Features of a Traditional Serrated Adenoma

(Poster No. 43)

Matthew Uy, DO ([email protected]); Douglas Walton, MD. Department of Pathology and Area Laboratory Services, San Antonio Military Medical Center, San Antonio, Texas.

Metastatic carcinomas that extend to the mucosal surface of the gastrointestinal (GI) tract can closely mimic a primary lesion with features of paradoxical maturation and adenomatous changes. These changes have been referred to as “mucosal colonization” and may lead to the misdiagnosis of a primary carcinoma as opposed to a recurrence or metastasis. We report a case of an 80-year-old man with a history of mucinous adenocarcinoma status post resection 2 years prior who presented with a new mass at the ileocolic anastomosis site. Histologic sections demonstrated mucinous adenocarcinoma involving the mucosal surface and areas of high- and low-grade dysplasia with features of traditional serrated adenoma (Figure 1.43, A and B). The diagnosis of recurrent mucinous adenocarcinoma with mucosal colonization was rendered. This assessment was based on the similar histology to the previous resection, identical mismatch repair studies (all intact), the subserosal position of most of the carcinoma, as well as the location at the anastomotic site. Mucosal colonization of the GI tract can present challenges in determining metastasis versus a second primary carcinoma. It is important for pathologists to be mindful of this phenomenon, particularly when dealing with a new luminal GI lesion in a patient with a history of carcinoma. To our knowledge, this is the only reported case of colonic adenocarcinoma with mucosal colonization showing features of a traditional serrated adenoma as well as mucosal colonization documented in the context of a recurrence.

Correlation of Reactive Lymph Node Hyperplasia and MS-Unstable Medullary Carcinoma of Colon

(Poster No. 44)

Ansa Mehreen, MD ([email protected]); Adesola Akinyemi, MD; Curtis Hall, MD. Department of Pathology, University of Chicago-Northshore, Evanston, Illinois.

Context: Medullary carcinoma (MC) of colon is a unique histologic subtype of microsatellite (MS)-unstable colorectal carcinoma, but little is known about its lymphocyte-rich tumor-immunoregulatory microenvironment. We found reactive lymph node hyperplasia in 1 of our routine cases of MC that prompted further workup for a lymphoid neoplasm, which was negative. This drove our interest to examine more cases of MC for reactive hyperplasia in lymph nodes (LNs) given the neoantigen-rich environment that results in tumor-infiltrating lymphocytes.

Design: H&E-stained slides of benign LNs were examined from 24 colonic resections diagnosed as MS-unstable medullary carcinoma of colon and MS-stable colonic adenocarcinoma from our pathology database. Sizes of LNs and germinal centers (GCs) were used as an objective criterion to determine the reactivity of nodes. Sizes were measured by using an ocular micrometer. Data were analyzed by using 2-tailed t test.

Results: Twelve cases were identified in each group. No significant difference was identified between the largest and average lymph node size (P = .60 and .37, respectively). However, the size of GCs was significantly larger in MS-unstable medullary carcinoma (P = .02; Table).

Conclusions: These limited data suggest that the immune-mediated response that results in lymphocyte infiltration in MC is not limited to the tumor only, but that the surrounding LNs also show reactive hyperplasia with significantly large GCs, which potentially can be an indication of systemic immune dysregulation. More studies are warranted with larger study populations to assess the phenomenon in other lymphoid tissue and using other indicators to access for immune modulation.

Anti-TNF-α–Induced Peritoneal Granulomatosis With Histoplasmosis Masquerading as Abdominal Carcinomatosis

(Poster No. 45)

Elnaz Panah, MD ([email protected]); Thanchanok Chaiprasit, MD; Andreas Kontosis, MD; Zachary Kimura, MS; Xiuxu Chen, MD; Xianzhong Ding, MD. Department of Pathology, Loyola University Medical Center, Maywood, Illinois.

Infliximab is a tumor necrosis factor α (TNF-α) antagonist that has established an important role in the treatment of many inflammatory diseases including inflammatory bowel disease. One of the most important side effects of TNF-α antagonists is the risk of opportunistic infections. We present an interesting case of a 57-year-old man with a long-documented history of Crohn disease who was taking infliximab. He presented with progressive abdominal pain, distention, and low-grade fever. Abdominal CT scan showed moderate abdominopelvic ascites and infiltration of the mesentery and omentum, concerning for peritoneal carcinomatosis. He underwent a diagnostic laparoscopy with omentectomy and partial small-bowel resection, and biopsies were taken of the liver and mesenteric lymph nodes. Histologic examination revealed numerous necrotizing and nonnecrotizing granulomas with multinucleated giant cells involving the small bowel, omentum, mesenteric lymph nodes, and liver parenchyma. GMS staining demonstrated numerous intracellular yeast-type fungal organisms measuring 3 to 6 μm in diameter, which is consistent with Histoplasma infection. A positive urinary histoplasmosis antigen test further confirmed the diagnosis. This case serves as a dramatic example of diffuse peritoneal granulomatous histoplasmosis masquerading as abdominal carcinomatosis due to TNF-α antagonist–induced immune suppression. Recognizing this infectious entity and making a prompt diagnosis is crucial to avoid delayed therapy.

Diagnostic Utility of Ordering Deeper Levels for Endoscopically Diagnosed Polyps With Initial Nondiagnostic Biopsy Specimen: A Retrospective Study

(Poster No. 46)

Mozibur Rahman, MBBS ([email protected]); Priyanka Patil, MD. Department of Pathology, Westchester Medical Center, Valhalla, New York.

Context: In our surgical pathology practice, there are no predetermined guidelines for ordering deeper levels in case of nondiagnostic initial biopsy for endoscopically diagnosed colorectal polyps. In our practice, 2 initial H&E levels are cut for every colorectal biopsy. Few pathologists order deeper levels before signing out the report as no significant pathologic diagnosis. The aim of the study is to determine the diagnostic yield of ordering deeper levels as well as introducing uniformity in our surgical pathology practice when we deal with these colorectal biopsies.

Design: Fifty-three cases with nondiagnostic pathology reports on endoscopically diagnosed colon polyps were identified after searching our laboratory information system for 7 months' duration. We cut 5 additional H&E deeper levels on these 53 paraffin blocks. The deeper levels were examined by the pathology resident and gastrointestinal pathologist for any additional findings corresponding to the level of cutting. The endoscopic correlation and the final result analysis were done.

Results: The deeper levels yielded new diagnostic information in 34 of 53 cases (64%) and specifically tubular adenoma in 9 of 53 cases (17%) (Table). Most of these adenomas were first detected on the third deeper level.

Conclusions: Our findings support routine ordering of at least 3 deeper levels to improve adenoma detection rate. If in the same case, biopsy of another part shows adenomatous polyp, examination of deeper levels may not be necessary. In such cases, referencing US colorectal cancer prevention task force guidelines would be helpful before ordering deeper levels.

Metastases to the Thyroid From Poorly Differentiated Intrahepatic Cholangiocarcinoma

(Poster No. 47)

Bo Young E. Lee, DO ([email protected]); Steven H. Adams, MD; Randolph A. Hennigar, PhD, MD; Jela Bandovic, MD. Department of Pathology, Stony Brook University Hospital, Stony Brook, New York.

Metastases to the thyroid gland are uncommon, with the most frequent primaries being renal, gastrointestinal, and lung malignancies. Metastasis from cholangiocarcinoma to thyroid has been described twice in prior literature. A 69-year-old woman was admitted for failure to thrive. Alkaline phosphatase was significantly elevated (607 IU/L). CT revealed innumerable masses throughout the liver and a lesion at the pancreatic head/body, and multiple nodules in the thyroid. Results of CT of abdomen/pelvis performed 5 months prior were unremarkable. Serum CA 19-9, AFP, and CEA tumor markers were negative; CA 125 (3397 U/mL) and CA 15-3 (960.6 U/mL) were elevated. Ascitic cytology revealed metastatic adenocarcinoma. She rapidly deteriorated and died. Postmortem examination revealed multiple well-circumscribed tan-pink lesions in the liver, the largest measuring 17 × 12.5 × 10 cm, in a noncirrhotic background (Figure 1.47, A); numerous tan-yellow punctate lesions throughout the pancreas; enlarged peripancreatic, para-aortic, and paratracheal lymph nodes; and thyroid nodules. Microscopy revealed poorly differentiated carcinoma within the liver; pancreas; gallbladder; peritoneum; stomach; small/large bowel; trachea; lungs; heart; kidneys; adrenals; spleen; peripancreatic, para-aortic, and para-esophageal lymph nodes; and the thyroid (Figure 1.47, B). The immunohistochemical profile of CK7+, CK19+, CEA+, CK20+ (focally), and CDX2, ER, GATA3, PAX8, WT1, and TTF-1 performed on liver lesion narrowed the differential diagnosis toward pancreatobiliary primaries. Gross findings of an enormous intrahepatic mass supported primary intrahepatic cholangiocarcinoma over pancreatic adenocarcinoma. Hepatocellular carcinoma was excluded by noncirrhotic background, and HepPar1, AFP, and BerEP4+. Intrathyroid metastases stained CK7+ (Figure 1.47, C), CK19+, while TTF-1 stained normal thyroid background (Figure 1.47, D). This is the third reported case of metastasis from a cholangiocarcinoma to the thyroid.

Gastrointestinal Mucormycosis With COVID-19 Pneumonia: A Case Series

(Poster No. 48)

Steven H. Adams, MD ([email protected]); Pons T. Materum, MD; Jela Bandovic, MD; Randolph A. Hennigar, PhD, MD. Department of Pathology, Stony Brook University Hospital, Stony Brook, New York.

Mucormycosis, which includes infection by Mucor and Rhizopus species and is colloquially called “black fungus,” is associated with diabetic and immunocompromised patients. Mucormycosis is rarely detected on blood cultures and the diagnosis is made from morphologic and staining patterns of GMS+, PAS+, broad, ribbon-like pauciseptate, wide-angle randomly branching hyphae. We report 2 cases of gastrointestinal mucormycosis occurring in the setting of COVID-19 pneumonia. Case 1 involves a 52-year-old man with history of dyslipidemia and obesity who was admitted for COVID-19 pneumonia and developed concurrent Stenotrophomonas maltophilia pneumonia. After 2 weeks on mechanical ventilation with respiratory function deterioration, the patient died. In addition to findings of COVID-19–related lung injury, autopsy discovered 3 gastric ulcers. Histology showed colonization and angioinvasion by GMS+, PAS+, broad, hollow, nonseptate, right-angle–branching hyphae morphologically compatible with Mucor species (Figure 1.48, A and B). Our second case involves a 41-year-old man with history of hypertension and prediabetes who was admitted for breathing difficulty. He was found to be COVID-19–positive with acute kidney injury. The patient became obtunded and was intubated. Sputum cultures grew Stenotrophomonas species. Owing to bloody bowel movements, a CT scan showed ischemic stomach and small-bowel infarction. During surgery, 150 cm of frankly necrotic small bowel was excised. Histology revealed transmural infiltration by GMS+, PAS+, broad, ribbon-like pauciseptate, wide-angled branching hyphae with angioinvasion (Figure 1.48, C and D) and bowel ischemic/hemorrhagic necrosis. The patient died 48 hours later. Mortality rates for gastrointestinal mucormycosis approximate 50%. Mucormycosis with COVID-19 has been previously described in rhino-orbital and pulmonary infections. Only 2 cases of COVID-19–associated gastrointestinal mucormycosis have been reported to date.

Challenging Cases of Cylindroma-like Basaloid Squamous Cell Carcinoma at Unusual Sites: A Unique Morphology

(Poster No. 49)

David Gustafson, MD ([email protected]); Lauren Pupa, BA; Julie Youngs, MD; Yve Huttenbach, MD; Shilpa Jain, MD. Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas.

Cylindromas are benign tumors of the skin with the potential for malignant transformation. Associations between CYLD mutations and basaloid carcinomas of the anus and head and neck have been reported. These tumors show cylindroma-like morphology that can be challenging to diagnose at unusual sites, as discussed in the following 2 cases. Case 1 involved a 58-year-old woman with a past medical history of reflux who presented with 1 month of progressive dysphagia and a 2-cm ulcerative lesion in the distal esophagus. Case 2 involved a 58-year-old woman who presented with a friable anorectal mass extending 5 cm into the anal canal. Subsequent MRI showed a 7.5-cm heterogeneous mass in the right hepatic lobe. Targeted biopsies of the esophagus and liver showed similar findings on hematoxylin-eosin staining. There were nests of pleomorphic basaloid tumor cells with thickened hyalinized basement membrane material with hyaline globules. Immunohistochemical staining of the liver showed tumor cells positive for CK7, p63, p40, and strong p16 staining. Immunohistochemical staining of the esophagus showed positivity with CK5/6, p63, and p40, and negative p16 staining. The cylindroma-like basaloid squamous cell morphology has been reported in 13% of anal carcinomas and 21% of head and neck tumors and is associated with high-risk HPV. Awareness of this unique morphology is important for determining the primary malignancy in cases of metastasis (case 1) and unusual sites (case 2), as only 100 cases of the esophagus with this morphology have been reported. A better understanding of this genotype-phenotype relationship may assist with correct classification, treatment, and prognosis.

Primary Squamous Cell Carcinoma of the Pancreas With Liver Metastasis: A Case Report and Literature Review

(Poster No. 50)

Fnu Sandeep, MD ([email protected]); Oluwole Odujoko, MD; Erdembileg Chuluunerdene, MS; Samuel Barasch, MD. Department of Pathology, Danbury Hospital, Danbury, Connecticut.

Most pancreatic malignancies are of primary origin. Although the pancreas lacks squamous epithelium, there can be metaplastic squamous epithelium in some pathologic settings. Endoscopic ultrasound–guided, fine-needle aspiration specimens obtained from chronic inflammatory conditions leading to metaplastic ductal epithelium, lymphoepithelial cysts, and adenosquamous carcinoma have shown foci of squamous epithelium. However, primary squamous cell carcinoma (SCCP) of pancreas is a rarely described malignancy, comprising 0.5%–5% of primary pancreatic malignancies. This wide range of incidences has been attributed to inaccurate categorization of adenosquamous carcinoma as SCCP in some cases, based on small tissue samples. In essence, this diagnosis of exclusion requires ruling out adenosquamous carcinoma and metastatic squamous carcinoma from other primary sites. Primary squamous cell carcinoma is considered an aggressive subtype of pancreatic carcinoma with a poor prognosis. Approximately 95% of patients present with advanced-stage disease including stage 3 and stage 4 disease at the initial presentation, with involvement of regional lymph nodes (unknown), liver (32%), lung (6%), and bone (unknown). We present a case of a 62-year-old man with a SCCP with liver metastasis. The subsequent investigation, treatment, outcome, and review of the literature are described. To the best of our knowledge, this is the first case we are reporting from our center.

Clinicopathologic Characterization and Molecular Alterations of Early-Onset Colorectal Cancer

(Poster No. 51)

Yan Feng, MD, PhD ([email protected]); Hongxing Gui, MD, PhD. Department of Pathology, Pennsylvania Hospital, Philadelphia.

Context: The overall incidence of and mortality from colorectal cancer (CRC) have decreased in recent years, while CRC in younger patients has trended higher. In this study, we aim to characterize early-onset CRC (age <45 years, EOCRC) versus late-onset (age >45 years, LOCRC), both clinicopathologically and molecularly.

Design: CRC patients were identified from our institutional database since 2012. The clinicopathologic characteristics were compared. Targeted sequencing and cBioportal database analysis were performed.

Results: We identified 55 EOCRC and 202 LOCRC patients (Table). Most EOCRC patients (78.2%) developed cancer in the left side, significantly higher than in the LOCRC group (50.5%, P < .001). EOCRC group had more G1 (27.3%) but less G2 (54.5%) than the LOCRC group (2.4% G1 and 76.8% G2, P < .001). EOCRC group had more T4 cases (16.3%) and fewer T3 cases (58.2%) than the LOCRC group (6.5% T4 and 65.3% T3, P < .01). Similarly, EOCRC group was associated with increased lymphatic metastasis (29.1% N2) compared to the LOCRC group (13.3% N2, P < .05). Consistently, EOCRC group had more remote metastasis at first diagnosis than the LOCRC group (20% versus 7.9%, P < .01). Finally, there was no significant difference in overall survival, but EOCRC group had statistically shorter disease-free survival than the LOCRC group (46.1 months versus 50.0 months, P < .001). Molecular analysis demonstrated rare genetic alterations in EOCRC in addition to APC, KRAS, and BRAF mutations.

Conclusions: Our data reveal that EOCRC is prone to be lower grade in the left colon, but with advanced stages. Molecular findings further support its uniqueness compared to the late-onset group.

Plexiform Fibromyxoma Misdiagnosed as Leiomyoma

(Poster No. 52)

Hetal Gujaria, MD ([email protected]); Mary Wong, MD. Department of Pathology, Oregon Health and Science University, Portland.

Plexiform fibromyxoma is a rare benign mesenchymal tumor with a predilection for the gastric antrum. It presents in adults with abdominal pain, hematemesis, ulceration, and anemia and has no sex predilection. We present a case of a 64-year-old woman, who upon endoscopy was found to have a 30-mm subepithelial mass arising from the muscularis propria. There was positive Doppler flow within the mass. Fine-needle aspiration showed a low-grade spindle cell neoplasm positive for smooth muscle actin on immunohistochemistry, consistent with leiomyoma. Laparoscopic partial gastrectomy was performed owing to the difficulty in excising the mass in toto. Grossly multiple tan-white fragments were received with whorled cut surfaces. Microscopy showed an unencapsulated, multinodular mass with plexiform architecture composed of bland spindle cells (Figure 1.52, A and B), and inconspicuous nucleoli, dissecting through the bundles of muscularis propria. The nodules were separated by prominent myxohyaline stroma. Mitotic figures were rare to absent. The spindle cells showed partial immunoreactivity for smooth muscle actin (Figure 1.52, C) and caldesmon (Figure 1.52, D), and were negative for SOX10, S100, CD117, DOG1, CKCKT, CAM 5.2, and ALK1, consistent with the diagnosis. Although gastrointestinal stromal tumors (GISTs) and leiomyomas are more commonly observed mesenchymal tumors in the antrum, they rarely have myxoid stroma. Leiomyomas are rarely multinodular, and myxoid GISTs are well circumscribed rather than plexiform. Thus, though rare, it is worthwhile to consider this benign tumor in the differential diagnosis at this location, as it follows a much less aggressive course than GIST and does not recur.

An Interesting Case of a Rare Variant of Intrahepatic Cholangiocarcinoma With Unique Features

(Poster No. 53)

Maria Kamal, MD ([email protected]); Wenyi Luo, MD, PhD. Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City.

Cholangiocarcinoma is a challenging diagnosis because of highly variable morphology and nonspecific immunohistochemical profile. We report a rare variant of intrahepatic cholangiocarcinoma with unique features. A 63-year-old woman presented with abdominal pain. CT of abdomen/pelvis revealed a right posterior lobe liver mass. The patient underwent a right posterior hepatectomy. Grossly, a well-defined pale-tan mass (11.5×10.3×6.0 cm) was identified. Microscopy showed a well-circumscribed tumor composed of monotonous columnar cells forming glands and acini with proteinaceous luminal secretions (Figure 1.53, A) in a noncirrhotic liver background. No cytoplasmic or luminal mucin was identified. Albumin in situ hybridization was positive, consistent with intrahepatic primary. No definitive hepatocellular carcinoma component was identified. Cytokeratin 7 and cytokeratin 19 positivity supported biliary differentiation. The tumor was diffusely inhibin positive and patchily synaptophysin positive (Figure 1.53, B and C). Focal acinar differentiation was demonstrated by trypsin positivity (Figure 1.53, D), not reported before. Extensive immunohistochemical workup excluded other liver primary tumors and possible metastasis. These findings are consistent with solid-tubulocystic variant of intrahepatic cholangiocarcinoma, a rare tumor seen in young females, characterized by positivity of inhibin and neuroendocrine markers. Fewer than 10 cases have been reported so far. This is a potentially aggressive tumor with misleadingly low-grade morphology, and accurate diagnosis is important to avoid undertreatment. Comparative genomic sequencing in our case and targeted next-generation sequencing in previously published cases did not identify recurrent chromosomal or genomic alteration. However, peculiar morphology, strong inhibin expression, and female preference are suggestive of specific molecular alteration. More detailed molecular studies are being conducted to further characterize this tumor.

Unusual Presentation of Metastatic Hepatocellular Carcinoma to the Shoulder

(Poster No. 54)

Juhi D. Mahadik, MD1 ([email protected]); Ryan Fernandez, MD2; Nisha Ramani, MD.1 Departments of 1Pathology and Immunology and 2Diagnostic Radiology, Baylor College of Medicine, Houston, Texas.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Its clinical presentation can be highly variable, and metastases to uncommon sites have been reported. However, HCC presenting as a large metastasis in the absence of a liver mass is rare. A 56-year-old man with a history of hepatitis C presented with back pain for a year. He also noticed swelling on his right shoulder and numbness of his lower extremities. Magnetic resonance imaging revealed a large heterogeneous mass (14.7 × 12 × 9.4 cm) in the right shoulder (Figure 1.54, A). Biopsy of the shoulder mass showed metastatic well-differentiated HCC (Figure 1.54, B). Tumor cells were positive for arginase (Figure 1.54, C), HepPar-1, and cytokeratin AE1/AE3 (focal), while negative for glypican-3, AFP, S100, synaptophysin, CK7, and CK20, confirming the morphologic impression of HCC. Subsequently, abdominal magnetic resonance imaging was performed, which did not reveal any hepatic masses/lesions (Figure 1.54, D). Serum α-fetoprotein level was normal. The patient also had large lumbar spinal metastasis and is currently receiving palliative radiation to his shoulder and spine. This case highlights an intriguing presentation of HCC as a shoulder mass in the absence of a liver primary tumor or elevated biomarkers. Metastatic HCC should be considered in the differential diagnosis of large masses at unusual sites, particularly in patients with hepatitis C, even when a primary tumor is not identified on imaging.

A Rare Case of Extranodal Rosai-Dorfman Disease Presenting as a Gallbladder Mass

(Poster No. 55)

Jamie J. Shah, DO ([email protected]); Cynthia N. Giraldo, MD; Allen R. Holmes, MD; Thomas A. Adams, MD. Department of Pathology and Laboratory Medicine, San Antonio Uniformed Services Health Education Consortium, San Antonio, Texas.

Rosai-Dorfman disease (RDD) is a rare form of nonclonal histiocytosis characterized by an expansion of non–Langerhans cell histiocytes and emperipolesis. RDD typically presents in adolescents and is commonly found in cervical lymph nodes. However, extranodal involvement is not uncommon and this may mimic other neoplasms or reactive disease. Very limited cases of extranodal RDD to the gallbladder have been reported in the literature. We present a case of a 37-year-old woman with a past medical history of extranodal RDD to her breast. She presented to the emergency department with a 10-day history of right upper quadrant abdominal pain. She was noted to have cholelithiasis and a mildly dilated bile duct on imaging and subsequently underwent a cholecystectomy. A masslike lesion involving the gallbladder body and proximal fundus was identified, measuring 3.8 cm in maximum dimension. On histology, the mass showed stroma with an abundant mixed inflammatory infiltrate and histiocytes. Foci of histiocytes demonstrated emperipolesis (Figure 1.55, A and B) and were highlighted with S100 (Figure 1.55, C), CD163 (Figure 1.55, D), and CD68 immunohistochemical stains. These findings were consistent with a diagnosis of extranodal RDD to the gallbladder. This is an unusual presentation of extranodal RDD occurring in the absence of nodal disease. Although the prognosis of RDD is generally favorable, extranodal disease may have a worse prognosis. Complications of extranodal disease are typically due to mass effect or parenchymal involvement. Extranodal RDD to the gallbladder represents an extremely rare condition and should be included in the differential diagnosis of gallbladder neoplasms.

Incidental Small and Large Cell Neuroendocrine Carcinoma of the Gallbladder With Associated Intracholecystic Papillary Neoplasm

(Poster No. 56)

Jack Harbert, MD ([email protected]); Jihuan Chen, MD, PhD; Tracy Dewenter, MD. Department of Pathology, Louisiana State University Health Sciences Center New Orleans.

Gallbladder neuroendocrine carcinomas are rare and aggressive, comprising 4% of gallbladder malignancies with a 5-year survival rate of 20%. Owing to its exceedingly scant presence in the literature, we present a case of a small and large cell neuroendocrine carcinoma of the gallbladder associated with an intracholecystic papillary neoplasm (ICPN). A 65-year-old woman underwent abdominal imaging revealing an incidental gallbladder polyp for which a cholecystectomy was performed. Upon gross examination, a single, white, firm 17-mm fundal polyp was noted with surrounding polyposis (25 × 13 mm). Most of the polyp was composed of sheets of large polygonal cells with ample cytoplasm, prominent nucleoli, moulded nuclei, and focal necrosis (Figure 1.56, A and B). An additional small cell component (~30% of tumor) was identified with traditional features, namely hypercellular organoid growth pattern with hyperchromatic, salt-and-pepper nuclei. Associated polyposis showed papillary growths of minimally atypical cuboidal mucosa with focal intestinal metaplasia (Figure 1.56, D). These lesions appear consistent with an ICPN of biliary morphology. Cystic duct lymph node showed lymphovascular invasion without identifiable direct extension. Immunohistochemical studies showed strong positivity for synaptophysin (Figure 1.56, C)with patchy positivity of CD56. Ki-67 proliferative index showed >90% positivity. Associated glandular tissue was positive for CK7, CAM 5.2, and Pan-CK, while malignant tissue was negative. All tissue was negative for chromogranin. A diagnosis of combined poorly differentiated large and small cell neuroendocrine carcinoma was made and subsequent staging radiologic studies were negative. The lesion was staged at pT2aN0, and chemotherapy consisting of cisplatin and etoposide was initiated.

Plasmablastic Lymphoma of Gastrointestinal Tract: A Series of 10 Cases With the Largest Collection of 8 HIV-Negative Cases

(Poster No. 57)

Zhiyan Fu, MD1 ([email protected]); Nushani L. Jayaratne, MD3; Gregory Y. Lauwers, MD1; Kun Jiang, MD, PhD1; Lugen Chen, MD4; Ling Zhang, MD, PhD.2 Departments of 1Pathology and 2Hematopathology and Laboratory Medicine, Moffitt Cancer Center, Tampa, Florida; 3Department of Pathology, University of South Florida Morsani College of Medicine, Tampa; 4Department of Pathology, Tampa General Hospital, Tampa, Florida.

Context: Plasmablastic lymphoma (PBL) is an uncommon but aggressive subtype of large B-cell lymphoma. The prototype is mainly found in the oral cavity, and frequently associated with HIV infection. Primary gastrointestinal PBL (GI PBL) is rare. Its unique immunophenotypic profile may be misleading, hampering an accurate diagnosis and proper clinical management. Our aim is to retrospectively analyze the clinicopathologic findings of GI PBL.

Design: GI PBL cases from 2008 to 2021 at our institution were searched. Clinical, pathologic, and laboratory data, and clinical course were reviewed.

Results: There were 10 patients confirmed with GI PBL (median age, 61 years; range, 39–92 years; 9 males). Patient demographic data and clinicopathologic features are summarized in the Table. The most common involved location was sigmoid colon (5, 50%). Sixty percent of patients showed isolated GI tract involvement. Two HIV-positive and 4 patients with chronic inflammatory and/or immunocompromised status (2 irritable bowel syndromes, 1 Crohn disease on treatment, and 1 status post kidney transplant) were identified. The mean follow-up duration for available patients was 18.9 months (range, 1.3–33 months). At the end of the follow-up, 62.5% (5 of 8) of patients showed complete remission (CR) after chemotherapy.

Conclusions: GI PBL is rare and a heterogeneous disorder in terms of etiology and clinical course. Sigmoid colon is the most common and 60% were GI isolated site. Patients were often associated with immunosuppression. It seems to have a fair response to chemotherapy with or without resection. Awareness and recognition of this rare entity is warranted to reach a correct diagnosis and improve patient care.

Lymphoepithelial Cyst of Pancreas: Incidental Finding of a Benign but Rare Pancreatic Cyst in a 64-Year-Old Woman

(Poster No. 58)

Raghunath Ramanarasimhaiah, MD ([email protected]); Kiran, MD; Shahbaz Khan, MD; Kokila Mody, MD. Department of Pathology and Laboratory Medicine, Staten Island University Hospital, Staten Island, New York.

Lymphoepithelial cyst of pancreas (LECP) is a benign and rare cystic lesion of pancreas. LECP is often an incidental finding during imaging. It can be confused with other cystic neoplastic lesions of pancreas. Herein, we present a case of a 64-year-old woman with multiple comorbidities who presented with abdominal pain. CT scan of the abdomen and pelvis revealed bilateral adnexal cystic lesions and an incidental 3.6-cm hypodense lesion in the tail of the pancreas (Figure 1.58, A). Serum levels of carcinoembryonic antigen (CEA) and cancer antigen 125 (CA 125) were increased (5.8 ng/mL and 211 U/mL, respectively) but CA 19-9 was within normal range. The patient underwent total abdominal hysterectomy with bilateral salpingooophorectomy for adnexal lesions and distal subtotal pancreatectomy with splenectomy for pancreatic lesion. Gross examination of the specimen revealed a unilocular cystic lesion measuring 3.8 cm, containing keratinous material. The cystic lesion was attached to the tail of the pancreas at its caudal surface but was not attached to the spleen (Figure 1.58, B). Histologic examination revealed a thin-walled cyst filled with keratinous material in the pancreatic tail near the splenic hilum (Figure 1.58, C and D). The cystic wall was formed by benign, mature, keratinizing squamous epithelium and surrounded by a cuff of benign mature lymphoid cells with few germinal centers. LECPs are benign and can be managed conservatively. We recommend that radiologic, serologic, and cytologic characteristics of LECP be reviewed carefully preoperatively to avoid more invasive treatment approaches like surgery.

Single-Institution Analysis of the Utility of Histopathologic Evaluation of Appendectomy Specimens

(Poster No. 59)

Varsha Prakash, MD ([email protected]); Charles E. Middleton, MD; Neha Varshney, MD. Department of Pathology, University of Mississippi Medical Center, Jackson.

Context: Appendectomy is one of the most performed surgical procedures worldwide. Although mostly mundane, the pathologic examination of the appendix may reveal an unexpected diagnosis. Our study aims to reveal the importance of routine histopathologic examination of appendectomy specimens by highlighting the unusual findings.

Design: A retrospective data review of all appendectomy procedures performed at our institution from September 2018 to September 2021 was performed. The surgical pathology report for each case was reviewed from our electronic medical record, and the findings were documented.

Results: A total of 793 appendectomy specimens were examined during the study period. Of the total specimens, acute appendicitis (663 cases, 83.6%) was the most common diagnosis, followed by no diagnostic alterations (75 cases, 9.5%) and mild lymphoid hyperplasia (32 cases, 4%). Unusual pathologic findings were identified in 23 cases (3%), which included sessile serrated lesion (4 cases), low-grade appendiceal mucinous neoplasm (4 cases), metastatic serous carcinoma (4 cases), endometriosis (2 cases), neuroendocrine carcinoma (2 cases), Enterobius vermicularis infection (2 cases), Burkitt lymphoma (1 case; Figure 1.59, A and B), metastatic alveolar rhabdomyosarcoma (1 case; Figure 1.59, C and D), adenocarcinoma with mucinous features (1 case), mesothelial inclusion cyst (1 case), and noncaseating granuloma (1 case).

Conclusions: The routine microscopic evaluation of appendectomy specimens remains worthwhile, especially when there is a suspicion of malignancy. Additionally, intraoperative consultation should be used for identifying any unknown pathologic process. Identifying the unusual findings that mimic acute appendicitis will undoubtedly impact clinical practice.

The Pathology of Endoscopic Mucosal Resection Specimens Related to Injectable Submucosa Lifting Agents: An Institutional Experience

(Poster No. 60)

Mohana Sopanahalli Narasimhamurthy, MBBS ([email protected]); Yan Feng, MD, PhD; Hongxing Gui, MD, PhD; Franz Fogt, MD. Department of Pathology, Pennsylvania Hospital, Philadelphia.

Context: Endoscopic mucosal resection is an important advance in therapeutic endoscopy, pioneered by Japanese endoscopists for removing flat sessile polyps. The technique involves expanding the submucosal space by injecting a solution to create optimal elevation to resect the lesion. Recently, gastrointestinal endoscopists started to use this technique at our institution. This study aims to review the pathologic changes produced by these injectable lifting agents.

Design: Twenty-seven endoscopic submucosal resection specimens and 1 interval surgical specimen with a history of lifting agent injection were included. Patient demographics and endoscopy reports were retrieved, and histologic slides were reviewed.

Results: Twenty-seven endoscopic submucosal resection specimens showed pale to dense amorphous eosinophilic material with giant cells resembling amyloid (Figure 1.60, A through D). Congo red was negative. One interval surgical specimen showed pale mucoid material with a cluster of pink hyalinized material associated with giant cell reaction with transmural extension. Congo red, mucicarmine, and AE1/3, CDX-2, and CK20 stains were negative.

Conclusions: Endoscopic submucosal resection uses injectable submucosal lifting agents to separate the lesion from the underlying connective tissue and thus mitigate perforation and bleeding. Several solutions have been tried, including a submucosal injectable gel marketed as ORISE (Boston Scientific) and methylene blue. These injectable lifting agents create some degree of artifact that may be mistaken for other pathologies like amyloid and mucin with a variable amount of giant cell reaction on routine H&E sections. Familiarity with these artifacts in the appropriate clinical context will help to avoid misinterpretation and unnecessary additional studies.

Helicobacter pylori–Associated Gastric Hyperplastic Polyposis With Synchronous Gastric Adenocarcinomas and Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue in a Single Gastrectomy Specimen: Case Report With Literature Review

(Poster No. 61)

Liz Yang, MD ([email protected]); Fernanda Da Silva Lameira, MD; Wenjing Qiu, MD, PhD; Rachna Jetly, MD, MPH. Department of Pathology, Louisiana State University Health Sciences Center New Orleans.

Synchronous gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (ENMZL) and carcinoma (GC) are rare, even though Helicobacter pylori is a risk for both. Endoscopic distinction and sampling in a background of inflammation may be difficult and diagnosis more likely occurs on gastrectomy, a possible reason for the low reported incidence rates. We present a case of an incidental ENMZL in a gastrectomy for GC and multiple polyps. A 68-year-old man with constipation, abdominal distention, and polyposis on gastric endoscopy had a few polypectomies. A 3.2-cm gastric-body adenoma with tubular GC prompted a partial gastrectomy demonstrating numerous hyperplastic polyps (0.2–3.2 cm) (Figure 1.61, A) with intestinal metaplasia; an antral poorly differentiated tubular GC (Figure 1.61, B) invading the submucosa and metastatic to regional lymph nodes; multifocal ENMZL infiltrates, CD5/CD10/CD20+/CD43+, with clonal immunoglobulin heavy-chain gene rearrangement (Figure 1.61, C and D); and Helicobacter-associated chronic active gastritis. In one study, incidence of synchronous GC and gastric lymphoma was 0.08%. Another retrospective study reports synchronous tumors in 8.3% of GCs and 20.0% of ENMZL cases. ENMZL preceding GC is postulated, since a high proportion of GCs are early stage in synchronous tumors. Metachronous GC risk after a new ENZML diagnosis is increased per long-term US population-based and Dutch histopathology registry–based studies (4.3 and 6 times, respectively). Latency periods vary from 6 months to 5 years. Helicobacter eradication can cause ENMZL regression; however, GC risk remains increased and ENZML-targeted chemotherapies confer additional risk. Long-term follow-up guidelines to detect early GC in ENZML are conflicting and require consensus.

Strongyloides stercoralis Infection Mimicking Inflammatory Bowel Disease in a Patient Status Post Steroid Treatment for COVID-19 Infection

(Poster No. 62)

Sepideh Besharati, MD ([email protected]); Michael J. Lee, MD; Huaibin M. Ko, MD. Department of Pathology, Columbia University Medical Center, New York, New York.

Strongyloides stercoralis is a parasitic nematode estimated to infect 30–100 million people worldwide; it is often asymptomatic in immunocompetent people. Disseminated infection typically affects immunocompromised patients and may rarely present with diffuse colitis, mimicking inflammatory bowel disease (IBD). We report a case of a 46-year-old woman from the Dominican Republic without prior history of immunodeficiency who was admitted to the emergency department with abdominal pain and dark stool. Laboratory results showed anemia, leukocytosis, and positive COVID-19 PCR test result. Imaging showed pancolitis and diffuse perihilar ground glass opacities in the lungs. She received oxygen therapy, antibiotics, and dexamethasone for COVID-19 infection. Initial sigmoidoscopy revealed mild inflammation from sigmoid to distal transverse colon. However, her clinical course worsened with rapid decline in mental status, abdominal distention and tenderness, and shock. She was intubated and an emergency total colectomy was performed in the setting of toxic megacolon. Gross examination of the surgical specimen revealed diffuse ileocolitis. On histology, innumerable nematodes were identified within ileal and colonic crypts, submucosa, and within submucosal and subserosal lymphatics, consistent with disseminated Strongyloides stercoralis ileocolitis (Figure 1.62, A and B). Nematodes with associated granulomatous reaction were identified (Figure 1.62, C). Multiple reactive lymph nodes, some with nematode organisms within lymphatic channels, were seen (Figure 1.62, D). Diffuse Strongyloides ileocolitis may mimic IBD and present after dexamethasone treatment for COVID-19 infection in immunocompetent individuals. Given the current COVID-19 pandemic, the possibility of asymptomatic Strongyloides infection should be considered in patients with travel or migration from endemic areas who require dexamethasone for COVID-19 treatment.

Histopathologic Changes in Liver in a Case of Turner Syndrome With Hypoplastic Left Heart Syndrome

(Poster No. 63)

Macy Cummins, BA1 ([email protected]); Natalie Bhesania, MD2; Neha Varshney, MD.3 1School of Medicine, Departments of 2Pediatric Gastroenterology and 3Pathology, University of Mississippi Medical Center, Jackson.

Turner syndrome (TS) is one of the most frequent inherited diseases in females that results from the total or partial loss of the X chromosome. Clinically, this syndrome is characterized by short stature, dysmorphic features, gonadal dysgenesis, and congenital heart and renal malformations. TS is often associated with hepatic manifestations that could be minimal abnormalities, steatosis, steatohepatitis, or even cirrhosis. Histologic changes include parenchymal nodules with or without intranodular fibrosis, abnormal arteries and ductules, and intrahepatic portal vein changes such as intimal thickening or replacement by fibrous scar containing numerous vessels. Hepatic changes of TS have been associated with vascular disorders of congenital origin and nonalcoholic fatty liver disease. Our case involves liver involvement in a 16-year-old adolescent girl with TS, hypoplastic left heart syndrome (status post Fontan), and recent cholecystectomy due to cholelithiasis. Additionally, ultrasonography determined increased hepatic echogenicity and coarsened echotexture; patent and normal direction of flow was found in hepatic vasculature. The median stiffness of the liver was 9.8 kPa, suggestive of compensated advanced chronic liver disease. At the time of cholecystectomy, the liver was found to be large, nodular, and congested with frank liver fibrosis, precipitating the recommendation for liver biopsy. Microscopic examination of biopsy revealed moderate sinusoidal dilation (Figure 1.63, A), extensive glycogenated nuclei, bile ductular proliferation, patchy arterialization (Figure 1.63, B), and no inflammation, steatosis, or fibrosis. It is unknown if the hepatologic changes in this patient are due to Fontan circulation or TS. Understanding these subtle histologic changes in such syndromes are crucial for optimal patient care.

Pseudomelanosis Duodeni in a Patient With Renal Transplant and Immunosuppression: A New Association

(Poster No. 64)

Imran Ajmal, MD ([email protected]); Hardik Sonani, MD; Neha Varshney, MD. Department of Pathology, University of Mississippi Medical Center, Jackson.

Melanosis coli is a common asymptomatic finding on colonoscopy and histologically characterized by deposition of dark melanin-like pigment (lipofuscin) in colonic macrophages that has been attributed to long-term laxative use. Melanosis in the upper gastrointestinal tract is termed pseudomelanosis. In these pigmented lesions, melanoma is a diagnostic pitfall, and the index of suspicion should be high. We report a case of pseudomelanosis duodeni in a 66-year-old woman with a past medical history of hypertension, heart failure, and status post deceased donor renal transplant caused by diabetic nephropathy, and taking tacrolimus and mycophenolate, who presented with chronic dry cough concerning for gastroesophageal disease. The patient reported no acute complaints, including dysphagia, abdominal pain, hematemesis, hematochezia, and melena. Esophagogastroduodenoscopy was performed and revealed diffuse mucosal changes characterized by dark discoloration and found in the entire duodenum (Figure 1.64, B). Microscopic examination of the duodenal biopsy showed coarse black pigment in the lamina propria of the duodenum with aggregates of pigment-laden macrophages consistent with pseudomelanosis duodeni (Figure 1.64, A). The duodenum was otherwise unremarkable with preserved villous architecture and no intraepithelial lymphocytes. Although the exact etiology, pathogenesis, and clinical significance remains unknown, it has been reportedly associated with the use of certain medications (including hydralazine, thiazide diuretics, furosemide, beta-blockers, and iron supplements), hypertension, chronic renal disease, gastrointestinal hemorrhage, and diabetes mellitus. Pathologists should be aware of this rare entity and its emerging associations to make an accurate diagnosis that would help new studies and better understanding of its diagnostic and prognostic significance.

Pathologic Characterization of Intractable Diarrhea Resulting From Vismodegib Treatment for Basal Cell Nevus Syndrome (Gorlin Syndrome)

(Poster No. 65)

Haneen T. Salah, MD1 ([email protected]); Ashmi Patel, MS2; Remi K. Hamel, MD3; Elizabeth L. Hall, MD3; Suzanne M. Crumley, MD1; Karen L. Woods, MD4; Leonard H. Goldberg, MD.3 Departments of 1Pathology and Genomic Medicine and 2Texas A&M College of Medicine, Houston Methodist Hospital, Houston, Texas; 3Department of Dermatology, Houston Methodist Hospital and DermSurgery Associates, Houston, Texas; 4Department of Gastroenterology, Underwood Center for Digestive Disorders and Houston Methodist Hospital, Houston, Texas.

Basal cell carcinoma (BCC) is the most common type of skin cancer, and most cases are slow growing and effectively treated with surgery, topical, or radiation therapy. However, BCCs can be aggressive and locally advanced (laBCC) or metastatic (mBCC), rendering conventional treatment inadequate. Vismodegib is an FDA-approved systemic hedgehog inhibitor used to treat laBCC and mBCC, including the multiple BCCs found in Gorlin syndrome. Common adverse effects ( 15% incidence) of vismodegib include muscle spasms, alopecia, weight loss, nausea, and diarrhea. Diarrhea is a common adverse effect, with 25% of patients experiencing diarrhea while receiving vismodegib therapy. Clinical studies have outlined the severity and the onset of vismodegib-associated diarrhea; however, pathologic findings have not been previously described. We present a case of a 62-year-old man with Gorlin syndrome and a 10-year history of vismodegib use who experienced intractable diarrhea requiring suspension of vismodegib use. Colonoscopy showed diffuse ileal congestion, colonic mucosa granularity, punctate erosions, and exudate. Biopsies showed active ileitis, villous blunting, diffuse chronic inflammation, crypt architectural distortion, epithelial apoptosis, and crypt abscesses. Temporary suspension of vismodegib resulted in the resolution of the patient's symptoms. In conclusion, vismodegib is an important treatment for patients with Gorlin syndrome. Diarrhea is a frequently encountered adverse event of vismodegib, and physicians should consider vismodegib-induced diarrhea in a patient with no signs of infectious or ischemic etiology. Recognizing these findings in association with vismodegib therapy is also important to prevent misdiagnosis of inflammatory bowel disease.

Prognostic Factors of Pseudomyxoma Peritonei: A Single-Institution Study

(Poster No. 66)

Changzhao Li, MD, PhD1 ([email protected]); Dali Huang, MBBS1; Dongpo Salas, MD1; Ryan Walters, PhD2; Nicholas Dietz, MD.1 Departments of 1Pathology and 2Clinical Research and Public Health, Creighton University, Omaha, Nebraska.

Context: Pseudomyxoma peritonei (PMP) is a rare malignancy characterized by extensive mucinous lesions in the peritoneal cavity, causing significant morbidity and mortality. This study aims to explore the pathologic or molecular prognostic factors for PMP.

Design: Twenty-five cases of PMP were identified from our archives. Parameters including histologic grade, presence of signet ring cells, Ki-67 index, and PTEN expression were analyzed and correlated with disease recurrence/progression, postsurgery survival, and overall survival.

Results: The cases were composed of 60% (n = 15) low-grade and 40% (n = 10) high-grade PMP. Forty percent (n = 10) of patients had signet ring cells either at the time of diagnosis or during the clinical course; 76% (n = 19) had Ki-67 labeling index of at least 20%. For PTEN expression, the median score was 180 (140–200) for cytoplasmic expression and 100 (20–190) for nuclear expression. Statistical analysis identified histologic grade and signet ring cells (Figure 1.66) as significant prognostic factors for postsurgery survival and overall survival. The risk of mortality for high-grade PMP is 7.9 times (P = .02; 95% CI, 1.5–42.2) higher than for low-grade PMP. Seventy percent (n = 7) of patients with signet ring cells died of the disease as compared to 7.1% (n = 1) of patients without signet ring cells (P = .002). The risk of mortality showed a trend decrease of 10% for every 10-point increase of PTEN cytoplasmic score (P = .09; 95% CI, 0.80–1.02). Ki-67 index showed no effects on survival.

Conclusions: Histologic grade and signet ring cells are prognostic factors for PMP. PTEN cytoplasmic score might be a novel prognostic marker in the future pending large-scale study.

Gastrointestinal Stromal Tumor Presenting as Primary Disseminated Peritoneal “Gistomatosis”

(Poster No. 67)

Andreas Kontosis, MD ([email protected]); Thanchanok Chaiprasit, MD; Elnaz Panah, MD; Geoffrey Chen, MS; Xiuxu Chen, MD, PhD; Xianzhong Ding, MD, PhD. Department of Pathology, Loyola University Medical Center, Maywood, Illinois.

Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the digestive tract, can occur anywhere in the GI tract. Infrequently, they can arise outside of the alimentary tract, such as in the omentum or mesentery, and they are named extragastrointestinal GISTs. In 10% of the cases, they are primarily disseminated. We present the case of a 68-year-old man with a past medical history of superficial spreading stage 1A melanoma with complaints of anorexia, fatigue, and weight loss during a period of 2 months. Physical examination revealed palpable nodularity in the right side of the abdomen. CT of the abdomen reported “innumerable” mesenteric and peritoneal nodules, with an overall appearance of extensive abdominal, pelvic, and peritoneal malignancy. Fine-needle aspiration of US-guided biopsies showed polygonal cells, with ample, finely vacuolated cytoplasm. As the patient's condition deteriorated rapidly and the abdomen became distended with signs of colonic ischemia, explorative laparotomy was performed with findings of diffuse implants in the omentum, mesentery (Figure 1.67, A and B), and ischemia of the colon. Histopathology revealed numerous tumor nodules in the omentum, the small bowel, and the colon, confined in the serosa and subserosa with no obvious involvement of smooth muscle (Figure 1.67, C). Tumor cells were diffusely positive for CD117 (Figure 1.67, D) and DOG-1 with retention of SDH-B, which is consistent with peritoneal GIST. The unique feature of this case is primary disseminated peritoneal GIST with numerous solid tumor nodules, which we define as primary peritoneal “gistomatosis.” This rare condition can be clinically misinterpreted as peritoneal carcinomatosis.

Jejunal Solitary Peutz-Jeghers Polyp With Accompanying Neuroendocrine Tumor in an Adult Patient

(Poster No. 68)

Sachie Ikegami, MD, PhD ([email protected]); Jiang Wang, MD, PhD. Department of Pathology and Laboratory Medicine, University of Cincinnati, Ohio.

Hamartomatous polyps of gastrointestinal tract are rare in adults. They can occur sporadically or as a part of hereditary syndromes. We report a case of a solitary Peutz-Jeghers polyp (PjP) accompanied with neuroendocrine tumor (NT) in the small intestine. Our patient was a 57-year-old man who presented to the emergency department owing to abdominal pain and hematochezia. CT scan revealed a small-bowel intussusception with an enhancing nodular lead point. A jejunal mass was visualized by follow-up imaging and was subsequently resected. Grossly, a 3.0 × 2.8 × 2.5-cm white-tan, well-circumscribed, pedunculated polypoid mucosal mass was identified. Histologically, the mass consisted of crypts and villi of varying lengths divided by abnormal arborizing smooth muscle bundles within the lamina propria, which were branched out from the center of the lesion. The histologic features were consistent with PjP. No dysplasia was present. Given an absence of clinical features of polyposis syndromes in this patient and his family, this lesion was considered to be a sporadic solitary PjP. In addition, a 0.6-cm nodule was incidentally found at the edge of the jejunum. It was composed of nests of monotonous round cells that were immunopositive for synaptophysin and chromogranin, and Ki-67 labeled 1% of tumor cells, confirming grade 1 NT. Sporadic PjP is generally considered not to confer an increased risk of malignancy and no associations have been reported between sporadic PjP and NT in the literature; hence, this case signifies the value of further investigation of the relationship between sporadic PjP and NT (Figure 1.68, A through D).

Clinical and Pathologic Correlation of Gastric Amyloidosis: A 10-Year Single-Institute Retrospective Experience

(Poster No. 69)

Swachi Jain, MBBS ([email protected]); Corey Chang, MD; Taisia Vitkovski, DO; Rebecca Thomas, MD; Arvind Rishi, MD. Department of Pathology and Laboratory Medicine, Zucker School of Medicine at Hofstra, Northwell, New Hyde Park, New York.

Context: Subclinical gastric amyloidosis has been reported in up to 8% of patients with systemic amyloidosis. It is frequently not clinically suspected and detected incidentally on biopsy. We report a clinicopathologic correlative series of gastric amyloidosis detected on endoscopic biopsies.

Design: This is a retrospective review of gastric biopsies with amyloidosis performed at a tertiary care institute from 2012 to 2021. Chart review with clinical, histologic, and endoscopic correlation was performed.

Results: Thirteen cases of gastric amyloidosis were identified with age range of 44–85 years and male predominance (5.5:1; Table). Most common symptom was dysphagia followed by early satiety and abdominal pain. Endoscopic findings were available in 11 cases and showed erosions (63.6%), erythema (18.8%), infiltrative lesion (9.1%), and normal mucosa (9.1%). Intragastric distribution was antrum (54%), gastric body (30.7%), and diffuse gastric involvement (15.3%). Additional involved sites were duodenum (57.4%), gastroesophageal junction (28.4%), and colon (14.2%). Extragastrointestinal involvement was identified in 4 cases with heart and kidney being most common, followed by liver, skin, and eye. Mass spectroscopy available in 7 cases showed AL-type amyloid (71%), transthyretin amyloidosis (14.5%), and AA type (14.5%). Clinical follow-up revealed 6 patients had multiple myeloma, of which 50% were diagnosed following the gastric biopsy. Four patients died within 1 year of biopsy with diagnosis of multiple myeloma (n = 2), gastric marginal zone lymphoma (n = 1), and ATTR amyloidosis (n = 1).

Conclusions: Gastric amyloidosis is extremely rare and may be the first detection of an underlying systemic disorder or hematologic malignancy. Endoscopic and clinical findings are frequently nonspecific. Regular clinical follow-up is highly recommended to detect associated plasma cell dyscrasia for early initiation of treatment.

Atypical Spindle Cell/Pleomorphic Lipomatous Tumor of the Rectum

(Poster No. 70)

Javier A. Baena-Del Valle, MD1 ([email protected]); Daniela M. Bertel-Rodriguez, MD2; Rafael García-Duperly, MD3; Mauricio A. Palau-Lá zaro, MD.4 1Department of Pathology and Laboratory Medicine, School of Medicine, Fundacion Santa Fe de Bogota University Hospital, Universidad de Los Andes, Bogota, Colombia; 2Department of Pathology and Laboratory Medicine, Centro Hospitalario Serena Del Mar, Cartagena, Colombia; Departments of 3Surgery and 4Pathology and Laboratory Medicine, Fundacion Santa Fe de Bogota University Hospital, Bogota, Colombia.

Atypical spindle cell/pleomorphic lipomatous tumor (ASCLT) is a recently described neoplasm characterized by lipoma-like appearance but with atypical and spindle cell histologic features. It typically arises in the subcutis and soft tissue, as visceral locations are exceedingly rare. We present a case of a 55-year-old woman who underwent an esophagogastroduodenoscopy and colonoscopy for dyspepsia. A yellow-tan 1.3-cm polypoid submucosal lesion with short and broad-based stalk was found in the rectum. An endoscopic resection was performed. Microscopy showed a predominantly well-differentiated adipocytic component with a smaller proportion of lipoblasts, and pleomorphic and multinucleated cells in a fibrous matrix (Figure 1.70, A through C). No necrosis or mitosis was identified. Tumor cells were positive for CD34 (Figure 1.70, D) and S100, and negative for MDM2 and CDK4. The Ki-67 proliferation rate was <5%. ASCLTs mostly occur in middle-aged adults with a slight male preference and a variable size (up to 28 cm). They have an indolent behavior with no or very low rate of local recurrence, and no risk for dedifferentiation or metastasis. To avoid aggressive surgical resections, we must always exclude atypical lipomatous tumor/well-differentiated liposarcoma, pleomorphic liposarcoma, and low-grade dedifferentiated liposarcoma. Immunohistochemistry helps in this situation, since even though weak and focal expression of MDM2 and CDK4 may be seen, it does not occur in combination. Also, loss of Rb expression is frequently seen (79%). To our knowledge, this is the first report of an ASCLT presenting in the colorectum. Only 3 visceral cases have been previously described (trachea/larynx, stomach, and appendix).

Congenital Loss of Serine Peptidase Inhibitor, Kunitz Type 2 (SPINT2) Presenting With Primary Immune Deficiency and Infantile Indeterminate Colitis Concerning for Early Inflammatory Bowel Disease

(Poster No. 71)

John Daines, BS ([email protected]); Mai He, MD, PhD. Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, Missouri.

A well-documented feature of inflammatory bowel disease (IBD) is impaired gut sodium transport. When intestinal sodium absorption is inhibited, dysbiosis of the gut microbiome is thought to occur, precipitating an inappropriate mucosal immune response. It is not known whether this impaired sodium absorption is a byproduct or a possible upstream agent of IBD pathogenesis. Congenital absence of serine peptidase inhibitor, Kunitz type 2 (SPINT2) causes congenital sodium diarrhea, presenting as chronic diarrhea with high sodium content and syndromic features. Histologically, this presents with tufting enteropathy. Inactivation of SPINT2 downregulates intestinal epithelial sodium channel activity. A nonsyndromic infant presented at 6 months of age with chronic, bloody diarrhea and new-onset respiratory distress. Workup revealed Pneumocystis jirovecii pneumonia, low B-cell counts, undetectable IgG, IgE, IgA, and very low IgM levels. Results of gastrointestinal workup for infectious etiologies were negative. Endoscopy showed vesicles and erythematous, ulcerated mucosa in the colon (Figure 1.71, A and B). Biopsy revealed active colitis with cryptitis, crypt abscesses, and no tufting enteropathy (Figure 1.71, C and D). Full exome sequencing revealed a heterozygous SPINT2 startloss mutation (c.3G>A) along with several variants of undetermined clinical significance in C2, KMT2D, NFKB2, POLE, RORC, TCF3, and TCN2. The cause of the infant's immunodeficiency is currently unknown. Prasad and Visweswariah proposed that impaired intestinal sodium transport alters the luminal ionic milieu, causing dysbiosis of the microbiome and an aberrant gut immune response. We report a case supportive of their hypothesis with evidence of infantile colitis concerning for early-onset IBD in the setting of SPINT2 loss of function.

Chronic Ulcerative Pancolitis Associated With Partial DiGeorge Syndrome

(Poster No. 72)

Thanchanok Chaiprasit, MD ([email protected]); Andreas Kontosis, MD; Elnaz Panah, MD; Geoffrey Chen, MS; Xiuxu Chen, MD, PhD; Xianzhong Ding, MD, PhD. Department of Pathology, Loyola University Medical Center, Maywood, Illinois.

Classic DiGeorge syndrome caused by a microdeletion in chromosome 22q is characterized by multisystem abnormalities including profound immunodeficiency. A striking histologic finding is a marked reduction/absence of lymphocytes and plasma cells in the gastrointestinal tract with frequent association of infections. In contrast, patients with partial DiGeorge anomaly are only mildly immunocompromised owing to thymic hypoplasia, and autoimmune diseases might be seen as a major clinical presentation. Our case involves a 20-year-old woman with partial DiGeorge syndrome who presented with a history of intermittent foulsmelling diarrhea, hematochezia, abdominal pain, weight loss, and persistent oral sores. Her fecal calprotectin was markedly elevated (4630 μg/mg). Her serum immunoglobulin was low owing to partial DiGeorge syndrome. CT imaging revealed colonic wall thickening, predominantly in the transverse, descending, and sigmoid colon and mesenteric lymphadenopathy. Colonic biopsies exhibited active chronic diffuse pancolitis featuring cryptitis, crypt abscesses, basal lymphoplasmacytosis, and crypt architecture disarray, which is consistent with ulcerative colitis. The patient's clinical symptoms improved on mesalamine therapy. This case nicely illustrates an early onset of chronic ulcerative pancolitis due to partial DiGeorge syndrome–related immune dysfunction. Although DiGeorge syndrome has a broad clinical presentation, including a myriad of gastrointestinal manifestations, inflammatory bowel diseases have not been commonly associated as one of them. It is crucial to maintain a high index of suspicion for a prompt and accurate diagnosis.

Rare Colonic Spindle Cell Tumors in a Pediatric Solid Organ Transplant Patient

(Poster No. 73)

Mine M. Yilmaz, MD ([email protected]); Huaibin M. Ko, MD. Department of Pathology, Columbia University, New York, New York.

Epstein-Barr virus–associated smooth muscle tumors (EBV-SMTs) are a rare entity occurring predominantly in immunocompromised patients, mostly in the setting of solid organ transplant or HIV. Histologically, EBV-SMTs are well-differentiated smooth muscle tumors with little atypia and lowmitotic activity, resembling leiomyomas. In this case study, we discuss the case of a 4-year-old girl with anomalous left coronary artery from the pulmonary artery (ALCAPA) status post heart transplant at 7 months of age who presented with abdominal pain and diarrhea and was found to have multiple scattered polypoid lesions in the colon (Figure 1.73, A). Biopsies of the polyps showed fragments of colonic mucosa with spindle cell tumor involving mucosa and submucosa (Figure 1.73, B). Immunohistochemical studies revealed the tumor to be positive for SMA, SMMS-1 (Figure 1.73, D), and caldesmon. Epstein-Barr–encoded RNA in situ hybridization (EBER-ISH; Figure 1.73, C) was strongly positive, confirming the diagnosis of EBV-SMT. She was treated with rituximab (given significant EBV viremia), and tacrolimus monotherapy was maintained with a goal of 3–5 ng/mL. Resolution of the abdominal pain and diarrhea was achieved, and the patient is now undergoing surveillance. EBV-SMT is an uncommon, underrecognized but distinct clinicopathologic entity that occurs in the setting of immunosuppression. In the pediatric population, EBV-SMT has been reported to occur in the brain, lung, liver, spleen, adrenal gland, lymph nodes, soft tissue, and extremities. Multiple scattered polypoid lesions in the colon are an atypical presentation. Hence, regardless of the location and age, a smooth muscle lesion in an immunocompromised patient should prompt consideration for EBV-SMT, and EBER-ISH should be performed.

Collagenous Gastritis in the Pediatric Population: A Single-Institution Experience

(Poster No. 74)

Jeffery Jean, MD1 ([email protected]); Meifang Wu, MD2; Christopher LePhong, DO3; Moe Takeda, MD3; Yinan Fu, MD4; Shengmei Zhou, MD3; Larry Wang, MD3; Ali Nael, MD3; Nick M. Shillingford, MD.3 1Department of Pathology and Laboratory Medicine, LAC+USC Medical Center, Los Angeles, California; 2Department of Pathology and Laboratory Medicine, Harbor-UCLA Medical Center, Los Angeles, California; Departments of 3Pathology and Laboratory Medicine and 4Gastroenterology, Children's Hospital Los Angeles, California.

Context: Collagenous gastritis (CG), an extremely rare disorder in children, is characterized by gastric mucosa with subepithelial collagenous bands and inflammation. Two phenotypes have been described: adult-onset CG, which is associated with collagenous colitis (CC), chronic diarrhea, and weight loss; and pediatric-onset CG (POCG), which usually presents with abdominal pain and iron-deficiency anemia. Prior studies showed that the colon is seldom involved in POCG.

Design: We performed a retrospective review of our patients diagnosed with CG between 2010 and 2022. Information on demographics, clinical characteristics, laboratory results, endoscopic findings, and histopathologic features were analyzed.

Results: Seven patients were diagnosed with CG during the period. Four (57%) were female. Most (6, 86%) were Hispanic. Five patients (71%) presented with abdominal pain. Six (86%) had a history of irondeficiency anemia. Mucosal erythema and nodularity were seen in 6 of 7 (86%) by endoscopy. Microscopically, all gastric biopsies showed prominent subepithelial collagenous bands, >10 μm (Figure 1.74, A) highlighted with Masson trichrome (Figure 1.74, B). Two biopsies (29%) also showed chronic active gastritis, while 3 (43%) showed increased eosinophils (Figure 1.74, C). Two of the 4 patients with colonoscopies had concomitant CC (Figure 1.74, D). Three patients (43%) did not have coloscopies.

Conclusions: In conclusion, while rare, CG is an important differential diagnosis in children with abdominal pain and anemia. Furthermore, contrary to earlier reports, a subset of POCG is associated with collagenous colitis, and colonic biopsies may be warranted. Additional studies are necessary to determine whether there is an ethnic predisposition given the prevalence of Hispanic patients in our cohort.

Biliary Adenofibroma of the Liver With High-Grade Dysplasia and Progression to Invasive Adenocarcinoma

(Poster No. 75)

Marcela Mejia-Arango, MD ([email protected]); Johanna Alvarez-Figueroa, MD; Rocio Lopez-Panqueva, MD. Department of Pathology and Laboratories, Fundación Santa Fe de Bogotá–Universidad de los Andes, Bogotá, Colombia.

Biliary adenofibroma is an unusual liver tumor. Malignant transformation is rare, and to our knowledge, fewer than 25 cases have been reported in the literature. We present a case of an 83-year-old man who underwent laparoscopic hepatic resection after a CT scan showed an incidental irregular mass localized in segments II–III of the liver, predominantly multicystic, and subcapsular. Clinically, the lesion was suspected to be benign. The specimen was received for frozen section. Grossly the tumor was a subcapsular, well-defined, unencapsulated, predominantly microcystic, white-tan mass measuring 3.5 cm in diameter (Figure 1.75, A). Two fragments were submitted for frozen section and an intraoperative diagnosis of an adenomatous lesion with at least high-grade dysplasia was rendered. The lesion was submitted in total, and histology showed a mass composed of multiple glandular structures of different sizes, some with cystic change, and others with a more complex architecture, embedded in an abundant fibrotic stroma (Figure 1.75, B). The epithelial lining was composed of a simple layer of cubical to low columnar, nonmucinous cells, with no or little atypia in most of the lesion, but in multiple foci there was a progression of atypia from low-grade dysplasia to high-grade dysplasia (Figure 1.75, C) and foci of invasive adenocarcinoma up to 5 mm in diameter (Figure 1.75, D). The diagnosis of this unusual tumor is a challenge, especially upon frozen section, and must be considered in the differential diagnosis of primary lesions of the liver. Although malignant transformation is unusual, it must be assessed in every case.

Is the Mutational Landscape of Gastric Adenocarcinoma Distinct in the Setting of Helicobacter pylori Infection?

(Poster No. 76)

Caitlyn J. Smith, BS ([email protected]); Deepthi S. Rao, MD, MS. Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia.

Context:Helicobacter pylori is a gastric pathogen that colonizes approximately 50% of the world's population. Infection with H pylori is the most substantial known risk factor for gastric cancer, yet its impact on driver mutations in gastric adenocarcinoma (GA) is largely unknown. This study aims to investigate the multifactorial role of H pylori on driver mutations, survival outcomes, and family history in patients with GA.

Design: Using the cBioPortal platform and systematic bioinformatical analysis of The Cancer Genome Atlas (TCGA) Firehouse Legacy data for stomach adenocarcinoma, 188 GA patients with H pylori testing were included in this study. Of these, 168 and 20 were H pylori–negative and H pylori–positive GA patients, respectively.

Results: The mutational landscape of H pylori–associated GA was distinct with statistically significant alterations in PCCA, SELE, PON1, SCNN1D, MCF2L, TRIM42, ATAD3C, FOXP2, GHRH, and GORAB driver mutation frequency (Figure 1.76). Further, the median overall survival for H pylori–positive GA patients was 42.5 months (95% CI, 22.17–NA) compared to 57.39 months (95% CI, 35.97–NA) for H pylori–negative GA patients. Additionally, a positive family history of stomach cancer was noted in 70.59% of H pylori–negative patients compared to 29.4% of H pylori–positive patients (P = .02).

Conclusions: The findings in this study highlight the complex multifactorial role of H pylori infection in GA. Further studies are essential for understanding the molecular and pathophysiologic impact of H pylori infection on functions of key genes that exert carcinogenic potential.

Metastatic Renal Cell Carcinoma Presenting as Gastric Ulceration: Case Series

(Poster No. 77)

Caitlyn J. Smith, BS ([email protected]); Deepthi S. Rao, MD, MS. Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia.

Context: Renal cell carcinoma (RCC) accounts for approximately 3% of all adult malignancies. RCC has a propensity to metastasize along the hematogenous route. About 25% of patients with RCC have distant metastases at presentation. True gastrointestinal metastases, specifically to the gastric wall, have been rarely observed.

Design: A retrospective review of patient records between 2000 and 2020 was performed. After identifying cases, further investigation was performed to evaluate macroscopic findings, duration between initial diagnosis of primary and detection of gastric metastasis, tumor variant, tumor size, Fuhrman grade, capsular invasion, and margin status.

Results: Our investigation identified 4 RCC patients with gastric metastasis. M:F ratio was 2:2. The mean age was 58.3 years (range, 45–70 years). Remarkably, all 4 cases were clear cell variant of RCC and presented with gastric ulceration (Figure 1.77, A through C). The average time between initial diagnosis of RCC and gastric metastasis was 46.5 months. Three patients had previously undergone radical nephrectomy with no capsular invasion and clear margins, while 1 patient presented with a renal mass and concomitant gastric metastasis. The mean initial tumor size was 8.73 cm. Fuhrman grading of II/IV, III/IV, and IV/IV was noted in 1, 2, and 1 case, respectively.

Conclusions: Although gastric metastasis mostly appears to be a late event in the course of RCC, it can rarely be the initial presentation as evidenced in one of our cases. Given the high mortality rate, considering metastatic RCC in the differential diagnosis for gastric ulceration is imperative in patients with atypical morphology or clinical presentation.

The Prevalence of Histologic Acute Alcoholic Hepatitis in Explanted Liver and the Correlation With Pretransplant Abstinence

(Poster No. 78)

Lakshmisree Akhila Vemulakonda, MBBS ([email protected]); Priyanka Patil, MD. Department of Pathology, Westchester Medical Center, Valhalla, New York.

Context: The meaning of the term acute alcoholic hepatitis (AAH) is quite different for clinicians and pathologists. For clinicians, AAH refers to the clinical syndrome (fever, jaundice, abdominal pain, anorexia, leukocytosis, and coagulopathy) in alcoholic patients. Pathologists use this term based on the presence of certain histopathologic findings. We aim to identify the prevalence of histologic AAH in liver explants of patients with alcoholic liver disease (ALD). We also aim to correlate histologic findings with clinical AAH and the pretransplant abstinence interval.

Design: After searching our database, a study group of 50 patients (undergoing transplant for ALD) and a control group of 40 (non-ALD) patients undergoing transplant from September 2020–December 2021 were identified. Patient age, sex, clinical AAH, MELD score, Maddrey score, history of heavy alcohol consumption for at least 5 years, and duration of abstinence before transplant were recorded. Pathology slides were reviewed to analyze presence of histologic AAH.

Results: Of 50 study cases, 29 had histologic AAH, while 21 had bland cirrhosis (Table). Patient demographics, jaundice, and coagulopathy did not differ significantly in 2 study groups. None of the patients had fever. Leukocytosis was significantly higher in the histologic AAH group. Most patients with histologic AAH (21 of 29) had only 3 months of abstinence. MELD score was not significantly different in study and control groups.

Conclusions: Presence of histologic AAH may not always correspond to clinical syndrome of AAH. Patients with clinical AAH syndrome can have bland cirrhosis histologically. The histologic AAH can be identified in patients with more than 12 months of abstinence.

Malignant Transformation of a Prerectal Tail Gut Cyst Presenting With Lymph Node Metastasis

(Poster No. 79)

Matthew Uy, DO1 ([email protected]); Ashleigh Tomkovich, MD1; Monica Purmalek, MD2; Erica Kao, MD.1 Departments of 1Pathology and Area Laboratory Services and 2Obstetrics & Gynecology, San Antonio Military Medical Center, San Antonio, Texas.

A tail gut cyst (TGC) is a rare lesion arising from the embryonic hindgut remnant, typically occurring in the perirectal/retrorectal region. Malignant transformation has been described. In our case, a 35-year-old woman presented with an enlarged inguinal lymph node. On excision, it was involved by a poorly differentiated adenocarcinoma with mucinous features (Figure 1.79, A). By morphology and immunophenotype, the differential diagnosis was broad and included genitourinary, gynecologic, and colorectal origin. The patient underwent workup for a primary site, including benign cervical and endometrial biopsies. No mass was identified in the visceral organs on imaging. Full body PET and abdomen/pelvis MRI imaging (Figure 1.79, B) highlighted a 2-cm subcutaneous cyst with sinus tract extending to the left buttock soft tissues with maximum SUV of 9.4. Excision of the presumed “pilonidal cyst” revealed mucinous adenocarcinoma with similar morphology and immunophenotype (CK7 positive, CK20 focal, CDX2 diffuse) to the lymph node metastasis. In addition, there were areas with cribriform gland formation and dirty necrosis (Figure 1.79, C and D) resembling moderately differentiated colorectal adenocarcinoma. Molecular cancer classification favored colorectal origin (probability of 90%). Overall, these findings are in conjunction with a reported history of a left gluteal congenital cyst excised during childhood that was supportive of colorectal-type adenocarcinoma arising from an embryonic gut remnant. Malignant transformations of TGCs are difficult to diagnose in the absence of residual benign elements. The prerectal location in our case contributed to the difficulty, as only 4 cases of prerectal TGCs have been reported and none with malignant transformation.

Newly Categorized Hepatoid Variant of Pancreatic Neuroendocrine Tumor Can Metastasize to the Liver, Creating A Diagnostic Pitfall: A Rare Case Report

(Poster No. 80)

Mark W. McNeely, MD1 ([email protected]); Yang Zhang, MD.2 1Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland; 2Division of Hepatic and Gastrointestinal Pathology, Joint Pathology Center, Silver Spring, Maryland.

Hepatocellular carcinoma has a distinctive appearance most notable for polygonal cells with abundant eosinophilic cytoplasm. When these features are seen in a biopsy of a liver mass, consideration of other diagnostic possibilities may not be given. Recently, a new morphologic variant of pancreatic neuroendocrine tumor with hepatoid features was described, based on 9 similar cases, all of which occurred without liver masses. We report a case of a previously healthy 56-year-old man presenting with a single pancreatic mass and multiple liver masses. A biopsy of the liver revealed a malignant epithelioid neoplasm with various morphologic appearances. In some areas, the tumor cells showed abundant eosinophilic cytoplasm and increased nuclear size variability, growing in anastomosing cords with intervening stroma (Figure 1.80, A), assuming an appearance similar to that of a well-differentiated hepatocellular carcinoma. Other areas of tumor showed small, round, monotonous nuclei with coarse chromatin, and grew in large trabeculae and nests (Figure 1.80, B). All tumor cells, irrespective of morphology, were positive for synaptophysin, chromogranin (Figure 1.80, C), and arginase-1 (Figure 1.80, D), while HepPar1 showed expression only in the hepatocellular carcinoma–like areas. This phenomenon has been rarely described and may be underreported. Furthermore, this entity could easily be mistaken for hepatocellular carcinoma in instances where the hepatoid areas are sampled in isolation on liver biopsy, a potentially significant diagnostic pitfall.

The views expressed in this abstract are those of the authors and do not necessarily reflect the official policy of the Department of Defense or the US Government.

Duplicate Gallbladder in Adolescent Girl Presenting With Cholelithiasis

(Poster No. 81)

Mohammed Athar, MD ([email protected]); Shadi Qasem, MD. Department of Pathology, University of Kentucky, Lexington.

Duplicate gallbladder or accessory gallbladder is a rare congenital anomaly. It can present as 1 cystic duct entering the common bile duct (split primordium) or as 2 separate cystic ducts arising from the biliary tree; this increases the chance for injuries during cholecystectomy or laparotomy procedures. The anomaly may be discovered incidentally, or patients can present with symptoms of acute cholecystitis, cholangitis, or even pancreatitis. A 16-year-old otherwise healthy adolescent girl presented with symptoms of cholelithiasis and was taken to the operating room where she was found to have a duplicate gallbladder (Figure 1.81, A). The procedure was postponed to obtain a magnetic resonance cholangiopancreatography, which favored the patient for having 1 cystic duct in the presence of a bilobed duplicate gallbladder and 2 cystic arteries. Abdominal ultrasonography also confirmed that there were 3 gallstones in the larger of the 2 gallbladders and that no signs of inflammation were detected. Surgery was performed, and pathology was also able to confirm the findings, including cholelithiasis, a duplicate gallbladder, and 1 cystic duct (Figure 1.81, B). The postoperative course of the patient was otherwise unremarkable. Recognition of this entity is important because it can decrease the risks of complications during cholecystectomy. Cholecystectomy is the treatment of choice in symptomatic patients after minimization of risks associated with duplicate gallbladder.

Diagnosis of Rectal Heterotopic Gastric Mucosa Confirmed by Molecular Microsatellite Testing

(Poster No. 82)

Joshua Fernandez de la Vega, BS1 ([email protected]); Joshua M. Peterson, MD2; Billie Shine, DO2; Yamam Al-Saadi, MD3; Gabriel Reep, MD3; Jing He, MD.2 1Medical School and Departments of 2Pathology and 3Gastroenterology, University of Texas Medical Branch at Galveston.

A 32-year-old woman presented for diagnostic colonoscopy to investigate chronic migratory abdominal pain. Findings in the colon included a 2-mm sessile sigmoid colon polyp, mild diverticulosis, and otherwise normal colonic mucosa. A 12-mm sessile polypoid lesion was found in the distal rectum near the dentate line, which was biopsied. Grossly, the rectal lesion had a focal area of villous-appearing mucosa as well as a focal area near the proximal border containing more elongated pits (Figure 1.82). Histopathologic evaluation of the biopsy revealed gastric pits lined by typical chief and parietal cells throughout the entire specimen, a fine lamina propria composed of smooth muscle, and a focal submucosal lymphoid aggregate (Figure 1.82). No colorectal mucosal architecture or cytomorphology was observed. As this patient had not undergone upper endoscopy at the time of colonoscopy, the possibility of specimen mix-up was suspected. Both the rectal lesion and sigmoid polyp underwent molecular microsatellite testing of 16 short tandem repeats, which revealed identical alleles between specimens. This result confirmed that both specimens originated from the same patient, ruling out specimen mix-up and establishing a diagnosis of heterotopic gastric mucosa (HGM) of the rectum. The patient was referred for surgical excision of the lesion. HGM is a rare entity that most often occurs in the upper esophagus; only rare cases of rectal HGM have been reported in the literature. The use of molecular microsatellite testing against known patient samples can identify specimen mix-ups and support rare diagnoses such as rectal HGM.

Morphologic Variance in CMV Colitis/Enteritis After Acyclovir Prophylaxis and Antiviral Pretreatment

(Poster No. 83)

Pooja Khonde, MD ([email protected]); Kathleen Byrnes, MD. Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, Missouri.

Context: Cytomegalovirus (CMV) infection of the gastrointestinal tract is a complication of immunosuppression. Identification of the classic owl-eye intranuclear and intracytoplasmic inclusions is the key morphologic feature on H&E. However, this feature is illustrated in pretreatment cases. The morphology of CMV inclusions in posttreatment/prophylaxis cases is not well described in the literature.

Design: A retrospective review of gastrointestinal biopsies and medical records from 2016–2021 was completed. A total of 68 cases with H&E and CMV immunohistochemistry (IHC) were included for review. Of these, only 33 cases with inclusions noted on both H&E and CMV IHC were selected and further subdivided into pretreatment/prophylaxis and posttreatment on the basis of clinical history.

Results: Of the 33 cases that met the inclusion criteria, 22 were pretreatment. Eleven patients were posttreatment and on antiviral prophylaxis. There were 18 cases with few to abundant inclusions. Of these, 28% (n = 5) were posttreatment. The pretreatment biopsies all demonstrated classic CMV inclusions (Figure 1.83, A). In contrast, posttreatment CMV-infected cells demonstrated extracellular and intracellular eosinophilic globules and degranulation with rare intranuclear inclusions (Figure 1.83, B). The IHC pattern was similar to that of the pretreatment CMV cases. All the patients were on acyclovir prophylaxis (average time, 5.8 months). Valganciclovir and ganciclovir were also added as therapy before the biopsy (average, 6 days).

Conclusions: Variant morphology of extracellular and intracellular globules and degranulation were seen in all posttreatment cases on acyclovir prophylaxis before biopsy. We hypothesize that prophylaxis/antiviral therapy alters the morphology of CMV-infected cells, recognition of which is key before IHC results are available.

Metastatic Pancreatic Adenocarcinoma Mimicking Colonic Adenocarcinoma

(Poster No. 84)

Annie E. Abraham, MD ([email protected]); Kerime Ararat, MD; James Mueller, MD. Department of Pathology, UMass Chan Medical School-Baystate, Springfield, Massachusetts.

Pancreatic ductal adenocarcinomas are clinically and pathologically insidious tumors with poor prognosis that commonly metastasize to the liver, lungs, lymph nodes, and peritoneum. Metastasis to the colon is very rare with only 8 cases reported in the English medical literature to date. We report an interesting case of pancreatic adenocarcinoma in a patient who also had a sigmoid colon mass. A 66-year-old woman was noted to have an incidental pancreatic tail mass that measured 3.0 cm and nonspecific segmental thickening of the sigmoid colon on computed tomography of the abdomen. A needle biopsy of the pancreatic tail mass revealed small cribriform infiltrative glands within a desmoplastic stroma. By immunohistochemistry, the tumor stained for cytokeratin 7 and was negative for SATB2, consistent with pancreatic primary. Colonoscopy revealed an ulcerated and villous 5-cm sigmoid mass, partially obstructing the colon with signs of recent hemorrhage. Biopsy of the mass revealed an infiltrative adenocarcinoma with the morphologic appearance of a primary colonic adenocarcinoma. Interestingly, the immunohistochemical staining pattern was identical to that of the pancreatic adenocarcinoma, establishing it as a metastasis to the colon. Subsequently, the patient was started on palliative chemotherapy. Colonic metastasis highlights an unusual pattern of spread of these tumors. In our case, the tumor morphologically mimicked a colonic adenocarcinoma with focal villous architecture grossly and microscopically. Hence in such a synchronous presentation of 2 tumors, pathologists must have a high suspicion for metastasis despite their apparent morphologic differences.

Morphologic Spectrum of Liver Tumors in Children and Young Adults in One Institution: Summary of the Largest Cohort to Date

(Poster No. 85)

Natalia Yanchenko, MD, PhD ([email protected]); Ali G. Saad, MD. Department of Pathology, UMH/Jackson Memorial Hospital, Miami, Florida.

Context: Liver neoplasms in people during their first 3 decades of life represent a heterogeneous group of disease. We study the experience at a major reference institution to analyze liver neoplasms in 4 age groups to clarify the distribution of liver neoplasms in each group (according to the 5th edition of the World Health Organization Classification of Digestive Tumors).

Design: The pathology databases (from 2003–2022) of Jackson Memorial Hospital were searched for “liver” and “hepatic” in the population from 0 to 30 years. Cases for which histologic materials were available were included in the study. Patients were divided into 4 age groups: 0–3 years (infants and toddlers), 4–14 years (children), 15–21 years (adolescents), and 22–30 years (young adults).

Results: Results are summarized in the Table. While in the toddler population most neoplasms were hepatoblastomas and benign mesenchymal tumors, in children hepatoblastomas were rare and hepatocellular carcinomas were most frequent.

Conclusions: Liver disease in the pediatric and young adult population is different and this needs to be considered when diagnosing neoplasms in these populations.

Evolution of the Liver Biopsy Through Revolutions in Hepatology

(Poster No. 86)

Nazire E. Albayrak, MD ([email protected]); Peizi Li, MD, MPH; Maryam Kooshesh, MD; Aishwarya Irri, MD, MPH; Joshua Onuiri, MD, PhD; Xia Qian, MD, PhD; Muhammad Qazi, MD; Russell McBride, PhD; Stephen C. Ward, MD, PhD; Swan Thung, MD. Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai/The Mount Sinai Hospital, New York, New York.

Context: The past decade has brought major innovations to the practice of hepatology. Historically, the diagnosis and management of hepatitis C virus (HCV) pre and post liver transplant has relied on biopsy. Direct-acting antivirals, approved by the US Food and Drug Administration in May 2011, revolutionized HCV treatment, improving sustained virologic response rates to >90%, while simultaneously reducing treatment duration to ≤12 weeks. Additionally, the availability of noninvasive imaging techniques (eg, magnetic resonance elastography and FibroScan) to assess liver fibrosis and steatosis beginning in 2009 has also reduced the need for grading/staging biopsies.

Design: Search of the pathology database at Mount Sinai Hospital revealed a total of 12 690 liver biopsies received from January 2002–December 2021. A cohort of 5000 cases (39%) was selected alphabetically by patients' last name (A–L). The cohort was sorted into four 5-year periods and comparatively analyzed along with demographics, histopathologic diagnoses, and biopsy indications (Figure 1.86).

Results: Since 2011, the annual number of liver biopsies has continually decreased, nearly halving from 418 in 2010 to 269 in 2011 (P < .01). Although diagnostic and lesional biopsies have not significantly declined over the years, fewer staging and posttransplant biopsies have resulted in an overall downtrend observed in linear regression analysis (P < .001).

Conclusions: Our study shows that the aforementioned advances in hepatology have shifted the role for liver biopsy. Between 2002 and 2011, staging and posttransplant protocol biopsies comprised the majority of liver biopsy practice, while diagnostic biopsies predominate after 2011. The remaining cases of our study are currently under review.

Ileocecal Epstein-Barr Virus–Associated Classical Hodgkin Lymphoma Arising in Patient With Crohn Disease on Adalimumab

(Poster No. 87)

Ani Toklu, MD; Katrina Collins, MD ([email protected]); Nishi Dave, MD; Hector Mesa, MD. Department of Pathology, Indiana University, Indianapolis.

A 41-year-old man with a 15-year history of ileocecal Crohn disease, maintained on long-term immunosuppression with adalimumab (40 mg/0.4 mL SC), presented with hematochezia and severe anemia (Hgb, 6.4 g/dL). Colonoscopy revealed a large, ulcerated noncircumferential mass at the ileocecal valve (Figure 1.87, A). Mucosal biopsies showed changes consistent with severe active inflammatory bowel disease and scattered large mononuclear, bilobated or polylobated cells with prominent eosinophilic inclusion-like nucleoli (Figure 1.87, B) that were positive for CD15, CD30 (Figure 1.87, C), PAX5, BCL6, and MUM1, while negative for CD3, CD20, and CD45, consistent with Hodgkin/Reed-Sternberg (HRS) cells. HRS cells were positive for EBV-encoded RNA (EBER) in situ hybridization (Figure 1.87, D), and all cells were negative for CMV and HSV immunostains. A diagnosis of EBV+ classical Hodgkin lymphoma (EBV+ CHL) arising in Crohn disease was made. Despite the histologic diagnosis, the patient underwent right hemicolectomy owing to near complete obstruction and significant bleeding. The resection confirmed transmural Crohn disease and EBV+ CHL involving the intestine and mesenteric nodes. Diagnosis of CHL in the context of Crohn disease is difficult given the presence of obscuring inflammation, reactive atypia in stromal cells and leukocytes, and potential presence of viral cytopathic changes. Most lymphomas occurring in the context of chronic inflammation or immunosuppression are non-Hodgkin type. The increased incidence is largely attributed to abnormal immune surveillance given the necessary use of steroids, immunomodulators, and biologics. In our case, long-term treatment with a tumor necrosis factor α inhibitor and EBV positivity support an iatrogenic immunodeficiency-associated, rather than a chronic inflammation-associated, lymphoma.

Large Epidermoid Splenic Epithelial Cyst in a Young Woman Presenting With Abdominal Pain: A Rare Occurrence

(Poster No. 88)

Bianca Puello Yocum, MD; Michael Hwang, MD; Hector Mesa, MD; Katrina Collins, MD ([email protected]). Department of Pathology, Indiana University, Indianapolis.

Primary splenic cysts are very rare in routine surgical practice, representing only 10% of benign nonparasitic splenic cysts. Splenic cysts are usually an incidental finding during imaging studies performed for an unrelated reason and occur predominantly in pediatric to young adult age groups with a female predominance. We describe an unusual case of an 18-year-old woman who presented with left-sided shoulder pain with radiation to the left upper quadrant and back. She had no history of previous trauma or foreign travel. CT imaging showed a large, multiseptated cystic lesion in the upper pole of the spleen (Figure 1.88, A). Splenectomy was performed revealing a 6.8-cm multiloculated cyst (Figure 1.88, B). Microscopically, the cysts were lined by benign stratified squamous epithelium (Figure 1.88, C) positive for CK5/6 and focal mucous cells positive for mucicarmine (Figure 1.88, D), characteristic of a primary epidermoid splenic epithelial cyst. The pathogenesis of primary splenic cysts remains unclear; hypotheses include a teratomatous origin, derivation from inclusion of fetal squamous epithelium, and origin from mesothelial invagination of the capsule during development. A definitive preoperative diagnosis was not possible; however, the absence of previous trauma, infection, or exposure to hydatid disease favored this diagnosis. Surgery was performed for diagnostic purposes and to avoid serious complications such as rupture or infection; conservative surgery is preferred, when possible, to maintain splenic function and avoid infectious complications related to asplenia.

IgG4-Lymphadenopathy in the Pediatric Age Group

(Poster No. 89)

Rachel Whitehair, MD1 ([email protected]); Nadine Aguilera, MD1; Patcharin Pramoonjago, PhD.2 1Department of Pathology, University of Virginia, Charlottesville; 2Department of Biorepository and Tissue Research Facility, University of Virginia, University of Virginia Health System, Charlottesville.

Context: IgG4-related disease (IgG4-RD) is a new entity first described in 2003 with a heterogeneous, insidious clinical course. IgG4-RD is a fibroinflammatory condition identified in adults with characteristic fibrosis and an IgG4-plasma cell infiltrate. IgG4-RD has been reported in children with only a few studies investigating IgG4 lymphadenopathy (IgG4-LAD). Isolated IgG4-LAD without coexisting IgG4-RD has been established in adults, but rarely in pediatric patients. IgG4-LAD has been hypothesized to represent a distinct entity, as many patients do not have any other signs of IgG4-RD.

Design: Thirty-seven lymph nodes classified as reactive were identified in children/adolescents 0–18 years of age between 2016 and 2020. The cases were stained for IgG, IgG4, and CD138 and the findings were recorded. The IgG-and IgG4-positive cells were counted by using the method proposed in Chen et al. Three high-power fields (HPFs) were counted (the areas with the highest IgG or IgG4 cells); the average number per HPF was calculated. An IgG4+:IgG+ ratio of >40% and/or an IgG4 count greater than 50 were considered probable IgG4-LAD.

Results: Seven cases were identified to have IgG4 counts greater than 50/HPF (18.9%). Nine cases were found to have IgG4:IgG ratios greater than 40% (24.3%) and 5 cases met both criteria (13.5%). The most common histologic finding overall and within the IgG4 cases was follicular hyperplasia.

Conclusions: IgG4-LAD may be more common in childhood than previously thought. The histologic findings in childhood IgG4-LAD resemble the most common findings identified in pediatric lymph nodes. There are no easily identifiable features to suggest IgG4-LAD without immunohistochemistry.

Myeloid/Lymphoid Neoplasm With FGFR1 Rearrangement and an Associated ASXL1 Mutation Identified by Whole Genome Sequencing

(Poster No. 90)

Lisa M. Marinelli, MD1 ([email protected]); Joshua T. Romain, MD2; William Ehman Jr, BS, CG(ASCP)3; Veronica Ortega, BA, CG(ASCP)3; Gopalrao Velagaleti, PhD, FACMG3; Thomas Gibbons, PhD4; Ashley Nazario-Toole, PhD4; Allen R. Holmes, MD.1 Departments of 1Pathology and Area Laboratory Services and 2Hematology-Oncology, Brooke Army Medical Center, Fort Sam Houston, Texas; 3Department of Pathology and Laboratory Medicine, UT Health San Antonio, Texas; 4Department of Clinical Investigations & Research Support Laboratory, Wilford Hall Ambulatory Surgical Center, Lackland AFB, Texas.

Myeloid/lymphoid neoplasm with fibroblast growth factor 1 rearrangements (MLN-FGFR1) represents a rare group of hematologic neoplasms, with approximately 100 cases reported to date. A 69-year-old woman with a 1-year history of polycythemia and leukocytosis with negative molecular testing for JAK2, CALR, and MPL presented with diffuse adenopathy. An excisional cervical lymph node (LN) biopsy revealed effacement by T lymphoblasts, consistent with T-cell acute lymphoblastic lymphoma (T-ALL). A staging bone marrow (BM) biopsy demonstrated trilineage hyperplasia, which, taken together with the patient's elevated hemoglobin and low serum erythropoietin level, fulfilled diagnostic criteria for polycythemia vera. Karyotype and fluorescence in situ hybridization on both the BM and LN demonstrated a FGFR1 rearrangement due to t(8;13), consistent with MLN-FGFR1. Whole genome sequencing on the LN additionally identified a pathogenic frameshift mutation of ASXL1 (20-32434638-A-AG; NM_015338.6(ASXL1):c.1934dup) predicted to result in loss of protein function, a finding also observed in 8.1% of BM reads. Both the BM and LN harbored mi ssense v a r iants in HDAC4 (NC_000 002.12:g.239068595C>T) and CHEK2 (NM_007194.4(CHEK2): c.538C>T (p.Arg180Cys)), with an unknown significance. Despite initial response to induction chemotherapy with Mini-CVD + Venetoclax, the patient subsequently developed acute leukemia, resulting in rapid clinical deterioration and death. We report the second case of MLN-FGFR1 with an ASXL1 mutation and the first case with HDAC4 and CHEK2 variants. Mutations in ASXL1 have been suggested as drivers in other myeloid neoplasms. Polycythemia vera represents a rare presentation, with just 4 cases reported to date. Our findings support previous suggestions that the translocation t(8;13) may be associated with T-ALL.

Marinelli received grant or research support from the 59th Medical Wing Clinical Investigation Program (DHA/Clinical Program Office).

CSF-1R Expression in Tumor Microenvironment of Follicular Lymphoma and Diffuse Large B-Cell Lymphoma

(Poster No. 91)

Michael Kozak, DO ([email protected]); Fai Chung, BS, HTL(ASCP); Sumire Kitahara, MD. Department of Pathology, Cedars Sinai Medical Center, Los Angeles, California.

Context: Tumor-associated macrophages, dependent on colony-stimulating factor-1 receptor (CSF-1R) for maturation, are associated with survival and are present in the microenvironments of various lymphomas including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). CSF-1R is implicated in activation of the PI3K/AKT/mTOR signaling pathway, which may indicate a role for the use of PI3K inhibitors in the treatment of lymphomas with increased CSF-1R expression. This study examines CSF-1R expression and tumor microenvironment in a larger sample of FL and DLBCL cases for which there is currently a paucity of data and explores whether CSF-1R can be used as a biomarker to identify cases potentially amenable to targeted therapy.

Design: Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue on a total of 45 FL (Figure 1.91, C) and DLBCL (Figure 1.91, D) cases in addition to reactive tonsillar (Figure 1.91, A and B) and lymph node tissue used as a control. CSF-1R (CD115) staining was quantified by the average number of positive cells in 10 high-power fields.

Results: Average CD115 expression was increased in DLBCL non-GC type (P = .02), non-GC and non–double expressor (P = .04), non-GC double expressor (P = .02), and overall DLBCL (P = .04) as compared to controls (P < .001). No significant difference was found between FL and its subtypes and the control. Significant difference was found between FL and DLBCL (P = .007) as well as FL and DLBCL non-GC type (P < .001), but not between FL and DLBCL GC type (P= .13).

Conclusions: These results support the presence of increased CD115-positive tumor-associated macrophages in DLBCL that could lead to new applications of anti-CD115 therapy.

Mature T-Cell Lymphomas With T-LBL Characteristics

(Poster No. 92)

Morgan Hrones, MD1 ([email protected]); Alexa Siddon, MD1; Sudhir Perincheri, MD2; Francine Foss, MD3; Mina L. Xu, MD.1 Departments of 1Pathology & Laboratory Medicine, 2Pathology, and 3Internal Medicine, Hematology & Stem Cell Transplant Section, Yale School of Medicine, New Haven, Connecticut.

Context: De novo T-cell neoplasms in young patients tend to be T-lymphoblastic lymphoma (T-LBL), particularly if arising from mediastinal and extranodal sites. CD34 and TdT are 2 standard blast markers; the absence of both typically rules out T-LBL in favor of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS). Since therapy differs, rare tumors that resemble T-LBL by clinical and cytologic features but are negative for blast markers warrant further study.

Design: We performed a retrospective review within our institutional database of all extranodal PTCLs, NOS in patients aged <40 years (2006–2021) and identified 4 cases. Clinical information, imaging findings, hematoxylin-eosin–stained slides, immunohistochemistry, and molecular studies were reviewed.

Results: All patients presented with a de novo T-cell neoplasm in the form of extranodal or mediastinal disease. Age at presentation ranged from 6 to 36 years. Cytologic evaluation showed blastoid tumor cytology (Figure 1.92, A through D) but CD34 and TdT negativity. Molecular analysis revealed pathogenic variants in KRAS, TP53, and DNMT3A. Patients were treated with a pediatric protocol–inspired acute lymphoblastic lymphoma chemotherapeutic regimen and achieved positive clinical responses.

Conclusions: De novo extranodal T-cell neoplasms in young patients tend to behave more similarly to T-LBL, irrespective of CD34 and TdT positivity. These patients achieved positive clinical responses with the use of a pediatric-inspired aggressive chemotherapeutic approach. Careful communication of such diagnosis must be made to highlight the neoplasms' particularly aggressive nature. Future study into their biology is necessary to differentiate them from more typical PTCLs.

An Unusual Case of Sclerosing Angiomatoid Nodular Transformation of the Spleen With Extramedullary Hematopoiesis

(Poster No. 93)

Leonard N. Yenwongfai, MD, MS ([email protected]); Sahar Nozad, MD. Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington.

Sclerosing angiomatoid nodular transformation (SANT) is a rare benign vascular lesion of the spleen with an unknown etiology and a limited number of cases described worldwide. Most patients are asymptomatic, with splenic lesions found incidentally, but some patients present with abdominal pain. A small number of patients might have associated leukocytosis, polyclonal gammopathy, elevated erythrocyte sedimentation rate, and pancytopenia. However, extramedullary hematopoiesis (EMH) is an unusual finding in SANT. We report a case of SANT with EMH. A 37-year-old woman presented with abdominal pain, and imaging revealed a single well-circumscribed splenic mass warranting a splenectomy. Histologic sections demonstrated a nodular pattern composed of bands of fibrosis with interspersed cellular nodules. Nodules consisted of many vascular spaces associated with inflammatory elements, stromal cells, and histiocytes (Figure 1.93, A and B). There was no cytologic atypia, and mitoses were not identified. Immunohistochemistry showed markers for splenic sinusoidal lining cells, capillary-like and venous-like elements, including CD34, CD31 (Figure 1.93, C), and CD8. EMH was identified, composed mainly of erythroid precursors, few myeloid cells, and megakaryocytes (Figure 1.93, D). There was no evidence of increased blasts or abnormal lymphoid populations, and the patient did not have any lymphohematopoietic abnormality. EMH in the spleen may suggest bone marrow suppression in the setting of a hematolymphoid pathology or a metastatic malignancy. However, EMH is an unusual feature in SANT. While SANT is a benign entity, it is essential to evaluate the splenic tissue thoroughly, as EMH could represent an undiagnosed bone marrow pathology, prompting further clinical workup.

Incidental Histologic Detection of Small Cell Lymphocytic Lymphoma in the Prostate

(Poster No. 94)

Steven H. Adams, MD ([email protected]); Tahmeena Ahmed, MD; Jela Bandovic, MD. Department of Pathology, Stony Brook University Hospital, Stony Brook, New York.

Diagnosis of small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) is ordinarily first suspected by findings of abnormal lymphocytes on blood smear review, lymphocytosis, cytopenia, lymphadenopathy, and/or splenomegaly. The disease is seldomly detected initially by histologic evaluation of hematoxylin-eosin–stained sections alone. A 77-year-old man underwent a simple prostatectomy for benign prostatic hyperplasia. On histology focal collections of monomorphic small lymphocytic infiltrate with dense clumped chromatin were noted throughout the prostate gland (Figure 1.94, A). On immunohistochemistry the infiltrate contained predominant CD20+ (Figure 1.94, B), CD23+, cyclin D B lymphocytes with aberrant expression of CD5 (Figure 1.94, C) and CD43, while CD3 highlighted background T cells (Figure 1.94, D). The diagnosis was SLL/CLL involving the prostate gland in a background of stromal and glandular hyperplasia, focal atrophic changes, and acute inflammation. Hematology found no lymphocytosis (absolute lymphocyte count, 1.17 K/μL). Subsequently, flow cytometry detected a small percentage of SLL/CLL phenotypic cells. Further workup by chest-abdomen CT and PET-CT (skull base to mid-thigh) showed no lymphadenopathy, splenomegaly, or other abnormalities. Negative findings on PET-CT support a prostatic primary (SLL), although this cannot be stated definitively as a bone marrow biopsy was not performed. Suspicion for SLL/CLL on histology is raised when small dense lymphocytes are seen in aggregates, away from vessels, and not admixed with other inflammatory cells (eg, eosinophils, plasma cells, histiocytes). Immunostains (eg, CD5, CD20, CD23) should then be used to confirm the diagnosis. It is possible that local CLL/SLL involvement contributed to the patient's prostatic hypertrophy. Literature review found only 10 cases of primary SLL of the prostate.

Pediatric Myelodysplastic Syndrome With t(3;5)(q21;q31), Transforming to Acute Myeloid Leukemia and Myeloid Sarcoma of Orbital and Sinonasal Cavities 10 Years After Allogeneic Bone Marrow Transplant

(Poster No. 95)

Leonard Yenwongfai, MD, MS ([email protected]); Sainan Wei, MD, PhD; Melissa Kesler, MD; Sahar Nozad, MD. Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington.

The balanced t(3;5)(q21;q31) is a rare translocation described in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). We report a case of pediatric MDS with t(3;5)(q21;q31) that evolved to AML and myeloid sarcoma 10 years after a bone marrow transplant. A 15-year-old adolescent girl was evaluated for anemia and thrombocytopenia in 2010. Bone marrow biopsy examination revealed a hypercellular bone marrow with trilineage dyspoiesis and 5% blasts containing Auer rods. Cytogenetic studies identified t(3;5)(q21;q31). She underwent an allogeneic stem cell transplant from a male donor. The patient presented in 2021 with a large orbital and sinonasal mass that was biopsied and showed involvement by myeloid sarcoma (Figure 1.95, A). The subsequent bone marrow biopsy demonstrated AML with 79% populations of myeloblasts (Figure 1.95, B and C). The cytogenetic analysis was significant for an abnormal female karyotype with t(3;5)(q21;q31) in 90% of metaphase cells (Figure 1.95, D). Next-generation sequencing of the bone marrow specimen identified mutations in FLT3-ITD, IDH2, and ETV6 genes. She underwent induction chemotherapy for AML with myelodysplasia-related changes. The reciprocal translocation between chromosomes 3 and 5 with breakpoints at 3q21 and 5q31 is rare but is reported in MDS and AML cases. The genes involved in this translocation remain unknown. It is yet to be determined whether patients with this translocation, similar to AML with t(3;5)(q25;q35.1) (MLF1-NPM1), which is classified as acute myeloid leukemia with myelodysplasia-related changes in the current World Health Organization classification, should also be classified in this category.

An Unusual Presentation of B-Lymphoblastic Leukemia/Lymphoma, BCR-ABL1–like, With Pronounced Eosinophilia

(Poster No. 96)

Leonard Yenwongfai, MD, MS1 ([email protected]); Zena Chahine, MD2; Ayman Qasrawi, MD2; Sainan Wei, MD, PhD1; Dava W. Piecoro, MD1; Sahar Nozad, MD.1 Departments of 1Pathology and Laboratory Medicine and 2Internal Medicine, University of Kentucky, Lexington.

BCR-ABL1–like B-lymphoblastic leukemia (B-ALL) is a provisional entity in the 2016 World Health Organization classification of lymphoblastic tumors. These neoplasms lack the BCR-ABL1 translocation but show a gene expression profile similar to B-ALL with BCR-Arch-ABL1, including alterations in cytokine receptors and signaling genes such as CRLF2, ABL1, ABL2, JAK2, PDGFRB, and EPOR. Cases with CRLF2 rearrangements account for approximately 50% of cases, and the frequency of specific genomic lesions varies with ethnicity such that IGH/CRLF2 translocations are more common in Hispanic and Native American persons. We report a case of B-ALL, BCR-ABL1–like, with significant eosinophilia. A 20-year-old Hispanic man presented with leukocytosis with 45% eosinophils and 3% blasts (Figure 1.96, A). Bone marrow flow cytometry revealed 31% lymphoblasts expressing CD19, CD10, partial CD20, CD22, CD79a, CD38, CD34, TdT, and HLA-DR. Examination of the bone marrow biopsy and aspirate exhibited a hypercellular bone marrow with increased blasts and elevated eosinophils (Figure 1.96, B). Chromosome analysis showed a normal male karyotype, whereas fluorescence in situ hybridization demonstrated a cryptic chromosomal rearrangement between the X chromosome and chromosome 14 at breakpoints involving IGH at 14q32 and CRLF2 at Xp22.33, t(X;14) (p22.33; q32) (Figure 1.96, C and D). These findings confirmed the diagnosis of BCR-ABL1–like B-ALL with IGH/CRLF2 rearrangement. The patient attained a complete remission with induction therapy, using the CALGB 10403 protocol. This case demonstrates an unusual presentation of BCR-ABL1–like B-ALL and emphasizes the importance of appropriate cytogenetic studies for correct diagnosis. When treated with conventional chemotherapy, these cases have a poor prognosis and might require allogeneic transplant.

A Case Report of Large B-Cell Lymphoma With Interferon Regulation Factor 4 Rearrangement

(Poster No. 97)

Bei Yang, MD, PhD ([email protected]); Lalarukh Aftab, MD. Department of Pathology and Anatomical Science, University at Buffalo, New York.

Large B-cell lymphoma (LBCL) with interferon regulation factor 4 (IRF4) rearrangement is rare and a provisional lymphoma entity included in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. We report a case of LBCL with IRF4 rearrangement in a 16-year-old adolescent male who presented with a rapidly growing left tonsil without fever, night sweats, or weight loss. CT noted an asymmetric enlargement of the left palatine tonsil of 3.4 cm. Histologic examination showed lymphoid tissue of left tonsil replaced by neoplastic follicles that were fused in some places and with focal diffuse areas. The neoplastic cells were medium sized, resembled centrocytes and centroblasts, and were positive for CD20, PAX-5, MUM-1, BCL6, and BCL2 and weakly positive for CD10. CD21 showed expanded, focally coalescent, and disrupted follicular dendritic cell meshwork. MYC was variably positive in about 30% of cells. CD5, CD34, TdT, and cyclin D1 were negative. Proliferation index (Mib1) was around 80%. FISH analysis detected IRF4/DUSP22 (6p25) gene rearrangement and no evidence of BCL2 or BCL6 gene translocations. LBCL with IRF4 rearrangement is more often seen in young ages with cervical localization, especially Waldeyer ring, and has a favorable outcome. To recognize this rare entity, which is important for future management, we recommend IRF4 rearrangement FISH test performed in all MUM-1–positive follicular lymphomas and diffuse LBCLs, especially in children involving tonsils/Waldeyer ring lymphoid tissue.

A Rare Case of Systemic Mastocytosis With Associated Clonal Hematologic Non–Mast Cell Lineage Disease Manifested as Monoclonal Gammopathy of Undetermined Significance

(Poster No. 98)

Bei Yang, MD, PhD ([email protected]); Lalarukh Aftab, MD. Department of Pathology and Anatomical Science, University at Buffalo, New York.

Systemic mastocytosis with associated clonal hematologic non–mast cell lineage disease (SM-AHNMD) is a subtype of systemic mastocytosis (SM). Most of the reported cases of SM-AHNMD are associated with the disorder of myeloid lineage, and SM-AHNMD as a plasma cell neoplasm is rare. We report a case of SM-AHNMD as plasma cell neoplasm. The patient is a 46-year-old man who presented with steadily increasing pancytopenia since beginning treatment with methotrexate and rituxan for rheumatoid arthritis. His medical history was also significant for chronic kidney disease secondary to drug toxicity on peritoneal dialysis, and monoclonal gammopathy of undetermined significance (MGUS). Bone marrow core biopsy showed multifocal aggregates of spindle mast cells (>15 cells per aggregate) in the paratrabecular area, intermingled with lymphoid aggregates and reticulin fibrosis. These spindle mast cells were positive for tryptase, CD117 (bright), and CD25. Plasma cells (5%–8% of marrow cellularity) were aberrant CD56 and CD117 (dim) positive and exhibited κ light-chain excess. The myeloid lineage was left shifted but progressively maturing with normal M:E ratio. Eosinophilia was also present. Further investigations showed increased serum tryptase (28.2 μg/L), but KIT mutations were not detected in peripheral blood sample. Indolent SM coexists with plasma cell neoplasm, which fits the definition of MGUS in this case. To our knowledge, rare cases of SM-AHNMD as MGUS have been reported.

Anaplastic Large Cell Lymphoma–Associated Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature

(Poster No. 99)

Mohamed O. Rabie, MD ([email protected]); Bayan Alzumaili, MD; Khawaja H. Bilal, MD; Wen Fan, MD. Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages. A 40-year-old woman presented with shortness of breath for 3 weeks. CT scan revealed mediastinal and bilateral axillary lymphadenopathy. Clinical history was notable for intermittent fever (103°F) and hepatosplenomegaly. CBC showed hemoglobin (5.8 g/dL; ref, 11.7–15.0 g/dL), hematocrit (17.6%; ref, 34.0–47.0%), WBCs (2.7 K/μL; ref, 4.5–11.0 K/μL), platelets (11 K/μL; ref, 150–400 K/μL), ferritin (>33 511 μg/L). Left axillary lymph node biopsy showed depletion of lymphoid cells that were replaced by histiocytes with hemophagocytosis (Figure 1.99, A). Numerous large atypical lymphoid cells were also identified that were positive for CD45, ALK (Figure 1.99, B), CD30 (Figure 1.99, C), CD7, CD56, CD8, and CD4, and were negative for CD20, PAX5, CD3, and CD5. Background histiocytes were positive for CD68 and CD163 (Figure 1.99, D). The histology and the immunoprofile supported the diagnosis of ALK-positive anaplastic large cell lymphoma with associated hemophagocytic lymphohistiocytosis. HLH presents in 2 forms, genetic and acquired, where the latter is triggered by malignancies or infections. Malignancy-associated HLH usually presents with variable overlaps of symptoms indistinguishable from sepsis or multiple organ dysfunction syndrome, similar to the presentation of this patient, resulting in higher incidence of misdiagnosis and mortality. Treatment of underlying cause and prompt initiation of immunochemotherapy is crucial for survival. Differential diagnoses considered are Rosai-Dorfman disease, myelodysplastic/myeloproliferative neoplasms, Langerhans cell histiocytosis, and such infections as leishmaniasis and histoplasmosis. Future efforts are required to develop evidence-based, tailored therapies to improve outcomes of this underrecognized heterogeneous entity.

Adult-Onset Hemophagocytic Lymphohistiocytosis in a Patient With Disseminated Mycobacterium tuberculosis Infection and a Heterozygous UNC13D Mutation

(Poster No. 100)

Hamza Tariq, MD ([email protected]). Department of Pathology, Rush University Medical Center, Chicago, Illinois.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, systemic hyperinflammatory syndrome broadly divided into primary/familial and secondary/acquired subtypes. Primary HLH is caused by homozygous mutations that impair the cytolytic functions of NK and cytotoxic T cells, whereas secondary HLH occurs in response to infectious, autoimmune, or neoplastic triggers. Recent studies have demonstrated that a substantial proportion of patients with secondary HLH carry heterozygous mutations in 1 or more of the primary HLH-associated genes, suggesting an underlying genetic predisposition. We report the case of a 63-year-old woman who presented with fever, shortness of breath, abdominal pain, and pancytopenia. An extensive laboratory workup led to the diagnosis of HLH. A bone marrow biopsy was performed and showed frequent hemophagocytic histiocytes (Figure 1.100, A). Core biopsy showed extensive necrotizing granulomatous inflammation (Figure 1.100, B and C). An acid-fast bacillus stain was positive for numerous acid-fast bacilli (Figure 1.100, D). Subsequent cultures performed on a bronchoalveolar lavage specimen and liver biopsy were positive for Mycobacterium tuberculosis. A next-generation sequencing panel for primary HLH was performed on a peripheral blood sample and identified a heterozygous mutation in the UNC13D gene (c.2346_2349del(p.Arg782fs), a gene that encodes Munc13-4 protein, which is essential in the intracellular trafficking and exocytosis of lytic granules. This case reinforces the fact that a substantial proportion of patients with secondary HLH carry heterozygous mutations in genes involved in the cytolytic functioning of NK and cytotoxic T cells, suggesting a genetic predisposition in these patients.

Intravascular Large B-Cell Lymphoma in 2 Patients

(Poster No. 101)

Saman S. Karimi, MD, MS1 ([email protected]); Victoria Angelova, MD2; Shiraz Fidai, MD.2 1Department of Pathology, University of Illinois at Chicago; 2Department of Pathology, John H. Stroger Hospital of Cook County, Chicago, Illinois.

Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal large B-cell lymphoma characterized by small vessel intravascular growth that presents with nonspecific symptoms and is commonly diagnosed on autopsy. IVLBCL predominantly affects the middle-aged and elderly population and is associated with an aggressive clinical course and poor prognosis. We present 2 cases: patient 1 (a 61-year-old man) and patient 2 (a 54-year-old woman), who presented with nonspecific, overlapping symptoms of abdominal pain, anemia, thrombocytopenia, and multiple metabolic derangements. Interestingly, the peripheral blood smear for patient 1 showed 25% circulating large lymphocytes (clonality confirmed by flow cytometry), while that of patient 2 lacked circulating large cells (in keeping with typical presentation). Abdominal CT in both patients showed hepatomegaly, and liver biopsies were subsequently performed. In both cases, biopsy showed diffuse intrasinusoidal infiltration by large lymphoma cells with prominent nucleoli and numerous mitoses (Figure 1.101, A and B); positivity for CD20, CD5 (Figure 1.101, C and D), BCL-6, and MUM1; lack of CD10 staining; and a 70%–80% Ki-67 proliferation index, consistent with a diagnosis of IVLBCL, non–germinal center phenotype. Owing to disease burden, patient 1 died the next day from overwhelming tumor lysis syndrome after steroid initiation. Patient 2 survived for 8 months and died from relapsed refractory CNS disease. We report these 2 cases to demonstrate the highly nonspecific presentation and antemortem diagnosis of such a rare entity and to emphasize the need for further studies to improve our understanding of its diagnosis, staging parameters, therapy, and outcome (especially the significance of circulating cells in patient 1).

Heterogeneous Minimal/Measurable Residual Disease (MRD) Testing Practices Highlight the Need to Standardize, Including the Use of First-Pull Aspirate for MRD: Results From a Survey of US Pathologists

(Poster No. 102)

Juliana Hidalgo-Lopez, MD1 ([email protected]); Gail J. Roboz, MD3; Brent Wood, MD, PhD4; Michael Borowitz, MD, PhD5; Elias Jabour, MD6; Ehab Elkhouly, MD, MBA1; Babatunde Adedokun, MD, PhD2; Faraz Zaman, MD1; Karim Iskander, PhD7; Aaron C. Logan, MD, PhD.8 Departments of 1Global Medical Affairs and 2Center for Observational Research, Amgen Inc, Thousand Oaks, California; 3Department of Medicine, Weill Cornell Medicine, New York, New York; 4Department of Pathology and Laboratory Medicine, Children's Hospital, Los Angeles, California; 5Department of Hematologic Pathology, Johns Hopkins University, Baltimore, Maryland; 6Department of Leukemia, MD Anderson Cancer Center, Houston, Texas; 7Department of Medical Affairs, BioMarin Pharmaceutical, Westlake Village, California; 8Department of Hematology/Oncology, University of California, San Francisco.

Context: Lack of B-cell acute lymphoblastic leukemia (B-ALL) minimal residual disease (MRD) assessment standards may impact patient outcomes.

Design: US pathologists took a 30-minute online survey on B-ALL MRD practices (April 2021–January 2022).

Results: Of 83 pathologists, 38 were academic (National Cancer Institute [NCI], n = 23; non-NCI, n = 15), 38 community, and 7 commercial. For MRD, pathologists used external (74%) or in-house (53%) laboratories; 27% used both. Challenges with external laboratories identified by academic pathologists included sample quality (69%), cost (54%), and reliability (54%), while community pathologists primarily flagged logistics (56%). For MRD samples, most pathologists (59%) received 2–5 mL in 2–3 tubes; 69% were not identified for MRD. Only 13% of pathologists consistently identified/used first-pull marrow aspirates (Figure 1.102), and 37% created smears from the same tube sent for MRD. Nearly all respondents (88%) reported hemodilution concerns; 9% of MRD tests were repeated for technical issues. Flow cytometry was mostly used (77%), typically with Children's Oncology Group/MD Anderson Cancer Center panels (in-house = 66%, external = 59%). Leukemia-associated immunophenotypes (LAIPs) alone were more commonly used by external laboratories (43%), while in-house testing used combined LAIP and different from normal (47%). Forty-six percent of respondents included sample quality and technical information in reports.

Conclusions: Wide variability in MRD testing practices, including inconsistent use of first-pull aspirates, continues to be a challenge and may adversely affect patient outcomes. Increased use of first-pull aspirates per National Comprehensive Cancer Network guidelines will improve sample quality and enhance patient care through early MRD detection. Relationships between first-pull aspirates, sample quality, and technical yield should be further investigated.

Hidalgo-Lopez is an Amgen shareholder. Roboz is a consultant with AbbVie, Actinium, Agios, Amgen, Astex, Astellas, AstraZeneca, Bayer, Blueprint Medicines, BMS, Celgene, Daiichi Sankyo, GSK, Janssen, Jasper, Jazz, MEI, Mesoblast, Novartis, Otsuka, Pfizer, Roche, Sandoz, and Takeda, and has received grant or research support from Cellectis and Janssen. Wood has a Laboratory Services Agreement and received honoraria from Juno, Pfizer, Amgen, and Seattle Genetics. Borowitz has received honoraria from Amgen and Blueprint Medicines. Jabour has received grant or research support from Amgen, AbbVie, Spectrum, BMS, Takeda, Pfizer, Adaptive, and Genentech. Elkhouly is an Amgen shareholder. Adedokun is an Amgen shareholder. Zaman is an Amgen shareholder. Iskander is a former employee and shareholder of Amgen. Logan is a consultant with Amgen, Agios, Pfizer, Incyte, and AbbVie, and has received grant or research support from Pharmacyclics, Astellas, Jazz, Kite, Kadmon, Autolus, and Genentech.

Diagnostic Utility of Flow Cytometric Evaluation for Classical Monocyte Determination in Chronic Myelomonocytic Leukemia

(Poster No. 103)

Juhi D. Mahadik, MD ([email protected]); Christine Roth, MD. Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas.

Context: Diagnosis of neoplastic monocytic neoplasms is often challenging owing to overlap with other entities. A marked increase in peripheral blood CD14+, CD16 classical monocytes (CMs) has been proposed as a diagnostic adjunct for chronic myelomonocytic leukemia (CMML). We evaluated the diagnostic utility of CM quantitation for CMML diagnosis in our practice setting.

Design: Twenty-one patients (13 inpatients, 8 outpatients) with a peripheral blood monocytosis of >1 ×109/L, with monocytes constituting >10% of the leukocytes, were identified. The 14 peripheral blood and 7 bone marrow samples comprised the following diagnoses: 7, CMML; 5, acute myeloid leukemia (AML) with monocytic differentiation, including 4 AML, NOS and 1 NPM1-mutated AML; 2, myeloproliferative neoplasm (MPN), NOS; 1, plasma cell neoplasm; 1, B-cell lymphoma; and 5, reactive monocytosis.

Results: The mean CM percentages were as follows: CMML (79.4%), AML (79.8%), reactive monocytosis (79.8%), MPN, NOS (81.2%), and nonmyeloid neoplastic cases (52.3%) (Table). Greater than 94% CMs were present in 3 of 7 CMML, 1 of 5 AML, 1 of 2 MPN, 0 of 5 reactive monocytosis, and 0 of 2 nonmyeloid neoplastic cases. Greater than 94% CMs showed an overall sensitivity of 42.8% and specificity of 87.5% for a CMML diagnosis and did not serve to discriminate between CMML and reactive monocytosis (P=.4) or AML (P=.38). However, 71% (5 of 7) of CMML cases were from inpatients, likely reflecting the greater acuity of presentation.

Conclusions: A cutoff of >94% CMs on flow cytometry appears relatively specific but does not impart a high sensitivity for identifying CMML in our practice setting; the possibility of clinical presentation acuity impacting the sensitivity requires further investigation.

Atypical Epstein-Barr Virus–Positive B-Cell Proliferation in Tonsils With Negative Serology

(Poster No. 104)

Leonard Yenwongfai, MD, MS ([email protected]); Sahar Nozad, MD. Department of Pathology, University of Kentucky, Lexington.

Infectious mononucleosis (IM) is a benign, self-limiting lymphoproliferative disease affecting adolescents and young adults, primarily caused by the Epstein-Barr virus (EBV). EBV infections are characterized by fever, tonsillar pharyngitis, and lymphadenopathy. The diagnosis is rendered clinically by a positive mono spot test. Serodiagnosis is confirmed by the presence of IgG and IgM antibodies against the EBV viral capsid antigen (VCA) for patients with persistent negative mono spot tests and clinical suspicion for IM. We report a case of a 13-year-old girl presenting with odynophagia and tonsillar bleeding. Infectious workup for EBV was negative, including negative serology for VCA IgM and IgG antibodies. Other infectious etiologies were also negative. Imaging revealed a left neck mass at level 2A, prominent lymphoid tissue in the bilateral palatine fossae, lymphadenopathy, and hypertrophy of the bilateral adenoids warranting bilateral tonsillectomy. Sections demonstrated partially distorted tonsillar architecture by diffuse proliferation of medium to large lymphoid cells with immunoblastic cytology mixed with plasma cells and plasmacytoid cells. Many mitoses and areas of necrosis were identified (Figure 1.104, A and B). The atypical cells were positive for CD20 (Figure 1.104, C) and PAX5 and showed a high proliferation index. Epstein-Barr encoding region in situ hybridization highlighted numerous cells, with a subset being positive for the latent membrane protein 1 and Epstein-Barr nuclear antigen 2 (Figure 1.104, D). These findings were compatible with IM. This case shows an example of acute primary EBV-IM with negative serology. These cases may represent a delayed serologic conversion or may be an indicator of immunodeficiency warranting further workup.

Acute Leukemia With PICALM::MLLT10 Fusion Associated With Extramedullary Involvement, CD4/CD8 Double-Negative Phenotype, and Poor Outcome

(Poster No. 105)

Jeffrey J. Wang1; Xinjie Xu, PhD2; Peng Li, MD, PhD3; Xueyan Chen, MD, PhD4; Xiaohui Zhang, MD, PhD5; Jinming Song, MD, PhD5; Rong He, MD2; Min Shi, MD, PhD2; Ji Yuan, MD, PhD2 ([email protected]). 1Mayo High School, Rochester, Minnesota; 2Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; 3Department of Pathology, University of Utah Health, Salt Lake City; 4Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle; 5Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Context:PICALM::MLLT10 fusion from t(10;11)(p12;q14) is a rare cytogenetic abnormality in acute leukemia. Comprehensive clinicopathologic and genetic characterization of patients with PICALM:: MLLT10 fusion, treated with contemporary therapy, is limited.

Design: Eleven cases of acute leukemia with PICALM::MLLT10 fusion were identified from 2013 to 2022. Clinicopathologic and genetic data were collected.

Results: Patients had a median age of 25 years (range, 0.3–51 years), with a male to female ratio of 5:6. Using the 2016 WHO classification, 7 (64%) had T-lymphoblastic leukemia/lymphoma (T-ALL), including 2 (18%) with early T-cell precursor lymphoblastic leukemia, 3 (27%) with acute myeloid leukemia (AML), and 1 (9%) with mixed-phenotype acute leukemia (MPAL) (T/B). All 9 patients with radiology studies had extramedullary involvement, with the mediastinum as the most common site involved. The characteristic phenotype of T-ALL was CD4/CD8 double-negative (7 of 7, 100%) with CD7 (6 of 6, 100%) and frequent CD79a expression (2 of 4, 50%). Variable numbers of pathogenic mutations (range, 0–7) were detected by NGS, but no recurrent genetic alteration was found among the 5 cases tested. A complex karyotype was observed in 2 of 7 patients (29%). All patients had intensive chemotherapy, and 2 underwent allogeneic stem cell transplant. Of the 10 patients with follow-up, 5 died after a median follow-up of 18 months (range, 1–61 months). The median overall survival (OS) and 5-year OS rate were 24 months and 38%, respectively.

Conclusions:PICALM::MLLT10 fusion can be detected in T-ALL, AML, and, rarely, in MPAL. It is associated with extramedullary involvement and poor outcome. T-ALL with PICALM::MLLT10 fusion has a characteristic CD4/CD8 double-negative phenotype and frequent CD79a expression.

Clinicopathologic Characteristics of CD5+ and/or CD10+ MYD88-Mutated Lymphoplasmacytic Lymphoma

(Poster No. 106)

Matthew X. Luo, MD1 ([email protected]); David P. Ng, MD2; Anton Rets, MD, PhD2; Madhu P. Menon, MD, PhD.1 Departments of 1Pathology and 2Hematopathology, University of Utah/ARUP Laboratories, Salt Lake City, Utah.

Context: CD5 and/or CD10 expression in lymphoplasmacytic lymphoma (LPL) is uncommon and could be a diagnostic pitfall vis-à-vis chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). We studied MYD88L265P-mutated CD5+ and/or CD10+ LPL.

Design: A 5-year archive search revealed 8 CD5+ and/or CD10+ MYD88L265P LPL cases (5 CD5+, 2 CD10+/CD5+, 1 CD10+). Bone marrow (BM) aspirates/cores/clots and immunohistochemistry findings for CD20, CD3, LEF1, cyclin D1, BCL6, and CD117 were reviewed. Flow cytometry data were evaluated for median fluorescence intensity (MFI) (FCSExpress 6), using Navios/FC500.

Results: Most patients were male (7 of 8) (median age, 70 years) and had lymphadenopathy (5 of 8). Median M-protein (IgM) was 1.27 g/dL. Morphologically, BMs had 30% median involvement, with predominantly interstitial (6 of 7), intertrabecular (5 of 7), paratrabecular (4 of 7), and diffuse (3 of 7) patterns. All BMs showed plasmacytic differentiation (7 of 7, 5% median plasma cells). Most BMs had a morphologic spectrum: plasma cells, plasmacytoid lymphocytes, and small lymphocytes (6 of 7); increased mast cells (6 of 7); and hemosiderin-laden macrophages (4 of 7). One of 7 cases had prominent Dutcher bodies. By flow cytometry, CD5+ LPL cases showed dim CD20 (3 of 7), CD23+ (4 of 7), CD38+ (5 of 7), and CD200+ (5 of 7). None had dim light chains (0 of 7). Compared with CLL, CD5+ LPL median CD5 and CD23 MFI ratios were consistently lower (Table).

Conclusions: We describe clues to diagnosing CD5/CD10+ LPLs. These cases had a marked male predominance (7:1) and frequent lymphadenopathy without lymphocytosis. Paratrabecular infiltrates and increased mast cells were commonly observed. CD5/CD23 were mostly dim to negative, while CD20 and light-chain intensities were retained (cf. CLL). Although CD200 can be expressed in CD5+ LPL, LEF1 and BCL6 were negative.

Atypical Presentation of Plasmablastic Lymphoma Mimicking Ovarian Cancer and Peritoneal Carcinomatosis

(Poster No. 107)

Jing Di, MD, PhD ([email protected]); Leonard N. Yenwongfai, MD; Andre N. Ene, MD; Sahar Nozad, MD. Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington.

Plasmablastic lymphoma (PBL) is an aggressive disease showing diffuse proliferation of large malignant cells. It frequently involves the oral cavity and is associated with HIV infection, but it may occur in other extranodal regions, including skin, bone, and central nervous system. Here, we report a case of a 43-year-old woman presenting with abdominal pain and bilious emesis who was found to be HIV positive. Imaging revealed an ovarian mass with extensive peritoneal involvement suggestive of carcinomatosis. She underwent an emergency exploratory laparotomy, salpingo-oophorectomy, and colectomy, which revealed a large 10-cm mass compromising the cecum with ischemic changes of the cecal wall and impending perforation and numerous deposits along the interface of the serosa and mesentery of the small bowel, as well as a large left ovarian mass resembling a Krukenberg tumor. Microscopic examination demonstrated that multiple tissues, including the ovary, fallopian tube (Figure 1.107, A), large and small intestine, and omentum were extensively involved with abundant atypical plasmablastic and plasmacytoid cells, associated with numerous mitoses and apoptotic debris. Immunohistochemical stains were positive for CD138 (Figure 1.107, B), MUM1 (Figure 1.107, C), EBER in situ hybridization (Figure 1.107, D), EMA, and C-MYC and displayed partial dim positivity for CD30 and CD45. They were negative for CD3, PAX5, HHV8, ALK, calretinin, SOX10, and CD68. The overall morphologic findings and immunophenotypic profile were diagnostic of PBL. This case shows an atypical presentation of PBL and emphasizes the importance of considering the possibility of lymphohematopoietic diseases, especially in immunocompromised patients, even in the absence of supportive radiographic findings, to avoid extensive surgery.

Focal Lymphoplasmacytic Lymphoma of the Bladder: An Extremely Rare Presentation

(Poster No. 108)

Ahmad M. Alkashash, MD ([email protected]); Mehdi Nassiri, MD. Department of Pathology, Indiana University, Indianapolis.

Focal lymphoplasmacytic lymphoma of the bladder has never been reported before. Here we present a case of urinary bladder lymphoplasmacytic lymphoma. The patient was a 61-year-old man who first presented with prostatic symptoms in 2014. A transurethral bladder biopsy was performed and showed significant inflammation with lymphocytes/plasma cells and no evidence of carcinoma. Tamsulosin treatment partially improved his symptoms, and he had another biopsy in 2019 that showed reactive-looking urothelium, with chronic inflammatory cells within the urothelium and lamina propria, in addition to numerous nests of amorphous, eosinophilic material that was surrounded by multinucleated giant cells. Immunohistochemistry showed a dense lymphoplasmacytic infiltrate of CD138-positive κ light-chain–predominant plasma cells. No further workup was done owing to loss of tissue. Two years later, the patient underwent cystoscopy and biopsy that showed extensive deposit of amorphous material and lymphoplasmacytic infiltrate. Immunohistochemistry showed B-cell nodules positive for PAX5, CD20, and CD23. Plasma cells had a larger population of IgM-expressing cells with κ light-chain restriction. Congo red and SSAB stains were negative for amyloid deposits. Liquid chromatography–tandem mass spectrometry was done, and the deposits were found to be composed of κ immunoglobulin light chains and μ immunoglobulin heavy chains. Molecular PCR studies revealed immunoglobulin heavy chain (IgH) and κ chain (IgK) clonal gene rearrangement and MYD88 L265 mutation. In summary, although primary lymphoma involving the bladder has been reported before, to our knowledge, this is the first report of focal lymphoplasmacytic lymphoma in this location (Figure 1.108).

Extranodal Marginal Zone Lymphoma in Ventricle of Central Nervous System

(Poster No. 109)

Nfn Kiran, MD ([email protected]); Raghunath Ramanarasimhaiah, MD; Meena Kashi, MD; Wei Xue, MD. Department of Pathology, Staten Island University Hospital, Northwell Health, Staten Island, New York.

Dural meningeal marginal zone lymphoma (MZL) has been well recognized; however, ventricle MZL is very rare. We report a case of an 80-year-old woman with a history of hypertension who presented with a 1-year history of frontal throbbing headache not associated with visual changes. Brain MRI showed enhancing soft tissue within the atrium, occipital, and temporal horns of the left lateral ventricle, with interval increase in associated periventricular edema. Histopathology revealed a dense diffuse infiltrate of small lymphoid cells with dark nuclei, inconspicuous nucleoli, and scant to moderate pale cytoplasm with occasional ill-defined aggregates of larger cells with the appearance of germinal centers. Scattered psammomatous calcification was seen in the lymphoid infiltrate and in adjacent dense fibrous tissue. No brain parenchyma was identified (Figure 1.109, A and B). The atypical cells were positive for CD20 (Figure 1.109, C) and PAX5 and negative for cyclin D1, CD5, CD10, CD43, and EBER. Ki-67 was about 20% (Figure 1.109, D). There was marked excess of κ+ plasma cells and plasmacytoid cells compared with λ. A diagnosis of B-cell lymphoma with features consistent with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) was rendered. Bone marrow biopsy consisted of 10%–20% lymphoma cells. Our patient had no lymphadenopathy or pathologic FDG uptake by whole-body PET-CT scanning; hence, the differential diagnosis included primary ventricle MZL versus systemic MZL involving the ventricle (both are very rare). Either way, the patient had a marked clinical response to radiation of the skull and spine followed by systemic treatment with chemotherapy.

Atypical Mast Cells With KIT Mutation May Be Overshadowed by Enteropathy-Associated T-Cell Lymphoma

(Poster No. 110)

Farshid Kashef, MD, MS1 ([email protected]); Liang Ding, MD, PhD1; Sharmila Ghosh, MD1; Kai Fu, MD, PhD2; Aftab Lalarukh, MD.1 1Department of Pathology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York; 2Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Enteropathy-associated T-cell lymphoma (EATL) is a rare (0.5–1.0 per million) peripheral T-cell lymphoma with a male predilection. We report a case of co-occurring EATL and mastocytosis in a 75-year-old White woman with newly diagnosed celiac disease (based on clinical presentation, serology, and duodenal biopsies). Her symptoms got progressively worse despite treatment. She underwent exploratory laparotomy and small-bowel resection. Histopathology showed mucosal ulceration with jejunum mucosal/submucosal polymorphic infiltration of many moderate-sized to large, atypical lymphocytes in a diffuse inflammatory background (Figure 1.110, A). Extensive necrosis involved the full thickness of the bowel wall. Immunohistochemistry studies highlighted positivity of CD3 and CD30 with diffuse CD7 (Figure 1.110, B) and TIA1 and negativity of ALK1, EBER, CD2, CD5, CD20, CD103, and CD56. The Ki-67 index was 40%. Clonal T-cell receptor γδ chain gene rearrangements were detected. The clinical and histologic features were compatible with EATL. Bone marrow biopsy performed for staging of lymphoma revealed spindle-shaped mast cells (Figure 1.110, C) positive for tryptase, CD117, and CD25 (Figure 1.110, D). The presence of c-Kit (D816V) mutation further confirmed mastocytosis. This case demonstrates that the diagnosis of EATL, which commonly involves the jejunum, may be missed if only the duodenum is biopsied, as is usual for evaluation of celiac disease. This is the first case report of co-occurring EATL and mastocytosis. EATL usually carries an aggressive course and a poor prognosis; how mastocytosis/c-Kit mutation affects the course and prognosis of EATL needs close follow-up. The mechanism of the occurrence of EATL and mastocytosis is unknown and needs further study.

Aggressive NK Cell Leukemia: A Rare Cause of Fulminant Hemophagocytic Lymphohistiocytosis

(Poster No. 111)

Asma Arshia, MBBS ([email protected]); Melissa V. Kesler, MD. Department of Pathology, University of Kentucky, Lexington.

Aggressive natural killer (NK) cell leukemia is a rare systemic neoplastic proliferation of NK cells frequently associated with Epstein-Barr virus (EBV) and an aggressive clinical course. Clinical manifestations include fever, hepatosplenomegaly, pancytopenia, and high serum LDH, and the course is frequently complicated by coagulopathy, hemophagocytic syndrome, and/or multiorgan failure. We report a case of aggressive NK cell leukemia in a 43-year-old woman admitted with shock, splenomegaly, and pancytopenia. Laboratory analysis showed high ferritin levels, markedly elevated serum EBV DNA by PCR, and increased LDH. Bone marrow touch prep showed abnormal large lymphoid cells with vacuolated cytoplasm and distinct nucleoli with associated hemophagocytosis (Figure 1.111, A), while the biopsy (Figure 1.111, B and C) showed an interstitial infiltrate of morphologically similar cells with an NK cell phenotype and EBER positivity comprising approximately 40% of marrow cellularity. Flow cytometry (Figure 1.111, D) showed an atypical NK cell population (10%–12% expressing bright CD45, bright CD38, bright CD56, CD2, bright CD7, CD8, and partial HLA-DR; negative for CD3, CD5, TDT, CD57, T-cell receptor α-β, and T-cell receptor γδ). Aggressive NK cell leukemia carries a poor prognosis with a median survival of only 2 months, and treatment is often difficult owing to accompanying organ dysfunction. Ideally, aggressive NK cell leukemia is treated with PEG asparaginase and ifosfamide-based treatment. However, given her poor liver function, the patient could not tolerate this regimen and was treated with gemcitabine and oxaliplatin. Although rare, timely diagnosis and good clinical information are essential for effective treatment.

IRTA1 Expression by Immunohistochemistry in Extranodal Marginal Zone Lymphomas at Various Anatomic Sites

(Poster No. 112)

Narendra Bhattarai, MD ([email protected]); James Cook, MD, PhD. Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio.

Context: The diagnosis of extranodal marginal zone lymphoma (MALT lymphoma) is challenging owing to the absence of sensitive and specific immunomarkers, along with morphogenetic heterogeneity at different anatomic sites. We examined the spectrum of immune receptor translocation–associated protein 1 (IRTA1) expression in MALT lymphomas at differing anatomic sites.

Design: Fifty-five cases of MALT lymphomas, from stomach (n = 10), salivary glands (n=10), lungs (n=8), conjunctiva (n=9), skin (n= 10), and breast (n = 8), were selected. IRTA1 immunohistochemistry was performed by using a commercial antibody (EPR21961, Abcam).

Results: At least some expression of IRTA1 was identified in 20 of the 55 cases (36%), with the highest incidence in lung (7 of 8, 87.5%) followed by conjunctiva (4 of 9, 44%). The percentage of B cells positive for IRTA1 ranged from rare scattered cells (<5%) to 50% in 1 pulmonary MALT lymphoma (Figure 1.112, A and B: breast MALT with approximately 10% IRTA1-positive B cells; Figure 1.112, C and D: lung MALT). Twenty-six cases contained lymphoepithelial lesions (LELs), of which 7 (27%) showed IRTA1 staining within the LELs (3 salivary glands, 2 lungs, 1 stomach, and 1 conjunctiva). At least focal areas of monocytoid cells were present in 37 cases, of which 6 (16%) showed positive IRTA1 staining in monocytoid cells.

Conclusions: IRTA1 expression is variable in extranodal MALT lymphoma, and, when present, IRTA1-positive cells typically represent only a small percentage of cells. The neoplastic cells in LELs and monocytoid areas in most cases are negative for IRTA1. The cases exhibiting at least some IRTA1 staining vary by anatomic site, consistent with the concept of differing pathologic features at distinct anatomic locations.

CD274-MLANA–Rearranged Epstein-Barr Virus–Negative Extranodal NK/T-Cell Lymphoma

(Poster No. 113)

Ronald K. Phillips III, BS1 ([email protected]); Karen Ferreira, PhD1; ThomasOllila,MD2; AdamOlszewski,MD2; Habibe Kurt, MD1; Diana Treaba, MD.1 Departments of 1Pathology and Laboratory Medicine and 2Division of Hematology-Oncology, The Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Extranodal natural killer cell/T-cell lymphoma (ENKTL) is classically associated with Epstein-Barr virus (EBV) infection. EBV-negative ENKTLs are rare, with exceptionally few detailed case reports published. We present a case of a 58-year-old White man with no significant medical history, admitted after 6 weeks of fever, night sweats, chills, and weight loss. Laboratory results revealed anemia, thrombocytopenia, neutropenia, and lymphocytopenia. Morphologic, immunophenotypic, and molecular analysis of a hypercellular bone marrow biopsy revealed involvement by an ENKTL. An incidentally found testicular mass removed via radical orchiectomy uncovered a 1-cm seminoma, areas of testicular atrophy, and patchy lymphoid infiltrates with marked cellular heterogeneity, angiocentricity, and angioinvasion (Figure 1.113, A), fibrinoid necrosis, and a high proliferation rate. The neoplastic lymphoid population coexpressed CD56+ (Figure 1.113, B), mostly cytoplasmic CD3+ (Figure 1.113, C), granzyme B+ (Figure 1.113, D), TIA1+, MUM1+, p53+, CD8+, variably CD30+, and PDL1+. EBV by in situ hybridization was negative. Molecular studies performed on the marrow and testis were negative for TRB and TRG rearrangements, supporting a diagnosis of non-nasal, EBV-negative ENKTL. Genomic analysis revealed a CD274::MLANA fusion, as well as SMARCA4 R1243W and TP53 R273H mutations. CD274::MLANA fusion has been previously described in a case of central nervous system primary diffuse large B-cell lymphoma, and the proposed mechanism of oncogenesis likely involves the loss of inhibitory microRNA binding sites, leading to overexpressed PD-L1 and immune system evasion. To our knowledge, this is the first case of CD274-MLANA–rearranged EBV-negative ENKTL reported, and the PD-L1 expression raises consideration for anti–PD-1 agents in the treatment of these aggressive lymphomas.

Chronic Lymphocytic Leukemia With Coexistent Herpes Lymphadenitis: Report of a Rare Case

(Poster No. 114)

Hossein Hosseini, MD1 ([email protected]); Ahmed Bendari, MBBCh1; Sunder Sham, MBBS1; Jordan M. Steinberg, MD1; Maiko Kondo, MD2; Randy Levine, MD1; Susan C. Jormark, MD1; Alyssa Yurovitsky, MD.1 Departments of 1Pathology and Laboratory Medicine and 2Medicine, Lenox Hill Hospital, New York, New York.

Patients with chronic lymphocytic leukemia (CLL) are at an increased risk of infectious complications. Herpes lymphadenitis is rarely encountered in patients with CLL and can mimic high-grade transformation. To our knowledge, there are only 25 cases of localized or regional herpes lymphadenitis in patients with hematologic malignancies reported in the English-language literature. We present a case of an 86-year-old man with a medical history significant for chronic kidney disease, CLL, and Waldenstro¨m macroglobulinemia who was admitted to our institution for uremic encephalopathy. He had been diagnosed with relapsed CLL 3 weeks before his admission but was not receiving treatment. Physical examination revealed cervical, axillary, and inguinal lymphadenopathy. Laboratory results were notable for anemia, thrombocytopenia, markedly elevated BUN and creatinine, and mildly elevated LDH. Imaging demonstrated splenomegaly and intensely FDG-avid retroperitoneal and pelvic lymphadenopathy, suggesting Richter transformation. Inguinal lymph node biopsy showed diffuse proliferation of monotonous small lymphocytes and large areas of necrosis (Figure 1.114, A). Immunohistochemically, the lymphocytes expressed CD5 (Figure 1.114, B), CD20 (Figure 1.114, C), and PAX5 extensively and strongly, and lacked expression of CD23. Cyclin D1 and SOX11 were negative, which excluded mantle cell lymphoma. The Ki-67 proliferation index was low (10%–15%). These findings were consistent with small lymphocytic lymphoma (SLL)/CLL. GMS and AFB stains were negative. Immunohistochemical stains for HSV1/HSV2 both showed positivity within the necrotic areas (Figure 1.114, D), which confirmed herpes lymphadenitis. The patient subsequently received appropriate antiviral treatment. Although it is rarely encountered, it is prudent to consider herpes lymphadenitis along with high-grade transformation in CLL/SLL patients with extensive lymphadenopathy to avoid unnecessary aggressive chemotherapy.

Extramedullary Hematopoiesis in an Inguinal Lymph Node: An Unusual Presentation of Primary Myelofibrosis

(Poster No. 115)

Nausheen Yaqoob, MBBS, FCPS1 ([email protected]); Neelum Mansoor, MBBS, FCPS2; Hania Naveed, MBBS, FCPS1; Saba Jamal.1 Departments of 1Histopathology and 2Hematology, Indus Hospital and Health Network, Karachi, Pakistan.

Extramedullary hematopoiesis (EMH) is a proliferation of hematopoietic tissue outside the bone marrow medullary space. It is a pathophysiologic response, associated with either a benign reactive hematologic disease or a myeloproliferative neoplasm (MPN). Identification of EMH in adults is always pathologic. It is highly unlikely for MPNs to present with inguinal lymphadenopathy. We report a case of a 61-year-old man who initially presented with anemia, fatigue, and weight loss. On examination, he had massive splenomegaly. Chest radiography revealed consolidation secondary to right-sided pleural effusion. He was suspected to have a lung carcinoma. Lymph node biopsy revealed extensive fibrosis effacing the nodal architecture. An abnormal blood picture raised the possibility of bone marrow infiltration. Bone marrow revealed hematopoietic precursors within the sinuses and megakaryocytic atypia. An extensive panel of markers tested on lymph node and bone trephine showed increased positivity for CD61. However, the diagnosis was made when cytogenetic analysis was performed. FISH for BCR-ABL1 was negative, while karyotyping revealed balanced and unbalanced translocations between chromosomes 4, 12, and 1, 6, respectively, resulting in gain of 1q. Translocations led to the diagnosis. These are known to be associated with genetic alterations involved in the pathogenesis of primary myelofibrosis. Loss of TP53 plays a critical role in cancer biology. Major protein regulators of TP53 are MDM2 and MDM4, located on chromosomes 1q and 12q, respectively. Awareness of unique clinical presentations and an integrated approach toward diagnosis is the key to challenging cases. Pathologists must consider and correlate all the diagnostic tools, including cytogenetic analysis, before signing out such ambiguous cases (Figure 1.115).

Lymphoma Cells Nonspecifically Bind to PerCp-Cy5.5 Fluorochrome Conjugates: A Rare Phenomenon and Diagnostic Pitfall

(Poster No. 116)

Michael M. Timm, BA ([email protected]); Matthew T. Howard, MD; Dragan Jevremovic, MD, PhD; Ji Yuan, MD, PhD; Dana J. Roh, MS; Pedro Horna, MD; Horatiu Olteanu, MD, PhD; Min Shi, MD, PhD. Department of Hematopathology, Mayo Clinic, Rochester, Minnesota.

PerCP-Cy5.5–based antibody conjugates are widely used for multicolor flow cytometry in clinical practice. We report the first case of a B-cell lymphoma nonspecifically binding PerCP-Cy5.5–conjugated CD34 antibody, mimicking B lymphoblastic leukemia. The patient was an 88-year-old man with a history of bladder carcinoma, heart failure, diabetes, and an unintended 30-lb weight loss for the past year without fever or night sweats. CBC showed Hb 6.8 g/dL, WBC 49 ×109/L, lymphocytes 41 ×109/L, and platelets 133×109/L. CT scanning showed splenomegaly without lymphadenopathy. Peripheral blood smear revealed lymphocytosis with a mature appearance, including condensed chromatin and moderate cytoplasm. Peripheral blood flow cytometry demonstrated a κ light-chain–restricted B-cell population (88% of lymphocytes) that was positive for CD19, CD20, CD22, CD45, and CD79a and negative for CD5, CD10, and CD200. Uniform expression of CD34–PerCp-Cy5.5 by the tumor cells suggested immaturity. However, further investigation revealed the tumor cells had strong immunoreaction to any PerCP-Cy5.5–conjugated antibodies, including CD3, CD11c, CD16, CD23, CD34, and an isotype control. The neoplastic cells were negative for CD3-V450, CD16-APC-H7, CD23-APC, and CD34-BV421. They showed no immunoreaction to other isotype controls for FITC, PE, PE-Cy7, APC, APC-H7, and V450. A PerCP-Cy5.5 “fluorescence minus one” control was negative (Figure 1.116, A through D). To our knowledge, this is the first report to demonstrate that B-cell lymphoma may strongly bind to PerCP-Cy5.5–conjugated antibodies in an idiotype-independent manner. Identifying this phenomenon could be challenging, especially when an isotype control is not routinely performed. This case emphasizes that integrating morphologic and immunophenotypic features is essential to making an accurate diagnosis.

Extracavitary Primary Effusion Lymphoma With Aberrant CD3 Expression

(Poster No. 117)

Charmaine Joyce L. Ilagan, MD ([email protected]); Yiannis Petros Dimopoulos, MD; Metin Ozdemirli, MD, PhD. Department of Pathology and Laboratory Medicine, MedStar Georgetown University Hospital, Washington, District of Columbia.

Primary effusion lymphoma (PEL) is a rare, aggressive HHV-8–associated large B-cell lymphoma occurring usually in the setting of HIV infection. Pleural, pericardial, or peritoneal effusions are the typical presentations; however, extracavitary solid variants can occur. Aberrant expression of T-cell markers is rare. We report a case of an extracavitary variant of PEL with this unusual immunophenotype. A 59-year-old man with a history of poorly controlled HIV infection (CD4 count: 10 cells/μL; HIV viral load: 85 597 copies/mL), Epstein-Barr virus viremia (1006 copies/mL), and skin squamous and basal cell carcinomas presented with dyspnea and upper extremity swelling, with concerns for superior vena cava syndrome. A right hilar mass (7.2 cm) was identified on imaging, initially concerning for metastasis. Endobronchial biopsies revealed atypical lymphoid cells in the submucosa (Figure 1.117, A). The cells showed diffuse positivity for MUM-1, Ki-67, HHV-8 (Figure 1.117, B), and EBER (Figure 1.117, C), and weak positivity for cytoplasmic CD3 (Figure 1.117, D), CD30, and CD45. The cells were negative for other B-cell markers and CD138. PCR studies revealed monoclonal immunoglobulin heavy-chain gene rearrangement and polyclonal T-cell receptor gene rearrangement. Pleural effusion was negative. The diagnosis of HHV-8–positive large B-cell lymphoma with aberrant CD3 expression was rendered, and treatment was administered (EPOCH-R). After initial response to treatment, the patient eventually developed a large brain mass and passed away. Pathologists should be cognizant of aberrant T-cell marker expression and lack of conventional B-cell marker expression in extracavitary PEL and maintain a high index of suspicion for this entity in HIV patients.

Blastoid Variant of Mantle Cell Lymphoma: A Case With Unusual Clinical Presentation and Coexisting BCL6 Gene Rearrangement

(Poster No. 118)

Jiani N. Chai, MD, PhD ([email protected]); Azal Al Ani, MD; Yanhua Wang, MD, PhD; Xuejun Tian, MD, PhD. Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York.

Mantle cell lymphoma (MCL) is an aggressive mature B-cell lymphoma with different variants that often cause diagnostic confusion. We present a case of a 61-year-old woman who presented with leukocytosis (WBC, 46.7 k/μL). A peripheral blood smear showed abundant intermediate-large cells with fine chromatin and moderate cytoplasm resembling blasts (Figure 1.118, A). Flow cytometry revealed an abnormal population in the blast gate (Figure 1.118, B), which raised concern for acute leukemia. Further flow analysis revealed the abnormal population to be positive for CD19, CD5, CD23 (heterogeneous), CD45, IgM, FMC7, ZAP70, and κ and negative for CD10, CD200, and λ. The immunophenotype was consistent with CD5+ mature B-cell lymphoma with blastoid morphology. Imaging studies revealed diffuse lymphadenopathy and splenomegaly. Axillary lymph node biopsy revealed atypical lymphoid infiltration with predominantly small lymphocytes (Figure 1.118, C). The atypical cells were positive for CD5, CD19, CD20, PAX5, BCL-1 (Figure 1.118, D), and BCL-2 and negative for CD10, TdT, BCL6, and LMP1. Ki-67 was up to 80%. p53 was weakly positive in a subset of cells. In addition to the characteristic t(11:14), FISH also detected BCL6 rearrangement. A diagnosis of MCL with aggressive features was rendered on tissue biopsy. The patient died shortly after initial presentation despite aggressive treatment. Autopsy showed multiorgan involvement of MCL, including the liver, lung, spleen, gallbladder, and bone marrow, with a spectrum of morphologic presentations. The discordant histomorphology of this case, including the blastoid variant/leukemic phase in the peripheral blood and smallcell variant in the lymph node, posed a diagnostic challenge. BCL6 rearrangement occurs rarely in MCL; whether this has any prognostic value remains to be investigated.

Atypical Lymphoid Infiltrates in Gastric Biopsies: Clinicopathologic Features and Follow-Up

(Poster No. 119)

Moyosore D. Awobajo, MD1 ([email protected]); Jacob P. Ritter, MD1; Raina R. Flores, MD1; Alia N. Nazarullah, MD1; Daniel D. Mais, MD.2 1Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at San Antonio; 2Department of Pathology and Laboratory Medicine, University of Louisville, Kentucky.

Context: Mucosa-associated lymphoid tissue (MALT) lymphoma mostly arises within gastric mucosa. Diagnosis can be challenging owing to lack of specific immunophenotypic or genetic abnormalities. Identifying atypical lymphoid infiltrates (ALIs) is a reflection of this diagnostic challenge. The criteria and significance of ALIs in gastric biopsies are not clearly established. We aim to study the clinicopathologic features of gastric ALIs and correlate them with follow-up data.

Design: A retrospective review was performed in patients diagnosed with ALI and MALT lymphoma on gastric biopsies from 2010 to 2020. Sixty-two cases were identified and correlated with clinicopathologic follow-up information to identify evidence of progression to lymphoma.

Results: Of 62 cases, 37 (60%) with gastric ALIs showed no evidence of lymphoma on follow-up biopsy. Four (6%) with ALIs showed evidence of MALT lymphoma on subsequent biopsy. Ten (16%) were diagnosed as MALT lymphoma on initial biopsy. Eleven ALI cases (18%) were lost to follow-up. Compared with ALIs without progression, ALIs with progression and MALT lymphoma cases showed frequent lymphoepithelial lesions (LELs), aberrant immunophenotype, and evidence of clonal B-cell gene rearrangement. No significant correlation with Helicobacter pylori was identified (Table).

Conclusions: Most gastric ALIs show no evidence of progression to lymphoma. Presence of frequent LELs, aberrant phenotype, and IgH clonality are high-risk features that warrant close follow-up for progression to MALT lymphoma.

Flow Cytometry Analysis of Pediatric Acute Promyelocytic Leukemia

(Poster No. 120)

Anup Jnawali, MD1 ([email protected]); Jacob Bledsoe, MD.2 1Department of Pathology, University of Massachusetts Memorial Medical Center, Worcester; 2Department of Pathology, Boston Children's Hospital, Boston, Massachusetts.

Context: Prompt diagnosis of acute promyelocytic leukemia (APL) is essential, and characteristic immunophenotypic features, including negativity for CD34 and HLA-DR, have been described mostly in adult populations.

Design: Flow cytometric and morphologic data from 24 cases of pediatric APL with PML-RARA at a single institution from 1999 to 2021 were reviewed. Comparison of frequency of antigen expression between hypergranular and microgranular variants was performed with a 2-tailed Fisher exact test.

Results: HLA-DR was negative or minor subset/dim in 100% of hypergranular and 55% of microgranular cases of APL (P=.01). CD34 negativity and combined HLA-DR/CD34 negativity were present in 69% of hypergranular and just 9% of microgranular cases (P=.005). CD34 was uniformly positive in 45% of microgranular and 15% of hypergranular cases (P = .18). Monocyte marker CD64, CD14, or dim/subset CD4 expression was present in 75%, 33%, and 30% of hypergranular cases and 63%, 25%, and 57% of microgranular cases, respectively. At least subset CD2 expression was seen in 88% of microgranular and 33% of hypergranular cases of APL (P=.049). The most common immunophenotype for hypergranular APL in this cohort was CD34 HLA-DR CD64+ CD14/+ CD4/+ CD2/+, while microgranular APL was CD34+/subset HLA-DR/subset CD64+ CD4dim/subset CD2dim/subset CD14/+ (Table).

Conclusions: In this pediatric cohort, HLA-DR negativity, along with negative or subset CD34, was a useful feature to identify hypergranular APL. In contrast, most microgranular APL cases expressed or partially expressed CD34 along with subset HLA-DR expression. CD2 expression was frequent in microgranular APL. Monocyte markers CD64, CD14, and CD4 were expressed at higher frequencies than in prior studies and do not preclude the diagnosis of APL.

Double-Hit B-Cell Lymphoma With Dim CD45 Expression and Absence of Surface Immunoglobulin Light Chains

(Poster No. 121)

Hafiz A. Yahya, MD ([email protected]); Varsha Prakash, MD; John T. Lam, MD. Department of Pathology, University of Mississippi Medical Center, Jackson.

Translocation of the MYC proto-oncogene with a concurrent BCL2 or BCL6 translocation as recognized by fluorescence in situ hybridization (FISH) or standard cytogenetics (karyotype) characterizes double-hit lymphoma (DHL). Cases of DHL with immature features favoring B lymphoblastic leukemia/lymphoma (B-LBL) are rare and may show TdT positivity, dim CD45 expression, lack of CD20, or lack of surface immunoglobulin light chain by flow cytometry and immature morphology. We present an unusual case of DHL with features of B-LBL. An 83-year-old man presented with thrombocytopenia and circulating blasts concerning for acute leukemia (Figure 1.121, A). Bone marrow evaluation revealed sheets of monomorphous precursors with scant cytoplasm and dispersed nuclear chromatin (Figure 1.121, B). Immunohistochemistry showed that the immature cells were positive for CD10, CD38, CD79a, and PAX5 and negative for CD3, CD20, CD34, CD117, TdT, BCL6, and cyclin D1. CD43 and BCL2 showed weak positivity in a few cells. The proliferative index was very high (Ki-67 approximately 100%). Flow cytometric studies performed on this patient's blood showed 18% immature cells with dim CD45 expression (Figure 1.121, C; immature cells are highlighted in blue) and absence of CD20 and surface Ig light chains (Figure 1.121, D; immature cells are highlighted in blue). FISH analysis performed on the patient's pleural fluid showed MYC and BCL2-IGH rearrangements. Chromosomal analysis performed on this patient's blood confirmed the presence of DHL. DHL with immature features is associated with a poor clinical outcome. This patient died 10 months after diagnosis.

AML Patients With Frameshifted RUNX1 May Show Superior Survival After Allogeneic Stem Cell Transplant Compared With Those With Other Types of Somatic RUNX1 Mutations

(Poster No. 122)

Sindha Madhav, MD1; Rawan Tahboub, MD1 ([email protected]); Lloyd Hutchinson, PhD1; Anthony Nunes, PhD2; William Selove, MD.1 Departments of 1Pathology and 2Population and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester.

Context: Allogeneic stem cell transplant (allo-SCT) is a mainstay of treatment for acute myeloid leukemia (AML). Its efficacy depends largely on the immune response of donor T lymphocytes against leukemia cells (graft versus leukemia effect). RUNX1 is a transcription factor that is commonly mutated in AML. RUNX1 alterations include frameshift mutations and other types of mutations (eg, substitutions). Previous studies have demonstrated enhanced immunogenicity of frameshift-derived proteins in many tumor types via the production of neoepitopes. We therefore hypothesized that AML patients with somatic frameshift RUNX1 mutations, undergoing allo-SCT, would experience superior outcomes to those with nonframeshift mutations through a more vigorous graft versus leukemia effect.

Design: We retrospectively searched our institutional electronic medical records and sequencing database for patients with RUNX1-mutated AML who had undergone allo-SCT between 2010 and 2019. We examined overall survival and relapse-free survival after transplant, using the Kaplan-Meier method.

Results: Fifteen patients were identified who fit the criteria: 7 with RUNX1 frameshifts and 8 with other types of RUNX1 mutations. Patient and tumor characteristics were similar in the 2 groups. Overall survival was superior in the frameshift group (Figure 1.122) versus the nonframeshift group (HR: 6.1; P = .008). Relapse-free survival trended better for patients with frameshift (P = .19).

Conclusions: Our findings suggest that patients with frameshift RUNX1-mutated AML may benefit more from allo-SCT than those with nonframeshift mutations, possibly owing to a greater likelihood for frameshift mutations to generate immunogenic neoepitopes. Larger studies exploring the posttransplant survival impact of somatic frameshift mutations in RUNX1 and other genes are warranted.

High-Grade B-Cell Lymphoma With MYC and BCL2 Rearrangements and Hodgkin-like Morphology

(Poster No. 123)

Zachary Chelsky, DO, MS ([email protected]); Kelly Bowers, DO; Richard Hammer, MD; Katsiaryna Laziuk, MD. Department of Pathology and Anatomical Sciences, University of Missouri, Columbia.

High-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL) is a distinct category in the WHO classification. Approximately 50% of cases show a diffuse large B-cell lymphoma morphology. We present a case of an 82-year-old man with a submandibular mass for whom molecular studies were critical to the diagnosis of HGBCL. Fine-needle aspiration demonstrated enlarged cells with variable nuclear pleomorphism and prominent nucleoli, with the differential diagnosis of Hodgkin lymphoma. Subsequent excision showed lymphoid tissue with pleomorphic neoplastic cells composed of medium to large cells with mononucleation, binucleation, and multinucleation reminiscent of Hodgkin–Reed-Sternberg cells (Figure 1.123, A). Neoplastic cells marked as B cells were positive for CD20 (Figure 1.123, B), PAX5, Oct2, and Bob1 and showed positivity for CD45, CD30 (Figure 1.123, C), BCL2, CMYC (80%) (Figure 1.123, D), MUM1, and PD-L1. Ki-67 proliferative index was 70%. EBV-LMP and EBER-ISH were negative. Flow cytometry did not reveal a clonal B-cell population or phenotypically aberrant T-cell population. Immunoglobulin gene rearrangement was negative. Fluorescence in situ hybridization identified rearrangements in CMYC and BCL2, leading to the diagnosis of HGBCL with MYC and BCL2 rearrangements. Flow cytometry may have been negative from lack of surface immunoglobulin expression, possibly resulting from numerous point mutations introduced during expansion in a follicle center (somatic hypermutation). Such a scenario may also explain the negative gene rearrangement studies, as hypermutation of immunoglobulin genes may have prevented binding of PCR primers. This case provides an example of HGBCL with atypical morphology and highlights the importance of molecular studies in the diagnosis of lymphoid neoplasms.

Hammer has received grant or research support from GE, Flagship Bioscience, Roche, and Foundation Medicine, is on the Foundation Medicine, Roche, and Caris Advisory Boards, and is a speaker for Roche.

A Clinically and Morphologically Challenging Angioimmunoblastic T-Cell Lymphoma Case

(Poster No. 124)

Anna Sarah Erem,MD ([email protected]); Saja Asakrah, MD, PhD. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive subtype of peripheral T-cell lymphoma originating from follicular helper T cells. AITL is characterized by abnormal immune and inflammatory response, with a range of features that mimic inflammatory disorders. Clinicians from different disciplines may be involved in the care of such patients. Effective collaboration among clinicians is essential for rendering an accurate diagnosis. We present a case of a 51-year-old man with a puzzling clinical course. Initially, he presented with multiple skin lesions and pleural effusion. Blood work revealed thrombocytopenia and plasmacytosis. Imaging showed lymphadenopathy and splenomegaly. The patient underwent multiple inconclusive needle biopsies. Laboratory tests showed hypoalbuminemia, abnormal liver function tests, and high levels of ferritin, triglyceride, soluble IL2 receptor, and IL6. Infection workup showed Epstein-Barr virus (EBV) viremia. During hospitalization, the patient experienced acute respiratory distress and cardiac arrhythmia. The patient's course instigated many discussions among physicians and raised the possibilities of EBV-associated hemophagocytic lymphohistiocytosis, EBV-driven lymphoma, and multicentric Castleman disease. Morphologic evaluation of the subsequent lymph node biopsy confirmed the diagnosis of AITL. It showed partial architecture effacement by lymphohistiocytic infiltrates with frequent EBV-positive plasmablasts/immunoblasts. CD4 T cells predominated and expressed T-follicular helper markers, including BCL6, PD1, and ICOS (Figure 1.124, A through D). Flow cytometry of the bone marrow biopsy, pleural effusion, and peripheral blood sample showed polytypic plasmablasts. HHV8 was negative. Treatment included CHOEP chemotherapy with excellent clinical response. This is an example of a challenging AITL case requiring extensive laboratory workup and efficient communication among the involved clinicians and pathologists to facilitate an accurate diagnosis.

Systemic EBV-Positive T-Cell Lymphoma of Childhood Presenting in an Adult

(Poster No. 125)

Kemin Xu, MD ([email protected]); Nicholas Ward, MD. Department of Pathology, NYU Langone Health, New York, New York.

Systemic Epstein-Barr virus (EBV)–positive T-cell lymphoma of childhood (S-EBV-TCL) is a life-threatening illness of children and young adults characterized by a clonal proliferation of EBV-infected T cells with an activated cytotoxic phenotype. It is extremely rare, but reports of this disease have most frequently been in Asia, mainly in Japan, China, and Taiwan. We present a case of S-EBV-TCL in a 73-year-old woman of Chinese descent who presented with fever, pancytopenia, hyperferritinemia, acute kidney failure, acute liver injury, and respiratory failure, concerning for hemophagocytic lymphohistiocytosis (HLH). No lymphadenopathy was noted on imaging. EBV qPCR testing revealed EBV viremia (837 000 IU/mL). Bone marrow aspirate smears showed occasional histiocytes with engulfed immature erythroid and granulocytic cells (Figure 1.125, A), consistent with clinical impression for HLH. Bone marrow, in addition, revealed scattered large pleomorphic lymphoid cells (Figure 1.125, B) exhibiting immunohistochemical positivity for CD3, CD2, CD30, and CD8 and negativity for ALK1, CD4, CD5, CD56, and granzyme-B, and HHV-8. EBER-ISH showed many positive cells (Figure 1.125, C). Molecular testing was reported as positive for a T-cell receptor γ chain monoclonal gene rearrangement, whereas clonality by B-cell immunoglobulin rearrangement was negative. Concurrent cytogenetics reported multiple aberrations with a complex karyotype including a del(17p). The overall features were consistent with a systemic EBV-positive T-cell lymphoma of “childhood,” which is typically described in children. Our case highlights the potential for this disease to occur in adults and shows that it should be highly considered in the context of patients presenting with EBV viremia, multisystem organ failure, and hemophagocytic syndrome.

Detection of Crystals in Joint Fluid With Polychromatic Polarization Microscope

(Poster No. 126)

Husam Jum'ah, MD1 ([email protected]); Adib Keikhosravi, PhD2; Bin Li, MS3; Michael Shribak, PhD4; Kevin Eliceiri, PhD3; Agnes Loeffler, MD, PhD1; Salman Ayub, MD.1 1Department of Pathology, MetroHealth Medical Center/Case Western Reserve University, Cleveland, Ohio; 2Department of Biomedical Engineering, National Cancer Institute, Bethesda, Maryland; 3Laboratory for Optical and Computational Instrumentation, University of Wisconsin, Madison; 4Department of Biology, Marine Biological Laboratory, University of Chicago, Woods Hole, Massachusetts.

Context: Detection of crystals in joint fluid to diagnose gout (monosodium urate crystals) or pseudogout (calcium pyrophosphate crystals) involves examination of joint fluid aspirates with compensated polarized light microscopy (CPLM). A new polychromatic polarization microscope (PPM) allows detection of light at all angles relative to a polarizing object. This microscope is based on standard light microscopy and is equipped with a special polychromatic polarization state generator and achromatic circular analyzer. It can differentiate crystals by their appearance; monosodium urate crystals (Figure 1.126, A) are thin, needle shaped, and monochromatic, while calcium pyrophosphate crystals (Figure 1.126, B) are rhomboidal and stick together in aggregates. All crystals display different colors, based on their orientation. We aimed to compare the diagnoses of joint fluid aspirates by PPM versus CPLM.

Design: We prospectively studied 10 slides of joint fluid aspirates, using the PPM, after the primary diagnosis was rendered with the conventional method. The slides were reviewed by 1 investigator (who was blinded to the primary diagnoses) using the PPM. The samples were selected by another investigator to have 8 positive and 2 negative crystal cases.

Results: The overall rate of discrepancy in identifying the presence/absence of crystals, type of crystals, and contaminants between both modalities was 0%. Overall, the PPM appeared more sensitive than CPLM in detecting even very small and sparse crystals.

Conclusions: PPM is noninferior to the traditional CPLM for identifying crystals in joint fluid aspirates. The ultrasensitivity of this method might lead to overdiagnosis. Studying a larger sample is needed to assess the sensitivity and specificity of PPM.

Primary Diffuse Large B-Cell Lymphoma of the Maxilla Mimicking Osteomyelitis

(Poster No. 127)

Hanae Benchbani, MD; Jwan A. Alallaf, MD ([email protected]); Valerica Mateescu, MD. Department of Pathology, University of Missouri–Kansas City.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Primary intraosseous non-Hodgkin lymphoma in the maxilla is uncommon, representing <1% of all extranodal lymphomas. We present 2 cases of incidental maxillary involvement by DLBCL. The first case involved a 75-year-old man who presented for right maxilla osteomyelitis after tooth extraction was treated with antibiotics for weeks without improvement. The biopsy revealed tissue infiltration by a diffuse proliferation of large atypical lymphocytes with irregular nuclear contours and variably conspicuous nucleoli (Figure 1.127, A). The neoplastic cells were positive for CD20 (Figure 1.127, C), BCL6 (>40%), and Ki-67 (60%) and negative for CD10, MUM1, and BCL2, consistent with germinal center B-cell type (GCB). The second case was that of a 76-year-old woman who presented with swelling of the left maxilla for 6 weeks. After several weeks of antibiotic treatment for suspected osteomyelitis, a biopsy revealed DLBCL with large atypical cells (Figure 1.127, B), positive for CD20 (Figure 1.127, D), BCL2 (70%), c-MYC (>40%), MUM1, and Ki-67 (90%) and negative for CD5, CD10, BCL6, and cyclin D1. According to the Hans classifier, this case was a non–germinal center B-cell type (non-GCB) and double expresser, without MYC, BCL2, or BCL6 rearrangement. While the first patient is in complete remission at 3 years from diagnosis, the second patient survived less than 1 year. Because of the nonspecific presentation of DLBCL, the diagnosis is usually delayed. A high index of suspicion, especially in patients older than 50 years, is required for a timely diagnosis and more efficient management.

Hepatitis-Associated Aplastic Anemia in a Pediatric Patient: An Uncommon Entity Presenting With a Rapid Clinical Course

(Poster No. 128)

Brett R. Kurpiel, MD ([email protected]); Julia C. Iezzoni, MD; Elizabeth L. Courville, MD. Department of Pathology, University of Virginia, Charlottesville.

Hepatitis-associated aplastic anemia (HAAA) occurs in up to 33% of patients who receive orthotopic liver transplants for acute liver disease of unknown origin (nonviral hepatitis). Nonviral hepatitis is a rare condition of mainly children and young adults. Herein we discuss the case of a 13-year-old boy who presented with severe liver failure of unknown etiology following 1–2 weeks of symptoms and subsequently underwent whole-organ deceased-donor liver transplant. Liver biopsy at presentation showed nonspecific findings, namely panacinar and multiacinar hepatocyte necrosis and a mixed inflammatory infiltrate (Figure 1.128, A). Three weeks after transplant, the boy remained persistently thrombocytopenic (platelets, 26 k/μL) and anemic (hemoglobin, 9.0 g/dL) and developed neutropenia (ANC, 0.1 k/μL), prompting bone marrow biopsy, which revealed a cellularity of 5% (Figure 1.128, B) with absent myeloid precursors/megakaryocytes and only rare erythroid precursors by E-cadherin immunohistochemistry (Figure 1.128, C). Marrow flow cytometry showed predominantly lymphocytes with a CD4:CD8 ratio of 1.8:1 (possibly peripheral blood). Cytogenetic studies were normal, PNH testing was negative, and workup for bone marrow failure syndromes was unrevealing. In addition to posttransplant tacrolimus, a 4-day course of high-dose steroids/antithymocyte globulin therapy was added for the aplastic anemia, with minimal improvement in counts. Four months after liver transplant, the patient remains transfusion dependent for cytopenias, with plans for future bone marrow transplant. This case serves to remind the practicing hematopathologist of HAAA as a cause for marrow aplasia. While the pathogenic mechanism is unclear, it is thought to be related to immune-mediated destruction of hematopoietic stem cells.

Gastrointestinal Leiomyomas: A Clinicopathologic Review

(Poster No. 129)

Sindhuja Sivanandham, MBBS ([email protected]); Paolo Gattuso, MD; Ram Al-Sabti, MD. Department of Pathology, Rush University Medical Center, Chicago, Illinois.

Context: Gastrointestinal leiomyomas are rarely encountered during routine pathology practice. Owing to their rarity, we sought to assess their clinical and pathologic characteristics.

Design: All cases of gastrointestinal leiomyomas from our institution from 1997 to 2021 were reviewed, and their clinical and pathologic data were collected.

Results: A total of 28 tumors from 25 patients (9 women [36%] and 16 men [64%]) were identified. The mean patient age was 60 years (range, 30–83 years). Ten tumors (40%) occurred in the esophagus, 10 (40%) in the stomach, 2 (8%) in the colon, and 3 (12%) in the rectum. Two cases in the stomach had multiple leiomyomas. Mean size was 2.79 cm (range, 0.2–11 cm). Patients most commonly presented as asymptomatic (34.8%) or with dysphagia (30.4%). Overall, 47.6% of patients had a smoking history, with this rising to 66.6% for esophageal leiomyomas. Four of 10 leiomyomas (40%) in the esophagus and 3 of 10 (30%) in the stomach had synchronous Barrett esophagus. Five of 10 leiomyomas (50%) in the esophagus and 4 of 10 (40%) in the stomach had synchronous adenocarcinoma. Leiomyoma was an incidental finding in 17 of 25 patients (68%) (9 found in adenocarcinoma resections, 1 in hernia repair, and 7 on routine screening). The remaining 8 procedures were primarily for leiomyoma.

Conclusions: In our cohort, gastrointestinal leiomyomas occurred more commonly in men, and the most common sites were the esophagus and stomach. Most (92%) were solitary; however, multiple lesions also occurred. Sixty-eight percent of leiomyomas were an incidental finding. Of 20 leiomyomas in the esophagus and stomach, 9 (45%) had synchronous adenocarcinoma. No recurrence or progression was seen during available follow-up. Gastrointestinal leiomyomas have a benign clinical course and good prognosis.

Acute Myeloid Leukemia With Monocytic Differentiation, Marked Leukocytosis, and Myeloperoxidase Expression Portends Poor Prognosis

(Poster No. 130)

Ahmed A. Ahmed, MD1 ([email protected]); Zubaidah I. Aljumaili, MD1; Wei Wang, MD1; Brenda Mai, MD1; M. J. You, MD2; Zhihong Hu, MD.1 1Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, Houston; 2Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston.

Context: Acute myeloid leukemia (AML) with monocytic differentiation can have abnormal cytoplasmic granules and myeloperoxidase expression.

Design: We retrospectively reviewed the clinicopathologic information of 3 AML patients who presented with marked leukocytosis and died before a BM procedure was performed.

Results: The first case was that of a 59-year-old woman with epigastric abdominal pain for 4 days. Her blood work revealed leukocytosis (41 200/MCL). FCI on peripheral blood (PB) showed 54% abnormal monocytic cells with MPO partial expression. FISH revealed KMT2A gene rearrangement. Her status rapidly worsened, and she died from disseminated intravascular coagulation (DIC) and respiratory failure. The second case was that of an 18-year-old woman with fatigue and night sweats for 2 weeks. Her PB smear showed leukocytosis (155 000/MCL) (Figure 1.130, A), and FCI showed 76% abnormal monocytic cells with MPO partial expression (Figure 1.130, C). Chromosome analysis showed inv(16)(p13.1q22) (Figure 1.130, B). She was subsequently treated with cytosine and idarubicin but died owing to DIC and tumor lysis syndrome. The third case was that of a 20-year-old man with no medical history who was found unresponsive, requiring intubation. CBC showed marked leukocytosis (151 800/MCL), and FCI showed 87% abnormal cells expressing monocytic markers and MPO. FISH demonstrated PML/RARA rearrangement. Despite receiving cytosine and all-trans retinoic acid immediately after his APL diagnosis, the patient died of DIC and showed extensive intracranial hemorrhage.

Conclusions: AML with monocytic differentiation and MPO expression is associated with DIC and tumor lysis syndrome. Urgent therapeutic strategies targeting high tumor burden should be considered in AML patients with marked leukocytosis, monocytosis, and MPO expression.

DDX41 Mutations in Nonmyeloid Hematologic Neoplasms

(Poster No. 131)

Fatima Z. Jelloul, MD1; Pei Lin, MD1; Courtney D. DiNardo, MD2; Mark J. Routbort, MD, PhD1; Rashmi Kanagal-Shamanna, MD1; Rajyalakshmi Luthra, PhD1; Joseph D. Khoury, MD1; Beenu Thakral, MD1; Wei Wang, MD, PhD1; C. Cameron Yin, MD, PhD1; Sanam Loghavi, MD1; Chi Y. Ok, MD1; Guillermo Garcia-Manero, MD2; Hagop Kantarjian, MD2; M. James You, MD, PhD1; L. Jeffrey Medeiros, MD1; Keyur P. Patel, MD, PhD1; Andres E. Quesada, MD1 ([email protected]). Departments of 1Hematopathology and 2Leukemia, MD Anderson Cancer Center, Houston, Texas.

Context: Myeloid neoplasms with DDX41 mutations are recognized as a distinct World Health Organization category. Earlier studies have shown DDX41 mutations in occasional nonmyeloid hematologic neoplasms. The purpose of this study was to investigate the prevalence and characteristics of DDX41 mutations in nonmyeloid hematologic neoplasms.

Design: All cases were acquired during a 4-year period and harbored a DDX41 mutation detected by using an 81-gene next-generation sequencing panel. Clinical and molecular data were collected for the remaining samples.

Results: Thirty unique patients with nonmyeloid malignancy and DDX41 mutation were identified. Of these, 20 (10%) had an established diagnosis: 6 (3%) plasma cell neoplasm, 6 (3%) B-lymphoblastic leukemia/lymphoma (B-ALL), 4 (2%) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 2 (1%) aplastic anemia, 1 (0.5%) mixed phenotype acute leukemia (B/myeloid), and 1 (0.5%) Epstein-Barr virus–positive cytotoxic T-cell lymphoproliferative disorder; 10 patients (33%) did not have a definitive diagnosis. All 30 patients harbored only a single DDX41 mutation. Two canonical mutations (p.M1I and p.D140fs) were seen in 5 cases (17%) each. No p.R525H mutations were identified. Based on variant allelic frequency, 5 of 30 DDX41 mutations were likely somatic, and 25 of 30 were presumably germline.

Conclusions: We found that the most common nonmyeloid hematologic disorders harboring DDX41 mutations were B-ALL, plasma cell neoplasms, and CLL/SLL. None of these cases coharbored both germline and somatic DDX41 mutations, suggesting that DDX41 mutations may be found incidentally and likely have a less significant role in the etiology of nonmyeloid neoplasms.

Jaundice and Hyperbilirubinemia: An Atypical Presentation of Multiple Myeloma

(Poster No. 132)

Leonard Yenwongfai, MD, MS ([email protected]); Jing Di, MD, PhD; Andre N. Ene, MD; Sahar Nozad, MD; Dava W. Piecoro, MD. Department of Pathology, University of Kentucky, Lexington.

Multiple myeloma (MM) is a clonal proliferation of bone marrow–based plasma cells associated with M protein in serum or urine and concomitant end-organ damage. Patients with MM typically present with hypercalcemia, renal failure, anemia, and lytic bone lesions. We present a case of MM manifesting as acute hyperbilirubinemia. A previously healthy 50-year-old woman presented with emesis and abdominal pain associated with scleral icterus. Evaluation for acute liver disease demonstrated significantly elevated total bilirubin (27.7 mg/dL), warranting liver biopsy. Liver sections showed expansion of portal areas by plasma cells with few intermixed lymphocytes, lobular damage, and mild cholestasis, resembling chronic hepatitis (Figure 1.132, A and B). Immunohistochemical stains of the liver biopsy revealed CD138-positive plasma cell infiltrates with κ light-chain restriction (Figure 1.132, C). Plasma cells were negative for CD56, cyclin D1, and IgG4. PAX-5 stain showed virtual absence of B cells. As findings were suggestive of a plasma cell neoplasm, the patient underwent evaluation by hematology/oncology. Serum κ/λ light-chain ratio was elevated at 575, while protein electrophoresis revealed marked hypogammaglobulinemia. Bone marrow aspirate demonstrated approximately 50% plasma cells, consistent with MM (Figure 1.132, D). This case represents an atypical case of MM presenting with symptoms associated with hepatic involvement. It is essential to recognize that liver involvement by MM can mimic entities such as drug-induced hepatitis, IgG4 disease, autoimmune hepatitis, and B-cell lymphoproliferative disorder with plasmacytic differentiation, requiring an appropriate clinical and histologic workup.

Flow Cytometric Evaluation of Cytoplasmic and Surface TRC1 Expression in the Identification of Clonal T-Cell Populations

(Poster No. 133)

Zach Chelsky, DO1; Meghan White, MD1 ([email protected]); Amanda Wheeler, MLS2; Richard Hammer, MD1; Katsiaryna Laziuk, MD.1 1Department of Pathology and Anatomical Sciences, University of Missouri, Columbia; 2University of Missouri Hospital, Columbia.

Context: T-cell receptor β constant region 1 (TRBC1) has shown monotypic expression in clonal T-cell populations. T cells must also express surface CD3 (sCD3) to be interpreted using TRBC1 by standard flow cytometry methods. Cytoplasmic TRBC1 (cTRBC1) evaluation can identify clonal populations negative for sCD3. We report our experience detecting T-cell clonality with sTRBC1 and present the utility of cTRBC1 evaluation in T-cell neoplasms.

Design: We examined the expression of sTRBC1 by standard flow cytometry methods in 22 clonal and 15 polytypic T-cell populations. We also evaluated sTRBC1 and cTRBC1 expression in a case of angioimmunoblastic T-cell lymphoma and a case of T-lymphoblastic leukemia. The TCRB1 antibody used was produced by Ancell (Stillwater, Minnesota). Analytical software and other antibodies were produced by Becton Dickinson (Franklin Lakes, New Jersey).

Results: Polytypic expression of sTRBC1 was detected in nonclonal T-cell populations (mean sTRBC1 expression patterns, 36.1% lymphocytes positive and 63.9% negative). Clonal T-cell populations showed a restricted pattern of sTRBC1 expression; 87% of monotypic cases were TRBC1 negative. In an angioimmunoblastic T-cell lymphoma, an aberrant T-cell population was negative for sCD3 but positive for cCD3 with monotypic expression of cTRBC1. A T-lymphoblastic leukemia was negative for sCD3 and sTRBC1 but positive for cCD3 with bright monotypic cTRBC1 positivity (Figure 1.133, A through D).

Conclusions: Our experience supports flow cytometric evaluation of sTRBC1 for identification of clonal T-cell populations. We also illustrate the utility of cTRBC1 in assessing clonality in mature and immature T-cell neoplasms, highlighting the finding that cytoplasmic components of TRBC1 can be detected despite no surface expression.

Hammer has received grant or research support from GE, Flagship Bioscience, and Roche, is a speaker for Roche, and is on the Roche, Caris, and Foundation Medicine Advisory Boards.

ALK+ Anaplastic Large Cell Lymphoma in Uterine Cervix

(Poster No. 134)

Seifeldin Awad, MBBCh1 ([email protected]); Ahmed Sabri, MD1; Erin Yang, MD2; Lesley B. Conrad, MD3; David Cantu, MD.1 Department of 1Pathology, 2School of Medicine, and 3Obstetrics & Gynecology, Creighton University Medical Center, Omaha, Nebraska.

ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) is an aggressive but rare form of mature T-cell lymphoma, accounting for 3% of non-Hodgkin lymphomas in adults. It typically presents in later stages (III-IV). ALK+ ALCL predominantly affects young patients and favors males over females. ALK+ ALCL frequently involves nodal and extranodal sites; however, secondary involvement of the gynecologic tract is uncommon. We present a case of 23-year-old woman with a 1-month duration of abnormal uterine bleeding accompanied by constitutional symptoms and a cervical lesion. A biopsy was obtained and demonstrated sheets of large pleomorphic cells with mitotic activity and apoptotic bodies in a background of necrosis, hemorrhage, and acute inflammation. These cells were of lymphoid lineage and had irregular nuclear borders with variably centered to eccentric nuclei and inconspicuous nucleoli, along with abundant eosinophilic cytoplasm (Figure 1.134, A and B). The characteristic hallmark cells were also present. By immunohistochemistry, the malignant cells were strongly positive for ALK (Figure 1.134, C), CD30 (Figure 1.134, D), CD10, CD4, CD43, and CD45. BCL-6 showed weak nuclear positivity in a subset of cells. Granzyme B was positive in a subset of malignant cells. ALK staining showed nuclear and diffuse cytoplasmic positivity in the malignant cells. The Ki-67 proliferation index was increased. CD15 was positive in a subset of cells. All other immunohistochemical stains, including cytokeratin, melan-A, SOX10, and CD20, along with the ancillary studies, were negative. To our knowledge, this is the first case of ALK+ ALCL with initial presentation as abnormal uterine bleeding and a cervical mass.

Acute Myeloid Leukemia With NPM1 Mutation Mimics Acute Promyelocytic Leukemia Phenotypically

(Poster No. 135)

Hania Shakeri, MD ([email protected]); Yanhua Wang, MD. Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York.

Nucleophosmin 1 (NPM1) mutation is considered to be one of the most common and specific mutations in acute myeloid leukemia (AML). Patients with NPM1 mutation usually present with anemia, thrombocytopenia, and higher white blood cell (WBC) and platelet counts in comparison with patients with other types. Acute promyelocytic anemia (APL) is a subtype with specific morphologic, biologic, and clinical presentations that is considered a true emergency owing to a higher risk of disseminated intravascular coagulation. However, an “APL-like” immunophenotype pattern reported in a subset of de novo AML cases with NPM1 mutation is not a common finding. We report a case of a 33-year-old woman who presented with dyspnea and headache. She was found to have a WBC of 36 K (82% blasts), an absolute neutrophil count of 200, and a platelet count of 54. She was diagnosed with bilateral pulmonary embolism and venous sinus thrombosis. Peripheral smears showed a single cell with possible Auer rod. Flow cytometry (Figure 1.135, A) showed blasts with a slightly higher side scatter and positivity for CD9, CD11b (minimal), CD11c (minimal), CD 13, CD33, CD38 (partial), CD58, CD45, CD64 (partial), CD117, and MPO and negativity for HLA-DR, phenotypically concerning for APL. The molecular study showed a low allelic ratio in FLT3-ITD, IDH1, and TP53 mutations. Morphology (Figure 1.135, B) showed leukemic cells with myeloblastic differentiation and medium size to large, along with irregular nuclear contours, prominent nucleoli, moderate cytoplasm, and cytoplasmic granules. The morphologic and immunophenotypic differences between APL and many cases of NPM1-mutated AML are subtle. The clinical implications of possible similarities in the biology underlying APL and NPM1-mutated AML with IDH comutations should be considered.

Concurrent EBV-Positive Diffuse Large B-Cell Lymphoma (Germinal Center Type) and Peripheral T-Cell Lymphoma, NOS: A Multisystem Diagnostic Dilemma

(Poster No. 136)

Caitlin M. Nickens, MD ([email protected]); Jeannie M. Muir, MD. Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland.

Epstein-Barr virus (EBV)-positive atypical B cells are known to occupy and even proliferate within a T-cell lymphoma. We present a case in which atypical B cells represented involvement of the T-cell lymphoma by a second, concurrent B-cell lymphoma with distant primary in a 74-year-old man with several months of progressive dry cough, rash of unclear etiology, and pulmonary nodules. When he was admitted for worsening symptoms, a skin biopsy (Figure 1.136, A) was performed, and the patient developed an ileal perforation requiring resection. The skin biopsy revealed dermal intermediate to large T lymphocytes with irregular nuclear contours that stained positively for CD3 (Figure 1.136, B), CD2, CD5, CD4 (subset), BCL6, granzyme B, ICOS, and PD1 and negatively for CD8, CD30, CD10, and ALK1. Scattered large B cells expressing CD20 (Figure 1.136, C), CD79a, PAX5, CD30, and EBER-ISH (Figure 1.136, D) were also noted. However, the resected ileum revealed infiltrative sheets of atypical large B cells that were immunoreactive for CD20, PAX 5 (subset), CD79a, CD30 (subset), BCL6, MUM1, CD10, and EBER-ISH. Bowel-associated lymph nodes were diffusely effaced by atypical CD3-positive T cells with a similar immunoprofile as the skin biopsy. Atypical B cells with a similar phenotype as the ileal process were scattered within the lymph node. Gene rearrangement studies detected T-cell receptor β, T-cell receptor γ, and IgH gene rearrangements with the same dominant peaks for the skin biopsy and the peri-ileal lymph nodes, supporting a common clonality. These findings demonstrate an extremely rare presentation of 2 distinct lymphomas presenting concurrently in multiple tissues: an EBV-positive diffuse large B-cell lymphoma (germinal center type), and a peripheral T-cell lymphoma, NOS.

Bone Marrow Granulomas: A Clinicopathologic Review

(Poster No. 137)

Sindhuja Sivanandham, MBBS1 ([email protected]); Ankica Braun, MD1; Swathi Reddy, MD2; Nicolas Lopez-Hisijos, MD1; Ira Miller, MD1; Vijaya Reddy, MD1; Paolo Gattuso, MD.1 Departments of 1Pathology and 2General Surgery, Rush University Medical Center, Chicago, Illinois.

Context: Granulomas occur infrequently in the bone marrow. Here, we evaluated the common causes of granulomas occurring in bone marrow to establish a differential diagnosis profile.

Design: All cases of bone marrow granulomas from our institution from 1993 to 2020 were reviewed, and their clinical and pathologic data were collected.

Results: A total of 60 cases were identified (33 women and 27 men). The mean age at biopsy was 52 years (range, 26–81 years). Indications for biopsies were cytopenia (19), cytopenia in HIV (9), lymphadenopathy (6), non-Hodgkin lymphoma (6), paraproteinemia (6), acute myeloid leukemia (AML) (5), sarcoidosis (3), fever (2), myelodysplastic syndrome (1), splenomegaly (1), leukemia (1), and myeloproliferative neoplasm (1). The histopathologic features were as follows: 56 nonnecrotizing, 2 lipogranulomas, 1 lipogranuloma with ring granuloma, and 1 necrotizing granuloma. Special stains revealed organisms in 11 cases (7 Mycobacterium avium and 4 Histoplasma). One case had EBER-ISH–stained scattered cells. In 22 of 60 cases, an etiology was established: 10 sarcoidosis, 7 M avium infection, 4 histoplasmosis, and 1 Epstein-Barr virus infection. The remaining 38 cases did not have a specific clinical or histologic etiology. Six granulomas were found in association with malignancies: 5 plasma cell neoplasms (PCNs) and 1 AML.

Conclusions: Bone marrow biopsies were performed most commonly for cytopenia (31.7%). Ninety-three percent of the granulomas were nonnecrotizing. A cause for granuloma could not be identified clinically or histologically in 63.3% of the cases, while, among the cases with an identifiable cause, sarcoidosis was most common (16.6%). Associated malignancy occurred in 10% of cases, with the most common type being PCN (8.3%). In patients with AIDS presenting with cytopenia, the most common cause of granuloma was M avium.

Plasmablastic Lymphoma Presenting as a Bladder Mass

(Poster No. 138)

Andy Gould, DO ([email protected]); Jeannie Muir, MD. Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland.

Plasmablastic lymphoma is a rare malignancy, especially outside the oral cavity and in HIV-negative individuals. We present a unique case of a 67-year-old man with an unremarkable medical history who presented with several days of gross hematuria, left groin swelling, and left lower extremity edema. CT revealed a large bladder mass with local tissue invasion and retroperitoneal lymphadenopathy. A urothelial malignancy was suspected, and a transurethral resection of the bladder tumor was performed. The specimen demonstrated sheets of intermediate to large neoplastic cells with centrally placed atypical nuclei and moderate amounts of amphophilic cytoplasm (Figure 1.138, A). Numerous mitotic figures and apoptotic bodies were identified. The neoplastic cells were immunoreactive for CD138 (Figure 1.138, B), MUM1 (Figure 1.138, C), EBER-ISH, CD117, CD30 (subset) (Figure 1.138, D), and CD3 (subset) and demonstrated a κ light-chain restriction. Rare cells expressed a dim CD45. The neoplastic cells were negative for CD20, PAX5, CD56, CD34, ALK1, HHVA-8, NKX3.1, uroplakin, PSA, TTF-1, AE1/AE3, CK 8-18, GATA3, CD5, λ, S100, chromogranin, and synaptophysin. FISH revealed a MYC gene rearrangement and was negative for BCL2 and BCL6 gene rearrangements. A bone marrow biopsy demonstrated no evidence of this neoplasm. The patient was HIV negative and EBV positive by serology. Given these findings, a diagnosis of plasmablastic lymphoma was confirmed. Literature review references only 6 cases of genitourinary involvement in HIV-negative individuals. Correct diagnosis of plasmablastic lymphomas is an important challenge because they are very aggressive, resist current therapies, and have a poor prognosis.

Concurrent Occurrence of Indolent T-Lymphoblastic Proliferation With Castleman Disease and Angioimmunoblastic T-Cell Lymphoma

(Poster No. 139)

Ahmed S. Arfa, MD1 ([email protected]); Nivin Omar, MBChB1; Nabin Karki, MD2; Natasha M. Savage, MD.1 Departments of 1Pathology and 2Hematology Oncology, Medical College of Georgia, Augusta.

Context: Indolent T-lymphoblastic proliferation (iT-LBP) is a rare, newly described benign proliferation of polyclonal immature T cells. However, immunophenotypically it resembles T-lymphoblastic lymphoma (T-ALL). iT-LBP can occur with epithelial malignancies and hematologic disorders such as Castleman disease and angioimmunoblastic T-cell lymphoma. We aimed to evaluate the concurrent occurrence of iT-LBP with Castleman disease and angioimmunoblastic T-cell lymphoma, as well as how to differentiate iT-LBP from T-ALL.

Design: We searched our institution's electronic databases for patients diagnosed with Castleman disease or angioimmunoblastic T-cell lymphoma during the past 10 years. Eighteen cases were identified between 2012 and 2021. Consequently, tissue blocks were requested and stained with a TdT to identify iT-LBP. Additionally, stains and other ancillary tests that had been ordered at the time of diagnosis were reviewed.

Results: Among the 18 cases, 12 were diagnosed with Castleman disease (Figure 1.139, A and C), and there were 6 cases of angioimmunoblastic T-cell lymphoma. All 18 cases showed positive TdT, ranging from numerous interfollicular cells staining (Figure 1.139, B) to rare positive scattered cells (Figure 1.139, D).

Conclusions: Pathologists should be aware of this rare indolent entity of nonclonal T-lymphoblastic proliferation and avoid overdiagnosis of T-ALL by ordering broad immunohistochemical stains, flow cytometry, and TCR rearrangement studies, as needed per case.

Rosai-Dorfman Disease Presenting as an Asymptomatic Pancreatic Mass

(Poster No. 140)

Yalda Soleimanifard, MD ([email protected]); Surendra Singh, MD; Gregory M. Prince, MD. Department of Pathology, University of Toledo, Ohio.

Rosai-Dorfman disease (RDD) is a histiocytosis of undetermined etiology, first identified as involving sinuses of massively enlarged lymph nodes, but subsequently also extranodally. It is characterized by proliferations of large S100-positive histiocytes with pale cytoplasm. Emperipolesis of lymphocytes by histiocytes is characteristic, but is neither necessary nor sufficient for diagnosis, and is less conspicuous in extranodal sites. Our patient was a 59-year-old man with a 5.2-cm mass of the pancreas. Sections from the distal pancreatectomy demonstrated a fibroinflammatory process (Figure 1.140, A). The triad of focally marked lymphoplasmacytic inflammation, storiform fibrosis, and obliterative vasculopathy suggested IgG4-related disease; however, serum IgG4 was normal, and immunostain for IgG4 demonstrated only a few positive cells. Closer inspection (Figure 1.140, B) revealed scattered plump histiocytes with large round nuclei, prominent nucleoli, abundant pale cytoplasm, and indistinct cell borders. Immunostain for S100 demonstrated cytoplasmic and nuclear staining, additionally highlighting emperipolesis (Figure 1.140, C), diagnostic of RDD. Further review of peripancreatic lymph nodes (Figure 1.140, D) identified rare intrasinusoidal histiocytes displaying emperipolesis. RDD is a rare disorder; very rare cases have been described involving the spleen. Recognition of characteristic RDD histiocytes on routine stains may be compromised in extranodal sites such as this, owing to the pale cytoplasm and indistinct cell borders of these large cells and the background of abundant lymphocytes, compromising their recognition and the identification of emperipolesis. Our case is illustrative of the importance of the consideration of this diagnosis in the evaluation of a fibroinflammatory process, and the utility of S100 immunostain in the appropriate setting.

Plasma Cell Leukemia With Soft Tissue Involvement: Report of a Rare Case

(Poster No. 141)

Sunder Sham, MBBS1 ([email protected]); Hossein Hosseini, MD1; Ahmed Bendari, MBBCh1; Jordan M. Steinberg, MD1; Sam Ngu, MD2; Colette M. Spaccavento, MD2; Oana E. Vele, MD1; Manju Harshan, MD1; Alyssa Yurovitsky, MD.1 Departments of 1Pathology and Laboratory Medicine and 2Medicine, Lenox Hill Hospital, New York, New York.

Plasma cell leukemia (PCL) is a rare aggressive variant of multiple myeloma. PCL is diagnosed when clonal plasma cells constitute more than 20% of the total circulating leukocytes or when the absolute plasma cell count exceeds 2 × 109/L. Extramedullary involvement, including cavity effusion, is frequently seen at the time of diagnosis. However, soft tissue involvement is rarely encountered, with only 1 published case in the English literature. We report a case of a 74-year-old man who presented with progressive shortness of breath for a few months. Laboratory studies showed leukocytosis (32 × 109/L) with 26% peripheral plasmacytoid cells and significantly elevated lactate dehydrogenase (> 2500 U/L). Serum protein electrophoresis detected a monoclonal IgG λ band. A 7.4-cm left hilar mass, bilateral pleural effusion, and multiple fluorodeoxyglucose-avid subcutaneous nodules in the pelvic and gluteal regions were demonstrated on imaging. Gluteal nodule biopsy (Figure 1.141, A) revealed diffuse infiltrative CD138+ (Figure 1.141, B) and MUM1+ cells with aberrant CD4, CD30, and BCL2 expression. The Ki-67 proliferation index was 70%. Bone marrow biopsy showed sheets of atypical plasma cells (Figure 1.141, C) with λ restriction and CD138 and MUM1 (Figure 1.141, D) expression without cyclin D1 and CD20 expression. These cells comprised approximately 70%–80% of the bone marrow cellularity. A similar immunophenotype was demonstrated on peripheral and bone marrow flow cytometry. Molecular cytogenetics showed an abnormal clone with a complex karyotype not limited to monosomy 13 and 14q deletion. Overall, these findings are consistent with a monoclonal plasma cell proliferative disorder. Our case study illustrates soft tissue involvement in PCL, which is rarely seen.

High-Grade Unclassifiable Follicular Lymphoma in a Pediatric Patient

(Poster No. 142)

Byron Barksdale, MD ([email protected]); Jennifer Dunlap, MD. Department of Pathology and Laboratory Medicine, Oregon Health & Sciences University, Portland.

A 14-year-old boy developed bilateral cervical lymphadenopathy and presented to his primary care physician. Imaging studies found bilateral cervical and mediastinal lymphadenopathy that demonstrated increased metabolic activity. An excisional biopsy was performed. The lymph node architecture was effaced by an atypical lymphoid proliferation with a follicular growth pattern. The follicles consisted of intermediatesized lymphocytes with irregular nuclei, coarse chromatin, and occasional nucleoli. Immunohistochemical stains were performed, and neoplastic cells were positive for CD10, CD20, BCL2, BCL6, and increased Ki-67 (80%) and negative for MUM1, cyclin D1, and MYC. CD21 stain disrupted follicular dendritic cell meshworks associated with the B-cell nodules. FISH studies demonstrated BCL2 amplification with no t(14;18), MYC, BCL2, or BCL6 rearrangement, and next-generation sequencing identified a NFKBIE mutation (p.7254fs*13), which has been described in mediastinal B-cell lymphomas but not follicular lymphomas. BCL2 expression by immunohistochemistry and BCL2 amplification (FISH) argued against pediatric follicular lymphoma, and a diagnosis of follicular lymphoma grade 3, not further subclassified, was rendered. These high-grade lymphomas are a newly emerging entity; they have been found to have novel cytogenetic and molecular mutations distinct from lower-grade follicular lymphomas and a more aggressive clinical course and worse prognosis than grade 3a follicular lymphomas. Grade 3 follicular lymphomas are unusual in pediatric patients, although they have been found in patients with abnormal immune states, including autoimmune lymphoproliferative disorder.

A “Triple Hit” B-Cell Lymphoma Involving the Stomach, Spleen, and Pancreas

(Poster No. 143)

Nicholas J. Dcunha, MBBS ([email protected]); Andreia N. Barbieri, MD. Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas.

High-grade B-cell lymphoma with MYC, BCL2, and BCL6 rearrangements (high-grade “triple hit” B-cell lymphoma) is a rare and highly aggressive B-cell lymphoma. This entity is often of germinal center B-cell immunophenotype and presents with coexpression of MYC and BCL2 (termed double expressor immunophenotype). A 77-year-old man presented with a history of diffuse abdominal pain and altered mental status. CT showed multiple heterogeneous masses involving the stomach, spleen, and pancreas, the largest of which measured 13.4 cm, multiple additional peritoneal nodules, and abnormal lymph nodes. A biopsy of the stomach showed involvement by a large B-cell lymphoma with high-grade features. The lymphoma cells stained positively for CD20, BCL-6, MUM1, and BCL-2 and negatively for CD3, CD5, and AE1/AE3. Germinal center versus non–germinal center phenotype could not be determined, as CD10 immunohistochemical stain was equivocal and predominantly stained areas of necrosis. c-MYC was positive in less than 40% (approximately 20%). Fluorescence in situ hybridization analysis of tissue showed BCL6, MYC, and BCL2 rearrangements, consistent with a high-grade “triple hit” B-cell lymphoma. Despite initiation of chemotherapy, the patient's condition continued to deteriorate, with development of sepsis; the patient died 4 weeks after initiation of treatment. High-grade “triple hit” B-cell lymphoma is associated with an aggressive clinical course and poor prognosis, as was observed in our case. Additionally, our case underscores the importance of testing for BCL2, BCL6, and MYC rearrangements, even with lower levels of MYC immunophenotype expression.

Clinicopathologic Spectrum of U2AF1 Mutations in Myeloid Neoplasms: A Single-Institution Experience

(Poster No. 144)

Sami Talibi, MD ([email protected]); Andrea Ferreira-Gonzalez, PhD; Rajeswari Jayakumar, MD. Department of Pathology, VCU Health System, Richmond, Virginia.

Context:U2AF1 belongs to the splicing-factor family of genes and encodes proteins that play a role in enhancer-dependent RNA splicing. We characterized the clinicopathologic features of myeloid neoplasms (MNs) with U2AF1 mutation.

Design: We reviewed 2 years of next-generation sequencing data of MNs in our institution. Cases with U2AF1 mutation were identified, and their peripheral blood, bone marrow, cytogenetics, and clinical presentation data were analyzed.

Results: Seventeen individuals were identified, including 5 women and 13 men, 42–88 years of age (median, 72 years). Ten patients (59%) presented with pancytopenia. Nine cases (53%) were diagnosed with acute myeloid leukemia (AML), 5 cases (29.4%) with myelodysplastic syndrome (MDS) (3 with excess blasts), and 3 cases (17.6%) with myelofibrosis. Of the AML cases, 3 had AML with myelodysplasia-related changes, and 2 had AML with monocytic differentiation. Eleven cases (65%) had increased storage iron, with none showing significant ring sideroblasts (> 15%). Concurrent cytogenetic abnormalities included trisomy 8 (3 cases), del(20q) (2 cases), KMT2A rearrangement (1 case), del(5q) (1 case), and del(13q) (1 case). Coexisting mutations included DNMT3A (23.5%), ASXL1 (23.5%), TET2 (17.6%), and RUNX1 (23.5%). All cases of myelofibrosis showed JAK2 mutation. Eight patients (47%) responded to therapy and achieved remission. Six patients (35%) did not respond to therapy.

Conclusions:U2AF1 often occurs concurrently with MDS-defining cytogenetic abnormalities and other mutations, notably DNMT3A, RUNX1, JAK2, ASXL1, and TET2. Patients commonly present with pancytopenia and increased storage iron. Contrary to our expectations, none of the cases showed significant ring sideroblasts.

Myelodysplastic Syndrome With Eosinophilia Versus Chronic Eosinophilic Leukemia: A Diagnostic Dilemma

(Poster No. 145)

Archana Sallagonda, MD ([email protected]); Madhavi Pandiri, MD; Jonathan K. Freeman, MD. Department of Pathology, UMMS Chan-Baystate Medical Center, Springfield, Massachusetts.

Absolute eosinophilia can be seen in numerous benign and malignant conditions. Among myeloid neoplasms, eosinophilia occurs in myeloproliferative neoplasms (including chronic eosinophilic leukemia [CEL]), myelodysplastic syndromes (MDSs), and myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2. Although the latter category is clearly defined by gene mutation, we report a case that demonstrates the ambiguity of definition between CEL and MDS. Our patient was a 71-year-old man who presented with shortness of breath and generalized body pains. Evaluation revealed marked absolute eosinophilia (58 k/mm3) without recognizable secondary causes. Peripheral blood testing for BCR-ABL, JAK2 V617F, JAK2 exon 12, CALR, MPL, PDGFRA/B, FGFR1, and TCR gene rearrangements were negative. Bone marrow examination revealed hypercellular marrow with marked eosinophilia, trilineage dysplasia, and increased ringed sideroblasts, with no increase in blasts. Molecular and cytogenetic studies demonstrated a complex karyotype characterized by loss of 1 copy of chromosome 17 and deletion of 3q, 5q, 14q, 7q, and 7p and TP53 mutation. This case met all the criteria for CEL, including eosinophilia, absence of other chronic myeloproliferative disorder, absence of specific gene rearrangements associated with eosinophilia, and the presence of cytogenetic abnormality. However, trilineage dysplasia and increased ringed sideroblasts in conjunction with several cytogenetic abnormalities characteristic of MDS appeared to better support MDS with eosinophilia, suggesting alternative classification as MDS/myeloproliferative neoplasm with eosinophilia, which is rare, with only a few cases reported in the literature. The case highlights the current diagnostic ambiguity between MDS with eosinophilia versus dysplasia permissible within CEL.

Extracavitary Primary Effusion Lymphoma: A Diagnostically Challenging Case Mimicking Alveolar Soft Part Sarcoma

(Poster No. 146)

Xiaohua Qi, MD, PhD ([email protected]); Mitul Modi, MD; Samer Ali, MD; Yanhua Wang, MD, PhD; Yang Shi, MD, PhD. Department of Pathology, Montefiore Medical Center/Einstein College of Medicine, Bronx, New York.

Primary effusion lymphoma (PEL) is a rare, aggressive neoplasm that typically manifests as malignant effusion in the body cavities of immunocompromised patients. Extracavitary effusion lymphomas are solid masses without definite body cavity involvement and are much less common than PEL. The diagnosis is particularly challenging and can be easily missed owing to the frequent absence of common hematopoietic markers. Here we report a case of a 32-year-old man with HIV, a 12-cm mass at the head of the pancreas, and diffuse lymphadenopathy. An abdominal mass needle core biopsy revealed extensive necrosis with viable poorly differentiated neoplastic cells in an alveolar pattern. They were negative for CD3, CD20, CD30, CD45, CD138, κ, λ, PAX5, S100, and cytokeratins. The only positive markers were MUM1 and cytoplasmic MyoD1, raising suspicion for alveolar soft part sarcoma. An incisional lymph node biopsy showed large, atypical cells with plasmablastic features. They were positive for CD30 (subset), CD138 (a small subset), MUM1, c-MYC, HHV-8, and EBER and negative for B/T cell markers and CD45, a profile most compatible with extracavitary PEL. MUM1 (multiple myeloma 1) can be seen in lymphomas (such as plasma cell myelomas, plasmablastic lymphomas, diffuse large B-cell lymphomas, and some T-cell lymphomas) as well as in some sarcomas and melanomas. Further workup with additional markers, including HHV-8 and EBER, is required for a definitive diagnosis, especially for immunosuppressed patients.

Elevated Fetal Hemoglobin and Marked Thrombocytosis in an Adult Patient With Hereditary Pyropoikilocytosis

(Poster No. 147)

Andrew Ly, DO ([email protected]); George Kostanian, MD; Zhan Ye, MD, PhD. Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City.

We report a case of a 29-year-old woman who presented to our institution with symptoms of thrombocytosis and anemia. Complete blood count demonstrated a hemoglobin level of 10.9 g/dL, a mean corpuscular volume of 50.1 fL, and a platelet count of 1234 K/μL. Iron studies were within normal limits. Peripheral blood showed microcytic hypochromic red cells and marked anisopoikilocytosis with numerous elliptocytes, spherocytes, and enlarged reticulocytes and marked thrombocytosis with normal morphology (Figure 1.147, A). Hemoglobin electrophoresis demonstrated elevated fetal hemoglobin (10.1%), and a Kleihauer-Betke test highlighted the enlarged reticulocytes (Figure 1.147, B). JAK2 mutation analysis was negative. The patient had been transfusion dependent up until the age of 3 years, when a splenectomy was performed. A diagnosis of hereditary pyropoikilocytosis (HPP) was rendered. Elevated fetal hemoglobin and marked thrombocytosis are most likely complications of HPP, owing to bone marrow regeneration and splenectomy, respectively. An autosomal recessive disorder with mutated α spectrin genes, HPP is defined by severe hemolytic anemia, anisopoikilocytosis, microcytosis, and thermal instability of red blood cells. The mutant variant induces hypersensitivity to heat, with subjects exhibiting red blood cell morphology resembling that seen in thermal burns. Disease course progresses from an infancy of anemia and hemolysis to one of elliptocytosis and splenic sequestration in later years, with splenectomy a last resort. The purpose of this case report is to highlight the possible hematologic complications of this rare entity and to confirm the diagnosis.

Utility of Optical Genome Mapping in Characterizing and Delineating a Complex Cytogenetic Profile in a Case of Acute Myeloid Leukemia

(Poster No. 148)

Nivin Omar, MD ([email protected]); Nikhil Sahajpal, PhD; Ashis Mondal, PhD; Vamsi Kota, MD; Natasha Savage, MD; Ravindra B. Kolhe, MD, PhD. Department of Pathology, Medical College of Georgia at Augusta University, Augusta.

Acute myeloid leukemia (AML) is characterized by clonal expansion of undifferentiated myeloid precursors, resulting in impaired hematopoiesis and bone marrow failure. Karyotyping, fluorescence in situ hybridization (FISH), and microarrays are required to obtain a comprehensive molecular profile for diagnosis and prognostication in patients with AML. We report a case of AML analyzed by using optical genome mapping (OGM), demonstrating the ability of OGM technology to better characterize and delineate structural variants (SVs) previously identified by conventional techniques. The karyotype analysis demonstrated a complex cytogenetic profile, namely 45,XY,-5,-11,-17,add(18)(p11.3),−20,+3mar[19]/46,XY[1], with FISH analysis showing loss of 5q and gain of 5p. The analysis with OGM confirmed the loss of 5q and gain of 5p and resolved the cytogenetic profile with higher resolution. OGM identified complex rearrangements on chromosomes 11, 17, and 20, with multiple translocations and fusions. The 3 marker chromosomes detected with karyotyping were identified as chromosomes 11, 17, and 20, which resulted from these complex rearrangements. In addition, the add(18)(p11.3) resulted from the amplification and complex rearrangement at 18p11.3 with a copy number state of 8 of the fused regions of the genome (Figure 1.148). This case demonstrates the beginning of next-generation cytogenetics with high-resolution methodologies/techniques that have this unique ability to resolve the complex genomic rearrangements with high resolution. The findings in this case of AML highlight the clinical utility of OGM for genomic characterization of SVs that are difficult to characterize and resolve by conventional techniques.

Kolhe is a consultant with Bionano, Agena, QIAGEN, Perkin Elmer, PGDx, and Cepheid, and has received grant or research support from Perkin Elmer and Bionano.

Gastric T-Cell Lymphoma Presenting as Perforation and Peritonitis

(Poster No. 149)

Joshua M. Peterson, MD1 ([email protected]); Lindsay Bigham, DO1; Jianli Dong, MD, PhD1; Tejo N. Musunuru, MD2; Jayati Mallick, MD1; Kirill A. Lyapichev, MD.1 Departments of 1Pathology and 2General Oncology, University of Texas Medical Branch, Galveston.

A 68-year-old man presented to the emergency department with sudden acute-on-chronic abdominal pain, nausea, and vomiting with a 50-lb unintentional weight loss during the previous 6 months. Pneumoperitoneum and 2 spiculated lung nodules were identified on CT and radiography (Figure 1.149, A). Emergent surgical exploration for peritonitis revealed gastric perforation with gastric and omental nodules. Peritoneal washings were negative for neoplastic cells. However, histologic evaluation of perforation margins showed diffuse involvement by large pleomorphic lymphoid cells with multilobate nuclei, numerous mitotic and apoptotic figures, and focal anaplastic morphology (Figure 1.149, B; luminal surface, × 100 magnification). Neoplastic cells were admixed with scattered eosinophils and plasma cells. Immunohistochemical stains were positive for CD3 (focally), CD4 (Figure 1.149, C; × 100 magnification), CD5, CD7 (Figure 1.149, D; × 100 magnification), CD43, CD45, BCL2, and BCL6 and negative for CD1a, CD2, CD8, CD10, CD20, CD21, CD23, CD30, CD34, CD56, ALK1, TdT, lysozyme, MPO, HHV-8, and keratin. Ki-67 showed a proliferation rate of 80%–90%, and in situ hybridization was negative for Epstein-Barr virus. The presence of a clonal T-cell population was supported by positive polymerase chain analysis for TCRγ and TCRβ. Chromosome microarray analysis identified complex DNA copy number aberrations, including multiple deletions, hyperploidy, and copy-neutral loss of heterogeneity. Subsequently, endobronchial ultrasound-guided biopsy of the lung nodules showed immunophenotypically identical lymphoma. Taken together, morphologic, immunophenotypic, and molecular findings supported the diagnosis of gastric T-cell lymphoma presenting as gastric perforation and peritonitis. Gastric T-cell lymphoma is exceptionally rare, with poorly defined prognosis and treatment, standing in need of further clinical studies.

A Case of Double-Hit Follicular Lymphoma With MYC and BCL2 Rearrangement

(Poster No. 150)

Swetha Gaddam, MD ([email protected]); Juan Gomez-Gelvez, MD. Department of Pathology, Henry Ford Hospital, Detroit, Michigan.

Cases of follicular lymphoma (FL) with MYC and BCL2 gene rearrangements (double-hit follicular lymphoma; DH-FL) are infrequent, with several cases reported in the literature. However, their clinical significance has not been well defined. We report a case of a 63-year-old man who presented with extensive lymphadenopathy. Biopsy of a lymph node (LN) (Figure 1.150, A) showed effacement of architecture by follicular proliferation of atypical lymphocytes showing a mixture of blastoid, centrocyte, and centroblast morphology. The neoplastic follicles were positive for CD20 and PAX5, with coexpression of CD10, BCL-6, and BCL-2, diagnostic of FL with blastoid features. FISH testing on LN was positive for IGH/BCL2 and MYC and negative for BCL6 rearrangements. Bone marrow (BM) biopsy (Figure 1.150, B) was performed for staging and showed 40%–50% involvement with FL with classic centrocyte morphology. FISH testing on BM was also positive for IGH/BCL2 and MYC and negative for BCL6 rearrangements. After 3 months of chemotherapy, the patient presented with worsening clinical symptoms. Peripheral blood and BM examination at this point showed diffuse high-grade B-cell lymphoma with blastoid features in leukemic phase and with MYC and BCL2 rearrangements on FISH testing. In the context of the clinical history, this lymphoma was most consistent with high-grade B-cell lymphoma with MYC and BCL2 rearrangements, transformed from FL. The patient progressively deteriorated and eventually died 4 months after the initial lymphoma diagnosis. To date, there are no appropriate recommendations on how to manage cases of DH-FL. Our case supports the literature in terms of being clinically aggressive and helps in improving our knowledge on DH-FH.

Primitive Non-Neural Granular Cell Tumor Presenting as Epidermal Inclusion Cyst

(Poster No. 151)

Jing Di, MD, PhD ([email protected]); Shadi A. Qasem, MD, MBA. Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington.

Primitive non-neural granular cell tumor is a rare mesenchymal neoplasm of unknown lineage with prominent cytoplasmic granularity. There are only 75 of these cases reported in the literature in the past 30 years. The negative stain for S100 protein distinguishes this entity from conventional granular cell tumors with neural differentiation. An underlying ALK rearrangement has been reported in a small subset of cases. Here we report a case of a 7-year-old girl who presented with a 2-month progressively growing inflamed itchy and painful epidermal inclusion cyst in the left shoulder. Physical examination showed a 5 × 4-cm fungating tender mass with minimal bloody fluid discharge upon palpation. Intraoperatively, a brown-tan to yellow-tan variegated fungating friable 3.8 × 3.2 × 2.0-cm mass was resected that did not invade underlying muscle but was adherent to fascia. Microscopic examination revealed well-circumscribed sheets of large polygonal cells with copious granular eosinophilic cytoplasm, mildly atypical vesicular nuclei, and rare mitotic figures (Figure 1.151, A). The tumor was positive for NKI-C3, ALK, α-1-anti-trypsin (Figure 1.151, B), factor XIIIA, CD68, and PAS (Figure 1.151, C). However, it failed to stain with S100 (Figure 1.151, D), smooth muscle actin, pankeratin, desmin, myogenin, and other melanocytic and epithelial markers. The panel of immunostains helped to rule out other differentials, and the diagnosis of primitive non-neural granular cell tumor was confirmed. Despite the scarce incidence, most of these tumors appear to behave in a benign fashion, and conservative management is recommended. Pathologists need to be aware of this entity and its unusual staining profile.

Follicular Lymphoma of the Oral Mucosa: Study of 5 Cases and Review of Literature

(Poster No. 152)

Ahmed F. Lazim, MD ([email protected]); Alisa Nobee, MD; Riya Kuklani, PhD; Ashish Bains, MD. Department of Pathology, Temple University Hospital, Philadelphia, Pennsylvania.

Context: Lymphomas represent approximately 5% of malignant neoplasms of the head and neck region; they are the second most common malignant lesions after squamous cell carcinoma. Most are non-Hodgkin lymphomas (NHLs). Occurrence of lymphoma in the oral cavity is relatively rare, accounting for approximately 3.5% of oral malignancies.

Design: The study included 5 patients with extranodal NHLs of the oral cavity and maxillofacial region. Follicular lymphoma (FL) represented 5 cases (20.83%) of 24 lymphomas of the head and neck region during a period of 5 years, between January 2016 until July 2021. The frequent site of occurrence was the palatal intraoral mucosa (4 patients) and maxillary buccal vestibule (1 patient). The diagnosis was confirmed in the 5 cases by using routine H&E stain, IHC stains, FISH, and PCR studies.

Results: The neoplastic cells of the cases showed reactivity for CD20, PAX5, CD10, BCL2, BCL6 and negativity for CD5, CD43, and cyclin D1 (Figure 1.152, A through D; H&E, CD10, BCL6, BCL2). The proliferative index using Ki-67 was relatively low. FISH analysis of 3 cases confirmed IGH rearrangement, which is consistent with B-cell lymphoma. IGH/BCL2 rearrangement was revealed in a single case. In FL of the maxillary buccal vestibule, PCR revealed clonal IGH rearrangement and κ light-chain genes; however, FISH studies were negative for IGH::BCL2 fusion and BCL6 rearrangement.

Conclusions: Follicular lymphoma is a rare extranodal NHL of the oral cavity, compared with variants of NHL. Although FLs share similar morphologic and immunohistochemical features, they can reveal some molecular and genetic differences.

Diffuse Large B-Cell Lymphoma of Oral Mucosa: Study of 11 Cases and Review of Literature

(Poster No. 153)

Ahmed F. Lazim, MD ([email protected]); Iryna Mazur, MD; Riya Kuklani, PhD; Ashish Bains, MD. Department of Pathology, Temple University Hospital, Philadelphia, Pennsylvania.

Context: We identified 11 cases of diffuse large B-cell lymphoma (DLBCL) involving the oral/maxillofacial area in which most were (non-GCB) lymphomas, based on immunohistochemical expression of CD10, BCL6, and MUM1 and other auxiliary studies. Morphologically, the infiltrating cells had large nuclei with nuclear size equal to or exceeding normal macrophage nuclei, or more than twice the size of a normal lymphocyte.

Design: The study included 11 patients with extranodal NHLs of the oral cavity and maxillofacial region. They represented 11 cases (45.83%) of 24 lymphomas of the head and neck region in a period of 5 years, between January 2016 and July 2021. There were 7 men and 4 women. The patients' ages ranged from 62 to 91 years (median, 75 years).

Results: Seven cases belonged to the non-GCB subtype (63.63%), and the remaining 4 cases were of the GCB subtype (36.36%). The neoplastic large B cells showed panreactivity for CD20, PAX5, CD45, BCL2, and BCL6 (Figure 1.153, A through D; H&E, BCL6, PAX5, KAPPA-ISH). The reactivity for MUM1 and CD10 was variable, and CD5, CD43, and cyclin D1 were negative. The proliferative index using Ki-67 was relatively high in all cases (40%–95%). EBV (using EBER-ISH) was negative in nearly all cases (81.81%). ISH was useful in confirming the monoclonality of some cases.

Conclusions: EBV-negative non-GCB DLBCL is the most common form of extranodal lymphoma of the oral cavity that involves mainly elderly men, and GCB lymphomas tend to exhibit a better prognosis than non-GCB lymphomas, as described in other studies.

Syringocystadenoma Papilliferum: A Rare External Auditory Canal Tumor

(Poster No. 154)

Brenda Bukowiecki, DO ([email protected]); Karleen Meiklejohn, MD; Manju Prasad, MD, MBBS. Department of Pathology, Yale–New Haven Hospital, New Haven, Connecticut.

Ceruminous gland adenomas are uncommon lesions in humans. They comprise less than 5% of external ear tumors. They are benign and originate from the ceruminous glands, which are modified apocrine glands that produce cerumen (ear wax) and are found within the dermis at the outer third of the external ear canal. These lesions tend to be more common in the sixth to seventh decade of life and have no sex predilection. We present a case of a 53-year-old woman who presented with a nodule in the left ear canal. The lesion was excised and received as a 0.5 × 0.5 × 0.3-cm nodular tan soft tissue mass. Grossly, these lesions tend to appear polyploid, lobulated, or ulcerated. Histologic evaluation of the lesion revealed a complex glandulocystic invagination arising from the surface squamous epidermis. The lesion was lined by a benign-appearing 2-cell-layered epithelium that threw papillary projections into the cystic space, morphologically consistent with syringocystadenoma papilliferum (Figure 1.154, A through D). There are only a handful of similar cases reported in the external auditory ear canal. Syringocystadenoma papilliferum is known to be associated with nevus sebaceous in some cases. Treatment consists of complete excision. Once the lesion is completely removed, the likelihood of recurrence is extremely low.

Human Papillomavirus–Related Multiphenotypic Sinonasal Carcinoma: A Unique New Entity Presenting as an Antrochoanal Polyp

(Poster No. 155)

Nivin Omar, MBChB ([email protected]); Kiran Madwani, MBBS; Alexandra Medeiros, MD; Nikhil Patel, MD; Rafik Abdelsayed, DDS, MS. Department of Pathology, Augusta University, Augusta, Georgia.

Human papillomavirus (HPV)–related multiphenotypic sinonasal carcinoma (HMSC) is a unique, recently described indolent high-risk HPV-related neoplasm. HMSC shows a peculiar feature of mixed histologic phenotypes, including myoepithelial, ductal, and squamous lines of differentiation, and it frequently mimics salivary gland neoplasia, especially adenoid cystic carcinoma. The mean age at diagnosis is 54 years, with no sex predilection. Our patient was a 69-year-old male nonsmoker with a history of asthma who presented to an outside hospital with nasal obstruction. CT of the sinus demonstrated findings suggestive of a right maxillary antrochoanal polyp extending into the nasopharynx without bone destruction. The patient was referred to our hospital for functional endoscopic sinus surgery. Intraoperative findings showed a large mass of the right nasal cavity extending into the nasopharynx and the left nasal cavity. An intraoperative frozen section consultation presented concerns of “basaloid carcinoma.” Histologically, the neoplastic cells were arranged in lobules composed of basaloid epithelial cells with dual morphology of adenoid cystic carcinoma and basaloid squamous carcinoma with extensive necrosis. Immunohistochemically, the neoplastic cells were diffusely positive for P16 and P40 (Figure 1.155, A through D), but they were negative for synaptophysin and EBV in situ hybridization. The final pathologic diagnosis was PT1NXM0 HMSC. The case was discussed at our institutional head and neck tumor board, and further imaging and close observation were recommended. In conclusion, we present a rare and unique case of HMSC that presented clinically and radiologically as an antrochoanal polyp. Intraoperative consultation helped to correctly manage the patient through complete excision with negative margins.

A Rare Entity of Primary Sebaceous Carcinoma of the Salivary Gland

(Poster No. 156)

Mohammed Abdelwahed, MBChB ([email protected]); Saroja Devi Geetha, MBBS; Dmitriy Milkis, MD; Amr Ali, MD; Hector Daniel Chavarria Bernal, MD; Jian Yi Li, MD. Department of Pathology, Long Island Jewish Medical Center, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Queens, New York.

Sebaceous carcinoma (SC) occurs in the skin, particularly in the eyelid. Extraocular SCs are uncommon, and most cases occur in the head and neck. However, it is exceptionally rare in salivary glands, with only 50 cases reported to date. We report a case of a 59-year-old man with a painless slowly growing left parotid mass. The patient underwent parotidectomy for the lesion, which was a well-circumscribed 5.5 × 5.0 × 3.0-cm mass with solid and cystic areas (Figure 1.156, A). Microscopically, the tumor formed isolated small irregular nests of sebocytes (Figure 1.156, B). Cytoplasm was clear and vacuolated, with bland nuclei (Figure 1.156, C). Nerves, margins, and submitted lymph nodes were negative for malignancy. Increased mitotic activity and tumor necrosis were noted (Figure 1.156, D). Sebaceous adenocarcinomas on major salivary glands are extremely rare, and their pathogenesis and biologic behavior are not yet well established. Morphologically, SC may be identified by its distinctive microscopic findings, including cells with foamy cytoplasm and presence of holocrine secretion. Immunohistochemical reactions are useful in such cases, particularly adipophilin, to identify intracellular lipid droplets expressed in normal sebocytes and in neoplastic cells of sebaceous lesions. The differential diagnosis includes sebaceous adenoma, which lacks cytologic atypia, mitosis, and necrosis. Direct extension from primary SC of the skin is another possibility and requires clinical and radiographic separation. It is important to distinguish SC from sebaceous differentiation of squamous cell carcinomas (clear cell variant), mucoepidermoid carcinomas, and epithelial-myoepithelial carcinoma.

Adamantinoma-like Ewing Sarcoma Involving the Submandibular Gland of a Multiple Myeloma Patient

(Poster No. 157)

Recep Nigdelioglu, MD ([email protected]); Jeremiah F. Molligan, MD. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Adamantinoma-like Ewing sarcoma is a variant of Ewing sarcoma with complex epithelial differentiation harboring EWSR-FLI1 translocation. These sarcomas are rarely reported in salivary glands, and the diagnosis of these unusual tumors can be challenging, as they show an overlapping immunophenotype of both Ewing sarcoma and basaloid salivary carcinoma. Here, we report an adamantinoma-like Ewing sarcoma involving the submandibular gland of a patient with a history of multiple myeloma. The patient was a 70-year-old man with a medical history of multiple myeloma status post autologous stem cell transplant and in remission whose screening CT showed a 2.4-cm slowly growing irregular mass involving the left submandibular gland. The radiologic impression was a nodal metastasis or extraosseous plasmacytoma. Fine-needle aspiration of the mass revealed a basaloid proliferation with nonspecific immunophenotype, and excisional biopsy was recommended for further characterization. The patient underwent excision, and a left neck dissection performed upon frozen pathology reported high-grade salivary tumor. Histologic sections of the salivary gland showed highly infiltrative tumor with lobulated appearance (Figure 1.157, A). The neoplastic cells expressed CKAE1/AE3 (Figure 1.157, B), CK5, p40 (Figure 1.157, C), p63, synaptophysin (focal), chromogranin (focal), INSM1 (focal), and CD99 (weak) (Figure 1.157, D). INI-1 and BRG-1 protein expression were retained. EWSR1 FISH was performed and showed rearrangement supporting the diagnosis of adamantinoma-like Ewing sarcoma. The patient was referred to genetic counseling. In conclusion, adamantinoma-like Ewing sarcoma occurring in a salivary gland might overlap with basaloid carcinomas, and the recognition of this tumor might be essential for appropriate therapy.

Nasopharyngeal Amyloidosis Presenting With Tongue Deviation Due to Compression of the Hypoglossal Nerve: Case Report and Literature Review

(Poster No. 158)

Lindsay Bigham, DO1 ([email protected]); Chukwuyejulumafor Nwanze, MD1; Yasir Ali, MD1; Rohan Joshi, MD2; Jing He, MD1; Suimin Qiu, MD, PhD.1 Departments of 1Pathology and 2Otolaryngology, University of Texas Medical Branch, Galveston.

Amyloidosis is a group of slowly progressive disorders with extracellular deposition of insoluble polymeric fibrillar proteins in tissues and organs. It is classified into 2 main forms, systemic and localized, with differences in prognosis between both forms. Common sites of involvement include the kidney, heart, and liver. Solitary nasopharyngeal amyloidosis, a type of localized amyloidosis, is very rare, with few reported cases. We present a case of a 60-year-old man, a former smoker with a medical history of type II diabetes, who presented with a 1-month history of recurrent sinusitis and new-onset left tongue paresis. A maxillofacial CT scan showed soft tissue thickening of the posterior nasopharyngeal wall, measuring 5 cm and resulting in severe narrowing of the nasopharyngeal airway, highly suggestive of a malignant neoplasm. Laryngoscopy revealed a mass of the right fossa of Rosenmüller, compressing the right eustachian tube. Biopsies of the mass showed eosinophilic extracellular aggregates on microscopy suggestive of amyloidosis, confirmed by Congo red staining with apple-green birefringence in polarized light (Figure 1.158). Further imaging did not reveal additional organ involvement or associated nasopharyngeal malignancy. The patient had no previous pertinent medical or family history. The absence of risk factors and the unremarkable κ:λ ratio was highly suggestive of primary amyloidosis. To our knowledge, this is the first reported case of nasopharyngeal amyloidosis presenting with tongue deviation. Identifying amyloidosis as a differential diagnosis is important, as early recognition of this disorder could prevent further complications for the patient, allow exploration of management options in a timely manner, and avoid unnecessary surgery.

Sinonasal Verrucous Carcinoma With Orbital and Gingival Invasion

(Poster No. 159)

Richard Chiu, DO ([email protected]); Hyunseok Kim, MD; Julie Y. Kim, DO; Matthew J. Crabtree, MD; Ping Ji, MD. Department of Pathology, Harbor-UCLA Medical Center, Torrance, California.

Verrucous carcinoma is an extremely rare malignancy and an uncommon variant of squamous cell carcinoma that has mostly been reported in the oral cavity and larynx, and much less commonly in the paranasal sinuses and nasal cavity. We report a rare case of a verrucous carcinoma involving the maxillary sinus, nasal cavity, orbit, and gingiva. Our patient was a 43-year-old man with long-standing nasal blockage resulting from a 5-cm mass in his right maxillary sinus. Over time, this mass extended into his right nasal cavity and eroded through bony structures to reach the right infratemporal fossa, inferior orbit, and gingiva. An anterior rhinoscopic biopsy yielded an initial diagnosis of a sinonasal papilloma with high-grade dysplasia, but subsequent resection of the tumor by endoscopic sinus surgery and maxillectomy revealed it to be a sinonasal verrucous carcinoma. This tumor consisted of papillary fronds lined by markedly hyperkeratotic, parakeratotic, acanthotic, keratinized, stratified squamous epithelium with abundant keratin debris, forming verrucous “church spire” structures (Figure 1.159, A). The epithelium showed broad-based, rounded, bulbous rete ridges with expansive pushing margins and intact basement membranes without infiltrating tumor cells/nests (Figure 1.159, B). The tumor cells showed enlarged nuclei, prominent nucleoli, vesicular chromatin, perinuclear halos, and cytoplasmic vacuolation (Figure 1.159, C). Ki-67 expression was increased beyond the basal cell layer, reaching full thickness of the epithelium (Figure 1.159, D). Sinonasal verrucous carcinoma is an exceedingly rare malignancy that can often be misdiagnosed as a papilloma and spreads via expansive invasion or pushing borders rather than by single cell infiltration.

A Rare Case of Intraosseous Papillary Hemangioma of the Head and Neck

(Poster No. 160)

Saroja Devi Geetha, MBBS1 ([email protected]); Mohammed Abdelwahed, MBBCh1; Morris C. Edelman, MD1; Arzu Buyuk, MD1; David Gordon, MD2; Rishi Arvind, MD.1 Departments of 1Pathology and 2Neurosurgery, Zucker School of Medicine at Hofstra/Northwell, Greenvale, New York.

We report a rare occurrence of intraosseous papillary hemangioma (PH) of the frontal bone in a 69-year-old man. The patient presented with a slowly enlarging swelling in the right frontal area, noticed following an accidental fall. Imaging demonstrated a 4.5 × 4.2 × 1.7-cm infiltrative-appearing mass in the right frontal bone with focal involvement of the right orbital roof (Figure 1.160, A). Clinical suspicion of an aggressive lesion was favored. The patient underwent right frontal craniectomy with resection of the mass. Microscopic examination revealed an intraosseous bland vascular lesion with plump endothelial cells arranged in papillary configuration (Figure 1.160, B). Endothelial cells also showed hobnailing and intracytoplasmic hyaline globules (Figure 1.160, C and D). The lesional cells were immunoreactive with CD34 and vimentin. Negative stains included AE1/AE3, EMA, PR, D2-40, inhibin, and S100. The Ki-67 proliferation index was less than 1%. First described in 2007, PH is a novel variant of intravascular capillary hemangioma. Most of the reported cases are solitary, cutaneous lesions located in the head and neck region. There are only 17 cases of PH reported so far in the English literature. To the best of our knowledge, our case is the first reported intraosseous PH of the skull bone. Clinically, this lesion differs from other reported cases by the absence of a bluish skin papule. Preceding trauma may be an incidental association. Owing to the rare clinical presentation, the prognosis is unknown. Such patients should be monitored for local recurrence or malignant transformation.

An Extremely Rare Case of Mixed Carcinoma Ex-Pleomorphic Adenoma With Salivary Duct Carcinoma and Squamous Cell Carcinoma: A Diagnostic Dilemma

(Poster No. 161)

Matthew C. Donald, BS1 ([email protected]); Anne C. Kane, MD2; Varsha Manucha, MD.3 1School of Medicine, University of Mississippi, Jackson; Departments of 2Otolaryngology and 3Pathology, University of Mississippi Medical Center, Jackson.

Carcinoma ex-pleomorphic adenoma (CXPA) commonly occurs as a poorly differentiated adenocarcinoma or salivary duct carcinoma. We report an extremely rare case of CXPA composed of salivary duct carcinoma combined with a keratinizing squamous cell carcinoma (SqCC). A 59-year-old woman presented with a 3-year history of a parotid mass that enlarged rapidly during a 2-month period with otalgia and facial nerve weakness. Fine-needle aspiration (FNA) of the parotid showed an SqCC (Figure 1.161, A). The patient underwent surgical resection, including a total parotidectomy with facial nerve sacrifice and radical neck dissection. Gross examination revealed an infiltrative solid tan-white mass (6.7 cm) with several matted lymph nodes. On microscopy, the tumor was well circumscribed and predominantly necrotic, with peripheral areas of hyalinization with residual ductal elements. Conventional SqCC (Figure 1.161, B) was seen in the viable areas transitioning to high-grade carcinoma, composed of solid sheets and nests of tumor cells with vesicular nuclei, prominent nucleoli, and central necrosis (Figure 1.161, C). While some of the neck lymph nodes showed metastatic SqCC (KRT5/6, p63, and p40 positive), others showed high-grade carcinoma (KRT7, AR positive, and ERB2 negative) (Figure 1.161, D). The diagnosis of SqCC in parotid FNA raises suspicion of metastatic SqCC from a head and neck site. However, rarely it may represent a component of primary CXPA, as shown in our case. Clinical distinction between metastatic SqCC and CXPA is important to delineate risks of recurrence and metastasis. As histologic subtypes of CXPA relate to clinical outcomes, suspicion and documentation of mixed CXPA may elucidate these differences.

Squamous Odontogenic Tumor: A Diagnostic Pitfall Mimicking Squamous Cell Carcinoma

(Poster No. 162)

Carla Ayala Soriano, MD1 ([email protected]); Hayk Simonyan, MD1; Timothy Shaver, MD2; Navjot Singh, MD3; Stephanie Barak, MD1; Arjun Joshi, MD2; M. Reza Taheri, MD.3 Departments of 1Pathology, 2Otolaryngology Head and Neck Surgery, and 3Radiology, The George Washington University Hospital, Washington, District of Columbia.

Squamous odontogenic tumor (SOT) is a rare, benign neoplasm of odontogenic epithelium origin, first described in 1975. The tumor is thought to originate from neoplastic transformation of the epithelial cells of the rests of Malassez. It is found in the mandible and the maxilla, favoring the anterior region of the maxilla and the posterior region of the mandible. Clinical presentation ranges from asymptomatic to painful local gingival swelling. We present a case of SOT of the anterior mandible in a 60-year-old man with an ulcerating lesion that was initially diagnosed on biopsy as a squamous cell carcinoma (SCC) of the right mandibular alveolus. Radiographic evaluation showed an expansile radiolucent lesion within the symphysis and right parasymphyseal mandible, causing thinning of the buccal cortex (Figure 1.162, A). A composite resection of the floor of the mouth and a mandibulectomy with right selective neck dissection were performed. Histologic examination revealed proliferation of epithelial nests and variably shaped islands, with bland cytology, paradoxical maturation, and single-cell keratinization. Microcysts within the cellular islands and laminated microcalcifications were present, with nests and islands separated by fibrous connective tissue (Figure 1.162, B through D). Because of histologic overlap, SOT has often been overdiagnosed as ameloblastoma and SCC. Our case highlights the importance of careful and comprehensive evaluation of limited samples such as fine-needle aspiration or biopsy, keeping in mind that not all squamous lesions in the jaw are SCCs. Clinical correlation and radiologic studies are helpful to differentiate SOT from other odontogenic tumors and to avoid unnecessary, aggressive interventions.

Gnathic Osteosarcoma: A Diagnostic and Therapeutic Challenge

(Poster No. 163)

Christina H. Wiedmer, MD1 ([email protected]); Kristine Vo, BS2; Kurtis Young, BS2; Daniel Alam, MD.3 1Department of Pathology, University of Hawaii, John A. Burns School of Medicine, Honolulu; 2John A. Burns School of Medicine, University of Hawaii, Honolulu; 3Head and Neck Institute, The Queen's Medical Center, Honolulu, Hawaii.

Osteosarcoma (OS) is a common primary bone malignancy across all age groups. Despite this, primary bone tumors are relatively uncommon, accounting for less than 1% of cancers diagnosed in the United States. With the metaphysis of long bones being the main sites of peripheral OS, less than 10% of OSs arise from the head and neck. Approximately half of head and neck OSs involve the jaw and are also known as gnathic osteosarcomas (GOSs). Although GOS and peripheral OS are histologically identical, patients with GOS tend to present at older ages and with a higher propensity for local recurrences than patients with peripheral OS. More importantly, patients with GOS tend to have less frequent metastatic spread at the time of diagnosis. Hence, the prognosis for GOS tends to be more favorable in contrast to most cases of peripheral OS. The etiologic differences between GOS and peripheral OS are poorly understood. Moreover, there is a lack of consensus regarding optimal treatment modalities. There is a paucity of data pertaining to GOS, and studies are limited by the rare nature of this disease. Conversely, the National Comprehensive Cancer Network offers well-established guidelines for the management of peripheral OS as compared to GOS. In the current study, we present a case series of 3 patients diagnosed with and treated for GOS. Additionally, we examine the possible association between inflammation caused by dental implants and the development of OS and provide our observations in the treatment of patients with GOS.

Single-Institution Retrospective Analysis of the Utility of Histopathologic Diagnosis of All Routine Tonsillectomies in Adult and Pediatric Populations

(Poster No. 164)

Tanya Shenoy, BS1 ([email protected]); Varsha Prakash, MD2; Varsha Manucha, MD.2 1School of Medicine and 2Department of Pathology, University of Mississippi Medical Center, Jackson.

Context: Tonsillectomy is a common otolaryngologic practice in the United States; however, there is no consensus on whether histopathologic examination should be performed on resected specimens. In our institution, a gross examination is performed for all specimens, while an additional microscopic examination is performed for patients > 14 years of age. This study aimed to evaluate our current practice and compare the findings of histopathologic examination of tonsillectomy specimens within different age groups.

Design: A retrospective review of tonsillectomy surgical pathology reports for a period of 3 years was performed. Histopathologic diagnoses were evaluated in 3 age groups: 14–18 years, 19–45 years, and > 45 years.

Results: A total of 2903 tonsillectomy specimens were examined. Of the 500 specimens (17%) with microscopic examination, 215 (43%) were obtained in the 14- to 18-year, 222 (44.4%) in the 19- to 45-year, and 63 (12.6%) in the > 45-year age group. In patients <18 years, all specimens were benign. In patients 19–45 years of age, 2 (0.9%) were malignant. In patients > 45 years, 24 (38%) were malignant (Figure 1.164). The malignant diagnosis was clinically suspected in all cases. The 3 clinically unsuspected findings in patients > 18 years were benign.

Conclusions: Our study supports the practice of performing a gross examination on palatine tonsils only in patients ≤18 years of age. While there is a possibility of unexpected findings in patients 19–45 years, a malignant diagnosis is rare (<1%) and is clinically suspected. The practice of microscopic examination of tonsillectomy specimens in patients > 18 years may be warranted only when clinically indicated.

First Report of a Mott Cell Infiltrate Presenting as a Base of Tongue Mass

(Poster No. 165)

Austin L. Gray, MD ([email protected]); Cody Carter, MD; Yan Liu, MD, PhD; Jun Wang, MD; Anwar S. Raza, MD; Camilla Cobb, MD. Department of Pathology, Loma Linda University Health, Loma Linda, California.

Mott cells are plasma cells containing Russell bodies, which are eosinophilic inclusions made up of immunoglobulins located within the endoplasmic reticulum and causing cytoplasmic distention. Mott cell infiltrates are primarily identified within the gastrointestinal tract in association with chronic inflammatory conditions, such as gastritis and Barrett esophagus. To our knowledge, this is the first report of a Mott cell infiltrate forming a mass in the tongue. A 51-year-old woman presented with a base of tongue mass with no other known significant history. Biopsy demonstrated a prominent submucosal collection of large, deeply eosinophilic cells with small round nuclei and fine chromatin (Figure 1.165, A and B). Immunohistochemical staining showed the cells to be negative for S100, pancytokeratin, epithelial membrane antigen, calretinin, inhibin, smooth muscle actin, myogenin, and desmin, which essentially ruled out an epithelial lesion, granular cell tumor, or rhabdomyoma. Additional workup showed positivity for MUM1 (Figure 1.165, C) with focal positivity for CD138 (Figure 1.165, D). κ and λ immunohistochemistry and in situ hybridization revealed these cells to be polytypic. These findings supported that the cytoplasmic eosinophilia and cell distention were due to immunoglobulins (Russell bodies). The immunoglobulin secretions were postulated to arise in response to antigenic stimulation. In addition to the gastrointestinal tract, Mott cell infiltrates have been infrequently reported in other sites associated with various inflammatory and neoplastic conditions. The patient case we report had no such known associations, and this appears to be the first report of a Mott cell infiltrate causing a mass in the tongue.

A Schwannoma Mimicker: Extranodal Palisaded Myofibroblastoma

(Poster No. 166)

Samikshya Neupane, MD ([email protected]); Mari Perez-Rosendahl, MD; Beverly Y. Wang, MD; William B. Armstrong, MD; Ifegwu Ibe, MD. Department of Pathology and Laboratory Medicine, University of California, Irvine, Orange.

Myofibroblastomas are rare benign myofibroblastic neoplasms with distinct entities that typically arise in mammary and soft tissue or lymph nodes. Loss of RB1 expression is characteristic of mammary and soft tissue myofibroblastomas, whereas B-catenin alterations result in cyclin D1 and B catenin expression in intranodal palisaded myofibroblastoma. Myofibroblastomas are composed of spindle cells with variably prominent amianthoid-like collagen and nuclear palisading, especially in palisaded intranodal myofibroblastoma. We describe a unique case of a 48-year-old woman who initially presented to an outside institution with a few months of dysphagia and an epiglottic mass that was biopsied and reported as a nerve sheath tumor. Upon the patient's arrival at our institution, the mass was causing airway obstruction, and she underwent direct laryngoscopy for resection. Macroscopic examination of the mass showed a well-circumscribed unencapsulated tan-gray solid nodule with sclerotic cut surfaces. Microscopy revealed a submucosal multinodular tumor composed of monotonous, plump bipolar spindle cells forming prominent nuclear palisades resembling Verocay bodies (Figure 1.166). No lymph node was seen. The tumor was immunonegative for S100 and SOX10, as well as other markers, including pancytokeratin, HMB-45, STAT6, and desmin, but immunopositive for SMA, h-caldesmon, cyclin D1, and RB1, consistent with an extranodal palisaded myofibroblastoma. Myofibroblastomas can show prominent palisading, causing significant morphologic mimicry with schwannoma. In addition, in this case, the mass caused airway obstruction, which often implies aggressive malignancy. Knowledge of this rare entity in unique locations and appropriate immunohisto-chemistry helps to evade diagnostic pitfalls and avoid misdiagnosis of this lesion as a more aggressive tumor.

Sporadic Endolymphatic Sac Tumor With Distant Lymph Nodal Metastasis: A Rare Case Report and Literature Review

(Poster No. 167)

Khaled S. Mohamed, MD ([email protected]); Basma Elhaddad, MD; Arun Gopinath, MD; Reeba Omman, MD. Department of Pathology, University of Florida College of Medicine, Jacksonville.

Endolymphatic sac tumor (ELST) is a low-grade adenocarcinoma of the endolymphatic sac/duct. ELST is indolent but locally aggressive, with multiple relapses. ELST is rare, associated with von Hippel–Lindau syndrome, and rarely sporadic (27%). A 56-year-old Black woman with long-standing diminished right-sided hearing and Ménière-like symptoms presented with sudden right facial droop. Imaging showed an expansile destructive mass (3 cm) within the posterior temporal bone and the middle ear that was clinically diagnosed as a jugulotympanic paraganglioma. The patient underwent radiotherapy. After 8 years of regression, there was regrowth and extension of the mass into the right carotid canal and cerebellum (Figure 1.167, A). A subtotal resection was performed. Microscopic examination showed follicular spaces with secretions and simple papillae (Figure 1.167, B) with bone invasion and postradiotherapy effect (Figure 1.167, C). The tumor cells were bland/low cuboidal (Figure 1.167, D), staining for pan-cytokeratin (CK) (Figure 1.167, inset in E). Based on negative von Hippel–Lindau screening and histology, sporadic ELST was diagnosed after excluding metastatic papillary thyroid carcinoma (negative TTF-1/thyroglobulin), ceruminous adenoma, paraganglioma, and adenomatous tumor of the middle ear. After 2.5 years, brain and head/neck imaging showed regrowth of the mass with right cervical lymphadenopathy. Neck dissection revealed 8 lymph nodes with metastatic hierarchical-branched papillae (Figure 1.167, F) of pseudostratified-columnar atypical cells with prominent nucleoli and few mitoses (Figure 1.167, inset in G). The cells expressed pan-CK/PAX8 (Figure 1.167, inset in H) favoring metastatic ELST and did not stain with PAS-D or mammaglobin/S100, excluding acinic-cell or secretory salivary carcinomas, respectively. Two cases of spinal drop metastasis were reported. This is the first case report of a sporadic ELST with lymph node metastasis. Early detection and wide excision improve the prognosis.

Posttraumatic Cutaneous Meningioma Presenting as a Midline Nasal Mass

(Poster No. 168)

Jerry J. Lou, MD1 ([email protected]); Mari Perez-Rosendahl, MD1; William H. Yong, MD1; William Armstrong, MD2; Beverly Y. Wang, MD.1 Departments of 1Pathology and 2Otolaryngology–Head and Neck Surgery, University of California Irvine Medical Center, Orange.

Cutaneous meningiomas are rare congenital or acquired tumors arising from meningothelial cells located in the cutis. We report an unusual case of cutaneous meningioma that may have resulted from remote head trauma. To the best of our knowledge, this is the first reported case of posttraumatic cutaneous meningioma involving the nasal bridge. A 64-year-old man presented with a recently growing 2.0 × 1.4 × 1.1-cm circumscribed superficial mass overlying the right nasal bridge. The mass showed heterogeneous enhancement and mixed fat and soft tissue signal intensity components. No bony erosion or central nervous system connection was seen by head CT or MRI. The patient's medical history was remarkable for head trauma with facial fractures status post right frontal cranioplasty 20 years prior. The nasal bridge mass was excised uneventfully. Histology revealed a meningothelial-like vascular-rich epithelial proliferation arranged in nodular nests heterogeneously distributed within fibroadipose tissue and skeletal muscle (Figure 1.168, A and B), resembling a glomus tumor or meningiolipoma. No nuclear pseudoinclusions, whorled growth pattern, or pseudovascular spaces were seen. Immunohistochemistry exhibited immunoreactivity for epithelial membrane antigen, progesterone receptor (Figure 1.168, C), somatostatin receptor 2 (Figure 1.168, D), and androgen receptor. Cytokeratin AE1/AE3, p63, S100, smooth muscle actin, desmin, and HMB-45 were negative. To the best of our knowledge, this is the only description of a cutaneous meningioma possibly related to prior head trauma presenting as a midline nasal mass. Posttraumatic cutaneous meningiomas are hypothesized to result from displacement of meningeal tissue during prior trauma or procedures.

Extranodal Rosai-Dorfman Disease Affecting the Sinonasal Cavity and Ear Canal

(Poster No. 169)

Jamie Nakagiri, MD ([email protected]); Ifegwu Ibe, MD; Edward Kuan, MD; Edward Kuoy, MD; Beverly Wang, MD. Department of Pathology, University of California Irvine, Orange.

Context: Rosai-Dorfman disease (RDD) is a rare, idiopathic histiocytic proliferative disorder. Although RDD can involve the head and neck lymph nodes, it can affect other extranodal sites. We present 4 cases of RDD affecting the sinonasal cavity and ear canal. The clinicoradiologic findings and histologic features are discussed.

Design: Case 1 involved a 61-year-old man who presented with nasal obstruction and bilateral polypoid sinonasal masses. Intraoperative consultation showed a pleomorphic neoplasm with scattered large atypical spindle cells resembling a high-grade sarcoma. Case 2 involved a 46-year-old man who presented with bilateral maxillary chronic sinusitis with mass formation, clinically suggestive of lymphoma. Excision showed large irregular spindled histiocytes with abundant cytoplasm. Case 3 involved a 36-year-old woman who presented with left-sided chronic otalgia. Imaging revealed an external auditory canal mass extending to the middle ear. Case 4 involved a 20-year-old woman with complaints of nasal swelling and epistaxis for more than 8 months. Imaging showed a 2.8-cm polypoid mass in the anterior nasal septum.

Results: All cases displayed large atypical spindled histiocytes resembling fibrohistiocytic or myofibroblastic neoplasms. Emperipolesis was seen. The large atypical cells were positive for S100, CD68, and CD163, confirming a diagnosis of extranodal RDD. No malignancy was identified. Case 3 showed RDD coexisting with cholesteatoma.

Conclusions: Owing to its rarity and variable clinical presentations, a diagnosis of extranodal RDD is seldom considered. Additionally, extranodal RDD can morphologically mimic other spindle cell neoplasms, especially at intraoperative consultation, thus creating diagnostic and therapeutic challenges. Correlation of radiologic findings with histologic features will help with diagnosis.

Intraoperative Use of Wide-Field Optical Coherence Tomography to Evaluate Tissue Microstructure in the Oral Cavity and Oropharynx

(Poster No. 170)

Arvind K. Badhey, MD1 ([email protected]); Julia Schwarz, MD2; Benjamin Laitman, MD, PhD2; Brandon Veremis, MD2; William Westra, MD2; Mike Yao, MD3; Marita Teng, MD2; Eric Genden, MD2; Brett A. Miles, MD, DDS.4 1Department of Otolaryngology, University of Massachusetts Chan Medical School, Worcester; 2Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York; 3Department of Otolaryngology, Westchester Medical Center, Valhalla, New York; 4Department of Otolaryngology, Northwell Health, New Hyde Park, New York.

Context: Involvement of the deep margins represents a significant challenge in the treatment of oropharyngeal cancer. Given the practical limitations of frozen section analysis, a need exists for real-time, nondestructive intraoperative margin analysis. Wide-field optical coherence tomography (WF-OCT) has been evaluated as a tool for high-resolution adjunct margin analysis in breast surgery. The clinical application of WF-OCT in head and neck surgery has not been explored.

Design: This was a prospective, single-center feasibility study to evaluate the utility of WF-OCT (OTIS, Perimeter Medical Imaging AI, Inc) to visualize microstructures at the margins of excised oral and oropharyngeal tissue. Adults undergoing primary ablative surgery of the oral cavity or oropharynx for squamous cell carcinoma were treated according to standard surgical care. Freshly resected specimens were imaged with high-resolution WF-OCT before routine pathology. Interdisciplinary interpretation was performed to correlate digitized pathology slides and WF-OCT images.

Results: Sixty-nine specimens from 53 patients were collected and scanned (42 tonsillar tissue, 17 base of the tongue, 4 buccal tissue, 3 mandibular, 3 other). Forty-one specimens were malignant, and 28 were benign. Correlation analysis between WF-OCT images and H&E slides demonstrated visual differentiation among mucosa, submucosa, muscle, dysplastic, and benign tissue in real time.

Conclusions: WF-OCT was able to scan specimens and did not interfere with surgical procedures or final pathology. Microarchitectural features observed in WF-OCT images were correlated with permanent histology with fidelity. Formal clinical studies investigating use of WF-OCT for intraoperative analysis of deep margins in head and neck surgery are warranted.

Oncocytic Epithelial Myoepithelial Carcinoma Misdiagnosed as an Inverted Sinonasal Papilloma

(Poster No. 171)

Yuanzhe Zhu, MBChB1 ([email protected]); Samantha Jakuboski, BS2; Elnaz Panah, MD1; Swati Mehrotra, MBBS, MD1; Vijayalakshmi Ananthanarayanan, MBBS, MD.1 1Department of Pathology, Loyola University Medical Center, Maywood, Illinois; 2Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois.

An 82-year-old man presented with a decade-long history of right sinus congestion, nasal discharge, and facial pressure. Head CT revealed a right nasal cavity mass with extension into the nasolacrimal duct. The mass was initially diagnosed as an inverted papilloma, and the patient underwent endoscopic resection of the mass. Histopathology revealed an oncocytic tumor with 2 distinct cell populations arranged in interconnecting nests, trabeculae, tubules, and glandlike structures (Figure 1.171, A through C). The biphenotypic tumor was composed of oncocytic luminal cells with an attenuated abluminal myoepithelial cell layer. Immunohistochemistry further accentuated this dual phenotype; the myoepithelial outer cell layer was highlighted by p40 (Figure 1.171, D), p63, SMA (Figure 1.171, E), and cytokeratin 5/6 immunostains. The oncocytic luminal cells were largely CD117 positive (Figure 1.171, F). Based on the morphology and immunophenotype, a diagnosis of epithelial myoepithelial carcinoma, oncocytic type, was rendered. Oncocytic epithelial myoepithelial carcinoma (OEMCa) is a rare variant of epithelial myoepithelial carcinoma (EMCa), comprising less than 10% of all EMCas. OEMCas are indolent in nature and have a later age of onset than conventional EMCas. Diagnosis is particularly challenging on smaller biopsies, as OEMCas are often mistaken for other oncocytic neoplasms, such as the oncocytic variant of Schneiderian sinonasal papilloma. The presence of a continuous layer of myoepithelial cells around oncocytic tumor nests is a helpful clue in reaching a definitive diagnosis.

9:00 AM–11:45 AM; Poster Focus, 9:00 AM–10:00 AM
Gynecologic and Placental Pathology; Kidney and Genitourinary Pathology; Bone and Soft Tissue Pathology; Cytopathology; Cardiovascular Pathology
Increased Pathologist Effort Required for Review of Total Versus Partial Salpingectomy Specimens

(Poster No. 1)

Mariangela Gomez Ferrer, MD ([email protected]); Lulu Sun, MD; Eleanor Castro, MD; Ariel Wu, MD; Nicolas Kostelecky, MD; Ian Hageman, MD. Department of Pathology, Washington University, St. Louis, Missouri.

Context: Total salpingectomy has the potential to reduce the incidence of pelvic high-grade serous cancer by microscopic examination of the fimbriated end for exclusion of serous tubal intraepithelial carcinoma, whereas a partial salpingectomy requires identifying a complete cross section. We hypothesized that it would require greater effort from pathologists to examine a total salpingectomy specimen than to examine a partial salpingectomy.

Design: Paraffin slides from a total of 20 bilateral salpingectomies, including 10 total and 10 partial salpingectomy cases, were retrieved and placed in random order for review. Each case consisted of 2 slides. No clinical information was provided. Six pathologists at different levels of training served as readers and were asked to review the slides, and the time required to review each case was recorded.

Results: Across all readers, the time required for microscopic examination of total versus partial salpingectomy cases was 60.5 versus 27.3 seconds, respectively (P < .001 by 2-way ANOVA). Level of training had a small but significant effect on reader speed (P < .002), with attending pathologists being fastest (Table).

Conclusions: The amount of time needed to examine paraffin slides from total salpingectomies was more than double that required for partial resections. The increased effort presumably reflects both the larger size of total salpingectomies and the increased cognitive burden of these specimens. Administrative tasks such as reporting, coding, and filing are likely to be similar for both types of cases. While these specimens are coded identically under Current Procedural Terminology, total salpingectomy requires additional effort and may be undervalued.

Adult Granulosa Cell Tumors of the Ovary: A Clinicopathologic Correlation Study of Hormone Receptor Expression

(Poster No. 2)

Andrii Puzyrenko, MD, PhD1 ([email protected]); Jennifer Gavina Chavez, MD2; Genaro Herrera-Cano, MD2; Janet S. Rader, MD2; Michelle Moh, MD, MS.1 Departments of 1Pathology and 2Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee.

Context: Most ovarian adult-type granulosa cell tumors (AGCTs) can be managed surgically; however, there is no effective treatment for advanced or recurrent tumors. Studies have shown equivocal results for the efficacy of adjuvant radiation or chemotherapy. Hormonal treatments have shown some promising results, but there are limited data available regarding use of hormonal adjunctive therapy.

Design: Sixty-five cases from 50 patients diagnosed with AGCT were immunohistochemically stained for estrogen (ER), progesterone (PR), and androgen (AR) receptors, and evaluated for percentage of positive tumor nuclei and staining intensity.

Results: Clinicopathologic characteristics were reviewed including somatic mutational analysis (Table). Of 65 cases, 42% were positive for ER, ranging from 1% to 50% of tumor nuclear staining; 91% were positive for PR, ranging from 1% to 95% of tumor nuclear staining; and 37% were positive for AR, ranging from 2% to 95% of tumor nuclear staining. Seven patients had multiple recurrent tumors available for staining, and the tumors tended to retain similar hormone expression profiles with each recurrence. Of the 17 patients with AR positivity ≥10%, 8 of them were either higher stage (2 or 3) and/or recurred.

Conclusions: Ovarian AGCTs in our cohort have variable expression of ER, PR, and AR. The hormone expression profile of tumors, along with the patient's specific clinicopathologic characteristics, including somatic mutations, could be utilized for hormonal modulation therapy and expand the therapeutic armamentarium for high-stage and/or recurrent tumors. In particular, as 47% of patients with tumors that showed AR positivity ≥10% were higher stage and/or recurred, this patient population may be targeted with antiandrogenic therapy.

Peritoneal Deciduoid Sarcoma Associated With Long-standing Endometriosis and Hormone Therapy: A Distinct Entity?

(Poster No. 3)

Rabia Zafar, MD ([email protected]); Debra A. Bell, MD. Department of Pathology, Mayo Clinic, Rochester, Minnesota.

Context: Neoplasms with decidual-like changes are rare on the peritoneum. We report 3 cases of low-grade epithelioid and spindled sarcomas with extensive decidual-like change occurring on the peritoneum in young women with long histories of peritoneal endometriosis and hormonal therapy, which we interpret as endometrial stromal sarcomas.

Design: The cases were obtained from consultation and surgical pathology files. Medical records and consultation letters were reviewed for clinical information and follow-up. Slides and immunostains were reviewed. Next-generation sequencing for 138 common sarcoma gene rearrangements was performed on all cases.

Results: Clinical features of cases including the following are shown in the Table. Histology in all cases showed deciduoid epithelioid and spindled cells with uniform, mildly atypical nuclei with prominent nucleoli and scattered mitotic figures. Case 2 showed a few areas with moderate atypia, necrosis, and an increased mitotic rate. Immunohistochemistry in case 1 was positive for CD10, PR, and BAP1. ALK and calretinin were negative. Case 2 was positive for PR, calretinin, and MCK, and Ki-67 was increased. Case 3 was positive for desmin, caldesmon, ER, PR, SMA, CD10, and WT1. NGS sarcoma panel did not detect any common sarcoma fusions in any of the 3 cases.

Conclusions: We present 3 cases of deciduoid sarcomas associated with long-standing, widespread endometriosis. These cases presented significant diagnostic difficulties that we interpret as endometrial stromal sarcomas with extensive decidual changes, based on the presence of endometriosis, the morphology, and the positivity for CD10/ER/PR. One patient died of tumor, confirming malignant behavior. These data suggest that these deciduoid low-grade endometrial stromal sarcomas may be a distinct entity that arises from long-standing endometriosis treated with hormonal therapy.

First Case of Small Cell Carcinoma of the Ovary of Large Cell Variant Diagnosed During Pregnancy With Placental Metastasis and Literature Review

(Poster No. 4)

Roselyne Choiniere, MD, MSc1 ([email protected]); Philippe Echelard, MD1; Sebastien Chenier, MD, BSc2; Claude Laplante, MD1; Perrine Granger, MD.1 Departments of 1Pathology and 2Genetics, University of Sherbrooke, Québec, Canada.

Small cell carcinoma of the ovary of the hypercalcemic type (SCCOHT) affects young women and rarely occurs during pregnancy. We report a case of SCCOHT of large cell variant diagnosed during pregnancy associated with a new mutational variant. A 32-year-old patient, gravida 1, without hypercalcemia, presented with intense acute abdominal pain at 32 weeks of an otherwise unremarkable pregnancy. A 12-cm right parauterine mass with suspicious abdominal lymphadenopathy was identified. Histologic analyses of the placenta following cesarean section revealed 2 clusters of carcinomatous cells on the maternal side consistent with placental metastasis (Figure 2.4, A). Within a month, the tumor rapidly progressed with extensive peritoneal, nodal, infra/supradiaphragmatic, and contralateral ovarian involvement. Histologic examination revealed an undifferentiated epithelial proliferation with loss of BRG1 by immunohistochemistry (Figure 2.4, B through D). The large cells showed epithelioid and rhabdoid features with prominent nucleoli and abundant eosinophilic cytoplasm. The patient died soon after surgical cytoreduction, before chemotherapy could be initiated. Next-generation sequencing of the lesion revealed a heterozygous likely pathogenic variant in SMARCA4 (NM_003072:c.1246-2A>G). To our knowledge, this variant has not been reported in the literature. This variant is predicted to alter the splicing donor site of exon 8 and result in loss of function of 1 copy of the SMARCA4 protein. Immunohistochemistry was consistent with a loss of BRG1 function, a subunit of the SWI/SNF ATP-dependent chromatin remodeling complex. SMARCA4 variant was found in mosaic in unaffected normal tissue, consistent with a germline origin. No other SMARCA4 pathogenic variant was found in cis in the affected tissue.

Granulosa Cell Tumor Presenting as a Ruptured Hematoma: Report of a Case With Molecular Analysis

(Poster No. 5)

Asma Arshia, MBBS ([email protected]); Shadi A. Qasem, MD. Department of Pathology, University of Kentucky, Lexington.

Granulosa cell tumor of the ovary, a sex cord–stromal tumor, is a rare type of ovarian cancer that accounts for approximately 2% of all ovarian tumors in adults. Symptoms due to excess estrogen may be present and vary according to the age of the patient. A 49-year-old woman, with history of end-stage renal disease and kidney transplant (2018), presented with acute onset abdominal pain and nausea. Grossly, there was an irregular large disrupted hemorrhagic mesenteric mass (11.5 × 6.0 × 5.0 cm) loosely adherent to the mesentery, adjacent to the appendix. On cross section, the mass was composed of a dark red-brown blood clot (hematoma). Microscopically, the majority of the mass was cystic and hemorrhagic, with limited neoplastic tissue lining the cystic cavity, and composed of solid sheets of polygonal cells with scant eosinophilic cytoplasm, round to oval nuclei and fine chromatin, and increased mitoses. Immunostains were focally positive for inhibin and estrogen receptor (ER) but negative for calretinin, pan-cytokeratin, epithelial membrane antigen (EMA), S100 protein, chromogranin, synaptophysin, and DOG1. A point mutation (c.402C>G) in the FOXL2 gene was identified, supporting the diagnosis of a granulosa cell tumor. Further inquiry of the patient revealed that, in 2011, she had undergone resection of an ovarian granulosa cell tumor at another facility. Recurrent and metastatic granulosa cell tumors may present as a hematoma many years after diagnosis, and pathologists need to be aware of this unique presentation. FOXL2 gene mutation can be helpful in unusual and challenging cases (Figure 2.5, A through D).

Placentas From SARS-CoV-2–Positive Unvaccinated Mothers: Eighteen Months of Institutional Experience in View of Literature Reports

(Poster No. 6)

Ahmed Lazim, MD ([email protected]); Suad Taraif, MD; Daniela Proca, MD. Department of Pathology, Temple University, Philadelphia, Pennsylvania.

Context: Several studies addressed histologic changes in SARS-CoV-2+ placentas in the past 2 years of the COVID-19 pandemic. Changes compatible with maternal vascular malperfusion (MVM) and fetal vascular malperfusion have been reported in most studies, as well as inflammatory changes, particularly chronic histiocytic intervillositis. We are adding our institutional experience with third-trimester placentas from COVID+ unvaccinated mothers delivering between March 2020 and August 2021.

Design: Three pathologists blindly reviewed pertinent clinical information, as well as pathologic features (gross and microscopic) from all placentas received by our surgical pathology service during 18 months of the pandemic from COVID-19+ unvaccinated mothers: 15 singleton third-trimester placentas and 1 twin third-trimester placenta.

Results: Six of 16 placentas (38%) were delivered through cesarean section (CS), 4 of the 6 CS patients being symptomatic for COVID-19, while 2 had CS for other reasons. The gestational ages ranged from 32 weeks 1 day (twin) to 40 weeks 5 days. The maternal age ranged from 17 to 35 years old. The placental weights ranged between 318 and 931 g (mean, 495.4 g) for singleton placentas. The major histologic findings were increased intervillous/perivillous fibrin deposition (14), infarcts (3), intervillous thrombus (2), increased Hofbauer cells in villi (6), delayed villous maturation for gestational age (9), villous hypoplasia (3), and accelerated villous maturation (2). Less common findings were focal acute chorioamnionitis, focal acute chorionitis, focal chronic villitis and intervillositis, and focal mild deciduitis.

Conclusions: Our experience shows that the main histologic findings in third-trimester placentas from COVID+ mothers are related to MVM and focal inflammatory changes and are concordant with other reports.

Leiomyosarcoma Arising From a Leiomyoma With Bizarre Nuclei: A Case Study and Making the Case for This Pathway to Leiomyosarcoma

(Poster No. 7)

Amanda L. Strickland, MD ([email protected]); Jian-Jun Wei, MD. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Leiomyoma with bizarre nuclei (LBN), a benign tumor, can be occasionally seen coexisting with leiomyosarcoma (LMS), but their connection remains largely unknown. Recent studies reveal some similar molecular changes in these 2 tumor types. Here we present the case of a 55-year-old woman who presented with a large uterine mass. Hysterectomy revealed a 10.5-cm tumor with high-grade nuclear atypia, geographic necrosis, and up to 40 mitotic figures per 10 HPF, consistent with LMS. There were also areas with features of LBN, such as nuclear atypia and fewer mitotic figures than in the markedly more pleomorphic areas, blending with leiomyosarcomatous areas. Immunohistochemically, both tumors shared HMB-45, p16, and p53 expression, but ER and PR were completely lost in LMS (Table). Genomic DNA from separately submitted LMS and LBN components for whole-genome copy number and OncoScan analysis showed some shared genomic copy number alterations and patterns of LOH between LBN and LMS along with loss of RB and PTEN genomic regions, as well as additional complex genomic alterations only in the LMS. These findings suggest a same tumor origin for these 2 areas, with a tumor progression for the LMS. LBN often presents with a benign clinical course, but its biological nature remains unclear. While the exact cause of LMS is unknown, the shared molecular findings between the 2 areas in this case suggest, along with growing data, that LMS may progress from a preexisting LBN as a pathogenic pathway from uterine leiomyoma to uterine leiomyosarcoma.

Endometriosis: A Retrospective Morphologic and Immunohistochemical Analysis Showing Evidence of Dualistic Origins of Implantation and Metaplasia

(Poster No. 8)

Michelle Lin, MD1 ([email protected]); Michael Deavers, MD1; Elvio Silva, MD.2 1Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas; 2Division of Pathology & Laboratory Medicine, MD Anderson Cancer Center, Houston, Texas.

Context: The most accepted theory on endometriosis pathogenesis remains the implantation, or retrograde menstruation, theory; the role of metaplasia has also recently been considered. The goal of our study was to analyze distinct morphologic characteristics of endometriosis suggestive of implantation versus metaplastic origins, and to analyze clinicopathologic characteristics of these cases.

Design: Cases of endometriosis with ovarian involvement were selected for review. Endometriosis located on the surface of tissues and with architecture resembling normal endometrium was categorized as “implantation-type” endometriosis, and endometriosis located within tissues and with abnormal architecture was categorized as “metaplastic-type” endometriosis. Clinicopathologic parameters including age, menstrual history, body mass index, and ovary histology were recorded. Immunohistochemistry for estrogen and progesterone receptors and WT-1 was performed in a subset of cases.

Results: Fifty-two cases of endometriosis were reviewed. Metaplastic-type endometriosis was seen in 51 cases and implantation-type endometriosis was seen in 12 cases (with 11 cases showing both types). Metaplastic-type endometriosis showed a greater association with distorted ovarian architecture than implantation-type endometriosis, as well as with smooth muscle metaplasia and endosalpingiosis (Table). Estrogen and progesterone receptor expression was strong in implantation-type endometriosis and variable in metaplastic-type endometriosis; WT-1 expression was frequent in metaplastic-type cases. No significant difference was found in patient age, menstrual irregularity, or body mass index.

Conclusions: Our results demonstrate 2 distinct types of endometriosis, suggestive of dualistic modes of pathogenesis via implantation and metaplasia. Metaplastic-type endometriosis was significantly more frequent and was nearly exclusively seen with ovarian abnormalities, suggestive of a possible causative relationship between these 2 phenomena.

Large Incidental Perivascular Epithelioid Cell Tumor of the Uterine Broad Ligament

(Poster No. 9)

Roopa Kumari, MBBS ([email protected]); Kevin Mijares, MD; Ahmed Ayad, MD; Nebras Zeizafoun, MD; Ippolito Modica, MD. Department of Pathology, Icahn School of Medicine Mount Sinai West, New York, New York.

Perivascular epithelioid cell tumor (PEComa) of the broad ligament is an extremely rare mesenchymal tumor with only 8 case reports in the literature. We report a case of a 27-year-old nulligravid woman with polycystic ovarian syndrome found to have an incidental left adnexal mass on fertility workup. Imaging showed a solid-cystic hemorrhagic mass abutting the left side of the uterus and causing asymmetrical ovarian enlargement and broad ligament vascular compromise. She underwent laparoscopic mass resection with left salpingo-oophorectomy. The mass measured 10 cm and appeared nodular and hemorrhagic, with an attached ovary. It had adhesions to the appendix. The uterus and right adnexa were unremarkable. Histology showed epithelioid ovoid to spindle cells with clear to eosinophilic cytoplasm forming nests and cords adjacent to thick-walled vessels. Neither necrosis nor lymphovascular invasion was identified. Mitotic count was 2/50 HPF. Tumor cells were positive for TFE3, smooth muscle marker (caldesmon), and melanocytic markers (HMB-45, MITF) (Figure 2.9, A through D). The ovary was negative. Molecular and genetic testing revealed TSC1 and CHEK2+ mutations. These findings were consistent with broad ligament PEComa of uncertain malignant potential. Broad ligament PEComas are rare and have variable clinical presentation. Most presented with abdominal pain and only 2 were incidental. Of the reported cases, 2 were of uncertain malignant potential and 6 were malignant. Other more common lesions involving this area include leiomyoma, Müllerian epithelial tumors, and fibroma. Broad ligament PEComas should always be considered in the differential diagnosis of neoplasms arising in this region, because of their rarity and uncertain malignant potential.

Primary Ovarian Carcinoid Arising in a Mature Cystic Teratoma: A Rare Entity

(Poster No. 10)

Tanya R. Lindenmuth, DO, MS1 ([email protected]); Rubina H. Mattu, MD.2 1Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland; 2Department of Breast & Gynecologic Pathology, Joint Pathology Center, Silver Spring, Maryland.

Mature cystic teratomas account for approximately 20% of ovarian neoplasms, with malignant transformation occurring in only 1%–3% of cases. Squamous cell carcinoma is the most common malignant transformation, followed by various adenocarcinomas and sarcomas. We present a case of a 60-year-old postmenopausal woman with a 3-month history of abdominal discomfort and distention. Computed tomography demonstrated a 29.4-cm simple cyst of the left ovary and an 8.0-cm complex cyst arising from the right ovary. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. The left ovarian cyst was grossly and histologically diagnostic of a serous cystadenoma. Grossly the right ovarian cyst measured 9.4 cm. Sectioning revealed a smooth-lined cyst filled with yellow caseous material and a solitary 4.5-cm tan-yellow solid nodule. Histologic evaluation of the cyst demonstrated mature ectodermal elements consistent with teratoma (Figure 2.10, A). The nodule showed solid nests and acini of uniform, round to oval cells with pink cytoplasm, abundant secretory granules, and centrally located nuclei with salt and pepper chromatin (Figure 2.10, B and C). Chromogranin and synaptophysin immunohistochemical stains were diffusely positive (Figure 2.10, D) and no mitotic activity was identified. These findings are indicative of a tumor of neuroendocrine origin, consistent with an insular-type primary ovarian carcinoid. Primary ovarian carcinoids account for 0.3% of all carcinoid tumors and less than 0.1% of ovarian cancers. This case emphasizes the importance of thorough sampling and accurate diagnosis, as ovarian carcinoids are often microscopic in nature and constitute a malignant transformation of an otherwise benign entity.

A Case of Uterine Tumor Resembling Ovarian Sex Cord Tumor With Recurrence

(Poster No. 11)

Ling Chen, MD, PhD ([email protected]); Wei Zhang, MD. Department of Pathology, Baylor University Medical Center, Dallas, Texas.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor that is considered benign in most cases but may have low malignant potential. Here, we report a case of UTROSCT with recurrence 8 years after the initial diagnosis. In 2013, a 40-year-old nulligravida African American woman had a laparoscopic resection of uterine masses, and a diagnosis of UTROSCT (Figure 2.11, A and B) was made. During follow-up in 2021, the patient presented with a 7.5-cm pelvic mass, which was adherent to the pelvic sidewall. A resection was performed. Bilateral ovaries were normal appearing. Grossly, the mass was lobulated with a smooth and glistening outer surface and a yellow tan cut surface. Microscopically, tumor cells displayed solid sheets, nests, and cores (Figure 2.11, C and D) resembling the previous resected UTROSCT. The findings are consistent with recurrent UTROSCT. Several cases of UTROSCT with recurrence or metastasis have been reported. Moore et al found that the presence of necrosis, significant mitotic activity, significant nuclear atypia, and older age were associated with risk of recurrence. In our case, the tumor recurred and displayed no necrosis, no significant mitotic activity or atypia, but an infiltrating growth pattern. The findings suggest that UTROSCT with an infiltrative pattern may have increased risk for recurrence. It has been reported that extended radical surgery prevented the development of recurrent disease. A radical surgery may be indicated for UTROSCT with an infiltrating growth pattern.

High-Grade Serous Tubo-ovarian Carcinoma: Can TLE-1 Expression Help Identify 2 Different Prognostic Subgroups?

(Poster No. 12)

Rebecca Graziano, MD ([email protected]); Jake Sharma, DO; Ronaldo DeLeon Zamuco, MD; Pratibha Sharma Shukla, MD. Department of Pathology, NYU Langone Health, New York, New York.

Context: TLE-1 plays an oncogenic role in various cancers via regulation of anoikis and protein transcription. High-grade serous tubo-ovarian carcinoma (HGSC) is an aggressive cancer that needs development of therapeutic and prognostic biomarkers. TLE-1 expression in HGSC and its effect on outcome of stage 3 patients was studied.

Design: TLE-1 immunohistochemistry was performed on 1 tumor section from each case (n = 37; clinical stage 3, status post optimal surgical debulking) and reviewed blinded to clinical outcome. Immunoscore (IS) was calculated as the sum of intensity (1 = mild, 2 = moderate, 3 = intense) and percentage of cells staining (0, 0%; 1, 1%–10%; 2, 11%–50%; 3, > 50%). Cases were divided into low expressors (IS = 0–3) and high expressors (IS = 4–6). Clinical outcomes of recurrence/disease progression, length of recurrence-free survival, and status at last follow-up were compared between the groups.

Results: Twenty cases (54%) were high expressors and 17 (46%) were low expressors of TLE-1. Three cases included foci of serous tubal intraepithelial carcinoma (STIC); IS was the same in STIC and HGSC of the same case. Clinical features and comparison of clinical outcome are summarized in the Table.

Conclusions: In this pilot study, high expression of TLE-1 in stage 3 HGSC appears associated with shorter average recurrence-free survival (38.5 versus 42.6 months) and higher rate of recurrence/disease progression during treatment (65% versus 53%) compared with low expression of TLE-1. TLE-1 expression may prove a useful tool for predicting prognosis of HGSC in larger studies in the future.

Proximal-Type Epithelioid Sarcoma of the Labia

(Poster No. 13)

Saman S. Karimi, MD, MS1 ([email protected]); Victoria Angelova, MD.2 1Department of Pathology, University of Illinois at Chicago; 2Department of Pathology, John H. Stroger Hospital of Cook County, Chicago, Illinois.

Proximal-type epithelioid sarcoma is an aggressive soft tissue tumor, accounting for <1% of all soft tissue sarcomas, with a high propensity to occur in proximal locations including the trunk, pelvis, perineum, and genital regions. Herein, we report a case of a 20-year-old nulliparous woman with no significant clinical history who presented to our institution with a 4-month history of progressively enlarging, painful left labial mass. Physical exam revealed a 9-cm firm, nonmobile mass in the region of mons pubis, extending to the left labia. CT scan of the abdomen and pelvis demonstrated a peripherally enhancing soft tissue density, measuring 9.1 × 8.2 × 6.0 cm, located predominantly in the subcutaneous tissue of the left inguinal region. A left labial mass IR-guided biopsy was performed, and the specimen was sent to pathology for histopathologic evaluation. Microscopic examination revealed highly pleomorphic cells with epithelioid and rhabdoid morphology. The lesional cells expressed cytokeratin AE1/AE3, CK8/18, and myosin (weak), were negative for desmin and CD99, and demonstrated loss of INI-1 expression. The morphologic and immunophenotype of the lesion was consistent with a diagnosis of proximal-type epithelioid sarcoma. While not unique to this entity, inactivation of the tumor suppressor gene SMARCB1 (INI-1) is a characteristic molecular finding in this entity. Proximal-type epithelioid sarcoma is an extremely rare sarcoma with an aggressive clinical course, and 60% of the cases have been reported to have distal metastasis. Accurate and timely diagnosis of this entity is imperative for treatment and survival of these patients (Figure 2.13).

Collision Tumor of the Ovary Involving Sertoli-Leydig Cell Tumor and High-Grade Serous Carcinoma: Report of the First Case

(Poster No. 14)

Allen C. Omo-Ogboi, MD1 ([email protected]); Michael T. Deavers, MD2; Kathleen M. Schmeler, MD3; Nidhi Tandon, MD, FRCPath.1 1Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston; 2Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas; 3Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston.

Collision tumors are the simultaneous occurrence of 2 distinct neoplasms in the same organ. Ovarian collision tumors are rare, with only a few reported cases. This is the first reported case between a high-grade serous carcinoma (HGSC) and a Sertoli-Leydig cell tumor (SLCT). A 60-year-old woman presented with postmenopausal bleeding. Imaging revealed a 9.4-cm solid left adnexal mass and a diffusely thickened endometrium. She underwent hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and bilateral pelvic sentinel lymph node biopsies. Gross examination showed a 202-g left ovarian mass, which revealed 3 distinct masses. Mass 1 was solid and tan-yellow, with a cystic area; mass 2 was solid and tan-brown; and mass 3 was lobulated and tan-yellow (Figure 2.14, A). Microscopically, masses 1 and 2 showed glands with marked nuclear atypia and increased mitosis (Figure 2.14, C). Immunohistochemistry was positive for WT1 (Figure 2.14, D), ER, and p16 (patchy) in both the tumors. P53 showed diffuse and strong staining in mass 1 and wild-type staining in mass 2. The presence of high-grade atypia together with positive staining for WT1 favored a diagnosis of HGSC in both tumors. Mass 3 showed lobules composed of tubules, cords, and sheets of Sertoli cells, admixed with Leydig cells and focal spindle cells (Figure 2.14, B). Immunohistochemistry showed positive staining for inhibin and calretinin. A diagnosis of moderately differentiated SLCT was made. The endometrium showed atypical hyperplasia. This is the first report of a collision tumor between an ovarian HGSC and SLCT. The prognosis in such cases is determined by the more aggressive tumor.

Pathologic Contributions to Uterine Prolapse: A Study of 150 Cases of Hysterectomy

(Poster No. 15)

Gloria Zhang, MD, MPH ([email protected]); Bin Yang, MD, PhD. Pathology and Laboratory Medicine Institution, Cleveland Clinic, Cleveland, Ohio.

Context: Currently, uterine prolapse is considered mainly a result of the weakening of its surrounding support structures. We speculate that uterine weight also contributes to the imbalance between a relatively heavier uterus and a weak pelvic floor supportive mechanism, especially in postmenopausal women.

Design: We identified 150 hysterectomy cases clinically indicated for moderate to severe uterine prolapse from our archives in the past 3 years. Clinicopathologic features including patient age, uterus weight, and microscopic findings were tabulated and analyzed.

Results: The patients' ages ranged from 35 to 86 years. Approximately 83% of women with prolapse were 50 years or older. Histopathologically, an endometrial polyp was seen in 7 patients. Five patients had unilateral ovarian serous cystadenoma or cystadenofibroma. The major pathologic findings were in the myometrium. Fifty-six patients (37.3%) had uterine leiomyoma, 40 patients (26.7%) had adenomyosis, and 32 patients (21.3%) had coexisting leiomyoma and adenomyosis. Twenty-two patients (14.7%) had neither leiomyoma nor adenomyosis. The uterine weight ranged from 25 to 638 g, with a mean of 79.8 g. The average uterine weights from patients with either leiomyoma (88.3 g), adenomyosis (60.7 g), or both (98.4 g) were heavier than those without leiomyoma or adenomyosis (34.5 g). The differences are statistically significant (P < .01). Malignancy is a rare finding in the prolapsed uterus. FIGO 1 endometrioid adenocarcinoma with less than 50% of myometrial invasion was found in 1 case.

Conclusions: Our study indicates that increased uterine weight, especially in postmenopausal women, is one of the important factors contributing to uterine prolapse, along with weakened pelvic floor support.

Uterus Didelphys With Unilateral Serous Carcinoma

(Poster No. 16)

Civan Altunkaynak, MD ([email protected]); Raafat Makary, MD; Jaime Morel, MD; Brett Baskovich, MD; Karina Hew, MD. Department of Pathology and Laboratory Medicine, University of Florida College of Medicine, Jacksonville.

Uterus didelphys (UD) is a rare abnormality resulting from fusion failure of Müllerian ducts between 12 and 16 weeks of fetal development resulting in 2 uterine cavities and cervices with common complete septum in between. Uterine anomalies with endometrial cancer, particularly serous carcinoma, in UD are extremely rare. We present a case of a 64-year-old woman with a history of UD and heavy postmenopausal bleeding. A Pap smear from bilateral cervices was positive for adenocarcinoma, and biopsy from the right endometrium showed serous carcinoma. Radical resection with pelvic lymph node dissection revealed UD with fungating papillary serous carcinoma filling the right endometrial cavity with surface endocervical involvement (Figure 2.16, A through C). The tumor invaded less than half of the myometrium thickness with negative lymph nodes (pT1aN0, FIGO stage 1A). The left side of the uterus had a benign endometrial polyp with no malignancy. About 25 cases of uterine malformation complicated by malignancy are reported in the English literature from the past 25 years. UD accounted for 52% of these cases with papillary serous carcinoma in only 2 cases. Preoperative diagnosis failed in 8 cases because of a failed D&C or hysteroscopy or negative endometrial biopsy because the tumor involved only one cavity/horn. This emphasizes the role of imaging studies, especially MRI, to assist in sampling and diagnosis. Uterine papillary serous carcinoma, an aggressive estrogen-independent (type 2) carcinoma, was reported in only 2 cases (one stage IIIC and the other IAC). The molecular mechanism underlying the selective unilaterality of carcinogenesis in UD is not yet known because of the extreme rarity of these cases.

PAX2 Is a Helpful Biomarker in Identifying Endometrial Atypical Hyperplasia

(Poster No. 17)

Gloria Zhang, MD, MPH ([email protected]); Bin Yang, MD, PhD; Christopher Przybycin, MD; Andres Chiesa-Vottero, MD. Department of Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio.

Context: A reliable biomarker is needed to improve the diagnostic accuracy of endometrial complex hyperplasia (CH) and atypical complex hyperplasia (AH). We assessed the sensitivity and specificity of PAX2 immunohistochemistry in separating AH from CH in 101 hysterectomy specimens.

Design: A total of 101 consecutive hysterectomy specimens were identified. All patients had a prior diagnosis of CH or AH or AH bordering on carcinoma. The endometrium was entirely submitted for microscopic examination. One representative section from each case was submitted for PAX2 immunohistochemistry. Sixty cases of benign endometrium were included as control cases. Negative PAX2 immunoreactivity was defined as total loss of PAX2 nuclear staining in clusters of at least 4 glands.

Results: All 60 cases of benign endometrium showed positive nuclear staining for PAX2 with variable intensity. A total of 101 hysterectomy specimens consists of 26 CH cases and 75 AH cases, including 24 cases with FIGO 1 endometrioid adenocarcinoma arising in lesions. A negative PAX2 immunostaining pattern was observed in 72 of 75 cases of AH and 4 of 26 cases of CH (P < .001). All carcinomatous lesions adjacent to AH, except one, showed negative PAX2 immunoreactivity. Loss of PAX2 expression by immunohistochemistry has a sensitivity of 84.6%, specificity of 96%, positive predictive value of 88%, and negative predictive value of 94.7% in identifying AH lesions.

Conclusions: Our study found loss of PAX2 nuclear expression present in the vast majority of AH lesions. PAX2 immunohistochemistry has high sensitivity and specificity in differentiating AH from CH lesions.

Adenomyosis With Sparse Glands and Intravascular Extension in a Case of Endometrioid Adenocarcinoma: A Potential Pitfall in Interpretation

(Poster No. 18)

Nada Mohamed, MD ([email protected]); Jaya R. Asirvatham, MD. Department of Pathology, Baylor Scott & White Health, Temple, Texas.

Intravenous adenomyomatosis (IVA) is characterized by the presence of benign endometrial stroma and glands admixed with smooth muscle in a vascular space within the myometrium. Most IVAs are associated with leiomyomata and intravenous leiomyomatosis (IVL). IVA is classified as a rare variant of IVL in the new WHO classification. We describe a case of adenomyosis with sparse glands with intravascular extension and endometrioid adenocarcinoma. A 56-year-old woman presented with postmenopausal bleeding. An endometrial biopsy demonstrated an endometrioid adenocarcinoma, and a total hysterectomy with bilateral salpingo-oophorectomy was performed. Grossly, the endometrial cavity was occupied by a 3.2-cm tan-white firm fundic mass. The myometrium was 2.5 cm thick, with a 0.8-cm tan-white whorled nodule. The periadnexal soft tissues were unremarkable. Histologic examination showed endometrioid adenocarcinoma, FIGO grade 2, involving less than 50% of the myometrium and no lymphovascular invasion. Diffuse adenomyosis with sparse glands was present, uninvolved by adenocarcinoma (Figure 2.18, A and B). A single focus (0.78 cm) of intravascular growth of benign inactive endometrial glands and stroma surrounded by bland smooth muscle (Figure 2.18, C) was noted. CD31 immunostain highlighted the surrounding vascular endothelium (Figure 2.18, D). There was no mitotic activity or atypia. Leiomyomata and IVL were absent. No metastatic or recurrent disease was identified at a 3-month follow-up. Although rare, it is important to be aware of IVA, particularly in the context of sparse glands (which may mimic a low-grade endometrial stromal sarcoma), as it could be misinterpreted as a malignant lymphovascular invasion.

Dystrophin as a Novel Biomarker for Leiomyosarcoma Classification and Prognosis

(Poster No. 19)

Brian Vadasz, MD, MSc ([email protected]); Christopher Felicelli, MD; Jian-Jun Wei, MD. Department of Pathology, Northwestern University, Chicago, Illinois.

Context: Uterine leiomyosarcoma (LMS) is a deadly disease with no reliable biomarkers to distinguish it from other mimics including leiomyoma with bizarre nuclei (LM-BN). Next-generation sequencing studies have shown a loss of dystrophin gene is associated with LMS of gynecologic origin and worse outcome.

Design: Cases for this study included usual-type leiomyoma (n = 35), fumarate hydratase–deficient leiomyoma (n = 31), LM-BN (n = 20), spindle cell LMS (n = 34), and myometrium (n = 48). Tissue microarray was prepared and immunohistochemical analysis for dystrophin was performed. Data from whole-genome sequencing in 10 LMSs were analyzed by BasePair; copy number alteration at the X chromosome and dystrophin gene location were examined. Kaplan-Meier analysis was used to estimate overall survival.

Results: Dystrophin expression was detected in 94% (45 of 48) of myometrium and in most benign leiomyoma variants, including 97% of usual-type leiomyoma (34 of 35), 87% of fumarate hydratase–deficient leiomyoma (26 of 31), 60% of LM-BN (12 of 20), and 18% of LMS (6 of 34) (Figure 2.19, A). Dystrophin expression was significantly different between benign and malignant tumors (P < .01) (Figure 2.19, B). There was downregulation, shown in red, in both copies of the dystrophin-coding region within the X chromosome in LMS samples. Although not significant, patients with dystrophin-positive LMS (n = 6) show a trend of higher survival compared with patients with dystrophin-negative LMS (P = .4).

Conclusions: Dystrophin is a novel biomarker for LMS, and loss of dystrophin is common and associated with worse outcome of LMS. Most benign variants of leiomyoma retain expression of dystrophin. Dystrophin may be a novel and useful surrogate biomarker in LMS.

Immunohistochemical Staining Pattern of Endometrial Adenocarcinoma With Microglandular Hyperplasia Features: A Diagnostic Challenge on Surgical Biopsy Specimen

(Poster No. 20)

Ayah Ali, MD ([email protected]); Changzhao Li, MD; Catherine Stoos, MD; Ahmed Sabri, MD; Poonam Sharma, MBBS. Department of Pathology, Creighton University Medical Center, Omaha, Nebraska.

Endometrioid adenocarcinoma (EAC) with microglandular hyperplasia (MGH)–like pattern is a rare histologic variant presenting a diagnostic challenge. It is difficult to differentiate EAC with MGH-like pattern from benign MGH of the cervix because of similar morphology and lack of sensitive and specific biomarkers. Additional biomarkers mentioned in the literature might be helpful. A CD10+/P63− staining pattern with high Ki-67 mitotic index would favor an EAC. In this case study, we describe 2 cases of EAC with MGH-like pattern. Two postmenopausal women presented with thickened endometrial stripe on imaging. Endometrial biopsy for case 1 showed packed glands with intraluminal mucin and inflammatory cells resembling cervical MGH. Case 2 (Figure 2.20, A) showed focal areas with endometrioid-type morphology in addition to the microglandular architecture and intraluminal inflammatory cells. Immunohistochemical (IHC) staining on case 1 showed positive staining for p16, CEA, ER, and vimentin, and wild-type p53 staining with a CD10+/P63 pattern within tumor cells. In case 1, a Ki-67 stain showed a > 10% mitotic index. The second case showed a similar IHC staining pattern to the first case. The hysterectomy specimen of case 1 showed endometrioid adenocarcinoma, FIGO grade 1, not otherwise specified. The hysterectomy specimen in case 2 (Figure 2.20, B) showed endometrial adenocarcinoma, endometrioid type, FIGO grade 1 with focal mucinous differentiation and microglandular architecture. IHC stains performed on the second hysterectomy specimen showed a similar pattern to its biopsy specimen. Review of these 2 cases demonstrated that IHC stain (CD10+/P63) supports ECA with MGH-like pattern (Figure 2.20, C and D).

Antigenicity of Frozen Section Versus Nonfrozen Section Tissue Blocks: An Immunohistochemical Comparison With Emphasis on Antibodies Commonly Used in Gynecologic Pathology

(Poster No. 21)

Quratulain Obaid, MD ([email protected]); Amal Shukri, MD; Andre Pinto, MD. Department of Pathology, University of Miami/Jackson Health System, Miami, Florida.

Context: Frozen section (FS) is a technique frequently utilized for intraoperative histopathologic diagnosis. We hypothesized that rapid freezing could potentially induce changes in antigenic expression, the principle utilized for immunohistochemistry (IHC). The aim of this study was to investigate variations in antigenicity by IHC in FS tissue samples.

Design: Whole-tissue sections of 113 cases with corresponding FS and nonfrozen (NFS) blocks were tested for 5 nuclear IHC stains (16 progesterone receptor [PR], 15 estrogen receptor [ER], 9 p53, 8 MSH6, and 8 PMS2), 2 membranous (10 HER2/neu, 18 PD-L1), 2 cytoplasmic (10 AMACR, 10 napsin A), and 1 nuclear/cytoplasmic (9 p16). Slides were reviewed by 2 pathologists (A.P., Q.O.) and classified as positive or negative, with positive cases scored quantitatively as focal (1%–50%) or diffuse (> 50%) and qualitatively as weak/moderate or strong. HER2/neu, PD-L1, and p53 were interpreted according to current guidelines. Cases were classified as concordant (similar qualitative and quantitative results), minor discrepant (quantitative differences in intensity/focality) or major discrepant (qualitative difference, ie, positive versus negative and vice versa, or changes in IHC properties with potential clinical impact, eg, discordant HER2/neu scores).

Results: Concordant IHC results on FS and NFS blocks were shown in 84.1% of cases. Fourteen cases (12.4%) showed minor discrepancy and 4 cases (3.5%) showed major discrepancy. Most major discrepancies were observed in nuclear stains (77.7%) followed by membranous stains (22.2%).

Conclusions: Generally, antigenicity is maintained in FS tissues samples. Most discordant cases may not be clinically or pathologically significant. However, awareness of cases with major discrepancies can help prevent erroneous interpretation of IHC results.

HER2 Immunohistochemical Expression in Clear Cell Carcinoma of Tubo-ovarian and Endometrial Primaries and High-Grade Serous Carcinoma of Tubo-ovarian Primary

(Poster No. 22)

Obianuju M. Anelo, MD1 ([email protected]); Jorge Solares, MSc2; Joel F. Gradowski, MD3; Farhan Khan, MD.3 1Department of Pathology, The University of Tennessee Health Science Center, Memphis; 2Department of Pathology and Laboratory Medicine, Methodist Lebonheur Healthcare, Memphis, Tennessee; 3Department of Pathology and Laboratory Medicine and Pathology Specialists of Memphis, Methodist Lebonheur Healthcare, Memphis, Tennessee.

Context: Human epidermal growth factor receptor 2 (HER2) overexpression is a prognostic as well as predictive biomarker (targeted therapy with trastuzumab) in breast, gastric, and endometrial serous cancers. The objective of our study is to evaluate the immunohistochemical (IHC) expression of HER2 in clear cell carcinoma (CCC) of Müllerian primary and high-grade serous carcinoma (HGSC) of tuboovarian primary.

Design: Sections from FFPE tissue blocks of 54 cases were stained with HER2 (Roche/Benchmark Ultra, 4B5). Of the total 54 cases, 37% (n = 20) were endometrial and 63% (n = 34) were ovarian. All (20 of 20) endometrial and 32% (n = 11) of ovarian cases were primary CCC, whereas 68% (n = 23) of ovarian cases were HGSC. HER2 IHC expression was scored using the ASCO and CAP 2018 focused update on HER2 testing in breast cancer.

Results: Of all ovarian cases, 6% were HER2 positive and 15% were equivocal, whereas for all endometrial cases, 5% expressed HER2 positivity and 20% were equivocal. HER2 expression was positive in 5% (3) of all cases, negative in 78% (42), and equivocal in 17% (9).

Conclusions: Our study shows the importance of HER2 IHC testing in ovarian serous carcinoma and CCC and warrants HER2 FISH testing in a relatively high percentage of equivocal cases. HER2 IHC and/or HER2 FISH testing must be evaluated on a larger cohort in Müllerian CCC and ovarian HGSC.

Synchronous Gynecologic Tract Neoplasms Associated With Endometrial Endometrioid Carcinoma

(Poster No. 23)

Ankica Braun, MD1 ([email protected]); Joanna Solarewicz, DO1; Lin Cheng, MD, PhD1; Indu Agarwal, MD1; Swathi B. Reddy, MD2; Paolo Gattuso, MD1; Lei Yan, MD, PhD.1 Departments of 1Pathology and 2General Surgery, Rush University Medical Center, Chicago, Illinois.

Context: Synchronous tumors of the gynecologic tract are rarely seen in practice. The majority of published literature is focused on synchronous malignant tumors. We undertook a retrospective study to assess synchronous neoplasms associated with endometrial endometrioid carcinoma.

Design: Our institution's database was searched for endometrial endometrioid carcinoma with associated synchronous neoplasms diagnosed on hysterectomy and bilateral salpingo-oophorectomy specimens.

Results: A total of 40 patients were identified. The ages ranged from 41 to 87 years. Of the endometrial endometrioid carcinomas, 22 (55%) were FIGO grade 1, 11 (27%) were grade 2, and 7 (18%) were grade 3. Thirty-one tumors (78%) were stage pT1a, 7 (18%) pT1b, 1 (2%) pT2a, and 1 (2%) pT3a. Forty-eight synchronous tumors were identified. Forty-four (92%) tumors involved the ovary, 2 (4%) fallopian tube, 1 (2%) cervix, and 1 (2%) endometrium. Eight (17%) were malignant, 2 (4%) borderline, and 38 (79%) benign. Of the malignant tumors, 2 were endometrioid carcinoma, 2 mucinous carcinoma, 2 adult granulosa cell tumor, 1 intraepithelial serous carcinoma, and 1 extranodal marginal zone B-cell lymphoma. Both borderline tumors were mucinous borderline tumors. Of the benign tumors, 10 tumors were mature cystic teratoma, 7 serous cystadenoma, 6 Brenner tumor, 3 mucinous cystadenoma, 3 serous cystadenofibroma, 2 adenofibroma, 2 fibroma, 2 fibrothecoma, 1 Leydig cell tumor, 1 seromucinous cystadenofibroma, and 1 adenomatoid tumor.

Conclusions: The most common synchronous neoplasms associated with endometrial endometrioid carcinoma were mature cystic teratoma, followed by serous cystadenoma and Brenner tumor. Of the malignant tumors, it was equally associated with endometrioid carcinoma, mucinous carcinoma, and adult granulosa cell tumor.

De Novo Clear Cell Carcinoma of Müllerian Origin of the Abdominal Wall: Apropos of a Case

(Poster No. 24)

Vidya Arole, MD ([email protected]); O. Hans Iwenofu, MD. Department of Pathology, The Ohio State University, Columbus.

Primary clear cell carcinomas (CCCs) arising in extraovarian sites such as the anterior abdominal wall (AAW) are extremely rare events. Their histogenesis is believed to be from presumed malignant transformation of scar endometriosis. Herein, we report a unique case of CCC arising in the AAW of a perimenopausal woman. A 49-year-old gravida 3, para 3 woman, with past medical history of poorly differentiated neuroendocrine carcinoma of the thymus and 3 previous cesarean sections, presented with a gradually increasing painful “lump/hard knot” at the umbilicus for 6 months. CT scan showed a 10-cm mass in the AAW without evidence of metastasis or primary lesion at any other site. CA19-9, CEA, and CA125 were within normal limits. Surgical resection was performed. Grossly, the tumor was a 10.3 × 8.1 × 5.9-cm, well-circumscribed, tan-white, lobulated mass (Figure 2.24). Histologic sections revealed predominantly monomorphic, round-polygonal clear to eosinophilic cells, high N:C ratio, round-angulated nuclei, and prominent nucleoli arranged in solid sheets/lobules separated by fibrous septa (Figure 2.24). No foci of endometriosis were seen. By immunohistochemistry, the tumor cells were positive for AE1/3, CAM5.2, PAX8, HNF1b, CK19, CK7, glypican-3, arginase-1 (focal and weak), napsin A, and AMACR, and negative for CK20, ER, PR and TTF-1. The p53 was wild type. The overall features were consistent with primary CCC of Müllerian origin. The patient is 32 months postsurgery with no evidence of recurrence or metastasis. In summary, we report a unique case of primary CCC of the AAW, highlighting the unusual clinical presentation and diagnostic challenges. The prognosis of this entity is unclear.

Correlation Between Positive High-Risk HPV (16, 18, Other) and Follow-up Cervical Biopsies in Patients With Negative Cervical Cytology in a Community Health Center

(Poster No. 25)

Hanae Benchbani, MD1 ([email protected]); Tara Krishnan, BA2; Emma M. Gloe, BS2; Soheila Hamidpour, MD.1 1Department of Pathology, University of Missouri Kansas City–University Health, Kansas City; 2School of Medicine, University of Missouri Kansas City, Kansas City.

Context: It is well established that the persistence of high-risk human papillomavirus (HR-HPV) infection is necessary for the development of cervical dysplasia. Currently, routine cervical cancer screening includes both HR-HPV testing and cervical cytology tests. The guidelines for managing HPV-positive and cytology-negative results are testing at 1 year or HPV genotyping for HPV-16 and HPV-18; however, if HPV-16 and HPV-18 infection(s) are positive, immediate colposcopy is recommended. We looked at the correlation between positive HR-HPV and negative cytology with cervical histology findings.

Design: Retrospective chart review was performed to identify all negative Pap smears with positive HR-HPV and follow-up colposcopy for patients who presented at our institution from January 2018 to December 2019. Our goal was to calculate the rate of normal cytology, low-grade squamous intraepithelial lesion (LGSIL) and high-grade squamous intraepithelial lesion (HGSIL) in these patients.

Results: A total of 179 patients with negative cytology and positive HR-HPV were included. The age range was 22 to 69 years. Among these, 166 patients (92.73%) had a normal follow-up biopsy result, 12 (6.70%) had LGSIL, and 11 (6.14%) had HGSIL on follow-up biopsy (Figure 2.25).

Conclusions: According to our data, a diagnosis of dysplasia (LGSIL and HGSIL) would have been missed in 23 of 179 patients (12.8%) in the absence of HPV testing. This finding further supports the benefits of simultaneous cytology and HPV testing as part of cervical cancer screening.

Fumarate Hydratase (FH)–Deficient Intravenous Leiomyomatosis Associated With FH-Deficient Leiomyoma: Report of an Unusual Case

(Poster No. 26)

Weiwei Shi, MD, PhD ([email protected]); Marisa R. Nucci, MD; Bradley J. Quade, MD, PhD. Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.

We present a case of a 49-year-old woman who underwent myomectomy for a large irregular fibroid. The resected cellular smooth muscle neoplasm was composed of large and atypical spindle cells with prominent orangeophilic nucleoli and eosinophilic cytoplasmic inclusions (Figure 2.26, A). By immunohistochemistry, fumarate hydratase (FH) expression was lost and 2-succinocysteine (2SC) adducts were present. Mitotic activity was low (1–2 per 10 high-power fields). Tumor necrosis was absent. Overall, the morphologic and immunophenotypic features were consistent with a smooth muscle tumor with FH deficiency. Two months after the myomectomy, the patient underwent hysterectomy. Gross examination showed multiple leiomyomata (up to 1.9 cm) and prior surgical site changes. Microscopically, there was residual tumor identical to the previously resected FH-deficient leiomyoma associated with healing biopsy site changes. Of note, there was a focus of tumor extending into a vascular space outside the confines of the leiomyoma, in keeping with intravenous leiomyomatosis (Figure 2.26, B). Immunohistochemically, the intravenous smooth muscle tumor was positive for 2SC (Figure 2.26, C), but negative for FH (Figure 2.26, D) and HMGA2. To our knowledge, this is the first reported case of FH-deficient intravenous leiomyomatosis associated with an FH-deficient leiomyoma. Because of the intermediate, quasi-malignant behavior of intravenous leiomyomatosis, clinical follow-up was recommended.

Unusual Endometrial and Endocervical Metastasis of Vulvar Extramammary Paget Disease

(Poster No. 27)

Elnaz Panah, MD ([email protected]); Thanchanok Chaiprasit, MD; Andreas Kontosis, MD; Geoffrey Chen, MS; Xiuzhen Duan, MD, PhD; Xianzhong Ding, MD, PhD. Department of Pathology, Loyola University Medical Center, Maywood, Illinois.

Extramammary Paget disease of the vulva is a clinically indolent disease and characterized by frequent local recurrence after resection. Distant metastasis is extremely rare. We present an interesting case of a 69-year-old woman with postmenopausal bleeding and biopsies of the endometrium and endocervix demonstrating metastasis of extramammary Paget disease. The patient was diagnosed with extramammary Paget disease of the vulva and underwent surgical resection and radiation therapy. Eighteen years later, she developed heavy postmenopausal bleeding. Endometrial and endocervical biopsies revealed infiltrating malignant epithelial cells in endometrial and endocervical stroma, associated with ulceration and hemorrhage. Tumor cells demonstrate enlarged nucleus, prominent nucleoli, and intracytoplasmic mucin with small solid nest and single-cell infiltrating patterns. Tumor cells were diffusely positive for CK7, GCDFP-15, GATA-3, CEA, and HER-2 with negative expression of PAX8 and P16, which is consistent with metastatic extramammary Paget disease. Subsequent imaging studies revealed a polypoid endometrial lesion at the uterine fundus. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. Histologic examination shows extensive endometrial stromal involvement by metastatic Paget disease on the resection specimen. The patient is doing well 1 year after the surgery. This case demonstrates a rare clinical and pathologic presentation of extramammary Paget disease and the importance of clinical history for correct diagnosis and treatment.

High-Risk Human Papillomavirus (HR-HPV) Genotype Prevalence in Histology Confirmed High-Grade Cervical Lesions From Colombian Women: Potential Impact in Vaccination Policies

(Poster No. 28)

Javier A. Baena-Del Valle, MD1 ([email protected]); Rocio López-Panqueva, MD1; Paula A. Rodriguez-Urrego, MD.2 1Department of Pathology and Laboratory Medicine, School of Medicine, Fundacion Santa Fe de Bogota University Hospital, Universidad de Los Andes, Bogota, Colombia; 2Department of Pathology and Laboratory Medicine, Fundacion Santa Fe de Bogota University Hospital, Bogota, Colombia.

Context: Cervical cancer is almost always associated with high-risk human papillomavirus (HR-HPV). It is the third most common cancer in Latin American women and still one of the deadliest. Recent studies have shown that HR-HPV included in current vaccines (vaccHR-HPV) is not necessarily predominant in Latin America, raising concern about the efficacy of the HPV vaccine program. The aim of this study was to determine the prevalence of type-specific HR-HPV in high-grade squamous intraepithelial lesion (HSIL) and infiltrating carcinoma in Colombian women screened for cervical cancer.

Design: A total of 6949 cervical swabs obtained from women aged 15 to 74 years old were included in this study from 2017 to 2021. Forty-seven percent had simultaneous BD SurePath liquid-based cytology (LBC). HPV detection and genotyping were performed by using HPV Direct-Flow CHIP (Master Diagnóstica, Granada, Spain).

Results: The overall HR-HPV prevalence was 18%. Non–vaccHR-HPV prevalence in atypical squamous cells cannot exclude HSIL (ASCH) + low-grade squamous intraepithelial lesion, and HSIL LBC was 40% and 60%, respectively. Non–vaccHR-HPV prevalence in biopsies with HSIL/invasive squamous cell carcinoma/adenocarcinoma was 27% (Figure 2.28, vaccHR-HPV in checkered pattern).

Conclusions: Non–vaccHR-HPV has a significant prevalence in histology-demonstrated HSIL or higher lesions. It is still not clear whether high-grade cervical preinvasive lesions caused by non–vaccHR-HPV bear the same invasion risk of vaccHR-HPV lesions. Therefore, more studies addressing this hypothesis are needed. Our findings also add up to the evidence that HR-HPV genotype distribution in Latin America is different from the distribution pattern seen in other parts of the world, thus affecting the potential vaccine impact in this population.

Multiple Somatic Malignancies Arising in a Mature Cystic Teratoma

(Poster No. 29)

Kevin Mijares, MD ([email protected]); Roopa Kumari, MBBS; Carla Calagua Bedoya, MD; Ippolito Modica, MD. Department of Pathology, Mount Sinai Morningside/West, New York, New York.

Mature cystic teratoma (MCT) comprises 20% of all ovarian neoplasms. Somatic malignancies occur in approximately 2% of cases, the most common of which is squamous carcinoma (SCC). A few MCTs with synchronous carcinomas and sarcomas have been reported; however, only 2 cases of SCC with chondrosarcoma are found in the literature. We report a case of a 30-year-old nulligravid patient with an 11.5-cm right ovarian cyst incidentally found during her annual gynecologic examination. Imaging showed a multiseptated mass with cystic, solid, and fat-containing components consistent with an MCT. She underwent right salpingo-oophorectomy. Grossly, the mass consisted of solid nodules and cysts containing hair and sebum. Histology showed cysts lined by dysplastic squamous epithelium, which were continuous with nodules of poorly differentiated SCC with undifferentiated carcinoma and chondrosarcomatous components (Figure 2.29, A through D). Immunostains CK5/6, p40, and p63 were positive in the SCC and negative in the undifferentiated component. Follow-up conservative staging surgery showed neither nodal metastasis nor peritoneal involvement. Preoperative diagnosis of malignant transformation in an MCT is challenging. Risk factors include older age, larger size, and rapid tumor enlargement. Tumorigenesis of multiple malignancies in this MCT is particularly interesting. The morphology suggests a stepwise progression from dysplasia to invasive SCC that transformed into an undifferentiated carcinoma and chondrosarcoma. Other possibilities include collision of synchronous malignancies or the presence of a totipotential progenitor cell differentiating into the various elements. Prognosis depends on tumor stage; however, data are mainly drawn from SCC. The prognostic impact of multiple malignancies in an MCT needs further investigation.

Strong Overexpression of HSP60 and C-MYC Proteins in High-Grade Serous Carcinoma of Tubo-ovarian Primary and Association With Advanced FIGO Stage

(Poster No. 30)

Obianuju M. Anelo, MD1 ([email protected]); Qandeel Sadiq, MD1; Jorge Solares, MSc3; Rongshun Zhu, PhD2; Elizabeth Tolley, PhD2; Joel F. Gradowski, MD4; Farhan Khan, MD.4 Departments of 1Pathology and 2Preventive Medicine, The University of Tennessee Health Science Center, Memphis; 3Department of Pathology and Laboratory Medicine, Methodist Lebonheur Healthcare, Memphis, Tennessee; 4Department of Pathology and Laboratory Medicine and Pathology Specialists of Memphis, Methodist Lebonheur Healthcare, Memphis, Tennessee.

Context: The objective of our study is to evaluate HSP60 and c-MYC expression in high-grade serous carcinoma (HGSC) of Müllerian primary and correlation with clinicopathologic factors.

Design: Immunohistochemistry for HSP60 (H1, Santa Cruz) and c-MYC (Y69, Roche) was performed on whole slides of 44 cases of HGSC of endometrium and tubo-ovarian primaries. Sections were evaluated for intensity of nuclear (c-MYC) and cytoplasmic (HSP60) staining (1–3) and percentage of reactive tumor cells. An overall H-score was calculated from product of these measurements. Statistical significance was assumed if P < .05). The HSP60 and c-MYC H-score was compared with primary site (endometrium versus tubo-ovarian) and pathologic FIGO stage using Wilcoxon-Mann-Whitney or Kruskal-Wallis tests.

Results: Cases were grouped with 38.6% (n = 17) as early stage (I and II) and 61.4% (n = 27) as advanced stage (III and IV) based on the FIGO staging. H-scores for HSP60 and c-MYC and combined H-scores for c-MYC and HSP60 showed statistical significance (P < .01, < .01 and .05, respectively) in ovarian versus endometrial primary. Combined H score of HSP60 and c-MYC was associated (P=.02) with advanced FIGO stage.

Conclusions: Selective overexpression of HSP60 and c-MYC in HGSC of tubo-ovarian versus endometrium primary suggests that targeting cell cycle regulators such as axin 1 tumor suppressor gene and stress-activated NF-kB pathway might be of therapeutic benefit, especially in cisplatin-resistant high-grade serous cancers. Combined overexpression of HSP-60 and c-MYC was associated with advanced FIGO stage (stage III and IV).

Incidental Alveolar Soft Part Sarcoma of the Uterine Corpus: A Case Presentation and Discussion of Histologic Mimickers

(Poster No. 31)

Alex Perez, MD1 ([email protected]); Lia Bos, MD2; Barry Grimm, MD2; Mirna Podoll, MD.1 Departments of 1Pathology, Microbiology, and Immunology and 2Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee.

We present a case of alveolar soft part sarcoma (ASPS) in a 43-year-old woman undergoing a hysterectomy for fibroids. The 7.5-mm incidental lesion was discovered on a routine (H&E) section in a background of leiomyoma. The endometrium, the remainder of adjacent myometrium, and the resection margins were uninvolved. The tumor shows an infiltrative growth pattern with well-defined nests separated by vascular septa (Figure 2.31, A and B). The cells demonstrate abundant granular eosinophilic cytoplasm, round to oval nuclei, and prominent nucleoli. Immunohistochemistry is strong and diffuse for cathepsin K and TFE3 (Figure 2.31, C). Desmin, h-caldesmon, MyoD1, HMB-45 (Figure 2.31, D), Melan-A, SOX10, synaptophysin, S100, AE1/AE3, and CK8/18 were negative, ruling out a variant leiomyoma, perivascular epithelioid cell tumor, paraganglioma, granular cell tumor, and carcinoma. Fluorescence in situ hybridization showed the presence of an unbalanced rearrangement of TFE3 at the Xp11.2 locus, confirming the diagnosis. While long-term follow-up from <10 reported cases in a multicenter study demonstrates indolent behavior of gynecologic ASPS, rare metastases have been reported. Observation, imaging, and use of MET-selective and VEGF signaling inhibitors have been used for treatment of ASPS. Presence of TFE3 expression alone is insufficient for a diagnosis of ASPS, as morphologic mimickers including clear cell carcinoma, TFE translocation–associated perivascular epithelioid cell tumor, and granular cell tumor also express the marker. Recognizing the histologic findings in an often-small lesion of the gynecologic tract and utilizing a thorough immunohistochemical panel with supporting cytogenetic studies are vital in the diagnosis and subsequent management of this uncommon entity.

Dedifferentiated Endometrial Carcinoma: Morphologic and Immunohistochemical Challenges

(Poster No. 32)

Yekaterina Belogrivtseva, MD ([email protected]); Suad H. Taraif, MD, MBA, FIAC; Israh Akhtar, MD. Department of Pathology and Laboratory Medicine, Temple University Hospital, Philadelphia, Pennsylvania.

Undifferentiated/dedifferentiated endometrial carcinoma is an evolving entity. The frequently challenging distinction from FIGO 3 endometrioid carcinoma brings into question the reliability of current morphologic, immunohistochemical, and molecular criteria. Because of variable therapeutic approaches and prognostic implications, correctly diagnosing this entity remains crucial. Here we present 2 cases. One is a 75-year-old woman with low-grade endometrioid carcinoma and myometrially invasive undifferentiated carcinoma arranged in diffuse cohesive sheets of cells with monomorphic medium-sized nuclei. The other is a 54-year-old woman with low-grade endometrioid carcinoma with squamous differentiation and myometrially invasive undifferentiated carcinoma made of solid sheets of cohesive cells with abrupt keratinization. The transition between the well-differentiated and undifferentiated components was histologically evident, as was a seamless merging of glandular and solid patterns. The undifferentiated components of both cases lost PAX8 and ER with only a focal EMA expression and a wild-type p53. E-cadherin is retained. p40 and p63 highlight only areas of squamous differentiation and abrupt keratinization. Synaptophysin and chromogranin are only focally positive (<10%). BRG1 and INI1 are retained in both cases. MLH1 and PMS2 are lost in 1 case with MLH1 promoter hypermethylation. Our cases only partially fulfill the morphologic and immunohistochemical diagnostic criteria of dedifferentiated carcinoma. Therefore, it is currently unclear what would be the proper assignment of such cases. Dedifferentiated carcinoma should not be underdiagnosed as conventional endometrioid carcinoma because of its fulminant clinical course. Further refinement of this entity is warranted to enable precise diagnosis, prognosis, and use of appropriate therapeutic options.

Somatic Adenocarcinoma of Colorectal Phenotype Arising From Mature Cystic Teratoma of Ovary: A Clinicopathologic Conundrum

(Poster No. 33)

Fnu Raja, MD ([email protected]); Gopal Kumar, MD; Azzam Hammad, MD; Santhi Ganesan, MD. Department of Pathology, MetroHealth Medical Center, Cleveland, Ohio.

Mature cystic teratoma (MCT) is the most common benign ovarian germ cell neoplasm in women of reproductive age. Rarely, somatic malignancies arise from MCTs, the most common being squamous cell carcinoma. Adenocarcinomas are less common and colorectal adenocarcinomas are extremely rare. We present a rare case of somatic adenocarcinoma of colorectal type that may pose challenges in diagnosis and treatment. A middle-aged woman presented to the emergency department with lower abdominal pain. CT scan revealed an 11-cm sharply demarcated left pelvic mass. Laparoscopy found a left ovarian mass with torsion, with smooth external surface and thick brownish contents. Intraoperative evaluation revealed an adenocarcinoma. Permanent histopathology revealed adenocarcinoma of colorectal phenotype with necrosis (Figure 2.33, A). Additional evaluation of the cyst showed benign colonic epithelial lining (Figure 2.33, B). Immunohistochemistry (IHC) profile of positive CDX2 and CK20 (Figure 2.33, C and D) and negative PAX8, CK7, ER and PR suggested colorectal-type somatic adenocarcinoma arising from MCT, and it was staged as 1A after negative endoscopic findings. Because of its rarity and atypical symptoms, distinguishing metastatic tumors from MCT somatic malignancy is a challenging process. Radiology and serum tumor markers can be helpful but are not definite. Thorough clinical evaluation and proper staging are necessary after pathology evaluation. Extensive sampling and IHC can further characterize the origin of the tumor. Diligent sampling and high index of suspicion in this case confirmed the correct diagnosis and clinical management. The patient is being treated as having stage 1A ovarian cancer as opposed to stage IV metastatic colorectal cancer.

Retroperitoneal Metastatic HPV-Associated Carcinoma Without an Identified Primary Site

(Poster No. 34)

Hula Taha, MD ([email protected]); Meaad Shitawi, MD; Anindita Ghosh, MD; Jamie Buryanek, MD; Songlin Zhang, MD. Department of Pathology, University of Texas, Health Science Center, Houston.

Carcinoma of unknown primary (CUP) is a metastatic carcinoma with no identifiable primary tumor. CUP represents 3%–5% of all cancers worldwide. Immunohistochemistry and molecular profiling are important to categorize tumors and search for actionable targets. Retroperitoneal human papillomavirus (HPV)–associated CUP has rarely been reported in the literature. Here we present a 48-year-old woman with worsening dizziness and vomiting. Imaging showed a left cerebellar mass. A resection was performed, and tissue sections showed a metastatic carcinoma. A female genital tract primary was suspected as the tumor expressed positive PAX8. A subsequent PET scan revealed only retroperitoneal mass adjacent to the right common iliac artery. She underwent hysterectomy, bilateral salpingo-oophorectomy, and retroperitoneal mass resection. Meticulous gross and microscopic examinations revealed no carcinoma in any part of the female genital tract. The retroperitoneal mass had nearly identical histology and immunohistochemical profile to the brain metastatic carcinoma. Both tumors expressed diffusely positive p16, AE1/AE3, and HMWK and patchy positive p63, PAX8, and GATA-3. Mucicarmine stain showed focal intracytoplasmic mucin. HPV in situ hybridization was positive in both metastatic carcinomas. A final diagnosis of HPV-associated adenosquamous carcinoma of unknown primary was rendered. The patient underwent chemotherapy and has been disease free for 7 months. When an HPV-associated carcinoma of the female genital tract presents with distant metastasis, a large primary tumor is commonly found in the cervix, vagina, or vulva. In our case, 2 metastases were detected without an identifiable primary tumor. Identification of HPV RNA in CUP can be useful for diagnostic, prognostic, and possibly therapeutic purposes.

An Unusual Case of Neuroblastoma Arising in a Mature Cystic Teratoma of the Ovary

(Poster No. 35)

Carlos M. Casiano, MD1 ([email protected]); Moe Takeda, DO2; Christopher LePhong, DO2; Amit Sura, MD3; Larry Wang, MD2; Shengmei Zhou, MD2; Ryan Schmidt, MD2; Nick M. Shillingford, MD.2 1Department of Pathology and Laboratory Medicine, University of California San Diego; Departments of 2Pathology and Laboratory Medicine and 3Radiology, Children's Hospital, Los Angeles, California.

Neuroblastoma is the most common extracranial solid tumor in childhood and arises in cells of neural crest origin. Primary ovarian neuroblastomas are exceedingly rare. We present a case of a neuroblastoma arising in a mature ovarian teratoma in a 10-year-old girl who presented with abdominal pain and weight loss. Laboratory studies showed elevated homovanillic acid and vanillylmandelic acid. Imaging detected a heterogeneous pelvic mass and enlarged periportal lymph nodes (Figure 2.35, A). Laparotomy revealed a mass involving the right ovary. Histologic examination showed a mature teratoma and a population of small round blue cells arranged in sheets and nests with Homer-Wright rosettes, clusters of ganglion cells, and neuropil (Figure 2.35, B and C). Immunohistochemistry showed diffuse positivity for PHOX2B (Figure 2.35, D), and tyrosine hydroxylase. A diagnosis of neuroblastoma, schwannian stroma poor, poorly differentiated with low mitosis-karyorrhexis index arising in a mature teratoma was rendered. Two lymph nodes were positive for metastatic neuroblastoma. Chromosomal microarray analysis of the tumor revealed near triploidy. A BRAF activating mutation (p.Gly469Ala) was detected by next-generation sequencing but N-myc was not amplified. The patient was lost to follow-up without receiving additional therapy. Primary ovarian neuroblastoma is reported to portend a poor prognosis. Patient age in this case would give an unfavorable prognosis, though it would be favorable for a similar disease in a younger patient. Literature review suggests that further investigation is needed to better elucidate the relationship between patient age and prognosis. The case highlights the importance of maintaining neuroblastoma in the diagnostic differential diagnosis when examining pediatric mature teratomas.

Uterine Lymphangioleiomyomatosis (LAM) in Tuberous Sclerosis

(Poster No. 36)

Payu A. Raval, MD1 ([email protected]); Kritika Prasai, MD1; Marika L. Forsythe, MD1; Omar A. Abdelsadek, MD1; Elena Moore, MD2; Kruti P. Maniar, MD1; John V. Groth, MD.1 Departments of 1Pathology & Laboratory Medicine and 2Obstetrics and Gynecology, University of Chicago, NorthShore University Hospital, Evanston, Illinois.

Tuberous sclerosis is associated with multiple benign tumors. Lymphangioleiomyomatosis (LAM) is a multisystem disorder that primarily affects the lung and rarely affects the female genital tract. The relationship between pulmonary and extrapulmonary origin is not clear. Still, several studies suggest LAM may originate from the uterus and spread to other sites through the lymphatic system in females. Here we present a case of uterine LAM in a 45-year-old woman with tuberous sclerosis and renal angiomyolipomas. She presented with the complaint of heavy menstrual periods. Curetting showed a small focus of complex hyperplasia with a small focus of atypia in a large polyp, and her final pathology report of hysterectomy showed atypical endometrial hyperplasia with foci bordering on FIGO grade 1 endometrioid adenocarcinoma with extensive background adenomyosis (Figure 2.36, A). Additionally, multiple microscopic foci of pale-staining spindle cells and focal adipocytic cells were focally associated with lymphovascular spaces (Figure 2.36, B). Those foci were positive for smooth muscle actin, desmin, HMB-45 (Figure 2.36, C), and Mart-1 (multiplex Mart-1/SOX10), and were focally wrapped by D2-40–(Figure 2.36, D) and CD31 (focal weak)–positive cells. No gross myometrial lesions were identified, and with the tuberous sclerosis background, findings were consistent with LAM and angiomyolipomatous proliferation. The patient has multiple ≤1-cm bilateral noncalcified lung nodules, which are stable (compared with previous scans), but radiologically there is no evidence of LAM in the lungs. This case uniquely adds to the literature regarding the spectrum of changes seen with LAM in the uterus.

A Case Report of Unusual Multifocal PEComa (PEComatosis) of the Uterus

(Poster No. 37)

Mohamed Eltahir, MBBS, PhD ([email protected]); Abubaker Elshaikh, MD. Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas.

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor that can involve multiple sites, including the female genital tract. The clinical picture of uterine PEComa can mimic leiomyoma presentation. Herein, we present a multifocal PEComa (PEComatosis) case in a 44-year-old woman who initially presented with pelvic pain, abnormal uterine bleeding, elevated CA125, and uterine fibroids. Pelvic imaging showed multiple uterine cystic lesions with solid-appearing masses concerning for uterine malignancy. The patient underwent a total hysterectomy and bilateral salpingo-oophorectomy. Microscopically, the endomyometrium displayed multiple nodules of epithelioid cells and a few spindle-shaped cells with abundant clear to eosinophilic cytoplasm, round to oval nuclei, vesicular chromatin, and small nucleoli (Figure 2.37, A). Aggregates of epithelioid cells were also noted throughout the myometrium, predominantly in a perivascular distribution (Figure 2.37, B). The tumor cells were diffusely positive for desmin, SMA, and caldesmon; patchy positive for HMB-45 and Melan-A; and negative for pancytokeratin, CD10, calretinin, and inhibin, consistent with a multifocal proliferation of perivascular epithelioid cells. Additionally, the endomyometrium displayed extensive complex atypical endometrial hyperplasia involving adenomyosis (Figure 2.37, C) and myometrial leiomyomata, as well as endometriosis of the serosa. The right fallopian tube showed a focus of serous tubal intraepithelial carcinoma (STIC) with p53 overexpression and Ki-67 >10% (Figure 2.37, D). PEComas are rare and multifocal PEComa is an even rarer entity. We report a case of complex pathologic entities, including PEComatosis, complex atypical endometrial hyperplasia, adenomyosis, leiomyomata, endometriosis, and STIC, which is, to our knowledge, the first report of this constellation of pathologies.

Response to Neoadjuvant Chemotherapy in High-Stage POLE-Mutated Endometrioid Carcinoma

(Poster No. 38)

Lixia Bai, MD, PhD1 ([email protected]); Kayla Lemmon, BS3; Mark Burkard, MD, PhD2; Stephanie M. McGregor, MD, PhD.1 Departments of 1Pathology and Laboratory Medicine and 2Medicine, University of Wisconsin–Madison Hospital and Clinics, Madison; 3Department of Precision Medicine Molecular Tumor Board, University of Wisconsin–Madison Carbone Cancer Center, Madison.

Polymerase epsilon (POLE) exonuclease domain mutations are associated with favorable prognosis in endometrioid carcinoma (EC) even when histologic grade is high. It has been proposed that patients with POLE-mutated tumors could forgo chemotherapy; however, recurrence and cancer-associated death do occur in some patients, and prospective trials to address this question are in process. Here we report response to neoadjuvant chemotherapy (NACT) in 2 patients with POLE mutation. We searched our institution's Molecular Tumor Board Database for EC with POLE mutations. Cases were reviewed for diagnostic agreement and chart review was performed. Two cases of EC with POLE V411L mutation status post NACT were identified (microsatellite stable, wild-type p53). Case 1 is a 66-year-old woman with stage IVB FIGO grade 3 EC of the endometrium metastatic to the lung (Figure 2.38, A). Posttreatment imaging showed resolution of the nodules and surgery was pursued, with residual disease confined to the uterus but with extensive lymphovascular invasion (Figure 2.38, B). She declined further chemotherapy and showed no evidence of disease (NED) at 38 months. Case 2 is a 57-year-old woman with peritoneal carcinomatosis. Post-NACT imaging showed resolution of peritoneal disease and the resected ovary revealed a single 1-mm focus of residual disease (Figure 2.38, C and D). Following adjuvant chemotherapy, she is NED at 37 months. Patients with advanced-stage POLE-mutated EC may show robust response to NACT. While some tumors may not require chemotherapy, further study is necessary to stratify POLE-mutated ECs and explore the role of chemotherapy in high-risk patients.

Diagnosing a Case of Mesonephric-like Adenocarcinoma on a Metastatic Focus

(Poster No. 39)

Kritika Prasai, MD1 ([email protected]); Payu A. Raval, MD1; Omar A. Abdelsadek, MD1; Marika L. Forsythe, MD1; Elena Moore, MD2; Thanh Lan, MD1; Lin Liu, MD1; John V. Groth, MD.1 Departments of 1Pathology and Laboratory Medicine and 2Obstretics and Gynecology, Northshore University Healthcare System, Evanston, Illinois.

Mesonephric-like adenocarcinoma (MLA) is a rare neoplasm and an underrecognized entity of the female gynecologic tract. It exhibits a diverse/mixed growth pattern between and within the same tumor mass. We present a case of metastatic MLA to the lung arising in the context of low-grade serous carcinoma of the ovary/peritoneum. The patient is a 58-year-old woman who underwent hysterectomy and bilateral salpingo-oophorectomy for an ovarian mass with CA 125 >800, outside of the United States. She presented 3 years later at our institution with peritoneal deposits consistent with low-grade serous carcinoma, positive for PAX8, ER, WT-1, and wild-type p53 and negative for CDX2, GATA-3, and TTF-1 (Figure 2.39, A). Her disease was stable on chemotherapy for 2 years until a PET scan showed an avid new pulmonary nodule. Pulmonary resection revealed a tumor with a pseudoendometrioid appearance, distinct from the known low-grade serous carcinoma, positive for TTF-1, PAX8, GATA3, and CK7 and negative for ER, PR, WT-1, napsin A, and CK20, consistent with MLA (Figure 2.39, B). Additional next-generation sequencing of both tumors (peritoneal and lung) revealed identical KRAS mutation in exon 2 pG12R. The molecular and histopathologic findings were in keeping with MLA arising in association with her prior low-grade serous carcinoma. This case highlights the importance of recognizing the combined nature of some cases of MLA with low-grade serous carcinoma of the female gynecologic tract, particularly at metastatic sites, and adds to the literature of the mutational changes possible in this context.

Perianal Vulvar Acanthosis With Altered Differentiation

(Poster No. 40)

Amy L. Austin, MD1 ([email protected]); Michael C. Royer, MD2; Jill I. Allbritton, MD.2 1Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland; 2Division of Dermatopathology, Joint Pathology Center, Silver Spring, Maryland.

Vulvar intraepithelial neoplasia demonstrates subtle histologic findings in human papillomavirus (HPV)–independent lesions. One HPV-independent lesion, differentiated vulvar intraepithelial neoplasia, is driven by TP53 gene mutations. More recently, other HPV-independent precursor lesions, vulvar acanthosis with altered differentiation (VAAD) and differentiated exophytic vulvar intraepithelial lesion, have been described. Both present a diagnostic challenge. We present a case of VAAD that presented on the vulva and perianus. A 66-year-old woman with past medical history of HPV-positive squamous cell carcinoma of the anus, treated with chemoradiation therapy, presented with new white and partially ulcerated plaques on her left vulva and perianus. On histology, both the vulvar and the perianal (Figure 2.40, A and B) lesions demonstrated diffuse hyperkeratosis, acanthosis, slight enlargement of the squamous cells with mild atypia, and overlying parakeratosis with loss of the granular layer. Immunohistochemical staining for p16 on both sites was non–block positive (Figure 2.40, C), and p53 demonstrated wild-type staining pattern (Figure 2.40, D). These features, despite the atypical perianal location, were consistent with the diagnosis of HPV- and TP53-independent VAAD. To our knowledge, no other cases of perianal VAAD have been reported. This case represents a unique presentation of a rare disease, highlighting the importance of utilizing subtle histologic clues and immunohistochemistry in the diagnosis of vulvar and perianal squamous lesions.

Mesonephric Adenocarcinoma: A Diagnostic Chameleon in the Gynecologic Tract With High Propensity for Inaccurate Diagnosis and Inaccurate Staging

(Poster No. 41)

Fnu Sapna, MD ([email protected]); Perry Cohen, MD; Esperanza Villanueva-Siles, MD; Javier Laurini, MD; Sonali Lanjewar, MD. Department of Pathology, Montefiore Medical Center, The University Hospital of Albert Einstein College of Medicine, Bronx, New York.

Mesonephric adenocarcinomas (MA) are uncommon neoplasms of the gynecologic tract showing multiple growth patterns, including tubular, ductal, solid, papillary, sex cord–like, and retiform areas. MAs most commonly originate from cervical mesonephric remnants, whereas mesonephric-like adenocarcinomas are postulated to have a Müllerian origin and are thought to arise by mesonephric trans-differentiation. We present 2 cases of MA and discuss the diagnostic challenges and staging dilemmas imposed by these lesions. The first case showed MA involving the cervix and left ovary and showing tubular, solid, and ductal patterns of growth. In addition, the tumor in the ovary showed a prominent papillary architecture simulating a more common ovarian high-grade serous carcinoma. However, both tumors showed characteristic immunohistochemical (IHC) results, including positivity for GATA3, TTF1, CD10 and negativity for ER, WT1, P16, and P53. A cervical primary with metastasis to the ovary was favored based on the gross and microscopic findings. The second case was centered in the myometrium, adjacent to mesonephric remnants, with characteristic histologic and IHC features. MAs arising in the myometrium are exceedingly rare, with only 7 cases reported to date. Furthermore, the presence of myometrial mesonephric rests is vanishingly rare. When these lesions arise in the myometrium, assessment of depth of myometrial invasion can be challenging. These cases highlight the morphologic spectrum and staging difficulties of MA, features that should prevent misdiagnosis and inaccurate staging of these aggressive neoplasms.

Lymphovascular Space Invasion by Chorionic Villi in Ectopic Pregnancy

(Poster No. 42)

Swetha Gaddam, MD ([email protected]); Ghassan Allo, MD. Department of Pathology, Henry Ford Hospital, Detroit, Michigan.

In patients with ectopic pregnancy, the presence of chorionic villi in paratubal blood vessels has not been reported in the literature so far. We present a case of 27-year-old woman, gravida 4 para 3, with all spontaneous vaginal deliveries and with no complications during prior pregnancies. She reported no history of prior ectopic pregnancies or infertility. She had chlamydia in the past that was treated. Now she presented to our hospital with severe upper quadrant abdominal pain with stable vital signs. β-hCG levels were high at 13 794 mIU/mL. Pelvic ultrasound showed large free fluid in cul-de-sac, with left adnexal thick wall cystic structure. She had emergent removal of the ectopic pregnancy with left salpingectomy. Intraoperatively, there was a ruptured left ectopic pregnancy with 400–500 mL hemoperitoneum. Histologic examination of the left fallopian tube showed chorionic villi consistent with tubal ectopic pregnancy (Figure 2.42). In addition, on histology there were foci of chorionic villi with some extravillous trophoblast both in the lumen and wall of thin- and thick-walled paratubal blood vessels with associated focal thrombus formation. However, there was no evidence of any malignant features like nuclear pleomorphism, mitoses, hemorrhage, or necrosis. In addition, there was no evidence of molar pregnancy. Upon follow-up for 6 months, the patient demonstrated stable clinical status, with a normalized β-hCG level (<5 mIU/mL). To our knowledge, this is the first reported case of intravascular invasion of chorionic villi in ectopic pregnancy. Based on this case, this phenomenon has been associated with an indolent course.

Comprehensive Evaluation of Melanocytic Biomarkers in Uterine Mesenchymal Tumors Using HMB-45, Melan-A, MiTF, TFE3, Cathepsin K, SOX10, and S100

(Poster No. 43)

Meaad Shitawi, MD ([email protected]); Hula Taha, MD; Michael Covinsky, MD; Xiaohong Wang, MD; Songlin Zhang, MD. Department of Pathology, The University of Texas Health Science Center, Houston.

Context: Dual expression of melanocytic and smooth muscle markers has been found in uterine mesenchymal tumors such as leiomyosarcoma and PEComa, and differentiating them is clinically relevant for targeted therapy in PEComa.

Design: We studied HMB-45, Melan-A, MiTF, TFE3, cathepsin K, SOX10, and S100 expressions in 20 leiomyosarcomas, 5 endometrial stromal sarcomas (ESSs), 2 malignant PEComas, and 32 benign leiomyomas using tissue microarray. Immunohistochemistry was scored for both intensity and percentage, but only 2+ and 3+ staining was considered as positive.

Results: SOX10 and S100 were negative on all tumors. One malignant PEComa was positive for HMB-45, Melan-A, MiTF, TFE3, and cathepsin K, but the second case was positive only for cathepsin K. The frequency of HMB-45, Melan-A, MiTF, TFE3, and cathepsin K expression was found in 2 of 20, 0 of 20, 4 of 20, 7 of 20, and 7 of 20 leiomyosarcomas; in 0 of 5, 0 of 5, 0 of 5, 2 of 5, and 2 of 5 ESSs; in 2 of 32, 0 of 32, 2 of 32, 0 of 32, and 3 of 32 benign leiomyomas. Rare leiomyosarcomas were positive for 3–4 melanocytic markers including HMB-45, MiTF, TFE3, and cathepsin K.

Conclusions: Some leiomyosarcomas can express multiple melanocytic markers; also, ESSs and benign leiomyomas can express some melanocytic markers. However, Melan-A expression is very rare in leiomyosarcoma, ESS, and benign leiomyoma (0 of 57). PEComa diagnosis requires expression of 2 melanocytic markers (frequently HMB-45 and Melan-A), but malignant PEComa can be positive for only cathepsin K. Molecular tests may be needed for confirmation in these cases.

A Rare Case of Cervical HPV-18–Associated Poorly Differentiated Clear Cell Carcinoma

(Poster No. 44)

Vandana Panwar, MD ([email protected]); Kyle Molberg, MD; Elena Lucas, MD. Department of Pathology, University of Texas Southwestern Medical Center, Dallas.

Cytoplasmic clearing in human papillomavirus (HPV)–associated cervical carcinoma is occasionally encountered in squamous, adeno-, and adenosquamous carcinomas. We report a case of poorly differentiated carcinoma with clear cytoplasm and unusual immunophenotype, and without evidence of a specific line of differentiation. A 31-year-old woman presented with intermittent bilateral lower abdominal pain. Colposcopy showed a friable cervical mass. On gross examination of the radical hysterectomy specimen, the cervix showed a 3-cm well-circumscribed exophytic anterior cervical mass (Figure 2.44, A). Histologic examination revealed a polypoid tumor composed of diffuse sheets of cells with abundant clear cytoplasm, prominent cell borders, high-grade pleomorphic nuclei, frequent multinucleation, and high mitotic activity (Figure 2.44, B). No morphologic evidence of squamous, glandular, or neuroendocrine differentiation was identified. By immunostains, the tumor cells were diffusely positive for cytokeratin AE1/AE3, CK7, CK20, vimentin (Figure 2.44, C), and p16, and negative for p40, CK5/6, ER, PR, napsin A, PAX8, CDX2, PAX2, and PTEN. CEA was predominantly negative, and mucicarmine was negative. Diffuse PAS positivity highlighted cytoplasmic glycogen. High-risk HPV in situ hybridization demonstrated diffuse positivity (Figure 2.44, D). High-risk HPV testing performed on the concurrent Papanicolaou specimen demonstrated positivity for HPV-18. Cervical clear cell carcinomas caused by HPV-18 are rare (only a few cases reported in the literature) and may be associated with aggressive behavior. This case highlights an uncommon histologic variant of poorly differentiated HPV-18–associated carcinoma without any specific line of differentiation and an unusual diffuse, strong expression of vimentin and CK20. Awareness of this variant is important to avoid misdiagnosis of this potentially aggressive tumor type.

The Value of Biomarkers PHH3, Ki-67, p16, and p53 for Differentiating Benign and Malignant Uterine Mesenchymal Tumors

(Poster No. 45)

Hula Taha, MD ([email protected]); Meaad Shitawi, MD; Wang Xiaohong, MD; Michael Covinsky, MD; Songlin Zhang, MD. Department of Pathology, University of Texas, Health Science Center, Houston.

Context: Differentiating between benign and malignant uterine mesenchymal tumors can be challenging.

Design: We studied the value of PHH3, Ki-67, p16, and p53 immunohistochemical stains for differentiating benign versus malignant uterine mesenchymal tumors using tissue microarrays (TMAs). Twenty-seven cases of malignant mesenchymal tumors, including 20 leiomyosarcomas, 5 endometrial stromal sarcomas, and 2 malignant PEComas, and 32 benign leiomyomas were used for TMA. p16 and p53 were scored for both intensity and percentage, Ki-67 was scored for percentage, and PHH3 was counted for positive cells per square millimeter.

Results: Malignant tumors (27) had PHH3 0–140/mm2 (mean, 38.22) and Ki-67 3%–95% (mean, 24.48%), versus benign leiomyoma (32) PHH3 0–18/mm2 (mean, 2.5) and Ki-67 0%–15% (mean, 2.81%) (P < .001). p16 and p53 were patchy or diffusely positive (2+ or 3+) in 17 of 27 and 13 of 27 malignant tumors versus 0 of 32 and 0 of 32 in leiomyomas (P = .001). The sensitivity, specificity, PPV, and NPV for diagnosis of malignant mesenchymal tumors were 62.96%, 100%, 100%, and 76.19% using p16; 48.15%, 100%, 100%, and 69.57% using p53; and 74.07%, 100%, 100%, and 82.14% using combined p16/p53.

Conclusions: PHH3 and Ki-67 are significantly higher in malignant mesenchymal tumors than in benign leiomyomas, but there is significant overlap between the malignant and benign lesions. Patchy or diffuse strong (2+ or 3+) p16 and p53 staining appear more specific for malignant mesenchymal tumors, with a 100% PPV in our study; however, the sensitivity is relatively low for p53 (48.15%), p16 (62.96%), or combined p16/p53 (74.07%).

Ovarian Carcinosarcoma: An Institutional Experience

(Poster No. 46)

Mira Kheil, MD1; Evi Abada, MD1; Deepti Jain, MD1; Tala Tawil, MD1; Omar Fehmi2; Haidy Elazzamy, MD3; Lamia Fathallah, MD3; Sudeshna Bandyopadhyay, MD1 ([email protected]). 1Department of Pathology, Wayne State University, Detroit, Michigan; 2Department of Literature, Science, and the Arts, University of Michigan, Ann Arbor; 3Department of Pathology, St John Hospital & Medical Center, Detroit, Michigan.

Context: Ovarian carcinosarcoma (OCS) is a rare, aggressive neoplasm. We evaluated clinicopathologic parameters and expression of p53, HER2, estrogen receptor (ER), progesterone receptor (PR), and E-cadherin by immunohistochemistry (IHC) in OCS.

Design: Thirty-two OCS cases were identified from 1990 to 2021. Data on lymphovascular invasion (LVI), heterologous elements, stage, recurrence, and overall survival (OS) were reviewed. IHC for p53, HER2, E-cadherin, ER, and PR was evaluated on 23 available samples and interpreted according to standard protocol.

Results: Median age at diagnosis was 68 years (range, 27–85). Epithelial component was classified as 43.75% (14) serous, 12.5% (4) endometroid, and 43.75% (14) mixed. Mesenchymal component was heterologous in 56.25% (18) of cases: 50% (9) chondroid, 33% (6) rhabdoid, 5.5% (1) osteoid, 5.5% (1) myxoid, and 5.5% (1) liposarcomatous. LVI was seen in 31.25% (10) of cases; 96.8% (31) were advanced stage (III/IV). Aberrant p53 staining was seen in 91% (21) of cases. HER2 was positive (>3+) in 17% (4) of cases, equivocal in 21.74% (5), and negative in 60.8% (14). ER was positive in 57% (13) of cases, PR was positive in 9% (2) of cases, and E-cadherin was positive in 87% (20) of cases. LVI and advanced stage were associated with worse OS (P = .004 and P = .02, respectively). However, immunoreactivity for p53, HER2, ER, PR, and E-cadherin had no prognostic effect on OS (P > .05). The 5-year OS was 47.34% (95% CI, 29.57–75.80) (Figure 2.46).

Conclusions: LVI and advanced-stage disease are associated with worse OS in OCS. Studies with larger cohorts are needed to further provide insight on this rare, aggressive tumor.

Unexpected Rapid Progression of Low-Grade Endometrial Adenocarcinoma Despite Conservative Therapy

(Poster No. 47)

Pramila Moideen, MD ([email protected]); Thomas Cotter, DO; Nivin Omar, MBChB; Joseph White, DO. Department of Pathology, Augusta University, Augusta, Georgia.

Low-grade endometrioid endometrial carcinomas have an excellent prognosis. Here, we present a case of a low-grade endometrioid endometrial carcinoma that followed an unusually aggressive course. Our patient, a 49-year-old woman, was diagnosed with a low-grade FIGO 1 endometrioid carcinoma at another institution. The biopsy was reviewed, and the diagnosis was confirmed at our institution. Dilatation and curettage along with Mirena placement were performed 1 month after initial biopsy, with further confirmation of the diagnosis. Follow-up was uneventful. She had an open cholecystectomy 7 months after diagnosis, during which no abnormal uterine/adnexal enlargement was noted. However, 1 month later, she presented with sepsis and acute kidney injury. Imaging revealed uterine enlargement with thickened endometrial stripe and bilateral adnexal involvement, as well as several pathologic lymph nodes. In addition, peritoneal implants, ascites, and partial intestinal obstruction were identified. The leukocytosis and acute kidney injury were found to be the result of tumor lysis syndrome. Biopsy of mesenteric mass revealed poorly differentiated carcinoma. Her respiratory status progressively declined, and she died of metastatic complications within 9 months of her initial diagnosis. Autopsy confirmed widely metastatic disease. The overall survival rate of low-grade endometrioid adenocarcinoma is well above 80%. There are data showing that low-grade endometrioid carcinoma can be managed or even cured without hysterectomy. However, this case is a reminder that early definitive surgical management may be the best treatment for some patients. More research should be performed to help distinguish and identify these high-risk tumors (Figure 2.47, A through D).

Synchronous Endometrial Endometrioid Adenocarcinoma and Female Adnexal Tumor of Probable Wolffian Origin (FATWO)

(Poster No. 48)

Asma Abu-salah, MBBS ([email protected]); Sheila Segura, MD. Department of Pathology, Indiana University School of Medicine, Indianapolis.

A 54-year-old woman with a diagnosis of endometroid adenocarcinoma underwent a total hysterectomy, bilateral salpingo-oophorectomy and suboptimal debulking. Preoperatively, omental/peritoneal carcinomatosis and liver lesions were noted on abdominal CT. During surgery, nodules involving the bilateral fallopian tubes, ovaries, uterine serosa, omentum, peritoneum, and falciform ligament were identified. Histopathologic examination of these nodules demonstrated epithelioid cells arranged in nested, sievelike, and glandular-like patterns with focal necrosis (Figure 2.48, A and B). The tumor cells exhibited moderate eosinophilic cytoplasm, enlarged round to ovoid nuclei with open chromatin, rare nuclear grooves, and scattered small nucleoli (Figure 2.48, C). Up to 7 mitotic figures were seen per 10 HPF. Immunohistochemically, the tumor cells were at least focally positive for CK7, calretinin, CD10, EMA, inhibin, CAM5.2, Ber-Ep4, CK5/6, and GATA-3, and negative for PAX8, WT-1 ER, AR, TTF-1, and CD117. The overall findings were consistent with a female adnexal tumor of probable Wolffian origin (FATWO). The uterus contained a noninvasive FIGO grade 1 endometrioid adenocarcinoma arising in a background of atypical hyperplasia (Figure 2.48, D). FATWO is a rare neoplasm of low malignant potential that originates from mesonephric (Wolffian) duct remnants. It frequently arises in the broad ligament and mesosalpinx, and less commonly in the fallopian tubes, ovary, and retroperitoneum. Complete surgical resection is the standard treatment for FATWO. It is important to recognize the existence of this rare lesion and to differentiate it from endometrioid adenocarcinoma, especially in cases of synchronous tumors, to avoid unwarranted upstaging and aggressive treatment for an early-stage endometrioid adenocarcinoma.

Expression of EZH2 and Histone H3K27-Ac in Prostate

(Poster No. 49)

Andrii Puzyrenko, MD, PhD1 ([email protected]); Suresh Kumar, PhD1; Cooley G. Pantazis, MD2; Kenneth A. Iczkowski, MD.1 1Department of Pathology, Medical College of Wisconsin, Milwaukee; 2Department of Pathology, Munroe Regional Medical Center, Ocala, Florida.

Context: Enhancer of zeste 2 (EZH2), an upregulated gene and adverse prognosticator in prostate cancer, contains a domain that catalyzes histone H3 lysine 27 methylation and acetylation (H3K27-Ac), which is a key metastasis facilitator. Studies report that EZH2 can also act independently. For the first time, we determine whether EZH2 and H3K27-Ac expressions are correlated in prostatic tissue.

Design: Tissue microarrays were made and immunohistochemistry was performed for EZH2 and H3K27-Ac. Slides were scanned and image data utilized software-assisted, unbiased quantification method. The software captured high- and low-intensity diaminobenzidine-positive regions and tissue areas.

Results: Benign prostate tissue expressed only minimal EZH2 but showed strong H3K27-Ac positivity (Table). Tumor cells were EZH2 positive with weak staining involving up to 25% of malignant cells. H3K27-Ac was increased in tumors with moderate intensity involving up to 100% of tumor cells, with stagewise and gradewise progressive increases, with the strongest staining in lymph nodes. Notably, relationship of H3K27-Ac and EZH2 expression was coupled in stages and Gleason grades of prostate cancers. Additionally, staining intensity and proportion of the cells were also independently evaluated manually by pathologists and a histology score was calculated. These results correlated with automated analysis.

Conclusions: EZH2 and H3K27-Ac had an inverse correlation in benign versus especially low-grade and low-stage prostate cancers; however, in high-stage and high-grade cancers and metastases, H3K27-Ac increased significantly. Findings support EZH2 and H3K27-Ac as targets for cancer prevention and localized or low-grade prostate cancer, but their epigenetic influence in advanced prostate cancer may be at variance from this.

Varieties of Renal Diseases Identified in Renal Biopsies of Patients Infected by COVID-19

(Poster No. 50)

Jessica D. Anderson, MD ([email protected]); Wei Li, MD, PhD; Hassan D. Kanaan, MD; Ping L. Zhang, MD, PhD. Department of Pathology, Beaumont Health, Royal Oak, Michigan.

Context: COVID-19 has been shown to cause renal pathology by multiple proposed mechanisms. However, studies evaluating renal biopsies for the effects of COVID-19 remain limited. We report our experience in our health system in a variety of renal pathologic diagnoses caused by COVID-19 infection.

Design: We performed detailed analysis of 5 renal biopsies related to COVID-19 infection, of 812 renal biopsies over the previous 22 months (0.6% of all cases).

Results: The first 3 patients were 2 African American men, 34 and 45 years old, and 1 48-year-old white male transplant recipient who developed acute kidney injury and nephrotic range of proteinuria after COVID-19 infections. Renal biopsies showed collapsing glomerulopathies in the patients. Patient 4, a 71-year-old white woman, developed acute kidney injury (serum creatinine at 5.56 mg/dL) with hematuria and proteinuria following COVID-19 infection. Her renal biopsy revealed moderate acute tubular necrosis and mild IgA nephropathy. Patient 5, a 15-year-old African American adolescent girl infected with COVID-19, developed nephrotic range proteinuria, which became negative soon after the renal biopsy. The renal biopsy revealed segmental fusion of foot processes compatible with minimal-change disease in remission.

Conclusions: The results of our 5 patients with COVID-19 infection included 3 collapsing glomerulopathies, 1 IgA nephropathy/acute tubular necrosis, and 1 minimal-change disease in remission, supporting previous reported varieties of renal diseases due to COVID-19 infection.

Synchronous Primary Renal Mucinous Adenocarcinoma and Neuroendocrine Tumor

(Poster No. 51)

Jane Hua-fang Lin, MD1 ([email protected]); Sunder Sham, MD1; Leon Telis, MD2; Brent Yanke, MD2; Pamela Unger, MD.1 Departments of 1Pathology and 2Urology, Northwell Lenox Hill Hospital, New York, New York.

We present a case of synchronous primary renal cystic adenocarcinoma and carcinoid tumor in a 53-year-old woman. The patient had a past medical history of breast cancer and mature ovarian teratoma. Imaging showed a large cystic lesion with mural nodules, and laboratory studies revealed a slowly rising serum CEA. She underwent a nephrectomy. Gross examination revealed a 11.5-cm cyst adherent to and tunneling through the lower pole of the kidney. It showed no connection to the pelvico-calyceal system. The cyst lining was predominantly smooth with focal gritty areas of calcification and contained yellow to tan semitransparent grumous to mucoid material. Microscopic examination revealed a 11.5 cystic enteric-type mucinous adenocarcinoma with moderate differentiation confined to the cyst wall. Closely approximating the adenocarcinoma was a 1.5-cm well-differentiated neuroendocrine tumor that extended focally into perirenal fat and had an area suspicious for lymphovascular invasion. Primary renal adenocarcinoma is an extremely rare entity. Most cases of primary renal adenocarcinoma are documented to occur in the background of a teratoma, horseshoe kidney, or metaplasia of pelvic urothelium. This case is unique in that it is an apparently de novo case of primary renal adenocarcinoma where neither teratoma nor metaplasia of the urothelium is present in the specimen.

Spontaneous Intratesticular Hemorrhage: A Challenging Clinical Diagnostic Entity

(Poster No. 52)

Khairya Fatouh, MD ([email protected]); Hadeel Altameemi, MD; Basim Al-Khafaji, MBChC, MHPE. Department of Pathology, Ascension St John, Detroit, Michigan.

Spontaneous intratesticular hemorrhage (SIH), first described in 1941, is a rare benign clinical entity with very few reported cases. The final diagnosis is made after orchiectomy. Spontaneous idiopathic intratesticular hemorrhage has no identifiable risk factors, but intratesticular hemorrhage in the setting of trauma or malignancy is common. Furthermore, because of SIH similarity to testicular malignancy on ultrasonographic imaging, it poses a diagnostic challenge. We present a case of a 29-year-old man with a significant past medical history of hypertension. The patient presented to the emergency department with sharp left testicular and left lower quadrant pain. Ultrasonography showed a 2-cm complex mass in the left testicle that was suspicious for a testicular neoplasm. Abdominal CT failed to show any abnormality or acute process. His laboratory workup was normal. Tumor markers were also negative. Clinical follow-up of the testicular mass showed it to be enlarging in size; thus, exploration with biopsy of the lesion was performed. Frozen section analysis showed fresh hemorrhage with normal seminiferous tubules, and the orchiectomy procedure was aborted. Permanent histopathologic evaluation showed diffuse intratesticular fresh hemorrhage with reactive changes and no associated coagulative necrosis. Despite the recent clinical/radiologic diagnostic tools available to evaluate SIH, such as colored Doppler imaging, it remains a clinically challenging diagnostic entity to distinguish malignant from benign intratesticular masses. Most cases are diagnosed postorchiectomy; rarely is the diagnosis done perioperatively as in our case. Clinical, radiologic, and pathologic awareness of the entity is critical to avoid unnecessary orchiectomy when possible and offer optimal clinical management.

Incidental Findings in Orchiectomy Specimens of Patients Seeking Male to Female Physical Adaptation

(Poster No. 53)

Natalie Tupper, BS ([email protected]); Christopher Jurief, DO; Ameer Hamza, MD. Department of Pathology, University of Kansas Medical Center, Kansas City.

Context: Hormonal therapy followed by orchiectomy is the standard of care in management of gender identity disorder in patients seeking male to female transition. There are no official guidelines regarding the pathologic evaluation of these specimens. It is currently at the discretion of the institution where the orchiectomy is performed whether to evaluate the testis histopathologically.

Design: The purpose of this study is to document and discuss incidental findings in the orchiectomy specimens from patients seeking male to female transition at our institution over a 3-year period from January 2019 to December 2021. Data collected included patient age, testicular weight, histopathologic findings, and incidental findings.

Results: A total of 105 specimens were identified. Mean age of the patients was 36.3 ± 14.5 years. Mean testicular weight (including weight of spermatic cord) was 28.1 ± 8.8 g (right) and 29.8 ± 14.3 g (left). Incidental findings were identified in 8 cases (7.6%) and included benign cysts in 3 cases (2.9%), ectopic adrenal tissue (2 cases; 1.9%), and 1 case (0.9%) each of adenomatoid tumor, lipoma, and Sertoli cell nodule.

Conclusions: Incidental findings were present in 7.6% of cases. Although no malignancy or clinically significant incidental findings were identified, the above-mentioned findings illustrate the significance of tissue sampling in these specimens.

Diagnostic Utility of Magnetic Resonance Imaging/Ultrasound-Fusion–Guided Transrectal Prostate Biopsies: A Tertiary Community Hospital Experience

(Poster No. 54)

Ishaq A. Asghar, MD ([email protected]); Momal T. Chand, MD; Khairya Fatouh, MD; Basim M. Al-Khafaji, MD. Department of Pathology, Ascension St John Hospital and Medical Center, Detroit, Michigan.

Context: Magnetic resonance imaging/ultrasound-fusion–guided transrectal biopsies (MRI/USBX) have been utilized with an elevated serum PSA level (cutoff 3 ng/mL) to improve the detection of clinically significant (CS) (Gleason score [GS] >7) prostate cancer (PCa). We aim to evaluate the diagnostic utility of targeted biopsy (TB) by MRI versus the systemic sextant biopsy (SB).

Design: This is a retrospective study of patients with elevated PSA who underwent MRI/USBX between September 2019 and September 2020. Age, clinical history, prostate imaging reporting and data (PI-RAD) score, GS of TB and SB, tumor volume, and presence of inflammation were reviewed in prostate biopsy–naïve patients.

Results: We identified 187 patients. TB identified CS or CiS PCa in 22 of 115 patients (19%) versus SB; meanwhile, SB identified CS or CiS PCa in 38 of 115 patients (33%) versus TB. PCa (CS or CiS) was identified solely by TB or SB in 11 of 92 (12%) and 23 of 104 (22%), respectively. Comparing PI-RAD =3 and >3 showed a P value of .007. Tumor volume higher in 6 of 55 (11%) with an equal GS in both TB and SB. Inflammation was the only finding in 7 of 72 (10%) benign TB and SB biopsies.

Conclusions: Identification of PCa both CS and CiS utilizing MRI/USBX by TB was superior to SB in 22 of 115 (19%). However, SB should remain an essential part of the diagnostic process as it identified a significant number of PCa that TB either missed or only showed CiS PCa. Inflammation can lead to an erroneous PI-RAD reading. Further studies to evaluate MRI imaging techniques are suggested to enhance screening.

BK Polyomavirus–Associated Micropapillary Urothelial Carcinoma in a Renal Transplant Recipient

(Poster No. 55)

Saman S. Karimi, MD, MS ([email protected]); Vikas Mehta, MD. Department of Pathology, University of Illinois at Chicago.

BK polyomavirus (BKPyV)–associated urothelial carcinoma is an emerging entity, and there have been infrequent cases reported in the literature in solid organ transplant recipients. Recent literature suggests BKPyV can have a significant role in the development of urothelial carcinoma. We report a case of a 66-year-old man with hepatitis C infection, remote history of simultaneous kidney-pancreas transplant 7 years prior, and biopsy-proven BKPyV nephropathy, who presented to the emergency department with chief complaint of abdominal pain and nausea. Abdominal and pelvic CT scan demonstrated a small bowel obstruction with the transition point terminating into a large pelvic mass. Emergent enteroenterostomy and transverse loop colostomy were performed to alleviate the mechanical obstruction. Postoperatively, the patient developed ascites, metabolic derangements, and complications leading to mortality. An autopsy examination was performed revealing an extensive white, firm, carcinomatosis mass measuring 22.5 × 18.5 × 7.5 cm, and obscuring the urinary bladder with multifocal metastases to the diaphragm, liver, and omentum. Microscopic examination revealed invasive urothelial carcinoma composed of predominantly micropapillary architecture. The neoplastic cells showed immunopositivity for AE1/AE3, CK7, p53, p16, and SV40 (Figure 2.55, A through D), suggestive of the pathogenic role of BKPyV in urothelial carcinoma. SV40, an antigenic protein expressed by the BKPyV, acts as a mediator to alter the tumor suppressor function of p53 and RB. Our case stained diffusely positive for SV40, p53, and p16, supporting the role of BKPyV in the pathogenesis of urothelial carcinoma. BKPyV is an important consideration in immunosuppressed renal transplant recipients who subsequently develop invasive urothelial carcinoma.

Defining the Clinicopathologic Significant Prognostic Factors of the Genitourinary Tract Sarcomas

(Poster No. 56)

Nada Shaker, MD, MS ([email protected]); Ankush Patel, MBBCh, BAO, LRCP, SI; Swati Satturwar, MD; Anil Parwani, MD, PhD, MBA. Department of Pathology, The Ohio State University Wexner Medical Center, Columbus.

Context: Sarcomas of the genitourinary (GU) tract are exceedingly rare, representing 1%–2% of malignancies. We aim to evaluate the incidence and prognostic factors for survival of GU sarcomas at a tertiary care academic medical center.

Design: The laboratory information system was queried during a period of 6 years (2015–February 2022) to identify cases of soft tissue sarcomas primarily arising in the GU tract. Data on tumor characteristics, recurrence, distant metastasis, and survival were collected.

Results: The search identified 40 patients with GU sarcomas. The most common tumor locations were kidney and bladder, followed by testis, paratesticular, scrotum, and prostate. The Table summarizes tumor type per organ. Despite of the presence of distant metastasis in 2 of 6 leiomyosarcomas in the kidney, patients exhibited a higher life expectancy and a better prognosis when compared with other tumor types. Rhabdomyosarcomas were the most frequently encountered tumors in the bladder, with the shortest median survival time. Angiosarcomas and pleomorphic sarcomas of the bladder also have shown less favorable survival rates (overall survival of 8 months) and worse prognosis when metastasized. Liposarcomas were the most commonly encountered tumors in the para-testicular area and the scrotum. Dedifferentiated liposarcoma represented 10 of 14 cases. The prognosis of dedifferentiated liposarcomas remained favorable with early detection and clear surgical margin tumor resection.

Conclusions: Survival and prognostic factors varied by location, histologic type, and tumor grade of sarcoma. Bladder rhabdomyosarcomas and pleomorphic sarcomas had the least favorable prognosis and overall survival rates. The lungs are a frequent site of metastases from various primary GU sarcomas.

Metastatic Adenocarcinoma of the Prostate in a 33-Year-Old Man: A Clinical Challenge

(Poster No. 57)

Nada Shaker, MD, MS ([email protected]); Vidya Arole, MD; Anil V. Parwani, MD, PhD, MBA; Hans Iwenofu, MD, FCAP. Department of Pathology, The Ohio State University Wexner Medical Center, Columbus.

Prostate adenocarcinoma is primarily a disease of older males. However, there have been reports of occurrence in younger adults (<40 years). The prognosis and the clinical course outcome are yet to be determined. We report a case of a 33-year-old man who presented with persistent back pain for 5 months. Relevant imaging studies were delayed because malignancy was not considered to be a clinical differential diagnosis. After several months of relentless pain, an MRI was performed, and showed extensive multifocal areas of marrow replacement throughout the thoracic spine, lumbar spine, sacrum, and medial left ilium. A CT-guided bone biopsy demonstrated tight clusters of cells with vague glandular architecture and focally prominent nucleoli (Figure 2.57, A and B). By immunohistochemistry, the tumor cells were positive for keratin-AE1/3, CAM5.2, NKX3.1 (Figure 2.57, C), androgen receptor, PSA (Figure 2.57, D), PSAP, with focally positive staining for CD56 and negative staining for CK7, CK20, ERG, synaptophysin, chromogranin, thyroid transcription factor 1 (TTF-1), CDX2, PAX8, CD45, CD3, CD20, SOX-10, CD30, SALL4, OCT3/4, and p40. The diagnosis was considered prototypic for metastatic prostate adenocarcinoma. The PSA at presentation was 12.8 ng/dL and alkaline phosphatase (ALP) was 221. The patient was treated with cytotoxic chemotherapy (Taxotere and carboplatin) and androgen derivation therapy with leuprolide. After 3 cycles of therapy, the PSA had dropped to an undetectable level (<0.1 ng/dL) with ALP of 75. Imaging studies were negative for evidence of choline avid metastasis. This case underscores the importance of broadening the differential diagnoses to include prostate adenocarcinoma in males presenting with bone metastasis regardless of age.

Mucinous Adenocarcinoma of Prostatic Urethra After Brachytherapy for Prostatic Adenocarcinoma: A Case Series

(Poster No. 58)

Ting Zhao, MD ([email protected]); Hao-Wen Chuang, MD; Rory K. Crotty, MD; Kristine M. Cornejo, MD; Chin-Lee Wu, MD, PhD. Department of Pathology, Massachusetts General Hospital, Boston.

Context: Mucinous adenocarcinoma of the urethra is an extremely rare disease. There are only a few cases reported as secondary to radiation therapy. The aim of study is to review the clinicopathologic features of this disease that occurred after brachytherapy for prostatic adenocarcinoma.

Design: We identified 4 cases of mucinous adenocarcinoma of prostatic urethra in patients who received brachytherapy for prostatic adenocarcinoma.

Results: The mean age was 72.3 years, and mean interval from brachytherapy to diagnosis was 14.8 years. The Gleason scores were 3 + 3. Patients presented with hematuria (3 of 4) and urinary retention (1 of 4). Papillary lesions (2 of 3) and white fibrinous debris (1 of 3) were present during cystoscopy. Three patients underwent colonoscopy, with normal findings. Moderate to poorly differentiated adenocarcinoma, intestinal type, with mucin production, was seen in all patients, and signet ring cells were identified in 3 patients (Figure 2.58). The tumor cells expressed CK20 (4 of 4), CDX2 (4 of 4), CK7 (2 of 4), β-catenin (3 of 3, membranous/cytoplasmic), AMACR (2 of 2), CK903 (2 of 3), and mucicarmine (1 of 1). PSA, PSAP, NKX3.1, p63, and GATA3 were negative in cases tested. Three patients underwent cystoprostatourethrectomy. Two patients were staged pT2N0, with tumor confined to the prostatic urethra and prostate. One patient was staged pT3N0, with tumor invading seminal vesicle (Figure 2.58). All patients were alive without disease with a mean follow-up period of 4.9 years.

Conclusions: Mucinous adenocarcinoma of the prostatic urethra after brachytherapy for prostatic adenocarcinoma is rare. These adenocarcinomas are moderate to poorly differentiated, displaying intestinal-type features with mucinous differentiation and a characteristic immunoprofile of CK20 and CDX2 positivity, while absent of staining for PSA and PSAP.

Primary Testicular Rosai-Dorfman Disease With Forme Fruste Features of IgG4 Sclerosing Disease

(Poster No. 59)

Nada Shaker, MD, MS ([email protected]); Vidya Arole, MD; Daniel Jones, MD, PhD; Anil Parwani, MD, PhD, MBA; Hans Iwenofu, MD, FCAP. Department of Pathology, The Ohio State University Wexner Medical Center, Columbus.

Rosai-Dorfman disease (RDD) is a non–Langerhans cell histiocytosis of unknown pathogenesis that affects mainly the lymph node. Primary testicular involvement is extremely rare. Increases in immunoglobulin (Ig) G4–positive plasma cells have been increasingly associated with RDD; however, the nature of that relationship remains controversial. We report a rare case of primary testicular RDD with forme fruste features of IgG4 sclerosing disease (ISD), clinically mimicking testicular malignancy. A 61-year-old man presented initially with groin pain. Physical examination was positive for bilateral testicular masses. A scrotal ultrasound showed solid hypoechoic masses in both testicles. The patient underwent bilateral orchiectomy because of clinical concern for testicular malignancy. Grossly, the left testicular tumor was intraparenchymal and firm with tan cut surface. (Figure 2.59, A). Histologic sections showed sheets of histiocytes with emperipolesis (Figure 2.59, B), lymphoplasmacytic infiltrates, obliterative phlebitis (Figure 2.59, B), and associated areas of testicular infarction (in the right testis). By immunohistochemistry, the histocytes were strongly and diffusely positive for S-100 (Figure 2.59, C) and negative for CD1a with increased IgG4-positive plasma cells (Figure 2.59, D). The overall features were consistent with RDD with forme fruste features of ISD. Given the rare anecdotal reports of BRAF V600E mutation in a subset of RDD, pyrosequencing was performed, and it was negative for hot spot BRAF V600E mutation. In summary, we report an exceptionally rare case of primary testicular RDD with overlapping features of ISD, suggesting a possible pathogenetic link between both entities. Comprehensive clinicopathologic characterization of these cases to define clinically relevant categories is warranted.

Enteric Adenocarcinoma With Osseous Metaplasia Arising in Ileal Neobladder: A Rare Case With Unique Morphology

(Poster No. 60)

Ahmad M. Alkashash, MD ([email protected]); Muhammad Idrees, MD; Omer Saeed, MD. Department of Pathology, Indiana University, Indianapolis.

Enteric (intestinal-type) adenocarcinomas arising in ileal conduits are rare. Similarly, only a handful of cases of osseous metaplasia in enteric adenocarcinoma in general have been reported in the literature. To our knowledge, enteric adenocarcinoma with osseous metaplasia arising in ileal conduit has never been reported before. Here we report a case of adenocarcinoma of ileal neobladder 14 years after cystectomy. The patient was a 79-year-old man with a history of muscle invasive bladder high-grade urothelial carcinoma grade 3, pT2, N0, M0. He had cystectomy and neobladder creation using a segment of the ileum in 2008. Postoperative course was uneventful. Fourteen years after the surgery, the patient presented with gross hematuria. Computed tomography urogram demonstrated left hydronephrosis and a large mass in the neobladder measuring 5.5 in greatest dimension (Figure 2.60). Transurethral resection of the tumor showed malignant epithelial proliferation with glandular formation, papillary, micropapillary, and focal cribriform architecture admixed with areas of osteoid deposition rimmed with osteoblasts. Immunohistochemistry showed that tumor cells were positive for SATB2, CK7, and CK20, but negative for p63, confirming the diagnosis of enteric adenocarcinoma (Figure 2.60). In summary, although enteric adenocarcinomas from ileal conduits have been reported before, to our knowledge, this is the first report of osseous metaplasia in malignancy in this location.

Identifying Novel Metrics for Predicting Cancer Burden in Prostate From the Biopsy Sample: A Morphometric Approach and Correlation Study in Paired Biopsy and Prostatectomy Samples

(Poster No. 61)

Kusum L. Sharma, MBBS ([email protected]); Wei Huang, MD. Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and Clinics, Madison.

Context: Correlation of prostate cancer volume (PCaV) is poor between biopsy (Bx) and prostatectomy (RP). Using a morphometric approach, this study explores alternative metrics able to reliably predict PCa burden (PCaB) in RP from the Bx.

Design: One H&E slide of the worst cancer of Bx and RP was selected from each of 143 PCa patients, with a mixed Gleason Grade Group (GGG 1–5). The slides were scanned with Aperio AT2 (Leica) at ×40. PCa annotations and epithelial (E) and stromal (S) segmentations and measurements were performed using Halo software (Halo v3.3.2541.345, Indica). Bx and RP cancer volumes (PCaV, %) for each patient were collected from the pathology reports. The cases were stratified by Bx PCa size (≤2 mm2 versus >2 mm2 per slide) and Bx PCa risk (low risk, GGG ≤2, versus high risk, GGG >2). Pearson correlations of the paired (Bx versus RP) PCa E:S ratios, E fractions (E/[E + S]), and PCaVs were analyzed with IBM SPSS Statistics 27, respectively.

Results: PCa E fraction (E/[E + S]) showed strongest correlations between Bx and RP (R2 = 0.734 and 0.553) in better Bx sampled PCa (PCa >2 mm2) of high- and low-risk PCa, respectively, whereas PCaV showed poor to moderate correlations (R2 = 0.141 and 0.425) for high-and low-risk PCa, respectively (Figure 2.61).

Conclusions: PCa E fraction can be used as a reliable metric to predict PCaB in prostate from the Bx sample for establishing the baseline PCaB and assessing the extent of treatment response in patients undergoing chemo-hormonal therapy.

Perivascular Epithelioid Cell Tumor of Kidney With CLTC-TFE3 Gene Fusion in a 52-Year-Old Woman With Early Brain Metastasis

(Poster No. 62)

Hilda Mirbaha, MD ([email protected]); Rajal Shah, MD; Liwei Jia, MD, PhD. Department of Pathology, UT Southwestern Medical Center, Dallas, Texas.

TFE3 gene translocation has been identified in a variety of tumors, including MiT family translocation renal cell carcinoma and perivascular epithelioid cell tumor (PEComa). Various fusion partners have been reported and contribute to diverse chimeric TFE3 fusion proteins. Here we report a 52-year-old woman who developed gradual onset of progressive left upper quadrant abdominal pain with weight loss, nausea, and dysuria. CT imaging revealed a 15.5-cm renal mass. A radical nephrectomy was performed and a tan-red to yellow-brown, soft, friable, and necrotic-appearing renal mass was predominantly composed of large alveolar growth pattern of tumor cells with clear to granular eosinophilic cytoplasm and round to ovoid dense nuclei. Extensive tumor necrosis was present. Her postoperative period was complicated by altered mental status, and a subsequent brain MRI revealed a large frontal mass with similar morphologic and immunophenotypic features to her renal mass on the resection. Tumor cells demonstrated strong and diffuse immunoreactivities for cathepsin K and melanocytic markers (HMB-45 and MART-1), but showed lack of immunoreactivity for PAX8, PAX2, and multiple epithelial markers (including pan-CK, AE1/AE3, CAM5.2, and EMA). TFE3 gene rearrangement was detected via fluorescence in situ hybridization in 100% of tumor cells. The unique morphologic and immunophenotypic features supported a diagnosis of Xp11 translocation PEComa. Further next-generation sequencing revealed a rare fusion partner, CLTC gene. Three months later, another brain mass was visible on MRI scan. Fractionated gamma knife stereotactic radiotherapy/radiosurgery started. She tolerated the treatment well and is clinically stable 13 months after initial presentation.

A Rare Systemic Complication of Intravesical Bacillus Calmette-Guerin (BCG) Leading to Death: A Diagnosis Confirmed at Postmortem

(Poster No. 63)

Saroja Devi Geetha, MBBS ([email protected]); Hector Chavarria, MD; Mohammed Abdelwahed, MBBCh; Vanessa Bijol, MD; Kasturi Das, MD. Department of Pathology, Zucker School of Medicine, North Shore University Hospital/Long Island Jewish Medical Center, Northwell Health, Greenvale, New York.

Intravesical bacillus Calmette-Guerin (BCG) is used as a standard adjuvant therapy for intermediate- and high-risk nonmuscle invasive urothelial cancers. Over 90% of patients tolerate the treatment well, usually with mild side effects, such as fever, rashes, muscle cramps, and cystitis. Systemic complications are extremely rare, occur because of BCG dissemination, and are associated with risk factors such as immunocompromised state and urothelial breach. We present a case of a 78-year-old man, a former smoker, with history of noninvasive urothelial carcinoma status post partial resection followed by intravesical BCG therapy. An autopsy was performed because of the sudden nature of his death. His recent clinical history was significant for an “on-and-off” fever. Autopsy showed multiple necrotizing granulomas in the brain, atrium, ventricles, lungs, kidneys, and urinary bladder. Stains for acid-fast bacilli and Grocott methenamine silver were negative. In addition, bilateral lungs showed evidence of bronchopneumonia secondary to cytomegalovirus. The patient, who had a history of urothelial cancer status post BCG therapy with history of fevers, and multiorgan granulomas on autopsy, appeared to have had a hypersensitivity reaction to intravesical BCG resulting in systemic BCG-osis. An immunodeficiency state demonstrated by CMV pulmonary infection could have been a predisposing factor. Arrhythmias induced by granulomatous myocarditis were the cause of death. Though there have been few cases of systemic BCG-osis associated with fatal sepsis leading to death, a cardiac cause of death from this condition is unique (Figure 2.63, A through D).

Chromophobe Renal Cell Carcinoma With Sarcomatoid Differentiation: Clinicopathologic Correlation and Molecular Findings of 5 Cases

(Poster No. 64)

Alcino Gama, MD1 ([email protected]); Haoliang Xu, MD2; Ximing J. Yang, MD, PhD1; Bonnie Choy, MD.1 1Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; 2Department of Pathology, Sinai Health System, Chicago, Illinois.

Context: Sarcomatoid differentiation has been reported in approximately 8% of chromophobe renal cell carcinomas (ChRCCs) and is associated with a worse prognosis. We present clinicopathologic findings of 5 cases of ChRCC with sarcomatoid differentiation from our institution.

Design: Surgical pathology database was searched to identify ChRCC with sarcomatoid differentiation from January 2015 to December 2021.

Results: Three patients were male and 2 were female. Median age at presentation was 57 years (51–61 years). Four cases were located on the left kidney. Median tumor size was 10.7 cm (5.6–13.6 cm). Median sarcomatoid component was 60% (10%–90%) and 1 had osteoid formation. All cases had necrosis (median, 30%; 10%–60%). Three cases had renal vein invasion and 2 showed lymphovascular invasion. Adrenal invasion was identified in 1 case and lung metastasis in 2 cases. After median follow-up of 12.1 months (1.6–18.2 months), 2 patients were alive. The patient with 90% sarcomatoid component, 50% necrosis, and adrenal invasion died after 1.6 months from time of diagnosis. Both patients with lung metastasis died after 18.2 and 12.1 months. PAX8, CK7, CD117, and Hale colloidal iron were positive in epithelial areas. Sarcomatoid areas had reduced PAX8 and cytokeratin markers, as well as positive vimentin, CD10, and higher Ki-67 index. Comprehensive NGS was performed in 3 cases; all were microsatellite stable and had TP53 mutations. One case had FLCN and TERT promoter site mutation.

Conclusions: ChRCC with sarcomatoid differentiation is a rare entity with aggressive behavior. Percentages of sarcomatoid component and necrosis appear to correlate with prognosis, as well as occurrence of metastasis.

Secondary Neoplasms of the Testis: A Clinical Pathologic Review

(Poster No. 65)

Dina Hassan, MD1 ([email protected]); Swathi B. Reddy, MD2; Lei Yan, MD1; Lin Cheng, MD1; Paolo Gattuso, MD.1 Departments of 1Pathology and 2General Surgery, Rush University Medical Center, Chicago, Illinois.

Context: Secondary involvement of the testis by a neoplastic process is rare. The majority of the published literature deals with isolated case reports. We undertook a retrospective study to assess the incidence and the histopathologic subtype.

Design: We searched our surgical files between 1992 and 2021 for secondary testicular tumors.

Results: A total of 256 orchiectomies were performed for neoplastic processes, including 238 for primary tumors: 126 seminomas, 82 malignant germ cell tumors, 14 Leydig tumors, 5 Sertoli tumors, 2 granulosa tumors, and 9 malignant lymphomas. Eighteen were performed for secondary neoplasms: 6 regional lesions including 3 sarcomas (leiomyosarcoma, myofibroblastic tumor, and liposarcoma) and 1 case each of periurethral adenocarcinoma, mesothelioma, and desmoplastic round cell tumor. The remaining 12 cases were 4 large cell lymphomas, 1 multiple myeloma, 1 myeloid sarcoma, 1 lymphoblastic leukemia, 2 Merkel cell carcinomas, and 1 case each of squamous cell carcinoma of the lung, prostatic adenocarcinoma, and renal cell carcinoma. Twelve tumors were intraparenchymal testicular metastasis and 6 tumors included 3 spermatic cord and 1 case each of epididymis, scrotum, and rete testis. There were 40% synchronous clinical manifestations. Nine were metachronous lesions and in 2 cases the testicular mass was the first manifestation, 1 of Merkel cell carcinoma, and 1 of lung squamous cell carcinoma.

Conclusions: Our study shows that secondary tumors of the testis account for 7%. The majority of them (70%) are regional neoplasms with direct invasion and hematopoietic lesions. Distant metastatic tumors are uncommon, 2% of the cases and 28% of all secondary tumors. Unusual clinical presentation can be confused with a primary testicular tumor.

IgG4-Related Interstitial Nephritis Ranges From Kidney Mass to Acute Kidney Injury

(Poster No. 66)

Mai Elzieny, MBBCH ([email protected]); Wei Li, MD, PhD; Hassan D. Kanaan, MD; Ping L. Zhang, MD, PhD. Department of Pathology, Beaumont Hospital Royal Oak, Michigan.

Context: IgG4-related interstitial nephritis (IRIN) can present as either a renal mass or with acute kidney injury (AKI). The goal of this study was to present our 4 IRIN cases with different clinical scenarios.

Design: Over the past 5 years, we identified 4 cases of IRIN. Each case was evaluated.

Results: Case 1 involved a 60-year-old man with a 3-cm kidney mass. The core biopsy revealed storiform fibrosis and increased IgG4-positive plasma cells (>30 per high-power field), thus diagnosed as IRIN. Case 2 involved a 69-year-old man with medical history of polymyalgia rheumatica and low complements who developed AKI (serum creatinine at 2.8 mg/dL). Light microscopy revealed diffuse interstitial nephritis with significant IgG4+ plasma cells (Figure 2.66). Immunofluorescent (IF) staining showed positive IgG staining along tubular basement membranes (TBM) and electron microscopy (EM) showed deposits along TBM, supporting a diagnosis of IRIN. Case 3 involved an 82-year-old woman who had base serum creatinine at 2.02 mg/dL and underwent a total nephrectomy, which showed 2.5-cm yellow mass and features of IRIN microscopically. In case 4, a 62-year-old man with history of lymphoma developed AKI (serum creatinine of 5.29 mg/dL) and the renal biopsy revealed typical IRIN including all features seen in case 2.

Conclusions: A renal biopsy from renal mass may be needed to confirm IRIN and avoid unnecessary surgical intervention. Also, IRIN can be accompanied by other immune disorders. IgG4 staining and IF/EM findings of TBM deposits are all helpful to reach a final diagnosis of IRIN.

Eosinophilic Cystitis: A Single Institutional Review of 26 Cases

(Poster No. 67)

Arkar Htoo, MD ([email protected]); Rose S. George, MD, MSc; Mahmut Akgul, MD. Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, New York.

Context: Eosinophilic cystitis is an uncommon diagnosis that can mimic urothelial carcinoma. Multiple etiologies are suggested, affecting both adult and pediatric populations.

Design: We conducted a retrospective clinicopathologic review of patients with eosinophilic cystitis from 2003 to 2021. Patient age, sex, symptoms, cystoscopic findings, and history of bladder instrumentation were recorded. Histologic changes in urinary bladder mucosa were reviewed. Mucosal eosinophilic infiltration was graded as mild (scattered eosinophils in the lamina propria), moderate (visible small clusters of eosinophils without brisk reactive changes), or severe (dense eosinophilic infiltrate with ulcer formation and/or muscularis propria infiltration) (Figure 2.67).

Results: Twenty-six patients (17 males and 9 females with median age of 58 [12–85] years) were studied. Presenting symptoms were hematuria (8 of 23; 35%), neurogenic bladder (6 of 23; 26%), and lower urinary tract symptoms (5 of 23; 22%). Fifteen percent (4 of 26) of patients had history of urothelial carcinoma of urinary bladder. Cystoscopy revealed erythematous mucosa (10 of 23; 43%) and/or urinary bladder mass (7 of 23; 30%). In patients with available medical records, 12 of 22 patients (55%) had history of long-term/frequent catheterization. Histologically, intensity of eosinophilic infiltrate was categorized into mild (4 of 26; 15%), moderate (9 of 26; 35%), and severe (13 of 26; 50%) cases. Proliferative cystitis (19 of 26; 73%), and granulation tissue (15 of 26; 58%) were additional common findings. All cases of long-term/frequent instrumentation cases had moderate or severe eosinophilic infiltrate.

Conclusions: Eosinophilic cystitis can mimic urothelial carcinoma and should be considered in the differential diagnosis, particularly in patients with long-term/frequent catheterization.

Tumor Volume as a Risk Factor of Biochemical Recurrence: A 30-Year Retrospective Cohort Study

(Poster No. 68)

Meagan Chambers, MD, MS, MSc1 ([email protected]); Yibai Zhao, PhD2; Roman Gulati, MS2; Funda Vakar-Lopez, MD1; Maria Tretiakova, MD, PhD1; Nicholas P. Reder, MD, PhD1; Michael Haffner, MD, PhD1; Lawrence True, MD.1 1Department of Pathology and Laboratory Medicine, University of Washington, Seattle; 2Department of Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Context: Quantification of cancer volume in prostatectomies is not included as a risk factor for biochemical recurrence (BCR) in current nomograms. We hypothesize that a lack of standardized methods for estimation contributes to conflicting reports in the literature.

Design: This single-institution retrospective cohort study consists of consecutive radical prostatectomies for prostate adenocarcinoma between 1990 and 2020. Exclusion criteria were hormone therapy before prostatectomy, incomplete resection, metastatic disease, and no postoperative serum prostate-specific antigen (PSA) values. Tumor volume was estimated by overlaying a grid on slides of entirely submitted prostates. Biochemical recurrence was defined as 2 postoperative PSA measurements >0.2 ng/mL. Tumor volume and the ratio of tumor volume to prostate volume was evaluated using multivariate Cox regression adjusted for age at diagnosis, preoperative PSA, margin status, pathologic T/N stage, and grade.

Results: We found 2485 cases with a median follow-up of 4.1 years (interquartile range, 1.6–6.7). BCR was found in 235 cases. Each 1-cm3 increase in tumor volume was associated with a 6% (95% CI, 2%–10%, P = .001) increase in the risk of BCR after adjusting for standard covariates. Each 1% increase in the tumor volume ratio was associated with a 3% (95% CI, 2%–5%, P < .001) increase in the risk of BCR after similar adjustments. Survival curves for BCR from fitted multivariate Cox regression models of the selected tumor volume ratios for a high-risk subgroup are shown in Figure 2.68.

Conclusions: Consideration should be given to standardized quantification of tumor volume based on prostatectomy specimens to provide improved prognostication about the risk of BCR.

Spectrum of C3 Glomerulopathies: A Single-Center Experience

(Poster No. 69)

Mustafa M. Deebajah, MD ([email protected]); Wei Li, MD; Hassan Kanaan, MD; Ping Zhang, MD. Department of Pathology, Beaumont, Royal Oak, Michigan.

Context: C3GNs represent a rare type of glomerulopathy due to the activation of alternative complement pathway, including C3-dominant glomerulonephritis (C3D-GN) and dense deposit disease (DDD). The goal of this study was to demonstrate a spectrum of C3GNs.

Design: The study searched 3165 renal biopsies to identify C3GNs and their clinical indices over an 8-year period.

Results: Thirteen C3GNs out of 3165 biopsies (0.41%) were identified, including 11 C3D-GNs and 2 DDD, with 7 female and 6 male patients (Table). The median age was 44 years (ranging from 5 to 69). The average urine protein to creatinine ratio was 4.09 mg/mg (ranging from 1.1 to 21). The median serum creatinine (sCr) was 4.06 mg/dL (ranging from 1.10 to 9.09). All patients with C3/C4 levels showed normal (N) C4 levels and 78% showed low C3 levels. Light microscopy ranged from mesangial proliferative pattern to membranoproliferative pattern. Immunofluorescent stains were consistent with dominant 2+ to 3+ stronger C3 staining than other stains. Electron microscopy ranged from mesangial deposits to subendothelial deposits or ribbon type of intramembranous deposits in DDD.

Conclusions: Our data indicate that C3GN cases had a consistent finding of dominant C3 staining, and low serum C3 in most, but exhibited a wide range of clinical and pathologic changes in pediatric to elderly patients. The findings support the previously reported characteristics of C3GN.

Are We Recognizing Gleason Pattern 5 on Preoperative Prostate Biopsies? A Comparison Between 2 Academic Institutions

(Poster No. 70)

Georges Tabet, MD1 ([email protected]); Reba Daniel, MD2; Priti Lal, MD2; Aileen Grace Arriola, MD.1 1Department of Pathology, Temple University Hospital, Philadelphia, Pennsylvania; 2Department of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia.

Context: Gleason pattern 5 (GP5) in prostate cancer is associated with worse outcomes and may be underrecognized on core biopsies (bx).

Design: Radical prostatectomies (RPs) with GP5 were identified retrospectively from 2 academic institutions (general [GEN] versus subspecialty [SS] models). Clinicopathologic variables such as RP and bx Gleason score (GS), margin status, extraprostatic or seminal vesicle involvement, pathologic stage, and biochemical recurrence were collected. Association of categorical and continuous values was assessed with χ2 and Student t test, respectively.

Results: We identified 263 RPs with GP5 (70% SS, 30% GEN), with clinicopathologic variables summarized in the Table. RP GSs were 4 + 5 = 210 (80%), 5 + 4 = 34 (13%), 3 + 5 = 16 (6%), and 5 + 5 = 3 (1%). GP5 detection rate on bx was significantly higher in the SS than the GEN institution (64% versus 50%, P = .03). GP5 on bx was more likely to be identified if GP5 was the RP primary pattern: 5 + 4 and 5 + 5 (82% and 100%, respectively) versus 3 + 5 and 4 + 5 (50% and 57%, respectively) (P = .01). The largest upgrade was 2 cases with bx GS 3 + 3. Identical GS on any bx and RP was found in only 47% of cases. Cases where GP5 was identified on bx had the following significant differences compared with those where GP5 was not identified: extraprostatic extension (82% versus 67%, P = .008), higher stage (P = .003), and more likely to undergo extended-template lymph node dissections (P = .006).

Conclusions: GP5 is underrecognized on bx and more likely to be identified in SS institutions. Detection of GP5 on bx impacts patient management and reasons for underrecognition should be further explored.

Large-Cell Neuroendocrine Carcinoma of the Kidney: A Case Report and Review of the Literature

(Poster No. 71)

Ellie Hong, MD; Allison H. H. Martin, MD ([email protected]); Francisco G. La Rosa, MD. Department of Pathology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora.

Neuroendocrine carcinomas of the kidney are rare, with about 166 cases reported since 1966, of which the large cell variant (LCNEC) is exceedingly rare, with 6 definitive cases reported. These aggressive tumors are nonfunctional, and patients are usually asymptomatic. We report a new case of renal LCNEC in a previously healthy 45-year-old man who presented to the emergency room with 5 hours of acute onset epigastric and abdominal pain, nausea, vomiting, diarrhea, and chills. Computed tomography showed a large left renal mass with possible rupture and extravasation, 6-mm left lung nodule, and enlarged left-external iliac lymph node. Emergency surgical procedure confirmed the renal mass with rupture through Gerota fascia and associated retroperitoneal hematoma. A radical nephrectomy with retroperitoneal washing was successfully performed, and the postop course was uneventful. Grossly, the kidney was largely replaced by a tan to yellow-orange, hemorrhagic, friable tumor (18 × 16 × 10 cm) that extended to Gerota fascia superiorly, inferiorly, and laterally, with tumor extrusion through the upper pole (Figure 2.71, A, arrow). Microscopically, the sections showed large tumor cells with high nuclear cytoplasmic ratio, vesicular-fine chromatin, prominent nucleoli, and frequent mitoses at >30/10 HPF. These cells displayed organoid nesting, palisading, rosettes, trabeculae, and solid growth patterns (Figure 2.71, B, ×400). Immunostains showed tumor cells with diffuse staining for pan-CK (AE1/E3) and CD56 (Figure 2.71, C, ×200), scattered staining for CK7 and synaptophysin, and a high index of >60% of nuclei staining for Mib-1 (Ki-67) (Figure 2.71, D, ×200). These features were consistent with a high-grade LCNEC of the kidney. The prognosis of LCNEC is still poor and management requires a multidisciplinary approach.

Unfavorable Architecture Patterns in Papillary Renal Cell Carcinoma

(Poster No. 72)

Natalia Lashmanova, MD ([email protected]); Ankica Braun, MD; Ji-weon Park, MD; Nicolas M. Lopez-Hisijos, DO. Department of Pathology, Rush University Medical Center, Chicago, Illinois.

Context: Papillary renal cell carcinomas (PRCCs) are mostly indolent; however, some behave aggressively. Nuclear grading and morphologic typing have shown limited prognostic value. In a recent study, the presence of adverse architectural patterns (micropapillary, solid, and hobnail) was correlated with worse outcomes. Our aim was to evaluate our PRCC cases for the presence of these patterns and their correlation with outcomes.

Design: We searched our database for PRCC cases from 2010 to 2021. We included cases that were classified as type 1, 2, or mixed, and excluded cases with associated neoplasms and cases that were reclassified based on newer guidelines. Micropapillary tumor budding was defined as a cluster of 3 to 10 cells, with no lumen or fibrovascular core in the center. Hobnail was defined as apically placed protruding nuclei in most of the cells in a papilla. Solid architecture is sheetlike tumor growth, without evidence of papillary architecture.

Results: We found 127 cases and excluded 32 based on design. The clinicopathologic findings are documented in the Table. Micropapillary architecture was found in 12 cases, hobnail in 8, and solid in 3. Concurrent micropapillary and hobnail was seen in 4 cases. Of the 6 cases with metastatic progression, 1 had micropapillary and 2 had both micropapillary and hobnail architectures.

Conclusions: Our results are similar to those from a recent publication correlating adverse architecture with worse outcomes. However, we also noted that the stage and grade were confounders. A larger sample is needed to determine the prognostic value for architecture.

Polycystic Kidney Disease With Renal Tumors: Analysis of 119 Patients

(Poster No. 73)

Natalie Tupper, BS ([email protected]); Ameer Hamza, MD. Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas.

Context: Intracystic papillary formations are common histologic findings in nephrectomy specimens from polycystic kidney disease patients. However, incidental tumors have also been reported in these specimens.

Design: The purpose of this study is to review the clinicopathologic features and follow-up data of renal tumors identified in polycystic kidney disease nephrectomy specimens at our institution from January 2011 to December 2021. Pathology reports of all specimens and glass slides of the specimens with tumors were reviewed. Data including patient age, gender, histologic type of tumor, tumor size and stage, and follow-up were collected.

Results: A total of 119 nephrectomy specimens were identified. Of these, 14 (11.8%) had tumors. Mean age of the patients with tumors was 58.8 ± 9.7 years. In 2 patients, preoperative imaging showed tumors, and in 12 patients, tumors were incidental. One patient had 2 tumors in the same kidney. Histologic types included papillary adenoma (n = 7), papillary renal cell carcinoma (n = 5), and clear cell renal cell carcinoma (n = 3). The tumor size ranged from 0.5 to 19.4 cm. Follow-up was available for 13 patients. One patient died 70 months after surgery because of unrelated causes. The remaining 12 patients were alive and without evidence of recurrence or metastasis 30.3 ± 32.1 months (range, 0.5–95 months) after nephrectomy.

Conclusions: Tumors were present in 14 cases (11.8%), of which 12 were incidental. Although most incidental tumors were benign papillary adenomas, the presence of papillary and clear cell renal cell carcinoma in some cases warrants careful gross inspection and adequate tissue sampling in these specimens.

Papillary Renal Neoplasm With Reverse Polarity: Our Experience With This Emerging Entity

(Poster No. 74)

Lokman Cevik, MD1; Anandi Lobo, MD2; Gabriela Quiroga-Garza, MD3; Anil Parwani, MD1; Sambit Mohanty, MD4; Swati Satturwar, MD1; Vidya Arole, MD1 ([email protected]). 1Department of Pathology, The Ohio State University, Columbus; 2Department of Pathology, Kapoor Centre of Urology and Pathology, Raipur, India; 3Department of Pathology, University of Pittsburgh, Pennsylvania; 4Department of Pathology and Laboratory Medicine, Advanced Medical Research Institute, Delhi, India.

Context: Papillary renal neoplasm with reverse polarity (PRNRP) is an emerging oncocytic tumor with papillary architecture lined by a single layer of cells with granular eosinophilic cytoplasm and apical localization of bland nuclei. Typically, these tumors are characterized by diffuse GATA3 expression, KRAS gene alterations, and negative staining for vimentin. Herein we report our experience with this emerging entity.

Design: We retrieved cases of papillary renal neoplasms with oncocytic cytoplasm that had a final diagnosis as PRNRP from 4 institutions to evaluate the demographics, clinical presentation, histopathologic, immunohistochemical, and molecular findings.

Results: A total of 6 cases were reviewed. The Table summarizes the study findings. The age range was 42–74 years with a female preponderance (M:F = 1:5). All tumors showed classic morphology and GATA3 and CK-7 positivity with variable AMACR expression. Vimentin, CAIX, and CD117 were negative in all cases. Fluorescence in situ hybridization assay showed monosomy 7 and 17 in 2 cases and trisomy 7 in 1 case. Two tumors harbored KRAS mutation involving exon 12 by RNA sequencing. The tumors were of low stage (pT1a), with no evidence of disease, metastasis, or tumor-related deaths on follow-up.

Conclusions: PRNRP is a rare and distinct oncocytic renal neoplasm that needs to be included in the differential diagnoses of papillary oncocytic tumors. As these tumors are indolent, we support the proposed name neoplasm over carcinoma. Although KRAS mutations have been described in PRNRP, a full spectrum of genetic alterations remains to be explored, particularly in a large cohort.

Renal Adenoid Cystic Carcinomas: Three Patients With Possible Primary Neoplasms

(Poster No. 75)

Rabia Zafar, MD ([email protected]); Loren P. Herrera Hernandez, MD; Sounak Gupta, MBBS, PhD; John C. Cheville, MD; Michael Rivera, MD; Joaquin Garcia, MD; Charles Sturgis, MD. Department of Pathology, Mayo Clinic, Rochester, Minnesota.

Context: Adenoid cystic carcinoma (ACCa) is common in the salivary glands but may be encountered as a primary tumor at other sites. Examples of ACCa metastatic to the kidneys have been reported, including metastases from salivary gland, lacrimal gland, auditory canal, lung, breast, and gynecologic tract primaries. To our knowledge, primary renal ACCa has not been described.

Design: We report 3 patients with renal ACCas. All patients were without history of ACCa at other sites. Physical examinations and imaging studies failed to detect occult primary disease. Aggregate findings were consistent with ACCa in all cases.

Results: Case 1 involved a 92-year-old woman with a 4.2-cm ACCa identified following right radical nephrectomy. Immunohistochemical (IHC) studies for p63 and WT1 were positive; PAX8 was negative. Fluorescence in situ hybridization (FISH) showed positive MYB rearrangement. Case 2 involved a 44-year-old woman with a 3.5-cm ACCa identified following left radical nephrectomy. IHC was positive for CK7, p63, CD117, and calponin and negative for S100, PAX8, TTF-1, and GATA3. FISH had positive MYB rearrangement. Case 3 involved an 80-year-old man with a 1.6-cm ACCa identified following right renal biopsy. IHC studies were positive for CK7, AE1/AE3 and PAX8, GATA3, AMACR, CAIX were negative. FISH showed negative MYB rearrangement (Figure 2.75).

Conclusions: To the best of our knowledge, no cases of potentially primary renal ACCa have been reported. Correlations with clinical and imaging findings are necessary to rule out renal metastasis from ACCas at distant occult primary sites. These cases suggest that rare primary renal ACCas may exist and confirm that diagnoses of renal ACCa may be rendered when no prior history of the disease exists and no occult primary is identified.

A Challenging Case of Upper Urinary Tract Urothelial Carcinoma In Situ With Florid Intratubular Spread Mimicking Invasive Urothelial Carcinoma

(Poster No. 76)

Ion Prisneac, MD ([email protected]); Reima El Naili, MD. Department of Pathology, Anatomy and Laboratory Medicine, West Virginia University, Morgantown.

Upper urinary tract urothelial cell carcinomas (UUT-UCs) are uncommon and are defined as urothelial carcinoma involving the urinary tract from the renal calyces, renal pelvis to the distal ureter. One peculiar histopathologic finding in UUT-UC is urothelial carcinoma in situ (CIS) with intratubular spread and retrograde spread within renal tubules. We present the case of a 75-year-old woman with a long-standing history of noninvasive UC for 30 years. The patient recently had CT imaging that was concerning for an upper-tract urothelial cell carcinoma. She underwent a biopsy that was indicative of high-grade urothelial carcinoma without stromal invasion. She was admitted now for radical nephroureterectomy. Histologic evaluation showed multifocal urothelial carcinoma in situ involving the renal pelvis and ureter. Focal areas within the renal pelvis demonstrated the presence of florid intratubular spread suspicious for invasive carcinoma (Figure 2.76, A). Immunohistochemical stains showed the tumor cells to be positive for cytokeratin AE1/AE3 (Figure 2.76, B), GATA3, and p63 (Figure 2.76, C), and negative for PAX8. PAS special stain highlighted the basement membrane of expanded renal tubules occupied by tumor cells (Figure 2.76, D). ERG stain showed negative lymphovascular invasion. Overall, these findings favor CIS with no definitive local invasion into the renal parenchyma. The purpose of this case report is to highlight the clinical and pathologic findings of UUT-UC with florid CIS and illustrate how it can be misdiagnosed as an invasive carcinoma into the renal parenchyma (which would make the tumor at least pT3 stage). Making the correct diagnosis of this rare entity is essential in the patient's management and prognosis.

A Case Report of Scedosporiosis Transmitted From the Near-Drowning Donor in Transplanted Kidney

(Poster No. 77)

Bei Yang, MD, PhD ([email protected]); Lin Liu, MD, PhD. Department of Pathology and Anatomical Science, University at Buffalo, Buffalo, New York.

Infection is a common complication after a near-drowning event. Near-drowning organ donors present potential risks for donor-derived infectious disease transmission. Here we report a rare case of near-drowning donor–derived scedosporiosis in a transplanted kidney. The patient was a 62-year-old man receiving his second deceased-donor kidney transplant for end-stage renal disease. The donor was a young man who died of freshwater drowning. The patient's clinical course was complicated when the heart recipient from the same donor died of invasive scedosporiosis, and the other kidney recipient from the same donor lost the grafted kidney because of fungal infection. Scedosporium species are the most common pathogen of invasive fungal infection following near drowning. The fact that 2 recipients from the same near-drowning donor developed fungi infections in grafted organs indicated a potential donor-derived transmission. Our patient had no symptoms, with negative urine and blood culture. Three renal biopsies were performed and revealed no evidence of fungi infection. However, given a slow progressive clinical course and high mortality of scedosporiosis, the grafted kidney was eventually explanted on the 37th day posttransplantation. Two cystic lesions were found, located in the superior (1.2 × 1.0 × 0.6 cm) and inferior (1.4 × 1.2 × 1.0 cm) poles of the explanted kidney. Microscopy and GMS stains showed fungal infection at these lesions, and Scedosporium species were detected by PCR using 28S primer set. Our case highlights the insensitivity of current tests that are used to detect transmissible scedosporiosis and the potential risk of infectious disease transmitted from near-drowning organ donors.

Clinicopathologic Features of Nephrotoxicity Associated With Immune Checkpoint Inhibitors

(Poster No. 78)

Felipe Camacho-Cordovez, MD1 ([email protected]); Zain Mithani, MD2; Yiqin Zuo, MD, PhD.1 Departments of 1Pathology and Laboratory Medicine and 2Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida.

Context: Immune checkpoint inhibitors (ICPis) have dramatically improved clinical outcomes in patients with cancer. However, ICPi-associated nephrotoxicity, although uncommon, is a severe side effect.

Design: We searched our archives from 2017 to 2021 and describe the pathologic findings, clinical features, and outcomes of patients who received ICPi either alone or with combined therapy and underwent kidney biopsy.

Results: Eleven patients were identified including 6 women and 5 men, with a mean age of 65 years. At the time of biopsy, serum creatinine increased in all patients and with a mean increase of 2.61-fold of the baseline value. All patients except one presented with mild proteinuria, 2 patients showed hematuria, and pyuria was present in 6 patients. The prevalent histopathologic finding was tubulointerstitial nephritis (TIN) in 5 patients with 1 having granulomatous features, acute tubular injury in 2 patients, and immune complex–medicated glomerulonephritis in 2 patients (1 with membranous nephropathy). Chronic thrombotic microangiopathy was present in 2 patients who also received medications known to cause endothelial damage. Arterionephrosclerosis, which is nonspecific and likely not related to ICPi, was seen in 1 patient. ICPi was discontinued in all patients. Ten patients received glucocorticoids, 6 with complete (serum creatinine return to <0.35 mg/dL above the baseline) and 2 with partial recovery of renal function.

Conclusions: TIN was the most common histopathologic lesion of ICPi nephrotoxicity in our study. A combination of chemotherapy might lead to histopathologic findings other than TIN. Most patients exhibited a favorable response to glucocorticoid treatment.

Precision Oncology for Urinary Bladder Carcinoma With Variant Histology: Immunohistochemical Expression of TROP2 and Ephrin B2

(Poster No. 79)

Katherine Case, BA1 ([email protected]); Dylan Martini, MD3; Melad N. Dababneh, MBBS1; Mehmet Asim Bilen, MD2; Lara R. Harik, MD.1 Departments of 1Pathology and Laboratory Medicine and 2Hematology and Oncology, Emory University School of Medicine, Atlanta, Georgia; 3Department of Medicine, Massachusetts General Hospital, Boston.

Context: Bladder carcinoma with variant histology (BCVH) is associated with poor clinical outcomes, and limited treatment options. Phase II clinical trials using TROP2-directed antibody-drug conjugates and a combination of pembrolizumab with sEphB4-HAS, a decoy receptor for ephrin B2, are ongoing for urothelial carcinoma. We investigate the expression of TROP2 and ephrin B2 in BCVH.

Design: We reviewed our database for BCVH from 2011 to 2021. TROP2 and ephrin B2 immunohistochemistry (IHC) was performed. IHC images were scored using the H-score method (H-score = [percentage of strong-positive tumor cells × 3] + [percentage of moderate-positive tumor cells × 2] + [percentage of weak-positive tumor cells × 1]). In samples with multiple histologic subtypes, each was analyzed separately.

Results: A total of 105 patients were identified with a median age of 69 years (range, 22–91), and 57.1% male patients (n = 60). Seven patients displayed mixed histology, resulting in a total of 112 subtypes reported. TROP2 expression was highest in squamous cell carcinoma (mean, 190.6; median [range], 180 [60–300]) followed by adenocarcinoma (mean, 164; median, 140 [2–300]) and plasmacytoid carcinoma (mean, 132.2; median, 130 [30–300]) (Table). Ephrin B2 expression was highest in adenocarcinoma (mean, 112.6; median, 120 [10–230]), and small cell carcinoma (mean, 102.5; median, 97.5 [10–210]).

Conclusions: Expression of TROP2 and ephrin B2 in BCVH potentially expands the therapeutic possibilities for these patients with limited treatment options. Clinical trials to investigate the efficacy of these novel treatments on BCVH is warranted.

M.A. Bilen has acted as a paid consultant for and/or as a member of the advisory boards of Exelixis, Bayer, BMS, Eisai, Pfizer, AstraZeneca, Janssen, Calithera Biosciences, Genomic Health, Nektar, EMD Serono, SeaGen, and Sanofi and has received grants to his institution from Merck, Xencor, Bayer, Bristol-Myers Squibb, Genentech/Roche, Sea-Gen, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Genome & Company, AAA, Peloton Therapeutics, and Pfizer for work performed outside of the current study.

Primary Renal Squamous Cell Carcinoma: Demographic Features and Survival Analysis

(Poster No. 80)

Pratik Q. Deb, MD, PhD ([email protected]); Siaditya Badeti, BS. Department of Pathology, Immunology, and Laboratory Medicine, Rutgers New Jersey Medical School, Newark.

Context: Primary renal squamous cell carcinoma (SCC) is a sporadic tumor, accounting for less than 1% of all renal malignancies. Squamous metaplasia induced by long-standing nephrolithiasis is considered the most important etiologic factor. Because of its rarity, the epidemiologic characteristics have not been systematically investigated. Moreover, the factors affecting patients' outcomes of this neoplasm are unknown.

Design: We queried the National Cancer Institute's Surveillance, Epidemiology, and End Results database for all histologically confirmed SCC with kidney designated as the primary site. All data were transferred to SPSSv.25, and analysis was performed to demonstrate descriptive statistics. We used Kaplan-Meier curves, log-rank test, and multivariate regression analysis to test the effect of each variable on the patients' overall survival.

Results: One hundred forty patients of primary renal SCC were found in the database. Our analysis shows that most of the patients were diagnosed after 70 years, with a predominantly white population (85%) and a slight male predominance (56%). Surgical treatment of the primary site was the choice of management for the majority of the patients. Our survival analysis shows that age at diagnosis, sex, or race of the patients did not affect their disease-specific survival. However, patients who received surgical management of the primary site showed significantly better outcomes than patients who received other management options (Figure 2.80).

Conclusions: Our data suggest that age at diagnosis, sex, or race do not affect the outcome of primary renal SCC patients. However, the patients with this malignancy managed with surgery of the primary site do significantly better.

Adrenal Endothelial (Vascular) Cysts: A Rare Entity

(Poster No. 81)

Hafsa Nebbache, MD ([email protected]); Shadi Qasem, MD, MBA. Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington.

Context: Adrenal endothelial cyst, also known as vascular adrenal cyst, is a rare entity with female predilection, usually presenting with abdominal pain. Smaller cysts can be detected as incidental findings during surgery or imaging.

Design: We retrospectively reviewed our archives for adrenal cysts and identified cases with the diagnosis of “endothelial” or “vascular” cyst. For each case, we recorded the patient's age, gender, race, size of the lesion, clinical presentation, and disease associations.

Results: Six cases were identified over the course of 30 years. Five of the patients were female (83%). The patients' ages ranged from 29 to 46 years (average, 37.8), and the majority of the patients were white (83%). Four cases (67%) were on the left side. The size of the cysts ranged from 5.2 to 11.2 cm (average, 8.2 cm) (Table). Two patients presented with left-sided abdominal pressure/pain. None of the patients had prior abdominal surgery, and none of the cases recurred. No other vascular lesions or tumors were present.

Conclusions: Adrenal endothelial cysts are rare, isolated lesions affecting adult white women in our population. The cysts can be large and symptomatic, and they do not recur after surgical excision. Awareness of this entity is important in patients with adrenal masses or cysts.

Lysozyme-Induced Nephropathy Secondary to Chronic Myelomonocytic Leukemia

(Poster No. 82)

Vasudevan D. Mahalingam, DO1 (vasudevan.mahalingam@ beaumont.org); Jamal Abukhaled, MD2; Ping L. Zhang, MD, PhD.1 Departments of 1Pathology and Laboratory Medicine and 2Division of Nephrology, Internal Medicine, Beaumont Health, Royal Oak, Michigan.

Lysozyme-induced nephropathy is a rare cause of acute kidney injury (AKI) in patients with chronic myelomonocytic leukemia (CMML). We report the case of an 85-year-old man with type II diabetes and hypertension who was being evaluated for an elevated serum creatinine of 2.27 mg/dL. Additional studies showed proteinuria (1 g), predominantly nonalbumin, along with an IgA λ monoclonal protein found on serum electrophoresis. His serum κ:λ ratio, however, was elevated and urinalysis showed free κ monoclonal protein. Further hematopathologic workup revealed CMML, and he also had progression of his AKI, for which a renal biopsy was performed. Light microscopy showed unremarkable glomeruli with dilated proximal tubules containing granular and strongly eosinophilic cytoplasm (Figure 2.82, A and B). Immunohistochemical staining for lysozymes showed strong positivity in the cytoplasm and nuclei of the proximal tubule cells (Figure 2.82, C). Electron microscopy showed expanded lysosomes with rounded, dense dots arranged in an annular “chocolate chip cookie” pattern ranging from 1.0 to 1.5 μm in diameter (Figure 2.82, D). No monoclonal proteins were detected by immunofluorescent stains in the renal biopsy. Plasma lysozyme level was >10.8 μg/mL (reference range, 2.6–6.0 μg/mL). Taken together, these data support the diagnosis of lysozyme-induced nephropathy likely secondary to overproduction of lysozymes from his CMML. He began treatment with azacitidine, and following 1 cycle of therapy, he had a reduction of his serum creatinine to 1.67 mg/dL after 1 month follow-up. Awareness and recognition of lysozyme-induced nephropathy as a cause of AKI in patients with CMML is important as it may have potential diagnostic and therapeutic considerations.

Renal Cell Carcinoma With (Angio)Leiomyomatous Stroma Associated With Recurrence

(Poster No. 83)

Lydia Du, MD ([email protected]); Angela Sanguino, MD. Department of Pathology, Allegheny Health Network, Pittsburgh, Pennsylvania.

Renal cell carcinoma with (angio)leiomyomatous stroma (RCCLMS) is a poorly described entity that is known to be a benign lesion with an indolent course. This case of RCCLMS is the first with an associated recurrence. We report a case of RCCLMS in a 73-year-old woman with a past medical history significant for right renal cell carcinoma associated with prominent smooth muscle stroma status post right partial nephrectomy in 2009. She presented in 2021 with a 2-cm lesion involving the anterior cortex lateral to the hilar area and just lateral to the likely site of her previous resection. She underwent right partial nephrectomy. Gross examination revealed a 1.4 × 1.2 × 1.1-cm tan-white well-circumscribed lesion. Microscopic analysis revealed a well-circumscribed neoplasm composed of clear cells arranged in nests and tubules within a stroma rich in smooth muscle (Figure 2.83, A). The epithelial cells had abundant clear to light eosinophilic cytoplasm and nuclei with variably conspicuous nucleoli. A rich vascular network was present surrounding the epithelial nests (Figure 2.83, B). No tumor necrosis or angiolymphatic invasion was present. Immunohistochemical stains show the epithelial cells were positive for AE1/AE3, carbonic anhydrase IX (Figure 2.83, C), CK7 (Figure 2.83, D), and CD10, and negative for racemase (p504S), HMB-45, and Mel-A. The smooth muscle stroma is positive for smooth muscle actin and negative for pankeratin, HMB-45, and Mel-A. The prior report for the renal cell carcinoma associated with prominent smooth muscle stroma from 2009 strongly suggests that this is a recurrence of the same entity.

Aberrant Expression of CDX-2 in Metastatic Adenocarcinoma

(Poster No. 84)

Andrea Agualimpia Garcia, MD1 ([email protected]); Bhuvaneswari Krishnan, MD1; Luis A. Velasquez Zarate, MD2; Farinaz Arbab, MD1; Nisha Ramani, MD.1 1Department of Pathology, Baylor College of Medicine, Houston, Texas; 2Department of Pathology, Medical College of Georgia–Augusta University, Augusta.

Context: CDX-2 is a marker of intestinal differentiation. Recently it has been reported to be positive in few primary prostatic adenocarcinomas (PCAs); however, expression in metastatic prostatic adenocarcinomas (MPAs) is not well documented. We present the analysis of CDX2 expression in MPA.

Design: After a computer search, 9 cases of MPA were included in the study. Review of clinical history, imaging, and pathologic findings was performed.

Results: Of 9 cases studied, the metastatic sites included 5 regional LNs, 3 bone, and 1 adrenal. All cases showed expression of prostate-specific antigen (PSA) or NKX3.1. Only 1 case showed CDX2 expression. The patient was a 63-year-old man with no prior history of malignancy, who presented with urinary frequency and weight loss. Imaging studies revealed enlarged prostate, lymphadenopathy, and sclerotic bone lesions. The PSA level was 104 ng/mL. Biopsy of retroperitoneal LN showed infiltration by tumor cells with cribriform architecture and prominent nucleoli (Figure 2.84, A). The tumor cells were positive for NKX3.1 (diffuse) (Figure 2.84, B), p504S (Figure 2.84, C), and CDX-2 (moderate, 40% cells) (Figure 2.84, D), and negative for PSA. The morphologic features and immunophenotype were consistent with metastatic prostatic adenocarcinoma. Next-generation sequencing analysis showed no significant alterations for therapy.

Conclusions: CDX2 can show moderate expression in rare cases of MPA. Awareness of such an unusual occurrence will help to avoid misdiagnosis as metastatic gastrointestinal carcinoma, especially during the histologic assessment of a metastasis from an unknown primary. PSA and/or NKX3.1 must always be included in the immunohistochemical panel for workup of metastasis from unknown primary.

An Uncommon Cause of Arterial Hypertension in Children: Juxtaglomerular Cell Tumor

(Poster No. 85)

Daniela M. Bertel-Rodriguez, MD1 ([email protected]); Tatiana Olier-Serra, MD2; Margarita Martinez-Villate, MD3; Javier A. Baena-Del Valle, MD4; Catalina Buritica-Cifuentes, MD4; Mauricio Palau-Lazaro, MD.4 Departments of 1Pathology and Laboratories and 2Pediatric and 3Surgery, Centro Hospitalario Serena del Mar, Cartagena, Colombia; 4Department of Pathology and Laboratories, Fundación Santa Fe de Bogotá, Bogotá D.C., Colombia.

Juxtaglomerular cell tumor (JCT) is a rare renal tumor, described by Robertson et al in 1967. Patients typically present with hypertension, hyperaldosteronism, and hypokalemia due to excessive renin secretion. This entity has been described predominantly in women and prevalent in the second and third decades. Approximately 30 cases have been described in children. We present an 11-year-old boy with blurred vision and frontal headache, documenting grade 4 papilledema with clinical suspicion of tumor in posterior fossa, and ruled out by magnetic resonance imaging. During hospitalization, sinus tachycardia, hypertension, hypokalemia, and increased plasma rennin were present. The abdominal tomography shows a solid lesion well delimited and encapsulated with internal vascularization in the upper pole and renal pelvis of the right kidney (33 mm) (Figure 2.85, A). Radical nephrectomy was performed (Figure 2.85, B). Histology showed a population of uniform polygonal tumor cells, with eosinophilic cytoplasm, minimal atypia, and low mitotic rate, arranged in sheets and trapping residual ductal structures, with fine capillary network and without necrosis (Figure 2.85, C). Immunostains showed diffuse and strong reactivity for CD34 (Figure 2.85, D), and occasional cells were positive for SMA and CD117. WT1, STAT6, and cytokeratin AE1/AE3 were negative. A diagnosis of JCT was made. Surgical resection is the treatment of choice and curative; most are benign with no risk of recurrence or metastasis, except for a few reported cases. Limited genetic studies are a limitation to predict the aggressiveness of the tumor. Although this tumor is infrequent, it must be considered within the differential diagnosis of renal masses in the pediatric population.

Clear Cell Adenocarcinoma of the Urinary Bladder in a 78-Year-Old Man With a Unique Molecular Profile

(Poster No. 86)

Hua Wang, MD, PhD ([email protected]); Liwei Jia, MD, PhD. Department of Pathology, UT Southwestern Medical Center, Dallas, Texas.

Clear cell adenocarcinoma (CCA) of the bladder is a rare subtype of bladder cancer with a female predominance, and the molecular signature of CCA remains largely unclear. Here we present a case of CCA with a unique molecular profile including fluorescence in situ hybridization analysis and next-generation sequencing (NGS), to increase awareness and highlight the novel molecular findings. A 78-year-old man presented with microhematuria and a papillary frond as well as erythema around the mouth of the diverticulum observed under a cystoscope. Transurethral resection revealed tubulopapillary structures lined by markedly atypical cells with nuclear pleomorphism and hyperchromasia, which showed immunoreactivity for PAX8 and Ki-67 labeling index of 20%, and negativity for GATA3 and p63. Singly atypical cells were focally present in the lamina propria. Frequent mitotic activities and hyalinized stroma were easily identified. Subsequent partial cystectomy was performed and further confirmed the diagnosis of CCA, with perivesicular soft tissue invasion (pT3aN0). Interestingly, UroVysion demonstrated multiple chromosomal gains (chromosomes 3, 7, and 17) and homozygous deletion of 9p21. Further, NGS detected pathogenic mutations of ARID1A (c.5531G>A and c.791C>A) and CREBBP (c.5293del), with resultant loss of function of these 2 proteins. The patient is alive without evidence of disease 18 months after the initial presentation. The molecular profiling of CCA provides better understanding of the pathogenesis of the disease and guidance of the potential targeted therapy. This case study enriches the clinical presentation and molecular profiling of CCA and shines a light on the future treatment of the disease.

Anaplastic Sarcoma of the Kidney Presenting as a Polypoid Mass in the Renal Calyx: A Newly Recognized Entity With DICER1 Mutations

(Poster No. 87)

Ani Toklu, MD ([email protected]); Katrina Collins, MD; Laura M. Warmke, MD; Michael J. Hwang, MD. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis.

Anaplastic sarcoma of the kidney is a rare and newly recognized entity characterized by DICER1 mutations, with fewer than 30 cases reported to date. The tumor is usually cystic and generally composed of a spindle cell proliferation showing marked cellular anaplasia, often with prominent areas of chondroid differentiation. We report a case of a 22-year-old man with flank pain and hematuria. Ureteroscopy was performed, which revealed a polypoid lesion in the left upper renal calyx. Histopathologic examination showed a spindle cell neoplasm concerning for a sarcomatoid malignancy, and the patient ultimately required radical nephroureterectomy for definitive treatment. The kidney revealed a 3.4-cm gray-tan, multicystic mass in the upper pole and projecting into the pelvicalyceal system. The tumor was composed of solid and cystic areas (Figure 2.87, A) with entrapped renal tubules and focal condensation of short spindle to round tumor cells beneath the cyst epithelium (Figure 2.87, B), and areas with branching capillaries reminiscent of clear cell sarcoma of the kidney were focally seen (Figure 2.87, C). Multiple foci of anaplastic changes with bizarre and multinucleated tumor cells were present (Figure 2.87, D). By immunohistochemistry, the tumor cells were focally positive for SATB2 and negative for cytokeratins (AE1/AE3, CAM5.2, 34βE12), BCOR, PAX8, synaptophysin, INSM1, desmin, myogenin, MyoD1, and SS18-SSX fusion-specific antibody. We present this case to share our experience and summarize featured pathologic findings for diagnosis. We recommend screening for both germline and somatic DICER1 mutations in suspected cases of anaplastic sarcoma of the kidney.

A Rare Presentation of Bladder Rhabdomyosarcoma in an Adult Man

(Poster No. 88)

Ankush Patel, MBBCh ([email protected]); Nada Shaker, MD, MS; Andrew McLoughlin, MS; Shawn Scully, MA, MFA; Swati Satturwar, MD; Hans Iwenofu, MD; Anil Parwani, MD, PhD, MBA. Department of Pathology, The Ohio State University Wexner Medical Center, Columbus.

Adult presentation of bladder rhabdomyosarcoma is strikingly rare and seldom reported in medical literature, comprising less than 0.5% of all bladder tumors, and is often found in children 2–6 years of age. A new bladder tumor was found in a 66-year-old man with a history of hypertension, primary carcinoid lung tumor, small cell carcinoma (SCC), invasive urothelial carcinoma of the bladder, and dilated cardiomyopathy secondary to malignancy. Following removal, tumor examination revealed rhabdomyosarcoma, alveolar type, and urothelial carcinoma in situ with papillary changes (high grade: pT3a, N0). Tumor invasion was found within the lamina propria, muscularis propria, and perivascular adipose tissue. No residual carcinoma, lymphovascular invasion, or evidence of lymph node neoplasia was found. Immunostaining was positive for CK20 (transurethral), myogenin (focal), synaptophysin, desmin, chromogranin (focal), vimentin, and INSM1, and negative for CK20, AE1/AE3, SMA, CK7, S100, GATA3, p63, CAM 5.2, and SOX10 (eg, Figure 2.88, A, H&E; Figure 2.88, B, desmin; Figure 2.88, C, synaptophysin; Figure 2.88, D, vimentin). On gross examination, 40% of the urinary bladder mass was necrotic with the remainder partially filled with an exophytic soft mass. Cut section through the mass revealed tumor infiltration into the perivesical fat. Recurrence of bladder rhabdomyosarcoma is common; therefore, complete excision is of importance. As adult tumors have significant morphologic and immunohistochemical similarities to SCC, a common round cell tumor, proper identification is vital. Adult tumors with alveolar or unclassified histology are typically uniformly aggressive, with less favorable prognosis than those arising in children. Exophytic growth pattern, as seen in our patient, is a favorable prognostic factor for bladder rhabdomyosarcoma.

Effect of Intraoperative Pathologic Assessment and Other Clinicopathologic Characteristics in Reducing Positive Surgical Margins and Biochemical Recurrence in NeuroSAFE Radical Prostatectomy

(Poster No. 89)

Swati Bhardwaj, MBBS, MD ([email protected]); Russell McBride, PhD, MPH; G. Kenneth Haines III, MD; Qiusheng Si, MD, PhD. Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai Hospital, New York, New York.

Context: NeuroSAFE radical prostatectomy (NSRP) utilizes intraoperative margin assessment (IMA) to allow a tight nerve-sparing procedure without compromising oncologic outcome. This study was undertaken to assess the effect of taking additional margins to address positive specimen margins (PMs) reported intraoperatively on the incidence of final positive margins (PMs) and biochemical recurrence (BCR).

Design: This is a retrospective cohort study of 1484 consecutive patients undergoing either NSRP or standard radical prostatectomy (StRP) between January 1, 2016, and December 31, 2018. Medical records were analyzed for clinical, laboratory, and pathologic variables, including BCR. The impact of IMA on final surgical margin status and BCR was evaluated.

Results: A total of 1261 patients underwent NSRP and 223 StRP. The groups had similar clinicopathologic characteristics (Table). The incidence of a final PM was significantly lower in the NSRP group compared with the StRP group (10.2% versus 21.9%, P = .001). The overall BCR was similar between groups (11.5% NSRP versus 11.7% StRP) with 1–59 months of follow-up. Stratified by tumor volume (>10 or ≤10 cm3), the BCR was lower in the NSRP group compared with StRP (4.9% versus 6.2%, P = .5). Preoperative PSA and biopsy Grade Groups both significantly correlated with BCR (P < .001 each).

Conclusions: NSRP significantly reduces the incidence of final PMs, compared with StRP. However, we found no significant difference in BCR between the 2 groups. This may reflect difficulties in identifying the exact site of a positive margin, differences in postoperative treatment based on margin status, or other factors. Studies to elucidate the reasons for this finding are ongoing.

MRI Findings Can Identify Men With Low-Risk Prostate Cancer Who Harbor a More Aggressive Disease

(Poster No. 90)

Fireneh N. Beshah, MD ([email protected]); Oleksii A. Lakymenko, MD; Oleksandr N. Kryvenko, MD; Merce Jorda, MD, PhD; Laurence M. Briski, MD. Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, Florida.

Context: Patients with low-risk prostate cancer defined as Grade Group 1 cancer on biopsy and PSA ≥10 may be considered for active surveillance. We analyzed if MRI findings can help identify men with a more aggressive disease.

Design: We assessed radical prostatectomy (RP) findings in men with preoperative low-risk prostate cancer who had MRI with Prostate Imaging Reporting and Data System (PI-RADS) 4–5 lesions (n = 94), PI-RADS 3 lesions (n = 44), and PI-RADS 1–2 or no radiologic lesions (n = 22). The outcomes were assessed for upgrading and cancer aggressiveness on a scale of 1–4. Multivariable analysis assessed the independent effects of PI-RADS on RP outcomes.

Results: Preoperatively, patients with MRI 3–5 lesions were older, had more core biopsies taken, more positive cores, and higher percentage of cores involved. Patients did not differ by PSA, gland weight, or ethnicity. At RP, the incidence of upgrade was significantly higher in PI-RADS 4–5 (68 of 94; 72%) versus PI-RADS 3 (21 of 43; 49%) versus PI-RADS 1–2 (8 of 22; 36%), P = .001. PI-RADS 4–5 cases had higher cancer aggressiveness (P < .001). In multivariable analysis including variables statistically significant in univariable analysis, referenced to PI-RADS 1–2 men, only PI-RADS 4–5 independently predicted upgrade (OR = 4.2; P = .006) and category 3–4 cancer aggressiveness (OR = 5.6; P = .03) RP.

Conclusions: In men with low-risk prostate cancer, RP findings are significantly worse in patients with PI-RADS 4–5 than PI-RADS 3 or PI-RADS 1–2 or no lesions. Such men with PI-RADS 4–5 may benefit from immediate rebiopsy for proper disease grading and should be counseled accordingly if active surveillance is considered.

Eosinophilic Solid and Cystic Renal Cell Carcinoma: A Single-Center Retrospective Review of 5 Cases

(Poster No. 91)

Selcuk Erturk, MD ([email protected]); Ayush C. Srivastava, MD; Varsha Manucha, MD. Department of Pathology, University of Mississippi Medical Center, Jackson.

Context: Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is an emerging entity described as the sporadic counterpart of tuberous sclerosis–associated RCC typically in females. We present a case series of 5 ESC-RCC diagnosed in a single institute in the southeast United States.

Design: A retrospective review of 175 nephrectomies for neoplasms from 2019 to 2021 retrieved 5 cases of ESC-RCC. The demographic data and histologic features were reviewed and compared with the original description of the tumor.

Results: All 5 renal tumors were unifocal, size range 12–46 mm (median, 28 mm), and pT1 stage. Four tumors were sporadic (3 women, age range 35–71 years, and 1 man, age 19 years) and 1 case (male, age 11 years) was associated with tuberous sclerosis. Four of 5 patients were African American and 1 white. The histology was consistent in all 5 tumors: solid-cystic with macrocysts and microcysts, voluminous eosinophilic cytoplasm, coarse granular cytoplasmic stippling, and prominent nucleoli. No necrosis or rhabdoid or sarcomatoid features were identified. One case was diagnosed as ESC-RCC on biopsy. All were KRT 20 positive (focal to strong diffuse) and CD117 negative (Table). All underwent partial or total nephrectomy and were without disease progression after last follow-up (2–27 months).

Conclusions: The ESC-RCCs in our case series (~2.8% incidence) matched the original description (demographic and pathologic features), except for one case in a 19-year-old man without association with tuberous sclerosis. The characteristic morphology enables easy recognition of ESC-RCC, and the incidence may be higher than reported.

Extended Validation on Artificial Intelligence–Based System for Prostate Cancer Diagnosis

(Poster No. 92)

Taryme Lopez Diaz, MD ([email protected]); Dibson D. Gondim, MD. Department of Pathology and Laboratory Medicine, University of Louisville, Kentucky.

Context: Clinical implementation of digital pathology and artificial intelligence (AI) has the potential to revolutionize how pathology is perceived in health care systems. We conducted a validation study to evaluate the most recent version of Paige Prostate Detect (Paige.AI Inc, New York). The novelty is that this new algorithm version (2.0.0) is capable not only of detecting carcinoma, but also of quantifying percentage of Gleason patterns, which is fundamental for clinical care.

Design: Fifty cases were randomly selected from a list of 80 consecutive cases. Whole slide images were acquired from 1220 H&E slides scanned in a Leica Aperio GT450 at ×400. Paige Prostate Detect was applied to each slide and results were compared with the original diagnoses. A data analysis pipeline was built with Python 3.9 program language and Pandas library.

Results: Paige Prostate Detect results were recorded for each whole slide image, and pathologists' evaluations were recorded by part, which consisted of evaluation of 2 or more slides. Approximately 4% (50 of 1220) of diagnostic discrepancies were found based on individual diagnostic categories assigned to each slide. The slide-based and case-based discrepancies of multiple variables (extent of involvement, Gleason pattern breakdown, Gleason score, Grade Group) were also calculated.

Conclusions: Clinical validation of AI-based systems is paramount. As the Paige Prostate Detect product has evolved, validation of each output is required. Accurate quantification has the potential to assist on documentation of all variables needed for clinical care. Prospective multi-institutional validation is required to further develop best practices related to application of AI in pathology.

Granulomatosis With Polyangiitis Masquerading as Urethral Cancer: A Unique Presentation

(Poster No. 93)

Pramila Moideen, MD ([email protected]); Thomas Cotter, DO; Sravan Kavuri, MBBS; Matthew Powell, MD. Department of Pathology, Augusta University, Augusta, Georgia.

Granulomatosis with polyangiitis (GPA), formerly known as Wegener granulomatosis, is a multisystem necrotizing vasculitis that typically involves respiratory system and kidneys. It has a male predilection and onset is typically around 50 years of age. Here we report a case of a 19-year-old woman with an unusual presentation of GPA, a urethral mass masquerading as a urethral cancer that progressively increased in size over the course of 5 months. She had persistent pain at the site of the lesion as well as lower urinary tract symptoms including urgency and frequency, as well as light vaginal bleeding. Malignancy was suspected on imaging and a biopsy was done for a bladder neck lesion, which showed a granulomatous infiltrate associated with extensive necrosis, acute and chronic inflammation, and granulation tissue. Not long after, she presented with fever, joint pain, acute kidney injury, skin lesions, sinus symptoms, and large lung lesions. The skin lesions were mostly on her elbow and forearm, and were biopsied and diagnosed as palisaded neutrophilic and granulomatous dermatitis, a reactive granulomatous dermatitis frequently associated with systemic vasculitides, including GPA. The kidney biopsy showed crescentic glomerulonephritis, pauci-immune type. The suspected diagnosis of GPA was confirmed with positive PR3-ANCA antibodies. Early diagnosis and appropriate treatment are essential since GPA is rapidly progressive and frequently fatal. A high index of suspicion is needed by clinicians and pathologists, as this case highlights that GPA can present in unusual ways.

Immunophenotyping Dedifferentiated Clear Cell Renal Cell Carcinoma: Is It a SMARC Decision?

(Poster No. 94)

Sanket Choksi, MBBS ([email protected]); Michael Kritselis, DO; Eric Burks, MD; Teresa Lims, Masters; David Wang, MD; Zhichun Lu, MD; Shaun Wason, MD. Department of Pathology, Boston Medical Center, Boston, Massachusetts.

Context: Clear cell renal cell carcinoma with rhabdoid features (ccRCC-R) is an aggressive high-grade tumor with poorly understood molecular alterations. Switch sucrose nonfermentable (SWI/SNF) chromatin remodeling complex has been recently identified as the molecular mechanism underlying dedifferentiation and rhabdoid transformation in some carcinomas. We sought to investigate the immunomorphologic features of ccRCC-R.

Design: A total of 95 ccRCC cases were retrieved from archives of the pathology department at Boston Medical Center from 2007 to 2019 with search criteria of “nephrectomy,” “tumor > 4 cm,” and “WHO/ISUP 3 & 4/Furman grade 3 & 4.” ccRCC-R was defined as the presence of rhabdoid component (>5%) with a detectable well-differentiated clone. A select IHC panel was performed and clinicopathologic features were recorded.

Results: A total of 13 ccRCC-Rs were included (4 women and 9 men), mean age 62 years (42–86 years), mean tumor size 8.7 cm (range, 6–15 cm); 10 pT3a cases, 2 pT3b cases, and 1 pT4 case. All 9 cases with follow-up showed metastasis (mean time from diagnosis to metastasis was 16.3 months). Immunoprofile was notable for strong diffuse expression of CA-IX (13 of 13), loss/diminished staining for Pax 8 (6 of 13), variable claudin 4 (5 of 13) and AE1/AE3 (3 of 13), and loss of nuclear staining for SMARCA2 (12 of 13) and SMARCA4 (1 of 13) (Figure 2.94).

Conclusions: ccRCC-R shows distinct immunophenotype with adverse prognosis. Most cases showed loss of SMARCA2 expression with variable expression of AE1/AE3 and claudin4 and with largely retained strong diffuse expression of CA-IX. Considering SMARCA2 loss, specific targeting of these mutations can have potential therapeutic implications.

Study on Clinicopathologic Characteristics of High-Grade High-Stage Early-Onset Prostate Cancer Treated With Robotic Radical Prostatectomy: A Single Metropolitan Institutional Experience

(Poster No. 95)

Isabela Medeiros, MD1 ([email protected]); Hanqiao Zheng, MD3; David S. Wang, MD2; Mark H. Katz, MD2; Shaun E. Wason, MD2; Zhichun Lu, MD.1 Departments of 1Pathology and Laboratory Medicine and 2Urology, Boston Medical Center, Boston, Massachusetts; 3Department of Pathology and Laboratory Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Context: Early-onset prostate cancer (ePCa), diagnosed at age ≤55 years, has shown different etiologic and clinical perspectives from prostate cancer in older men. Many ePCa presented with low-grade/stage disease; however, a subset of ePCa presented with high-grade/stage tumors associated with poor clinical outcomes. We sought to investigate clinicopathologic characteristics of high-grade, high-stage ePCa.

Design: We retrospectively analyzed clinicopathologic data of 88 men ≤55 years old who underwent radical prostatectomy from 2013 to 2019. High-grade, high-stage ePCa was defined by pT stage ≥3a and/or nonfocal positive margins and/or Gleason pattern 5 present. Clinicopathologic parameters were recorded (Table).

Results: A total of 40 high-grade high-stage ePCa were included, 19 African American (48%) and 14 white (35%); 14 men (35%) had a positive family history. PSA ranged from 2.8 to 30.0 ng/mL (mean, 10.1). Follow-up period ranged from 1 to 78 months (mean, 35.4). Biochemical recurrence was 25% (10 of 40). Pathologic characteristics included 55% tumors with tumor volume > 10%, 40% (16 of 40) tumors with intermediate to high-risk disease (GG ≥3), and 45% (18) of cases with Gleason pattern 5. All tumors with Gleason pattern 4 showed the following features: fused glands (65%), cribriform glands (25%), glomerulation (20%), and poorly formed glands (13%). Intraductal carcinoma was present in 7 cases (18%). Fifteen cases (38%) showed positive margins.

Conclusions: Early-onset prostate cancer can present with high-grade/stage tumors that show high prevalence (45%) and high biochemical recurrence (25%). Race and family history had no significant impact on the overall biochemical recurrence. Further genomic molecular analysis is essential to determine the mechanism.

Racial and Ethnic Disparities in Genomic Profiling of Bladder Cancer

(Poster No. 96)

Busra N. Bacik Goksu, MD ([email protected]); Suleyman Y. Goksu, MD; Saman Karimi, MD; Vikas Mehta, MD. Department of Pathology, University of Illinois at Chicago.

Context: Bladder urothelial carcinoma is one of the most common urinary system cancers in the United States and the fourth most common cause of cancer in males. Racial and ethnic differences exist in the outcome of urothelial carcinoma. Therefore, we aimed to evaluate the molecular features of urothelial carcinoma among race and ethnicity.

Design: We identified the patients with urothelial carcinoma using the American Association for Cancer Research Project GENIE (11.0) data. Mutational profiles were compared between race and ethnicity (non-Hispanic Asian [NHA], non-Hispanic black [NHB], non-Hispanic white [NHW], and Hispanic) using the Fisher exact test with the Benjamini-Hochberg method.

Results: Among 2144 urothelial carcinoma patients (1919 NHW, 71 NHB, 64 NHA, 90 Hispanic), overall, most enriched mutations were TERT (54.8%), followed by TP53 (49.5%), KDM6A (29.8%), and ARID1A (27.8%). NHB patients had higher rates of TERT mutations (92% NHB versus 60% NHA versus 57% NHB, P < .001, q < 0.001), whereas NHA patients had higher rates of DDR2 mutations (16% NHA versus 6% NHB versus 5% NHW, P < .001, q = 0.02).

Conclusions: This study showed the racial differences in genomic profiling of bladder urothelial carcinoma. Further investigations are warranted to enlighten these disparities to identify potential diagnostic markers and influence target treatment options.

Ischemic Changes in Noninvasive Papillary Urothelial Carcinoma Can Induce Architectural Changes Mimicking Invasion

(Poster No. 97)

Amr G. Abulaban, MD ([email protected]); Oleksii A. Iakymenko, MD; Laurence M. Briski, MD; Merce Jorda, MD; Oleksandr N. Kryvenko, MD. Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, Florida.

Context: Retraction, paradoxical differentiation, desmoplasia, and complex irregular growth are criteria of invasion in urothelial cancer. We describe changes in noninvasive cancer mimicking invasion where cancer cells have irregular proliferation in hyalinized acellular stroma.

Design: After encountering 2 consult cases where pseudoinvasion was misclassified as invasion, we reviewed 170 consecutive in-house patients with noninvasive papillary urothelial carcinomas for the presence of pseudoinvasion (Figure 2.97, A through C) or preceding stromal changes without epithelial architectural alteration (Figure 2.97, D). We describe the correlation of these findings with age, sex, and tumor grade and size.

Results: There were 34 females and 146 males (mean age, 70.5 versus 71.5 years; P = .48) with 227 separate tumors (130 high grade and 97 low grade). Twenty patients (21 tumors) had pseudoinvasion and 15 (24 tumors) had precursor findings. Pseudoinvasion and precursor findings were present in 2 of 34 females (6%) and 33 of 136 males (24.3%) (P = .02). Tumor size did not differ between females and males (1.31 versus 1.51 cm; P = .44). The findings were present in 26 of 130 high-grade (20%) and 19 of 97 low-grade tumors (19.6%) (P = 1). Larger tumor size correlated with the presence of pseudoinvasion and precursor lesion (mean size 2.6 versus 1.21 cm, P < .001). The patient age did not correlate with the findings (mean age, 69.9 versus 71.6 years; P = .48). Other criteria of invasion were not present.

Conclusions: Pseudoinvasion in bladder cancer shows areas of irregular proliferation of cancer cells in hyalinized acellular stroma. The presence of these findings positively correlates with larger tumors and male sex, raising the possibility of tumor ischemia/infarction as possible etiology with reactive epithelial proliferation.

Are There Racial Differences in the Location and Aggressiveness of Prostate Cancer Lesion of Interest Detected by Targeted Multi-Parametric MRI Fusion Biopsy?

(Poster No. 98)

Hovsep Ohan, MD ([email protected]); Daniel Schultz, MD; Oudai Hassan, MD; Nilesh Gupta, MD. Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, Michigan.

Context: Fusion biopsy (FBx) has superior detection rates of prostate cancer (PCa) over standard template biopsies, especially for PCa localized anteriorly. African American (AA) men have increased risk of PCa, higher mortality rates, and more frequent anterior tumors. We investigated any significant association between positive FBx locus and age, race, PSA value, or aggressiveness of the cancer detected.

Design: This study included all positive FBx between 2016 and 2020 with only one targeted PIRAD lesion. Fisher exact test and Mann-Whitney U test studied statistically significant (P ≥ .05) associations.

Results: A total of 117 patients met our inclusion criteria in the study. Ages ranged from 43 to 82 years (median, 68). Nineteen were AA and 86 white. PSA values ranged from 1.4 to 50.0 (median, 5.9). Lesions of interest (LOIs) were posteriorly located in 61 (58%), and 44 (42%) were anterior. The Table shows distribution of location of the tumors in AA and white males. There was no significant difference in location of LOI based on race. Similarly, there was no location impact on Grade Group of the detected PCa. There was no significant age correlation with location of the tumor (P = .34). PSA value at the time of biopsy significantly correlated with the LOI location (anterior versus posterior) and the value was higher in the anterior location (median PSA in anterior and posterior LOIs are 6.3 were 5.2, respectively).

Conclusions: There are no significant differences in tumor location or Grade Group detected on FBx in AA or white men. Correlation with final pathology to include final grade and stage will be a useful study to confirm the findings of this biopsy study.

Matrix-Associated Sarcomas Clinically Mimicking a Thrombosed Pseudoaneurysm: An Important Diagnostic Pitfall

(Poster No. 99)

Bianca Puello Yocum, MD ([email protected]); Laura Warmke, MD. Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis.

High-grade sarcomas can occasionally present as a perivascular mass with associated calcification/matrix production, clinically mimicking a thrombosed pseudoaneurysm. CT and ultrasound findings may be misleading, and biopsy may be deferred because of the perceived risk of bleeding, thereby delaying definitive histologic diagnosis. We present 2 cases of matrix-associated sarcomas that were initially favored to represent a thrombosed pseudoaneurysm. Case 1 involved a 42-year-old woman presented with left lower leg swelling. Venous Doppler revealed presumed thrombosis, and she was prescribed apixaban with residual swelling. Follow-up CT scan favored a thrombosed pseudoaneurysm. Resection revealed a soft tissue mass (5.2 cm) with focal left common femoral vein invasion. Microscopically, the lesion demonstrated poorly differentiated, oval-to-spindle cells interspersed with areas of well-differentiated hyaline cartilage. Next-generation sequencing revealed a HEY1-NCOA2 gene fusion, confirming the diagnosis of extraskeletal mesenchymal chondrosarcoma. Case 2 involved a 65-year-old man presented with severe left groin pain. CT angiogram showed an inguinal mass adjacent to the left femoral artery, favored to represent a thrombosed pseudoaneurysm. Because of concern for pulsatile flow on ultrasound, biopsy was not attempted. Piecemeal resection revealed a high-grade sarcoma with areas of coarse calcification. Fluorescence in situ hybridization revealed SS18 gene rearrangement, confirming the diagnosis of synovial sarcoma. High-grade sarcomas should be considered when dealing with a perivascular mass with evidence of calcification/matrix production. These cases show that both mesenchymal chondrosarcoma and synovial sarcoma can clinically mimic a thrombosed pseudoaneurysm. MRI may be helpful in establishing soft tissue origin, and consultation with vascular surgery may be beneficial.

Periosteal Osteosarcoma With Medullary Cavity Extension in an Older Woman

(Poster No. 100)

Leonard Yenwongfai, MD, MS ([email protected]); Shadi Qasem, MD, MBA. Department of Pathology, University of Kentucky, Lexington.

Periosteal osteosarcoma is uncommon, accounting for less than 2% of osteosarcomas. It is a predominantly chondroblastic, intermediate-grade bone-forming tumor, typically arising from the periosteum of long bones, with infrequent medullary cavity extension. We report a case of a 52-year-old woman who presented with a 2-month history of persistent ankle pain and swelling after an exercise program. A computerized tomography scan demonstrated an abnormal density within the medullary space of the anterior distal tibial diaphysis with adjacent cortical heterogeneity extending from the cortex into the adjacent soft tissues (Figure 2.100, A). After performing a fine-needle aspiration of the lesion, a sarcoma diagnosis with chondroid differentiation was rendered, warranting a below-the-knee amputation. Sectioning the bone revealed a superficial tibial diaphyseal variegated mass with irregular borders located on the bony surface with extension into the soft tissue, medullary cavity, and joint cavity (Figure 2.100, B). Histologic sections revealed lobules of neoplastic cartilaginous matrix with foci of bone formation, surrounded by fascicles of intermediate-grade malignant spindle cells with occasional prominent nucleoli and mitosis (Figure 2.100, C and D). No mutations in IDH1 and IDH2 were identified on exon 4. These radiologic and histopathologic findings are compatible with periosteal osteosarcoma. Periosteal osteosarcoma carries an intermediate prognosis compared with other types of surface osteosarcomas (parosteal osteosarcoma and high surface osteosarcoma). The role of neoadjuvant therapy is debatable; it may be advocated for tumors with high-risk features (high grade and medullary involvement). Pathologists need to be aware of this tumor, given its overlapping histologic features and unique presentation.

Protuberant Fibro-Osseous Lesion of the Temporal Bone (Bullough Lesion)

(Poster No. 101)

Couger Jaramillo, MD ([email protected]); Thomas Adams, MD; Erica Kao, MD. Department of Pathology, Brooke Army Medical Center, Fort Sam Houston, Texas.

Bullough lesion is a rare, benign, exophytic fibro-osseous lesion confined to the surface of the temporal bone. Based on the few cases described in the literature, it has a female predilection and occurs in a wide age range. The histologic differential diagnosis includes fibrous dysplasia and ossifying fibroma. Other possible entities presenting in the calvaria include osteoma, osteosarcoma, osteoblastoma, giant cell tumor of bone, myeloma, and eosinophilic granuloma. We relate the case of a 59-year-old man with a 1-year history of a painless, slow-growing postauricular mass. Magnetic resonance imaging demonstrated a calcified periosteal mass arising from the left temporal bone; computer tomography was notable for an aggressive surface matrix without intracranial extension concerning for malignancy. The patient subsequently underwent wide local excision. Grossly, the lesion was well circumscribed and white-tan with a homogeneous, firm cut surface. Histologic sections demonstrated fascicular and storiform bland spindle cells in a collagenous matrix with scattered, rounded islets of woven and lamellar bone, favored to represent a benign fibro-osseous lesion such as fibrous dysplasia. However, the surface location and radiographic findings did not fit. Fluorescence in situ hybridization performed on EDTA-decalcified tissue demonstrated no MDM2 gene amplification, which excludes parosteal osteosarcoma. Pyrosequencing was performed and was negative for a GNAS mutation (R201 codon), making fibrous dysplasia less likely. Radiologic-pathologic correlation in conjunction with ancillary testing helped support this extremely rare and unusual diagnosis of protuberant fibro-osseous lesion of the temporal bone (Bullough lesion).

Osteolipoma Involving the Paraspinal Space: A Case Report and Literature Review

(Poster No. 102)

Sachie Ikegami, MD, PhD1 ([email protected]); Mohsin Rahman, MD, MBA2; Aisha Sethi, MD.3 1Department of Pathology, University of Cincinnati, Ohio; Departments of 2Radiology and 3Pathology, Cincinnati VA Medical Center, Cincinnati, Ohio.

Osteolipoma is the rarest subtype of lipoma. Because of heterologous differentiation, the differential diagnosis includes lipomatous and nonlipomatous tumors including well-differentiated liposarcoma and osteosarcoma. Here, we present a case of osteolipoma, emphasizing its importance as a distinct clinical entity. Additionally, we highlight the histologic features helpful in identifying it from other more aggressive neoplasms, including liposarcoma and osteosarcoma. A 50-year-old man presented with a painless right back mass. Computerized tomography showed a well-circumscribed mass with dense coarse calcifications. Magnetic resonance imaging demonstrated a heterogeneous lobular lipomatous mass, located at the right perivertebral paraspinal space spanning T3–T6. No enhancement or adjacent osseous destruction was observed. An excisional biopsy demonstrated a 7.0 × 4.2 × 3.0-cm well-circumscribed soft tissue mass with cut surface demonstrating bony areas. Microscopic examination revealed mature adipocytes with thin delicate fibrous septa, with islands of dense cortical and trabecular lamellar bone. The specimen was extensively sampled. There were no cytologic atypia, atypical hyperchromatic stromal cells, necrosis, or mitosis identified. Based on these histologic features, a diagnosis of osteolipoma was rendered (Figure 2.102, a through d). Given the large size, deep location, and presence of heterologous elements, this entity can mimic liposarcoma and extraskeletal osteosarcoma, among others. We present this case to emphasize the importance of this rare clinical entity that can be diagnosed based on histologic features in conjunction with clinical and imaging findings. Although rare, it should be recognized as a distinct clinical entity when encountered with a lipomatous tumor with ossification.

Epithelioid Hemangioendothelioma With an Atypical Presentation as an Inguinal Mass

(Poster No. 103)

Mary E. Doan, MD1 ([email protected]); Nisha Ramani, MD2; Linda K. Green, MD2; Farinaz Arbab, MD.21Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas; 2Department of Pathology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.

Epithelioid hemangioendothelioma is a rare, malignant vascular neoplasm. It is usually a solitary, often painful mass arising in the superficial or deep soft tissue. Two-thirds of cases are found in the extremities, but tumors can also be seen in the head and neck, trunk, and mediastinum. We present a rare case of epithelioid hemangioendothelioma in a 44-year-old man who presented with left inguinal hernia. On CT scan, a left inguinal mass suggestive of an enlarged lymph node was identified. No other lymphadenopathy was noted. The lymph node was excised, and H&E-stained sections revealed small epithelioid cells with vesicular nuclei arranged in aggregates, cords, and single cells with an infiltrative growth pattern that formed occasional abortive vascular spaces in a fibrous stroma (Figure 2.103, A). Rare cells showed intracytoplasmic vacuoles. Immunohistochemical stains demonstrated tumor cells positive for ERG, CD31, and CD34 (Figure 2.103, B). These stains highlighted occasional thin-walled vessels within the tumor. Staining for CAMTA1 was negative. TFE3 stain was strongly and diffusely positive in the tumor cells (Figure 2.103, C). These findings are most consistent with an epithelioid hemangioendothelioma with a YAP1-TFE3 fusion gene. Epithelioid hemangioendothelioma has rarely been described in inguinal lymph nodes, typically as a metastasis from a lower extremity lesion. However, no primary lesion was identified in this case. There have been only 2 other published cases that were also associated with YAP1-TFE3 fusion genes. These tumors are typically indolent; however, local recurrence and metastasis may occur.

ASPSCR1/TFE3 Fusion Sarcoma With Neuro-Melanocytic Differentiation: Variant of Alveolar Soft Part Sarcoma or a New Entity?

(Poster No. 104)

Saba Shafi, MD1 ([email protected]); Edward Calomeni, BS1; Tibor Nadasdy, MD1; Julia Bridge, MD2; Anil V. Parwani, MD, PhD, MBA1; Hans O. Iwenofu, MD1; Swati Satturwar, MD.1 1Department of Pathology and Laboratory Medicine, The Ohio State University Wexner Medical Center, Columbus; 2Department of Pathology and Laboratory Medicine, University of Nebraska Medical Center, Omaha.

Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma of uncertain lineage. ASPS is defined by a specific aberration, der(17)t(X;17)(p11;q25), resulting in fusion of the ASPSCR1 and TFE3 genes. Unusual clinical presentation, morphologic and IHC marker ambiguity, and lack of typical ultrastructural features can make the diagnosis quite challenging. A 35-year-old hypertensive man presented with an insidious onset of diarrhea, constipation, and pain in the lower outer quadrant of his abdomen, and a CT scan showed a large retroperitoneal mass compressing the duodenum (17.3 × 16.9 × 15.1 cm) with a heterogeneous irregular peripheral enhancement, multiple septations, cystic changes, and calcifications. Histology revealed an epithelioid neoplasm with a prominent solid nested architecture, thin fibro-vascular septa, focal tumor necrosis, and occasional mitoses (Figure 2.104, A). The lesional cells were positive for S100, SOX10, TFE3, CD56, and HMB-45 (focal), but negative for AE1/AE3, CK7, MNF116, EMA, synaptophysin, chromogranin, Melan-A, tyrosinase, PAX8, CD10, RCC, GATA3, CAIX, SMA, desmin, h-caldesmon, myogenin, MDM2, FH, SDH, and inhibin. Electron microscopy showed primitive melanosomes (Figure 2.104, C) and secretory granules depicting neuro-melanocytic differentiation and inclusions reminiscent of the prototypical rhomboid crystals seen in ASPS (Figure 2.104, D). FISH was negative for loss of chromosome 3p. An ASPSCR1:TFE3 gene fusion was detected by RNA sequencing (Figure 2.104, B). An extended DNA RAS panel for melanoma-related mutations was negative. Our findings support the neural crest origin of ASPS with specific neuro-melanocytic differentiation not described before. Whether this is a completely new entity remains to be explored.

A Rare Case of Upper Extremity Amyloidoma

(Poster No. 105)

Nivin Omar, MBChB ([email protected]); Nkechi Arinze, MBBS; Pramila Moideen, MD; Intisar Ghleilib, MBChB. Department of Pathology, Augusta University, Augusta, Georgia.

Primary amyloidoma is a solitary mass of amyloid protein deposit with no evidence of systemic amyloidosis. It can occur in different body sites. However, it is exceedingly rare in the upper extremities. Our patient is a 74-year-old woman with a history of hypertension and no known chronic problems. She inadvertently discovered a mass on her left shoulder 2 months previous. The mass was painless, stable in size, and not associated with any symptoms. Imaging showed a 5.6 × 2.4 × 2.1-cm mass centered near the level of the left deltoid fascia with nonspecific imaging characteristics, and a biopsy was recommended. Accordingly, an ultrasound-guided core needle biopsy was done, and the final pathology diagnosis was amyloidosis/amyloidoma. Therefore, a complete workup was done to rule out systemic amyloidosis. All results came back negative from complete general blood workups, serum protein electrophoresis, urine protein electrophoresis, serum immunofixation, cytogenetic testing, and bone marrow biopsy. Consequently, surgical excision was recommended, and grossly the mass showed a tan-yellow homogeneous cut surface (Figure 2.105, A). Microscopically, the mass sections showed amorphous eosinophilic material with foreign body giant cell reactions (Figure 2.105, B). The diagnosis was confirmed with Congo red stain that showed a brick red color and a characteristic apple-green birefringence on polarized microscopy (Figure 2.105, C and D). The final pathologic diagnosis was amyloidoma. To our knowledge, only 3 cases of primary amyloidoma of upper extremity have been reported, and pathologists need to be aware of this rare entity.

Mycobacterium avium Complex Septic Arthritis Presenting as Avascular Necrosis of the Femoral Head

(Poster No. 106)

Ahmed Alhusseiny, MD ([email protected]); Rahul Jawale, MD. Department of Pathology, Baystate Medical Center, Springfield, Massachusetts.

Mycobacterium avium complex is a group of nontuberculous mycobacteria that typically infects immunocompromised patients. Musculoskeletal infection is rare, and difficulty with isolating the organism causes treatment delay. We report a case of M avium complex septic arthritis of the right hip with possible systemic dissemination. A 53-year-old man with biopsy-proven sarcoidosis 29 years prior, for which he received no treatment, presented with fever and right hip pain. His laboratory studies were remarkable for leucopenia and elevated erythrocyte sedimentation rate and C-reactive protein. Blood cultures were negative. Serologic and immunologic workups were unremarkable. Chest imaging showed bilateral patchy opacities that were thought to be due to sarcoidosis. Right hip imaging revealed cystic changes in the femoral head consistent with avascular necrosis. He was started on steroids for the first time and was discharged after fever resolution. Five months later, his right hip pain significantly worsened with inability to walk. He lost 30 pounds and was found to have acute kidney injury and pancytopenia. He underwent total hip arthroplasty. Femoral head histology revealed abundant necrosis and acute and chronic inflammation with ill-defined granulomata (Figure 2.106, A). AFB stain highlighted abundant acid-fast bacilli (Figure 2.106, B). Sequencing revealed the infection was due to M avium complex. A disseminated infection was suspected, and the patient underwent renal and bone marrow biopsies, which showed nonnecrotizing granulomata (Figure 2.106, C and D) with negative AFB stains. This is a unique case of M avium complex infection presenting as femoral head avascular necrosis in a patient with sarcoidosis and no previous history of immunosuppressive treatment.

First Reported Jumping Translocation in a Sarcoma

(Poster No. 107)

Megan Gage, DO ([email protected]); Cory Broehm, MD. Department of Pathology, University of New Mexico, Albuquerque.

Jumping translocations are rare chromosomal alterations in which a segment of 1 chromosome (commonly 1q) fuses to 2 or more recipient chromosomes (often a telomere). They have been most commonly reported in hematopoietic neoplasms, but in only a few cases of solid tumors. They have not been described in sarcomas. We report a case of epithelioid angiosarcoma with 2 jumping translocations arising in a 71-year-old man with a right gluteus maximus mass present for at least 3 years, which was thought to be a fluid collection of unknown etiology on imaging. Two previous biopsies were inconclusive. Without a diagnosis, the patient elected for resection because of continued discomfort. The resected tumor was composed of 3 adjacent masses measuring 20 cm in total. Histologic evaluation demonstrated a cellular neoplasm composed of epithelioid cells with abundant cytoplasm, atypical nuclei, vesicular chromatin, and prominent nucleoli. Irregular vascular structures, abundant hemorrhage, and prominent mitotic activity with occasional atypical forms were also present. ERG and CD31 immunostains were positive, consistent with vascular differentiation (Figure 2.107, A through D). Cytogenetics demonstrated a complex tetraploid karyotype in a composite of 3 of 20 cells with 86–98 chromosomes and 2 jumping translocations: 1q21 translocated with 7q11, 8p21, and 17q25; 21p11.1 translocated with 1p13 and 17q21: 86–98<4n>,−Y,−Y,−1,−1,+7,+7,der(7)t(1;7)(q21;q11)x2,der(8)t(1;8)(q21;p21), +10,+10,−14,−14,−7,der(17)t(1;17)(q21;q25)x2,+18,+18,+21,der(21)t(1;21) (p13;p11.1)x2,der(21)t(17;21)(q21;p11.1)x2,−22,+3–5mar[cp3]. Jumping translocations of 1q21 in hematologic malignancies may be associated with worse prognosis, but little is known about the significance of these abnormalities in solid tumors, including sarcomas. There are many theories about the exact mechanisms for this process and the impact these translocations have on tumorigenesis.

Validation of Wide-Field Optical Coherence Tomography for Microstructural Analysis of Tissue From Multiple Organs

(Poster No. 108)

Beryl Rabindran, PhD1 ([email protected]); Adriana D. Corben, MD.2 1Department of Clinical Research, Perimeter Medical Imaging AI, Inc, Toronto, Ontario, Canada; 2Department of Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, New York.

Context: The presence of positive margins following tumor resection is a frequent cause of re-excision surgery. Nondestructive, label-free, real-time intraoperative histopathologic imaging may improve the assessment of margin status at the time of surgery; optical coherence tomography (OCT) with artificial intelligence to identify areas suspicious for residual malignancy has been identified as one promising solution.

Design: This was a preclinical validation of a novel device that uses wide-field OCT (WF-OCT; OTIS 2.0 System) to image specimens intraoperatively across a variety of tissue types. Cadaveric tissues from a single autopsy were imaged using WF-OCT; specimens were subsequently processed for histology, whereafter digitized slides were reviewed and annotated. One pathologist and 1 clinical scientist evaluated the quality and resolution of WF-OCT images compared with histology.

Results: Thirty tissue specimens were collected, 3 from each of the following 10 tissue types: breast, thyroid, kidney, liver, lung, colon, heart, pancreas, spleen, and adrenal glands. For all specimens, tissue-specific microarchitecture and features consistent with the known clinical history of the patient could be identified on WF-OCT images and histology slides, and corresponding sections were correlated to each other. WF-OCT volumetric analysis was used to follow features through adjacent image slices.

Conclusions: The WF-OCT images captured in this study displayed the key identifying features of various types of normal and pathologic human tissue features with a utility comparable to histology. Thus, WF-OCT has potential as a platform technology to bridge the gap between the immediate information needs of the operating room and the longer timeline inherent to histology processing.

A Rare Case of Extragastrointestinal Stromal Tumors (EGIST) at an Unusual and Unreported Location

(Poster No. 109)

Bebu Ram, MD ([email protected]); Fnu Samarta Alias Monika, MD; Norbert Sule, MD. Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Extragastrointestinal stromal tumors (EGISTs) originate from organs outside the gastrointestinal tract and demonstrate immunohistochemical features and molecular characteristics similar to gastrointestinal stromal tumors. The diagnosis of EGIST is challenging because of rarity and unusual locations. The majority of EGISTs have been reported in intra-abdominal and retroperitoneum locations and rarely in the pancreas, prostate, testis, or abdominal wall. The behavior of EGISTs generally tends to be more aggressive. We present a case of EGISTs in spermatic cord, an unusual location that has never been reported. A 69-year-old man presented with left groin abnormality with normal testicular serum tumor markers. Ultrasound revealed a 7.1-cm extratesticular mass. A left radical orchiectomy showed a 7.7-cm circumscribed, tan mass of the spermatid cord with unremarkable testis. Histology revealed a low-grade spindle cell neoplasm demonstrating interspersed inflammatory cells, no necrosis, 3 mitoses/50 HPF, with focal SMA expression (Figure 2.109, A through D). A diagnosis of “low-grade spindle cell proliferation” was rendered. The 12-month follow-up CT of the pelvis discovered multiple, biopsy-confirmed, metastatic mesenteric masses. The patient was referred to us to discuss therapeutic options. On additional histopathologic investigation, the neoplastic cells showed strong positivity for CD117 and DOG1 and molecular testing confirmed C-KIT gene mutation. The patient was put on imatinib with periodic follow-up. This case highlights the possibility of this rare tumor involving spermatid cord. Risk factors for predicting a more aggressive behavior include large size, increased mitotic count, and necrosis. EGIST tends to demonstrate a more aggressive behavior, and early diagnosis with complete resection is recommended.

Thoracic SMARCA4-Deficient Undifferentiated Tumors With Unusual Presentations

(Poster No. 110)

Ahmad B. Alshomrani, MBBS ([email protected]); Austin Helmink, MD; Scott R. Lauer, MD; Ana Yuil-Valdes, MD. Department of Pathology, University of Nebraska Medical Center, Omaha.

Context: Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently described aggressive neoplasm defined by SMARCA4 inactivating mutations. SMARCA4-UT is a poorly differentiated neoplasm characterized by cells with rhabdoid morphology, high mitotic activity, and abundant necrosis. Cases often present in young adults with a heavy smoking history. Here we describe 3 cases of SMARCA4-UT in older adults, including 1 presenting as a metastatic lesion mimicking a primary bone sarcoma.

Design: Three cases of SMARCA4-UT were identified utilizing a natural language search in CoPath. H&E-stained sections and a broad range of immunohistochemical stains including SMARCA4 were evaluated.

Results: The patients were aged 58, 70, and 70. Two patients had a significant smoking history and the third was unknown. The lesions presented as a paratracheal mass, enlarged mediastinal lymph nodes, and an iliac bone mass. The iliac mass was originally incorrectly diagnosed as an undifferentiated sarcoma, but the patient was subsequently also found to have a lung mass and mediastinal adenopathy. A fine-needle aspiration from a mediastinal lymph node demonstrated similar morphology to the iliac mass (Figure 2.110, C). All cases showed pleomorphic rhabdoid cells, frequent mitoses, and necrosis (Figure 2.110, A and B). SMARC4 immunohistochemistry was negative in all cases (Figure 2.110, D).

Conclusions: Thoracic SMARCA4-UT should be considered in the differential diagnosis of pleomorphic rhabdoid tumors in older adults with a smoking history. Although most present as lung and/or mediastinal masses, they may occasionally present as a metastasis and mimic an undifferentiated sarcoma, representing a potential diagnostic pitfall.

The Correlation Between the Expression of DDIT3 by Immunohistochemistry and DDIT3 Gene Rearrangement Detected by Fluorescence In Situ Hybridization in 52 Myxoid Liposarcoma Cases

(Poster No. 111)

Mengmeng Tian, MD ([email protected]); Ming Zhang, BS; Xiaoqi Sun, BS; Yi Ding, MD. Department of Pathology, Beijing Jishuitan Hospital, Beijing, China.

Context: Myxoid liposarcoma (MLPS) is a malignant adipogenic neoplasm with typical DDIT3 gene rearrangement. Detection of DDIT3 gene by FISH has been the gold standard for MLPS. We studied the expression of DDIT3 by immunohistochemistry and compared with the results by FISH in 52 MLPS to explore the prospect of DDIT3 immunohistochemistry in clinical diagnosis.

Design: Fifty-two MLPS from Beijing Jishuitan Hospital were collected and confirmed by DDIT3 gene rearrangement with FISH. Fifty control cases mimicking MLPS were also collected. DDIT3 immunohistochemistry was applied, and at least 10% expression of cell nuclei were scored as positive; the intensity of staining was graded as weak, moderate, or strong. We also applied FUS break-apart probe by FISH in 52 MLPS and EWSR1 break-apart probe in FUS-negative cases.

Results: The immunohistochemical expression of DDIT3 was positive in all 52 cases (100%) of MLPS; ≥ 50% positive staining of cell nuclei was found in 90.4% of cases (47 of 52), and 8 cases (15.4%) showed weak intensity of staining. No positive expression was found in the control group cases; only scattered individual cell (<10%) expression was detected in 3 pleomorphic liposarcomas. There was no significant correlation between the proportion or intensity of DDIT3 immunohistochemistry and the proportion of DDIT3 gene rearrangement–positive cells detected by FISH. Forty-eight MLPS (92.3%) coharbored FUS gene rearrangements and 3 (5.8%) coharbored EWSR1 gene rearrangement. DDIT3 phenotype was not associated with the DDIT3 rearrangement partner genes.

Conclusions: The immunostaining of DDIT3 is highly sensitive and specific in MLPS and consistent with FISH. We recommend DDIT3 immunohistochemistry as a convenient and economical surrogate in the diagnosis of MLPS.

Intracortical Diaphyseal Chondroblastoma: Report of a Rare Entity

(Poster No. 112)

Paul Stegelmeier, BS1 ([email protected]); Madeline Sauer, BS2; Julia R. Crim, MD3; Andrea Evenski, MD4; Lester Layfield, MD.1 Departments of 1Anatomic and Clinical Pathology, 2University of Missouri School of Medicine, 3Diagnostic Radiology and 4Missouri Orthopedic Institute, University of Missouri, Columbia.

Chondroblastomas are uncommon neoplasms representing 1% to 3% of primary bone tumors. The majority (98%) arise within the epiphysis of a long bone, with 50% extending into the metaphysis. Most arise intramedullary. Extremely rare cases of diaphyseal and/or intracortical chondroblastomas have been reported. A 27-year-old man presented to the orthopedic clinic with a several-month history of shoulder pain. Imaging disclosed a 2-cm lytic diaphyseal lesion centered in the lateral humeral cortex (Figure 2.112, A and B). The lesion demonstrated a narrow nonsclerotic zone of transition with severe thinning of the periosteal surface and faint intralesional small calcifications. Core biopsy disclosed a uniform population of ovoid cells lying in a fibrous stroma (Figure 2.112, C). Rare multinucleated giant cells were present. A diagnosis of chondroblastoma was entertained, but because of the unusual location of the tumor, the patient's age, and scant biopsy material, immunohistochemistry for S100 protein, DOG-1, and H3K36M was obtained. The neoplastic cells were positive for all 3 markers. Subsequent curettage disclosed histologically typical chondroblastoma with pale, bluish extracellular matrix and myxoid cartilage (Figure 2.112, D). The majority of chondroblastomas arise within the epiphysis, but rare cases have been reported in the diaphysis. Nonepiphyseal cases and those arising in a purely cortical location make up less than 2% of chondroblastomas. The unique presentation of our case and limited sampling associated with the core needle biopsy complicated the diagnosis and required immunohistochemical confirmation by demonstration of staining for the specific marker H3K36M.

Multiple Palisaded Encapsulated Neuromas (Solitary Circumscribed Neuroma) in a Patient With Neurofibromatosis Type 2: An “Incidentaloma” or New Association?

(Poster No. 113)

Vidya Arole, MD ([email protected]); Nada Shaker, MD; O. Hans Iwenofu, MD. Department of Pathology, The Ohio State University, Columbus.

Palisaded encapsulated neuroma (PEN) is a rare, benign neural tumor that usually presents as a painless firm nodule or papule on the face and within the oral cavity, although they can occur elsewhere on the body. No association with neurofibromatosis or multiple endocrine neoplasia syndrome type 2B has been reported in the literature. Herein, we report a previously unreported unique association of neurofibromatosis type 2 (NF-2) with multiple cutaneous PEN in a 24-year-old woman. The patient with a history of NF-2 presented with 2 slow-growing face soft-to-firm papules on the chin and forehead that had been gradually increasing in size over a period of 5 years. The mass on her chin was increasingly tender to palpation. Histologic sections demonstrated a dermal-based, almost encapsulated, smoothly contoured tumefactive mass composed of spindle cell proliferation with neuroid structures and foci of palisaded growth (resembling schwannoma) and intralesional cleftlike spaces. By immunohistochemistry, the lesional cells were strongly and diffusely positive for S-100 and SOX10, whereas the “capsule” was diffusely reactive for epithelial membrane antigen (Figure 2.113, A through D). The overall features are considered prototypic for PEN. The patient is 2 years post–surgical resection with no evidence of recurrence, consistent with the benign behavior of these tumors. In summary, we report for the first time a case of multiple PENs in a patient with known NF2. We highlight pertinent diagnostic clues relevant to surgical and dermatopathology practitioners to facilitate recognition, as this tumor is often mistaken for schwannoma or neurofibroma. Clinical behavior is excellent, and surgical resection is considered curative.

Periosteal Chondrosarcoma From the Rib: Rare Tumor Location With Extraordinary Size and Massive Abdominal Retroperitoneal Extension

(Poster No. 114)

Khaled S. Mohamed, MD ([email protected]); Shiguang Liu, MD; Raafat Makary, MD, PhD. Department of Pathology, University of Florida College of Medicine, Jacksonville.

Chondrosarcomas account for 20% of bone tumors and histologically encompass conventional, dedifferentiated, clear cell, and mesenchymal types. Based on location, conventional chondrosarcomas (CC) are classified into central or intramedullary (85%–90%), secondary peripheral arising from preexisting osteochondroma (10%–12%), or rarely periosteal/juxtacortical (<1%–2.5%). Periosteal chondrosarcoma (PC) occurs mainly in metaphysis of long and pelvic bones. We present an exceptionally rare case of large intra-abdominal/retroperitoneal PC from the thoracic rib. A 71-year-old woman presented with left upper abdominal heaviness. Computed tomography showed a large intra-abdominal/retroperitoneal lobulated hypodense mass with punctate calcifications displacing the spleen and the kidney with attachment to the surface of the left 11th rib (Figure 2.114, A). Marginal tumor excision was performed. The resected tumor (23 × 13 × 11 cm) was lobulated and gray glistening with a gritty nodular cut surface (Figure 2.114, B). Histopathology revealed grade 2 CC of moderate cellularity in chondromyxoid matrix (Figure 2.114, C) with skeletal muscle invasion (Figure 2.114, D), and positive resection margin. The tumor cells displayed moderate nuclear atypia with prominent nucleoli (Figure 2.114, inset). Other differential diagnoses were excluded, such as periosteal chondroma (soft tissue invasion, >5 cm, hypercellularity, and atypia), secondary peripheral CC (no preexisting osteochondroma), periosteal osteosarcoma (no osteoid formation) and extraskeletal myxoid chondrosarcoma (histology and absence of NR4A3 rearrangement). The patient is under evaluation for radiotherapy and imaging surveillance. PC is rare and costal origin is exceedingly rare (2.8% of PC) with a favorable prognosis after complete surgical excision (5-year metastasis and local recurrence-free survival are 83% and 70%, respectively). The tumor presented was massive in size with unusual intra-abdominal/retroperitoneal extension/presentation.

Digital Intravascular Neurofibroma Colliding With Papillary Endothelial Hyperplasia (Masson Tumor): A Rarely Observed Phenomenon

(Poster No. 115)

Bindu Challa, MD ([email protected]); O. Hans Iwenofu, MD. Department of Pathology, The Ohio State University Wexner Medical Center, Columbus.

Intravascular neural tumors including neurofibroma (NF) and schwannoma are extremely rare. Most reports of intravascular NF have occurred in the context of neurofibromatosis type 1. Papillary endothelial hyperplasia (PEH), also known as Masson tumor, is an uncommon benign vascular lesion characterized by a reactive proliferation of endothelial cells. They can occur as de novo lesions or secondary to other benign or malignant entities. Herein, we report an exceptionally rare case of sporadic digital intravascular NF colliding with PEH. A 76-year-old woman presented with a slow-growing mass involving the distal phalanx of her left middle finger. There was no prior history of NF-1 or any tumor elsewhere. Grossly, the tumor was approximately 3 cm in size and cut surfaces showed tan, white solid areas with adjacent cystic and hemorrhagic areas. Histologic sections show an encapsulated neoplasm containing solid areas composed of sheets of spindled wavy nuclei and shredded carrotlike collagen, colliding with cystic and hemorrhagic areas with thrombus and papillary endothelial proliferation. By immunohistochemistry, the tumor cells in the solid areas were positive for S100, SOX10, and CD34, consistent with NF. In cystic-appearing areas, the endothelial cells lining papillary proliferation showed positive staining for CD34 and ERG, prototypic for PEH (Figure 2.115, A through D). The SMA highlights “capsular” smooth muscle wall. In summary, we report a unique case of sporadic NF occurring in the intravascular location, colliding with PEH. We expand upon the spectrum of soft tissue tumors occurring primarily in the intravascular location. The histogenesis of NF in the intravascular space is not known.

Adamantinoma With a Prominent Spindle Cell Component Is a Mimic of Intraosseous Synovial Sarcoma: Clinicopathologic Features of 3 Cases

(Poster No. 116)

Bharat Rekhi, MD, DNB, MIAC, MCAP(Affl) ([email protected]). Department of Surgical Pathology, Division of Molecular Pathology and Translational Medicine, Tata Memorial Hospital, Mumbai, India.

Context: Adamantinoma is subclassified into classic/biphasic, osteofibrous dysplasia–like, and dedifferentiated adamantinoma. Intraosseous synovial sarcoma (SS) is a rare tumor. We present 3 cases of adamantinoma with a prominent spindle cell component mimicking SS.

Design: Three cases were referred to us with a diagnosis of intraosseous SS. Two cases were tested for SS18 gene rearrangement by FISH and a single case for SS18::SSX fusion by reverse transcriptase–polymerase chain reaction.

Results: There were 2 boys (8 and 15 years old) and 1 woman (31 years old). Radiologically, in all cases, a lytic lesion was seen in the tibia (middle one-third of diaphysis in 2 cases and distal metaphysis in the third case). Two cases were diagnosed as synovial sarcoma and the third case as a sarcomatoid carcinoma, elsewhere. On histopathologic review, all cases showed cellular tumor composed of spindled cells arranged in fascicles (n = 3), including “herringbone-like” pattern (n = 1), focal tubules (n = 2), and pseudocystic component (n = 2). Tumor cells were positive for p63 (3 of 3), p40 (2 of 2), EMA (1 of 1), AE1/AE3 (2 of 3), CK (1 of 1), and TLE1 (2 of 2, variable staining). Two cases tested for SS18 gene rearrangement were negative, and another case, tested for SS18::SSX fusion, was negative (Figure 2.116, A through D).

Conclusions: Adamantinomas with spindle cell morphology display overlapping histopathologic and immunohistochemical features with SS. An index of suspicion, tibial location, certain radiologic features, and application of immunostains are useful in diagnosing an adamantinoma. In cases suspicious for intraosseous SS, molecular testing for t(X;18) translocation is necessary in order to avoid an underdiagnosis of adamantinoma. The distinction between the 2 entities has treatment-related implications.

SATB2 Is Extensively Expressed in a Wide Variety of Benign and Malignant Soft Tissue and Bone Tumors

(Poster No. 117)

Vincent Lee, MS ([email protected]); Christian Kunder, MD, PhD. Department of Pathology, Stanford Hospital, Palo Alto, California.

Context: Special AT-rich binding protein 2 (SATB2) is an immunohistochemical marker for osteoblastic differentiation and is expressed in virtually all osteosarcomas, but its specificity is uncertain as expression has also been reported in other primary bone and soft tissue tumors. Our goal is to examine SATB2 expression in various bone and soft tissue tumors, both benign and malignant, to further evaluate its usefulness as a marker in general and in specific for osteoblastic differentiation.

Design: We evaluated 240 cases (70 whole sections and 170 tissue microarray cases) by SATB2 immunohistochemistry. Expression of SATB2 was evaluated as either diffuse, if 60% or more was stained positive, or focal, if less than 60% was positive. Staining intensity was graded as either weak (+1), moderate (+2), or strong (+3). Each specimen was scored from 1 to 4 as described in the Table.

Results: Results are shown in the Table. All 13 osteosarcomas evaluated showed at least moderate SATB2 expression. Of 105 benign primary bone tumor samples, extensive staining was seen in fibro-osseous lesions, giant cell–rich lesions, aneurysmal bone cyst, chondroblastoma, and chondromyxoid fibroma. In the malignant soft tissue tumor samples, SATB2 staining was seen in several sarcomas, including rhabdomyosarcoma, malignant peripheral nerve sheath tumor, myxofibrosarcoma, and undifferentiated pleomorphic sarcoma.

Conclusions: We can confirm that SATB2 is a sensitive marker for osteosarcoma, but its usefulness is limited by its lack of specificity. We have observed at least partial expression of SATB2 in a diverse group of bone and soft tissue entities.

Primary Mesenteric Low-Grade Endometrial Stromal Sarcoma With JAZF1::SUZ12 Fusion: A Rare Presentation With Diagnostic Pitfall

(Poster No. 118)

Sintawat Wangsiricharoen, MD ([email protected]); John M. Gross, MD, MS. Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland.

Low-grade endometrial stromal sarcoma (LGESS) is an uncommon hormone-responsive low-grade sarcoma typically occurring in the uterine corpus of women; however, rare cases have been reported in men. LGESS is characterized by recurrent gene fusions, with the most common being JAZF1::SUZ12. Extrauterine ESS is very rare, is often associated with endometriosis, and has been reported in diverse anatomic sites, including the vagina, ovary, and bowel wall, as well as pelvic and abdominal cavity. Herein, we report a case of a 69-year-old woman with a nonsignificant past medical history presenting with a 5.5-cm mesenteric mass. Her gynecologic evaluation was unremarkable. Surgical resection revealed a circumscribed, solid, tan-pink, lobulated mass within the omentum. We received the case in the consultation setting with a suggested diagnosis of mesenteric leiomyoma. Histologic sections showed a monotonous ovoid to spindle cell neoplasm growing in sheets and lobules separated by dense fibrous septa (Figure 2.118, A) with fine powdery chromatin and inconspicuous nucleoli (Figure 2.118, B) lacking significant mitotic activity. Background endometriosis was absent. Immunohistochemistry highlighted the tumor cells with CD10 and ER (Figure 2.118, C and D) with much more limited expression of desmin, whereas CD34, CD117, DOG1, STAT6, SMA, and HMB-45 were negative. Molecular analysis detected a JAZF1::SUZ12 gene fusion, supporting our diagnosis. This case emphasizes the importance of including LGESS in the differential diagnosis of monotonous spindle cell neoplasms in extrauterine sites. Finally, an IHC panel to include ER and CD10 as well as judicious application of molecular fusion analysis should resolve most problematic cases.

Hybrid Schwannoma/Neurofibroma: A Study of 2 Rare Cases

(Poster No. 119)

Hafiz A. Yahya, MD ([email protected]); Varsha Prakash, MD; Charles E. Middleton, MD; Youssef Al Hmada, MD. Department of Pathology, University of Mississippi Medical Center, Jackson.

Neurofibromas and schwannomas are common benign peripheral nerve sheath tumors. A hybrid tumor that contains characteristics of both neurofibroma and schwannoma has been rarely described. We present the clinical and pathologic findings of 2 such rare cases diagnosed at our institute over the previous 5 years. The first patient, a 62-year-old woman, presented with a 1.1-cm left dorsal hand mass of 2 years. The second patient, a 71-year-old man, presented with an enlarging 4.0-cm left intra-articular knee mass. Both patients underwent biopsies of the masses followed by their resection. The histology of both masses was similar, showing an encapsulated neoplasm with 2 morphologically distinct areas. The first area was composed of fascicles of bland spindle cells with elongated tapering nuclei and moderately abundant eosinophilic cytoplasm; the fascicles in this region showed multiple foci of nuclear palisading (Figure 2.119, A). The second area was composed of a population of elongated spindle cells with poorly defined, palely eosinophilic cytoplasmic processes and wavy hyperchromatic nuclei, admixed with a population of short spindle cells in a myxoid matrix (Figure 2.119, B). Immunohistochemistry showed that the neoplastic cells are immunopositive for S100 and SOX10 in both areas but immunonegative for CD34 in the first area (Figure 2.119, C), and immunopositive for CD34 in the second area (Figure 2.119, D). A diagnosis of hybrid schwannoma/neurofibroma was made. No recurrences were identified at the time of the 3-year postoperative follow-up visits in both patients.

Infantile Fibrosarcoma Harboring ETV6::NTRK3 Fusion Successfully Treated With Tropomyosin Kinase Inhibitor

(Poster No. 120)

Hans Magne Hamnvåg, MD ([email protected]); Yuanzhe Zhu, MBChB; Thanchanok Chaiprasit, MD; Dariusz Borys, MD. Department of Pathology and Laboratory Medicine, Loyola University Medical Center, Maywood, Illinois.

Our case involves a 11-day-old male infant with an infantile fibrosarcoma involving the right forearm. The tumor was subcutaneous, firm, and well circumscribed, and measured 5.0 × 3.2 × 2.5 cm. Magnetic resonance imaging (Figure 2.120, A and B) demonstrated that the tumor involved vital structures such as the brachial artery. The biopsy performed showed a cellular proliferation composed of monomorphic spindled cells forming intersection fascicles (Figure 2.120, C and D). The ETV6::NTRK3 fusion gene was detected by NTRK next-generation sequencing fusion panel. The association between infantile fibrosarcoma and the ETV6::NTRK3 gene fusion has been well established. The NTRK3 gene codes for tropomyosin receptor kinase C, influencing pathways essential for growth, proliferation, and survival. Recent studies show that the tumor responds well to the tropomyosin kinase inhibitor larotrectinib. Because of involvement of vital structures, surgery would have required amputation of the forearm. Therefore, a decision was made to attempt to shrink the tumor prior to resection using larotrectinib as neoadjuvant therapy. Five months after initiating therapy the mass had decreased significantly in size to 3.2 × 1.0 × 0.3 cm, and it was decided to continue treatment with larotrectinib and monitor the tumor until the patient could undergo surgery with minimal sacrifice of normal tissue. This case demonstrates the importance of performing molecular studies in cases of infantile fibrosarcoma, as it provides valuable information to further guide therapy. The detection of the ETV6::NTRK3 fusion gene will no longer be used only for diagnostic purposes but also to provide information to help with therapeutic decisions.

ESWR1-SMAD3–Positive Fibroblastic Tumor

(Poster No. 121)

Doaa Morrar, MD ([email protected]); Reham Al-Refai, MD; Ryan Des Jean, MD. Department of Pathology and Laboratory Medicine, Lenox Hill Hospital, New York, New York.

ESWR1-SMAD3–positive fibroblastic tumor (ESFT) is a fusion defined and recently described neoplasm. It usually presents as a painless tumor in the subcutaneous tissue of the lower extremities with foot predilection. It is considered benign but prone to local recurrence. To help understand this entity better, we report a case of ESWR1-SMAD3–positive fibroblastic tumor in a 31-year-old woman. The patient presented with metatarsal pain for 3 months. Magnetic resonance imaging demonstrated a mildly infiltrative mass (2.1 × 1.6 × 1.2 cm), located along the dorsal aspect of the first metatarsal and encasing the extensor hallucis brevis tendon. She underwent surgery for diagnosis and treatment. Histologic examination revealed an infiltrative tumor (Figure 2.121, A), composed of cellular, intersecting fascicles (Figure 2.121, B) of bland spindle-shaped tumor cells and minimal hyalinization. Tumor cells had elongated and focally wavy nuclei (Figure 2.121, C) with a moderate amount of eosinophilic cytoplasm. Focal calcifications were also identified (Figure 2.121, A). Tumor cells were negative for SMA, SOX10, CD31, and CD34 and demonstrated strong nuclear staining for ERG (Figure 2.121, D). Fluorescence in situ hybridization analysis showed EWSR1 gene rearrangement and positivity for EWSR1-SMAD3 gene fusion. She is now 3 years postsurgery without recurrence. Our case is consistent with prior case reports describing this entity. More importantly, it highlights the need to recognize ESFTs to prevent patients form receiving unnecessary treatment such as chemotherapy.

Primary Intraosseous Rosai-Dorfman Disease With BRAF V600E Mutation and Increased IgG4-Positive Plasma Cells

(Poster No. 122)

Lokman Cevik, MD1 ([email protected]); Swati Satturwar, MD1; Daniel Jones, MD, PhD1; Joel Mayerson, MD2; Steve Oghumu, PhD1; O. Hans Iwenofu, MD.1 Departments of 1Pathology and 2Orthopedic Surgery, The Ohio State University, Columbus.

Rosai-Dorfman disease (RDD) is a rare histiocytosis of unknown pathogenesis, most commonly presenting with nodal involvement. Increases in immunoglobulin (Ig) G4–positive plasma cells have been increasingly associated with RDD; however, the nature of that association remains controversial. Further, BRAF V600E mutation has been documented in only 1 case of nodal and central nervous system RDD. Primary intraosseous involvement in RDD is extremely rare. Herein, we report the first case of primary RDD of bone harboring BRAF V600E mutation. A 33-year-old woman presented with 3 months of progressive left medial knee pain. Radiographic studies showed a lytic lesion in the proximal/mid femur (Figure 2.122, A). Following 2 nondiagnostic CT-guided biopsies, complete curettage of the lesion revealed diffuse sheets of histocytes with emperipolesis (Figure 2.122, B) and associated benign-appearing lymphoplasmacytic infiltrate and fibrosis. By immunohistochemistry, the histiocytes were strongly and diffusely positive for CD163 and S-100 (Figure 2.122, C) and negative for CD1a, with increased IgG4-positive plasma cells (Figure 2.122, C, inset). BRAF V600E was detected by immunohistochemistry (Figure 2.122, D), pyrosequencing analysis, and amplicon-based next-generation sequencing. We report here a first case of primary intraosseous RDD with both increased IgG4 plasma cells and BRAF V600E mutation supporting a clonal neoplasm. Given the opportunity for use of BRAF-targeted inhibitors, if needed for disease control, routine molecular evaluation of histiocytic lesions with RDD features is warranted.

Retroperitoneal Inflammatory-Type Well-Differentiated Liposarcoma With Increased IgG4 Plasma Cells: An Unusual Phenotype Easily Mistaken for Other Hematolymphoid Entities

(Poster No. 123)

Lokman Cevik, MD ([email protected]); O. Hans Iwenofu, MD. Department of Pathology, The Ohio State University, Columbus.

Well-differentiated liposarcoma (WDLPS) is the most common type of liposarcoma with a locally aggressive and nonmetastasizing behavior. The histologic types, including lipoma-like, sclerosing, and inflammatory, can occur either purely or mixed, though these have not been shown to have any prognostic implications. However, the inflammatory type of WDLPS, because of preponderance of lymphoid tissue, are notoriously known to obscure critical diagnostic clues and lead to erroneous diagnoses. Increased IgG4 has been rarely reported with unknown significance. We report herein a case of inflammatory WDLPS with increased IgG4 plasma cells, mimicking sclerosing IgG4 disease. An 83-year-old woman presented with a past medical history of WDLPS, resected 11 years prior. She had been followed in surveillance screen until detection of a new 2-cm nodule in the retroperitoneum in 2021. A repeat scan 6 months later revealed progression of the disease to 3.9 cm. Histologic sections showed an obscuring lymphoid tissue admixed with scattered atypical hyperchromatic cells and lymphoplasmacytic inflammation (Figure 2.123, A and B). By immunohistochemistry, the scattered single atypical hyperchromatic cells were diffusely positive for p16 and mdm2 (Figure 2.123, C). The IgG4-positive plasma cells were increased (Figure 2.123, D). Fluorescence in situ hybridization for MDM2 amplification was positive, confirming the diagnosis of recurrent WDLPS. In summary, we report an unusual phenotype of WDLPS with obscuring lymphoid tissue, lymphoplasmacytic inflammation, and increased IgG4, initially suggesting an alternate hematolymphoid disease such as IgG4 sclerosing disease. However, careful examination for atypical hyperchromatic cells and unusual clinical context should prompt appropriate ancillary studies to evaluate for inflammatory variant of WDLPS.

Anastomosing Hemangioma Presenting as a Posterior Mediastinal Mass: A Case Report and Review of the Literature

(Poster No. 124)

Omar A. Abdelsadek, MD1 ([email protected]); Marika L. Forsythe, MD1; Payu A. Raval, MD1; Kritika Prasai, MD1; Seth Krantz, MD2; John V. Groth, MD.1 Departments of 1Pathology and 2Surgery, University of Chicago–NorthShore, Evanston, Illinois.

Anastomosing hemangioma is a benign vascular tumor that can mimic angiosarcoma. Since its original description of involvement of the genitourinary tract, additional sites of involvement including the testis, spermatic cord, ovary, adrenals, liver, colon, gastrointestinal tract, and soft tissue and bone, particularly in paraspinal locations, have been reported. We present a case of a 61-year-old man with past medical history of COVID pneumonia, with an incidentally identified 3.5-cm posterior mediastinal mass on computed tomography imaging (Figure 2.124, A), which abuts the left side of the descending thoracic aorta and straddles the fissure between the superior segment of the lower lobe and the posterior segment of the upper lobe. This mass was surgically excised and we received a cystic mass with attached rim of soft pink-red tissue with a variable yellow-tan and pink-tan cystic and solid cut surface. Microscopically, this lesion was vasoformative, with variably sized anastomosing vessels with intralesional adipose tissue imparting an infiltrative-like appearance (Figure 2.124, B and C), with areas of thrombosis and extramedullary hematopoiesis (Figure 2.124, D), without high-grade atypia, multilayering, or abundant mitosis. Immunohistochemical stains were performed and CD31, CD34, and ERG were positive, HHV8 was negative, and SMA highlighted perilesional cells. These findings are consistent with anastomosing hemangioma. This case adds to the literature through its posterior mediastinum soft tissue location and highlights the importance of considering anastomosing hemangioma at this site.

GLI1-Amplified Soft Tissue Sarcoma in a Pediatric Patient: Unique Molecular Findings in an Emerging Mesenchymal Neoplasm

(Poster No. 125)

Carla Saoud, MD ([email protected]); John Gross, MD. Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland.

GLI1-altered mesenchymal tumors are a recently described family unified by either GLI1 fusions involving various partners (most commonly ACTB, MALAT1,or PTCH1)or GLI1 gene amplifications. Currently, a varied clinical presentation, behavior, histologic, and immunophenotypic spectrum leads to significant diagnostic challenges. Histologically, most consist of bland ovoid-spindle to epithelioid cells growing in a nested or trabecular pattern within a variably myxohyaline stroma with intervening fibrous septa in a delicate capillary support network. The immunophenotype is often inconsistent, but reported cases have expressed varying degrees of S100, SMA, CD56, and STAT6 but lack SOX10. Herein, we report an 8-year-old girl with a 2.0-cm shoulder mass. Histologic evaluation revealed a cellular spindle cell neoplasm growing in intersecting fascicles with monotonous nuclei, smooth chromatin, and scattered mitotic activity (Figure 2.125, A and B). Immunohistochemistry showed strong expression of S100 (Figure 2.125, C) with a limited expression of CD56, SMA, and STAT6. SOX10 (Figure 2.125, D); CD34, collagen IV, and HMB-45 were negative. We suspected a GLI1-altered sarcoma. RNA sequencing failed to detect a GLI1 fusion; however, chromosomal microarray revealed multiple high-level gains/amplifications spanning 12p13.33q21.31, including KRAS, GLI1, and CDK4. This case emphasizes the importance of making the correct diagnosis of this rare and emerging mesenchymal neoplasm currently unified by GLI1 alterations. In the appropriate morphologic and immunophenotypic setting, judicious application of molecular sequencing, including both RNA fusion and DNA copy number analysis, can resolve most challenging cases. Finally, we believe our patient is possibly unique among GLI1-amplified sarcomas by showing high-level amplification of regional genes including KRAS.

Immunohistochemical Expression of H3.3G34W in a Series of Giant Cell Tumors of The Bone: A Single Institutional Study at a Tertiary Cancer Referral Center

(Poster No. 126)

Bharat Rekhi, MD, DNB, MIAC, MCAP(Affl) ([email protected]); Vinayak Dave, MBBS; Sonali Khetale, BSC, DMLT. Department of Surgical Pathology, Division of Molecular Pathology and Translational Medicine, Tata Memorial Hospital, Mumbai, India.

Context: Despite its classic histopathologic features, it can be challenging to differentiate giant cell tumor of the bone (GCTB) from its mimics. Lately, histone 3.3G34W has been identified as a useful immunostain. We evaluated H3.3G34W immunostaining in 67 GCTBs.

Design: Immunohistochemical staining for H3.3G34W (monoclonal, RM263, 1:100) was graded in terms of intensity (1+ to 3+) and the percentage of tumor cells showing nuclear staining. Seventy-one GCTBs (65.7%) occurred in patients 15–66 years old (average, 32; median, 9), in the femur (26; 36.6%), proximal tibia (11; 15.5%), distal radius (9; 12.6%), pelvis, including sacrum (8; 11.2%), and other bones (17; 23.9%), with a single multicentric tumor.

Results: Of 67 GCTBs, 55 (82.1%) showed positive staining in the mononuclear cells, including tumors with fibrous histiocytoma–like areas, sparing the osteoclast-like giant cells (Figure 2.126, A and B). The average percentage of tumor cells showing positive immunostaining was 69%, with 3+ staining intensity in 42 of 55 cases (76.4%) and 2+ in 13 GCTBs (23.6%). All 4 of 4 malignant GCTBs (100%) showed positive staining, including the mononuclear and pleomorphic/sarcomatous cells. Three cases (4.3%) developed metastasis (axillary nodes, mediastinum, and lung). All 3 of 3 metastatic GCTBs (100%) showed positive immunostaining in the metastatic lesions. Of 7 post–denosumab-treated GCTBs, 4 showed no residual giant cells and lacked H3.3G34W immunostaining. None of the other 37 “giant cell–rich” lesions displayed H3.3G34W immunostaining.

Conclusions: The diagnostic sensitivity of H3.3G34W for GCTB was 82.1% and specificity was 100%. This study, constituting one of the first reports from our country, further validates the value of H3.3G34W in differentiating GCTB, including metastatic and malignant GCTB, from its diagnostic mimics. Its utility in identifying residual tumor cells in post–denosumab-treated GCTBs is worth exploring.

Neuroectodermal Melanocytic Tumor in Infancy: Case Report of a Rare Tumor in the Differential Diagnosis of Small Round Blue Cell Tumors

(Poster No. 127)

Catalina Buriticá Cifuentes, MD1 ([email protected]); Javier A. Baena Del Valle, MD1; Juan C. López Takegami, MD1; Oscar E. Gonzalez, MD2; Sonia Bermudez Muñoz, MD3; Mauricio A. Palau Lázar, MD.1 Departments of 1Pathology, 2Pediatric Oncology, and 3Radiology, Fundacion Santa Fe de Bogota, Colombia.

A 7-month-old infant presented with vomiting and irritability and a history of a recent growing mass in the left frontotemporal side of the head, with no history of previous trauma. Relevant antecedents included a preterm birth with 32 weeks of a twin pregnancy. Physical examination revealed a frontal firm mass, without neurologic involvement or other physical abnormalities. A computed tomography scan of the skull showed a 5 × 3.5-cm expansile bone occupying lesion on the left parietotemporal region, with partial destruction of the orbit and alisphenoid (Figure 2.127, A). A thoracic radiography was normal and a PET scan of the skull was the only site of abnormal uptake. The patient went to tumor resection, and a gray tumor was found. Microscopy showed irregular infiltrating nests and cords surrounded by a fibrocollagenous stroma (Figure 2.127, B), with 2 types of cells, some of them epithelioid with melanocytic granular cytoplasmic pigment and others with small round hyperchromatic nuclei with scant cytoplasm (Figure 2.127, C). Only a few mitoses were identified and there was no necrosis. Immunohistochemistry showed cytokeratin AE1/AE3, CD99, synaptophysin, and HMB-45 (Figure 2.127, D). SOX10, S100, desmin, myogenin, and SATB-2 were negative. This rare tumor is found most often in infancy, with more than 90% presenting in the first year of life, and the predominant localization is craniofacial (skull, 11%). The differential diagnosis includes other small round blue cell tumors (eg, neuroblastoma, Ewing sarcoma, rhabdomyosarcoma) with different behavior and prognosis.

Proximal-Type Epithelioid Sarcoma: Report of a Challenging Case With Literature Review

(Poster No. 128)

Tiyana J. McCullough, BS ([email protected]); Ahmed S. Arfa, MD; Nivin Omar, MBChB; Pramila Moideen, MD; Michael Toscano, MD; Lakshmi K. Vemavarapu, MD; Suash J. Sharma, MD. Department of Pathology, Medical College of Georgia, Augusta.

Epithelioid sarcoma is a rare malignant mesenchymal neoplasm of adults (usually 20–40 years) with epithelioid histomorphology and immunophenotype, with characteristic SMARCB1/INI1 loss. It has 2 clinicopathologic subtypes: classic affects acral sites and has pseudogranulomatous histology, whereas proximal affects proximal/truncal areas and has nests/sheets of large epithelioid cells. Deep location, proximal type, older age, and nodal/distant spread are adverse prognostic factors. We report an 81-year-old man with history of bladder urothelial carcinoma, who presented with painful swelling of the left thigh. MRI demonstrated a large heterogeneous soft tissue mass of left upper thigh concerning for sarcoma. PET-CT showed a metabolically active thigh mass and left para-aortic and para-iliac lymph nodes, but no distant metastasis. Histopathology of core biopsy showed a poorly differentiated malignant neoplasm with areas of necrosis. The tumor was composed of loosely cohesive intermediate- to larger-sized cells, with amphophilic cytoplasm, illdefined cytoplasmic outline, moderately pleomorphic vesicular nuclei, and variably prominent nucleoli (Figure 2.128, A and B). There was high mitotic activity including atypical mitoses. Immunostains showed positivity for pan-keratin (diffusely, Figure 2.128, C), CD34 (majority, Figure 2.128, D), CK7 (subset), TTF-1 (focally, nuclear), and loss of INI1. In contrast, stains for Melan-A, S100, desmin, CD20, CD3, CK20, napsin A, synaptophysin-chromogranin, CDX-2, GATA-3, NKX3.1, P40, ERG, and CD31 were negative. The patient succumbed shortly thereafter. In summary, despite the patient's age, history of urothelial carcinoma, and aberrant TTF1 staining, the tumor histomorphology and immunophenotype on this biopsy, including coexpression of pankeratin and CD34 and loss of INI1, in the given clinical context, were diagnostic of proximal epithelioid sarcoma.

Dedifferentiated Leiomyosarcoma of the Uterus: Clinicopathologic Characteristics of a Series of 10 Cases

(Poster No. 129)

Carla Saoud, MD ([email protected]); John Gross, MD. Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland.

Context: There is no definitive consensus regarding the terminology of “dedifferentiated leiomyosarcoma” (DDLMS). Most authors accept DDLMS as a biphasic tumor showing a low-grade leiomyosarcoma associated with a high-grade sarcoma lacking morphologic or immunophenotypic features of myogenic differentiation.

Design: We performed a 5-year retrospective search of our archives for cases coded as “dedifferentiated leiomyosarcoma.” Available data regarding patient demographics, tumor site, and size were recorded. DNA NGS molecular analysis with 435 genes is currently underway in 5 cases.

Results: Ten cases were identified. The median age was 60 years (SD = 10.1; range, 43–76) and mean tumor size was 10.6 cm. Dedifferentiation occurred de novo in 9 cases, whereas 1 case presented as a metastatic retroperitoneal mass in a patient with a history of conventional leiomyosarcoma. All patients (except the one presenting with metastatic disease) underwent hysterectomy with salpingo-oophorectomies. All cases showed biphasic morphology with a conventional leiomyosarcoma juxtaposed with a secondary high-grade sarcoma. Four cases displayed high-grade undifferentiated pleomorphic sarcoma morphology, including 1 showing osteoclastic giant cell–rich pattern. The remaining 6 cases showed heterologous differentiation as follows: osteosarcoma (n = 2), pleomorphic liposarcoma (n = 2), combined osteosarcoma and liposarcoma (n = 1), and chondrosarcoma (n = 1). Of the 7 patients with follow-up, 2 died of disease, 4 were alive with metastatic disease, and 1 had no evidence of disease. The Table summarizes the clinicopathologic characteristics of the cases.

Conclusions: DDLMS of the uterus is a rare and aggressive disease that requires adequate sampling and careful histologic evaluation for a high-grade sarcomatous component.

A Rare Case of Myxoid Liposarcoma With Extensive “Lipoma-like” Changes in a Patient Without Previous Neoadjuvant Treatment

(Poster No. 130)

Zhengfan Xu, MD ([email protected]); Shannon Rodgers, DO; Christian Keller, MD; Kyle Perry, MD. Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, Michigan.

Myxoid liposarcoma is a malignant soft tissue neoplasm that typically consists of bland-appearing mesenchymal cells in the background of myxoid material, delicate branching capillaries, and lipoblasts. We present a case of a 22-year-old man who was experiencing hip pain over the previous year. MRI demonstrated a 13.4-cm mass in the left tensor fasciae latae muscle that was predominantly composed of fat and radiologically concerning for lipoma or atypical lipomatous tumor. During the procedure, the surgeon suspected the mass was composed of necrotic fat and excised a portion for diagnostic purposes. Histologically, the tumor was overwhelmingly composed of irregular adipocytes (Figure 2.130, A and B). In very focal areas of the tumor (less than 2%), there was increased capillary density, minimal myxoid material, and occasional lipoblasts (Figure 2.130, C and D). The tumor was negative for MDM2 gene amplification by FISH studies. Next-generation sequencing identified a FUS-DDIT3 fusion transcript. Although myxoid liposarcomas can exhibit increased areas of adipocytes following radiation therapy, it is extremely rare to encounter such extensive lipoma-like changes in an untreated tumor. If sampled by needle core biopsy, such a tumor could be easily misdiagnosed as a benign lipoma if only MDM2 gene status were assessed. Consequently, additional assessment of DDIT gene status could help avoid a potential diagnostic pitfall in adipocytic tumors with unusual intraoperative or imaging findings.

Primary Extraosseous Ewing Sarcoma of the Rectum: A Rare Clinical Presentation Mimicking a Prolapsed Hemorrhoid

(Poster No. 131)

Jessica L. Muldoon, MD1 ([email protected]); Rachel P. Kowal, MD2; Laura M. Warmke, MD.1 Departments of 1Pathology and 2Dermatopathology, Indiana University School of Medicine, Indianapolis.

Ewing sarcoma is a small round cell sarcoma that frequently presents as a malignant bone tumor in children and young adults. The diagnosis is often confirmed genetically, demonstrating the characteristic EWSR1-FLI1 fusion in approximately 85% of cases. Recently, rare extraosseous cases of primary cutaneous/superficial Ewing sarcoma have been described, frequently presenting in older patients with an indolent clinical course. A primary superficial Ewing sarcoma of the rectum is extremely rare, with only one molecularly confirmed case having been previously reported. Herein, we report the second confirmed case of a 38-year-old man who initially presented with rectal bleeding. Physical exam noted an ulcerated rectal polyp near the dentate line, which was initially presumed to be a prolapsed hemorrhoid. Biopsy of the lesion revealed a small round cell malignancy involving the subcutaneous tissue with necrosis and marked mitotic activity (Figure 2.131, A and B). Immunohistochemical studies showed that the tumor cells were positive for CD99 (diffuse, membranous) (Figure 2.131, C) and synaptophysin (weak, focal) (Figure 2.131, D), whereas they were essentially negative for CK AE1/AE3, CAM5.2, SOX10, S100 protein, CD45, INSM1, desmin, and myogenin. Next-generation sequencing revealed the pathognomonic EWSR1-FLI fusion, confirming the diagnosis of Ewing sarcoma. Subsequent imaging revealed no evidence of metastatic disease, and re-excision showed no residual tumor. Primary superficial Ewing sarcoma is extremely rare, and this is only the second molecularly confirmed case of rectal origin. Further studies are needed to better understand the clinical behavior of rare rectal and superficial Ewing sarcomas compared with their more common bone and deep soft tissue counterparts.

Histiocyte-Rich/Inflammatory Rhabdomyoblastic Tumor With Malignant Transformation and Metastasis to the Lungs

(Poster No. 132)

Guohua Liang, MB, PhD ([email protected]); Rumeal D. Whaley, MD; Shaoxiong Chen, MD, PhD. Department of Pathology, Indiana University School of Medicine, Indianapolis.

Histiocyte-rich/inflammatory rhabdomyoblastic tumor is a rare/emerging entity with 21 reported cases. The proposed classification is a tumor of intermediate malignancy. We present a new histiocyte-rich/inflammatory rhabdomyoblastic tumor with metastatic disease. A review of the literature reveals only one other case with metastatic disease. Our patient was a 52-year-old man who presented with right lower extremity pain. Imaging revealed a 12-cm enhancing mass in the right gluteus minimus and multiple pulmonary nodules. Lung nodule biopsy revealed sheets of atypical rhabdomyoblastic cells with enlarged and hyperchromatic nuclei. Mitotic activity was conspicuous with at least one atypical mitotic figure. The most striking feature was that the rhabdomyoblastic cells were bathed in the inflammatory infiltrate that consisted of histocytes and lymphocytes. Immunohistochemical stains revealed positive staining for desmin (diffuse), myoD1 (>50%), and myogenin (scattered cells). Chromosomal microarray revealed hypodiploid karyotype with retained copies of chromosomes 5 and 20. The gluteus minimus mass molecular profiling revealed a deletion in the NF1 gene (c.6277_6287del11) with an allele frequency of 32%. The morphology, immunophenotype, karyotype, and molecular data support the diagnosis of histiocyte-rich/inflammatory rhabdomyoblastic tumor with malignant transformation. The patient is currently undergoing chemotherapy. This case highlights the emerging entity of rhabdomyoblastic differentiation and is the second reported case with metastatic disease. It is important for practicing pathologists to be familiar with this entity. The morphologic clues can lead to the appropriate selection of ancillary testing to reach the correct diagnosis, which provides the best available information to medical oncologists for appropriate management.

Fifteen Years After Treatment for Multiple Gunshot Wounds: Is This a Soft Tissue Mass or Is It Thoracic Splenosis?

(Poster No. 133)

Lacey Durham, MD ([email protected]); Borislav A. Alexiev, MD; Farres Obeidin, MD. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Trauma to the abdominal cavity that includes disruption of the spleen can result in transplantation of splenic tissue to anatomic structures that are accessible at the time of injury. Successful autoimplantation promotes maturation of the splenic pulp into a functional unit capable of removing aged red blood cells from circulation. This phenomenon, referred to as splenosis, most commonly occurs in structures in the abdominal and pelvic cavities. Splenosis in the thoracic cavity is exceptionally rare and is known as thoracic splenosis (TS). TS can occur only if a concomitant tear in the diaphragm is sustained at the time of splenic disruption, allowing access to the thoracic cavity. Fewer than 100 cases of TS have been published, with lung/pleural nodules representing the majority of TS implantation sites. We present a 34-year-old man with a 15-year history of a slowly growing aggregate of 8 to 10 lateral chest wall subcutaneous nodules, first noticed after recovering from multiple gunshot wounds to the chest and abdomen. Physical exam revealed multiple nonmobile nodules, the largest of which was 1.6 cm, directly underlying scar from a prior chest tube insertion site. CT imaging was suggestive of a vascular lesion, lymph node, or soft tissue neoplasm, which led to surgical resection of the area. Histopathologic evaluation revealed multifocal heterotopic splenic tissue in the subcutaneous tissue associated with scar formation and suture granulomas, consistent with TS. This case highlights the importance of obtaining an accurate history, particularly with regard to prior trauma, in the diagnosis of TS.

Hybrid Schwannoma/Perineurioma: A Study of 2 Rare Cases

(Poster No. 134)

Varsha Prakash, MD ([email protected]); Hafiz A. Yahya, MD; Hansini Laharwani, MD; Youssef Al Hmada, MD. Department of Pathology, University of Mississippi Medical Center, Jackson.

Hybrid peripheral nerve sheath tumors are rare benign neoplasms that show combined features of more than one type of conventional benign peripheral nerve sheath tumor. The common hybrid tumors are schwannoma/perineurioma, neurofibroma/schwannoma, and neurofibroma/perineurioma. Hybrid schwannoma/perineurioma usually presents as a painless mass localized in the dermis or subcutaneous adipose tissue of young adults. Surgical excision is the treatment of choice. We are presenting 2 patients diagnosed with hybrid schwannoma/perineurioma at our institution over the last 5 years. The first patient was a 24-year-old woman with a 2.0-cm painless neck mass for 3 years, and the second patient was a 51-year-old woman with an 8.0-cm painless mass on her foot for 30 years. Both patients underwent biopsies of the masses followed by their resection. On microscopy, 2 populations of spindly cells arranged in vague storiform and fascicular patterns were noted. The first population had plump, tapering nuclei and palely eosinophilic cytoplasm with indistinct cell borders (Figure 2.134, A), whereas the second population had slender nuclei and delicate elongated bipolar cytoplasmic processes (Figure 2.134, B). No mitotic activity or necrosis was identified. On immunohistochemistry, one population showed diffuse and strong positivity for S100 (Figure 2.134, C), and negativity for claudin-1 (Figure 2.134, D), EMA, and CD34, whereas the second population showed scattered positivity for S100 (Figure 2.134, C), claudin-1 (Figure 2.134, D), EMA, and CD34. A diagnosis of hybrid schwannoma/perineuroma was made. No recurrences were identified in 1-year postresection follow-up in both patients.

Angiofibroma of Soft Tissue: A New Staghorn is in Town

(Poster No. 135)

Feifan Chen, MD ([email protected]); Kossivi Dantey, MD. Department of Pathology, Allegheny General Hospital, Pittsburgh, Pennsylvania.

Angiofibroma of soft tissue is a rare benign neoplasm of uniform bland spindle cells in a variably myxoid to collagenous stroma with prominent vascular networks. It recently has been recognized in the latest World Health Organization classification of tumors of soft tissue and bone (2020). It is a slow-growing painless mass that typically arises in the extremities; however, it may involve the trunk and pelvic cavity. Additionally, it can present as a superficial or deep lesion. We report a case of a 71-year-old woman who presented for a lump on her back that was painless and had been slowly growing for 3 months. The lesion measured 2.5 × 2.3 × 1.7 cm and was well circumscribed with a thin pink-white capsule and a tan-pink cut surface. Histologic sections demonstrated a well-circumscribed lesion with a fibrous capsule. There were areas of myxoid and collagenous stroma and extensive branching vasculature and perivascular hyalinization accompanied by focal infiltrates of chronic inflammation. The tumor cells were uniformly bland and spindled. Immunohistochemical stains were performed. The lesional cells were focally positive for epithelial membrane antigen (EMA) and negative for smooth muscle actin, CD34, desmin, STAT6, MUC4 and S100. Histologically, the branching vasculature may present as “staghorn” channels and there may be variably myxoid to collagenous stroma. The differential diagnosis is broad, depending on location and morphology, and correct diagnosis of a benign neoplasm is important. Awareness of this new officially recognized entity will help to avoid misdiagnosis.

MDM2-Negative High-Grade Osteosarcoma With Background Low-Grade Osteosarcoma in a Pregnant Woman With Rothmund-Thomson Syndrome

(Poster No. 136)

Raheel Rizwan, MD1 ([email protected]); Thomas R. Bowen, MD2; Shaobo Zhu, MD1; Jerad M. Gardner, MD.1 Departments of 1Clinical and Laboratory Pathology and 2Orthopedic Oncology, Geisinger Medical Center, Danville, Pennsylvania.

Rothmund-Thomson syndrome (RTS) is an autosomal-recessive genodermatosis with an increased risk for cancer, particularly osteosarcoma. A 20-year-old, 17 weeks pregnant woman with RTS and prothrombin mutation presented at an outside hospital with left elbow pain for 2 years since her left ulnar fracture, which had recently worsened. Imaging showed a 5-cm mixed sclerotic and lytic mass within the olecranon and proximal ulna suggestive of an aggressive lesion like chondrosarcoma or degeneration of osteosarcoma with chondroid components. An image-guided needle biopsy was interpreted as fibrous dysplasia (immunostaining positive for SATB2, negative for MDM2). The pain continued to worsen, for which curettage of the lytic lesion with cementing was performed, which showed similar pathologic findings. Later, the patient delivered a term baby and was discharged without complications. She was then referred to our hospital, where the previous curettage specimen was reported as low-grade central osteosarcoma (grade 1). Fluorescent in situ hybridization for USP6 rearrangement and MDM2 amplification were negative. Wide excision was performed, which showed low-grade osteosarcoma (Figure 2.136, A) as well as hypercellular fascicular zones with marked pleomorphism and many atypical mitotic figures representing high-grade osteosarcoma (Figure 2.136, C and D). Soft tissue invasion was present (Figure 2.136, D) with negative resection margins. Low-grade osteosarcomas often have MDM2 amplification, as do high-grade osteosarcomas arising from them. The negative MDM2 here may represent an alternative non-MDM2 molecular pathway related to RTS.

Multifocal Spindle Cell Hemangioma With Background Benign Vascular Malformation: CD34 Immunostaining Pattern Is Important to Recognize

(Poster No. 137)

Raheel Rizwan, MD ([email protected]); Jerad M. Gardner, MD. Department of Clinical and Laboratory Pathology, Geisinger Medical Center, Danville, Pennsylvania.

Spindle cell hemangioma (SCH) is a rare tumor that often occurs in distal extremities and can resemble Kaposi sarcoma. A 65-year-old man with a history of multiple right forearm masses since adolescence (sebaceous cysts or benign vascular tumors) now presented with 2 soft tissue masses on the dorsal right hand since a few years ago: one over the third metacarpal base and the other over the fifth metacarpal neck. Both masses were approximately 1 cm and were compressible but refilled, and neither transilluminated. Both masses were surgically removed. On microscope, both masses demonstrated a multinodular vascular lesion having abnormal blood-filled cavernous spaces with organizing thrombosis without calcification. Between these spaces, there were cellular zones with spindle and epithelioid endothelial cells with thin intervening vascular lumina. Focal endothelial vacuolation was present (Figure 2.137, A). Immunostaining was positive for ERG and CD31 (Figure 2.137, B and C) and negative for HHV8 in the spindle and epithelioid endothelial cells and the endothelial cells lining the cavernous spaces. CD34 highlighted the cavernous endothelial lining but was mostly negative in the spindle and epithelioid cellular zone, showing only weak focal staining in thin vascular lumina and the vacuolated cells (Figure 2.137, D). These findings were diagnostic of SCH. In this case, the SCH had a background suggestive of benign vascular malformation. Immunohistochemistry is usually not needed for diagnosis, but if used, it is important for pathologists to be aware that the cellular zones of SCH may lack CD34 expression, as that could incorrectly deviate a pathologist away from vascular neoplasia.

Pediatric Ovarian Immature Teratoma Presenting With Metastasis: Touch Preparation Cytology Findings

(Poster No. 138)

Juanita E. Ferreira, MD ([email protected]); Dana Richards, MD; Julie Dueber, MD. Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington.

Immature teratomas (IT) are tumors characterized histologically by immature neuroepithelial tissue including immature stroma, premature neural tubes, or immature rosettes. Although teratomas comprise the most common histologic subtype of ovarian germ cell tumors, immature teratomas of the ovary are rare, representing less than 1% of all ovarian teratomas. Furthermore, these tumors are rarely seen in cytologic preparations. We report findings from touch preparation cytology of a 15-year-old adolescent girl who presented with diffuse abdominal pain, intraabdominal fullness, nausea, and vomiting, and was found to have an ovarian mass and peritoneal carcinomatosis on MRI imaging. Her α-fetoprotein (AFP) level was increased at 6597 ng/mL (reference range, <10 ng/mL) with other tumor markers within normal range. Initial core biopsy touch preparations from the ovarian mass showed mature teratomatous elements including mature squamous elements and ciliated respiratory epithelium during rapid on-site evaluation (Figure 2.138, A and B). Given that the findings did not explain the patient's peritoneal carcinomatosis, the pathologist urged further sampling from other sites, and the omentum and peritoneum were biopsied. Eventually, immature teratomatous elements and an undifferentiated component were obtained, which helped to explain the clinical presentation. The undifferentiated component appeared distinct morphologically with crowded groups of hyperchromatic epithelioid cells with scant cytoplasm (Figure 2.138, C), whereas the focal immature neural component was composed primarily of small blue cells in a fine fibrillary background (Figure 2.138, D). This case highlights the utility of rapid on-site evaluation for assessment and diagnosis of gynecologic nonseminomatous germ cell tumors, and the unique cytologic findings of these cases.

A Rare Case of Parotid Sebaceous Lymphadenoma Diagnosed by Fine-Needle Aspiration Biopsy

(Poster No. 139)

Negin Shafizadeh, MD ([email protected]); Jianhong Zhou, MD; Aylin Simsir, MD. Department of Pathology, NYU Langone, New York, New York.

Sebaceous lymphadenoma is an unusual benign salivary gland neoplasm that mainly occurs in parotid gland and rarely transforms to carcinoma. Preoperative diagnosis of this tumor is challenging because of unfamiliarity with its cytologic features. Also, presence of squamoid/oncocytic epithelium and lymphocytes leads pathologists to consider other diagnoses, including intraparotid lymph node, Warthin tumor, pleomorphic adenoma, low-grade mucoepidermoid carcinoma, and metastatic carcinoma in a lymph node. The majority of cases are diagnosed on excisional specimen. We describe a case in which a definitive diagnosis was made on fine-needle aspiration biopsy (FNAB). A 66-year-old man presented with an incidental parotid mass detected on a brain MRI performed for memory loss. The mass was described as a 2.1 × 2.0-cm circumscribed homogeneous lesion in the superficial aspect of the left parotid gland (Figure 2.139, A). Cytology smears from FNAB of the mass revealed cohesive, 3-dimensional aggregates of squamoid epithelial cells, often with cytoplasmic vacuoles characteristic of sebaceous differentiation and multinucleated giant cells distributed in a polymorphous lymphoid background (Figure 2.139, B and C). A diagnosis of sebaceous lymphadenoma was made on FNAB and was confirmed on left superficial parotidectomy. On histology, the tumor was lymphoid follicles with germinal centers admixed with squamoid and sebaceous epithelium (Figure 2.139, D) with no mitosis, necrosis, or atypia. Sebaceous lymphadenoma should be considered in the differential diagnosis of a solitary parotid mass when faced with a lymphoid-rich epithelial proliferation on FNAB. Recognition of its cytologic features will allow the patient to receive the appropriate surgical treatment based on FNAB.

Diagnostic Accuracy of the Papanicolaou Society of Cytopathology Guidelines in Pancreatic Fine-Needle Aspiration Cytology

(Poster No. 140)

Zaid Khreefa, MD ([email protected]); Jihuan Chen, MD; Jonathan Somma, MD; Maryam Sadough, MD; Ritu Bhalla, MD. Department of Pathology, Louisiana State University Health Science Center, New Orleans.

Context: Fine-needle aspiration cytology (FNAC) is the mainstay of pancreatic malignancy diagnosis and a structured, 6-tiered reporting system, the Papanicolaou Society of Cytopathology (PSC) Pancreaticobiliary Guidelines, was recently developed to optimize reporting and clinical management: nondiagnostic (I), negative (II), atypical (III), neoplastic (benign or other) (IV), suspicious (V), and positive (VI).

Design: In order to assess the accuracy of this system in predicting high-grade malignancy, we retrospectively evaluated 222 patients who underwent pancreatic FNAC in our institution from 2013 to 2021 and determined outcomes by histologic and/or clinical follow-up. We combined the patients into 2 groups for statistical analysis: categories I–IV (those with no evidence of high-grade malignancy on FNAC) and categories V–VI (suspected or definite high-grade malignancy). The risk of malignancy is compared between the 2 groups and correlated with serum CA19-9 level and survival time.

Results: The sensitivity, specificity, positive predictive value, and negative predictive value were 95%, 97%, 97%, and 94%, respectively, with an absolute risk of malignancy of 97% in the high-grade malignancy group versus 5% in the other group. Other significant findings included both higher mean levels of serum CA19-9 in the high-grade group and a shorter survival time (26.4 months) with a hazard ratio of 5.3 (2.6–10.7) versus 0.2 (0.1–0.4) (Table).

Conclusions: Our study corroborates that the PSC guidelines in pancreatic FNAC are sensitive and specific for predicting high-grade malignancy; grouping of categories V and VI provides maximal predictive values. The system hence proves to be a reliable tool for guiding management.

SMARCA4-Deficient Undifferentiated Tumor: An Uncommon, Diagnostically Challenging Entity on Cytology

(Poster No. 141)

Mohammad M. Al-Attar, MD ([email protected]); Xiaoqin Zhu, MD, PhD. Department of Pathology, University of Massachusetts, Worcester.

Thoracic SMARCA4-deficient undifferentiated tumor is a rare, highly aggressive, malignant neoplasm with frequent metastases at initial presentation. It is a diagnostic challenge with a wide range of differential diagnoses, often requiring extensive workup. Cytologic diagnosis of this entity is exceedingly challenging because of the often-limited tissue material available for ancillary studies. We report a case of a 54-year-old man, a former smoker (25 pack-years) presenting with back pain, persistent cough, and hypercalcemia. Chest CT scan revealed mediastinal lymphadenopathy and multiple irregular left upper lobe nodules. Additional imaging studies revealed multiple lytic and blastic lesions in the pelvic girdle and spine, a pathologic L3 fracture, bilateral adrenal nodules, and evidence of peritoneal carcinomatosis. Fine-needle aspiration of the left paratracheal lymph node (4L) revealed a poorly differentiated malignant epithelioid neoplasm composed of dyscohseive epithelioid tumor cells with a moderate amount of cytoplasm, eccentrically placed round to oval nuclei, and prominent nucleoli (Figure 2.141, A: smear; Figure 2.141, B: H&E, cell block). Some cells showed rhabdoid features. Frequent mitoses and tumor necrosis were present. A panel of immunohistochemical studies was performed to characterize the tumor cells. Hematopoietic malignancies, melanoma, germ cell, and neuroendocrine tumors were ruled out. Rare cells were positive for pancytokeratin (Figure 2.141, C), CD34, and SALL4. SMARCA4 immunostain was negative in the neoplastic cells (Figure 2.141, D). SMARCA4-deficient undifferentiated tumor needs to be distinguished from SMARCA4-deficient lung carcinoma and other tumors. In addition to ancillary studies, the specific cytomorphologic features and clinical history are the key and aid in the diagnosis of this uncommon entity.

Diagnostic Accuracy of Endoscopic Ultrasound-Guided Fine-Needle Aspiration Cytology of Subepithelial Gastrointestinal Lesions: A 10-Year Retrospective Single-Institution Analysis

(Poster No. 142)

Omer Saeed, MD; Hector Mesa, MD; Harvey Cramer, MD; Katrina Collins, MD ([email protected]). Department of Pathology, Indiana University, Indianapolis.

Context: The aim of this study is to evaluate both the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUSFNA) in diagnosing gastrointestinal (GI) subepithelial lesions and the concordance rate with endoscopic core needle biopsies (E-CNB) and resection.

Design: All patients who underwent EUS-FNA of upper and lower GI subepithelial lesions over a 10-year period (2010 to 2019) were retrospectively reviewed. The medical records of all patients were reviewed, and data were analyzed from endoscopy, pathology, and surgical reports.

Results: In total, 284 patients with ages ranging from 21 to 92 years underwent upper GI EUS-FNA for subepithelial lesions. Of these, 159 (56%) were women and 125 (44%) were men. There were 112 patients (39%) with concurrent E-CNB, and 85 (30%) had surgical resection. EUS-FNA was obtained from the stomach in 169 patients (60%), duodenum in 51 (18%), esophagus in 38 (13%), and colon in 26 (9%). The originating layers of the lesions on EUS were the muscularis propria in 36% of the lesions, submucosa in 26%, deep mucosa in 8.1%, and not specified in 21.5%. The concordance between EUS-FNA and E-CNB was fair (κ = 0.597, P < .001). In the cases where resection was performed, sensitivity and specificity for EUS-FNA and biopsy were 81% versus 37% and 77% versus 100%, respectively.

Conclusions: EUS-FNA is more sensitive than CNB for diagnosing GI subepithelial lesions with a modest concordance with surgical biopsy.

Papanicolaou Smear Volume and Provider Specimen Submission Metrics in the COVID-19 Pandemic: A Retrospective Review of Quality Control Data at a Single Institution

(Poster No. 143)

Steven Capen, MD ([email protected]); Cynthia N. Giraldo, MD; Grant Williams, MD; Melissa Van Dellen, MD. Department of Pathology, San Antonio Uniformed Services Health Education Consortium, San Antonio, Texas.

Context: Primary care visits and cervical cancer screenings were disrupted by the COVID-19 pandemic, leading clinicians to perform and submit fewer Papanicolaou smears.

Design: Papanicolaou smear quality control data at a large military health care facility between June 2018 and December 2021 were retrospectively reviewed. Trends in these data in the immediate postpandemic period (April 2020–September 2020) and late postpandemic period (October 2020–December 2021) were compared with the baseline prepandemic period (June 2018–February 2020) using 2-tailed t tests.

Results: Papanicolaou smear volume in the immediate postpandemic period decreased from 5290 to 2898 cases/mo compared with the prepandemic period. Volume in the late postpandemic period recovered to near-baseline levels at 4924 cases/mo. Unsatisfactory rate and percentage of specimens without endocervical sampling increased in the immediate and late postpandemic period compared with the prepandemic period. These results are summarized in the Table with P values compared with baseline in parentheses.

Conclusions: As Papanicolaou smear volume decreased in the immediate postpandemic period, an increasing number of specimens were determined to be unsatisfactory or without endocervical sampling. Surprisingly, these trends appear to have continued into the late postpandemic period. Clinicians should be aware of the potential negative impacts of the COVID-19 pandemic on cervical cancer screening and, if necessary, implement measures to ensure adequate sampling.

Targeted Next-Generation Sequencing Analysis of 2 Undifferentiated Carcinomas With Osteoclast-like Giant Cells of the Pancreas

(Poster No. 144)

Byungjoon Chae, MD1 ([email protected]); Nfn Kiran, MD1; Joel Lanceta, MD, PhD1; Youssef El Douaihy, MD2; Basem N. Azab, MD3; Sheriff Andrawes, MD4; Guo-Xia Tong, MD, PhD.5 Departments of 1Pathology, 2Medicine, 3Surgical Oncology, 4Endoscopy, and 5Cytopathology, Staten Island University Hospital, Staten Island, New York.

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas (UC-OGC) is a rare tumor with unique morphology. Data of its cytogenetic alterations are sparse because of its rarity. Here we report the findings of targeted next-generation sequencing (NGS) analysis of 2 UC-OGCs. Fine-needle aspiration (FNA) was performed on a 4.3- and a 7-cm pancreatic mass from a 44-year-old man and a 78-year-old man, respectively. Immunohistochemistry and NGS analysis by FoundationOneCDx (F1CDx) were performed on cell block material. Both cases showed scattered single/small clusters of atypical epithelioid cells, many osteoclast-like giant cells, and few mitoses. The epithelioid cells were focally positive for AE1/3 or CAM 5.2; the osteoclast-like giant cells were positive for CD68 and CD45; one case had positive p53 staining; both cases had increased Ki-67 index (~10%). The diagnosis was UC-OGC for both cases. No surgery was performed because of their comorbidities. F1CDx showed KRAS (G12A or G12V) and TP53 (Y220C or W91fs*55) mutations in both cases, one with additional CDKN2A (H83Y) and KDM6A (R1279*), changes commonly associated with pancreatic ductal carcinomas (PDC). In addition, MED12 mutations (R4420Q or Q2119_Q2120insHQQQ) were identified in both cases and 7 other new mutations were detected once in these cases. Detection of KRAS and TP53 mutations further supports UC-OGC as a variant of PDC and may be used for confirmation of cytologic diagnosis. MED12 mutations have been recently identified in other tumors. Recurrent detection of MED12 mutations in UC-OGC warrants further evaluation of its roles in this unique tumor.

Gastroesophageal Junction Adenocarcinoma With Enteroblastic Differentiation Presenting as Liver Metastasis From an Unknown Primary

(Poster No. 145)

Juanita E. Ferreira, MD ([email protected]); Emmy Mbagwu, MD; Eun Y. Lee, MD; Nathan R. Shelman, MD; Derek B. Allison, MD. Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington.

Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare and underrecognized aggressive malignancy that resembles fetal gut epithelium, secretes α-fetoprotein (AFP), and expresses the oncofetal proteins SALL4 and glypican-3, as well as CDX2, which is a transcription factor important in intestinal embryonic development. This tumor may present a diagnostic challenge, especially in the setting of an unknown primary, because of the immature-appearing morphology and AFP production. We report a case of gastroesophageal junction adenocarcinoma with enteroblastic differentiation in a 57-year-old man who presented for consultation with AFP levels elevated at 1897 ng/mL (reference range, <10 ng/mL) in the setting of multifocal hypointense liver lesions on abdominal CT. CT-guided core biopsy touch preparations of the liver lesions showed 3-dimensional clusters of pleomorphic tumor cells (Figure 2.145, A). On H&E, the neoplastic cells showed focal tubulopapillary architecture composed of columnar cells with clear cytoplasm and prominent nucleoli (Figure 2.145, B). Tumor cells were positive for SALL4 (Figure 2.145, C), CDX-2, and glypican-3 by immunohistochemical staining. Given the histologic and immunophenotypic overlap between GAED and a glandular yolk sac tumor, endoscopic evaluation of the gastrointestinal tract and testicular imaging were recommended. A commercial assay classified the tumor as germ cell in origin with 90% probability; however, subsequent follow-up revealed a gastroesophageal junction ulcer that proved to be adenocarcinoma with identical features as the liver sample (Figure 2.145, D). Next-generation sequencing revealed somatic mutations in TP53 and CDKN2A. This case highlights the morphologic features of GAED and the diagnostic challenge it presents.

Mucoepidermoid Carcinoma With Warthin-like Features: Cytology Features With H&E Correlation

(Poster No. 146)

Kapitolina Semenova, MD ([email protected]); Di Lu, MD; Mahra Nourbakhsh, MD; Behdokht Nowroozizadeh, MD. Department of Pathology and Laboratory Medicine, University of California, Orange.

Mucoepidermoid carcinoma is the most common malignant neoplasm of salivary glands in adults and children. Mucoepidermoid carcinoma with Warthin-like features is one of the low-grade morphologic variants that was recently described. Our abstract describes a clinical presentation, cytologic features, and correlation with H&E of the resection specimen of the Warthin-like variant of mucoepidermoid carcinoma. A 75-year-old nonsmoking Asian woman presented with a complex 4.9 × 1.5 × 1.2-cm partially cystic right neck mass at neck levels II–III. On imaging, the mass was attached to the right submandibular gland. FNA biopsy of the mass showed a moderately cellular smear with intermediate-sized squamous cells of low-grade atypia and few mucinous cells (Figure 2.146, A and B). The background demonstrated a mucinous background with macrophages and large numbers of lymphocytes. Cytologic findings were most compatible with low-grade mucoepidermoid carcinoma; however, other considerations included Warthin tumor and mucinous cystadenoma. FISH testing revealed MAML2 rearrangement that further supported a diagnosis of mucoepidermoid carcinoma. The patient was subsequently managed with dissection of neck levels I–III. Two of 4 lymph nodes of neck levels I–II showed metastatic carcinoma with Warthin-like morphology (Figure 2.146, C and D) and extranodal extension. It is important to distinguish Warthin-like variant of mucoepidermoid carcinoma from Warthin and other tumors because of differential prognoses and treatment courses. Cytologic findings such as the presence of admixed squamous and mucinous cells on a background of dense lymphocytes, paired with MALM2 FISH testing, may help to make the appropriate diagnosis based on cytologic evaluation.

Urine Cytology Findings in Cases of Pseudocarcinomatous Urothelial Hyperplasia of the Bladder Often Represent a Diagnostic Challenge

(Poster No. 147)

Nicolas Millan, MD1 ([email protected]); Jaylou Velez Torres, MD2; Merce Jorda, MD2; Oleksandr Kryvenko, MD.2 1Department of Pathology and Laboratory Medicine, Jackson Memorial Hospital/University of Miami Hospital Miller School of Medicine, Miami, Florida; 2Department of Pathology and Laboratory Medicine, University of Miami Hospital Miller School of Medicine, Miami, Florida.

Context: In tissue specimens, pseudocarcinomatous urothelial hyperplasia (PCUH) has architectural and cytologic features that mimic cancer. The urine cytology features of PCUH have not been previously described. Here, we report its features in urine cytology and potential diagnostic challenges.

Design: We reviewed urine cytology cases with concurrent PCUH tissue specimens. The Paris System criteria were used to assess each case. The clinical data were obtained from medical records.

Results: We identified 39 cases (31 men; 8 women) with a mean age of 67. All patients had prior pelvic irradiation and most patients presented with hematuria (n = 27). Original interpretations were negative for high-grade urothelial carcinoma (HGUC) (n = 28), atypical urothelial cells (AUC; n = 10), and HGUC (n = 1). Twenty-five urine cases (64%) had findings consistent with PCUH. These specimens were moderately cellular and composed of sheets or isolated urothelial cells. The nuclei were round with minimal nuclear membrane irregularity. The chromatin was vesicular, glassy, and rarely hyperchromatic. Nuclear grooves and nucleoli were identified in the majority. The cytoplasm was dense to finely vacuolated. N:C ratio <0.5 was present in 14 cases (56%), and N:C ratio >0.5 was seen in 11 cases (44%). All cases originally interpreted as AUC and HGUC had PCUH features.

Conclusions: The cytomorphologic features of PCUH in urine specimens can have overlapping features with AUC, HGUC, and other malignancies. Forty-four percent of the cases with PCUH were initially misclassified. Therefore, recognition of the key cytologic features of PCUH is important to avoid overcalling reactive changes.

Core Needle Biopsy of Skeletal Lesions: Diagnostic Accuracy

(Poster No. 148)

Lester J. Layfield, MD ([email protected]); Liangli Wang, MD; Magda Esebua, MD. Department of Pathology, University of Missouri, Columbia.

Context: Appropriate biopsy of musculoskeletal lesions is of paramount importance for diagnosis and successful treatment. Traditionally, biopsies were excisional with relatively large tissue available for analysis. More recently, core needle biopsies have become a popular alternative. We studied a series of core needle biopsies of skeletal lesions to determine diagnostic accuracy.

Design: Following institutional review board approval, the records were searched for all skeletal core needle biopsies obtained between January 1, 2015, and December 31, 2020. Only cases with subsequent surgical pathology specimens were included in the study.

Results: During the study period, 207 core needle biopsies were performed, and 86 had subsequent surgical specimens. generally represented by curetting or resection specimens. Sixty-four specimens were obtained from primary bone lesions, and 22 were obtained from metastases. Eleven major discrepancies (17%) were found between core biopsy diagnoses and subsequent surgical diagnoses. with an additional 5 minor discrepancies (8%). There were 22 core biopsies of metastases, of which 4 (18%) were associated with major diagnostic errors.

Conclusions: Open biopsy of skeletal lesions had been considered the optimal diagnostic technique, but even this method has been shown to have major diagnostic issues in approximately 15% of biopsies. Early studies of core needle biopsies revealed a 78% to 85% accuracy in separating benign from malignant lesions, but diagnosis of specific types of neoplasms was less accurate. Our study reveals a diagnostic accuracy similar to that seen in older studies. No difference in rates of diagnostic accuracy was seen for primary or metastatic lesions.

Two Cases of Rare Lingual Thyroid Diagnosed by Fine-Needle Aspiration

(Poster No. 149)

Fei Chen, MD, PhD ([email protected]); Thaira Oweity, MD; Negin Shafizadeh, MD. Department of Pathology, New York University Langone Health, New York City, New York.

Lingual thyroid is a rare embryogenic abnormality that results from failure of thyroid migration from the foramen cecum to the pretracheal region. Dysphonia, dysphagia, and upper airway obstruction can occur in advanced cases. Because of the location and rarity of the condition, it is commonly misdiagnosed as abnormal lymph node or soft tissue mass by imaging. Here we report 2 cases of lingual thyroid diagnosed by fine-needle aspiration (FNA). The 2 cases are male patients aged 28 and 69 years old. The first patient was found to have a mass in the floor of the mouth in brain MRI obtained during workup for COVID-19 symptoms. It was described as a multilobular and well-defined mass with a cystic component extending to the base of the tongue, similar to the ultrasound findings during FNA (Figure 2.149). The second patient was known to have a stable submental mass for years. MRI reported an enhancing structure within the floor of the mouth without invasion into surrounding structures. In both cases, MRI revealed a lacking thyroid gland in its regular anatomic location. Ultrasound-guided FNA was performed in each patient, showing benign thyroid follicular cells in the colloid background and macrophages consistent with ectopic thyroid tissue (Figure 2.149). One patient underwent surgical removal of the mass, which was confirmed to be benign thyroid tissue. Our observation of these 2 patients suggests that the ultrasound-guided FNA provides an accurate diagnosis for lingual thyroid and potentially avoids unnecessary surgical removal of the patient's sole thyroid tissue.

Diagnostic Utility of Rapid On-Site Evaluation Using Tissue Smears in Core Needle Biopsies of Renal Lesions

(Poster No. 150)

Seyed Amin Hojat, MD1 ([email protected]); Nakul Ravish, MD2; Zhongbo Yang, MD.1 1Department of Pathology and Laboratory Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York; 2Department of Pathology and Laboratory Medicine, University of Buffalo, New York.

Context: The role of core needle biopsy (CNB) of renal lesions for diagnosis has been expanded in recent years. Rapid on-site evaluation (ROSE) during the procedure improves diagnostic yield of CNBs and helps triage the samples. The aim of this study is to evaluate the utility of ROSE in tissue biopsies of kidney in our institute.

Design: All cases of kidney CNBs with available ROSE interpretations between 2018 and 2021 were retrieved from the pathology database. ROSE interpretations were compared with final diagnosis of CNBs, and the concordance rate was calculated accordingly.

Results: A total of 142 cases were identified, including 60.5% males and 39.5% females. The average size of the lesions was 4.1 cm (1.2–13 cm). A majority of cases (90.1%) had more definitive diagnosis on the CNBs, including renal cell carcinomas (68.3%), oncocytic neoplasms (13.3%), urothelial carcinomas (2.8%), metastatic carcinomas (2.1%), lymphomas (2.1%), melanoma (0.7%), and spindle cell neoplasm (0.7%). The remaining cases included suspicious for renal cell carcinoma (0.7%), atypical cells (0.7%), benign renal tissue (6.3%), and nondiagnostic (2.1%). ROSE interpretations were adequate in 85.2% and inadequate in 14.8% of cases. The average number of passes to reach adequate samples was 2 (1–4). The overall concordance rate between ROSE and the final CNB diagnosis was 86%.

Conclusions: In our study we found a relatively high concordance rate (86%) between ROSE interpretation and final diagnosis on CNBs of renal masses. This indicates that ROSE evaluation of renal tissue core biopsies is helpful to ensure the adequate diagnostic material is obtained.

Cytologic Features of Desmoplastic Small Round Cell Tumor in Pleural Fluid

(Poster No. 151)

Pierre Tran, BA1 ([email protected]); Catherine A. Gonsalves, MD2; Jacquelyn A. Knapik, MD2; Marino E. Leon, MD.2 1Department of Pathology, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California; 2Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville.

Desmoplastic small round cell tumor (DSRCT) is a rare malignant mesenchymal neoplasm with poor prognosis that affects children and young adults with a male predominance and a characteristic EWSR1-WT1 gene fusion. A 21-year-old woman presented with worsening abdominal pain and a palpable abdominal mass. Abdominal/pelvic computed tomography (CT) revealed a cystic mass arising from the pelvis, and a solid mass arising from the vagina and endometrial cavity. The patient underwent bilateral salpingo-oophorectomy and omentectomy, showing DSRCT with EWSR1-WT1 fusion. After surgery, a positron emission tomography–computed tomography (PET/CT) revealed hypermetabolic lymph nodes in the subcarinal space and retroperitoneum suspicious for metastases. The patient was treated with vincristine, doxorubicin, and cyclophosphamide combined with ifosfamide and etoposide. After 1 year and 14 chemotherapy cycles, PET/CT showed no signs of metastases or recurrence. On second-look surgery, DSRCT was found involving the pelvis, bladder, and round ligament. Radioimmunotherapy was initiated and completed without complications. At 2 and 4 years after her initial surgery, endobronchial ultrasound–guided needle aspirations of mediastinal lymph nodes indicated DSRCT relapse. Five years after initial presentation, a pleural effusion was encountered; the cytologic material displayed cells in clusters and linear arrangements with high nuclear to cytoplasmic ratios, round to oval nuclei with homogeneous chromatin, and minimal nuclear irregularities. These cells were desmin positive and calretinin negative (Figure 2.151, A through D). The patient succumbed 1 month later. This case report aims to draw attention to the cytologic features of fluid involvement by DSRCT, adding to the body of knowledge.

Ovarian Fine-Needle Aspiration Cytology: Performance Characteristics and Histologic Follow-up

(Poster No. 152)

Alexis S. Calderon, MD ([email protected]); Gulisa Turashvili, MD, PhD; Daniel Lubin, MD; Krisztina Hanley, MD. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia.

Context: Fine-needle aspiration cytology (FNAC) can be performed for intraoperative or diagnostic evaluation of ovarian cystic lesions, with high specificity but variable sensitivity in prior studies. We report our institutional experience with ovarian FNAC.

Design: The departmental database was searched between January 2010 and January 2021 for ovarian FNAC samples, with available concurrent or follow-up surgical pathology specimens. FNAC and surgical diagnoses were compared. Cases without paired surgical specimens were excluded.

Results: The patients' median age was 37 years (18–84). A total of 172 ovarian FNACs met the study criteria, including 133 (77.3%) reported as “negative for malignant cells” (group A), 14 (8.1%) as “atypical cells present” (group B), 2 (1.2%) as “suspicious for neoplasia” (group C), 2 (1.2%) as “neoplastic cells present” (group D), 4 (2.3%) as “malignant cells present” (group E) and 17 (9.9%) as “nondiagnostic” (group F). Cytohistologic correlation revealed that the rate of borderline or malignant diagnosis was 0.8% (1 of 133) for benign FNAC, 7.1% (1 of 14) for atypical FNAC, 100% (2 of 2) for suspicious FNAC, and 100% (4 of 4) for malignant FNAC (Table). The common causes of cytohistologic discrepancies included lack or paucity of lesional cells, obscuring cyst contents, and degenerative atypia of the epithelial cells. Overall, ovarian FNAC had 75% sensitivity and 100% specificity, with positive predictive value of 1.00 and negative predictive value of 0.99.

Conclusions: Our findings confirm high specificity and suboptimal sensitivity for ovarian FNAC. FNAC is a useful “rule-out” diagnostic and therapeutic modality for cystic ovarian lesions, especially in young patients who desire fertility preservation.

Large Pelvic Histiocytic Sarcoma in a Patient With Presumed Transformed Chronic Lymphocytic Leukemia

(Poster No. 153)

Adeyinka O. Akinsanya, MBBS ([email protected]); Hector Mesa, MD, PhD; Nishi Dave, MD; Harvey Cramer, MD. Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis.

Histiocytic sarcoma (HS) is an extremely rare, highly aggressive hematopoietic neoplasm showing histiocytic differentiation. A subset of HS has been shown to represent transdifferentiation of low-grade lymphomas and chronic myeloid neoplasms. A 74-year-old woman with a history of chronic lymphocytic leukemia and multiple comorbidities presented with acute onset diffuse abdominal pain and constipation. Imaging studies revealed a 9-cm pelvic mass causing partial small bowel obstruction and widespread bulky lymphadenopathy suggestive of Richter transformation. A computed tomography–guided fine-needle aspiration of the pelvic mass showed discohesive large pleomorphic cells with abundant cytoplasm (Figure 2.153, A and B). An extensive immunohistochemical workup on the cell block showed that the tumor cells were positive for CD68, CD163 (Figure 2.153, C and D), lysozyme, CD4, CD10, CD45, BCL6, and vimentin, and negative for CD1a, Langerin, CD21, FXIIIA, and other hematolymphoid, epithelial, melanocytic, and mesenchymal markers. The immunomorphologic findings were diagnostic of histiocytic sarcoma. The patient's clinical condition deteriorated rapidly; she was transitioned to comfort care and passed away shortly after. HS comprises <1% of all hematopoietic neoplasms. Currently available immunophenotypic markers allow its consistent diagnosis and separation from other hematopoietic malignancies. Advances in molecular genetic techniques have shown that a subset of HS is clonally related to other hematolymphoid neoplasms, most commonly B-cell neoplasms, representing a high-grade transformation with transdifferentiation, resulting in aggressive clinical course and poor response to therapy. Clonality studies were not performed in this case because the information would not have resulted in added benefit for patient care.

Melanotic Medullary Thyroid Carcinoma: Case Report and Literature Review

(Poster No. 154)

Katarzyna Brzezinska, MD1; Swati Bhardwaj, MBBS, MD1 (swati. [email protected]); Jihong Sun, MD1; Qiusheng Si, MD, PhD1; Marita S. Teng, MD2; Maureen F. Zakowski, MD1; William H. Westra, MD1; Arnold H. Szporn, MD.1 Departments of 1Pathology and 2Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York.

Melanotic medullary thyroid carcinoma is morphologically defined by the presence of melanin deposits in the cytoplasm of tumor cells. It is an extremely rare variant, with only 15 cases described in the literature to date and only 1 report of diagnosis by fine-needle aspiration biopsy. A 51-year-old woman presented with neck swelling. An ultrasound examination revealed a single solid nodule in the right thyroid lobe that measured 5.4 × 4.7 × 4.3 cm. Laboratory examination revealed elevated levels of serum calcitonin (8643.0 pg/mL), carcinoembryonic antigen (86.2 ng/mL), and chromogranin A (123.2 ng/mL). A fine-needle aspiration biopsy of the thyroid nodule revealed predominantly single plasmacytoid cells with round to oval eccentric nuclei and dark brown intracytoplasmic granules (Figure 2.154, A). Immunohistochemical studies with Melan-A performed on a cell block slide confirmed that the granules contained melanin (Figure 2.154, B). The tumor cells were also positive for calcitonin, CEA, synaptophysin, AE1/AE3, and CAM5.2; the tumor cells were negative for chromogranin, thyroglobulin, PAX8, and TTF-1. The diagnosis was reported as melanotic variant of medullary thyroid carcinoma. The patient underwent a total thyroidectomy that revealed tumor cell expression of insulinoma-associated protein 1 and confirmed neuroendocrine differentiation (Figure 2.154, C and D). A short time later she presented with tumor recurrence. The tumor cells were positive for S100, SOX10, and Melan-A. Molecular analysis with the SEMA4 Solid Tumor Panel revealed mutations in the HRAS, PIK3CA, PIK3R1, MYC, and CCND3 genes. The diagnosis was reported as melanocytic medullary thyroid carcinoma with high-grade transformation and loss of epithelial and neuroendocrine expression.

Diagnostic Accuracy of Large Cell Neuroendocrine Carcinoma of Lung on Fine-Needle Aspiration and Exfoliative Cytology: An Institutional Review of a Challenging Diagnosis

(Poster No. 155)

Agha Wajdan Baqir, MD ([email protected]); Samer Khader, MD; Sigfred Lajara, MD. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Context: Large cell neuroendocrine carcinoma (LCNEC) of the lung is an uncommon entity and the diagnosis can be difficult on cytology, which may lead to underdiagnosis. The aim of this study was to evaluate the diagnostic accuracy of LCNECs diagnosed on FNA and exfoliative cytology specimens.

Design: Our database was queried for FNA and exfoliative cytology cases with diagnosis or consideration for LCNEC with corresponding surgical pathology (SP), tissue biopsy, or resection specimens for a period of 24 years. Demographic data, site of specimen, cytology, and SP diagnoses were recorded. The accuracy was determined as concordance of cytologic and histologic diagnoses.

Results: Among the 56 cytology cases, 48 (86%) were FNAs, and 8 (14%) were exfoliative specimens. Thirty-five cases (63%) were from the lung, and 21 (37%) represented metastatic tumors. The cases were diagnosed as LCNEC (66%), combined small cell lung carcinoma (SCLC) and LCNEC (21%), and “cannot exclude LCNEC” (13%). Thirty LCNEC cytology cases (81%) were concordant with SP, and 11 (92%) with combined features showed a LCNEC component on histology. Four of the “cannot exclude LCNEC” cases (57%) showed LCNEC component on SP. Overall, 45 of 56 cases (80%) showed an LCNEC component on the corresponding surgical specimens (Table). The discordant cases included poorly differentiated squamous cell carcinoma, SCLC, adenocarcinoma with neuroendocrine features, carcinosarcoma, and necrosis only.

Conclusions: The diagnosis of LCNEC can be made with good accuracy, and a LCNEC component (in combined cases) can be detected in cytology specimens. Discordant cases highlight the possibility of sampling bias, as well as the importance of considering other differential diagnoses when faced with a high-grade tumor with neuroendocrine features.

Early Experience With the Use of p16/Ki-67 Dual Stain on ThinPrep Cervical Cytology Specimens

(Poster No. 156)

Taylor Bronson, MD ([email protected]); Bonnie Choy, MD; Natasha Sichula, CT(ASCP); Ritu Nayar, MD. Department of Pathology, Northwestern University, Chicago, Illinois.

Context: When using p16/Ki-67 dual stain (DS) on ThinPrep cervical cytology specimens, coexpression of p16 and Ki-67 in the same cell indicates transforming human papillomavirus (HPV) infection and a higher risk of precancer (high-grade squamous intraepithelial lesion/adenocarcinoma in situ [HSIL/AIS]). In 2020 the Food and Drug Administration approved DS for triage of women 25–65 years old who had either a positive primary high-risk HPV screen or NILM/HPV-positive cotest. We share our experience as one of the earliest US laboratories to evaluate DS in house.

Design: We stained and evaluated 168 ThinPrep HPV-positive cases using DS. A cytotechnologist, cytopathology fellow, and cytopathologist blindly and independently evaluated each DS slide as “positive” or “negative” and provided a semiquantitative estimate of the number of DS-positive cells. Clinical follow-up was collected.

Results: The overall concordance rate between the investigators during independent review was 79%. Cases without complete consensus (35) were reviewed by all 3 investigators simultaneously and consensus attained. Forty-eight cases (29%) were DS positive and 6 (4%) were unsatisfactory. A total of 96 cases (57%) had follow-up colposcopic biopsies, of which 24 were precancer (HSIL/AIS) and 2 were squamous cell carcinoma. Among precancer cases, DS was positive (19), negative (4), and unsatisfactory (1). DS was positive in both invasive carcinoma cases. Overall DS sensitivity for precancer/cancer was 84%, and specificity was 62% (Table).

Conclusions: Interpretation of DS positivity showed good interobserver concordance, which generally increased with the number of DS-positive cells. Attaining group consensus was useful in equivocal cases. DS sensitivity and specificity was similar to that previously reported in the literature.

Fine-Needle Aspiration as a Powerful Modality to Detect Malakoplakia of Soft Tissue

(Poster No. 157)

Iryna Mazur, MD ([email protected]); Nirag Jhala, MD; Aileen Grace P. Arriola, MD. Department of Pathology, Temple University Health System, Philadelphia, Pennsylvania.

Malakoplakia is a chronic granulomatous inflammatory disease of infectious etiology. It is most frequently noted in the organs in the abdominal cavity. Malakoplakia involving soft tissue is, however, very rare. We present here an unusual case of soft tissue malakoplakia that clinically presented as metastatic carcinoma. A 69-year-old woman with a history of renal transplant and breast carcinoma presented with a 13-cm painful ulcerated mass on the upper left thigh. CT scan showed soft tissue mass with necrosis invading into the muscle. Metastatic carcinoma was suspected. Fine-needle aspiration (FNA) with concurrent needle core biopsy of the mass was performed. FNA revealed large granular macrophages (von Hansemann cells), and chronic inflammation, which suggested malakoplakia. Concurrent core biopsy revealed von Hansemann cells as well as laminated calcium structures (Michaelis-Gutmann bodies) that were confirmed by von Kossa stain (Figure 2.157, A through C, cell block, von Kossa, H&E). CD68 stain was positive in macrophages. A review of literature from the past 5 years shows that most reported cases are from the GI tract (27%), genitourinary tract (24%), and skin (17%). Reports of the involvement of soft tissue are very rare (pelvis, neck, 0.99%). This case highlights that soft tissue malakoplakia is rare and can be detected by relatively noninvasive but powerful modalities like FNA and needle core biopsies. Involvement of soft tissues by malakoplakia may occur in a setting of immunosuppression.

Cytologic Features of Ovarian Immature Teratoma in Peritoneal Fluid

(Poster No. 158)

Christina Maldonado, BS1 ([email protected]); Catherine A. Gonsalves, MD2; Zehra Ordulu Sahin, MD2; Marino E. Leon, MD.2 1Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa; 2Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville.

Immature teratomas (ITs) are rare malignant neoplasms. They typically present in young women and have a more prominent fleshy-solid component than mature cystic teratomas. Metastases are rare, with the majority being reported in the liver, lungs, and brain. We describe the cytologic features of an immature teratoma of the ovary involving the peritoneal fluid. A 22-year-old woman presented with a large pelvic mass, mesenteric involvement, and large-volume ascites. A 20-cm right ovarian mass was resected; the pathologic examination showed a 17.2-cm high-grade IT with neuroectodermal tubules and rosettes having primitive cells with scant cytoplasm, hyperchromatic nuclei, and frequent mitoses. The pelvic peritoneum and cul-de-sac were also involved by IT. On immunohistochemical stains, the tumor cells expressed SALL4; rare cells showed staining with CD117, CD30, and glypican-3; these cells were negative for PLAP and OCT-4. The concurrent peritoneal fluid cytology specimen (6000 mL) showed rosettes and tridimensional clusters of cells with clear delicate vacuolated cytoplasm and clear nuclei with folding, grooves, and moderate irregular outlines expressing SALL4, consistent with IT (Figure 2.158, A through D). At 5 months follow-up, a recurrent ascites cytology specimen showed rare clusters of atypical cells with similar features to those seen in the prior cytologic material. These cells were positive for synaptophysin and glypican-3 but negative for SALL4 and CD117. This material was interpreted as suspicious for high-grade IT. A concurrent omental biopsy showed metastatic IT. The cytologic features of IT in this patient are highlighted.

Enteric-Type Adenocarcinoma Arising in a Tubulovillous Adenoma of the Bladder: A Case Report With Emphasis on the Urine Cytologic Features

(Poster No. 159)

Javier A. Baena-Del Valle, MD1 ([email protected]); Daniela Silva-Rodriguez, CT2; Adolfo Serrano-Acevedo, MD3; Paula A. Rodriguez-Urrego, MD2; Mauricio A. Palau-Lázaro, MD.2 1Department of Pathology and Laboratory Medicine, School of Medicine, Fundacion Santa Fe de Bogota University Hospital, Universidad de Los Andes, Bogota, Colombia; Departments of 2Pathology and Laboratory Medicine and 3Surgery, Section of Urology, Fundacion Santa Fe de Bogota University Hospital, Bogota, Colombia.

Primary adenocarcinomas of the urinary bladder are rare (<2% of primary carcinomas), and even more so are the nonurachal enteric subtypes. These are usually associated with intestinal metaplasia, intestinal-type cystitis glandularis, and villous adenoma. Diagnosis in urine cytology specimens is very challenging because of the morphologic confusion with other benign and malignant glandular lesions. We present a 62-year-old woman with macroscopic hematuria; 3 serially voided urine cytology specimens showed clusters of columnar cells with elongated, stratified, and hyperchromatic nuclei (Figure 2.159, A), and focal pleomorphism (Figure 2.159, B). Cells were positive for CDX-2. Urothelial cells were normal. A cystoscopy showed a 4-cm papillary tumor in the bladder dome and a transurethral resection was performed. Microscopy revealed a tubulopapillary neoplasm composed by columnar epithelial cells with pencillate nuclei intermixed with few goblet cells (Figure 2.159, C). Dysplasia ranged from low to high grade, with areas of invasive adenocarcinoma, with no muscular invasion (Figure 2.159, D). Tumor cells were diffusely positive for CK20, CDX-2, and SATB-2, focally positive for CK7, and negative for PAX8, GATA-3, and p63. β-catenin showed a membranous staining pattern. Subsequent colonoscopy and gynecologic examination were conducted to rule out secondary involvement. This case highlights the importance of having a high level of suspicion when glandular cells are identified in urine cytology. Precursor lesions could be very deceiving and simulate benign conditions with glandular differentiation and intestinal meta-plasia. Features like nuclear stratification, hyperchromasia, and pleomorphism are clues to consider tubular/villous adenoma and adenocarcinoma in the differential diagnosis, leading to prompt detection and treatment.

Tenosynovitis With Psammomatous Calcification: A First Case in the Cytology Literature of This Rare Pseudotumor

(Poster No. 160)

Shannon Rodgers, DO ([email protected]); Swetha Gaddam, MD; Sameer Chhetri Aryal, MD; Christian Keller, MD; Kyle Perry, MD. Department of Pathology, Henry Ford Hospital, Detroit, Michigan.

Tenosynovitis with psammomatous calcification is an extremely rare condition. It is a benign pseudotumor that has been associated with repetitive trauma. We present a 16-year-old adolescent girl, a competitive cheerleader (associated with repetitive midfoot strain), who presented with right foot pain and swelling of the first metatarsophalangeal joint for several months. She had no history of hyperphosphatemia. After being unresponsive to conservative treatments, surgical intervention was undertaken, which showed a firm granulomatous mass surrounded by gouty tophi. The granulomatous tissue mass protruded and white chalky material was removed and sent entirely for cytologic evaluation. A liquid-based cytospin and cell block were prepared. Cytospin demonstrated numerous laminated calcified psammoma bodies (Figure 2.160, A and B). On cell block, psammomatous calcifications are noted in a background of fibroblasts, histiocytes, and lymphocytes (Figure 2.160, C and D). Bacterial cultures revealed no growth with a negative Gram stain. A diagnosis of tenosynovitis with psammomatous calcification was made. Very few cases of this entity have been reported in the literature previously, and to our knowledge, this is the first case that has been diagnosed on a cytologic preparation. This benign condition should be considered in the differential diagnosis of fine-needle aspirates from para-articular soft tissue masses. Furthermore, psammomatous calcifications on liquid cytologic preparations appear hyperchromatic, and can be confused for malignant cells, indicating a potential diagnostic pitfall.

Ocular Lymphoma: A Clinicocytopathologic Analysis of 17 Cases Over a 10-Year Period

(Poster No. 161)

Azadeh Samiei, MD ([email protected]); Mehdi Nassiri, MD; Harvey M. Cramer, MD. Department of Pathology, Indiana University School of Medicine, Indianapolis.

Context: Vitreous fluid cytology constitutes a miniscule proportion of nongynecologic cytology cases. In this study, we examine the clinical and cytopathologic findings in 17 cases of vitreous fluid cytology obtained from patients evaluated for suspected ocular lymphoma.

Design: A computerized search from 2012 through 2021 was performed to identify all vitreous cytology cases at our institution in which a diagnosis of ocular lymphoma was either established or considered in the cytomorphologic differential diagnosis. The reports were reviewed together with the cytology slides and flow cytometry. The clinical findings on presentation and treatment were reviewed in relation to the cytologic diagnoses.

Results: Of 132 vitreous fluid cytology cases over a 10-year period, 17 were sent for evaluation of possible ocular lymphoma. All patients presented with decreased visual acuity, mostly due to viteritis (67%) or uveitis (20%). Of the 17 cases, there were 11 lymphomas (65%), 3 were negative, 2 were hypocellular, and 1 had abnormal flow cytometry findings. The 11 lymphomas (65%) included 7 large B-cell lymphomas (64%), 2 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (18%), and 2 B-cell lymphomas NOS (18%). Of the 11 lymphoma patients, 6 received chemotherapy (55%), 2 radiotherapy (18%), and 1 chemoradiation therapy (9%). Treatment of 2 lymphoma patients (18%) was not documented.

Conclusions: Vitreous cytomorphology in combination with flow cytometry is an effective method for diagnosing intraocular lymphomas and is accepted by physicians as a basis for initiating treatment in these patients.

Experience Using Whole Slide Imaging for Digitization of Cytology Education Slides

(Poster No. 162)

Gloria H. Sura, MD ([email protected]); James V. Doan, DO; Michael J. Thrall, MD. Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas.

Context: Many institutions have cytopathology case archives for education. These slides deteriorate and have limited accessibility. Whole slide imaging (WSI) can overcome these limitations. However, suboptimal image quality and scanning effort are barriers.

Design: We selected 123 cases from cytopathology study sets for WSI scanning at ×400 magnification without z-stacking. The Ventana DP 200 scanner and Virtuoso software were used. Slides were scanned in 2 rounds, one with light cleaning of slides and a second round after thorough cleaning for slides with low WSI quality. Slides were assessed with the grading system shown in the Table. Time to scan each slide was recorded.

Results: A total of 96 slides scanned within the first round (78%) were determined to be acceptable quality, with 45.5% of slides being “excellent.” Twenty-seven slides in the first round of scanning were categorized as “poor” or “acceptable” (22%); these were rescanned. After the second round of scanning, only 3.3% remained “poor” or “acceptable.” The average time needed to scan each slide was 213 seconds.

Conclusions: The majority of slides scanned were of good quality in the first round of scanning. After cleaning and rescanning, nearly every case investigated was of acceptable quality. The primary objective is to provide a benchmark for other institutions that may be considering a similar project so that they know what to expect in terms of slide scan success rate and the amount of time needed to digitize slides. This pilot study demonstrates the feasibility of using WSI for cytology education cases.

Cytopathologic Diagnosis of Idiopathic Fibrosing Pancreatitis in a Pediatric Patient

(Poster No. 163)

Robert Propst, DO ([email protected]); Andrea Shields, MD; Jeremy Deisch, MD; Camilla Cobb, MD; Nikhil Ravi Thiruvengadam, MD; Anwar Raza, MD. Department of Pathology, Loma Linda University Medical Center, Loma Linda, California.

Idiopathic fibrosing pancreatitis (IFP) is a rare cause of pancreatitis in children. An 11-year-old obese boy presented to the emergency department with a 3-day history of pruritus and jaundice. Workup showed a total bilirubin of 26.8 and gallbladder distension. Endoscopic ultrasound showed signs of chronic pancreatitis. Choledocolithiasis was suspected, and he underwent endoscopic retrograde cholangiopan-creatography (ERCP), which revealed intrapancreatic biliary stricture with upstream dilatation. He underwent common bile duct (CBD) stent placement, with CBD brushings and fine-needle aspiration (FNA) of the pancreatic head. CBD brushings were unremarkable; pancreatic head FNA revealed scattered epithelial cells and fibrous stromal tissue fragments. (Figure 2.163, A). A diagnosis of IFP was suggested to the clinician. Follow-up imaging a week later revealed persistent distal CBD stricture and a 1.4-cm lesion of the pancreatic head, concerning for tumor. A repeat FNA of the pancreatic head revealed a fibroinflammatory lesion with stromal fragments (Figure 2.163, B). The cell block showed stromal fibrosis surrounding entrapped pancreatic ducts with rare lymphocytes (Figure 2.163, C and D). Plasma cells were not appreciated in the aspirate. Based on imaging and cytomorphologic findings, a diagnosis of IFP was favored. Subsequent IgG4 and hereditary pancreatitis panel testing in this patient have been normal. Since discharge, the patient has been doing well, is anicteric, and is being followed up by interval imaging and ERCP studies. This is the first reported case of IFP diagnosed through cytopathology and highlights the importance of having an index of suspicion for IFP in cases of pediatric cholestasis with a pancreatic mass.

Metastatic Cutaneous Angiosarcoma Involving Bilateral Pleural Effusions: A Rare Case Presentation

(Poster No. 164)

Fouad El-Dana, MD ([email protected]); Hanna Siatecka, MD; Bettye Cox, MD. Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas.

Primary cutaneous angiosarcoma accounts for more than half of all reported cases of angiosarcoma, with an overall 5-year survival rate ranging from 30% to 50%. Local recurrence and distant metastasis via hematogenous spread to lungs, liver, and lymph nodes are common. We report an unusual case of a 92-year-old man with a history of cutaneous angiosarcoma of the face with metastases to the lung, mediastinal, thoracic, and abdominal lymph nodes. He presented to the emergency room for evaluation of shortness of breath and hypoxia. Chest X-ray revealed bilateral pleural effusions. Ultrasound-guided thoracocentesis was performed and right and left pleural fluids were sent for cytologic evaluation. The right and left pleural fluids had similar findings; the specimens were composed of atypical epithelioid cells with eccentrically located nuclei, irregular nuclear contours, and abundant eosinophilic cytoplasm. CD31, ERG, and CD34 immunohistochemical stains were performed, and the atypical cells were positive for ERG and CD31. Scattered atypical cells stained positive for CD34. These findings were interpreted as metastatic angiosarcoma involving the right and left pleural fluids. While cutaneous angiosarcoma is known to metastasize to the lung and lymph nodes, the presence of angiosarcoma in pleural effusion specimens evaluated by cytology represents less than 1% of malignant effusions sent for pathologic evaluation. Clinical history and judicious use of immunohistochemistry are paramount to establish the appropriate diagnosis of sarcomas to rare sites such as pleural fluids.

Metastatic Salivary Duct Carcinoma of the Submandibular Gland Into the Pleural Fluid

(Poster No. 165)

Sandra Haddad, MD ([email protected]); Irem Kilic, MD; Khin Su Mon, MD; Swati Mehrotra, MD; Vijayalakshmi Ananthanarayanan, MD; Güliz A. Barkan, MD; Mohammed Atieh, DO, MS. Department of Pathology, Loyola University Medical Center, Maywood, Illinois.

Salivary duct carcinoma is a relatively rare, aggressive tumor with a poor prognosis and high rate of lymph node/distant metastasis at initial presentation, commonly seen in the elderly population with a male predominance. The most common site is the parotid gland, followed by the submandibular gland. The lung is the most common site for metastasis. In addition, there have been 3 cases of salivary duct carcinoma with metastasis to pleural fluid reported. We present a case of a 78-year-old man who presented to the ER with worsening shortness of breath and a past medical history of chronic respiratory failure. His imaging studies showed left-sided pleural effusion, multiple lung nodules, and mediastinal lymphadenopathy. A thoracentesis was performed, and a ThinPrep slide of the pleural fluid showed a cellular specimen exhibiting pleomorphic enlarged cells with vacuolated cytoplasm and high N:C ratio with prominent nucleoli and background lymphocytes. The tumor cells were present as dispersed single cells and clusters (Figure 2.165, A). The cell block section revealed glandular structures with occasional cribriforming in the lacunae (Figure 2.165, B). Immunohistochemical stains were performed, and the tumor cells were positive for pan-cytokeratin, CK7, HER2/neu (Figure 2.165, C), AR (Figure 2.165, D), GCDFP-15, and GATA-3 (weakly), while being negative for D2-40, calretinin, CK20, TTF-1, napsin A, NKX3.1, p40, and CDX2. Further clinical workup showed a tan-white ulcer in the buccal mucosa with biopsy revealing a high-grade adenocarcinoma infiltrating the submucosa with comedo-type necrosis. Taken together, the morphology and immunoprofile were consistent with a salivary duct carcinoma with pleural fluid metastasis.

A Single-Institution Experience of Atypical Glandular Cells in Cervical Papanicolaou Smears: Focus on Cytologic Features Differentiating Squamous and Glandular Lesions

(Poster No. 166)

Yinan Hua, MD, PhD ([email protected]); Lina Liu, MD; Bing Leng, MD, PhD. Department of Pathology, Baylor Scott and White Health, Texas A&M, Temple.

Context: This study is to correlate atypical glandular cell (AGC) diagnoses with follow-up histologic diagnoses, with a focus on finding the cytologic features to differentiate squamous and glandular lesions on smears.

Design: A retrospective search identified cervical cytology results interpreted as AGC. Cytopathology-histology correlation was performed. Papanicolaou (Pap) smears from patients with AGC interpretations and histology evidence of high-grade squamous intraepithelial lesion (HSIL) were reviewed.

Results: During a 5-year period, 395 Pap smears were interpreted as AGC (0.25% of all cases) in our institute. Eighty-five on follow-up histology were diagnosed with adenocarcinoma in situ (25.76%), 48 were HSIL (14.55%), and 196 were negative for malignancy (59.39%). HPV-16, HPV-18, and high-risk HPV were positive in 26 (9.39%), 23 (7.93%), and 56 patients (20.97%), respectively. Within the adenocarcinoma in situ group, infection rate was higher for HPV-18 than HPV-16 (57.89% versus 36.84%). In contrast, infection rates were similar for HPV-16 and HPV-18 (29.73% versus 21.62%) in HSIL patients. Thirty-six of 40 AGC smears with HSIL on follow-up histology had hyperchromatic cell clusters. The majority of them showed loss of polarity, lack of feathering, cell overlapping, anisonucleosis, increased N:C ratio, irregular nuclear membrane, and coarse chromatin. Elongated or elongated-to-oval cells were seen in 52% of smears. Oval or oval-to-elongated cells were seen in 48% of smears. Granular cytoplasm showed in 11 smears. Dense or dense-to-granular cytoplasm showed in 19 smears. Thirty-four of 40 cases (85%) turned out to be HSIL with glandular extension.

Conclusions: HPV-18 infection rate is higher than HPV-16 infection rate in adenocarcinoma in situ patients. HSIL cells extending to endocervical glands mimic AGCs on Pap smears.

Cardiac Sarcoidosis in Transplanted Heart

(Poster No. 167)

Lakshmisree Akhila Vemulakonda, MBBS ([email protected]); Fouzia Shakil, MD. Department of Pathology, Westchester Medical Center, Valhalla, New York.

Sarcoidosis is a systemic nonnecrotizing granulomatous disease of unknown etiology characterized by multiorgan involvement. Only 5% to 10% of patients with sarcoidosis show cardiac involvement. We present a case of cardiac sarcoidosis that recurred in an allograft heart 15 days after transplantation. A 45-year-old woman with past medical history of asthma and Lyme disease complicated by Bell palsy presented with complaints of shortness of breath, nonproductive cough, and chest pain for a few weeks. Cardiac catheterization showed elevated right heart pressures and pulmonary capillary wedge pressure with normal coronary arteries. CT of the thorax without contrast showed a markedly dilated left ventricle with extensive symmetric mediastinal and bilateral hilar lymphadenopathy. Endomyocardial biopsy revealed well-formed nonnecrotizing granulomas in the myocardium. Infectious etiology was ruled out by negative acid-fast bacilli (AFB), Grocott-Gomori methenamine silver (GMS) and periodic acid–Schiff (PAS) stains. Heart transplantation was performed, and the heart explant showed the same pathologic findings as the previous biopsy. During her postoperative visit 15 days after transplantation, the patient complained of dyspnea on exertion. The endomyocardial biopsy of the allograft right ventricle showed nonnecrotizing granulomatous inflammation in vessels and myocardium (Figure 2.167, A through C) along with mild acute cellular rejection, and was negative for AFB, GMS, and PAS stains. With the concern of return of sarcoidosis in the transplanted heart, the patient was started on steroids. Subsequent endomyocardial biopsies showed mild acute cellular rejection with no features of granulomatous inflammation. This is a rare case showing recurrence of sarcoidosis in transplanted heart of short duration.

An Unusual Case of Staphylococcus Epidermidis Aortic Valve Endocarditis

(Poster No. 168)

Alok K. Sinha, MD1 ([email protected]); Christopher Hauch, MD.2 1Department of Pathology, East Tennessee State University, Johnson City; 2Department of Pathology, William L. Jenkins Forensic Center, Johnson City, Tennessee.

Infectious endocarditis is a known complication of intravenous drug use. Most cases are due to Staphylococcus aureus, and the tricuspid valve is usually involved. We present a case of a 32-year-old man with a history of intravenous drug use who was found unresponsive in his residence. He was taken to the hospital, where testing revealed an intracerebral hemorrhage, ST-segment elevation myocardial infarction, and pneumonia. He died despite treatment. Significant autopsy findings included aortic valve and left coronary artery ostium vegetations, thrombosis of the left anterior descending coronary artery, acute myocardial infarct involving the left ventricle, pulmonary edema with patchy consolidation, and a splenic abscess. Sectioning of the brain revealed a large intracerebral hemorrhage centered in the left basal ganglia with extension into the left frontal, temporal, and parietal lobes. Organizing infarcts were also noted within the right frontal lobe and insular cortex. Microscopic examination revealed aortic valve vegetations with bacterial clusters, neutrophilic vasculitis involving the brain and left anterior descending coronary artery, acute myocardial infarction, and acute bronchopneumonia. Intravascular bacterial clusters were found in all examined sections, and immunohistochemical staining confirmed the presence of staphylococcus epidermidis. Toxicology performed on antemortem blood detected methamphetamine/amphetamine. The cause of death was complications of infectious endocarditis, with the toxic effects of methamphetamine contributing to death. The manner of death was ruled an accident. The unique features of this case include a nontypical causative agent (S epidermidis) and valve involvement, as well as devastating multi-organ sequelae of septic emboli.

Twin Reversed Arterial Perfusion Syndrome With Pericentric Inversion of Chromosome 5

(Poster No. 169)

Xulei Liu, MD, MS1 ([email protected]); Muhammad Qazi, MD2; Fumiko Dekio, MD.2 Departments of 1Diagnostic Pathology and Laboratory Medicine and 2Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.

Twin reversed arterial perfusion (TRAP) is a rare condition specific for monochorionic multiplets. We report a case of TRAP with pericentric inversion of chromosome 5, which may shed light on its pathogenesis and early diagnosis. A 24-year-old woman with monochorionic diamniotic twin pregnancy was sonographically diagnosed with TRAP at 25 weeks showing absent cardiac activity of twin B (acardiac twin) and reversed umbilical artery blood flow toward twin B. Cytogenetics of twin A (pump twin) showed a female karyotype with pericentric inversion of chromosome 5, 46XX. inv(5)(p11q34) (Figure 2.169, A). She subsequently received radiofrequency ablation at 28 weeks, 2 days. Four days later, she delivered twins after preterm premature rupture of membranes. The pump twin was alive with fetal anomalies including hydrocephalus, increased nuchal translucency, single umbilical artery, and pulmonary atresia with ventricular septal defect. Twin B was a nonviable “fetal mass.” Grossly, it had severe malformation including anencephaly with maldevelopment of the facial structures, severe edema with excessive soft tissue in the upper body, omphalocele, and abnormal extremities (Figure 2.169, B). An x-ray of twin B showed scoliosis (Figure 2.169, C). Dissection showed absence of thoracic organs, diaphragm, proximal gastrointestinal tract, and genital organs (Figure 2.169, D). Early treatment of TRAP syndrome can relieve the pump twin's burden of perfusing acardiac twin, thus decreasing the pump twin's risk of congenital anomalies and cardiac failure. Twin A died at 7 weeks of age because of the cardiovascular anomalies and complications of prematurity. The finding of pericentric inversion of chromo-some 5 in this case may serve as an early diagnostic clue.

Differentiating Infiltrating Quilty Lesions From High-Grade Acute Cellular Rejection by PD-L1 Immunohistochemistry

(Poster No. 170)

Derald Charles, MD ([email protected]); Carolyn Glass, MD, PhD. Department of Pathology, Duke University Medical Center, Durham, North Carolina.

Context: Infiltrating Quilty (IQ) lesions are mononuclear cell infiltrates present in postcardiac transplant biopsies that histologically mimic acute cellular rejection (ACR). Differentiating between IQ and ACR can be diagnostically challenging and impacts transplant treatment decisions. We describe a novel biomarker, PD-L1, to help distinguish these 2.

Design: Endomyocardial transplant biopsies diagnosed as IQ and high-grade ACR were obtained as part of standard of care from our institution, one of the highest-volume cardiac transplant centers in the country. PD-L1 (Agilent, Santa Clara, California) immunohistochemistry was performed and quantified for both IQ and ACR within the (1) lymphocytic dominant inflammatory component and (2) myocyte structures as follows: negative (0%), minimal (1%–10%), focal (11%–50%), and diffuse (>50%).

Results: PD-L1 staining of both myocytes and lymphocytes was significantly increased in IQ (Figure 2.170, A and B) versus ACR (Figure 2.170, C and D) (P < .01). The IQ cohort (n = 9) showed 2 diffuse (22%), 4 focal (44%), and 3 minimal positivity (33%) within the lymphocytes and 5 diffuse (56%), 1 focal (11%), 1 minimal (11%), and 2 negative (0%) within the myocytes. The majority of the ACR cohort (n = 7) had no PD-L1 positivity within the lymphocytes or myocytes; 1 minimal (14%) and 6 negative (87%) within lymphocytes and 1 minimal (14%) and 6 negative (87%) within myocytes.

Conclusions: We propose a novel IHC biomarker to improve distinguishing IQ lesions from ACR, 2 common entities in heart transplant patients managed with different treatment protocols. Our study may potentially decrease interobserver variability for difficult lesions that are challenging to even the most experienced cardiac pathologists.

Pu.1/CD31 Double Stain for the Diagnosis of Pathologic Antibody-Mediated Rejection in Cardiac Transplantation

(Poster No. 171)

Megan F. Lee, MD1 ([email protected]); Isabella B. Dreyfuss, OMS-IV2; Carolyn Glass, MD, PhD.1 1Department of Pathology, Duke University Medical Center, Durham, North Carolina; 2Department of Pathology, Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Florida.

Context: Heart disease is the leading cause of death in the United States; in parallel, the number of heart transplants in the United States has steadily increased during the last decade. Despite improved therapy with potent immunosuppressants, cardiac transplant patients are on lifelong surveillance for rejection. Pathologic antibody-mediated rejection (pAMR), the type of acute rejection that portends the worst graft outcome, can be challenging to diagnose. Endomyocardial biopsy is the primary diagnostic tool for pAMR detection; however, identifying the intravascular location of macrophages, which histologically defines pAMR, is difficult and associated with interobserver variability.

Design: We developed a double immunohistochemical stain with macrophage (Pu.1) and endothelial (CD31) specificity (Figure 2.171) to improve the diagnostic accuracy of pAMR. The double stain was performed on 25 endomyocardial cardiac transplant biopsies obtained as part of the standard of care at our institution (one of the highestvolume cardiac transplant centers in the country). The double stain was interpreted as positive for a pAMR diagnosis if >10% of Pu.1-staining macrophages were visualized within CD31-staining capillaries. To determine whether the double stain improved diagnostic accuracy or changed the frequency of pAMR diagnosis, the original diagnoses were retrospectively reviewed.

Results: The double stain altered pAMR diagnosis in 7 cases (28%); all showed >10% positivity with the double stain but were not originally diagnosed as pAMR (undercall). No cases were overcalled as pAMR.

Conclusions: We demonstrate the value of using a novel double stain to increase diagnostic accuracy of pAMR. A multi-institutional study, including additional high-volume cardiac transplant centers, is in progress.

Noon–3:00 PM; Poster Focus, Noon–1:00 PM Pulmonary and Mediastinal Pathology; Quality Assurance; Molecular Pathology; Breast Pathology; Autopsy and Forensic Pathology; Dermatopathology; Microbiology; Neuropathology; Pathology Education; Endocrine Pathology; Practice Management; Informatics; Clinical Chemistry; Clinical Immunology; Transfusion Medicine; Administrative and Regulatory Affairs
Systemic Rosai-Dorfman Disease Presenting as a Radiographically Evolving Breast Asymmetry Mimicking Fat Necrosis on Biopsy

(Poster No. 1)

Josef Venable,MD1 ([email protected]); Katie M. Davis, DO2; Mirna B. Podoll, MD.1 Departments of 1Pathology, Microbiology, and Immunology, and 2Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.

Rosai-Dorfman disease (RD) is a rare subtype of non–Langerhans cell histiocytosis typically involving lymph nodes and, less commonly, extranodal tissues. RD primary to the breast is uncommon, and although it mimics a breast malignancy clinically, histologically it may go underdiagnosed as inflammation or fat necrosis. We present a case of a 53-year-old woman with prior biopsies for fibroadenomas and fat necrosis presenting with an enlarging focal asymmetry on mammography, measuring up to 40 mm. The focal asymmetry was biopsied, yielding multiple cores of mammary parenchyma with dense lymphoplasmacytic infiltrate and histiocytes (Figure 3.1, A and B). The intermingling of the inflammatory process with the background benign mammary parenchyma was noted, without evidence of hemosiderin, acute inflammation, granulomas, or paucity of terminal ducts lobular units. CD163 immunostain (Figure 3.1, C) highlighted abundant histiocytes that also showed strong S100 (Figure 3.1, D) expression. Immunostains for CD1a, langerin, and CD30 were negative. A diagnosis of RD was rendered, and the patient's subsequent position positron emission tomography computed tomography scan revealed FDG-avid lymph nodes in the right axilla and left proximal thigh, consistent with widespread RD. Retrospectively, a previously biopsied focal asymmetry in the same breast, thought to be fat necrosis, was also consistent with RD. The presence of emperipolesis is not always readily noted on routine (hematoxylineosin) sections, and RD in the breast may go underdiagnosed as a reactive process due to trauma, idiopathic, or iatrogenic etiologies, among others. It is important to keep RD in the differential diagnosis of histiocyte-rich inflammatory breast lesions to avoid misclassification and delay in diagnosis.

The Clinical Significance of Flat Epithelial Atypia on Breast Core Biopsy: A Single-Institution Experience

(Poster No. 2)

Yujun Gan, MD, PhD ([email protected]); Rouzan Karabakhtsian, MD; Sonali Lanjewar, MD. Department of Pathology, Montefiore Medical Center, New York, New York.

Context: Flat epithelial atypia (FEA) is being increasingly recognized as a pathologic entity on breast core needle biopsies (CNBs). However, the management of FEA diagnosed on CNB varies between institutions, largely because of wide variation of its upgrade. In this study, we attempted to determine the upgrade rate of FEA in subsequent excisions at our institution.

Design: Retrospective review of all FEA cases diagnosed on CNB and the findings in subsequent excision was performed for an 11-year period (January 2010 through December 2021). Cases with coexisting atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), or invasive carcinoma were excluded.

Results: Review of pathology reports revealed 30 patients (mean age, 48.9 years) with FEA diagnosis on CNB and subsequent excision. All cases still showed FEA on excision. In 73.3% (22 of 30), no upgrade on excision was identified. The remaining 26.7% (8 of 30) showed upgrade, including coexisting ADH (6 of 30; 20%), and markedly atypical ductal hyperplasia (MADH) and DCIS (2 of 30; 6.6%), respectively. Associated lobular intraepithelial neoplasia (LIN) was seen in 11 of 30 (36.6%).

Conclusions: In our study, FEA diagnosed on CNB was upgraded to more advanced lesions (ADH, MADH, DCIS) in about 27% of cases, thus justifying a surgical approach. Our results are in keeping with dominating published data in support of surgical excision recommendation for FEA. About one-third of FEA was associated with LIN. Larger multi-institutional studies are necessary for a standardized nationwide approach in management of FEA.

Secretory Breast Carcinoma: Rare Subtype of Triple-Negative Invasive Breast Carcinoma With Indolent Behavior

(Poster No. 3)

Jacob Dear, MD1 ([email protected]); Justin Wells, MD1; Philip Branton, MD2; Rubina Mattu, MD.2 1Department of Pathology, Walter Reed Naval Military Medical Center, Bethesda, Maryland; 2Department of Pathology, Joint Pathology Center, Silver Spring, Maryland.

Secretory carcinoma of the breast (SCB) is a rare form of breast cancer (<1%) reported in a wide age range of patients (ages 3–86 years; mean age, 53 years) and affecting both sexes. We report 2 cases of SBC with differing morphologies in women, ages 23 and 31 years. Case 1 showed microcystic architecture and tumor cells with vacuolated amphophilic cytoplasm, bland nuclei, and intraluminal pools of eosinophilic material (Figure 3.3, A). The tumor cells were triple negative (ER/PR/HER2) with basal-like markers (CK 5/6+) and positivity for pan-TRK+ (Figure 3.3, B), which is specific for SCB in the breast. Case 2 showed tumor with papillary architecture (Figure 3.3, C) that was also triple negative and basal-like. The vesicular, polymorphic nuclei and nondefinitive pan-TRK staining pattern in this patient prompted a fluorescence in situ hybridization study that identified an ETV6-NTRK3 gene fusion (Figure 3.3, D). SCB typically has radiologic findings of a circumscribed mass, suggestive of a benign disease process, such as fibroadenoma. Although these tumors are triple negative and express basal markers, they have a favorable prognosis. SCB can be diagnosed with pan-TRK IHCs that target the constitutively activated chimeric tyrosine kinase receptor or molecular and fluorescent in situ hybridization techniques that identify the ETV6-NTRK3 gene fusion, which is pathognomonic for SCB. This characteristic molecular expression can support the diagnosis of SCB and help exclude benign and malignant histologic mimics (eg, lactating adenomas, cystic hypersecretory lesions, and carcinomas with apocrine differentiation), especially in limited core biopsies.

Upgrade Rate of Flat Epithelial Atypia on Core Needle Biopsy and Management

(Poster No. 4)

Dina Hassan, MD1 ([email protected]); Suzanne Iwaz, MD2; Robert Zhang, MD1; Lin Cheng, MD1; Paolo Gattuso, MD1; Indu Agarwal, MD.1 1Department of Pathology, Rush University Medical Center, Chicago, Illinois; 2Department of Pathology, Northwestern University, Chicago, Illinois.

Context: The identification of flat epithelial atypia (FEA) has increased through screening mammography. It is thought to have a relative risk of ~1.5 for development of invasive carcinoma (IC). Currently, no consensus exists on excising FEA after diagnosis on core needle biopsy (CNB). We studied the upgrade rate of FEA on subsequent excisions to collect data for the same.

Design: Retrospective analysis was performed on CNBs between January 2010 and 2022. Biopsies with a diagnosis of FEA were identified. FEAs with concurrent IC, ductal carcinoma in situ (DCIS), and/or atypical ductal hyperplasia (ADH) were excluded. The rate of upgrade of FEA was evaluated, being defined as IC and/or DCIS on subsequent excision.

Results: Of 12 355 CNBs, a total of 40 CNBs from 40 patients had a diagnosis of FEA. Follow-up was available in 31 cases. Eighty percent of biopsies were done for calcifications, and the remaining were done for other imaging findings (eg, architectural distortion, masses, and nonmass enhancement). One hundred percent of CNBs were deemed radiology-pathology concordant. Follow-up excision showed the following: 7 had ADH, 4 had lobular neoplasia (LCIS or ALH), 1 had radial scar, 4 had FEA as the worst diagnosis, and 15 showed no residual FEA or any atypia. None of the patients upgraded to IC or DCIS.

Conclusions: None of the patients had IC or DCIS on excision, although ADH and lobular neoplasia were observed. Because substantial variability has been reported among pathologists for diagnosing FEA, based on our findings, we conclude that nonsurgical management should be considered in patients without prior/concurrent carcinoma and a radiologic-concordant CNB diagnosis of FEA, although surveillance is warranted.

Concomitant Breast Fibromatosis and Invasive Ductal Carcinoma

(Poster No. 5)

Billie Shine, DO ([email protected]); Joshua M. Peterson, MD; Rasha Alfattal, MD; Jing He, MD. Department of Pathology, University of Texas Medical Branch, Galveston, Texas.

A 45-year-old woman presented to her primary care physician for a palpable left breast mass. Ultrasound revealed a 30-mm spiculated mass in the left breast and multiple enlarged axillary lymph nodes. These were biopsied, and histopathologic evaluation of the breast biopsy demonstrated sheets of uniform spindle cells, no nuclear hyperchromasia or cytologic atypia, and a low mitotic rate without necrosis (Figure 3.5). These spindle cells were negative for cytokeratin markers and stained positive for nuclear β-catenin (Figure 3.5). However, the lymph node biopsy contained foci of metastatic invasive ductal carcinoma (IDC), found to be ER/PR positive and HER2. Based on morphology, fibromatosis was the favored diagnosis for the breast mass, although metaplastic carcinoma with fibromatosis-like features could not be excluded, and excision was recommended. Given the discordant biopsy results, magnetic resonance imaging was performed, which showed a suspicious lesion 2.5 cm from the previously biopsied lesion. Biopsy of the second lesion showed IDC. After neoadjuvant therapy, lumpectomy of both breast lesions was performed together with axillary regional lymph node dissection. Both lesions were completely excised, and 2 distinct lesions were identified: fibromatosis and IDC. Although concomitant lesions in the breast are rare and interesting phenomena, this case highlights the potential pitfalls of designating cancers as locally recurrent. Had the first palpable mass been IDC instead of fibromatosis, the proximity of the second malignant lesion may have been assigned as a local recurrence instead of a distinct malignant focus. In some proportion of cases, locally recurrent breast cancer may in fact be persistence of preexisting disease.

Sudden Cardiac Death in the Setting of Anomalous Right Coronary Artery

(Poster No. 6)

Jing Di, MD, PhD ([email protected]); Jason D. Gilbert, DO; Hafsa Nebbache, MD; James Warwick, MS, BS; Victoria Jones, MS, BS; William N. O'Connor, MD. Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington.

Anomalous aortic origin of the coronary arteries is a rare congenital abnormality typically incidentally found on angiography or at autopsy. We report autopsy findings from a 41-year-old previously healthy woman with sudden cardiac arrest. The patient was initially found unconscious in her home without a pulse. Return of spontaneous circulation was achieved en route to the hospital, but later imaging revealed severe hypoxic-ischemic brain injury and brain herniation. Brain death was declared 4 days after initial presentation. Autopsy examination of the aortic root revealed a coexisting patent 2.5-mm left main coronary ostium and a patent 2.0-mm (anomalous) right coronary artery ostium, both arising from the left aortic sinus of Valsalva with high right ostial takeoff (Figure 3.6, A). The proximal anomalous right coronary artery had a slitlike lumen and coursed intramurally for 10 mm before continuing between the aorta and the pulmonary trunk. The right coronary artery gave origin to the acute marginal and posterior descending arteries for a right dominant circulation, whereas the left main coronary artery gave off the left anterior descending and left circumflex arteries. Sectioning revealed patchy, subendocardial mottling of the posteroseptal and lateral left ventricular myocardium (Figure 3.6, B). Histologic examination revealed moderate hypertrophy of the left ventricular myocardium with mild punctate lesions, extensive coagulative necrosis, and macrophage infiltrates (Figure 3.6, C), as well as marginal contraction band necrosis (Figure 3.6, D). Overall, anomalous right coronary artery is a rare occurrence that can be associated with significant adverse cardiac outcomes, as demonstrated in this case.

Differential Diagnosis of a Rare Liver Finding at Autopsy: Diffuse Biliary Microhamartomas

(Poster No. 7)

Emilie Cook, DO1; Thi Le Na Pham, MD1 ([email protected]); John Grove, BS.2 1Department of Pathology, East Tennessee State University, Johnson City; 2Department of Pathology, Lincoln Memorial University–DeBusk College of Osteopathic Medicine, Knoxville, Tennessee.

We present a case of a unique liver finding at autopsy in a 55-yearold man with no significant past medical history. Autopsy findings were significant for an enlarged liver (2750 g) that had innumerable small, white-yellow subcapsular nodules and firm, variegated white-yellow to red parenchyma. At the time of autopsy there was immediate concern for tuberculosis of the liver or liver metastasis. There were no significant findings in the lungs and no other evidence of extrahepatic tuberculosis. The bile duct was normal in width and no evidence of a primary malignancy was identified during a thorough autopsy examination. Although not directly related to the cause of death in this case, a histologic workup was performed to rule out hepatic tuberculosis or find the origin of metastasis. Microscopic examination of the liver revealed increased periportal fibrosis with septal formation but no true bridging fibrosis. There were innumerable irregularly shaped periportal bile ducts, some with canalicular cholestasis. The histologic features were consistent with diffuse biliary microhamartomas. Biliary microhamartomas are benign dilated cystic bile ducts whose etiology stems from a failure of involution during embryogenesis. Most patients have no symptoms, and no treatment is required. Our case highlights the importance of this differential diagnosis of hepatic tuberculosis, metastatic disease, and diffuse biliary microhamartomas which present similarly at autopsy.

Autopsy Findings in a Case of Primary Pulmonary NUT Carcinoma Harboring a BRD3-NUTM1 Fusion and Lacking Squamous Morphology

(Poster No. 8)

Lisa M. Marinelli, MD ([email protected]); Hannah R. Rose, MD; Thomas A. Adams, MD. Department of Pathology and Area Laboratory Services, Brooke Army Medical Center, Ft Sam Houston, Texas.

NUT carcinoma is a rare, aggressive subtype of squamous cell carcinoma characterized by a rearrangement of the nuclear protein in testis (NUTM1) gene. We present the autopsy findings of a woman with metastatic NUT carcinoma found to have a BRD3-NUT fusion and lack squamous morphology. The decedent is a 49-year-old woman who presented with worsening dyspnea and was found to have a 9.5 cm in diameter right upper lobe lung mass, causing superior vena cava syndrome. Biopsy of the mass and an additionally identified left retroperitoneal mass revealed a proliferation of small round blue cells with prominent nucleoli and abundant tumor necrosis, without areas of squamous morphology (Figure 3.8). The neoplastic cells stained positively for NUT and focally positive for AE1/AE3, consistent with NUT carcinoma. TEMPUS transcriptome analysis identified a BRD3-NUTM1 chromosomal rearrangement. The patient received palliative chemoradiation but died of her disease 2 months later. Findings at autopsy included unchanged pulmonary and retroperitoneal masses, diffuse alveolar damage, a pulmonary infarction, postmortem lung cultures growing Pseudomonas aeruginosa, consistent with findings on premortem sputum cultures, multifocal subdural and subarachnoid hemorrhages, and coalescing foci of bladder mucosal ulceration and hemorrhage, consistent with hemorrhagic cystitis. Although most cases of NUT carcinoma are characterized by the reciprocal translocation t(15;19), a translocation t(9;15), resulting in a BRD3-NUT fusion transcript, has been observed in less than 5% of cases. The lack of squamous morphology identified in the present case highlights the importance of consideration of this diagnosis in small round blue cell tumors, especially in young adults.

Postmortem Lung Findings in a Decedent With a History of Dysphagia and Cognitive Impairment: Kayexalate, Seed Storage Cell (Lentil), Lipids, and Striated Meat

(Poster No. 9)

Steven H. Adams, MD ([email protected]); Bo Young E. Lee, DO; Prerna Khetan, MD; Randolph A. Hennigar, PhD, MD. Department of Pathology, Stony Brook University Hospital, Stony Brook, New York.

The coexistence of dysphagia with cognitive impairment sets an increased risk of aspiration pneumonia. We report the postmortem lung findings of aspirated Kayexalate and various food particles. A 79-year-old man with a history of mild cognitive impairment, schizophrenia, smoking, renal insufficiency, and oral phase dysphagia with a suspected aspiration pneumonia described 5 years prior to death presented with shortness of breath, hypoxia, hyperkalemia, hyperphosphatemia, and acute kidney injury. Despite resuscitative efforts he deteriorated and died. An autopsy was performed. Although gross examination of the lungs showed only mild thickening of the apical pleural surfaces, microscopy revealed extensive emphysema, pulmonary fibrosis with chronic inflammation and osseous metaplasia, acute bronchopneumonia/bronchiolitis, and numerous foreign bodies, including striated muscle (Figure 3.9, A, hematoxylin-eosin [H&E], original magnification ×100); seed-derived storage cells (called “lentil pneumonia” in the older literature; Figure 3.9, B, H&E, original magnification ×40); lipoid changes; and multifaceted, basophilic, Gram-positive, PAS-positive foreign body inclusions with paracrystalline substructure (Figure 3.9, C, H&E, original magnification×40), staining black-green on AFB staining (Figure 3.9, D, H&E, original magnification ×20), consistent with sodium polystyrene sulfonate (Kayexalate). Although crystals in some lobes were associated with foreign body giant cell reactions and acute and chronic inflammation, 1 lobe had only minute crystal-associated acute inflammation, suggestive of recent or terminal aspiration. Reviewing 17 years of hospital records did not reveal any polystyrene sulfonate or sevelamer medication history. We concluded that the patient had been taking Kayexalate at home. Review of the literature reveals a dearth of similar cases described here.

Zymogen Granules in Pancreatic Acinar Cells in an Adult With Shwachman-Diamond Syndrome: An Autopsy Case Study

(Poster No. 10)

Phillip Bennett, DO ([email protected]); Taylor Jackson, DO; Frederic Clayton, MD. Department of Pathology, University of Utah, Salt Lake City.

Shwachman-Diamond syndrome (SDS) is a genetic disease caused by a mutation in the SBDS gene that can lead to hematologic abnormalities, skeletal defects, and pancreatic insufficiency. Children with SDS often develop pancreatic insufficiency with steatorrhea, although pancreatic symptoms often improve as they mature into adulthood. There are differences in the results from studies to explain the pathophysiology for SDS-related pancreatic insufficiency, specifically concerning zymogen granules within pancreatic acinar cells. Pancreatic biopsies of children with SDS have shown atypical acinar cells with no zymogen granules. A mouse model demonstrated granules in decreased numbers with normal morphology and function. A study using in vitro human pluripotent stem cells showed large dysfunctional granules. To our knowledge, no histologic findings of adult pancreas with SDS have been published to demonstrate zymogen granularity in acinar cells. In this autopsy case study, we present a 41-year-old man with SDS-related acute myeloid leukemia, who died from myeloid blast crisis. Gross examination revealed an atrophic pancreas with fat replacement. Microscopy further revealed acinar cells with bizarre nuclear atypia and increased zymogen granules, confirmed by positive trypsinogen immunohistochemical staining. Developing acinar pancreatic zymogen granules in adulthood can explain the improved pancreatic function in adults with SDS.

Acute Pericarditis and Acute Pleuritis/Empyema Following Submandibular Infection in a COVID-19–Positive Patient: An Autopsy Revealing the Danger Space of the Neck

(Poster No. 11)

Jessica D. Anderson, MD ([email protected]); Seyedalireza Fatemi, MD; Joseph Fullmer, MD; Ping L. Zhang, MD, PhD. Department of Pathology, Beaumont Hospital, Royal Oak, Michigan.

Acute pericarditis and empyema are life-threatening complications of severe odontogenic infections; reports of these findings from an autopsy perspective are rare. We report an autopsy case demonstrating infection from the mandibular molars to the pericardium and pleura in a patient following COVID-19 infection. A 53-year-old woman with history of COVID-19 (and on repeat testing at admission) presented with submandibular abscess that grew Streptococcus anginosus. Despite incision and drainage of the neck abscess and medical treatment, her condition deteriorated, with sudden death a week after admission. An autopsy with histologic analysis was performed. Externally, a surgical incision containing purulent drainage was present in the right submandibular area. Internally, there were large, purulent pleural and pericardial effusions. The lungs had patchy green discoloration, and the epicardial and pericardial surfaces were covered with fibrinous exudates. Histologically, abscess and Gram-positive bacteria were identified in the soft tissue surrounding the thyroid. Gram-positive bacteria and fibrinous, necrotic exudate with acute inflammation were present on the pleural and pericardial surfaces, consistent with acute pleuritis/empyema, and acute pericarditis. This is the first reported autopsy case describing acute pleuritis with empyema and acute pericarditis complicating submandibular infection in a patient with history of COVID-19. The mechanism is consistent with descending infection by deep cervical fascia and spaces such as the “danger space” communicating with the mediastinum. COVID-19 infection may add an important factor compromising her health; this case highlights the importance of recognizing life-threatening complications of oral infections.

Death by Head Lice?

(Poster No. 12)

Donna M. Hill, MS, MAEd, DO ([email protected]); Alexander Fenwick, MD; Nathan Shelman, MD; Eun Lee, MD. Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington.

Pediculus humanus capitis, the head louse, is an ectoparasite that feeds on human blood. Research has suggested that heavy infestation could lead to daily blood loss of approximately 1.26, or 37.76 mL per month. Although this is a small amount of blood, a chronic, heavy lice infestation could potentially lead to severe iron deficiency anemia; a few case reports in recent years have documented this phenomenon in children. We report the autopsy findings of a white girl age 8 years and 11 months with a significant history of morbid obesity and severe, longstanding pediculosis capitis (Figure 3.12, A). Immediately prior to presentation, she experienced acute dyspnea and collapsed. Her family reported that she complained of abdominal pain, diarrhea, and lower extremity edema for several days before her acute presentation. She was transferred to our institution and died shortly thereafter. Autopsy revealed significant cardiomegaly (438 g) with acute myocardial necrosis (Figure 3.12, C), pneumonia, anoxic brain injury, pseudomembranous colitis (Figure 3.12, B), severe iron deficiency anemia (hemoglobin 2.0 g/dL; Figure 3.12, D), and severe pediculosis capitis. Testing for heavy metals and other metabolic causes of anemia was unrevealing. The cause of death was determined to be acute myocardial necrosis and pneumonia with multiorgan failure, in the setting of obesity-related cardiomyopathy and severe anemia. We propose that the longstanding heavy lice infestation contributed greatly to the severe anemia in this child with underlying comorbidities. The report of this autopsy adds to the literature by further establishing morbidity and even possible mortality in certain at-risk patient populations with severe longstanding pediculosis capitis.

Liver Injury in COVID-19: Direct Evidence of Hepatic SARS-CoV-2 Infection and Associated Histopathologic Findings

(Poster No. 13)

Zaid Khreefa, MD ([email protected]); Jihuan Chen, MD; Gordon Love, MD; Luis Del Valle, MD. Department of Pathology, Louisiana State University Health Science Center, New Orleans.

Context: COVID-19 is a multiorgan systemic infectious disease. Multiple studies have shown functional and morphologic changes in COVID-19 patients and postmortem autopsies. However, the route of viral entry, the expression and distribution of viral proteins within the liver, and a direct link between SARS-CoV-2 and hepatic impairment have not been demonstrated.

Design: Autopsy liver samples were obtained from 35 COVID-19 and 39 non–COVID-19 patients with no history of viral hepatitis, cirrhosis, malignancy, or hepatotoxic medication usage. Antemortem hepatic biomarkers were reviewed. Portal and lobular inflammation, fibrosis, and steatosis were graded using the Batts-Ludwig system. The expression of SARS-CoV-2 nucleocapsid and spike proteins was evaluated in the liver by immunohistochemistry.

Results: Antemortem aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels were significantly higher in the COVID-19 group (443, 222.3, and 219.7 U/L, respectively) than in non–COVID-19 controls (88.1, 61.9, and 101.5 U/L, respectively). No significant difference in bilirubin, albumin, or total serum protein levels was found. The liver exhibited more significant portal and lobular inflammation in the COVID-19 group compared with controls (Figure 3.13, A). No significant difference in fibrosis or steatosis was found. Viral nucleocapsid and spike proteins were expressed in hepatocytes, vascular endothelial cells, and areas of lobular inflammation in the COVID-19 group (Figure 3.13, B through D).

Conclusions: This is the first report of a large cohort of COVID-19 autopsy cases exhibiting hepatic inflammation and elevated liver biomarkers, with hepatic parenchymal and vascular SARS-CoV-2 involvement that is strongly associated with subsequent liver damage. Viral proteins in blood vessels suggest a hematogenous entry into the liver.

Characterization of the Early COVID-19 Deaths in Hillsborough County, Florida

(Poster No. 14)

Alexandra L. Mease, BS1 ([email protected]); Victoria Sands, BS, BA1; Sarah Nestler, BS1; Nazia Hossain, BS1; Emily Coughlin, MPH2; Rahul Mhaskar, MD1; Kelly Devers, MD.3 1Morsani College of Medicine, and Departments of 2Medical Education and 3Pathology, University of South Florida, Tampa.

Context: The COVID-19 pandemic has claimed 5.73 million lives worldwide to date since its emergence in Wuhan, China, in December 2019. Deaths in the United States account for 15.7% of that figure, with Florida accounting for 7.35% of the nation's total. Information about the number of COVID-19 cases and deaths by state and county has been readily available since early in the pandemic; however, there is need for an in-depth look at postmortem data.

Design: Decedents were identified for this study using medical records provided by the Hillsborough County Medical Examiner. Deaths that occurred between March 2020 and March 2021 were reviewed and those that had COVID-19 listed as the cause of death or contribution to cause of death were selected. In total, 503 cases were used in this study. Demographics, relevant medical history, and lifestyle factors were collected.

Results: The mean age of death was 75.53 ± 12.6 years. The most common comorbidities documented were hypertension (78.1%), diabetes mellitus (45.9%), coronary artery disease (24.9%), hyperlipidemia (24.7%), chronic kidney disease (22.7%), and chronic obstructive pulmonary disease (22.5%). A total of 22.9% of decedents had a history of tobacco use, whereas 24.1% were intubated and 13.3% were placed on a ventilator. Mean days from positive COVID-19 testing to death was 11.05 ± 8.9 days. The most common location at death was at the hospital (69.0%).

Conclusions: Comorbidities, advanced age, and tobacco use placed individuals at a significant risk for dying of COVID-19 infection in Hillsborough County, Florida. This information can be used to prepare for future health crises and allocate resources to the appropriate communities.

De-differentiation in a Rare Extra-Gastrointestinal Stromal Tumor Arising in the Greater Omentum

(Poster No. 15)

Samreen Fathima, MBBS1 ([email protected]); Ian T. Bui, BS2; Joseph M. Guileyardo, MD.1 1Department of Pathology, Baylor University Medical Center, Dallas, Texas; 2Department of Pathology, Texas A&M College of Medicine, Dallas.

Gastrointestinal stromal tumors (GISTs), the most common mesenchymal neoplasms of the gastrointestinal tract, originate from interstitial cells of Cajal. These tumors harbor mutations in the protooncogene KIT, which results in positive staining for CD117. They usually arise within the gastrointestinal tract; however, they are rarely reported to arise in the mesentery or omentum (extra-GIST [E-GIST]). A small percentage of GISTs and E-GISTs undergo transformation into an aggressive, poorly differentiated tumor with features of rhabdomyosarcoma, angiosarcoma, or undifferentiated pleomorphic sarcoma. Such tumors lose c-KIT staining but often retain DOG1 immunohistochemistry positivity. De-differentiation may be more common after imatinib therapy but can occur without it. We present a 73-year-old woman with an abdominal mass found to be GIST on biopsy. This tumor harbored both KIT and PDGFRA mutations and the patient received imatinib. She returned weeks later with expanding masses. Autopsy revealed massive expansion of the greater omentum and right hepatic lobe by soft and partially necrotic tumor. Portions of the omental tumor were consistent with classic GIST; however, undifferentiated portions contained sheets of small blue cells with loss of CD117 staining but retained DOG1 (Figure 3.15, A through D). No primary tumors were identified within the GI tract, and a diagnosis of E-GIST with de-differentiation was made. De-differentiated GISTs present a diagnostic challenge, having lost CD117 staining. However, retained positivity for DOG1 or finding undifferentiated tumor merging with classic GIST are both useful if present. Awareness of a possible GIST origin of undifferentiated tumors is essential for accurate diagnosis.

Diffuse Congenital Supravalvular Aortic Stenosis in the Setting of Williams-Beuren Syndrome With Associated Giant Omphalocele

(Poster No. 16)

Hafsa Nebbache, MD ([email protected]); Jing Di, MD, PhD; William O'Connor, MD; Nathan Shelman, MD. Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington.

Congenital supravalvular aortic stenosis (SVAS) is characterized by localized or diffuse narrowing of the ascending aortic lumen starting at the sinotubular junction, due to a loss of function mutation in the elastin gene (ELN) on chromosome 7q11.23. SVAS may occur as an isolated/sporadic disease, or may be inherited in an autosomal dominant fashion, and sometimes manifests as part of a complex developmental disorder including mental deficiency and dysmorphic facies, Williams-Beuren syndrome (WBS). Here we report the autopsy findings of a 9-month-old girl (born at 35 weeks' gestation) with WBS (via microarray) as well as a giant omphalocele containing the liver (590 g) and loops of bowel (Figure 3.16, B). At autopsy, mild supravalvular aortic stenosis with diminutive right and left coronary ostia accompanied diffuse medial arteriopathy affecting ascending thoracic aorta and arch vessels, which extended past the isthmus into the descending thoracic aorta with narrowing (mild coarctation) from an intimal shelf opposite the insertion site of the ligamentum arteriosum (Figure 3.16, A). The typical medial arteriopathy with thick and dysplastic lamellar units also involved the main pulmonary trunk, and right and left pulmonary artery branches (Figure 3.16, C and D; elastic trichome), with resultant peripheral pulmonary stenosis. There was marked accompanying cardiomegaly. To our knowledge, there is only 1 prior report of omphalocele associated with WBS microdeletion, this being the first such patient to survive to term.

Clusters of Spherical Basophilic Structures in a Fetal Autopsy: An Unresolved Mystery

(Poster No. 17)

Steven H. Adams, MD ([email protected]); Tahmeena Ahmed, MD; James Davis, MD. Department of Pathology, Stony Brook University Hospital, Stony Brook, New York.

We describe an unusual, unresolved finding on fetal autopsy of spherical basophilic structures present in alveolar spaces in the lungs (Figure 3.17, A and B) and in small vessels in periadrenal fat (Figure 3.17, C and D). This was a male fetus with sudden unexplained intrauterine fetal demise at 36 1/7 weeks' gestational age, delivered by cesarean delivery to a 30-year-old gravida 2, para 1, 0-0-1 mother. The autopsy was performed approximately 85 hours after delivery. Placenta examination showed marginal cord insertion, focal thrombus, focal villous infarct, and chorionitis of the fetal membranes. The umbilical cord was unremarkable. Cytogenetics showed a normal male karyotype. Antenatal (12-week) genetic testing and ultrasound at 30 weeks showed no significant fetal abnormalities. During pregnancy the mother had iron deficiency anemia, but all other antenatal tests were negative. No intra-amniotic injections or procedures were performed. Fetal activity and heartbeat were detected at 35 weeks 0 days. Significant postmortem findings were bilateral pleural effusions, pericardial effusion, ascites, bilateral pulmonary hemorrhage and intra-alveolar squames, skin maceration, and organ autolysis. The structures of interest were seen in the lung and adrenal sections. Special stains revealed the basophilic structures as PAS positive, GMS negative; immunohistochemistry showed CD138, MUM1, pancytokeratin negative, and HCG. Considerations include multinucleate viral inclusions, myospherulosis, and aspirated foreign material. Fungi and parasites were ruled out. Similar structures were reported in hepatic sinuses from a COVID-19 adult autopsy series but were not found in the autolyzed fetal liver. The identity of these structures remains unknown, but this case illustrates the utility of fetal autopsy and a multifaceted approach to unusual findings.

A 5-Year Retrospective Review of Cardiac Findings in Fetal and Pediatric Autopsies at a Single Large Academic Institution

(Poster No. 18)

Jusmita B. Saifullan, MD ([email protected]); Matthew G. Charles, BA; Carolyn Glass, MD, PhD. Department of Pathology, Duke University Hospital, Durham, North Carolina.

Context: The following review aims to characterize and evaluate the spectrum of cardiac findings for all fetal and pediatric autopsies performed within the past 5 years at Duke University Hospital (2017–2021).

Design: A total of 238 pediatric autopsies were retrospectively analyzed via review of the autopsy reports, with a selective emphasis on cardiac findings.

Results: Of the 238 cases reviewed, 143 cases (60.1%) with significant cardiac findings were identified. Within this group, 73 (51.1%) were stillborn and 70 (49.0%) were liveborn autopsies, with 69 cases (48.3%) being males, 73 cases (51.1%) being females, and 1 case (0.7%) being undetermined sex. Structural congenital heart defects were identified in 62 cases (43.3%), with atrial septal defect and ventricular septal defects being most common. Noncongenital structural abnormalities were present in 77 cases (53.8%), with the most common defects being dilation and hypertrophy of the cardiac chambers. Infectious cardiac etiologies were identified in 8 cases (5.6%). Ischemic changes and infarcts were identified in 33 cases (23.1%), with the most common location of infarcts being the left and right ventricles. Lastly, primary cardiac tumors, including pericardial teratoma and rhabdomyosarcoma, were identified in 4 cases (2.8%).

Conclusions: These findings support current existing literature on the spectrum of cardiac findings seen within the pediatric postmortem population and further highlights the importance of thorough examination of the cardiac system in pediatric autopsies for a comprehensive assessment of the etiologies leading to death within the pediatric population.

Evaluating the Utility of the Modern Medical Autopsy Using the Goldman Criteria

(Poster No. 19)

Meagan Chambers, MD, MS, MSc ([email protected]); Desiree Marshall, MD. Department of Pathology and Laboratory Medicine, University of Washington, Seattle.

Context: With the recent change from 50 to 30 required autopsies for residency graduates, there has been renewed interest in evaluating the utility of the medical autopsy.

Design: We apply the Goldman criteria to a subset of medical autopsies at a large academic medical center to evaluate the utility of the modern medical autopsy. Using a random number generator, 100 autopsies from the year 2019 were selected and evaluated for diagnoses that were not known or were inconclusive prior to death. Cases were excluded if they were organ-restricted or pediatric cases.

Results: Of the 100 autopsies reviewed, 78 had additional diagnoses at autopsy that were unknown or inconclusive prior to death. Of these 78, there were an average of 2.5 diagnoses per autopsy. Sixteen autopsies had diagnoses that would have led to an increase in prognosis/survival if they had been known prior to death. An additional 48 autopsies had missed diagnoses that were directly related to the cause of death, including contributing conditions or sequelae, but without a change in prognosis. Fourteen autopsies had only diagnoses unrelated to the cause of death.

Conclusions: In this retrospective review most had diagnoses unknown prior to death (78%). In 16% of cases, autopsy revealed the primary cause of death or other additional information related to the cause of death that would have resulted in improved prognosis in the patient had it been known prior to death. These results argue for the continued importance of high-quality medical autopsies.

Unstable Aortic Thrombus as an Initial Presentation in a Patient With Prothrombin G20210A Mutation

(Poster No. 20)

Allen C. Omo-Ogboi, MD ([email protected]); Robert L. Hunter, MD; Amer Wahed, MD. Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston.

Prothrombin (factor II) is the precursor of thrombin, the final effector of the clotting cascade that leads to the formation of fibrin. Genetic variation of prothrombin to G20210A mutation results in increased levels of prothrombin in plasma, which increases the risk of thrombosis. The role of venous thromboembolism has been well established, but that of arterial thromboembolism has been a matter of debate and usually occurred as a rare entity. Here, we describe this case as the first documented case of unstable aortic thrombus as an initial presentation in a patient with prothrombin G20210A mutation. A 64-year-old woman with history of hypertension, hyperlipidemia, heart murmur, tetralogy of fallot (surgically repaired as a child), gastroesophageal reflux disease, and pancreatitis presented with dysarthria and left upper extremity weakness. She did not have any history or family history of thromboembolism. Computerized tomography angiography of the head and neck revealed an unstable aortic thrombus at the level of the right subclavian artery, and chronic-appearing left insular infarct. Genetic studies revealed a prothrombin G20210A mutation. Although arterial thromboembolisms in patients with prothrombin G20210A mutation are rare, meta-analysis of recent studies has shown an overall increased risk. Clinical presentation depends on the location of the blood clot, and a high index of suspicion is needed to help diagnose cases of arterial thromboembolism in patients with unknown history of prothrombin G20210A mutation.

Unexpected Sudden Death With an Unexpected Finding: An Autopsy Chronicle of What to Keep Your Eye On

(Poster No. 21)

Stephanie Conrad, MD ([email protected]); Knarik Arkun, MD. Department of Pathology, Tufts Medical Center, Boston, Massachusetts.

We report a case of a 60-year-old woman with sickle cell trait, chronic kidney disease on hemodialysis, well-differentiated neuroendocrine tumors in the liver, diabetes, coronary artery disease, and critical limb ischemia. She was admitted for bilateral transmetatarsal amputation. Her postoperative course was complicated by sepsis and severe hypotension requiring vasopressor support. Her condition stabilized and she was receiving dialysis when she unexpectedly experienced cardiac arrest. The inciting factor for cardiac arrest was clinically unclear; the differential included acute coronary event, massive pulmonary embolism, septic shock, or related to possible carcinoid involvement of the heart. Gross and microscopic exam of the organ block could not identify a cause of death. So, the differential diagnosis swayed to the clinical pathology realm. Perhaps an arrhythmia due to electrolyte imbalance was the culprit. Weeks later brain dissection showed no gross lesions. On microscopic examination of the brain, sickled red blood cells were found filling vascular lumens within the brain parenchyma with surrounding, multifocal incipient infarcts and necrosis consistent with sickle cell vaso-occlusive crisis. Consideration for vaso-occlusive crisis would have entered the differential early on had the patient carried a diagnosis of homozygous sickle cell disease; however, vaso-occlusive crisis in sickle cell trait is less common. This case highlights the importance of full autopsy and thorough microscopic examination, not overlooking the blood vessels and what may be in them, as well as considering rare presentations in the context of known medical history.

Clinicopathologic Findings of Patients With Hematologic Malignancies: A Retrospective Autopsy Study

(Poster No. 22)

Brandon T. Gehris, MD ([email protected]); Ahmed Ahmed, MD; Wei Wang, MD; Lei Chen, MD, PhD; L. Maximilian Buja, MD. Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, and the John P. and Katherine G. McGovern Medical School, Houston, Texas.

Context: Hematologic malignancies have myriad presentations, from ambiguous systemic symptoms to sudden death. This nonspecificity can hinder timely diagnosis, thus delaying diagnosis. Identifying common clinical, laboratory, and autopsy findings in patients with hematologic malignancies can help diagnosis and treat patients sooner.

Design: We retrospectively reviewed our institutions 2013 to 2021 autopsy and medical records for patients with hematologic malignancies. New patients were defined as diagnosed postmortem or within 1 month of death.

Results: A total of 19 patients were identified; of these, 7 were new. Three were lymphoma patients, with diffuse large B-cell lymphoma, peripheral T-cell lymphoma, and anaplastic lymphoma. Four were leukemia patients: 2 with acute myelocytic leukemia and 2 with acute promyelocytic leukemia. All new lymphoma patients had an international prognostic index score of at least 3. The most common presenting symptoms in new patients were pain, dyspnea, and gastrointestinal symptoms. Elevated lactate dehydrogenase, elevated prothrombin time, and cytopenias were common in both leukemia and lymphoma patients. These findings were similar to those in patients with prior diagnoses. Common autopsy findings included hepatomegaly, central nervous system, and bone marrow involvement. The most common immediate causes of death were multiorgan failure through malignant organ infiltration, brain herniation, and septic shock.

Conclusions: Hematologic malignancies are an underrecognized cause of multiorgan failure and sudden death. Elevated lactate dehydrogenase, bone marrow and central nervous system involvement, and hepatomegaly are pertinent findings in infiltrating lymphomas and leukemias. These findings can help render diagnoses for and treat critically ill patients via increasing awareness and consideration of hematologic malignancies in the differential diagnosis.

Microscopic Polyangitis Masquerading as COVID-19 Diagnosed at Autopsy

(Poster No. 23)

Jeffrey A. Sanford, MD ([email protected]); Robert J. Kitz, MD; John M. Childs, MD. Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland.

We present a case of microscopic polyangitis masquerading as COVID-19 pulmonary complications. A 61-year-old African American man with a past medical history of hypertension, hyperlipidemia, cerebrovascular disease, chronic kidney disease, type 2 diabetes mellitus, and admission 2 weeks prior for acute ischemic stroke complicated by pneumonia came back to the emergency department with worsening cough, increased work of breathing, and acute kidney injury. Computed tomography of the chest showed bilateral patchy infiltrates consistent with multifocal pneumonia and an extensive infectious workup was negative. He was subsequently admitted to the intensive care unit, where he developed diffuse alveolar hemorrhage and died on the second day of admission. An autopsy was requested given the rapid deterioration and possibility of COVID-19–related sequelae. The significant findings at autopsy included marked bilateral pulmonary congestion, hemorrhage, and consolidation as well as bilateral renal cortical petechial hemorrhage. Postmortem SARS-CoV-2 polymerase chain reaction was negative. The corresponding microscopic examination revealed diffuse alveolar hemorrhage (Figure 3.23, A) and capillaritis in the bilateral lungs, and a necrotizing glomerulonephritis (Figure 3.23, B and C) and small vessel vasculitis in the bilateral kidneys (Figure 3.23, D). Granulomas were not identified. Postmortem direct immunofluorescence studies performed on the lung and kidney were negative for immunoglobulin (Ig) A, IgG, IgM, C3, C1q, κ, and λ. Antemortem serologic testing for ANCA resulting after the autopsy revealed elevated anti-MPO and positive p-ANCA. This case illustrates the importance of medical autopsies as a way to provide insight into rare disease processes, correctly determine complicated causes of death, and to provide valuable clinical information during infectious outbreaks.

Extensive Myocardial Calcifications and Their Significance After Extracorporeal Membranous Oxygenation: Autopsy Findings in 2 Cases

(Poster No. 24)

Claudia Rojas, MD ([email protected]); Elena Ladich, MD; Alicia Hirzel, MD. Department of Pathology, Memorial Health System/Joe DiMaggio Children's Hospital, Miramar, Florida.

Myocardial calcification in neonates and infants is a nonspecific pathologic tissue reaction to injury and marker of severe myocardial damage that may begin in utero in patients with complex congenital heart disease. We present 2 cases with complex congenital heart disease who underwent surgical repair with need of extracorporeal membranous oxygenation (ECMO). Case 1 was a preterm female born at 35 1/7 weeks' gestational age with tricuspid valve dysplasia. She developed mixed acidosis and was placed on ECMO. She ultimately died after surgery. Among the microscopic findings were extensive biventricular myocardial and pulmonary calcifications. Case 2 was a 37-day-old male, full term, with a hypoplastic left heart, mitral and aortic valve atresia, atrial septal defect, tubular and markedly hypoplastic ascending and transverse aorta, and wide-open ductus. He underwent a modified Norwood, developed persistent lactic acidosis, and was placed on ECMO but ultimately died. Histologic examination of the right ventricle showed organizing infarcts of different ages, associated with extensive subendocardial and subepicardial calcifications. Diffuse myocardial calcification may lead to compromised myocyte function resulting in heart failure, sudden cardiac death, or life-threatening arrhythmias. Subendocardial calcification may occur due to subclinical ischemia without coronary occlusion in the setting of low coronary flow. Turbulent flow, multiple ischemic episodes occurring at delivery and/or surgery, prolonged hemodynamic failure, and old infarcts due to congenital heart disease may contribute to myocardial calcification in vulnerable pediatric patients. Recently it has also been hypothesized that prolonged ECMO support and high vasopressor doses may lead to myocardial calcification.

Autopsy Case Report of Amelanocytic Plasmacytoid Metastatic Melanoma

(Poster No. 25)

Denise S. Dailey, MD ([email protected]). Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York.

There are fewer than 40 case reports of plasmacytoid melanoma, and not enough data are available regarding demographic, primary sites, and immunohistochemistry patterns. We present the case of a dead 70-year-old woman with a previous diagnosis of malignant melanoma of the left upper extremity in 2020, status post wide local excision. Skin biopsy was positive for melanoma; however, the excised specimen did not show melanoma. In 2021 the patient presented to the emergency department with complaints of severe left chest pain and dyspnea. Computed tomography (CT) showed a destructive t5 vertebral body mass measuring 5 cm, an increase from a previous CT scan of 3 cm. The mass extended into the adjacent left rib and into the spinal canal, causing cord compression, while abutting the pleura. The mass was biopsied, and immunohistochemistry was obtained. Three weeks later, the patient died of her respiratory distress. The mass was sampled on autopsy and histology, and immunohistochemistry was compared to previous findings. Skin biopsy results confirmed the diagnosis of metastatic malignant melanoma positive for S100 and Melan-A, negative for HMB-45, and scattered CD138 benign plasma cells. Molecular diagnostics also confirmed our patient was positive for BRAF V600E mutation. Autopsy histology revealed amelanocytic plasmacytoid metastatic melanoma. Immunohistochemistry was the same; however, the plasma cell percentage increased from 2% to 100%. This was a rare case of undiagnosed plasmacytoid variant of metastatic melanoma. The delay in diagnosis seemed to be a result of plasmacytoid component absent on initial biopsy, but instead increasing gradually.

Mystery of Fever of Unknown Origin Solved by Autopsy

(Poster No. 26)

Hans Magne Hamnv°ag, MD1 ([email protected]); Chelsea Gertze, MD2; Yuanzhe Zhu, MBChB1; Thanchanok Chaiprasit, MD1; Vijayalakshmi Ananthanarayanan, MBBS, MD.1 Departments of 1Pathology and Laboratory Medicine and 2Internal Medicine, Loyola University Medical Center, Maywood, Illinois.

We present the case of a 66-year-old man with monoclonal gammopathy of uncertain significance, anemia, thrombocytopenia, fever of unknown origin, and B symptoms. Infectious, rheumatologic, and malignancy workup was unrevealing for a source of his fevers. A bone marrow biopsy showed hemophagocytic histiocytes (Figure 3.26, A) and no evidence of malignancy. Laboratory studies showed elevated triglycerides, ferritin, and CD25/soluble interleukin-2, and imaging revealed splenomegaly. A total of 6 of 8 criteria for hemophagocytic lymphohistiocytosis (HLH) were met, and the patient received empiric dexamethasone and antibiotics. Positron emission tomography scan demonstrated hypermetabolic foci throughout the liver and increased uptake within the pituitary. A liver biopsy showed vacuolization of the sinusoidal lining, without evidence of malignancy, or inflammatory or infectious process. After biopsy the patient developed hypovolemic shock due to hepatic bleed. Despite right hepatic artery embolization, the patient continued to decompensate. The patient's family withdrew care, and the patient died. The autopsy demonstrated wedge-shaped infarct in the liver at previous biopsy sites. Evidence of multiorgan failure was present, including acute kidney injury, liver centrilobular necrosis, and acute lung injury. The capillary/venular channels of the subcutaneous, pericardial (Figure 3.26, B), and retroperitoneal fat pads contained large atypical lymphoid cells. The cells were also present in the intraparenchymal vascular channels of the testis and the pituitary (Figure 3.26, C and D). The cells were CD20+ (Figure 3.26, D) and PAX-5+ and CD3. Intravascular large B-cell lymphoma was diagnosed. The underlying lymphoma could explain the patient's presentation. This case highlights the importance of autopsy examination in the setting of fever of unknown origin.

Autopsy Case Report: Moyamoya Syndrome in an Infant With Neurofibromatosis Type 1

(Poster No. 27)

Udit K. Naik, MD1 ([email protected]); Michelle M. McDonald, MD1; Garrett T. Phillips, MD2; Glenn D. Sandberg, MD2; Varsha Podduturi, MD.2 1Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston; 2Department of Pathology, Harris County Institute of Forensic Sciences, Houston, Texas.

Moyamoya disease (MMD) is a rare, progressive vaso-occlusive disorder that affects the terminal portions of the internal carotid arteries, with subsequent compensatory development of abnormal collateral vessels. Moyamoya syndrome (MMS) is used when MMD is associated with another neurologic or extraneurologic symptom due to an acquired or inherited cause. An association of neurofibromatosis type 1 and MMD has been occasionally reported in the literature. We present the autopsy and neuropathologic findings of MMS in a 6-month-old Hispanic female infant who was found unresponsive in a bassinet and declared dead 20 minutes after transportation and arrival to a hospital. Findings at autopsy consistent with NF-1 included macrocephaly, hypopigmented and hyperpigmented skin lesions of the torso and left lower extremity (café-au-lait-spots; Figure 3.27, A), and bilateral cervical/thoracic plexiform neuromas (Figure 3.27, B). A left acoustic neuroma was also identified. Evaluation of the brain revealed left hemispheric atrophy and an atrophic left internal carotid artery (Figure 3.27, C and D). The left anterior cerebral artery and left middle cerebral artery were composed of several very small atrophic arteries that anastomosed with the right cerebral arteries. Cut sections of the brain showed left-sided cortical thinning, reversal of normal gray-white matter coloration, and hypoxic-ischemic changes with associated resolving and resolved infarcts. Other findings included cortical dysplasia, a right temporal lobe hamartoma, and periventricular nodular heterotopia. The cause of death was classified as complications of neurofibromatosis, including MMS; the manner of death was natural. Recognition of this entity is important because of possible testing and counseling for relatives.

Leukocytoclastic Vasculitis in a Patient With Bedbugs

(Poster No. 28)

Roman Brudnik, MD1 ([email protected]); George A. Youngberg, MD1; Stuart Leicht, MD.2 1Department of Pathology, Quillen College of Medicine, East Tennessee State University, Johnson City; 2Department of Dermatology, East Tennessee Medical and Surgical Dermatology, Johnson City.

Cutaneous vasculitis in conjunction with bedbug bites is rare. We report a case of a 62-year-old woman with a new minimally itchy eruption that involved the left arm, followed by the left leg and trunk, and ultimately evolved into generalized cutaneous spread. There was no systemic involvement. Anti-neutrophil cytoplasmic antibody testing was negative. The rash consisted of red punctate macules and barely elevated papules, with a pattern of arcuate swirls and linear streaks. The differential diagnosis included pigmented purpura, granulomatous progressive pigmented purpura, cutaneous T-cell lymphoma, and leukocytoclastic vasculitis. Biopsy demonstrated a neutrophil-rich perivascular and interstitial inflammatory infiltrate, accompanied by leukocytoclasis, erythrocyte extravasation, and fibrinoid change involving vascular walls. A diagnosis of leukocytoclastic vasculitis was made. Several vasculitis therapies were employed during the next 3 months, without satisfactory results. A decision was made to obtain a second biopsy, but in the procedure room, numerous bugs were noted to be crawling over the patient's clothes and on the surgical chair. These were identified by the dermatologist as bedbugs. Following treatment of the bedbug infestation, the patient reported that the cutaneous lesions resolved. A PubMed search recovered only 1 published article on the subject of vasculitis secondary to bedbug bites. The vasculitis in that report manifested as bullous vasculitis. The patient in the present case did not have bullous lesions. The current case report will contribute to the scientific evidence supporting the occurrence of leukocytoclastic vasculitis in association with a bedbug infestation. Most importantly, this case documents that the vasculitis can be nonbullous.

Rubella Virus–Associated Chronic Inflammation in Inborn Errors of Immunity Diseases

(Poster No. 29)

Mahyar Khazaeli, MD1 ([email protected]); Ludmila Perelygina, PhD2; Susan Pei, MD.3 1Department of Pathology, University at Buffalo, New York; 2Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; 3Department of Dermatology/Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Many inborn errors of immunity have been identified with recent advancements in next-generation sequencing. Cutaneous granuloma, a severe complication in these patients, is caused by immunologic dysregulation, and treatment has focused on suppressing the immune system. Rubella virus (RuV) vaccine strain can persist for decades subclinically in body site(s) before emerging in granulomas. This review highlights recent findings of vaccine-derived Rubella virus persistence in granulomas of a patient with inborn errors of immunity. A 46-year-old woman with common variable immunodeficiency with a diagnosis at age 11 years presented for knee lesion evaluation. Examination showed reddish purple lesions (Figure 3.29, A), slowly growing for 20 years, which have been biopsied. Tests for fungi/bacterial species, syphilis, Kaposi sarcoma, and tuberculosis were negative. On biopsy, the epidermis showed pseudoepitheliomatous hyperplasia with lobules of squamous epithelium extending into the upper dermis. Throughout the dermis and into the subcutis there was a palisaded granulomatous inflammatory infiltrate with multinucleated giant cells and neutrophils with focal areas of fibrosis (Figure 3.29, B). CD68 showed the histiocytes forming palisades with central caseating necrosis (Figure 3.29, C). Double immunofluorescent staining with RuV capsid antibody (red) and either CD206 M2 macrophage-specific or MPO neutrophil-specific antibody (green) revealed neutrophils were positive for RCV staining (Figure 3.29, D). Vaccine-derived RuV was detected in lesion biopsy by polymerase chain reaction and sequencing. This case represents the identification of a vaccine-derived RuV strain in an immunocompromised adult and has potential implications for the diagnosis of other cutaneous granulomatous diseases. This entity should be considered in atypical cutaneous granulomas.

Pyoderma Gangrenosum Versus Necrotizing Fasciitis

(Poster No. 30)

Alexandra K. Medeiros, MD ([email protected]); Joseph White, DO; Intisar Ghleilib, MD; Matthew Powell, MD. Department of Pathology, Medical College of Georgia at Augusta University, Augusta.

Pyoderma gangrenosum and necrotizing fasciitis are 2 entities that can clinically present in a similar fashion; however, their treatments are vastly different and can exacerbate each other. Pyoderma gangrenosum is treated with high-dose corticosteroids, and it is exacerbated by trauma (including surgery). Necrotizing fasciitis is treated with serial debridement and antibiotics and can be worsened with immunosuppression (steroids). We present the case of a 51-year-old woman who had a routine hysterectomy performed for menometrorrhagia and was later found to have surgical wound complications on postoperative day 8. She was taken to the operating room to undergo wound debridement for suspected necrotizing fasciitis on 3 different occasions. After each debridement, her surgical wound continued to worsen. Microscopically, the abdominal tissue was ulcerated with marked underlying neutrophilia. After examining multiple debridement specimens, the degree of neutrophilia, negative wound cultures, and lack of bacterial organisms with necrosis brought a neutrophilic dermatosis (pyoderma gangrenosum) into the differential diagnosis. The patient was placed on high-dose corticosteroids and displayed marked improvement. Histologic clues that favor pyoderma gangrenosum are the degree of neutrophilia, dermal involvement with relative lack of subcutaneous involvement, abundant karyorrhexis, and the absence of bacterial organisms with necrosis. Necrotizing fasciitis and other infectious entities often involve the subcutaneous adipose tissue, display a lesser degree of neutrophilia, and show necrosis with bacterial organisms. We present this case to exhibit not only the importance of histologic clues pointing toward neutrophilic dermatosis but also the importance of how clinical presentation can further improve medical management.

Primary Cutaneous Adenosquamous Carcinoma

(Poster No. 31)

Mahyar Khazaeli, MD1 ([email protected]); Alicia Goldenberg, MD.2 1Department of Pathology, University at Buffalo, New York; 2Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Adenosquamous carcinoma of the skin is a rare but unique disease that usually has an aggressive course. Primary cutaneous adenosquamous carcinoma is best considered as a locally aggressive high-risk subtype of cutaneous squamous cell carcinoma. A few well-documented and uncontested instances of primary cutaneous adenosquamous carcinoma have been described to date. However, given its rarity, data about local recurrence and distant metastasis rates are sparse, and guidelines for the optimal method of excision and the role of adjuvant therapy are lacking. We reported a primary adenosquamous carcinoma of the skin. A 71-year-old woman presented with a right cheek lesion evaluation. The patient had no previous medical history. Physical examination revealed a raised, 2 × 1.5 × 0.5 cm, red, nontender, ulcerated plaque with slight exudate and gelatinous texture on the right cheek. The lesion was biopsied. The hematoxylin-eosin–stained section demonstrated an atypical neoplasm displaying both squamous and glandular differentiation (Figure 3.31, A). There was a proliferation of cytologically atypical P40-positive keratinocyte components that appeared to arise from the overlying epidermis (Figure 3.31, B). CK 5/6 immunohistochemical stain demonstrated strong and diffuse positivity, which also supported a primary cutaneous origin (Figure 3.31, C). Multiple glandular structures, some demonstrating mucinous differentiation, were also observed, which stained positive for mucicarmine (Figure 3.31, D). Adenosquamous carcinoma is a locally aggressive, high-risk form of cutaneous squamous cell cancer. Tumors with the abovementioned appearance should be designated as adenosquamous carcinomas by pathologists. In such cases, the possibility of a metastatic origin must always be ruled out.

Which Features, If Any, Are Diagnostically Specific for Allergic Contact Dermatitis?: A Detailed Review of 69 Clinically Confirmed Cases With Clinically Relevant Controls

(Poster No. 32)

Jiejun Wu, MD, PhD1 ([email protected]); Sydney D. Nigro-Sullivan, BS2; Peggy A. Wu, MD2; Maxwell A. Fung, MD.3 Departments of 1Pathology and Laboratory Medicine, 2Dermatology, and 3Pathology and Laboratory Medicine and Dermatology, University of California at Davis, Sacramento.

Context: The gold standard for diagnosing allergic contact dermatitis (ACD), patch testing, can be limited by access and expense. The histologic differential diagnosis of ACD, which shares similar or identical clinical and histopathologic features with other eczematous lesions, is challenging. Herein we report a comprehensive histopathologic evaluation on our ACD cohort that, to our knowledge, represents the most comprehensive study of the largest number of patch test–confirmed ACD cases to date.

Design: Patients at an academic tertiary referral center were seen by a board-certified and nationally recognized expert in patch testing. The selected histopathologic features (Table) were reviewed by an experienced board-certified dermatopathologist and resident physician in a blinded fashion and included the most significant features reported in the largest published ACD studies from Europe and North America.

Results: We examined 109 cases, of which 69 were patch test–confirmed ACD. The predominate presence of Langerhans cell collections within spongiotic vesicles, but not dermal eosinophilic infiltration, was significantly positively associated with ACD (χ2P = .008). In contrast, heavy dermal eosinophilic infiltration showed a significant association with patch test–negative cases (χ2P = .004). Similarly, epidermal eosinophilic spongiosis also had a negative association with ACD (χ2P=.02). All other features compared between patch test–positive and patch test–negative ACD cases, including multinucleated dermal dendritic cells, papillary dermal edema, and hypogranulosis, were not significantly associated with diagnosis of ACD (Table).

Conclusions: These results challenge the long-standing dogma of eosinophils supporting the diagnosis of ACD but support the recent finding that Langerhans cell collections are consistent with ACD.

Atypical Hidradenoma With Unusual Features and CRTC1-MAML2 Rearrangement

(Poster No. 33)

Ahmed F. Lazim, MD1 ([email protected]); Anjali Seth, PhD1; Hong Wu, MD, PhD3; Yuri Persidsky, MD, PhD1; Suad Taraif, MD1; Jian J. Fu, MD, PhD.1 1Department of Pathology, Temple University Hospital, Philadelphia, Pennsylvania; 2Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Eccrine hidradenoma (acrospiroma) is a benign adnexal neoplasm with eccrine and probable apocrine derivation. Atypical hidradenoma and hidradenocarcinoma are rare and challenging to diagnose. A 22-year-old woman with history of anemia, eczema, obesity, and dysmenorrhea presented with a large pedunculated lesion attached to her left lower eyelid. The lesion grew rapidly during the last year after being stable for 5 years. Computed tomography scan revealed a cutaneous/subcutaneous mass with a stalk at the left infraorbital preseptal soft tissue without involvement of the orbit and the maxillofacial osseous structures. Biopsy was performed and demonstrated a skin adnexal neoplasm, favoring hidradenoma. The lesion was later entirely excised with clear margins. The specimen showed a globular circumscribed tumor measuring 4.2 × 3.0 × 1.8 cm. The highly cellular tumor was composed of polygonal cells and clear cells with minimal nuclear pleomorphism and interspersed prominent mucinous metaplasia. The tumor cells extended from the surface epidermis into the dermis, arranged in trabecular and solid growth patterns. Increased mitosis was present focally (up to 8 mitotic figures per 10 high-power fields) without necrosis. Focal ductal differentiation was highlighted by positive diastase-resistant PAS stain and EMA immunostain (Figure 3.33, A through D, hematoxylin-eosin, EMA, mucicarmine, and Ki-67). The tumor was found to harbor t(11,19) (q14-21; p12-13) translocation resulting in the CRTC1-MAML2 fusion gene. The patient has been followed up for 8 months with no tumor recurrence. To our knowledge, this is the first report of atypical hidradenoma occurring in an eyelid with unusual features including prominent mucinous metaplasia, exceptionally high mitotic figures, and CRTC1-MAML2 translocation.

PRAME-Positive Cells in Dermal Scars: A Potential Diagnostic Pitfall

(Poster No. 34)

Woo Cheal Cho, MD ([email protected]); Phyu P. Aung, MD, PhD. Department of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston.

Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry has been widely used in the field of dermatopathology in recent years, proving its diagnostic utility for the distinction of benign and malignant melanocytic lesions. However, little is known about PRAME expression in dermal scars, which could potentially lead to an erroneous diagnosis of invasive melanoma when evaluating melanoma-excision specimens. We report 2 cases of aberrant PRAME expressions seen in dermal scars. The first case was from a 66-year-old woman with melanoma in situ on the left superior upper back. The excision specimen showed healing surgical wound/scar (Figure 3.34, A) and adjacent atypical melanocytic proliferation, consistent with residual melanoma in situ, which was positive for PRAME and MART1. Also noted within the scar were numerous PRAME-positive cells (Figure 3.34, B and C). These cells, however, lacked immunoreactivity for MART1 (Figure 3.34, D), and thus were interpreted as reactive fibroblasts/myofibroblasts. The second case was from a 63-year-old woman with left elbow melanoma, status after wide local excision, who presented with a brown macule at the site of prior excision clinically concerning for residual melanocytic lesion. Punch biopsy specimen revealed suture granuloma along with dermal fibrosis and scar. Similarly to the first case, anti-PRAME highlighted numerous PRAME-positive cells within the scar, which were negative for MART1. There was no histopathologic evidence of atypical melanocytic proliferation. To our knowledge, aberrant PRAME expressions in scar tissues have not been previously described. Awareness of this peculiar phenomenon, albeit rare, is crucial to avoid a potential overdiagnosis of melanoma in melanoma-excision specimens.

Metastatic De-Differentiated Melanoma With NRAS Mutation

(Poster No. 35)

Recep Nigdelioglu, MD ([email protected]); Ruifeng Guo, MD, PhD; Malvika H. Solanki, MBBS, PhD. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Melanomas are malignant tumors that arise from melanocytes. The diagnosis of these tumors requires morphologic features of in situ or invasive component and immunohistochemical evidence of melanocytic markers. Exceptionally, primary or metastatic melanoma can show transition between conventional and de-/trans-differentiated components by lacking these histologic and immunophenotypical features or gaining differentiation toward other lineages. The diagnosis of these exceptional de-/trans-differentiated melanomas relies on previous history and molecular evidence of melanoma. Here, we report a metastatic de-differentiated melanoma with NRAS mutation. The patient was a 57-year-old man without previous history of malignancy who presented for evaluation of swelling in his right axilla. The computed tomography showed an 8-cm irregularly shaped soft tissue mass within the right axilla and anterolateral chest wall. The core biopsy showed a S100 and SOX-10+ malignant neoplasm, and next-generation sequencing analysis demonstrated a NRAS Q61R (c.182A>G) mutation. He underwent right axillary dissection after neoadjuvant therapy. The histologic sections of the dissection showed a mixture of spindle and epithelioid neoplasm with necrosis and minimal treatment effect (Figure 3.35, A). A major component of the metastatic neoplasm did not express any melanocytic markers, including S100, SOX-10 (Figure 3.35, B), HMB-45 (Figure 3.35, C), and Melan-A; however, a small component expressed diffuse SOX-10 (Figure 3.35, B) and focal CKAE1/AE3 (Figure 3.35, D), supporting a diagnosis of metastatic de-differentiated melanoma. Our patient was referred to immunotherapy after surgery. In conclusion, de-/trans-differentiated melanomas are unusual, underrecognized tumors that can be challenging for pathologists. Thorough tumor sampling and previous clinical history might be essential for diagnosis.

Primary Malignant Melanoma of the Penis With a Rare Molecular Alteration

(Poster No. 36)

Suzanne J. Tintle, MD, MPH1 ([email protected]); Travis W. Vandergriff, MD2; Liwei Jia, MD, PhD.1 Departments of 1Pathology and 2Dermatology, University of Texas Southwestern, Dallas.

Primary malignant melanomas of the penis are extremely rare, accounting for an estimated 0.18% of all melanomas and less than 2% of all primary penile malignancies. We present a case of penile melanoma in an 82-year-old man, who was evaluated for a well-demarcated, homogenously dark brown, slightly raised plaque with irregular borders of the penile urethra with extension to the glans penis. Histologic examination of his subsequent partial penectomy revealed irregular nests of spindle and epithelioid pigmented melanocytes in the epithelium of the meatus, extensively involving the dermis and extending into the corpus spongiosum. The tumor measured 1.7 cm, with a Breslow depth of 9 mm (Clark level V), 6 mitoses/mm2, and no ulceration. Melanoma in situ and lymphovascular invasion were identified. Surgical resection margins were negative for tumor. Immunohistochemical stains showed patchy CD117 positivity and lack of BRAF V600E expression in tumor cells. Postoperative positron emission tomography (PET) scan showed no evidence of metastatic disease. However, 6 months later inguinal lymph node uptake was detected during follow-up PET scan. A pigmented lesion in the distal aspect of the penile shaft was concerning for recurrence. Subsequently, excision of the lesion confirmed recurrent melanoma with ulcerated surface and 3.5-mm Breslow depth, and inguinal lymph node dissection demonstrated metastasis in 1 of 8 lymph nodes with extranodal extension. Molecular analysis via multiplex PCR revealed a BRAF c.1780G>A mutation with resulting D594N alteration and was negative for c-Kit and NRAS mutations. The patient died of disease 18 months after his first presentation.

Diagnostic Differentiation Between Evolving Melanoma In Situ or Unusual Clark Nevus With the 35-Gene Expression Profile Test

(Poster No. 37)

Harold Rabinovitz, MD1 ([email protected]); Daniel Rivlin, MD2; Matthew S. Goldberg, MD.3 1Department of Dermatology, Medical College of Georgia at Augusta University, Augusta; 2Department of Dermatology, Miami Beach Skin Center, Miami, Florida; 3Department of Research & Development, Castle Biosciences Inc, Friendswood, Texas.

An 80-year-old man with a history of extensive sun damage and nonmelanoma skin cancers presented with a 12-mm–wide, multicolored skin lesion near the superior thoracic spine (Figure 3.37, A). Dermoscopy revealed an atypical network, gray granules, and pigmented structures predominant at the periphery with central, structureless areas (Figure 3.37, B). Reflectance confocal microscopy showed an atypical cobblestone pattern/pagetoid cells in the epidermis. Loss of meshwork pattern replaced by numerous spindle-shaped structures was noted at the dermoepidermal junction (DEJ; Figure 3.37, C). Clinical/noninvasive imaging features were characteristic of melanoma on sun-damaged skin; diagnostic shave biopsy was performed. Histopathologic review showed lentiginous epidermal hyperplasia/hyperpigmentation, discohesive nests of melanocytes, and atypical melanocytic hyperplasia at the DEJ (Figure 3.37, D, arrows). The underlying dermis contained a superficial perivascular lymphohystiocytic infiltrate with melanophages (Figure 3.37, D, circles). S100/MART-1 immunostaining showed a focal confluence of melanocytes at and above the DEJ. These findings favored a diagnosis of Clark nevus with unusual features with background of lichen planuslike keratosis. Re-excision was recommended because of unusual features/positive biopsy margin. Lacking definitive histologic features of melanoma, further diagnostic testing with the 35-gene expression profile (GEP) test was suggestive of a malignant melanocytic neoplasm. Considering histopathologic findings together with clinical information, imaging, and GEP results, the final pathology report was amended to a diagnosis of evolving melanoma in situ. The 35-GEP is a valuable ancillary tool to help achieve clinicopathologic correlation for melanocytic neoplasms with uncertain malignant potential and discordance between clinical features, noninvasive imaging, and histopathology.

H. Rabinovitz is a consultant with Castle Biosciences Inc. M.S. Goldberg is a Castle Biosciences Inc. shareholder. Acknowledgment: Writing assistance provided by Jason Rogers (Castle Biosciences).

Isocitrate Dehydrogenase Expression and Pathologic Correlations of Skin Disorders Associated With IDH1/2 Mutant Myeloid Malignancies

(Poster No. 38)

Jiani N. Chai, MD, PhD1 ([email protected]); Prateek Pophali, MD2; Aditi Shastri, MD3; Bijal Amin, MD4; Beth McLellan, MD5; Yang Shi, MD, PhD4; Yanhua Wang, MD, PhD.4 1Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York; 2Department of Medicine, Jacobi Medical Center, Bronx, New York; Departments of 3Medicine, 4Pathology, and 5Dermatology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York.

Context:IDH1/2 mutations are seen in up to 14% (IDH1) and 19% (IDH2) of acute myeloid leukemia (AML) and 3% (IDH1) and 5% (IDH2) myelodysplastic syndrome (MDS) cases. Cutaneous manifestations of myeloid malignancies can be specific lesions or nonspecific skin eruptions. It is established that IDH mutations promote leukemogenesis; however, their etiologic role in myeloid malignancy–associated skin disorders remains unclear. We investigated skin lesions for isocitrate dehydrogenase (IDH) expression in IDH mutant myeloid malignancies.

Design: AML/MDS patients with IDH mutation and skin biopsies were searched retrospectively (2015–2021). Clinical presentation and pathology features were reviewed. IDH1-R132H and IDH2 immunohistochemistry stains were performed to assess IDH mutation on the skin biopsies.

Results: A total of 6 AML patients and 1 MDS patient were identified, including 5 patients with IDH1 mutation and 2 with IDH2 mutations. One patient presented with skin lesion prior to MDS; other cases presented with skin lesions in the setting of AML. Skin biopsy revealed 1 case with leukemia cutis and 1 case with histiocytoid Sweet syndrome; the remaining cases had other nonneoplastic lesions. Immunohistochemistry (IHC) showed strong IDH2 expression in the myeloid infiltrates in the leukemia cutis case, corresponding to the patient's IDH2 mutation (Figure 3.38, A and B). In the Sweet syndrome case, IDH1-R132H IHC was positive in the immature histiocyte-like myeloid cells, corresponding to the patient's IDH1 mutation (Figure 3.38, C and D). In other cases, IDH stains were negative or weakly positive.

Conclusions: This limited study suggests that IDH mutated cells may be implicated in the pathogenesis of myeloid malignancy–associated neoplastic skin lesions and neutrophilic dermatoses. Future investigation is important to elucidate this pathway.

A. Shastri is a consultant with Jansen Pharmaceuticals, has received grant or research support from Kymera Therapeutics, and has received honoraria from Onclive.

From Moulage to (Survey) Metrics: More Than 100 Years of Publications Related to the Visual Arts in the Fields of Dermatopathology (Pathology) and Dermatology

(Poster No. 39)

Aayushma Regmi, MBBS1 ([email protected]), Madhu Dahiya, MD.2 1Department of Pathology and Laboratory Medicine, Loyola University Medical Center, Maywood, Illinois; 2Pathology and Laboratory Medical Service, Edward Hines Jr Veterans Affairs Hospital, Hines, Illinois.

Context: We performed a full bibliometric analysis of publications found via multiple medical search engines and select key words meant to “capture” art-related publications in the fields of dermatopathology (pathology) and dermatology.

Design: Key words and key word combinations were entered into the search engines PubMed, Google Scholar, Science Direct, Pubs Hub, and Scopus. The following keywords were used: art, picture, diagram, portrait, sculpture, painting, skin, dermatology, dermatopathology, pathology, and various combinations of the aforementioned words (eg, portraits/dermatology, art/dermatopathology). Topics of articles, years of publication, countries of origin, and contributing journals were compiled and analyzed.

Results: A total of 80 publications were retrieved during the period between January 1903 and August 2021. No publications were retrieved from Pubs Hub or Scopus. Most articles were found in more than 1 search engine: 54 articles in PubMed and Google Scholar, followed by 12 articles in PubMed, Google Scholar, and Science Direct. Top publication years were 2020 (n = 10), 2017, and 1990 (n = 5). Geographically, the United States (n = 34) had the most articles, followed by the United Kingdom (n= 13). The following key words, or key word combinations, yielded the most journal articles: dermatology/art (n = 32), art/dermatology/dermatopathology (n = 23) and dermatopathology/sculpture (n = 6). The maximum number of publications were retrieved from JAMA Dermatology (n = 13), followed by the American Journal of Dermatopathology (n = 10) and Clinics in Dermatology (n = 8; Figure 3.39).

Conclusions: To our knowledge, this is the first study of its kind. We believe that our data analysis and survey will provide useful insights and information for the physician and researchers interested in this field.

Giant Size Pilomatricoma Protuberans in Chest Wall

(Poster No. 40)

Raafat Makary, MD, PhD; Matthew T. Carpenter, MD (Matthew. [email protected]); Amal Shukri, MD. Department of Pathology, University of Florida Health, Jacksonville.

Pilomatricomas (calcifying epithelioma of Malherbe) are uncommon tumors derived from the skin-hair matrix. They occur at any age but are most common in childhood, adolescence, and more than 60 years of age, with predilection for the scalp, face, and upper extremities. Clinically, they present as a subcutaneous nodule or cyst (0.5–3.0 cm) with unremarkable overlying epidermis. The prognosis is typically good, and excision is curative. Few cases of giant pilomatricoma (>5 cm in size) are reported and may be clinically concerning for a malignant tumor or complicated by ulceration and infection. We report a case of a 56-year-old man with a 5.8-cm mass protruding from the anterior chest wall. Chest computed tomography scan showed a cutaneous/subcutaneous mass with internal amorphous calcification (Figure 3.40, A, arrow). The resected mass was well circumscribed, with fungating and surface ulceration, inflammation, and necrosis with calcification on its cut surface (Figure 3.40, B and C). Microscopically, it was formed of anucleate squamous “ghost cells,” viable basaloid squamous cells (Figure 3.40, D), calcification, foreign body giant cell reaction, and no features of malignancy. Giant pilomatricomas, generally defined as tumors larger than 5 cm, are rare (less than 10% of pilomatricomas). The large tumor size, complicated by ulceration and infection, may raise clinical concern for malignancy. The pathogenesis has not been completely elucidated. However, the Wnt/β-catenin signaling pathway has been shown to be upregulated in normal matrix cells of the hair follicle. Activating mutations in β-catenin appear to be fundamental in the development of this tumor. Malignancy in pilomatricoma is extremely rare and simple excision/resection is curative.

Localized Cutaneous Amyloidosis Due to Insulin Injections: A Unique Presentation in an Underreported Condition

(Poster No. 41)

David Gustafson, MD ([email protected]); Daniel Rosen, MD; Bhuvaneswari Krishnan, MD; Yve Huttenbach, MD. Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas.

Insulin-derived amyloidosis is typically a localized process at sites of insulin injections. Fewer than 100 cases have been reported. Pathogenesis is poorly understood but thought to involve the ability of insulin to self-assemble into fibrils in tissue. Typical presentation is a subcutaneous nodule at the site of injections, and lymph node involvement is rare. Clinical history was obtained from electronic medical record review. Skin punch biopsy was evaluated with hematoxylin-eosin stain. Congo red stain was performed to evaluate the amyloid deposits. A 61-year-old man with diabetes mellitus presented with a hyperpigmented rash and subcutaneous dermal nodules on the abdomen at sites of prior insulin injections. Clinically, the differential diagnosis included morphea, erythema ab igne, and confluent and reticulated papillomatosis. Punch biopsy showed epidermis with mild acanthosis with perivascular eosinophilic amorphous material in the dermis with foreign body giant cell reaction. Amorphous material was congophilic and showed focal apple-green birefringence on polarization. Cutaneous amyloidosis due to insulin injections is rare and likely underreported. Our patient had a unique presentation that involved a hyperpigmented rash with multiple subcutaneous nodules. These findings may be described as acanthosis nigricans–like changes due to high concentrations at the site of injection. Histologic findings were similar to those in the literature and included deposition of amorphous, eosinophilic material, foreign body giant cell reaction, and Congo red staining with green birefringence by polarization. Accurate diagnosis of these lesions is important in diabetic patients because amyloidogenic nodules may hinder insulin absorption, leading to worsening glycemic control.

Varicella Zoster Virus Infection Presenting as a Subcorneal Pustule Dermatosis

(Poster No. 42)

Aayushma Regmi, MBBS ([email protected]); Kumaran M. Mudaliar, MD. Department of Pathology and Laboratory Medicine, Loyola University Medical Center, Maywood, Illinois.

An 88-year-old nonimmunocompromised man presented with bowel obstruction and underwent bowel resection that was complicated by perforation. Two days after the admission, he was noted to have painless, purpuric bullous lesions on the arms and legs at different stages of healing (Figure 3.42, A). Dermatology was consulted and the differential diagnoses included the favored diagnosis of bullous impetigo (BI) and bullous pemphigoid (BP). Right forearm biopsy was performed. Histologic sections showed a subcorneal pustule with neutrophils and karryorechtic debris. The superficial dermis showed red blood cell extravasation and perivascular inflammation with neutrophils and karyorrhectic debris (Figure 3.42, B through D). Direct immunofluorescence studies were negative, excluding BP. A subcorneal pustular dermatosis (SPD) was favored. SPD is an umbrella term encompassing various diagnostic entities. Of these entities, BI was favored given clinicopathologic correlation, and a leukocytoclastic vasculitis was included in the differential diagnosis as well. A week after case sign-out, a previously performed varicella zoster virus (VZV) swab came back positive for VZV by polymerase chain reaction (PCR). The histologic sections were rereviewed, and viral cytopathic changes were not identified. Still, given the karyorrhectic debris and overall histopathologic findings in conjunction with the positive VZV PCR, a diagnosis of disseminated zoster infection became the favored diagnosis. The patient was started on IV acyclovir and the lesions started to improve with therapy. We present this case of an atypical presentation of disseminated zoster infection that was both clinically and histopathologically challenging.

Seborrheic Keratosis With Histologic Features of Epidermodysplasia Verruciformis: Correlated or Coincidental?

(Poster No. 43)

Aayushma Regmi, MBBS ([email protected]); Jodi J. Speiser, MD. Department of Pathology and Laboratory Medicine, Loyola University Medical Center, Maywood, Illinois.

A 72-year-old man with a past medical history of superficial spreading melanoma on right upper arm presented with a 0.6 × 0.5-cm brown papule with black crust at right antecubital fossa for about 6 months. He stated that the lesion had been growing in size and bled spontaneously; however, he denied pain, pruritus, and clear exacerbating or alleviating factors. Shave biopsy was performed for definitive diagnosis. Biopsy sections showed a squamous acanthoma with hyperkeratosis, papillomatosis, acanthosis, pseudo–horn cyst formation (Figure 3.43, A). Focal areas were noted to have large, epithelioid, and irregularly shaped keratinocytes with abundant, pale gray-blue cytoplasm and numerous, round, basophilic keratohyaline granules and nuclear vacuolization (Figure 3.43, B through D). Although the population of paler-staining cells was histologically suspicious for epidermodysplasia verruciformis (EV), given the clinical presentation (single lesion and no proven history of human papillomavirus [HPV]), seborrheic keratosis (SK) with histologic features of EV was favored. EV is a rare, inherited disorder characterized by widespread HPV infection (mostly by HPV5 and HPV8) and cutaneous squamous cell carcinoma. Lesion can present as a scaling patch or plaque, with tinea versicolor–like, verruca vulgaris–like, and SK-like subtypes. EV-like changes have been previously reported as an incidental finding in a variety of benign skin lesions, including SK. When histologic changes of EV and EB-HPV PCR are present in an isolated skin lesion (without clinical evidence of EV), a diagnosis of EV acanthoma is rendered. We present this case to raise the awareness of this diagnosis.

Lymphomatoid Papulosis With DUSP22-IRF4 Rearrangement: A Case Report and Review of Literature

(Poster No. 44)

Na Niu, MD, PhD1; Zhenya Tang, MD2; Carlos Torres-Cabala, MD1; Woo Cheal Cho, MD1 ([email protected]). Departments of 1Pathology and 2Hematopathology, University of Texas MD Anderson Cancer Center, Houston.

Lymphomatoid papulosis (LyP) with DUSP22-IRF4 rearrangement is a rare variant of LyP, with fewer than 20 cases reported to date in the English literature. We describe another case of LyP with DUSP22-IRF4 rearrangement in a 63-year-old man who presented with an erythematous papule on the left neck and provide a comprehensive literature review. Histopathologically, the lesion showed an atypical dense lymphoid infiltrate with epidermotropism, with biphasic morphology (Figure 3.44, A). By immunohistochemistry, the infiltrate was predominantly composed of CD3+/CD8+ T cells, with a CD4/CD8 (Figure 3.44, B) ratio of 1:6–8 and loss of CD7 expression. The infiltrate was diffusely CD30+ (Figure 3.44, C), with stronger expression in the dermal component than the epidermotropic cells. Most neoplastic cells were also positive for TCR β F1 and GATA3 but negative for TCR δ, granzyme B, ALK1, and EBER (by in situ hybridization). Anti-TIA1 highlighted scattered cells in the infiltrate. Fluorescence in situ hybridization using the IRF4/DUSP22 dual-color break-apart rearrangement probe revealed the presence of DUSP22-IRF4 rearrangement (Figure 3.44, D). The overall findings were consistent with CD30+ lymphoproliferative disorder, with differential diagnoses, including LyP and primary cutaneous anaplastic large cell lymphoma with DUSP22-IRF4 rearrangement. The localized nature of the lesion, which resolved clinically following biopsy, and the lack of additional tumoral nodules or patches/plaques favored the former. He has remained free from clinical recurrence for 4 months since the initial biopsy. To our knowledge, this represents the 15th reported case of LyP with DUSP22-IRF4 rearrangement, adding to the growing pool of documented cases featuring this novel entity.

A Rare Case of Axillary Extramammary Paget Disease With an Underlying Adenocarcinoma

(Poster No. 45)

Colby Felts, MS ([email protected]); Victoria Durkin, MD; Ali Jassim, MD, PhD. Department of Pathology, University of South Dakota, Sanford School of Medicine, Sioux Falls.

Extramammary Paget disease (EMPD) is an uncommon cutaneous neoplasm almost exclusively located in the vulvar, perianal, and male genitalia regions. Evaluation and management are complicated given the average delay in diagnosis is 2 years and approximately 30% of cases are associated with underlying malignancies. The axilla is a unique location for EMPD. We report a rare case of a 78-year-old man with axillary EMPD associated with an underlying adenocarcinoma. A 1-cm tender and pruritic erythematous plaque with surrounding erythema appeared in the patient's axilla. An irritated seborrheic keratosis secondarily impetiginized along with irritant contact dermatitis was suspected. Treatment of cefdinir and topical hydrocortisone failed, and a biopsy was taken. Microscopic and immunohistochemical examination showed ulceration with an underlying proliferation of atypical glands (Figure 3.45, A) and a nested intraepidermal proliferation with pagetoid spread (Figure 3.45, B). The atypical cells were positive for gross cystic disease fluid protein 15 (Figure 3.45, C), epithelial membrane antigen (Figure 3.45, D), and cytokeratin 5/6/7. These findings were supportive of an apocrine adenocarcinoma arising in association with EMPD. Wide location excision was performed. Screening for associated malignancies or lymphatic spread is the primary goal during evaluation. Outcomes are favorable when the primary neoplasm is of limited distribution. The accepted treatment for primary lesions is wide local excision, although anatomic tissue constraints necessitate further research into other treatment modalities. To our knowledge, this is the 14th reported case of axillary EMPD with an underlying adenocarcinoma, which may help with identification and management of future cases.

Histologic Evaluation of Wound-Bed Preparedness Following Microsurfaced Skin Grafts for the Treatment of Deep Burn Wounds: Interim Analysis From a Randomized Controlled Trial

(Poster No. 46)

Lisa M. Marinelli, MD1 ([email protected]); Kevin Krauland, MD1; Shannon Alcorta, MHS2; Bounthavy Homsombath, MD3; Shawn Fagan, MD3; Beretta Craft-Coffmann, PA-C3; Zaheed Hassan, MD.3 1Department of Pathology and Area Laboratory Services, Brooke Army Medical Center, Ft Sam Houston, Texas; 2Department of Pathology Reference Laboratory, Pathology Reference Laboratory, San Antonio, Texas; 3Department of Joseph M. Still Burn Center, Doctors Hospital, Augusta, Georgia.

Context: Allogeneic skin grafts play an important role in the temporary skin coverage of large skin defects prior to autograft application. We conducted a prospective, randomized controlled trial to investigate the effectiveness of microsurfaced versus control cadaveric split thickness skin grafts in promoting wound-bed preparedness, as assessed histologically.

Design: Twenty patients with deep partial or full thickness burns were enrolled. Each patient was treated with a microsurfaced and control graft at adjacent sites (each at least 4.0 cm2), with randomized, blinded assignment. Grafts were removed at 12 to 19 days following application and histologically assessed for maximum cell concentration (over 1.0 mm2), maximum incorporation depth (1 to 5 scale), maximum total graft thickness, and predominant dermal cell type.

Results: Interim analysis of the first 10 completed patients revealed a greater maximum cell concentration in the microsurfaced skin grafts in comparison with the control grafts (median 3661 versus 1510 cells/mm2; P = .004). A predominant cell type of neutrophils was observed more frequently in the microsurfaced grafts (9 of 10 versus 1 of 10 cases; P = .001). Similarly, the microsurfaced grafts had a greater maximum thickness (mean, 1.5 versus 0.92 mm; P = .02). Ninety percent of microsurfaced grafts achieved an incorporation depth score of at least 4 in comparison with 44% of control grafts, although this difference did not achieve statistical significance (median, 4 versus 2; P = .4; Table).

Conclusions: Microsurfaced skin grafts resulted in consistent incorporation and greater cellular infiltration and graft thickness than their control graft counterparts, a finding we attribute to increased surface area at the graft-to-host interface. Z. Hassan has received grant or research support from Markman Biologics Corporation.

Spindle Cell Melanoma in a Background of Myxoid Matrix in an African American Patient: A Diagnostic Challenge

(Poster No. 47)

Hardik Sonani, MD ([email protected]); Imran Ajmal, MD; Youssef Al Hmada, MD. Department of Pathology, University of Mississippi Medical Center, Jackson.

Spindle cell melanoma (SPM) is a rare histologic type of melanoma characterized by the presence of spindle-shaped melanocytes. Microscopically, it is frequently confused with other skin and soft tissue tumors with spindle cell proliferation. We are presenting a case of a 78-year-old African American woman who presented with a complaint of a lump on the posterior back, which slowly increased in size. Excisional biopsy showed a poorly marginated intradermal spindle cell neoplasm with a notably infiltrative growth pattern. The lesional cells were mildly atypical ovoid or more tapering nuclei with scattered mitotic figures and arranged in fascicles and cohesive bundles (Figure 3.47, A). There were small foci of perineural invasion (Figure 3.47, B). The lesion was associated with a multifocal myxoid matrix, which is a relatively uncommon finding. Immunostains showed strong and diffuse positivity for S100 (Figure 3.47, C) and SOX10 (Figure 3.47, D), which also demonstrated the tumor cells were indeed infiltrating in cohesive bundles. CD34, H3K27me3, HMB-45, tyrosinase, and MART-1 were negative. Based on these morphologic and immunohistochemical findings, we have rendered the diagnosis of spindle cell malignant melanoma. She subsequently underwent wide local excision with uninvolved margins and negative sentinel lymph nodes. She is currently on active surveillance with a positron emission tomography scan with no metastases. SPM is typically nonpigmented, which, combined with its proclivity for subtle pathologic features, contributes to its frequent misdiagnosis. Knowledge of its clinical features and morphologic appearances, as well as a high index of suspicion, are required to establish the diagnosis at an early and potentially curable stage.

A Novel Case of Vitiligoid Lichen Sclerosus Presenting in an Extramucosal Location

(Poster No. 48)

Ashleigh M. Tomkovich, MD1 ([email protected]); Jonathan T. Colston, MD2; Mark S. Lincoln, MD.1 Departments of 1Pathology and 2Dermatology, San Antonio Uniformed Services Health Education Consortium, Fort Sam Houston, Texas.

Vitiligoid lichen sclerosus (LS) is a rare variant of LS characterized by concurrent clinical and histologic features of vitiligo and LS. This variant has been previously described predominantly in oral and anogenital regions. Herein, we describe a novel case of extramucosal vitiligoid LS. A 59-year-old African American woman presented with a 3-month history of a pruritic rash on her left hip with areas of white discoloration. Physical exam demonstrated a 5 × 5 cm, poorly defined plaque composed of several smaller atrophic, hypopigmented and depigmented, irregularly shaped macules and patches. The remainder of her dermatologic exam, to include the oral and anogenital regions, was unremarkable. A punch biopsy demonstrated epidermal atrophy, homogenized superficial dermal collagen, a lichenoid interface dermatitis, and dermal pigment incontinence. Immunohistochemical staining with Melan-A confirmed an absence of melanocytes. These findings, taken together with the patient's clinical history, were consistent with vitiligoid LS. The patient was treated with topical clobetasol. Although typically found on mucosal sites, the present case highlights the importance of consideration of vitiligoid LS in patients presenting with depigmented lesions with associated atrophy and/or pruritis on extramucosal sites as well. Although conventional vitiligo may present with mild associated atrophy and/or sclerosis, the findings of a diffusely vacuolar interface dermatitis or persistence of basement membrane changes after recession of the lymphocytic infiltrate, in addition to a hyalinized, rather than mildly fibrotic, dermis, favor a diagnosis of vitiligoid LS.

Intravascular Large B-Cell Lymphoma Mimicking an Allergic/Hypersensitivity Reaction

(Poster No. 49)

Precious Fortes, MD ([email protected]); Chandra Smart, MD. Department of Pathology, UCLA School of Medicine, Los Angeles, California.

Intravascular large B-cell lymphoma (IVLBCL) is a rare, large B-cell lymphoma characterized by a selective, intravascular growth pattern that is often associated with an aggressive clinical course. Cutaneous manifestations of IVLBCL vary greatly, which may delay diagnosis. We report a case of IVLBCL mimicking an allergic/hypersensitivity reaction in a 65-year-old man with a history of antiphospholipid syndrome and recent COVID-19 infection, who was admitted to the hospital for recurrent strokes. Dermatology was consulted for a pruritic rash on his right leg for the past 2 weeks. On clinical exam, there were many excoriated papules on the extremities, initially thought to be secondary to an arthropod bite. A punch biopsy was performed for further evaluation of the lesions. Histologic sections showed large, neoplastic B cells with vesicular nuclear chromatin and distinct nucleoli within multiple small dermal vessels (Figure 3.49, A). Immunohistochemical stains were performed and highlighted the neoplastic B cells that were positive for pan–B-cell markers, including (Figure 3.49, B) CD20, (Figure 3.49, C) PAX-5, and (Figure 3.49, D) CD19 consistent with IVLBCL. The Ki-67 proliferation index was more than 90%. Additionally, background changes showed a concurrent allergic/hypersensitivity process. Given the variable cutaneous clinical signs, including nodules/plaques, macules, and/or telangiectatic patches, a skin biopsy is critical in aiding in the diagnosis of IVLBCL. Review of the literature demonstrates relatively high percentages of increased overall survival with new therapies available, further highlighting the importance of early recognition, rapid diagnosis, and initiation of therapy in improving prognosis.

Higher Prevalence of Cutaneous Squamous Cell Carcinoma in Patients With Colorectal Adenocarcinoma

(Poster No. 50)

Tarneem Darwish, MD ([email protected]); Wei Xin, MD, PhD. Department of Anatomical and Clinical Pathology, Case Western Reserve University/University Hospitals of Cleveland, Ohio.

Context: Ultraviolet B radiation had been linked to both cutaneous squamous cell carcinoma (CSCC) as a causative factor and colorectal cancer (CRC) as a predictive factor. Meanwhile, heat shock protein 105 (HSP105), produced in response to heat stress and recently postulated as a potential new biomarker for CSCC, was found to be overexpressed in patients with a diagnosis of CRC as well. Our group is interested in understanding if there is an increased risk for patients with a diagnosis of CRC to have a higher incidence of CSCC diagnosis during their life.

Design: Pathology reports of patients at our institute with a diagnosis of CRC from August 2010 to August 2021 were retrieved and analyzed for synchronous or metachronous diagnosis of either CSCC or actinic keratosis (AK).

Results: CSCC was found to be diagnosed in 1.8% of colorectal adenocarcinoma cases, whereas none of the colorectal adenoma with high-grade dysplasia or the neuroendocrine neoplastic cases showed a diagnosis of CSCC. AK was diagnosed in 1.7% of colorectal adenocarcinoma cases, and in 0.9% of colorectal high-grade dysplasia cases: odds ratio, 2.07 (95% CI, 0.27–15.9). None of the colorectal neuroendocrine neoplastic cases showed a diagnosis of AK.

Conclusions: Although not statistically significant there are notably increased rates of CSCC and AK in patients with a diagnosis of colorectal adenocarcinoma. Further studies are needed to understand the pathophysiology behind this association.

An Elderly Woman With Posttransplantation Immunosuppression-Associated Disseminated Nocardia Thailandica

(Poster No. 51)

Shannon A. Rodgers, DO1 ([email protected]); Linoj P. Samuel, PhD1; Robert J. Tibbetts, PhD1; Anita B. Shallal, MD2; Mayur Ramesh, MD2; Madhu Menon, MD, PhD.3 Departments of 1Pathology and Laboratory Medicine and 2Infectious Diseases, Henry Ford Health System, Detroit, Michigan; 3Department of Pathology, ARUP Labs and University of Utah School of Medicine, Salt Lake City.

Nocardia is a known opportunistic pathogen that was first isolated and reported from a Thai patient's abscess in 2004 and subsequently has been isolated from respiratory, eye, and skin infections. A 63-year-old woman with a past medical history of renal transplantation on immunosuppression for 3 years was admitted with a history of malaise, body aches, cough, and headaches. On physical examination, she had an enlarged cervical lymph node and a 1.5-cm erythematous nodule on left thigh. Brain magnetic resonance imaging demonstrated multiple ring-enhancing lesions, and chest x-ray revealed a well-circumscribed right lung nodular opacity. Subsequent biopsy of the enlarged lymph node revealed histiocytic proliferation; acute inflammation with neutrophils; necrosis; and beaded, branching organisms (Figure 3.51, A) that were GMS positive and Gram stain positive but were negative by AFB (Ziehl-Neelsen) and modified AFB stain. Skin nodule biopsy demonstrated septic vasculitis and acute inflammation with numerous Gram-positive filamentous organisms. Routine microbiology cultures (blood, chocolate, and buffered charcoal yeast extract agars at 35°C and 6% CO2) from skin, bronchoalveolar lavage, and cerebrospinal cultures grew white, rough-surfaced colonies (Figure 3.51, B). Gram stains revealed the same Gram-positive branching filamentous organisms (Figure 3.51, C and D). Direct colony method identification from the skin tissue through matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was attempted but failed to generate a reliable identification at our laboratory. Subsequently, the state department resulted a positive identification of the organism as Nocardia thailandica. Our case is the first reported disseminated N thailandica infection involving the central nervous system, lung, lymph nodes, and skin in an immunocompromised setting.

Colonic Involvement in Disseminated Histoplasmosis of an Immunocompetent Child: A Case Mimicking Crohn Disease

(Poster No. 52)

C. Quinn Miller, MD; Omer Saeed, MD; Katrina Collins, MD ([email protected]). Department of Pathology, Indiana University, Indianapolis.

Infection with Histoplasma capsulatum can lead to disseminated disease involving the gastrointestinal tract presenting as diffuse abdominal pain and diarrhea which may mimic inflammatory bowel disease. We report a case of 12-year-old boy with a presumptive diagnosis of Crohn disease (CD) who presented with several months of abdominal pain, weight loss, and bloody diarrhea. Colonoscopy showed patchy moderate inflammation characterized by erythema and numerous pseudopolyps involving the terminal ileum (Figure 3.52, A), cecum, and ascending colon. Histologic sections from the colon biopsy revealed diffuse cellular infiltrate within the lamina propria with scattered histiocytic aggregates, and occasional nonnecrotizing granulomas (Figure 3.52, B and C). Grocott-Gomori methenamine silver staining confirmed the presence of numerous yeast forms suggestive of H capsulatum (Figure 3.52, D), which was further confirmed with positive urine histoplasma antigen (6.58 ng/mL; range, 0.2–20 ng/mL) and immunoglobulin G (IgG) antibodies to Histoplasma (35.9 EU). Intravenous amphotericin was administered then transitioned to oral itraconazole. Follow-up computed tomography imaging showed a left lower lung nodule and mesenteric lymphadenopathy consistent with disseminated histoplasmosis infection. Gastrointestinal involvement with H capsulatum with no accompanying respiratory symptoms is exceedingly rare, and recognition is often delayed because of the overlap of symptoms with manifestations of inflammatory bowel disease. This case illustrates the importance of excluding infectious etiologies in patients with “biopsy-proven” CD prior to initiating immunosuppressive therapies. Communication between clinicians and pathologists is crucial because blood cultures and antigen testing are key studies that should be performed in all suspected histoplasmosis cases.

Prevalence of ESBL Production in AmpC Derepressed Enterobacterales Isolated From Body Fluids

(Poster No. 53)

Pranav S. Renavikar, MBBS ([email protected]); Barbara J. Cabrera, BS; Paul D. Fey, PhD. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha.

Context: Plasmid-mediated extended-spectrum and chromosomally encoded AmpC β-lactamases mediate the resistance of Enterobacterales to the expanded-spectrum cephalosporins. ESBLs cannot be phenotypically detected in Enterobacterales that produce AmpC β-lactamases. Organisms producing ESBLs are resistant, whereas AmpC β-lactamases are typically susceptible to cefepime. The goal of this study was to determine cefepime susceptibility in Enterobacterales producing a derepressed AmpC β-lactamase that also produced an ESBL.

Design: We tested 99 AmpC β-lactamases producing Enterobacterales (ceftriaxone and cefoxitin resistant, isolated from body fluid sources) for the presence of ESBLs using polymerase chain reaction and gel electrophoresis. The isolates underwent Microscan susceptibility testing for cefepime, followed by resistance verification using E-test methodology.

Results: A total of 9 of 99 isolates were resistant to cefepime. A total of 3 of 9 resistant isolates expressed a CTX-M ESBL, whereas 1 isolate expressed a likely SHV ESBL. A total of 5 of 9 resistant isolates expressed no other β-lactamase. Of the 90 cefepime-susceptible isolates, only 1 encoded another β-lactamase. Overall, 4 of 99 isolates (4%) demonstrated the coexistence of AmpC and ESBL genes, and all (100%) were resistant to cefepime.

Conclusions: A small percentage of AmpC-producing Enterobacterales coexpressed an ESBL (4%). All 4 isolates were resistant to cefepime, suggesting that cefepime very major error rates in AmpC-producing Enterobacterales is rare. Further, we found 5 other cefepime-resistant isolates that did not encode a TEM, SHV, OXA, or CTX-M β-lactamase, suggesting that these isolates may have enhanced AmpC β-lactamase production and/or mutations in outer membrane porins. Lastly, it was unexpected that we did not detect common TEM/SHV β-lactamases that are seen in other Enterobacterales, such as Escherichia coli and Klebisella pneumoniae.

JC Virus Detection in Symptomatic Patients Suspected of Having Urinary Tract Infection

(Poster No. 54)

Rajan Dewar, MD, PhD1 ([email protected]); Dakun Wang, MB, PhD2; Xinhua Zhao, PhD3; Natalie Luke, PhD1; Patrick Cacdac, MD4; Dave Baunoch, PhD.1 1Department of Pathology, Pathnostics Inc, McLaren Greater Lansing & Michigan State University, Lansing; Departments of 2Writing and 3Statistics, Stat4ward, Pittsburgh, Pennsylvania; 4Department of Clinical Research, Outcomes, and Education, Pathnostics Inc, Irvine, California.

Context: JC virus is ubiquitous, with primary infection during childhood and latent/persistent infection in renal tissues of adults. JC virus has been detected in the urine of immune-compromised/healthy adults. However, the pathogenetic mechanisms, or associations with other putative etiologies, are unknown.

Design: JC virus and 28 urogenital microbes in urine samples from 2512 patients with urinary tract infection (UTI) symptoms (1360 female and 1152 male patients; mean age, 73.2 years) from 37 urology clinics in 7 US states between July 2018 and February 2019 were evaluated with Guidance UTI, a multiplex polymerase chain reaction–based test.

Results: A total of 367 patients (14.6%) were positive for JC virus, with or without other microbes. It was associated with male sex (20.1% versus 10.0%; P < .001), older age (75.0 versus 72.8 years; P < .001), and fewer urinating incontinence symptoms (24.3% versus 29.5%; P = .04). Urinalysis results showed a lower leukocyte positivity rate (56.4% versus 63.8%; P = .009) associated with JC virus detection (34% when only JC virus was detected). Bacterial detection rates were lower in JC virus–positive than JC virus–negative patients (57.5% versus 63.8%; P= .02). Most of the positive patients (approximately 85%) were taking nephrotoxic medications or drugs metabolized/excreted primarily through kidney. A total of 13.3% of patients were taking medications with immunosuppressive effects.

Conclusions: JC virus is seen in a significant (14.6%) proportion of patients and is often in male/older age individuals. It may be associated with a nephrotoxic or immunosuppressive medications. JC virus may not be of pathogenetic significance in UTIs, and further study of its pathogenetic significance in urine is required.

D. Wang and X. Zhao are consultants with Pathnostics.

Age- and Gender-Based Differences in Organisms Associated With Urinary Tract Infections

(Poster No. 55)

Shenbagam Dewar, MD1; Natalie Luke, PhD2 ([email protected]); Dakun Wang, MB, PhD4; Xinhua Zhao, PhD5; Patrick Cacdac, MD2; Rajan Dewar, MD, PhD6; David Baunoch, PhD.3 1Department of Geriatrics, University of Michigan, Ann Arbor; Departments of 2Medical Research, Education & Outcomes and 3Research and Development, Pathnostics Inc, Irvine, California; Departments of 4Writing and 5Statistics, Stat4ward, Pittsburgh, Pennsylvania; 6Department of Pathology, McLaren Greater Lansing, Pathnostics Inc, and Michigan State University, Lansing.

Context: Multiplex polymerase chain reaction (M-PCR) is more sensitive than culture and sensitivity and identifies polymicrobial infections. This abstract focuses on the differences in M-PCR detections of bacteria by age and gender in urinary tract (UT) infections. Because voided urine/lower UT commonly introduces contamination, only catheter-collected samples were analyzed in this study.

Design: We used Guidance UTI, an M-PCR–based test, to detect 27 urogenital bacteria/bacterial groups in catheter-collected urine samples from 3442 patients with UTI symptoms from September 2021 to February 2022. Bacterium at 1000 cells/mL or more was defined as “detected.”

Results: Bacterial detection rate was higher in male (n = 602) than female (n = 2840) patients (74.1% versus 60.5%, P < .001), and higher in the younger than 65 years (n = 1060) than the 65 years and older (n = 2382) group (55.1% versus 66.4%, P < .001). The most frequently detected bacteria for male patients were Enterococcus faecalis (34.2%), Pseudomonas aeruginosa (18.6%), and Escherichia coli (17.3%), and for female patients E coli (27.1%), E faecalis (15.0%), and Actinotignum schaalii (9.6%). Escherichia coli (21.2% and 27.3%) and E faecalis (17.4% and 18.8%) were the 2 most frequently detected bacteria in both age groups. Gardnerella vaginalis (13.7%) and A schaalii (11.7%) were the third most frequently identified for patients <65 and ≥65 years, respectively. Compared with younger patients, the bacterial detection rate in patients ≥65 years decreased in male (83.7% versus 71.1%, P = .003) and increased in female (50.7% versus 65.2%, P < .001) patients.

Conclusions: M-PCR reveals different microbial profiles among different sexes and age groups of patients with UTI.

D. Wang and X. Zhao are consultants with Pathnostics.

Cutaneous Mucormycosis Due to Mucor circinelloides in a Burn Unit

(Poster No. 56)

Liz Yang, MD ([email protected]); Gordon L. Love, MD. Department of Pathology, Louisiana State University Health Sciences Center, New Orleans.

Mucormycosis is a rare but often fatal infection in immunocompromised patients. Mucor circinelloides is thermodimorphic, exhibiting mycelia in aerobic conditions and yeast in anaerobic/high-CO2 conditions. Mucor circinelloides may infect severely burned patients, producing small outbreaks in burn units. We are reporting a case of M circinelloides infection in a 68-year-old man with a 22% total body surface area third-degree burn injury in our Burn Unit at LSU Medical Center. He underwent tangential excision and placement of split-thickness of allograft over his back and bilateral legs. He developed a graft infection over the knee that was cultured. KOH preparation showed large, distorted hyphae and budding yeast of varying sizes (Figure 3.56, A and B), which grew as flat, white colonies on Sabouraud dextrose media. The yeasts were identified as M circinelloides by MALDI-TOF (bio-Merieux, Durham, North Carolina). Subsequent isolation on Sabouraud dextrose produced rapidly growing, off-white mold. Microscopic examination of the mold by lactophenol cotton blue staining revealed unbranched sporangiophores supporting round sporangia; rhizoids were absent, all consistent with Mucor spp (Figure 3.56, C). The mold colonies converted back into yeast incubated under anaerobic conditions (Figure 3.56, D). The identity of the M circinelloides was confirmed by genomic sequencing. Mucor circinelloides yeast was directly identified by MALDI-TOF from yeast in a wound culture prior to appearance of a mold. We could not find a similar rapid identification in our review of the literature.

Soft Tissue Infection by Medicopsis romeroi in an Immunocompetent Patient Detected by DNA Sequencing

(Poster No. 57)

Negin Farsi, MD1 ([email protected]); Jennifer Lee, MD2; James Cotelingam, MD.2 1Department of Pathology, University of Tennessee Health Science Center, Memphis; 2Department of Pathology, Louisiana State University Health Science Center, Shreveport.

Medicopsis romeroi, previously known as Pyrenochaeta romeroi, is a dematiaceous fungus mainly found in soil and plants and can produce a rare phaeohyphomycosis infection of dermal and subcutaneous tissues resulting from implantation of the fungus. Previous case reports have detected Medicopsis romeroi in immunocompromised patients with kidney transplant, corticosteroid use, and diabetes. This patient, an immunocompetent 44-year-old male resident of Louisiana with no past medical history, presented with a painless subcutaneous mass in the left ankle increasing in size during 6 weeks. MRI showed an ill-defined heterogeneous subcutaneous mass with cystic change. Histologic examination (Figure 3.57, A) of the mass revealed multiple neutrophilic abscesses with periodic acid-Schiff–positive (Figure 3.57, B) and Grocott-Gomori methenamine silver–positive (Figure 3.57, C) colonies of nonbranching hyphae and sporulating structures with a prominent Splendore-Hoeppli phenomenon (Figure 3.57, D). Fungal culture was not done at the time of excision because of a low suspicion of an infectious process. Medicopsis romeroi was identified by DNA sequencing of rDNA. To our knowledge, this is the first reported case of subcutaneous M romeroi in a North American immunocompetent patient. Further history revealed that the patient had sustained a thorn prick while gardening. Clinical improvement and resolution were followed by surgical excision and antimycotic therapy. In the absence of culture confirmation, specific identification of soft tissue infection by dematiaceous fungi, as in this case, can be confirmed using DNA sequencing and highlights the importance of M romeroi as cause of phaeohyphomycosis in immunocompetent patients.

Correlation of SARS-CoV-2 Viral Growth on Cultures, Cycle Threshold Values, and Symptom Status in Asymptomatic, Presymptomatic, and Postinfection Asymptomatic COVID Patients

(Poster No. 58)

Harsimar Kaur, MBBS ([email protected]); Christopher P. Morris, MD, PhD; Jaiprasath Sachithanandham, PhD; Nicholas Gallagher, BSc; Julie M. Norton, MSc; Andrew Pekosz, PhD; Heba H. Mostafa, MBBCh, PhD. Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland.

Context: COVID-19 presents with a wide range of symptoms. Some asymptomatic patients who test positive for SARS-CoV-2 polymerase chain reaction (PCR) remain asymptomatic (truly asymptomatic), whereas others develop symptoms later (presymptomatic). Some continue to have viral shedding after COVID (postinfection asymptomatic). It is unclear whether these asymptomatic patients have infectious potential.

Design: We searched our institutional laboratory database for all patients who tested positive for SARS-CoV-2 RNA assay (July 2020–December 2020) and selected asymptomatic patients (n=34) who were classified as “truly asymptomatic,” “presymptomatic,” and “postinfection asymptomatic” based on detailed chart reviews. Ct values in the patients' leftover nasopharyngeal swab samples and the recovery of infectious virus in cell culture were compared.

Results: Of a total of 34 patients, 12 (35%) were truly asymptomatic, 15 (44%) were presymptomatic, and 7 (21%) were postinfection asymptomatic. The postinfection asymptomatic patients had a median duration of 63 days (range, 7–99 days) after symptom onset at the time of sample collection. Of the truly asymptomatic patients' samples, 11 of 12 (92%) were negative for infectious virus recovery on cell culture, and only 1 sample was positive (culture day 3). Of the presymptomatic patients, 12 of 15 (80%) were positive for virus recovery with viral growth on day 3 (33%), day 4 (58%), or day 5 (9%). Of the postinfection asymptomatic patients, 7 of 7 (100%) were negative for viral growth. Presymptomatic patients had significantly lower mean Ct values (20.96) compared with truly asymptomatic and postinfection asymptomatic patients (27.94 and 29.39, respectively; P = .03).

Conclusions: Truly asymptomatic and postinfection asymptomatic patients shed less infectious virus compared with presymptomatic patients.

Splenic Actinomycosis in an Immunocompetent 39-Year-Old Man

(Poster No. 59)

Zane Conrad, MD ([email protected]); Dominick Cavuoti, DO; Clare McCormick-Baw, MD, PhD. Department of Pathology, University of Texas Southwestern Medical Center, Dallas.

Actinomyces are a group of Gram-positive filamentous bacteria that are normal flora of the gastrointestinal and genitourinary tracts. Actinomycosis is a slowly progressive infectious process characterized by mass-like lesions, progression across tissue planes, and development of sinus tracts. Although infections can occur anywhere, spleen involvement is rare, with case reports describing mainly immunocompromised patients. We present a case of an immunocompetent 39-year-old man with a past medical history of diverticulitis, complicated by colovesicular fistula requiring left hemicolectomy, who was admitted with left upper quadrant abdominal pain. Computed tomography imaging revealed splenomegaly with a 5.9-cm air-fluid collection abutting the posterior inferior border of the spleen with multiple micro abscesses (Figure 3.59, A). Because of the location of the abscess and difficulty with image-guided drainage, the patient was managed with antibiotic therapy alone and discharged. Two months later, he represented with new left upper quadrant abdominal and left flank pain. Computed tomography imaging demonstrated a 3.5 × 1.9 cm air-fluid collection of the posterior inferior border of the spleen and another fluid collection on the lateral aspect of the spleen measuring 5.2 × 1.6 cm (Figure 3.59, B). The patient underwent laparoscopic splenectomy and diaphragm repair. Pathologic examination revealed multifocal abscesses containing granules composed of mixed bacterial morphologies with a predominance of filamentous rods typical of Actinomyces (Figure 3.59, C and D). Figure 3.59, C, demonstrates a central aggregate of bacteria encased by Splendore-Hoeppli material in the midst of a robust neutrophilic abscess (×100 magnification). Figure 3.59, D, highlights the filamentous bacteria with Grocott-Gomori silver stain (×200 magnification).

False-Positive and False-Negative BD Veritor Rapid Antigen Testing Compared With PCR During Delta and Omicron SARS-CoV-2 Surges

(Poster No. 60)

Shivani Satia, MD ([email protected]); Ithiel James L Frame, MD. Department of Pathology, University of Mississippi Medical Center, Jackson.

Context: The Delta and Omicron variants of SARS-CoV-2 rapidly proliferated in the United States. These surges led to shortages of laboratory supplies for reverse transcription–polymerase chain reaction (RT-PCR) testing in our medical system. Consequently, we widely used SARS-CoV-2 rapid antigen (BD Veritor) testing as a primary testing method. When patients test negative by antigen testing, clinicians are encouraged to follow up with PCR testing. We hypothesized a substantial number of false rapid antigen results that were observed, compared with PCR.

Design: Retrospective review of rapid antigen testing results during the Delta and Omicron surges from June 2021 through February 2022.

Results: A total of 10 786 rapid antigen tests were performed. Of those, 5263 had concurrent PCR tests performed within 1 day of the antigen test. A total of 141 samples were positive by rapid antigen test but negative by PCR (2.7% of total samples with corresponding PCR; false-positive antigen test). A total of 421 samples were negative by rapid antigen test but positive by PCR (8.0% of total samples with corresponding PCR; false-negative antigen test).

Conclusions: A substantial number of false-positive and false-negative rapid antigen results were observed during the study period. The false-positive antigen results were surprising, given the reported high specificity of the assay described as well as the high prevalence of SARS-CoV-2 transmission during Delta and Omicron surges. The false-negative antigen results may be due to differences in the assay or due to additional mutations that may affect assay reagent antibodies to bind to viral antigens.

Rapid SARS-Cov-2 Antigen Detection Assay in Comparison With Real-Time RT-PCR Assay and 2 Other Rapid Tests for Laboratory Diagnosis of COVID-19

(Poster No. 61)

Jung J. Moon, MD, MMSc1 ([email protected]); Jung Hye Hwang, PhD2; Sung Woo Moon, MD, PhD.3 1Department of Research, Cellgenemedix, Newark, New Jersey; 2Department of Research, Diamedi Clinic, Seoul, Republic of Korea; 3Department of Internal Medicine, Pulmonology, Yonsei University, Seoul, Republic of Korea.

Context: The Good Ag COVID-19 Antigen test (a SARS-CoV-2 antigen test; Cellgenemedix, Newark, New Jersey) is a new patented latex-based lateral immunoassay that targets nonrecombinant regions of the SARS-CoV-2 nucleocapsid protein antigen, which is a conserved area free from mutations yet to be found in the COVID-19 mutation algorithm. We hypothesized that it would have better clinical performance in Omicron compared with other rapid tests.

Design: We evaluated Good Ag, with Euroimmun reverse transcription–polymerase chain reaction (RT-PCR) as a reference test. We examined a total of 90 SARS-CoV-2 PCR-negative and 150 SARS-CoV-2 PCR-positive respiratory swab samples (100 Omicron, 86 Delta, 8 Alpha, 46 un-typeable by sequencing) collected from August 2021 until February 2022 in the United States and Korea.

Results: Among 150 RT-PCR positive specimens, 132 were positive with the Good Ag test. Positive predictive value was 88.0% (95% CI, 81.70%–92.73%) and negative predictive value 100% (95% CI, 95.98%–100.00%). Sensitivity in Delta and Omicron was 98.4% and 80%, respectively, and specificity was 100% in Delta. The mean N Ct value was 29.44 and 29.01 in Delta and Omicron specimens, respectively (Table).

Conclusions: Although the overall sensitivity of the Good Ag test in Omicron is less than in Delta, this antigen test can be useful in identifying people with recent symptom onset with high viral loads and is useful for diagnosing Omicron variant COVID-19.

J. J. Moon is a Cellgenemedix shareholder. J. Hwang has received grant or research support from Cellgenemedix. S. Moon has received grant or research support from Cellgenemedix.

Development of Novel Reverse Transcription Real-Time Polymerase Chain Reaction Assay for Detection of COVID-19 in the Era of Pandemic of Omicron Variant

(Poster No. 62)

Jung J. Moon, MD, MMSc ([email protected]). Department of Research, Cellgenemedix, Newark, New Jersey.

Context: Genetic variants of SARS-CoV-2, especially the Omicron variant and recently the Omicron stealth variant, may lead to false results with molecular tests for detection of SARS-CoV-2. We therefore need to develop a new reverse transcription–polymerase chain reaction (RT-PCR) assay that is tailor made to the Omicron variant.

Design: GG Omicron and Delta COVID-19 PCR test detects the mutant region of 142 to 145 of S which is specific to omicron variant (S142–145 assay), which was combined with RT-qPCR of codon S452/478, S69/70, and internal control to make a new single-tube, quadplex RT-qPCR assay of COVID-19. We evaluated the performance of this test in comparison with 2 RT-PCR assays in detecting Delta, Alpha, and Omicron clinical specimens from August 2021 to February 2022, and results were compared with sequencing.

Results: Analytic performance showed a limit of detection of 100 to 300 copies of RNA per reaction and 100% specificity. In January 2022, 149 SARS-CoV-2–positive samples were collected and tested, of which 148 were positive for the Omicron variant and 1 Delta variant. The S142–145 assay was superior to other assays. GG Omicron and Delta COVID-19 PCR showed higher sensitivity than conventional RT-qPCR and 100% specificity in detecting SARS-CoV-2 and could differentiate all of the Omicron variants. All 85 with Delta variant were correctly detected by S452/478 of GG Omicron and Delta COVID-19 PCR.

Conclusions: These results indicate that our GG Omicron and Delta COVID-19 PCR may become a new standard tool to detect COVID-19 in a post-Omicron era of COVID-19.

J. J. Moon is a Cellgenemedix shareholder.

PRAME Expression in Chordoma: Expanding the Understanding of PRAME Expression in Human Malignancy

(Poster No. 63)

Joseph Coppock, MD, PhD1 ([email protected]); Wei Jiang, MD, PhD2; Paul J. Zhang, MD.1 1Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia; 2Department of Pathology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.

Context: Chordoma is a rare, malignant tumor of notochordal differentiation with a median overall survival of approximately 6 to 7 years. Treatment options are limited and poor, especially for the 30% of patients who develop metastasis. Preferentially expressed antigen in melanoma (PRAME) is a cancer testis antigen initially employed as a diagnostic marker for melanoma. It has subsequently been identified in a growing list of solid and hematologic malignancies and appears to have prognostic value in some. PRAME may also have predictive value, because cancer vaccination strategies and adoptive T-cell transfer targeting this molecule are currently under clinical investigation, and it may also identify candidates for retinoid therapy. Its expression has not been well studied in chordoma, which shares some histomorphologic and immunophenotypic features with melanoma.

Design: PRAME expression was evaluated by immunohistochemistry in 85 chordomas using tissue microarray.

Results: Of the evaluated chordomas 10.6% (9 of 85) demonstrated some degree of nuclear PRAME expression. Diffuse (>50%) expression was observed in 3.5% (3 of 85) of cases. The figure depicts an example of negative PRAME expression (Figure 3.63, A and B) and diffuse PRAME expression (Figure 3.63, C and D) in chordomas.

Conclusions: Expression of PRAME in a subset of chordomas suggests that care must be taken when using this antigen diagnostically, particularly when the differential diagnosis includes melanoma, and expands our understanding of PRAME expression in human malignancies, emphasizing its growing lack of specificity. Furthermore, expansion of testing of PRAME-based therapies to the subset of expressing chordomas may be of interest.

A Rare Case of Primary Central Nervous System Anaplastic Lymphoma Kinase–Negative Anaplastic Large Cell Lymphoma

(Poster No. 64)

Yujie Zhang, MD, PhD1 ([email protected]); Fatemeh Fekrmandi, MD, MSc2; Jingxin Qiu, MD, PhD.3 1Department of Pathology and Anatomical Sciences, University at Buffalo, New York; Departments of 2Radiation Oncology and 3Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Primary central nervous system (CNS) lymphoma represents approximately 4% of CNS tumors, among which most originated from B cells and only 2% from T cells. Anaplastic large cell lymphoma (ALCL), a subtype of T-cell lymphoma, is classified into anaplastic lymphoma kinase (ALK)–positive and ALK-negative subtypes. Although the former accounts for 70% to 80% of cases, ALK-negative ALCL represents only a minority of cases. Here we present a case of primary CNS ALK-negative ALCL in a 73-year-old African American man. He initially presented with significant fatigue and was treated for malaria with minimal improvement. He was subsequently found to have leukocytosis and developed left-sided weakness and facial droop. Magnetic resonance imaging (MRI) showed a large temporoparietal intra-axial mass with vasogenic edema and mass effect. He was placed on steroids and pursued further workup in our institution. Initial brain biopsy was nondiagnostic. Upon tapering steroids, he developed left leg weakness. Repeat MRI revealed multiple intracranial lesions, with one showing progression after steroid tapering. Repeat biopsy was performed and a diagnosis of primary CNS ALK-negative ALCL was rendered 80 days after the initial outside MRI and 47 days after the initial nondiagnostic biopsy. Literature review showed 39 reported cases of primary CNS ALCL, among which only 11 cases were ALK-negative. We present this case to demonstrate the nonspecific clinical presentation poses a diagnostic challenge, multiple intracranial lesions, along with waxing and waning clinical course with steroid administration, could be a sign of CNS lymphoma, and biopsy prior to start of steroids is preferred for diagnosis.

Molecular Classification and Grading of Diffuse Gliomas:Correlation of Molecular and Clinical Features

(Poster No. 65)

Bilge Dundar, MD ([email protected]); Mouaz Alsawas, MD; Amr Masaadeh, MBBS; Ramakrishna R. Sompallae, PhD; Aaron D. Bossler, MD, PhD; Anthony N. Snow, MD; Kyle Conway, MD, JD. Department of Pathology, University of Iowa, Iowa City.

Context: Per the 2021 World Health Organization central nervous system tumor classification, both molecular and histologic characteristics are necessary to classify diffuse gliomas. The new criteria require histologically lower-grade, IDH–wild-type diffuse gliomas to be classified as “Glioblastoma, IDH-wild-type,” in the presence of molecular findings, including TERT promoter mutation and EGFR amplification. Histologically lower-grade, IDH-mutant diffuse astrocytomas with homozygous CDKN2A/B deletion are classified as “Astrocytoma, IDH-mutant, grade 4.” We identified diffuse glioma cases, investigated molecular and histologic grade 4 tumors, and correlated the findings with the molecular and clinical information.

Design: Diffuse glioma cases between June 2020 and August 2021 were reviewed. Nucleic acid extracted from macrodissected, formalinfixed, paraffin-embedded tissue was used to create next-generation sequencing libraries. A 213-gene sequencing panel was performed on Illumina MiSeq.

Results: There were 85 IDH-wild-type glioblastomas, including 4 molecular diagnoses (4.7%). Except for CDKN2A/B loss, there was no significant difference in molecular features, enhancement on imaging (Figure 3.65), or mortality of histologic versus molecular glioblastomas (hazard ratio [HR], 1.35 [95% CI, 0.18–9.99]; P = .76]. CDK4 amplification in IDH–wild-type histologic glioblastomas did not significantly change mortality (HR, 0.73 [95% CI, 0.17–3.12]; P = .66). Nine IDH-mutant grade 4 astrocytomas included 1 molecular diagnosis. CDKN2A/B loss did not significantly change mortality in patients with histologically defined grade 4 IDH-mutant astrocytomas (HR, 0.54 [95% CI, 0.048–5.95]; P = .60).

Conclusions: Molecularly defined grade 4 glioblastomas did not have significantly different molecular features, enhancement, or mortality compared with histologically defined tumors. CDKN2A/B loss was not associated with mortality in patients with histologically defined grade 4 IDH-mutant astrocytomas.

Multifocal High-Grade Glioma (Glioblastoma, IDH–Wild-Type, World Health Organization Grade IV)

(Poster No. 66)

Refaat Makary, MD, PhD; Basma Elhaddad, MD ([email protected]); Khaled Sabry, MD. Department of Pathology, UFHealth (Shands), Jacksonville, Florida.

Multifocal/multicentric gliomas are rare, with worse prognosis, particularly the high-grade tumors. Multicentric ones are distinguished from multifocal ones, by being separate in location and in time. Multifocal tumors may represent spread via commissural route, cerebrospinal fluid, or local metastasis. We present a case of a 62-year-old woman complaining of transient episodes of confusion and ear ringing. Magnetic resonance imaging showed multifocal enhancing brain lesions. The largest lesion (1.9 cm in size) located in left parietooccipital junction, was a centrally necrotic ring-enhancing mass (Figure 3.66, A). In addition, 2 smaller lesions (ranging in size from 0.7 to 1.4 cm) showed faint diffuse enhancement in the left subinsular white matter and posterior left mesial temporal lobe. Biopsy of the left parieto-occipital lesion showed extensive geographic necrosis with focal markedly pleomorphic gemisto-astrocytic cellularity and vascular endothelial proliferation (Figure 3.66, B and C). Immunohistochemistry showed diffuse GFAP staining (Figure 3.66, D), increased p53 expression, and Ki-67 proliferation index up to 10%. Stains for bacterial, fungal, or viral organisms/inclusions were negative. Molecular studies were negative for IDH1/IDH2 mutation, 1p/19qco-deletion, or MGMT gene promotor methylation. The diagnosis was consistent with glioblastoma, IDH–wild-type (World Health Organization grade IV), multifocal by imaging. The patient is under follow-up. Multifocal high-grade glioblastoma has a worse prognosis, with median survival as low as 8 months, despite aggressive treatment. The pathogenesis and pathophysiologic differences from unifocal glioma are not fully understood. The optimal treatment for multifocal high-grade glioma is not defined in the current guidelines; therefore, individual case series may be helpful as guidance for clinical decision-making.

Meningiomatosis With Atypical World Health Organization Grade II Histology 3 Decades After Intracranial Irradiation for Acute Leukemia

(Poster No. 67)

Tasnuva Rashid, MD, PhD ([email protected]); Raafat Makary, MD, PhD. Department of Pathology, University of Florida College of Medicine, Jacksonville.

Cranial irradiation for childhood acute leukemia is marred by latent risk of induction of secondary intracranial tumors, particularly meningiomas. Meningiomatosis is rare and defined by the presence of at least 2 simultaneous lesions at different intracranial locations without associated neurofibromatosis type 2. We report a case of meningiomatosis with atypical histology (World Health Organization [WHO] grade II) in a 38-year-old woman, 3 decades after intracranial radiation and chemotherapy for acute lymphoblastic leukemia at 20 months of age. Meningiomatosis was discovered during workup for migraine headaches (6 years ago) without features of neurofibromatosis in the patient or family. Recent imaging follow-up (Figure 3.67, A) showed multiple enhancing meningiomas (right frontotemporal/right occipital/anterior falcine and left frontoparietal intraosseous) with interval increase in the right frontotemporal one (to 3.6 cm), which was resected. Histology showed features of atypical meningioma (WHO grade II). These features included large pleomorphic nuclei with prominent nucleoli, mitosis up to 6 of 10 high-power fields with atypical figures (Figure 3.67, B and C), focal tumor necrosis, and diffuse sheet growth pattern. Ki-67 proliferation marker labeled up to 10% tumor cells (Figure 3.67, D). Meningiomatosis accounts for 1% to 10% of meningiomas. In a nonneurofibromatosis setting, most are sporadic. Nearly 10% of cases are radiation induced and tend to occur in younger patients as multiple, more aggressive, and have higher rates of recurrence than spontaneous meningiomas. However, different histologic subtypes and grades of meningiomas are not uncommonly seen in the same patient. The case presented is illustrative for post–intracranial radiation meningiomatosis after long latency and the importance of long-term monitoring for early detection and treatment of postradiation–induced tumors.

ADEM-like Neuropathology COVID-19 Infection: Report of a New Neuro-Autopsy Case

(Poster No. 68)

McKenzie Wallace, BS ([email protected]); Timothy Parrett, MD. Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia.

A growing body of evidence supports that COVID-19 infection results in short and long-term central nervous system sequelae, yet the mechanisms by which COVID-19 infection affects the central nervous system remain incompletely understood. The current body of neuropathologic findings is evolving, but it generally supports the idea that neurologic damage in the setting of COVID-19 occurs indirectly, via systemic inflammation and/or hypoxic/ischemic injury. There are multiple reports of clinical cases of acute disseminated encephalomyelitis (ADEM) associated with COVID-19; however, only a single neuro-autopsy report with ADEM-like neuropathology in the setting of COVID-19 has been described. We report a second case. A previously healthy 48-year-old man who developed respiratory failure secondary to COVID-19 infection was found to have postmortem ADEM-like neuropathologic changes without significant inflammation or hypoxic/ischemic injury. The patient presented with shortness of breath and polymerase chain reaction–confirmed COVID-19 infection; his respiratory status rapidly declined, resulting in hemodynamic instability and death. Neuropathologic examination revealed numerous submillimeter ADEM-like perivenous demyelinating white matter plaques (Figure 3.68, B and C) with a penumbra of CD68+ microglial cells (Figure 3.68, D), with little other acute or chronic inflammation. The demyelinating lesions were most prominent in subcortical white matter, internal capsule, and descending corticospinal tracts of the brain stem. Some lesions were associated with similarly sized perivascular and parenchymal hemorrhages (Figure 3.68, A) at various stages of evolution. To our knowledge, these findings represent the second reported case of ADEM-like neuropathology in the setting of COVID-19 infection. Routine myelin stains (LFB) should be performed in COVID-19 cases to characterize this novel, subtle neuropathology.

Optical Genome Mapping for Enhanced Structural Variation Detection in a Case of Glioblastoma

(Poster No. 69)

Nivin Omar, MD ([email protected]); Nikhil Sahajpal, PhD; Ashis Mondal, PhD; Ravindra B. Kolhe, MD, PhD. Department of Pathology, Medical College of Georgia at Augusta University, Augusta.

Glioblastoma accounts for more than 60% of all brain tumors in adults; yet, despite the research and various therapies available for its management/treatment, it is still a deadly disease with a poor prognosis. The current cytogenetic analysis of glioblastoma relies on conventional methods. However, karyotyping is limited by the need for cultured cells, and although it can detect copy number variations (CNVs), and balanced and unbalanced structural variations (SVs), it has a banding resolution of ~5 to 10 Mb. Chromosomal microarray analysis (CMA) has a higher resolution of approximately 50 to 100 kb for the detection of CNVs but cannot detect balanced SVs. We demonstrate the ability of a next-generation cytogenomic technology called optical genome mapping (OGM) for chromosomal characterization in the case of glioblastoma. OGM was concordant with CMA in the detection of chromosome 2, 7, 10, 14, and 22 aneuploidies, and loss of 6q and 19q. In addition, OGM detected amplification of chr1q32 harboring MDM4 gene, and a mosaic gain of chr2q32 harboring IDH1 gene. Furthermore, OGM detected a complex profile with t(1;2), t(1;12), t(1;16), t(1;17), t(6;19), t(7;9), t(11;16), t(11;X), t(12;16), t(12;17), t(15;16), t(16;X), +2, 6q−, +7, −10, −14, 19q−, and −22, impacting key oncogenic genes (BRAF, CCND3, CDK6, CDKN2A, CIC, CNOT3, EGFR, FGFR2, IDH1, KLK2, MDM4, MET, MLLT3, PDE4DIP, PIM1, PPP2R1A, PTEN, SLC45A3, TFE3, TFEB, and ZNF331). This case demonstrates the unique ability of OGM to detect all classes of SVs in a single assay, which leads to the detection of a significant amount of clinically actionable data, that could result in better management of patients with glioblastoma (Figure 3.69).

R.B. Kolhe is a consultant with Illumina, Bionano, Agena, QIAGEN, Perkin Elmer, PGDx, and Cepheid, and received grant or research support from Perkin Elmer and Bionano.

Detection of SARS-CoV-2 in the Brain with Implications for Postacute Neuro-COVID: A Literature Review of 305 Brain Autopsies

(Poster No. 70)

Jerry J. Lou, MD1 ([email protected]); Mehrnaz Movassaghi, MD2; Dominique Gordy, BS4; Madeline G. Olson, BS2; Michael Wang, BS5; Maya Khurana, BS6; Alexandra So, BS7; Elyse J. Singer, MD3; William H. Yong, MD.1 1Department of Pathology, University of California Irvine Medical Center, Orange; Departments of 2Pathology and 3Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California; 4Columbia University Irving Medical Center, New York, New York; 5California Northstate University School of Medicine, Elk Grove; 6Department of Neuroscience, Yale University, New Haven, Connecticut; 7Massachusetts Institute of Technology, Cambridge.

Context: Patients with COVID-19 commonly have neurologic disorders in the acute and postacute phases. The relative contribution of direct viral infection, autoimmune phenomena, or systemic sequelae to clinical symptoms remains debated.

Design: We reviewed 25 papers encompassing 305 patients with brain autopsies. Of these cases 168 cases underwent reverse transcription–polymerase chain reaction (RT-PCR) for severe acute respiratory coronavirus 2 (SARS-CoV-2), and 150 cases underwent immunohistochemistry. We identify samples that are positive for virus confirmed by both testing modalities and assess persistence (1 test available only) of virus detection.

Results: SARS-CoV-2 immunoreactivity is detected in 32 of 150 specimens; sites include endothelial cells of the olfactory bulb, medulla oblongata, and cerebellum; olfactory mucosal cells; soma of cerebral cortical neurons; cranial nerve fascicles; and unidentified cells in the medulla oblongata. SARS-CoV-2 is detected by both immunohistochemistry and RT-PCR in 17 of 89 specimens (locations include olfactory bulb, medulla oblongata, and cerebellum). SARS-CoV-2 genomic RNA is detectable within the brain up to 47 days after symptom onset and subgenomic RNA for up to 18 days. Olfactory mucosal cells and cerebellar endothelial cells can show spike protein immunoreactivity 59 days after symptom onset.

Conclusions: Detection by 2 testing modalities in individual specimens provides strong evidence that SARS-CoV-2 infection is present in the brain in a subset of cases. SARS-CoV-2 spike protein and RNA are detectable in the postacute phase by single-modality testing, but recent controversial in vitro evidence for SARS-CoV-2 integration into host genomes raises questions regarding the significance of the detection.

Clinically Unsuspected Multiorgan Metastatic Breast Carcinoma Misdiagnosed and Mismanaged as Well-Differentiated Neuroendocrine Tumor

(Poster No. 71)

Zhiyan Fu, MD1 ([email protected]); Daniela Pereira, MD2; Yasamin Mirzabeigi, MD3; Marilin Rosa, MD1; Kun Jiang, MD, PhD.1 1Department of Pathology, Moffitt Cancer Center, Tampa, Florida; 2Department of Anatomic Pathology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal; 3Department of Pharmacy, the American Society of Health-System Pharmacists/Accreditation Council for Pharmacy Education, Bethesda, Maryland.

Breast neuroendocrine neoplasms are rare and can be histologically ambiguous. Although metastatic breast carcinomas primarily involve regional lymph nodes, they can metastasize to remote organs and mimic nonbreast entities. Pathologists need to build a wide differential list and make decisions independent of available clinical history. A 78-year-old woman with no cancer history presented to an outside hospital with leg pain and difficulty breathing. Radiology detected numerous bone lesions, pleural effusion, mediastinal, and axillary lymphadenopathy. Bone and axillary biopsies were diagnosed as metastatic well-differentiated neuroendocrine tumor (WD-NET). Several gastric submucosal 1-cm tumors were identified and biopsied, and similarly called WD-NET, grade 2. Four months of Sandostatin treatment targeting neuroendocrine tumors showed no effectiveness. Subsequently, the patient was referred to our institution for consultation. The provided stomach biopsy showed minute tissue with tubular nests of tumor cells with occasional mitoses and rare, subtle intracellular vacuoles. No background atrophic gastritis or intestinal metaplasia was seen. Therefore, outside tissue was requested for additional immunohistochemistry, which labeled tumor cells with pankeratin, synaptophysin, and chromogranin. Importantly, endrogen receptor, progesterone receptor, mammaglobin, and GATA3 all highlighted tumor cells. This investigation uncovered a clinically unsuspected, originally missed, multiorgan metastatic breast carcinoma. The treatment was immediately tailored toward breast cancer. Two-year follow-up imaging studies revealed diminished lesions in multiple organs. A breast biopsy was not performed. Pathologists need to be aware that breast carcinomas can mimic WD-NET clinically and immunophenotypically. Essential ancillary evaluation is warranted when facing a WD-NET–like neoplasm regardless of location and clinical presentation.

Utility of Immunofixation as a Follow-Up to Select Abnormal Serum Protein Electrophoresis Patterns and Suggestions for Clinical Correlation

(Poster No. 72)

Curtiss V. Johnson, MLS ([email protected]); Stephen L. Strobel, MD. Department of Pathology, Mercy St Vincent Medical Center, Toledo, Ohio.

Context: Serum protein electrophoresis (SPE) is a tool to identify various protein abnormalities and disease states. Given certain SPE patterns, it is beneficial to know if subsequent immunofixation electrophoresis (IFE) is warranted to detect abnormal bands and if further clinical correlation is recommended.

Design: A total of 160 SPE samples were collected and reviewed for the following patterns: acute-phase reaction, fibrinogen bands, β zone abnormalities, polyclonal hypergammaglobulinemia, and hypogammaglobulinemia. A medical technologist correlated results from patients exhibiting these patterns with published literature and a consulting pathologist to assess clinical significance and whether a subsequent immunofixation was indicated.

Results: Of the 160 samples collected, 70 were normal. The results for patterns of interest are summarized in the Table. Two acute-phase reaction patterns with positive IFE demonstrated diclonal immunoglobulin (Ig) G λ and free monoclonal λ chains, respectively. One sample with a fibrinogen band had a negative subsequent IFE. All 4 samples with β zone abnormalities had a positive IFE. Two were identified as diclonal IgA λ, whereas the others were monoclonal IgG κ and IgA κ, respectively. Three polyclonal hypergammaglobulinemia samples with positive IFE showed zones of restriction, including diclonal IgG lambda, monoclonal IgG kappa, and monoclonal IgG lambda. The 13 hypogammaglobulinemia samples with positive IFE exhibited differing zones of restriction in the gammaglobulin region.

Conclusions: Medical technologists can be trained to recognize these SPE patterns and take appropriate action to characterize abnormalities in consultation with a pathologist. Involving both parties in these decisions can help improve the efficiency of SPE testing for the performing laboratory.

Revised 6-Day Surgical Pathology Rotation Improves Resident ACGME Milestone Performance and Resident Education

(Poster No. 73)

Christopher J. Felicelli, MD ([email protected]); Yevgen Chornenkyy, MD; Kruti Maniar, MD; Luis Z. Blanco Jr, MD; Jorge E. Novo, MD. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Context: Pathology resident training lacks quality control and graduated responsibility to train independent pathologists capable of entering practice after residency. The traditional 3-day cycle negatively impacts resident education by reducing preview time, case follow-up, and immunohistochemical stain (IHC) and ancillary study interpretation. We aimed to develop a new rotation model to improve Accreditation Council for Graduate Medical Education (ACGME) milestones and internal quality metrics

Design: An innovative “6-day cycle” surgical pathology rotation model was designed, consisting of 2 grossing days, 1 frozen/biopsies/preview day, and 2 dedicated sign-out days, followed by 1 frozen/biopsies/case completion day (Figure 3.73, A). To track training, residents completed surveys prior to the implementation of the new curriculum and 6 months after implementation, consisting of ACGME milestones levels 4 and 5 and internal quality control metrics.

Results: In the previous surgical pathology rotation, residents disagreed or strongly disagreed that they reached ACGME levels 4 and 5 for milestones, and internal quality metrics needing improvement included specimen fixation, preview time, IHC interpretation, and readiness of independent practice. After implementation of the revised curriculum, there was a statistically significant (P < .05) increase in level of agreement across all ACGME level 4 and 5 milestones (Figure 3.73, B). The rotation significantly (P < .05) improved internal quality metrics, including specimen fixation, preview time, reviewing IHC, and readiness for independent practice.

Conclusions: The 6-day surgical pathology rotation is a practical approach to improve resident education, with statistically significant improvements in both ACGME milestones and internal quality metrics, leading to reproducible and measurable enhancement of resident education.

Expanding Interspecialty Medical Education: Pathology for Nonpathologists

(Poster No. 74)

Kyle M. Haggerty, BS1 ([email protected]); Brian Brinkerhoff, MD2; Mandy VanSandt, DO.2 1School of Medicine and 2Department of Pathology, Oregon Health & Science University, Portland.

Context: Pathology is a broad field of medicine that interacts with nearly every other medical specialty. Many nonpathology providers and trainees do not fully recognize the scope of pathology, but many seek additional understanding. These authors anecdotally noticed areas of miscommunication or misunderstanding between pathology and non-pathology specialties at our institution. This project aims to identify common communication and knowledge gaps between pathology and nonpathology medical specialties and identify if didactic sessions can effectively address these gaps.

Design: Learning objectives were identified through expert interviews with faculty, graduate medical trainees, and staff in multiple specialties, including pathology, otolaryngology (ENT), family medicine (FM), and dermatopathology. Lectures for 2 medical specialties were designed based around learning objectives. Prelecture and postlecture surveys were administered to lecture attendees to quantify comfort with learning objectives on a 5-point Likert scale.

Results: Although the number of lecture attendees and survey respondents was small (prelecture response, n = 14; postlecture response, n = 11), survey results showed a significant increase in learning objective confidence before and after lectures, specifically the learning objectives of (1) understanding who Oregon Health & Science University pathology is and how to contact the department, and (2) understanding indications for standard, rush, and frozen specimens.

Conclusions: This education project demonstrates that didactic-format interspecialty education is an effective method to share valuable information between medical specialists. These data are promising in suggesting that additional education reaching a wider audience may further improve interspecialty understanding and communication.

The Clinical Pathology Laboratory in Virtual Reality for Medical Education

(Poster No. 75)

Hamilton C. Tsang, MD ([email protected]); Ryan J. Morse, MD; Rida Hasan, MD; Joshua A. Lieberman, MD, PhD. Department of Laboratory Medicine and Pathology, University of Washington, Seattle.

Context: During the SARS-CoV-2 pandemic, in-person laboratory medicine clerkships were converted to remote learning. To maintain learner engagement, interactive educational 360° virtual reality (VR) walkthrough tours of the Transfusion Service and Microbiology Laboratories were created to simulate experiential content of the laboratory environment.

Design: Still images were captured with 360° cameras (Samsung Electronics Co Ltd, San Jose, California) to create both traditional static-image and immersive VR tours (Figure 3.75, A through C) for medical students and evaluated in a controlled cross-over study with interspersed learning assessment (8-point quiz) and activity survey (5-point Likert scale; Figure 3.75, D). Web-based software (Kuula LLC, Santa Monica, California) was used to create VR tours, adding navigation and interactive elements (Figure 3.75, C) while blurring faces and sensitive information.

Results: A total of 55 students participated in 6 cohorts from May 2021 to March 2022. All respondents except 1 completed the tours in the allotted time (average VR, 16.3 minutes; static, 14.75 minutes; P = .08). Students rated the VR activity as more interactive (average VR, 4.40/5; static, 3.54/5; P < .001). VR tour learning retention assessment score was lower compared with static tour (average VR, 5.73/8; static, 6.30/8; P = .03). Survey results for whether participants understood the laboratory environment better, including relevancy to education and course goals, were not statistically different.

Conclusions: The clerkship is likely to continue as hybrid remote learning, so VR tours will remain relevant. VR tours maintain learner interactivity, although an adjustment period should be observed where stakes are low for learners. This technology can be applied globally to other departments and institutions for education.

A Comprehensive Model for the Introduction and Optimization of a Diversity, Equity, and Inclusion Needs Assessment

(Poster No. 76)

Jaclyn M. Plotzke, MD1; Julianne M. Szczepanski, MD1 ([email protected]); Alexander S. Taylor, MD1; Haley Amoth, MD1; Batoul A. Aoun, DO1; Ashley A. Brent, MD1; Elaina R. Daniels, MD1; Laurie M. Griesinger, MD2; Justin T. Kelley, MD1; Lauren Kroll-Wheeler, MD1; Anna B. Owczarczyk, MD, PhD1; Lauren B. Smith, MD1; Cathryn J. Lapedis, MD.1 1Department of Pathology, Michigan Medicine, Ann Arbor; 2Department of Pathology, University of Virginia Health System, Charlottesville.

Context: Diversity, equity, and inclusion (DEI) are essential components to create a strong and successful training environment for pathology residents. Our residency program, like many others, does not have specific initiatives focused on recruiting diverse residents or assessing the existing culture and inclusivity. We aimed to create a needs assessment to provide a data-driven understanding of the current state of DEI in our program.

Design: A survey was designed with guidance from existing reputable DEI surveys and faculty member feedback. The survey used Likert scale responses to statements pertaining to 1 or more aspects of 7 prominent categories of DEI (Table). The voluntary anonymous survey was approved by departmental leadership and distributed to 28 pathology residents. A third-party organization aggregated responses and combined minority demographic groups to ensure anonymity of our small sample size for future data analysis.

Results: A simple, comprehensive 88-item assessment was developed to evaluate baseline DEI data of a pathology residency program. The survey had a response rate of 96%. Demographic data were compiled into an infogram. Grouped data analysis is currently in progress by a third-party organization and includes comparing average scores of each question category for various combined demographic groupings.

Conclusions: A needs assessment is a valuable way to establish a baseline measurement of residency program DEI. We propose a method for creating, validating, and administering a survey-based needs assessment, the results of which can be used to identify actionable items. This survey will be repeated annually to measure ongoing progress of residency culture and DEI initiatives.

A Cost-Conscious Whole Slide Imaging System for Teaching and Teleconsultation in Pathology

(Poster No. 77)

Christopher A. Thorburn, MD1 ([email protected]); Mustafa Deebajah, MD1; Keran Zhao, PhD2; Zhenhong Qu, MD.1 1Department of Anatomic & Clinical Pathology, Beaumont Health System, Royal Oak, Michigan; 2C. T. Bauer College of Business, University of Houston, Texas.

Context: Whole slide imaging (WSI) systems can provide multiple users with concurrent access to slides without the need to be physically present at the same location. However, the cost of an all-in-one WSI system can be prohibitive for programs that do not already use WSI systems at a clinical scale. Here, we delineate a simple, inexpensive WSI system that is easy to implement and meets the need of a resident teaching environment.

Design: A digital camera (Basler acA2500, Mannheim, Germany) is mounted to a brightfield microscope with a 0.63× C-mount and connected to a computer with the manual WSI program (Micro-Visioneer, Esslingen, Germany). Areas of interest on the slide are manually scanned, and the program stitches these images together to create an SVS file. We explored 2 possible access configurations: Web server based and intranet based (Figure 3.77).

Results: A collection of slides were manually scanned as described above. To assess the quality of these images, the slides were scanned a second time with an Aperio AT2. Both resulting sets of images were then compared to one another and the original glass slides to ensure suitable concordance of the images.

Conclusions: Our proposed solution for low-cost WSI for teaching and teleconsultation avoids the high upfront cost of an all-in-one packaged solution. High-quality whole slide images comparable to those generated by an Aperio scanner can be easily produced and accessed by multiple viewers simultaneously. Our proposed access solutions are similarly low cost, using open-source software and preexisting organizational network drives.

Application of an England Finder–Based Quantitative Framework to Anatomic and Clinical Pathology Practice

(Poster No. 78)

Muhammad Tahir, MD, MS1 ([email protected]); Nemanja Rodić, MD, PhD2; John-Paul Lavik, MD, PhD.3 1Department of Pathology, University of South Alabama Health Hospital, Mobile; 2Department of Pathology, EPIARX, Washington, DC; 3Department of Pathology, Indiana University School of Medicine, Indianapolis.

Context: At present a vast majority of pathologists do not routinely use a microscope slide holder and its accompanying coordinate system when examining tissue sections clinically. This practice likely became a dominant work habit because exclusion of a slide holder allows quick placement of slides onto the microscope stage. However, some cases require careful assessment of minute areas of interest, and, in those cases, it is often important to communicate clearly about an exact area of interest such that it could be navigated to by another pathologist. This issue is particularly pertinent to cytopathology and subdisciplines of clinical pathology, hematopathology, and clinical microbiology.

Design: Consequently, we have developed a strategy for employing an existent device (England Finder) that, when used per our specifications, allows for the easy and exact recording of the position of areas of interest. This approach eliminates the need to “dot” slides.

Results: Using our England Finder–based graticule technique, we achieved routine designation of areas of interest well within 250 μm on a slide, enabling identification of small cellular aggregates. Our technologic improvement allows clearer communication among pathologists and can be applied in daily intradepartmental and extradepartmental consultations. To help facilitate future use of this new technology, we developed controlled language termed “Pathology ZIP code” for communicating the area of interest using minimal and unambiguous 5-mark codes.

Conclusions: Thus, we report a means by which any pathologist can describe an area of interest on a slide and aid a colleague in locating that area without annotating the slide itself.

Primary Benign Vascular Tumors of Adrenal Gland: A Clinicopathologic and Radiologic Analysis of 35 Cases

(Poster No. 79)

Saman Karimi, MD, MS1 ([email protected]); Busra Nur B. Goksu, MD1; Maria M. Picken, MD2; Vikas Mehta, MD.1 1Department of Pathology, University of Illinois at Chicago; 2Department of Pathology, Loyola University Medical Center, Maywood, Illinois.

Context: Vascular lesions of the adrenal gland are seen infrequently in surgical pathology practice, and mostly single case reports are encountered in literature. They can mimic malignancy and pose diagnostic challenges radiologically and pathologically.

Design: We identified 35 specimens harboring primary adrenal gland vascular/lymphatic lesions from files from 2 institutions (2003–2021). Following Institutional Review Board approvals, the cases were subjected to a detailed clinicopathologic evaluation by 2 genitourinary pathologists and a dedicated vascular radiologist.

Results: There were 15 men and 20 women with an age range of 31 to 86 years (mean, 61). Lesions ranged from 1.5 to 24 cm (mean, 8.6). There were 16 pseudocysts, 12 hemangiomas, 1 arteriovenous malformation (AVM), 2 anastomosing hemangiomas (AHs), 3 lymphangiomas, and 1 intravascular papillary endothelial hyperplasia (IPEH). In pseudocysts, morphologically normal adrenal gland surrounded cystic space filled with blood, but most pseudocysts (>75%) were semisolid or solid. Extensive sampling was required to rule out ruptured malignancy, including pheochromocytoma. Cavernous hemangiomas and lymphangiomas were noninfiltrative and lacked atypia and mitotic activity. AH showed tightly packed capillary channels lined by bland endothelial cells. IPEH lesion was relatively circumscribed but unencapsulated, variably cellular with a pseudopapillary arrangement, admixed with extravasated red blood cells and fibrin. AVM had typical morphology. Radiologically, these lesions raised concerns for malignancy leading to adrenalectomies.

Conclusions: Vascular adrenal lesions are relatively rarely reported, and radiologically are associated with a high rate of misdiagnosis and may have a varied morphology. Awareness of these entities helps to discriminate them from other common adrenal gland lesions. Extensive sampling of such lesions may be necessary.

Adrenal Pseudocysts Are Frequently Misdiagnosed as Malignant Lesions on Radiology

(Poster No. 80)

Saman Karimi, MD, MS1 ([email protected]); Busra Nur B. Goksu, MD1; Maria M. Picken, MD, PhD2; Vikas Mehta, MD1. 1Department of Pathology, University of Illinois at Chicago. 2Department of Pathology, Loyola University Medical Center, Maywood, Illinois.

Context: Pseudocysts are uncommon lesions of the adrenal gland and often present with nonspecific clinical and radiologic features. Radiologic diagnosis of pseudocysts is often obscured by the presence of extensive hemorrhage and necrosis, which can masquerade as malignant neoplasm. As such, these lesions are often treated surgically by adrenalectomies, even when risk of rupture is low.

Design: We identified 16 specimens harboring pseudocysts of the adrenal gland from files of 2 institutions between 2003 and 2021. Following Institutional Review Board approvals, the cases were reviewed independently by 2 genitourinary pathologists and a dedicated vascular radiologist.

Results: We identified 10 women and 6 men with an age range of 31 to 86 years (mean, 63). Lesion size ranged from 2.5 to 24 cm (average, 8.6). The pseudocysts showed morphologically normal adrenal gland surrounding the cystic space filled with blood. No true cyst lining was identified with extensive sampling, and immunostains for epithelial, endothelial, and lymphatic markers were negative. Most of the pseudocysts (>75%) were semisolid or solid with extensive necrosis and hemorrhage and fibrosis forming a pseudocapsule. Calcifications were observed in 3 cases. Two cases showed foreign body giant cell reaction. Extensive sampling was required to rule out ruptured malignancy.

Conclusions: Adrenal pseudocysts may be pure cystic, semisolid, and occasionally predominantly solid with calcifications. The evaluation of pseudocysts poses a challenge because these lesions often share radiologic and clinical features with malignant adrenal neoplasms. Pathologic diagnosis of adrenal pseudocysts requires the exclusion of more common lesions, in particular pheochromocytoma; hence, extensive sampling of such lesions is mandatory.

Lymphoid Neoplasms Involving Endocrine Organs: A Clinical/Pathologic Review

(Poster No. 81)

Hamza Tariq, MD ([email protected]); Ji-Weon Park, MD; Lei Yan, MD; Swathi Reddy, MD; Paolo Gattuso, MD; Lin Cheng, MD. Department of Pathology, Rush University Medical Center, Chicago, Illinois.

Context: Although the vast majority of malignancies involving endocrine organs are epithelial, lymphomas can also involve these organs and need to be recognized for a timely diagnosis.

Design: We retrospectively reviewed all cases of lymphoma involving adrenals, thyroid, and pancreas in our database from 1995 to 2020 for a better understanding of their clinical and histologic characteristics.

Results: A total of 47 cases were identified, including 18 pancreas, 16 adrenal, and 13 thyroid lymphomas. The most common lymphoma was diffuse large B-cell lymphoma (DLBCL; 34 [72.3%]), including 19 (55.9%) with germinal center and 15 (44.1%) with activated B-cell phenotype. Other cases include 2 each of classic Hodgkin lymphoma, follicular lymphoma, and mantle cell lymphoma (MCL), and 1 each of peripheral T-cell lymphoma, posttransplantation lymphoproliferative disorder, intravascular large B-cell lymphoma (IVLBCL), marginal zone lymphoma, T-cell/histiocyte-rich large B-cell lymphoma (TCHRLBCL), double-hit lymphoma, and natural killer/T-cell lymphoma. A total of 37 (78.8%) were primary endocrine lymphomas, whereas 10 (21.2%) had a prior history of extra endocrine lymphoma. A total of 23 of 47 cases (48.9%) were diagnosed on fine-needle aspiration (FNA; see Table).

Conclusions: Our study shows that extranodal endocrine lymphomas can arise primarily in endocrine organs as well as show secondary involvement in systemic disease. The most common subtypes are aggressive B-cell lymphomas (80.8%), most commonly DLBCL but also double-hit, IVLBCL, TCHRLBCL, and MCL. This proportion is higher compared with nodal lymphomas, where approximately 50% are aggressive B-cell subtypes. The differential diagnosis of endocrine tumors is complex and must always include lymphoid neoplasms. Furthermore, FNA is effective and accurate in diagnosing lymphomas involving endocrine organs.

Metastatic Thyroid Medullary Carcinomas Involving Liver and Pancreas Misdiagnosed as Metastatic Well-Differentiated Neuroendocrine Tumors From Digestive System: A Potential Pitfall

(Poster No. 82)

Daniela V. Pereira, MD1 ([email protected]); Zhiyan Fu, MD2; Kun Jiang, MD, PhD.2 1Department of Pathology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal; 2Department of Pathology, H. Lee Moffitt Cancer Center, Tampa, Florida.

Thyroid medullary carcinoma (TMC) is prone to early metastasis, primarily in the regional lymph nodes and organs. The familiar forms (30%) are more aggressive, and Ras mutations seem to be associated with better clinical course. Distant metastasis can be seen, but they are easily misdiagnosed as well-differentiated neuroendocrine tumors (WD-NET) from other organs, particularly if no previous history of malignancy is known. We report 2 originally misdiagnosed metastatic TMCs. A 69-year-old woman who presented with 1-year–long diarrhea and weight loss; core biopsy of a 3.5-cm liver mass was diagnosed as metastatic WD-NET, presumably from a digestive system primary. The second patient was a 53-year-old man with persistent abdominal pain; a 1.2-cm pancreatic lesion was biopsied and diagnosed as pancreatic WD-NET. Upon gastroenterology expert pathology review, both biopsies showed rosettes and trabeculae formed by monomorphic plasmacytoid tumor cells with eosinophilic cytoplasm, occasional mitoses, and no necrosis; positive immunostaining for pancytokeratin, synaptophysin, and chromogranin; and Ki-67 of 6.8% and 8.3%, respectively. Additionally, calcitonin, TTF-1, PAX-8, and CEA-polyclonal highlighted all tumor cells. These investigations uncovered 2 originally missed metastatic TMCs, despite an absence of clinical history or suspicion. Further investigation identified no prior thyroid case for the first patient but discovered a thyroidectomy history for the second patient 20 years prior (no pathology materials available). These cases illustrate that pathologists need to be aware that metastatic TMC could mimic WD-NET from other origins. Ancillary studies evaluating thyroid lineage should be considered when facing a WD-NET–like neoplasm with limited clinical information or unknown primary origin.

Primary Thyroid Carcinoma With Mucinous Differentiation: A Rare Entity

(Poster No. 83)

Laura A. Gomez-Isaza, MD1 ([email protected]); Catalina Buritica-Cifuentes, MD1; Mauricio A. Palau-Lázaro, MD1; Gustavo A. Triana-Rodriguez, MD2; Juan J. Santivañez-Palomino, MD3; Jose A. Hakim, MD3; Paula A. Rodriguez-Urrego, MD.1 Departments of 1Pathology and Laboratory Medicine, 2Radiology, and 3Surgery, Section of Head and Neck Surgery, Fundacion Santa Fe de Bogota, Colombia.

Primary mucinous carcinoma of the thyroid is an extremely rare entity, with only 9 cases reported in the English-language literature. It is believed that it may originate from a remnant of the last branchial arch. We report the case of a 64-year-old patient, with no relevant medical history, who complained of 1 month of cervical mass. Thyroid ultrasound reported an isoechoic well-defined lobulated mass measuring 1.7 cm in greatest dimension (Figure 3.83, A). Thyroid cytology was compatible with a follicular neoplasm, in the background a thin blue extracellular material that was interpreted as thin colloid (Bethesda IV; Figure 3.83, B). Total thyroidectomy specimen showed a well-circumscribed, encapsulated, white right lesion, measuring 1.5 cm in greatest dimension. Sections revealed an encapsulated mass formed by microfollicles with regular nuclei, and prominent nucleoli, embedded in an extracellular mucin matrix; focally there was capsular invasion (Figure 3.83, C and D). Immunohistochemistry was positive for PAX-8 and TTF-1 (Figure 3.83, E), and negative for calcitonin. Findings were consistent with a primary thyroid carcinoma with mucinous differentiation. Differential diagnosis included primary mucinous thyroid carcinoma versus other primary thyroid carcinomas with mucinous differentiation (follicular carcinoma with mucinous differentiation). Diagnosis of this pathology can be challenging, and carcinomas metastatic from another primary must be ruled out. For primary diagnosis, features of other primary carcinomas cannot be present. Mortality in primary mucinous carcinoma is increased (about 50%) within following 6 months to 4 years. Because of the small number of cases the treatment is not standardized. Our patient is being followed and was treated with iodine ablation.

Metastatic Paraganglioma at First Diagnosis With Retained Succinate Dehydrogenase B

(Poster No. 84)

Badal Savariya, MD ([email protected]); Haval Ali, MD; Meenakshi Bhattacharjee, MD. Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston.

Metastatic paraganglioma is rare and is usually associated with succinate dehydrogenase B mutation. We present a patient with metastatic paraganglioma at first diagnosis, with retained succinate dehydrogenase B. A 32-year-old African American man with no known past medical history presented with progressively worsening bilateral lower extremity weakness and numbness for 4 to 5 weeks. Magnetic resonance imaging showed multiple enhancing lesions throughout the thoracolumbar spine, sacrum, and iliac bones, along with cervical adenopathy, and a large 7.9-cm mass in the left carotid space with splaying of the proximal internal and external carotid arteries. The lesion involving the T6 vertebral body resulted in epidural extension and cord compression. The patient underwent T6 to T7 laminectomy and T6 vertebral biopsy. On microscopic examination, the marrow space of the thoracic vertebral bone had a tumor consisting of lobules and clusters of relatively bland cells delineated by thin blood vessels (zellballen). The tumor cells had moderate amount of pale eosinophilic cytoplasm, and round nuclei with fine chromatin. There was no tumor necrosis or appreciable mitotic activity. On immunohistochemistry staining, the tumor cells were positive for CD56, synaptophysin, chromogranin, and S100; CD34 highlighted the vascular pattern and Ki-67 labeling index was ~5%. The tumor cells were negative for CD45, CD68, pankeratin, CAM 5.2, CK7, CK20, CDX2, RCC, PAX 8, TTF-1, Napsin, pan-melanoma, NKX 3.1, PAP, CD45, and CD68, excluding metastatic carcinoma, a lymphoproliferative process, and hematologic malignancy. Additional immunohistochemistry for parathyroid hormone, β-catenin, and succinate dehydrogenase B (retained expression) did not suggest a familial or aggressive sporadic tumor.

How the COVID-19 Pandemic Affected the Point-of-Care Testing Numbers in the Municipal Public Health System–Based Ambulatory Care and School Health Clinics in New York City

(Poster No. 85)

Tenzin Choesang, MA1; Tshering Sherpa, BS2; Shana Ahmad, MBA, MLS1,2; Faisal H. Ronny, MD, PhD1,2 ([email protected]). 1Department of Laboratory Operations, NYCHHC Central Office, New York, New York; 2Department of Laboratory Services, Gotham Health NYCHHC, New York, New York.

Context: Our New York City Municipal Public Health System–based multisite ambulatory and school-based clinics offer various waived point-of-care tests (POCTs) and provider-performed microscopy (PPM) to the local communities. Our laboratory service conducts system-wide centralized implementation, monitoring, and oversight of the POCT operations.

Design: We identified the issues that directly affected the POCT performance, causing a reduction in the test numbers, and also elaborated the measures taken to resolve that and to recover.

Results: The impact on our POCT started after the laboratory staff relocated to the acute care hospital labs to provide testing support during the pandemic's peak. That caused significant delays or complete cessation of POCT operations in the clinics due to a lack of oversight support. Focus started to shift toward an increase in POCT numbers in the ambulatory care clinics when COVID-19 testing was more accessible through reference laboratories and the city-initiated community testing (Figure 3.85). Another issue was manual result entry at the patient portals due to the initial lack of interface with the reference laboratories. Furthermore, the orientation and training of nursing staff at many testing sites to access the COVID-19 specimens in the laboratory information system also harnessed the POCT oversight staff. Telecommuting by the providers in the clinics, the nursing staff shortage, and absence due to illness and fatigue were the other issues that impacted the POCT numbers.

Conclusions: Identifying the factors that affected the POCT numbers during COVID-19 pandemic in our ambulatory care clinics will help us prepare for such future crises.

Glomerular Count Field Correlations in Kidney Donor Biopsies: An Evaluation of Minimal Required Field

(Poster No. 86)

Ahmed I. Younes, MD ([email protected]); Abdullah Thayyil, MD. Department of Pathology and Laboratory Medicine, East Carolina University, Greenville, North Carolina.

Context: Glomerular counts on frozen renal procurement biopsies are the most important determinant in the acceptance or rejection of a kidney allograft's suitability for transplantation. Renal wedge resections are routinely performed for that purpose. Here, we aim to find the minimal area/sample size of a biopsy that correlates with the pathologic criteria for acceptance or rejection of a donor's kidney.

Design: A total of 64 donor kidney frozen renal procurement wedge biopsies were performed between March 2019 and June 2020. Of these, 17 biopsies with no glomerulosclerosis were excluded. The remaining 47 wedge biopsies of the kidney were analyzed for the degree of glomerulosclerosis. We manually counted the total number of sclerosed glomeruli and compared that to 1-, 2-, and 3-mm–thick core section areas demarcated for each wedge biopsy. The lines were drawn along the short axis of the biopsy from the cortex inwards (Figure 3.86, A through D).

Results: The correlation between the percent of sclerosed glomeruli in the whole wedge biopsy versus 1-, 2-, and 3-mm core section areas was determined. The correlation coefficients of 1-mm core, 2-mm core, and 3-mm core were 0.6863, 0.7471, and 0.8078, respectively.

Conclusions: The data reveal a moderately high-to-high statistical correlation of the degree of glomerulosclerosis between the wedge biopsy and 1- to 3-mm core section areas. This corresponds approximately to 17 G, 12 G, and 9 G biopsy needle size. Therefore, a 1- to 3-mm core biopsy could be sufficient for assessing the adequacy of donors' kidneys for transplantation with a minimal discordance rate.

The Cost of Management of Patients With Chest Pain Is Affected by the Reference Population Chosen to Establish 99th Percentile for High-Sensitivity Troponin

(Poster No. 87)

Mennatallah Ewais, MD ([email protected]); Wieslaw Furmaga, MD, MS. Department of Pathology, UT Health San Antonio, Texas.

Context: High-sensitivity troponin I (HSTnI) has been promoted as a better option than classic troponin to manage patients with chest pain in the emergency department (ED) and acute care facilities. The 99th percentile for HSTnI is a clinically important point, and its validation requires testing on the reference “healthy population.” We demonstrated that the value of the 99th percentile differs for different reference populations, and the decision of which value to use affects the cost of management of patients with chest pain.

Design: To establish the 99th percentile, 300 female and 300 male individuals were tested from 2 populations: blood donors and ED patients with no history of cardiac, renal, or liver diseases. Vista Siemens instruments were used, and the 99th percentiles for these 2 populations were calculated. The difference of length and cost of stay between these two 99th percentile values was projected.

Results: The 99th percentiles for the female blood donors and “healthy ED patients” were 17 and 28 ng/L, but for male individuals it was 21 and 37 ng/L, respectively. The assumption for cost calculation was that no patients with cardiac events were discharged from the ED. With such an assumption, if the 99th percentile for blood donors is used, the calculated cost of management of patients with chest pain was $2.5 million higher than that calculated for the 99th percentile for the “healthy ED patients.”

Conclusions: The reference group used for the calculation of the 99th percentile for HSTnI significantly affects the cost of managing patients with chest pain in the ED.

Review of the Utility of Grocott-Gomori Methenamine Silver, Acid-Fast Bacilli, and Fite Stains in Current Practice of Pathology

(Poster No. 88)

Nuha Shaker, MD, MS ([email protected]); Justin Rueckert, DO; Shadi Qasem, MD, MBA. Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington.

Context: Grocott-Gomori methenamine silver (GMS) and acid-fast bacilli (AFB)/Fite stains are widely used in our daily practice as ancillary tests to identify fungal and mycobacterial organisms. In this study, we aim to review the utility of GMS and AFB/Fite stains and the distribution of positive cases.

Design: We retrospectively reviewed the results of 2164 GMS and 415 Fite/AFB stains that were ordered during the course of 1 year (2020). The cases included both surgical and cytology specimens. Cases with positive staining were identified, and we recorded specimen type, specimen source, organism, and patient demographics.

Results: Overall, 1 Fite (0.2%) and 219 GMS (10%) stains were positive. Positive cases included a wide age range (3 months to 85 years) with a male to female ratio of 1.2. GMS stain was positive in 6% (95 of 1469) of surgical cases and 18% (122 of 695) of cytology cases. A significant percentage (56%) of the cytology-positive cases was due to Candida in bronchoalveolar lavage specimens (likely a contaminant). The second most common location was esophagus followed by lung. Overall, the most common organism was Candida followed by Histoplasma (Table). One case with Fite-positive organisms had negative serology and culture results.

Conclusions: GMS stain is effective in detecting a variety of fungal organisms. The aerodigestive system is often positive, and common organisms include Candida and Histoplasma. Pneumocystis and Mycobacterium are rare in our patient population. The current practice for ordering stains should be re-evaluated in light of current epidemiologic and clinical evidence.

Microscopic Evaluation of Trauma Surgical Specimens Is an Overuse of Health Care Resources

(Poster No. 89)

Joseph V. Calderaro, MD ([email protected]); Haaris Iqbal, DO; Jennifer Anderson, MBA; Julie M. Jorns, MD. Department of Pathology, Medical College of Wisconsin Affiliated Hospitals, Milwaukee.

Context: Trauma surgery can generate numerous clinical and surgical pathology specimens, the latter of which are often processed for microscopic examination. The clinical utility and financial viability of this policy have not yet been closely examined.

Design: Archives (2013–2020) identified 191 patients with 201 trauma surgical pathology cases. Data collected included demographics, slide/block volumes, billed charges, and actual reimbursement. Slide production cost was estimated at $4.62 per slide. Cost estimates of pathologist assistant and pathologist time were not included.

Results: Patients were predominantly male (149 of 191; 78%) versus female (42 of 191; 22%), with median age of 30.2 years (range, 16.9–85 years). There were 321 parts submitted (range, 1–5 parts per case) with a median of 5 blocks per case (range, 1–22). Resection specimens were bowel (242 of 321; 75.4%), bone/soft tissue (36 of 321; 11.2%), pancreas/spleen (28 of 321; 8.7%), lung (7 of 321; 2.2%), kidney/adrenal (5 of 321; 1.6%), head/neck (2 of 321; 0.6%), and reproductive (1 of 321; 0.3%). Final diagnoses all had expected findings for trauma specimens identifiable via gross examination except for 1 case that identified low-grade intraepithelial neoplasia in a pancreatectomy specimen. Partial financial analysis (82 of 201 cases; 40.5%) revealed 14.4% reimbursement after factoring in slide production costs (Figure 3.89).

Conclusions: The clinical utility of trauma specimen microscopic examination does not justify the cost. A total of 99.7% (320 of 321) of specimens demonstrated expected findings, whereas the lone finding of low-grade intraepithelial neoplasia has a questionable potential impact on patient management. Estimated overall revenue was 14.4%, even without accounting for factors such as pathologist time. Adopting a broad policy of gross examination only for trauma specimens would improve health care resource use without affecting patient care.

Pathology Residents' Perspective on Informatics Education

(Poster No. 90)

James Fry, DO, MS ([email protected]); Hoda Hagrass, MD, PhD. Department of Pathology, UAMS, Little Rock, Arkansas.

Context: In pathology specifically, informatics is the integration of patient data, their flow through the laboratory, and their incorporation into health records. The field has steadily been growing, with the advent of new technologies, and is shown in the greater emphasis that both the ASCP and the ABP have put on it within their examinations.

Design: Residencies have been implementing various approaches to informatics education, and we set out to investigate residents' outlooks on those practices and on informatics in general, using a simple 10-question survey distributed through our program and the Internet. We also examined our own training by using precourse and postcourse scores and subscores in the RISE.

Results: Although they did not know the definition of “pathology informatics” or have a background in computer information, most responders agreed that being trained in the field can help find employment and increase job performance, and a smaller majority believed that informatics education can help with examinations. Scores in the postcourse examination increased on average by 21%, with some being as high as 50%. RISE subscores remained steady during the last 3 years, but there was a 15–percentage point jump in the average from 2019 to 2020.

Conclusions: The implementation of a structured informatics curriculum had a positive impact on knowledge of the field, reflected in their course examinations and RISE scores during the last few years. This can carry through to board examinations and help graduates throughout their careers. Although informatics education has a way to go, we are heading in the right direction.

Expanding Digital Pathology Services in the Community Hospital Setting

(Poster No. 91)

Bindu Challa, MD1 ([email protected]); Swati Satturwar, MD1; Melinda Schumacher, MD1; Brenna Simmons, MS2; Zaibo Li, MD1; Giovanni Lujan, MD1; Anil Parwani, MD1; Manisha Mishra, MD.1 1Department of Pathology, The Ohio State University Wexner Medical Center, Columbus; 2Department of Pathology, Highland District Hospital, Columbus, Ohio.

Context: With an increasing demand for intraoperative frozen sections caused by more hospitals being added to the community hospital network, we aimed to expand our digital pathology services in the community setting and evaluate their utility.

Design: Our information system was queried during a period of 2 years to identify the cases where remote robotic frozen section consultation (FSC) and digital surgical pathology consultations (DSPCs) were performed. Frozen sections were prepared by experienced histology technicians using standard protocols. FSC was performed using remote robotic-assisted Q2 (Mikroscan SL5, Carlsbad, California) software. Two community hospital pathologists read the FSCs remotely; and for consults 1 pathologist rendered digital diagnoses.

Results: A total of 71 FSCs (Highland District Hospital) and 72 DSPCs (Wyoming) were included. Of 71 FSCs, diagnoses were rendered in 69 cases (97.18%) and deferred to permanent sections in 2 cases (2.82%). The FSC diagnosis and final pathology diagnosis were discordant in 7 of 69 cases (10.15%). Turnaround time (TAT) ranged from 10 to 59 minutes. Technical difficulties were encountered in 6 FSC cases. For DSPCs, the specimen type is depicted in the pie chart (Figure 3.91). The number of specimen parts ranged from 1 to 15 and the number of digital images ranged from 1 to 34. Final diagnoses were given for all cases. There were no technical difficulties. TATs ranged from 46 minutes to 14 days, 1 hour, 13 minutes.

Conclusions: Our data show that remote FSC is an efficient and reliable tool with acceptable TAT in the community hospital setting, and they affirm the utility of digital pathology for remote DSPCs.

Smartphone Deployment of Neural Network Ki-67 Interpretation Tool

(Poster No. 92)

Christopher Jackson, MD ([email protected]); Joshua Levy, PhD; Lou Vaickus, MD, PhD; Xiaoying Liu, MD. Department of Pathology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire.

Context: The Ki-67 index is used in grading neuroendocrine neoplasms from the lungs, pancreas, and gastrointestinal tract. Measuring this index can be time-consuming. Although digital pathology machine learning analytic tools are available to perform this task, none have been deployed as a standalone smartphone application. The creation of such an application may improve pathologist efficiency and reproducibility, especially in low-resource settings.

Design: A smartphone application was created using Python 3.8 and Kivy 2.0.0 that allows pathologists to automatically compute the Ki-67 index using an artificial neural network. The application was deployed to a Samsung Note 10 (Samsung, Suwon-Si, South Korea; Figure 3.92, A). Ten clinical Ki-67 immunohistochemistry slides from neuroendocrine neoplasms were collected. One photomicrograph was obtained from each case using the smartphone and an Olympus BX41 microscope. A pathologist used the images to compute the Ki-67 index by (1) manually dotting the images and (2) using the smartphone application. Wilcox paired sign rank tests and Spearman correlations were used to compare performance (Figure 3.92, B and C). CIs were generated with nonparametric bootstrapping.

Results: The average time to measure the Ki-67 index was 621 ± 300 seconds with the manual method, and 70.18 ± 19 seconds with the smartphone, with a median time difference of 559.4 seconds (95% CI, 336.8–816.8 seconds; P = .002). The median absolute difference in Ki-67 indexes between the methods was 7.9% (95% CI, 1.7%–18.5%; P = .19), and the correlation was 0.79 (95% CI, 0.26–0.93).

Conclusions: The smartphone application reduced the time required to evaluate the Ki-67 index and yielded a moderately high correlation.

Comparing the Immunohistochemistry Scoring of Breast Tumor Tissue Microarrays Using Definiens, InForm, and QuPath

(Poster No. 93)

Gabrielle M. Baker, MD1 ([email protected]); Hanqiao Zheng, MD1; Vanessa C. Bret-Mounet, BS1; Tengteng Wang, PhD2; Mitko Veta, PhD3; Laura C. Collins, MD1; A. H. Eliassen, ScD4; Rulla M. Tamimi, ScD5; Yujing J. Heng, PhD.1 1Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; 2Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts; 3Medical Image Analysis Group, Eindhoven University of Technology, Eindhoven, the Netherlands; 4Department of Epidemiology, Brigham and Women's Hospital and Harvard T. H. Chan School of Public Health, Boston, Massachusetts; 5Department of Population Health Sciences, Weill Cornell Medicine, New York, New York.

Context: Understanding potential biases in immunohistochemistry data acquired using different software is important. We compared immunohistochemistry quantification of ER, PR, HER2, epidermal growth factor receptor (EGFR), and cytokeratin 5/6 (CK 5/6) across 3 software applications with manual scores.

Design: Four tissue microarrays were constructed with invasive breast carcinomas from 385 women given a diagnosis between 2001 and 2008. ER, PR, HER2, EGFR, and CK 5/6 immunostained slides were digitized into 2 file formats. Definiens Tissue Studio analyzed .mrxs files and InForm analyzed .qptiff files. Because of file format incompatibility between applications, QuPath was employed for comparison. The %positive score/core between manual and each software (Spearman ρ) was compared. For case-level comparisons, we correlated the tumor's highest manual score and software-derived weighted average %positive. Receiver operating characteristic curves (AUCs) were used to determine the sensitivity/specificity of software against dichotomized manual assessment (negative versus low positive/positive).

Results: At a core level, the correlations between manual score and each software were the highest for HER2 (ρ 0.75–0.79) and lowest for EGFR (ρ 0.38–0.45; P < .001). At case level, PR had the best correlations between manual and software (ρ 0.79–0.82), whereas EGFR had the lowest (ρ 0.43–0.49; P < .001). Although software forms were highly comparable to each other (ρ 0.80–0.99 across 5 markers), QuPath had the highest ρ when benchmarked against manual read for ER, PR, HER2, and EGFR. All AUCs were ≥0.83.

Conclusions: The software applications were highly comparable to each other and to manual scores, particularly for ER, PR, and HER2. QuPath, an open-source application, is a remarkable tool in the automated evaluation of immunohistochemistry.

Five Years of Full Digital Workflow at a High-Volume Academic Pathology Center: Experiences and Perspectives

(Poster No. 94)

Ankush Patel, MBBCh ([email protected]); Nada Shaker, MD, MS; David Kellough; Martha Yearsley, MD; Giovanni Lujan, MD; Zaibo Li, MD, PhD; Anil Parwani, MD, PhD, MBA. Department of Pathology, The Ohio State University Wexner Medical Center, Columbus.

Context: Following an early push for digital laboratory integration in 2016, the Digital Pathology Scan Center (James Cancer Center, The Ohio State University Wexner Medical Center, Columbus) has converted scores of glass slides to build one of the largest collections of whole slide image (WSI) repositories in the world, serving the gamut of needs for a high-volume academic pathology department, including a litany of use-cases for research and education.

Design: More than 2 551 085 glass slides and more than 263 642 cases representing surgical pathology, cytopathology, hematopathology, autopsy, and consults have been digitized by 8 in-house Philips UFS scanners owned and operated by the institution since workflow transition went “live” on May 26, 2017.

Results: Digital pathology integration, including pathologist and staff training, greatly mitigated disruptions in academic and clinical practice prevalent in pathology departments throughout the globe and other nondigitized specialist workflows within the same hospital network following the inception of the COVID-19 pandemic. The digital transition, predating the pandemic by 2 years, has facilitated clinical and academic duties for the pathology department, with practitioner satisfaction increasing from improved office ergonomics, efficiency from rapid retrieval and review of case material, computational image analysis and image management system tools, and increased flexibility.

Conclusions: Exploitation of digital pathology tools and their applications continues to flourish at Wexner, with cell block scanning recently commencing in aiding in surgical-cytopathologic correlation. A robust quality control system mitigates uncommon instances of WSI scan failure (1.19%) for a department with an average daily volume of 2409 slides within the past 12 months.

No Simple Correlation Between Concentration of the High-Sensitivity Troponin I and Classic Troponin I Tested on Siemens Vista Instruments

(Poster No. 95)

Mennatallah Ewais, MD ([email protected]); Wieslaw Furmaga, MD, MS. Department of Pathology, UT Health San Antonio, Texas.

Context: High-sensitivity troponin I (HSTnI) has been implemented as a replacement for classic troponin I (TnI). HSTnI would expedite evaluations of emergency department (ED) patients with chest pain. ED patients with chronic cardiac diseases may have chronic troponin elevation, and clinical evaluation requires correlation between previous and current troponin concentrations. Majority institutions have replaced TnI with HSTnI, and no overlapping testing and correlation study has been done. The attempt to correlate TnI concentration with HSTnI results by a simple conversion factor of 1000 leads to erroneous conclusion. To establish a precise correlation between TnI and HSTnI concentrations, and to provide the tools allowing for an evaluation of patients with chronic cardiac diseases, or with previous abnormal troponin results, parallel testing must be performed.

Design: One thousand patient samples from the ED were tested for the HSTnI and TnI concentrations at the same time and at different levels. The correlation between these 2 assays was established.

Results: No simple correlation between HSTnI and TnI concentrations has been established. The linearity of these 2 assays crossed twice at 17 and 100 ng/L. At the levels of <50 ng/L and >100 ng/L, TnI concentration is higher than HSTnI, but at concentrations between 50 and 100 ng/L, HSTnI concentration is higher than TnI.

Conclusions: There is no simple correlation between HSTnI and TnI concentrations, and no simple calculation converting HSTnI to TnI. To help clinicians evaluate cardiac patients, a correlation graph or a table with parallel values should be provided.

Effect of COVID-19 on Test Ordering and Use

(Poster No. 96)

Rita H. Khoury, MD ([email protected]); Peter Gudaitis, BA; Asha Gandhi, BA; Prital Patel, BA; Dauna Gudaitis, BA. Aculabs Inc, East Brunswick, New Jersey.

Context: COVID-19 is a pandemic infection caused by SARS-CoV-2 virus, with more than 450 million cases and 6 million deaths worldwide. Because of the lack of accurate testing for COVID-19 infection at the beginning of the pandemic, physicians turned to alternate tests, like blood culture, ferritin, D-dimer, and procalcitonin, to manage their patients. Procalcitonin has been shown to be a clinically useful marker for sepsis and to help antibiotic stewardship.

Design: We collected 1836 samples for procalcitonin and 37 238 samples for SARS-CoV-2 from residents in long-term care facilities from March 2020 to December 2020. The percentage of positive SARSCoV-2 and procalcitonin >0.15 ng/mL were calculated on a monthly basis. Statistical analysis was done using Analyse-it.

Results: The positivity rate for SARS-CoV-2 was higher in March and April 2020 and decreased in the following months and went up in November and December 2020. The percentage of patients with elevated procalcitonin was negatively correlated with positivity rate for SARS-CoV-2 (Table).

Conclusions: An increased prevalence of COVID-19 in the geriatric population causes an increase in procalcitonin orders. The low percentage of patients with elevated procalcitonin in March and April is most likely due to an increase in unnecessary orders that biased the results. COVID-19 had a major impact not only on SARS-CoV-2 virus testing but extended the overuse of other tests. An open dialogue between physicians and laboratorians is very important during pandemic crises to help concentrate the effort on diagnosis and treatment.

High-Sensitivity Troponin T Value in Relation to the Conventional Cardiac Troponin I Value and Performance Characterization

(Poster No. 97)

Nuvaira Ather, MD ([email protected]); Raul Benavides, MD. Department of Pathology, Baylor University Medical Center, Dallas, Texas.

Context: Comparison of the reportable concentrations of high-sensitivity troponin T (hsTnT) versus conventional cardiac troponin I (cTnI) and its characterization in hospitalized and emergency department patients in a large-sized academic medical center.

Design: Electrochemiluminescence immunoassay (Roche, Indianapolis, Indiana) was used to determine hsTNT, and cTnI was determined using sandwich chemiluminescent immunoassay (Siemens Vista, Erlangen, Germany). Data were collected in 438 serial patients; electronic medical records were reviewed. They were categorized into 2 groups clinically, patients with and without acute myocardial infarction, after listing them in a spreadsheet. Acute myocardial infarction was adjudicated by an in-house cardiologist. In addition, ratio of hsTnT to cTnI was determined.

Results: The sensitivity and the positive predictive values decreased from 99.3% to 59.4% as the cutoff for hsTnT concentrations increased from 14 ng/L to 1000 ng/mL, whereas the opposite (increase) was seen for specificity and negative predictive values. Comparison of the hsTNT and cTnI ratios does not allow for a direct mathematical correlation, but a rough estimate can be provided, as seen in the Table.

Conclusions: The findings at our institute replicated and reinforced the findings from previous studies. Also, although our data provide a rough estimate as to what cTnI value could be for a given hsTnT value, the many examples of significant outliers prove that there is no direct mathematical correlation or conversion and it is not reliable on an individual patient-by-patient analysis.

Can First-Trimester Maternal Serum Biomarker Screening Also Predict Subsequent Development of Gestational Diabetes Mellitus? A Study in an Iranian Population

(Poster No. 98)

Mitra Shavakhi, MD1; Agha Wajdan Baqir, MD2 ([email protected]). 1Department of Pathology, Sajad Medical Laboratory, Shahin Shar, Islamic Republic of Iran; 2Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Context: Gestational diabetes mellitus (GDM) is a pregnancy-related complication with adverse outcomes. Oral glucose tolerance test (OGTT) is used to diagnose GDM, usually in the late second trimester. This study aimed to investigate the role of first-trimester maternal serum biomarker screening in early diagnosis of GDM in an Iranian population with no prior history of GDM.

Design: Clinical database was searched for the previous 3 years to identify 140 singleton pregnant women aged 19 to 42 years. A total of 20 patients had documented GDM (positive OGGT at 24–28 weeks) and 120 acted as negative controls. Pregnancy associated plasma protein A (PAPP-A), free β-human chorionic gonadotropin (β-HCG), and fetal nuchal translucency (NT) measurement were assessed retrospectively for a possible relationship to development of GDM. Analysis of multiples of the median values was performed and independent t-test was used to identify the differences between 2 groups. Statistical significance was defined as P < .05. Receiver operating characteristic (ROC) curves analysis was used to determine the prognostic value.

Results: PAPP-A was significantly lower in GDM patients than in the control group (P = .02), whereas there was no statistical difference in β-HCG (P = .41) and NT (P = .55; Table). ROC curve analysis of PAPPA yielded an area under the curve (AUC) of 0.66, sensitivity of 60%, and specificity of 70%. Differences in maternal age, weight, and gravidity were not statistically significant.

Conclusions: Although a statistically significant association between low PAPP-A and subsequent GDM development was found in our study, the low AUC, sensitivity, and specificity limit its use in an early diagnosis of GDM. Nonetheless, this emphasizes the need for further evaluation of these parameters in larger prospective study.

Utility of Procalcitonin in the Diagnosis of Sepsis: An Institutional Experience

(Poster No. 99)

Paul E. Young, MD ([email protected]); Anthony O. Okorodudu, PhD, MBA. Department of Pathology, University of Texas Medical Branch, Galveston.

Context: Sepsis is a life-threatening condition caused by a dysregulated host response to infection. According to the US Centers for Disease Control and Prevention, 1.7 million Americans develop sepsis each year, with a mortality rate of about 15%. This underlines the need for early and accurate diagnosis of sepsis in hospitalized patients. At present, there is no gold standard biochemical test for diagnosing sepsis and blood cultures are not reliable. Procalcitonin (PCT) has shown some potential in the diagnosis and monitoring of sepsis. In this study, we aimed to evaluate the performance of PCT in the diagnosis of bacterial sepsis, using positive blood culture as gold standard for diagnosis.

Design: We retrospectively reviewed results of all PCT tests performed at our institution during a 6-month period, correlating them with blood culture results performed within 24 hours.

Results: For the study 728 patient-results were identified. Of these 56 patients had elevated PCT and concomitant positive blood culture (true positive), 38 patients had normal PCT with positive blood culture (false negative), 174 patients had elevated PCT with negative blood culture (false positive) and 460 patients had negative PCT with negative blood culture (true negative), yielding a sensitivity of 59.57%, specificity of 72.56%, negative predictive value of 92.36%, and positive predictive value of 24.35%.

Conclusions: At this time, PCT alone does not appear to be a sensitive and specific marker for predicting patients with sepsis; however, PCT demonstrated significantly high negative predictive value, indicating that individuals within the reference range have a low likelihood of having sepsis.

T-Cell Receptor Chemistry and Survival Data Support the Consideration of ARMC3 as a Breast Cancer Antigen

(Poster No. 100)

Nagehan Pakasticali, MD1 ([email protected]); Andrea Chobrutskiy, MD3; Dhruv N. Patel, PhD2; Monica Hsiang, MD2; Saif Zaman, MD2; Konrad J. Cios, MD2; George Blanck, PhD2; Boris I. Chobrutskiy, MD.4 Departments of 1Pathology and 2Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa; Departments of 3Pediatrics and 4Medicine, Oregon Health and Science University, Portland.

Context: Given advances in cancer immunotherapy, further understanding of potential antigens will improve treatment protocols. Cancer testes antigens (CTAs) are normally expressed in benign testis and placenta, and they show aberrant expression in many malignancies, including breast cancer. This work indicated that CTA, ARMC3 (Armadillo repeat-containing protein 3) is commonly expressed in breast cancer. There was T-cell response to ARMC3 when evaluated for its chemical relationship to T-cell receptor (TCR) chemical features.

Design: TCRα and TCRβ recombination data were extracted from National Institutes of Health genomics data sets. Linkage of chemical complementarity scores (CSs) to survival rates, and to RNAseq values, was done with a Web tool designed for these purposes termed adaptivematch.com. Kaplan-Meier analysis was conducted to compare survival probability for the upper and lower 50th percentiles of CSs. Multivariate analysis of age, race, menopause, and cancer stage was performed for ARMC3-based CSs.

Results: Among a set of approximately 280 CTAs, ARMC3 expression stood out as representing a strong distinction for survival rates for both overall survival (OS) and disease-free survival (DFS) (OS, P = .01; DFS, P = .01). We next considered the possibility that a TCR CDR3-ARMC3 interaction would be consistent with the expression of immune biomarkers. Results indicated higher RNA expression of certain immune markers with increasing CS values. Only the tumor stage and the ARMC3-based CS represented independent factors associated with survival distinctions.

Conclusions: For the ARMC3 expression, the higher the expression level, the better the survival probability. CS assessments of TCR CDR3-CTA pairs may indicate targetable antigens and may be useful for risk stratification and guiding therapy in breast cancer.

Kinetics and Durability of Humoral and Cellular Response of SARS-CoV-2 Messenger RNA Vaccine in a Lung and Kidney Transplant Recipient

(Poster No. 101)

James O. Long, MD1 ([email protected]); Kathleen Conry-Cantilena, MD1; Pawel Muranski, MD2; Mithil Soni, PhD2; Valeria De Giorgi, PhD.1 1Department of Transfusion Medicine, National Institutes of Health, Bethesda, Maryland; 2Department of Medicine, Columbia University Irving Medical Center, New York, New York.

The ongoing evolution of the SARS-CoV-2 virus has resulted in multiple variants of concern that pose a significant threat to global public health. These variants contain variable mutations within the receptor binding domain and more broadly the spike protein which may offer escape from neutralizing antibodies produced from both natural infection and immunization, resulting in breakthrough infections. Reports of immunogenicity of the SARS-CoV-2 messenger RNA vaccine show that solid organ transplant recipients are less likely to form antibodies after 2 doses. A 63-year-old healthy woman health care worker who was at 15 years' status after a double lung transplant and 6 years' status after a living related donor kidney transplant on chronic prednisone, tacrolimus, and mycophenolate, received the SARS-CoV-2 messenger RNA vaccine (Pfizer-BioNTech BNT162b2) primary series on December 28, 2020, and January 14, 2021, with a booster dose on August 24, 2021. Neutralizing, immunoglobulin G (IgG), and total antibodies against the SARS-CoV-2 spike protein were assessed every 1 to 2 months from February 2021 to January 2022 using an in-house fluorescence reduction neutralization assay and the VITROS Anti-SARS-CoV-2 Total and IgG assays, respectively (Figure 3.101, A through C). Robust T-cell responses to full-length spike peptide libraries and variants including α, β, γ, δ, and o (data pending) were detected in peripheral blood upon in vitro priming of peripheral blood mononuclear cells, underscoring the role of cellular immunity (Figure 3.10, D). This case demonstrates persistent albeit diminished in vitro humoral and cellular responses against SARS-CoV-2 infection including novel variants for up to 6 months following primary vaccination and booster in an immunosuppressed individual.

Rare Case of Transfusion-Transmitted Malaria With Immature Peripheral Blood Plasmodium falciparum Gametocytes

(Poster No. 102)

Fernanda da Silva Lameira, MD ([email protected]); Shaun D Lawicki, MD; Gordon L. Love, MD; Rachna Jetly Shridhar, MD. Department of Pathology, Louisiana State University Health Sciences Center, New Orleans.

Blood components are rare causes of transfusion-transmitted malaria (TTM) in nonendemic regions. We report TTM with unusual Plasmodium falciparum forms in a 22-year-old sickle cell disease patient on monthly red blood cell (RBC) exchange transfusions with no history of international travel or intravenous drug abuse. Two months after transfusion with 8 RBC units the patient presented with fever, hemoglobin 7.8 g/dL, and mild neutrophilia. All blood, urine, respiratory, and cerebrospinal fluid infectious evaluations were negative. Peripheral blood smear had sickled gametocytes and ring trophozoites of P falciparum (Figure 3.102, A, C, and D). Additional immature (nonsickled) gametocytes (Figure 3.102, B and C, arrows) were concerning for coinfection with a second Plasmodium species; however, molecular testing confirmed P falciparum. In natural infections immature P falciparum gametocytes sequester in internal organs and do not circulate in the peripheral blood. Since Plasmodium can survive in stored blood for variable durations, in our case the storage conditions may have altered gametocyte development allowing for formation and peripheral circulation of all gametocyte stages. The patient was treated with antimalarial agents and responded well. In the United States, TTM incidence is <1 per million units of blood transfused. In patients receiving multiple RBC units frequently, source determination is challenging. Donor blood screening is not feasible in malaria non-endemic countries that rely mostly on screening questionnaire and deferral policies. COVID pandemic–related blood product shortages led to a 3-month deferral duration (previously 1 year) for donors traveling to malaria endemic regions, likely increasing the TTM risk.

A Novel Hybrid Mutation of RHCE Genotype in a Family Discovered After Investigation of Anti-Rh46

(Poster No. 103)

Mehrnoosh Ghandili, MD1 ([email protected]); Christina S. Warren, MS, MLS(ASCP)SBB2; Gregory J. Pomper, MD1; Emmanuel Fadeyi, MD1; Danielle L. Maracaja, MD, MS.1 1Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina; 2Department of Pathology, Atrium Health Wake Forest Baptist, Winston-Salem, North Carolina.

Rh is encoded by 2 homologous genes, RHD and RHCE. Rh46 (Sec) is a high-frequency antigen associated with variants of the RHCE. If immunized by pregnancy or transfusion, anti-Rh46 can be produced, which reacts with all Rh phenotypes except for RN, Rhnull, D–, and related phenotypes. We report a 56-year-old African American woman with a known history of anti-Rh46 and anti-E who presented with heart failure due to aortic and mitral valve insufficiency. She was scheduled for an elective heart surgery, and a single autologous unit was available that had been stored for 14 years. The patient was ineligible for additional autologous donation because of her low weight. Furthermore, compatible units were not found through the American Rare Donor Program and an investigation of family members was performed. Among 7 relatives, only her 2 sisters were crossmatch compatible. Genotyping and sequencing performed on the patient and 3 relatives revealed a novel hybrid reported as RHCE*ce48C,505A,509-T,514A,733G. Unfortunately, these relatives were unable to donate. Ultimately, donors were selected using monocyte monolayer assay with medium-resolution testing allele-matched units from the American Rare Donor Program. The patient underwent a percutaneous procedure without needing blood. The phenotype of this novel allele is unknown; however, it shares 3 amino acids with the RHCE*CeRN allele that is associated with the loss of Rh46. In conclusion, this case highlights the importance of studying family members in identifying novel mutations on the RHCE gene.

Late Presentation of Solid Organ Graft-Versus-Host Disease and Presumed Autoimmune Hemolytic Anemia With Recipient Allo-Anti-E and Anti-E of Probable Donor Lymphocyte Origin

(Poster No. 104)

Yiannis Petros Dimopoulos, MD; Charmaine Joyce L. Ilagan, MD ([email protected]); Colleen W. Gilstad, MD. Department of Pathology and Laboratory Medicine, MedStar Georgetown University Hospital, Washington, DC.

Graft-versus-host disease (GvHD) as a complication of solid organ transplantation usually occurs within the first 3 months after transplantation and presents with fever, skin rash, and diarrhea. Hemolysis due to passenger lymphocyte syndrome typically presents 1 to 3 weeks after transplantation and resolves within 3 months. We present a case of late presentation GvHD with a direct antiglobulin test positive hemolytic anemia. A 59-year-old woman (blood group O RhD-positive) with a history of type I diabetes and end-stage renal disease underwent simultaneous pancreas-kidney transplantation (donor blood group O RhD-positive). Her posttransplantation course was complicated by a psoriasiform rash responsive to topical and systemic therapy (120 days), posttransplantation lymphoproliferative disorder (203 days), cold autoagglutinin (209 days), anti-E alloimmunization, and warm autoimmune hemolytic anemia (256 days). Despite treatment, the patient's plasma reactivity to E-negative cells increased while reactivity to E-positive cells weakened on serial antibody identification panels. An eluate of the patient's red blood cells revealed anti-E. Red blood cell antigen genotyping on pretransplantation patient and donor samples revealed the donor to be E antigen negative and the patient to be E antigen homozygous positive. The patient eventually developed aplastic anemia (475 days) with peripheral blood chimerism demonstrating donor T-lymphocyte predominance, further supportive of GvHD and probable donor lymphocyte origin of the detected anti-E. In conclusion, presumed “autoimmune” hemolytic anemia in solid organ transplant recipients may be due to donor lymphocyte–derived antibodies even in patients beyond the period where passenger lymphocyte syndrome usually occurs and should prompt consideration of GvHD as the underlying diagnosis.

The Use of Red Blood Cell Exchange to Treat Methemoglobinemia in a Young Woman With Serotonin Syndrome

(Poster No. 105)

Shannon B. May, MD ([email protected]); Yong-Sang Park, MD; C John Luckey, MD, PhD. Department of Pathology, University of Virginia, Charlottesville.

Methemoglobinemia results in impaired oxygenation of tissues as the oxidized ferric hemoglobin molecules cannot irreversibly bind oxygen. The clinical presentation can range from asymptomatic cyanosis to severe hypoxemia and death. Acquired cases are usually due to exposure to oxidative drugs or toxins. Treatment with methylene blue typically decreases methemoglobin levels within 30 to 60 minutes. However, methylene blue can have serious adverse effects in patients with G6PD deficiency and can precipitate serotonin syndrome. Alternative treatments for severe, acute methemoglobinemia are needed for these patient populations. We report a case of a 27-year-old woman who intentionally ingested sodium nitrate. She presented profoundly cyanotic, hypoxemic, and hypotensive with chocolate-colored blood. Her initial methemoglobin concentration was 86.2% (reference range, 0.4%–1.5%). She was emergently given methylene blue (2 mg/kg). After 30 minutes, her methemoglobin mildly improved to 71.7% but her hypoxemia worsened, with sustained oxygen saturations of 51% to 56% (Figure 3.105). She developed hyperreflexia and ocular clonus concerning for serotonin syndrome—she was prescribed fluoxetine—precluding additional methylene blue. Unfortunately, she decompensated and was placed on extracorporeal membrane oxygenation, during which she had 3 units of blood replaced. She then underwent emergent red blood cell exchange of 2100 mL with marked improvement in her methemoglobinemia and hypoxemia. She continued to improve and was discharged on hospital day 10. Although there are currently no guidelines for therapeutic apheresis in the setting of methemoglobinemia, this case highlights its potential use in patients for whom methylene blue treatment is insufficient or contraindicated.

“Trash in the Cloud”: How Irresponsible Whole Slide Imaging Can Impact the Environment—Carbon Footprint Calculation in Digital Pathology

(Poster No. 106)

Hiran M. Dewar, BS1 ([email protected]); Bilal Ahmad, MD2; Rohit Ratnala, MD3; Rajan Dewar, MD, PhD.4 1Department of Computer Science and Human Rights, Stanford University, Stanford, California; 2Department of Pathology, Spectrum Healthcare, Portland, Maine; 3Department of Pathology, McLaren Greater Lansing, Lansing, Michigan; 4Department of Pathology, McLaren Greater Lansing and Michigan State University, Lansing.

Context: Studies from Carnegie Mellon University and Stanford University show digital data storage significantly contributes (~30% total by 2035) to the global carbon footprint. Given the explosion of digital pathology, we studied the carbon footprint contributions of unstructured and indiscriminate whole slide image (WSI) scanning and long-term storage.

Design: Total carbon footprint is a function of process, servers, and energy consumption for facility maintenance. We modeled a midsized pathology department adopting global WSI, scanning all the slides produced everyday with 4 different commercial scanners. We estimated a local server's energy use for the processors as well as facility maintenance (continual air exchange, emergency backup power generator, climate control). Lastly, to show waste involved, we calculated the number of slides retrieved in any given days from storage for any purposes (tumor boards, consultation, second opinion). The intent was to estimate %usage of stored material.

Results: Every day we generate 40 cases and 320 slides; scanning times drastically differ between scanners and tissue types. Scanning consumes approximately 1614.75 kwh/y (range, 667–3646 kwh). Storage for 10 years (based on slide storage requirements of the College of American Pathologists) involves 63291566.667 total pounds of CO2. Retrieval data showed that on average <5% of slides were retrieved for rereview.

Conclusions: An average midsized hospital can consume 63291566.667 total pounds of CO2. Unplanned scanning/storage functions can result in enormous waste. Some steps in planning will involve an expert digital pathology architect's input—compression/decompression algorithms, cloud/local servers, limited scanning of particular case types (commonly retrieved), and recycling unnecessary storage with possible glass slide as backup.

A Rare Case of Hepatoid Adenocarcinoma of the Lung With Liver Metastasis: A Diagnostic Challenge With Potential for Misdiagnosis

(Poster No. 107)

Rokana Taftaf, MD, PhD, MS ([email protected]); Surendra P. Singh, MD. Department of Pathology, The University of Toledo Medical Center, Toledo, Ohio.

Hepatoid adenocarcinoma of the lung (HAL) is an extremely rare type of primary lung adenocarcinoma that contains both adenocarcinoma and hepatocellular carcinoma–like characteristics. Here, we report a case of HAL in a 61-year-old man with an aberrant immunohistochemical (IHC) profile. He initially presented with a 1.5-cm left upper lobe lung nodule and subsequently underwent a wedge resection. The pathology showed invasive adenocarcinoma that was TTF1+ (Figure 3.107, A), CK7+, CK20, and CDX2. A new enlarged aortopulmonic window lymph node was found afterward to have metastatic adenocarcinoma. Later, multiple new liver lesions were discovered and misdiagnosed as hepatocellular carcinoma (HCC) because of the suggestive IHC expression profile of tumor cells: HepPar1+, TTF1 (Figure 3.107, B and D), CK7+, CK20, and CDX2. The patient eventually underwent a transarterial chemoembolization procedure to treat the diagnosed HCC with no response and presented later with an increase in the size and number of the liver lesions. Therefore, liver biopsy was repeated, and the diagnosis was revised as adenocarcinoma with hepatoid features, instead of HCC. A thorough investigation showed that the liver neoplasm is intracytoplasmic mucin+ and Glypican3. Moreover, further workup on the previous lung resection and lymph node samples showed that the tumor cells are HepPar1+ in both specimens (Figure 3.107, A through D), supporting the diagnosis of the rare HAL metastasizing to the liver (stage IV). This unique case demonstrates the challenge in differentiating metastatic HAL to the liver from de novo HCC. We present this case as an important reminder that metastatic HAL to the liver may histologically and immunophenotypically resemble HCC.

Distinction of Tumor Heterogeneity From Synchronous/Collision Tumors in Lung Biopsies Using Targeted Next-Generation Sequencing Panel: A Retrospective Study

(Poster No. 108)

Mary Torrez, MD1 ([email protected]); Michaela Grenados, BS1; Khalil Sheibani, MD2; Mohammad A. Vasef, MD.1 1Department of Pathology, University of New Mexico, Albuquerque; 2Department of Pathology, Orange County Global Medical Center, Santa Ana, California.

Context: Variation in histomorphology and immunophenotype is typically attributed to tumor heterogeneity. However, the differential diagnosis of heterogeneous tumors also includes synchronous/collision tumors. A reliable separation of tumor heterogeneity from synchronous/collision tumors can be difficult on morphologic and immunophenotypic grounds. In this study, we evaluated the utility of a targeted next-generation sequencing (NGS) gene panel in distinguishing these entities.

Design: Six cases were identified, including 5 synchronous and 1 collision tumor, diagnosed between 2002 to 2021. Available molecular profiles in 5 of 6 cases were reviewed.

Results: Histologic review of the 5 cases with available molecular data revealed the following in each: 3 separate invasive adenocarcinomas (case 1); adenocarcinoma and large cell neuroendocrine carcinoma (case 2); poorly differentiated adenocarcinoma and small cell carcinoma (case 3); adenocarcinoma and carcinoid (case 4); and a contiguous but distinctly different TTF1+ (Leica Biosystems, Buffalo Grove, Illinois) well-differentiated adenocarcinoma and TTF1−, moderately differentiated adenocarcinoma (case 5). Mutually exclusive driver mutations were not present in limited available molecular studies in 4 of 5 cases. However, targeted NGS panel (Thermo Fisher Scientific, Waltham, Massachusetts) performed on the fifth case revealed 2 sensitizing EGFR mutations (G719C and S768I variants) in a portion of tumor with TTF1 expression and KRAS G12A mutation in the less differentiated component of tumor (Figure 3.108, A through D), supportive of 2 separate collision lung primaries.

Conclusions: Our results demonstrate that molecular profiling on DNA obtained from separately microdissected foci in heterogeneous tumors can prove helpful in separating true tumor heterogeneity from synchronous/collision tumors. This separation could be of utmost clinical importance to guide appropriate treatment management.

PD-L1 Expression in Non–Small Cell Lung Cancer in Adenocarcinomas With Lepidic Growth Pattern

(Poster No. 109)

Andrii Puzyrenko, MD, PhD ([email protected]); Carley Taylor, MD; Yuri Sheinin, MD, PhD. Department of Pathology, Medical College of Wisconsin, Milwaukee.

Context: The treatment of lung adenocarcinoma can be tailored to whether the tumor cells express the programmed death-ligand 1 (PDL1). Pulmonary adenocarcinoma frequently displays various histologic patterns, including lepidic ones, and this heterogeneity could affect PD-L1 evaluation. In this study, we sought to determine a correlation between expressing the PD-L1 and lepidic adenocarcinoma (LAC).

Design: There were 13 consecutive cases of LAC, including 2 adenocarcinomas in situ, 4 minimally invasive adenocarcinomas, and 7 adenocarcinomas with lepidic predominant. The control group included 10 consecutive cases of acinar adenocarcinomas. Immunohistochemistry for PD-L1 (clone 73-10, Leica Biosystems) was performed in all cases. The tumor proportion score (TPS) was calculated, with a threshold TPS >1%.

Results: Patient age ranged from 61 to 84 years in the main group. LACs were mainly unifocal (only 3 patients had multiple nodules in the same lung) with no site predominance. Tumor size ranged from 0.8 to 3.1 cm. Twelve cases (92%) of the LACs were negative for PD-L1 (Figure 3.109). One minimally invasive adenocarcinoma showed PD-L1 expression in the invasive component only with an overall TPS 5%. All cases of the invasive adenocarcinomas with acinar predominant in the control group were positive for PD-L1 stain with at least TPS 20%.

Conclusions: This pilot study demonstrates that most LACs are PDL1 negative, indicating that corresponding immunotherapy would be ineffective in these patients. The results are further supported by the Leica PD-L1 clone used in the study, because this clone 73-10 was reported to be more sensitive compared with the Dako PD-L1 22C3 pharmDx clone.

Nodular Pulmonary Light Chain Deposition Disease: An Uncommon Entity With Important Diagnostic Implications

(Poster No. 110)

Mohammad Al-Attar, MD ([email protected]); Salwa M. Khedr, MD, MSc; Ali Akalin, MD. Department of Pathology, University of Massachusetts, Worcester.

Nodular pulmonary light chain deposition disease (NPLCDD) is a rare entity that poses a diagnostic challenge because of its uncommon nature and close morphologic resemblance to amyloidosis and other unrelated entities. Accurate and timely diagnosis is essential in guiding further workup to identify and treat potential underlying lymphoproliferative or autoimmune disorders. We report a case of a 41-year-old asymptomatic woman presenting with multiple scattered pulmonary cysts and nodules measuring up to 8 mm that were discovered incidentally on imaging performed for an unrelated abdominal surgery. Wedge resections from the right upper and middle lobes grossly revealed multiple tan-white, well-circumscribed nodules measuring up to 6 mm and cystic areas measuring up to 4 mm. Microscopy revealed nodular aggregates of dense, amorphous, eosinophilic material (Figure 3.110, A, arrowhead) along the bronchial and vascular tracts, cyst formation (Figure 3.110, A, asterisk), and associated lymphoplasmacytic infiltrate and multinucleated giant cell reaction (Figure 3.110, B). The plasma cells were positive for CD138 and showed j restriction on κ (Figure 3.110, C) and λ (Figure 3.110, D) in situ hybridization studies. Immunoglobulin G4 (IgG4) immunostain and Congo red special stain were negative. Further immunohistochemical and B-cell clonality studies revealed the presence of an underlying MALT lymphoma with plasmacytic differentiation. NPLCDD is a rare entity that requires a high index of suspicion and diligent workup to exclude mimickers. Although NPLCDD is indolent by itself, an accurate timely diagnosis is essential to guide treatment and identification of potentially life-threatening or debilitating underlying lymphoproliferative or autoimmune disorders.

Lineage Infidelity of Nuclear Markers in Small Cell Lung Carcinoma

(Poster No. 111)

Peter Mannion, MD ([email protected]); Jesse McKenney, MD; Erika Doxtader, MD; Sanjay Mukhopadhyay, MD. Department of Pathology, Cleveland Clinic Foundation, Cleveland, Ohio.

Context: Having occasionally encountered expression of unexpected nuclear markers (SATB2, CDX2, GATA3, and myogenin) in small cell lung carcinoma (SCLC), we undertook this study to clarify the incidence of positivity for these markers (“lineage infidelity”) in SCLC. We also examined the expression of immunohistochemical markers commonly used for the diagnosis of SCLC.

Design: A total of 95 cases of SCLC (43 biopsies, 20 resections, and 32 fine-needle aspirations) were stained with SATB2 (clone EP 281), CDX2, GATA3, and myogenin. Staining for commonly used markers (keratins, TTF-1, p40/p63, neuroendocrine markers) was also reviewed. Staining was semiquantified using the H score (range, 0–300).

Results: In SCLC, SATB2 was positive in 41 of 95 cases (43.2%), with an H score ranging from 5 to 285 (mean, 60; median, 94.1). CDX2 was positive in 7 of 95 cases (7.4%; H score, 5–60; mean, 30; median, 30). GATA3 (0 of 95) and myogenin (0 of 95) were negative in all cases. TTF-1 was positive in 21 of 25 SATB2-positive cases and 4 of 4 CDX2-positive cases. Overall, 55 of 62 cases (88.7%) were positive for TTF-1, 91 of 93 (97.85%) for synaptophysin, 69 of 94 (73.4%) for chromogranin, and 54 of 55 (98.2%) for either CAM5.2 or AE1/AE3. Only 2 of 54 cases (3.7%) expressed p40 or p63 (focal).

Conclusions: This is the largest reported series of SATB2 expression in SCLC. It confirms the findings of 2 recent smaller series that SATB2 expression occurs in a surprisingly high proportion of these tumors; a smaller subset also expresses CDX2. Hence, SATB2 and CDX2 cannot be considered specific for gastrointestinal origin in this context. Lineage infidelity for GATA3 and myogenin is uncommon in SCLC.

Tumor-to-Tumor Metastasis: Report of a Rare Case

(Poster No. 112)

Sarah Cain, DO1 ([email protected]); Saqib Abbasi, MD2; Ameer Hamza, MD.1 1Department of Pathology, University of Kansas Medical Center, Kansas City, Kansas; 2Department of Oncology, The University of Kansas Cancer Center, Kansas City, Kansas.

Tumor-to-tumor metastasis is a rare phenomenon. Literature review suggests that the most frequent donor tumor is lung cancer, whereas renal cell carcinoma is by far the most common recipient. The purpose of this report is to describe a case of prostate adenocarcinoma metastasizing to lung squamous cell carcinoma. A 67-year-old man with a 75 pack per year smoking history was diagnosed with Gleason grade 3 + 4 = 7 prostatic adenocarcinoma on biopsy in 2011. He subsequently underwent prostatectomy with pelvic lymph node dissection, revealing Gleason grade 4 + 3 = 7 disease with focal extraprostatic extension and no lymph node involvement. The patient developed biochemical recurrence in 2019. Imaging studies in January 2022 showed a solitary 10- to 12-mm spiculated nodule suspicious for malignancy in the right lower lobe of lung and bony lesions suspicious for metastatic disease. Biopsy of the lung nodule revealed squamous cell carcinoma that was positive for p40. Additionally, a portion of the core biopsies showed different histology with histiocytic appearance. On immunohistochemical staining those cells stained positive for PSA, PSAP, AR, and NKX3.1 and negative for p40, TTF1, ERG, CD68, and GATA3. Therefore, final diagnosis of squamous cell carcinoma and metastatic prostate adenocarcinoma was rendered. This case shows the rare phenomenon of tumor-to-tumor metastasis and highlights the importance of comprehensive morphologic assessment of the tissue, including utility of immunohistochemical staining, despite the presence of an obvious lesion.

Adenosquamous Carcinoma Arising in a Congenital Intrapulmonary Bronchogenic Cyst after 53 Years of Follow-Up

(Poster No. 113)

Adeyinka O. Akinsanya, MBBS ([email protected]); Hector Mesa, MD, PhD; Sheila Segura, MD; Harvey Cramer, MD. Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis.

Intrapulmonary bronchogenic cysts (IPBCs) are congenital malformations due to abnormal budding of the tracheobronchial tree. They may be asymptomatic or manifest with cough or compressive symptoms, such as dysphagia, atelectasis, or postobstructive pneumonia. Complications include hemoptysis, pneumothorax, and infection. Malignancy arising from bronchogenic cysts (BCs) is extremely rare. A 74-year-old woman with a history of an IPBC diagnosed 53 years earlier was noticed to have worsening hyponatremia, the most common electrolyte disorder in lung cancer. This prompted a chest x-ray that revealed a 4.5-cm left lower lobe mass. Fine-needle aspiration showed an adenosquamous carcinoma. The prognostic biomarker panel was positive for a G12D KRAS mutation, and negative for EGFR, BRAF, ROS-1, and ALK mutations/rearrangements. The patient underwent a lobectomy that showed an AJCC stage pT3N0 adenosquamous carcinoma. Histologic examination showed an IPBC with areas of borderline mucinous neoplasm progressing to mucinous adenocarcinoma, intimately admixed with a squamous cell carcinoma (Figure 3.113, A through D). The few existing reports of malignant transformation of BC include adenocarcinoma, squamous cell, and large cell carcinoma. To our knowledge, this is the first report of transformation to an adenosquamous carcinoma. There is a variable but consistent risk of malignant transformation of all congenital pulmonary airway malformations; it is high and associated with a short latency in congenital cystic adenomatoid malformation, and low with a long latency in BC. Our case supports the recommendation of complete surgical removal of these lesions to prevent complications, including malignant transformation, which may occur at any age.

Human Papillomavirus–Mediated Squamous Cell Carcinoma of Oropharynx With Pulmonary and Mediastinal Lymph Nodes Metastases: A Rare Case and Review of Literature

(Poster No. 114)

Obianuju M. Anelo, MD1 ([email protected]); Farhan Khan, MD.2 1Department of Pathology, The University of Tennessee Health Science Center, Memphis; 2Department of Pathology and Laboratory Medicine, Pathology Specialists of Memphis, Methodist Lebonheur Healthcare, Memphis, Tennessee.

Pulmonary metastasis from human papillomavirus (HPV)–mediated squamous cell carcinoma (SCC) of oropharynx is extremely rare and accounts for less than 2% of endobronchial neoplasms. We report a case of a 62-year-old man who presented with cough, fatigue, and weight loss. Patient had a history of HPV-related SCC of the tongue base, status after glossectomy, neck dissection, and chemoradiation 8 years ago. He was a nonsmoker. Chest computed tomography scan showed a left central lung mass with left hilar and mediastinal lymphadenopathy concerning for primary lung cancer. Positron emission tomography scan showed increased uptake in the left lung mass and the left hilar, paratracheal, and subcarinal lymph nodes. The patient underwent endobronchial ultrasound with biopsy of the lung mass and mediastinal lymph nodes. Microscopic examination showed nonkeratinizing basaloid SCC. Tumor cells were diffusely reactive to p40 and p16 immunostains and nonreactive to TTF-1 and synaptophysin immunostains. The subsequent mediastinal lymph node biopsy showed metastatic SCC that was positive for p16 immunostain, and HPV RNA ISH High Risk Cocktail was detected, suggestive of recurrent metastatic HPV-mediated SCC of the base of tongue. This case study highlights the diagnostic challenge and importance of testing for p16 and HPV RNA ISH in SCC arising in lung to diagnose metastatic HPV-related SCC, especially in patients with a positive history.

Challenging Diagnosis of a Sarcomatoid Mesothelioma With Negative Mesothelioma Markers: Recapitulating the Guideline for Malignant Mesothelioma Diagnosis

(Poster No. 115)

Linlin Yang, MD, PhD ([email protected]); Caroline Abramovich, MD. Department of Pathology, MetroHealth Medical Center, Cleveland, Ohio.

Pathologic diagnosis of sarcomatoid neoplasms in the pleura can be quite challenging given their similar histologic morphology and overlapping immunoprofiles. Use of a combination of immunohistochemical markers is always required, as well as correlation with the clinical and radiographic findings. Here we report a case of pleural sarcomatoid mesothelioma with unusual immunohistochemical features. A 67-year-old woman was evaluated for recurrent left pulmonary effusion since COVID pneumonia. Thoracentesis for cytology and culture were nondiagnostic, showing only exudative lymphocytic effusion. Two months later, she was found to have circumferential nodular pleural thickening throughout the left pleura with mediastinal invasion and lymphadenopathy by imaging. She denied any history of occupational or para-occupational asbestos exposure. Biopsy revealed sheets of pleomorphic and hyperchromatic spindle cells with prominent nucleoli and areas of necrosis (Figure 3.115, A). The major differential diagnostic considerations included sarcomatoid carcinoma involving the pleura versus sarcomatoid mesothelioma. Immunohistochemistry staining revealed tumor cells were positive for AE1/AE3, CK7 (Figure 3.115, B), and SMA (Figure 3.115, C), although they were negative for all established common mesothelial markers, including calretinin, D2-40, WT1, and CK 5/6, as well as other markers including TTF-1, Napsin A, p40, p63, desmin, CD34, BCL-2, PAX8, Melan-A, and EMA. Of note, tumor cells were diffusely positive for GATA3, which, in conjunction with negative staining for polyclonal CEA, was interpreted as evidence of mesothelial differentiation. This interpretation also aligned with the radiographic findings. This case highlights how the accurate diagnosis of malignant mesothelioma is accomplished by a multidisciplinary approach that includes clinical presentation, radiologic findings, and ultimately pathologic features.

Correlation of Histopathology and Microbiology Cultures of Lung Infectious Diseases

(Poster No. 116)

Diana M. Oramas, MD1 ([email protected]); Xavier L. Zepeda, MD2; Cesar A. Moran, MD.3 1Department of Pathology, University of Alabama at Birmingham; 2Department of Pathology, Women's Hospital of Texas, Houston; 3Department of Pathology, University of Texas MD Anderson Cancer Center, Houston.

Context: Recognition of pulmonary infections in oncologic-immunocompromised patients treated with chemoimmunotherapy/radiotherapy is usually delayed because of the decreased inflammatory response. Histopathology mimicking an infective condition may be misinterpreted if a thorough assessment is neglected. Although the use of imaging is critical for a differential diagnosis of the pulmonary infiltrates, the definitive diagnosis and target antimicrobial therapy are based on prompt histopathologic/microbiologic assessment.

Design: Single cohort of patients with a history of malignancy treated with chemoimmunotherapy/radiotherapy at MDACC between the months of July and December 2020. Tissue slides, microbiology cultures, and special stains for fungal and bacterial microorganisms were reviewed. Statistical analysis was performed.

Results: Of 854 patients, 29 showed lung tissue with possible infection conditions. The most common histopathologic findings were necrotizing and nonnecrotizing granulomas and fibrinous and organizing pneumonia. Microbiology and histopathologic records showed that of 29 patients, 8 (28%) had positive findings in histopathology evaluation and 5 (17%) for microbiology cultures. Histopathology and microbiology were compatible in 3 cases (10%). Using the microbiology culture results as a reference standard, histopathology shows a sensitivity 80% and a specificity 87%, with a positive predictive value (PPV) of 57% and negative predictive value (NPV) of 95%. Using the histopathologic assessment results as a reference standard, microbiology shows a sensitivity of 57% and a specificity of 93%, with a PPV of 80% and NPV of 82%. The analysis did not reach statistical significance (t score: 0.13, P = .5).

Conclusions: Comprehensive histopathologic evaluation of lung specimens showed to be more sensitive, promptly recognizing infective in origin infiltrates than microbiology cultures. However, the latter demonstrated to be more accurate in diagnosing a causative agent and allowing a specific targeting therapy.

Postmortem Finding of Dendriform Pulmonary Ossification in a COVID Patient With Sepsis

(Poster No. 117)

Linlin Yang, MD, PhD ([email protected]); Joseph F. Tomashefski Jr, MD. Department of Pathology, MetroHealth Medical Center, Cleveland, Ohio.

Dendriform pulmonary ossification is characterized by branching metaplastic bony formation in the lung parenchyma. It can be idiopathic or often associated with underlying interstitial lung disease. A recent report showed accelerated pulmonary ossification after COVID-19 pneumonia on imaging. Here we present a postmortem case of a COVID-19 patient with extensive dendriform pulmonary ossification found incidentally on histology. Decedent was a 44-year-old woman with a medical history of obesity, end-stage renal disease, sacral decubitus ulcers, and notable persistent COVID infection for a month who was hospitalized for sepsis in the setting of peritonitis. Grossly, autopsy revealed bilateral atrophic kidneys, moderate coronary artery atherosclerosis, and remarkable bilateral lung changes with congestion, edema, and diffusely distributed vaguely nodular induration, in addition to dispersed whitish firm ossification-like granular areas, particularly involving the perihilar areas (Figure 3.117, A). These corresponded to the imaging findings, showing progressive enhanced perihilar opacities. Microscopically, bilateral lung parenchyma showed diffuse alveolar damage with hyaline membrane formation, intra-alveolar fibrosis with lymphocytic infiltration, and patchy acute bronchopneumonia (Figure 3.117, B). Numerous irregularly branching spicules of mature bones were present in the alveolar spaces (Figure 3.117, C), some of which contained fat marrow tissues and showed a close association with surrounding intra-alveolar fibrosis and mixed inflammatory cell infiltration (Figure 3.117, D). The pathologic changes after COVID infection and sepsis in the lung might play an important role in the acceleration of pulmonary ossification in this case. However, it is difficult to determine whether the effect of COVID infection, the bacterial sepsis, or other factors led to the accelerated pathogenesis, and further investigation is needed.

Pulmonary Amyloidosis: A Rare but Important Consideration of Nodular Lung Disease—Report of 2 Cases

(Poster No. 118)

Ruchi Patel, MD ([email protected]); James Mueller, MD; Jonathan Freeman, MD. Department of Pathology, UMass Chan Medical School – Baystate Medical Center, Springfield, Massachusetts.

Amyloidosis comprises a wide spectrum of diseases, all resulting from misfolding of proteins into fibrils that are deposited extracellularly. Proteins derived from immunoglobulin light chains cause amyloid light-chain (AL) amyloidosis, the most common form of primary amyloidosis. The respiratory system is involved in half of cases but is rarely symptomatic or radiographically evident, but when recognized, it manifests in a nodular, alveolar, or tracheobronchial pattern. We present 2 cases of pulmonary amyloidosis, pleural and nodular, with unusual clinical presentations that resulted in unexpected diagnoses. Case 1 involved a 69-year-old man with heavy asbestos exposure who presented with increasing shortness of breath. Computed tomography revealed calcified bilateral pleural plaques with mediastinal, hilar, and axillary adenopathy and bilateral pleural effusions. Subsequent lung biopsy showed nodular amyloid deposition with associated lymphoplasmacytic infiltration. Bone marrow biopsy demonstrated plasma cell neoplasm with λ-clonal plasma cells comprising 5% of marrow cellularity. Case 2 involved a 42-year-old woman with systemic lupus erythematosus with multiple lung nodules and left axillary lymphadenopathy. Biopsy of the nodule showed amyloid deposition in lung parenchyma and blood vessel walls. Mass spectrometry in both cases revealed AL composed of λ light chain. Although nodular lung disease occurs in systemic AL amyloid, it is sufficiently rare to warrant biopsy identification. Clinical knowledge of pulmonary amyloidosis is important because of unusual clinical presentation and nonspecific radiologic findings. Recognition of AL amyloid is particularly important because therapy and prognosis are largely driven by the likely underlying plasma cell or mature B-lymphoproliferative neoplasm.

Aberrant LCA (CD45) Immunoreactivity in Tumors With Neuroendocrine Features: A Diagnostic Pitfall

(Poster No. 119)

Joshua Pantanowitz, BSc ([email protected]); Tao Huang, MD, PhD; May P. Chan, MD; Richard Cantley, MD; Rohit Mehra, MD; Liron Pantanowitz, MD, MHA. Department of Pathology, University of Michigan, Ann Arbor.

Context: Leukocyte common antigen (LCA) expression is typically restricted to leukocytes. However, rare publications report unusual LCA expression in neuroendocrine carcinomas. We aimed to characterize aberrant LCA immunoreactivity in tumors with neuroendocrine features.

Design: A retrospective review was undertaken of carcinomas with neuroendocrine features (n = 811) where LCA by immunohistochemistry (IHC) was performed. Clinical findings, IHC platform, LCA antibody, and pathology findings were recorded. LCA and other biomarker immunoexpression was evaluated.

Results: A total of 8 cases (1%) were positive for LCA. Patients were of mean age 70 years, including mostly male patients (n = 7). Tumors included small cell carcinoma of pulmonary origin (n = 5), and 1 each of poorly differentiated lung adenocarcinoma with neuroendocrine differentiation, combined lung squamous and small cell carcinoma, and prostate adenocarcinoma with neuroendocrine transdifferentiation. Different IHC platforms (4 Ventana, 1 Leica, and 3 unknown) and LCA clones (5 Cell Marque, 2 Dako, and 1 unknown) were used. LCA was variably positive within tumor cells and showed moderate to strong staining, with different cellular compartmentalization (4 cytoplasmic, 3 membranous, and 1 nuclear) and a clean background. LCA controls were acceptable. Keratins were positive (often focal) in 7 cases and absent in 1 case. Neuroendocrine markers were positive in most (n = 7) cases. When performed, other lymphoid markers were negative.

Conclusions: Aberrant LCA immunoreactivity with different anti-CD45 clones can rarely occur in diverse high-grade neuroendocrine carcinomas, including small cell carcinoma and tumors with neuroendocrine features. Given that keratin expression in such tumors may be focal or even lost, avoidance of this diagnostic pitfall by employing a broader panel of IHC stains is recommended.

Placental Transmogrification of the Lung in a Pregnant Female With Diffuse Bilateral Lung Involvement Mimicking Metastasis: A Rare Case Report

(Poster No. 120)

Archana Sallagonda, MD ([email protected]); Nupur Jadhav, MD; Rahul Jawale, MD. Department of Pathology, UMMS Chan-Baystate Medical Center, Springfield, Massachusetts.

Placental transmogrification of the lung (PTL) is a rare, benign lesion with fewer than 50 cases reported in the English literature. With male predominance, the cases are associated with cigarette smoking, emphysema, and hamartoma. The entity derives its name from histopathologic resemblance to placental tissue, although no biologic/biochemical properties of placenta are identified. We report an unusual case of PTL in a never-smoker, pregnant woman with bilateral cavitary lung lesions. A 31-year-old gravida 3, para 1 pregnant woman presented with incidental finding of numerous, bilateral cavitary and noncavitary lung nodules on chest computed tomography (CT) scan. The patient reported presence of lung nodules for 3 years and was lost to follow-up. The comparison chest CT demonstrated new lesions, suspicious for metastasis. Microscopic examination of the lung biopsy revealed placental villi–like structures lined by cuboidal epithelial proliferations, hyaline cartilage, and entrapped respiratory epithelium in fibromyxomatous background. No nuclear atypia, mitoses, or necrosis was identified. Because of unique clinical history and diffuse lung involvement the differential diagnosis was mainly metastasis of gestational trophoblastic disease. Immunohistochemically, epithelial cells were positive for TTF-1 and negative for PLAP, HPL, and HCG supporting the diagnosis of PTL. In a limited follow-up of 27 weeks, the patient remains asymptomatic with uneventful progression of pregnancy. Although treated by surgical excision, bilateral involvement in our case makes definitive management challenging, which necessitates the need for further studies to explore the treatment strategies. The case highlights awareness among histopathologists of this rare, benign entity in pregnant females that can mimic gestational trophoblastic disease.

Pancreatic Lymphoma Fine-Needle Aspiration: A Diagnostic Challenge

(Poster No. 121)

Gabriel L. Collins, DO; Ryan S. Sauls, DO ([email protected]); James W. Vaughan, MD; Laurentia Nodit, MD. Department of Pathology, University of Tennessee Medical Center, Knoxville.

Context: Pancreatic lymphoma is rare, and distinction from adenocarcinoma is important. Medical history is often unrevealing, and the patient's symptomatology is similar. We reviewed our experience for pitfalls in interpretation and points of intervention to improve cytologic diagnosis.

Design: Search of pathology database for 22 years identified pancreatic fine-needle aspiration (FNA) cases with lymphoma. Clinical history, specimen preparation, cytodiagnosis, and ancillary studies were recorded and correlated with additional biopsies.

Results: A total of 14 aspirates from 13 patients were included. Clinical histories were pancreatic mass (84%; n = 11), jaundice (23%; n = 3), and bile duct obstruction (15%; n = 2); 3 cases had prior lymphoma. Endoscopic ultrasound FNA cytology smears were present in 10 cases (77%) and cell block/biopsy in 7 (50%). Only 7 aspirates were interpreted as lymphoma by FNA (50%), 1 was suspicious, 2 were atypical, 1 negative for malignancy, and 3 aspirates were correctly identified as malignant without distinction between carcinoma and lymphoma. All lymphomas were of B-cell lineage: large B-cell type (n = 3), follicular (n = 2), not otherwise classifiable (n = 1), and small lymphocytic (n = 1). Flow cytometry was absent in 77% of cases, with only 4 aspirates submitted for flow, which was optimal in 2. The false-negative case was hypocellular (sampling) and diagnosis was made on cellblock by IHC. All cases were secondary involvement from systemic disease.

Conclusions: Pancreatic lymphoma is difficult to diagnose by FNA alone. Sample limitation and necrosis preclude proper classification. To improve diagnostic accuracy, increased awareness of pancreatic involvement by lymphoma, rapid on-site evaluation during sample collection, and ancillary studies are main points of intervention.

Impact of Inappropriate Storage of Reagents on Test Results

(Poster No. 122)

Alyssa Mathew-Joseph, DO1 ([email protected]); Farheen Sana, MD1; Alice F. Gallegos, BS, MT2; Vivek Kumar, PhD.2 1Department of Pathology, Baylor University Medical Center, Dallas, Texas; Department of Chemistry, Quest Diagnostics, Lewisville, Texas.

Context: During reagent storage, temperatures may briefly exceed vendor-specified ranges. We challenged the performance of 10 laboratory tests by storing reagents at room temperature for longer than normal duration and assessed the impact on quality control (QC) and patient results (Table).

Design: Serum samples from 10 patients and QC material were analyzed on Siemens ADVIA 1800/Centaur analyzers at 0 hour (reagents stored at 2°C–8°C per vendor's specifications), and after reagents were stored at 22°C–28°C for 6 hours or 48 hours. QC results were compared to established ranges (mean ± 2 SDs). For patient results, a difference or % difference ≤ one-third of total allowable error (TEA) per Clinical Laboratory Improvements Amendments or College of American Pathologists proficiency testing evaluation criteria was considered acceptable.

Results: QC results for all tests except creatinine were within established ranges when reagents were stored at 22°C–28°C for 6 hours or 48 hours. Patient results for 7 tests were acceptable with reagents stored at 22°C–28°C up to 48 hours. Unacceptable results were observed for creatinine (6 hours and 48 hours), thyroid-stimulating hormone (6 hours), and thyroxine (48 hours).

Conclusions: Prolonged reagent storage at 22°C–28°C had minimal impact on QC and patient results for most tests, suggesting that modest temperature fluctuations during storage should have even smaller impacts on results. If reagent storage is compromised for a long duration, QC monitoring alone may not be adequate to predict deviations in patient results.

Urine Epithelial Cell Reporting: Practices and Performance of Participants in the College of American Pathologists Clinical Microscopy Proficiency Testing Program

(Poster No. 123)

Megan O. Nakashima, MD1 ([email protected]); Maria E. Vergara-Lluri, MD2; Stephanie Salansky, MEd, MS3; Natasha M. Savage, MD4; Eric D. Hsi, MD5; Timothy P. Skelton, MD, PhD.6 1Department of Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio; 2Department of Pathology, Keck School of Medicine of USC, Los Angeles, California; 3Department of Laboratory Accreditation Program, Surveys, College of American Pathologists, Northfield, Illinois; 4Department of Pathology, Medical College of Georgia, Augusta; 5Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina; 6Department of Laboratory Medicine, Beth Israel Lahey Health, Burlington, Massachusetts.

Context: The presence of renal tubular epithelial (RTE) cells in urine has been cited as an important indicator of acute tubular necrosis. Discriminating these from other epithelial cells (ECs) can be challenging. This study aimed to determine current practices for EC reporting and the ability to identify RTE, transitional epithelial (TE), squamous epithelial (SQ), and leukocytes in laboratories subscribed to the College of American Pathologists urinalysis proficiency testing program.

Design: Supplemental questions designed to determine the current state of RTE reporting were sent with the CM-A 2021 mailing. A supplemental “wildcard challenge” (WC1) including 8 cell images (3 RTE, 3 TE, 1 SQ, and 1 leukocyte) was distributed in CM-B 2021. The subsequent participant summary report (PSR) 2021-B included education on how to discriminate RTE, TE, SQ, and leukocytes and cell identifications. A second WC challenge (WC2) with additional images of the same cell types was distributed with the CM-A 2022 (results pending).

Results: Of the laboratories we sampled 65.0% (3469 of 5335) stated that they report RTE. Among those that did not, 56.1% (942 of 1678) reported a ll ECs as “ECs”; 26.8% (450 of 1678) reported ECs as “SQ” or “non-SQ.” For WC1 images, participants accurately identified RTEs at a rate of 51.9% to 60.6% and TEs at 60.3% to 73.9% (Table). Most incorrect answers were in distinguishing RTE from TE.

Conclusions: Reporting practices for urine ECs varied. Although most (65%) of the responding laboratories reported RTE, their ability to discriminate between RTE and TE is relatively poor. The results of the WC2 will be examined to determine if targeted education in the 2021-B PSR improved performance.

Impact of Tissue Decalcification on Immunohistochemical Detection of TRPS1 Breast Carcinoma Marker

(Poster No. 124)

Mohammed Amer Swid, MD ([email protected]); Jianhui Shi, MD; Betti ZB Pang, MD; Haiyan Liu, MD; Fan Lin, MD. Department of Pathology, Geisinger Medical Center, Danville, Pennsylvania.

Context: Bone is one of the most common sites for metastatic breast carcinoma. The application of an immunohistochemical assay on decalcified tissues is frequently performed on such samples. In this study, we investigated the impact of decalcification on the detection of the trichorhinophalangeal syndrome type 1 (TRPS1), which is a highly sensitive and specific marker for diagnosing breast carcinomas, including triple-negative breast carcinomas, using breast cancer cell lines.

Design: Three breast cancer cell lines were obtained from the American Type Culture Collection. The cell pellets have a mixture of 3 cell lines. Each were first fixed in 10% neutral buffered formalin for 8 hours and then decalcified in Decalcifier B (item No. 23245683, Fisher Healthcare) for multiple durations, as shown in the results section. A tissue microarray block containing these tissue/cell line cores with the different decalcification times was then constructed. The TRPS1 (1:400 dilution; clone PA5-84874, Thermo Fisher) was applied to the tissue microarray sections using the Ventana Ultra staining platform. The staining intensity was recorded as strong, intermediate, or weak. The percentage of cells stained was recorded as 0 (no stain), 1+ (any to 25%), 2+ (26%–50%), 3+ (51%–75%), or 4+ (>75%) and compared to the sample with no decalcification.

Results: The results are summarized as (Time/TRPS1 marker) (0 to 30 min/4+, Strong) (60 min/3+, intermediate)(3 hr to 1 week/3+, weak). Expression of TRPS1 on different decalcification times is shown in Figure 3.124 (A through D).

Conclusions: These data demonstrate that tissue decalcification has a significant negative impact on TRPS1 detection after 30 minutes of decalcification.

Papanicolaou Smear Volume, Results, and Performance in the COVID-19 Pandemic: A Retrospective Review of Quality Control Data at a Single Institution

(Poster No. 125)

Cynthia N. Giraldo, MD ([email protected]); Steven Capen, MD; Grant Williams, MD; Melissa Van Dellen, MD. Department of Pathology, Brooke Army Medical Center, Fort Sam Houston, Tex.

Context: Cervical cancer screening was disrupted by the COVID-19 pandemic, leading to a decreased volume of gynecologic cytopathology.

Design: Papanicolaou smear quality control data at a large military health care facility between June 2018 and December 2021 was retrospectively reviewed. Trends in these data in the immediate postpandemic period (April 2020–September 2020) and late postpandemic period (October 2020–December 2021) were compared with the baseline prepandemic period (June 2018–February 2020) using 2-tailed t tests.

Results: Volume in the immediate postpandemic period was decreased from 5290 to 2898 cases per month compared with the prepandemic period. Volume in the late postpandemic period recovered close to baseline levels at 4924 cases per month. Atypical squamous cells of undetermined significance (ASCUS) rate, ASCUS to squamous intraepithelial lesion (SIL) ratio, and ASCUS to human papillomavirus (HPV) percent were not significantly different from baseline in the immediate postpandemic period, but they did show changes in the late postpandemic period. These data are summarized in the Table, with P values compared with baseline in parentheses.

Conclusions: Papanicolaou smear performance as determined by the ASCUS rate, ASCUS/SIL ratio, and ASCUS/HPV percent did not change in the lower volume immediate postpandemic period. These values are benchmarks that can be used to monitor quality performance. These results provide reassurance that quality was maintained during periods of low volume in light of the possible decrease in future Papanicolaou smear volume due to implementation of primary HPV screening. The decrease in ASCUS rate and ASC/SIL ratio and increase in ASCUS/HPV rate in the late postpandemic period are interesting findings that require further investigation.

Sleeve Gastrectomy: Preoperative Endoscopic Biopsy and Specimen Sampling—A 10-Year Comprehensive Review

(Poster No. 126)

Sherehan Zada, MD ([email protected]); Whayoung Lee, MD; Vishal Chandan, MD; Xiaodong Li, MD. Department of Pathology, University of California Irvine, Orange.

Context: Sleeve gastrectomy (SG) is a common surgical specimen. The importance of preoperative esophagogastroduodenoscopy (EGD) has not been well investigated.

Design: The pathology database was searched from 2010 to 2021 for SG and EGD specimens. Gross findings, block number, and final diagnoses were reviewed.

Results: A total of 541 SG cases were reviewed, with accompanying EGD in 63 cases (11.6%). Of these, 49 EGDs (77.7%) were performed for asymptomatic preoperative screening and 14 (22.3%) for diagnostic procedures. There was no diagnostic abnormality in 54 cases (85.7%), followed by Helicobacter pylori gastritis (n = 6), intestinal metaplasia, granuloma, and xanthoma (n = 1 each). In SG specimens, there was no pathologic abnormality in 479 cases (88.5%), followed by H pylori gastritis (n = 41, 7.6%), intestinal metaplasia (1.5%), autoimmune gastritis (1.5%), and granuloma (0.4%). Significant incidental findings included gastrointestinal stromal tumor (n = 1), fundic gland polyp with low-grade dysplasia (n = 1), and eosinophilic gastritis (n = 1). Fifty-seven cases (90.4%) were concordant in final diagnoses of EGD and SG except for 6 cases: treated H pylori gastritis (n = 4), intestinal metaplasia (n = 1), and granuloma (n = 1). A total of 13.5% (n = 73) had abnormal gross findings: polyps (n = 66), and ulcers and atrophy (n = 7). The median number of blocks submitted was 3.1 for gross abnormality and 2.1 for normal grossing examination. There were no significant differences in specific diagnosis between these 2 groups.

Conclusions: We recommend routine preoperative EGD due to high prevalence of treatable H pylori gastritis. For SG specimens with normal preoperative EGD, gross examination only is enough. For abnormal EGD or SG without preoperative EGD, 1 to 2 blocks are adequate for diagnosis and cost-effectiveness except the incidental neoplasm.

Extramammary Paget Disease of the Penoscrotal Region

(Poster No. 127)

Pranav P. Patwardhan, MD ([email protected]); Gabriela M. Quiroga Garza, MD. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Context: Extramammary Paget disease (EMPD) is an uncommon slow-growing intraepithelial malignant neoplasm. It can be classified into primary and secondary subtypes, with secondary subtype associated with underlying malignancy. EMPD of the penoscrotal region is extremely rare, with very limited literature available describing its clinicopathologic characteristics.

Design: A total of 6 cases from our 20-year case files were studied to make us more aware of this entity and to characterize the clinicopathologic characteristics.

Results: Five cases of scrotal EMPD and 1 case of penile EMPD were studied (Table). The mean age at diagnosis was 68.6 years (range, 61–78 years). One case of scrotal EMPD had a history of renal cell carcinoma and prostatic adenocarcinoma, whereas 1 other case presented as recurrent EMPD with initial disease in the left groin. EMPD in the glans penis was associated with a history of urothelial carcinoma in the ureter with pagetoid spread. Three cases had no progression of the disease until recent follow-up, 2 were lost to follow-up, and 1 case rapidly deteriorated, resulting in death. This case had bone metastasis and associated peritoneal carcinomatosis.

Conclusions: Thus, EMPD of the penoscrotal area is extremely rare, can be primary or associated with visceral malignancies, and usually tends to present at an older age. Peritoneal spread and distant metastasis are associated with rapid progression of the disease. Analysis of these 6 cases helped in improving our understanding of this rare entity.

Can Tissue Specimens Also Be Used for Metabolomic Profiling Without Influencing Morphologic Interpretation?

(Poster No. 128)

Bei Yang, MD, PhD1 ([email protected]); Lin Liu, MD1; Frank Chen, MD3; Dean Troyer, MD4; Weiguo Liu, MD5; Chris D'Angelis, MD6; Rafal Kozielski, MD1; Troy Wood, PhD2; Alexandra M. Lzydorczak, PhD2; Wilfrido Mojica, MD.1 Departments of 1Pathology and Anatomical Science and 2Chemistry, University at Buffalo, New York; 3Quest Diagnostics, Buffalo, NY; 4Department of Pathology, Eastern Virginia Medical School, Norfolk; 5Department of Pathology, New York University Langone Medical Center, New York, New York; 6Department of Pathology, VA Western New York Healthcare System, Buffalo, New York.

Context: Metabolomics is the systematic analysis of small molecules in biologic specimens. It holds promise as an emerging tool for the early detection of diseased tissue from peripheral sites like blood. Blood-based discovery investigations traditionally interrogate large numbers of specimens to discern differences attributable to the underlying disease. An alternative approach would be to profile targeted tissues and determine if distinctive biomarkers are present. This would entail manipulation of clinical tissue specimens from traditional processing methods. Scant information exists on how strategies designed to extract metabolites would affect tissue morphology. Alterations in morphology would negate the use of clinical tissue specimens for metabolomic profiling. This study sought to determine if an alternative processing approach capable of extracting metabolites from tissue specimens preserved or altered morphology.

Design: Fourteen tissue specimens were processed immediately in either formalin or methanol. The latter was incubated first for 2 hours, and then fixed in formalin. Seven pathologists examined the matched tissues in a blinded manner looking for appreciable differences. The methanol aliquot underwent analysis by liquid chromatography-mass spectrometry.

Results: Minor changes in tissue presentation existed between the matched tissue specimens. These changes were not significant enough to affect interpretation. Distinctive peaks were noted in the methanol aliquots from each tissue specimen.

Conclusions: The presence of nearly identical morphologic features present in the matched tissue specimens opens the possibility to extending the utility of tissue specimens beyond surgical pathology to now include metabolomic profiling. The opportunity now exists to fully characterize the metabolome of normal and diseased tissues for biomarker discovery.

Construction of an Artificial Control Tissue as a Standard to Be Used for Immunohistochemistry and Other Specific Staining Techniques

(Poster No. 129)

Anne-Sophie Wegscheider, MD1 ([email protected]); Pablo Gottheil, Msc2; Jürgen Lippoldt, PhD2; Dimitrij Tschodu, MSc2; Olga Rosin1; Josef Käs, PhD2; Axel Niendorf, MD.1 1Department of Pathology, MVZ Prof. Dr. Med. A. Niendorf Pathologie Hamburg-West GmbH, Hamburg, Germany; 2Faculty of Physics and Earth Science, University Leipzig, Peter Debye Institute of Soft Matter Physics, Leipzig, Germany.

Context: A major problem in immunohistochemistry is the lack of inexhaustible control tissue that can be used as a positive control and further be suitable in a computer-assisted approach to quantify specific staining.

Design: We have constructed an artificial control tissue (ACT) by mixing microtome-cut slices (5 μm) of formalin-fixed, paraffin-embedded tissue of 100 consecutive cases of invasive breast cancer. These were mortared under liquid nitrogen, centrifuged, and re-embedded in paraffin. Tissue cores were taken from these blocks (n = 6) constructing a tissue microarray (TMA). Additionally, core biopsies were taken from the 100 breast cancer cases that had contributed to the ACT construction and were placed in a TMA together with the ACT core that represented the mixture of these cases.

Results: Image analysis of hematoxylin-eosin–stained and immunohistochemically stained (with 13 different antibodies) slides revealed a reproducible high degree of similarity between the different cores of the same ACT as well as slides from different depth levels of the respective tissue blocks. This step considers particle number, size variance, and intensity of immunohistochemical reaction within an ACT, compared with the average of individual cases that had contributed to the respective ACT. Increased sample sizes of ACT improved the representation of underlying cases, which avoids outliers.

Conclusions: ACT can be considered as an inexhaustible material that can be used as a reference to quantify specific staining, allowing standardization of stained images from independent laboratories for scientific, medical, and computer-based collaborations by paving the way for the development of standardized automated analysis software.

Blood Culture Contamination in Long-Term Care Facilities: Quality Indicator During COVID-19 Pandemic

(Poster No. 130)

Rita H. Khoury, MD ([email protected]); Prital Patel, BA; Asha Gandhi, BA; Dauna Gudaitis, BA; Peter Gudaitis, BA. Aculabs Inc, East Brunswick, New Jersey.

Context: Long-term care facility residents were the first to be affected by the COVID-19 pandemic because of their setting, fragility, and comorbidity. Fever was the most common symptom among the patients that led to a massive increase in blood culture orders during the peak of the pandemic. However, increasing blood culture orders might come with an increase in blood culture contamination, which is equally important as positive cultures; they are very costly for the laboratory and health care system and increase the use of unnecessary antibiotics.

Design: Blood culture sets, a combination of 1 aerobic and 1 anaerobic bottle from a single blood sample, were collected from 7734 long-term care facility patients in 2020. Positive culture was considered contaminated if 1 or more of the following organisms was identified in only 1 set: coagulase-negative Staphylococcus species, Propionibacterium acnes, Micrococcus species, “viridans”-group streptococci, Corynebacterium species, or Bacillus species. Statistical analysis was done using Analyse-it.

Results: The highest orders were in March (1090 sets); contamination rate ranged from 1.4% to 2.8%. The highest percentage was the first 2 weeks of March 2020. Most of the samples were drawn by our phlebotomists.

Conclusions: Contamination rate was highest in the beginning of March 2020 where the facilities had the highest prevalence of COVID-19 and the phlebotomists/nurses were forced to rush the process of drawing samples. The contamination rate was still lower than the nationally reported rate during COVID-19 pandemic, which was due to the extensive training and the strict aseptic technique used by our phlebotomists. Efforts should be made to reduce blood culture contamination by educating staff and clinicians about the importance of collecting and interpreting contamination during pandemics more than during nonpandemic periods.

The Impact of the COVID-19 Pandemic on Critical Results Notification

(Poster No. 131)

Rita H. Khoury, MD ([email protected]); Peter Gudaitis, BA; Asha Gandhi, BA; Prital Patel, BA; Dauna Gudaitis, BA. Aculabs Inc, East Brunswick, New Jersey.

Context: Critical result notification is more than life saving, especially in the geriatric setting. COVID-19 is a pandemic infection caused by a new strain of coronavirus, SARS-CoV-2. The United States alone has more than 77 million confirmed cases and more than 900 000 deaths. COVID-19 has impacted laboratories and long-term care facilities as well, with infection and reduced staff and supplies. Turnaround time for reporting critical results is considered one of the important quality indicators for the laboratory.

Design: All critical results generated in 2020 were included in this study. A call was considered successful when the results were given to the patient's caregiver. Average time from posting critical results to successful call and time to fax were calculated per quarter and used as a postanalytic quality indicator. Statistical analyses were performed using Analyse-it.

Results: A total of 107 881 critical results were called in 2020 (Table). The second quarter had the greatest number of critical results and took longer to relay the results to the caregiver. Faxing or posting in the EMR did not change throughout the year.

Conclusions: COVID-19 had a major impact on laboratories and medical facilities. Both laboratories and medical facilities have suffered from short staff, which delayed reporting critical results. The time to reach a caregiver was doubled during the second quarter of 2020. The ability to post and/or fax the results helped communicate the results to physicians faster than making a call. A reliable communication system is needed to improve critical value reporting through automation, standardization, and to have the ability to monitor the process.

Assessing the Utility of Whole Slide Imaging for Intraoperative Consultation: Experience of a Large Academic Center During the COVID-19 Pandemic

(Poster No. 132)

Ahmed Shehabeldin, MD ([email protected]); Prih Rohra, MD; Denái Milton, MS; Nadia Hameed, MD; Zongshan Lai, MD; Yi Tong, DO; David Sellen, MD; Hermineh Aramin, MD; Doaa Alqaidy, MD; Jianping Zhao, MD; Ydamis Estrella Perez, MD; Leomar Ballester, MD, PhD; Victor G. Prieto, MD, PhD; Aung Phyu, MD. Department of Pathology, MD Anderson Cancer Center, Houston, Texas.

Context: Digital pathology can provide specialized histopathology services to less-accessible locations, facilitate consultations, and help maintain pathology operations during emergencies, like the COVID-19 pandemic. Our study aimed to compare conventional microscopy using glass slides (GS) with digital pathology using whole slide imaging (WSI) to evaluate the efficiency, sensitivity, and specificity of these techniques when used in the intraoperative consultation setting.

Design: Ninety-three cases were randomly selected from the routine frozen section (FS) workload and scanned. Nine board-certified anatomic pathologists who did not routinely perform primary diagnosis on WSI reviewed the WSI. After a washout period of at least 2 weeks, the pathologists subsequently reviewed the corresponding GS. The diagnosis and the time required to reach the diagnosis using the GS and WSI were recorded. Intraobserver concordance, the time required to make the diagnosis on GS versus WSI, and the specificity and sensitivity compared with the original diagnosis were evaluated.

Results: There was a significant difference in the time required to reach a diagnosis using GS (mean, 1.25 minutes) compared with WSI (mean, 1.76 minutes), with a mean difference of 0.51 minutes (P < .001). The specificity (GS, 91%; WSI, 90%) and sensitivity (GS, 92%; WSI, 92%) of these techniques were similar.

Conclusions: The use of WSI for intraoperative consultation requires more time compared with GS. However, WSI appears to be a safe alternative to conventional GS to allow reporting from a remote site during a public health emergency, such as the COVID-19 pandemic or for facilitating subspecialty histopathology services.

V. G. Prieto is a consultant with Orlucent, Merck, and Castle Biosciences.

Reduced Intraobserver Correlation of Blast Identification by Digital Scans of Peripheral Blood Smears Compared With Other Morphologic Criteria: A Comparative Diagnostic Quality Assessment

(Poster No. 133)

Pranav S. Renavikar, MBBS1 ([email protected]); Robin R. High, MBA, MA2; Jeffrey J. Cannatella, MD1; Ana G. Yuil-Valdes, MD1; Joseph M. Rohr, MD, PhD.1 Departments of 1Pathology and Microbiology and 2College of Public Health, University of Nebraska Medical Center, Omaha.

Context: Peripheral blood smears provide invaluable information about patients' hematologic status. Our institution provides primary and secondary review for smaller organizations. Delays in specimen or patient arrival may affect our patient triage ability. Prior studies have partially addressed digital pathology in peripheral smear review. However, generalized intrainstitutional validation and quality assessment data are lacking. We used a clinically validated slide scanner to evaluate digital microscopy for peripheral smear review.

Design: Institutional archival peripheral blood smears from 36 cases with varied diagnoses were randomized. Two board-certified hematopathologists reviewed the cases at 2 separate time points with appropriate washout (range, 2–6 weeks). Cases were evaluated on glass and digitally scanned slides (Aperio CS2, Leica, Deer Park, Illinois). Free response diagnoses were encoded for theme. Concordance correlation coefficients (CCCs) were generated with SAS/STAT software, v9.4 (Cary, North Carolina).

Results: Across both reviewers and between replicate reads, blast identification and myeloid morphology demonstrated weak agreement (CCC range, 0.42–0.67 and 0.50–0.67, respectively). Erythrocyte and lymphocyte morphologies strongly agreed (range, 0.72–0.88; Table). Numeric evaluations demonstrated moderate to strong agreement (range, 0.67–0.96). CCCs were overall consistent across time points. Monocytic and platelet morphologies and “no pathologic abnormality” did not generate enough data for analysis.

Conclusions: The diagnostic quality of peripheral blood smear digital microscopy shows promise in identifying most assessed morphologic and numeric findings. Because of the poor reproducibility of blast and abnormal myeloid identification, the data do not currently support its use in primary triage at our center. Technical issues with scanning and storage may also reduce its applicability in smaller settings.

Quantification of Hematoxylin Staining Variability in Esophageal Carcinoma From 5 Institutions

(Poster No. 134)

Anna Sarah Erem, MD1 ([email protected]); Elissa Sandra J. Woo, BSc, MLT2; Matthew J. Cecchini, MD, PhD.3 1Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia; 2Department of Health Sciences, Ontario Tech University, Oshawa, Ontario, Canada; 3Department of Pathology and Laboratory Medicine, London Health Sciences Centre and Western University, London, Ontario, Canada.

Context: The diagnosis of dysplasia and malignancy relies upon assessing subtle differences in nuclear staining and morphology. The nature of reagents used in hematoxylin-eosin (H&E) staining causes substantial nuclear hematoxylin staining variation between institutions. Given the importance of accurate nuclear staining, a representative H&E stain is critical for review. Variation in appearance often requires local recuts in consultation cases, using additional tissue and increasing costs. However, this may not be needed in some cases that align with local norms of staining appearance. There are currently limited options to assess H&E variation beyond subjective visual inspection.

Design: Esophageal squamous cell carcinoma cases were selected from the TCGA data set from 5 institutions. Digital slides were rapidly assessed on QuPath for the intensity of hematoxylin staining and optical density in lymphocytes and tumor nuclei. Prism was then used to conduct analysis of variance analyses and create violin plots to represent the data (Figure 3.134, A through D).

Results: Significant variation (P < .05) was observed in hematoxylin staining across institutions. Three demonstrated comparable intensities for hematoxylin staining and optical density. These would likely be acceptable for interchangeable diagnoses. There were 2 outliers—1 site with very strong hematoxylin staining and another with very light staining.

Conclusions: Using this system, the variation in hematoxylin staining can be rapidly quantified. This system could be used to identify cases that fall outside normal, acceptable ranges of hematoxylin staining and identify cases that need to be restained at the local institution.

Electronic Safety Reporting Systems May Misrepresent Patient Harm Attributed to Clinical Laboratory Errors

(Poster No. 135)

Hariharan Bharadwaj, MBBS ([email protected]); Soma Chakraborty, MBBS; Michelle Dicienzo; Darlene Cloutier; Rahul Jawale, MD; Vandita Johari, MD. Department of Pathology, UMass Chan-Baystate Medical Center, Springfield, Massachusetts.

Context: Clinical laboratory errors (CLEs) are a known cause of patient harm. Our hospital system employs a cloud-based Safety Reporting System (SRS; RLDatix, Toronto, Ontario, Canada) for patient harm reporting due to medical errors, including CLEs. This information is shared with laboratory and hospital leadership and guides institution-wide quality improvement efforts.

Design: Our institution applies the “National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) Index for Categorizing Errors” to evaluate patient harm. By this scale, level E and above is actual patient harm, whereas level D and below is potential patient harm or “near harm.” When a CLE associated with “E harm” or above is reported, the resident and laboratory director review patient electronic medical records (EMRs) and reassign a harm score if appropriate.

Results: Between November 15, 2021, and February 28, 2022, a total of 25 SRS events of level “E” or above (22 “E,” 1 “F,” and 1 “G”) were reported. Following chart review, 22 of 25 (88%) were downgraded to “no harm” (level D or below), whereas 3 of 25 (12%) remained unchanged at “E” level harm. No events were upgraded to higher harm levels. A total of 21 of 25 (84%) of CLEs were preanalytic: wrong order entry (6 of 25; 24%), phlebotomy (11 of 25; 44%), and specimen processing (4 of 25; 16%). A total of 4 of 25 (16%) were analytic errors.

Conclusions: Providers tend to overascribe patient harm when using electronic systems to report CLEs. Most CLEs are preanalytic and associated with low levels of patient harm. Improper test ordering accounts for a significant proportion of CLEs. Our study emphasizes the importance of EMR review in the investigation of CLEs.

Factors Contributing to High Negative Loop Electrosurgical Excision Procedure and Cone Biopsy Rates at a Tertiary Care Hospital

(Poster No. 136)

Joan Ngichabe, MD ([email protected]); M. A. Haseeb, PhD; Joanne Sheu, MD; Raavi Gupta, MD. Department of Pathology, SUNY Downstate Health Sciences University, Brooklyn, New York.

Context: Cervical conization and loop electrosurgical excision procedures (LEEPs) are treatment options following biopsy diagnosis of high-grade squamous intraepithelial lesions (HSILs). Some excisions do not support the HSIL diagnosis. Our objective was to investigate factors contributing to high rates of negative LEEP and cone biopsies so they could be addressed.

Design: A total of 200 consecutive LEEP and cone cervical biopsies done between 2016 and 2021 were reviewed for indications, pathologic diagnoses, specimen quality, and processing, and were analyzed in relation to the source of antecedent cervical biopsies preceding the LEEP/cone procedures. Negative results were defined as low-grade squamous intraepithelial lesion (LSIL) and negativity for dysplasia.

Results: Half of the patients had antecedent cervical biopsies done outside the hospital and did not have a preoperative review in-house, whereas the other half had in-house biopsies; 45% (90 of 200) of the specimens either lacked dysplasia or had LSIL. Patients who had in-house diagnostic biopsies had a significantly lower negative LEEP/cone biopsy rate in comparison with those without in-house preoperative review (P = .03). There was no significant difference in specimen quality between the 2 groups with regard to orientation (P = .59) and fragmentation (P = .69). Pathologists performed recuts on 32% (29 of 90) and immunohistochemistry on 35.5% (32 of 90) of the negative specimens (Table).

Conclusions: Identification of a higher rate of negative LEEP/cone biopsy results (44%) compared with the national average of 20% is a cause for quality check. Preanalytic causes appear to be responsible for most of the negative results. Presurgical in-house review of previous biopsies should be strongly considered for optimum results in excision.

Evaluation of Whole Exome/Transcriptome Sequencing for the Molecular Characterization of Plasma Cell Neoplasms in a Routine Clinical Setting: A Single-Institution Experience

(Poster No. 137)

Bella L. Liu, MD ([email protected]); Xintong Wang, MD; Beerinder P. Karir, MD; Matthew Croken, PhD; Meenakshi Mehrotra, PhD; Christian Salib, MD; Jane Houldsworth, PhD. Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.

Context: In plasma cell neoplasms (PCNs), mutations, gain/loss, and IGH rearrangements with prognostic/therapeutic relevance are mostly assessed by targeted fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS). After clinically implementing a workflow for whole exome/transcriptome sequencing (WES/WTS), we sought to evaluate the effectiveness of this approach.

Design: During 9 months, bone marrow aspirates/biopsies were collected during routine clinical care from 160 patients with or with a history of PCN. DNA/RNA was extracted from CD138+-enriched cell fractions and sent out for WES/WTS. FISH was performed outside on similarly enriched CD138+ fractions for 122 cases.

Results: The sensitivity of detection by WES of PCN-relevant gains (1q, 9, 11, 15) and losses (1p, 13/13q14, 17p/17) ranged from 67% to 83%, with a specificity of ≥ 91% compared with FISH. Lack of detection was in those with FISH-detected gain/loss <20%. For 9 of 10 IGH-FGFR3 cases, IGH-NSD2 fusions were detected, whereas for 3 of 6 IGH-MAF, IGH-WWOX fusions were detected. IGH-CCND1 could not be detected by WES/WTS. Of 14 with nonevaluable smear %PC, 50% failed WES/WTS, compared with 7% (10 of 142) with evaluable %PC. There was no morphologic evidence of PCN in 41 cases, but 17% exhibited a PCN-relevant mutation/gain/loss by WES/WTS. Diagnostic yield increased to 93%, with >20%PC (Table). Unlike NRAS/KRAS, BRAF mutations occurred more frequently in λ-restricted (7 of 39) than κ-restricted (2 of 57; P = .03), but hyperdiploidy was significantly enriched in κ-restricted (30 of 57; λ 10 of 39; P = .01).

Conclusions: WES/WTS has a high diagnostic yield except for those cases with limited %PC despite enrichment and IGH-CCND1 cannot currently be detected. Importantly it will afford the detection of additional relevant abnormalities (4p, 16q loss) and correlative analyses with pathologic features.

Fusion Gene Analysis Reveals Novel CSF1 Fusion Gene Partners, Expanding the Molecular Profile of Tenosynovial Giant Cell Tumors

(Poster No. 138)

Haider A. Mejbel, MD1 ([email protected]); Shi Wei, MD, PhD2; Gene P. Siegal, MD, PhD1; Shuko Harada, MD.1 1Department of Pathology, University of Alabama at Birmingham; 2Department of Pathology & Laboratory Medicine, University of Kansas School of Medicine, Kansas City.

Context: Tenosynovial giant cell tumors (TSGCTs) are a group of neoplasms encompassing tumors arising from the joint synovium, bursa, and tendon sheath that exhibit synovial cell differentiation. TSGCT is mostly diagnosed by histomorphology in correlation with radiologic features. However, in challenging cases, molecular testing for a CSF1 rearrangement harbored by a small subset of mesenchymal stromal cells is used to confirm the diagnosis.

Design: We performed a 24-month retrospective analysis of clinically and pathologically characteristic TSGCTs that were submitted for fusion gene analysis using RNA-based Archer FusionPlex (Invitae, Colorado). The panel targets 94 cancer-related genes (AKT1, AKT3, ALK, AR, ARHGA26, AXL, BCOR, BRAF, BRD3, BRD4, CAMTA1, CCNB3, CIC, CSF1, CSF1R, DNAJB1, EGFR, EPC1, ERBB2, ERBB4, ERG, ESR1, ESRRA, ETV1, ETV4, ETV5, ETV6, ESR1, FGFR1, FGFR2, FGFR3, FGR, FOXO1, FOXO4, FUS, GLI1, HMGA2, INSR, JAK2, JAZF1, MAML2, MAST1, MAST2, MEAF6, MET, MKL2, MN1, MSMB, MUSK, MYB, MYBL1, NCOA1, NCOA2, NOTCH1, NOTCH2, NR4A3, NRG1, NTRK1, NTRK2, NTRK3, NUMBL, NUTM1, PAX3, PDGFB, PDGFRA, PDGFRB, PHF1, PIK3CA, PKN1, PLAG1, PPARG, PRKACA, PAKCA, PRKCB, RAF1, RELA, RET, ROS1, RSPO2, RSPO3, SS18, STAT6, TAF15, TCF12, TERT, TFE3, TFEB, TFG, THADA, TMPRSS2, USP6, VGLL2, YAP1, and YWHAE).

Results: Seven clinically and pathologically characteristic TSGCTs were identified, in all of which (100%) a CSF1 rearrangement was detected. Two novel TGFBR3L (1 of 7; 15%) and DDX24 (1 of 7; 15%) partners were detected (Table).

Conclusions: Our molecular findings confirmed the accuracy of the histologic diagnoses. The detection of novel CSF1 partners expands the molecular profile of TSGCTs and suggests additional molecular changes yet to be explored.

Protein-Protein Interaction Networks in Bladder Cancer

(Poster No. 139)

Yigit Baykara, MD1 ([email protected]); Charissa Chou, BS2; Alper Uzun, PhD3; Ece D. Gamsiz Uzun, PhD.1 Departments of 1Pathology and Laboratory Medicine, 2Biology, and 3Pediatrics, Brown University, Providence, Rhode Island.

Context: Urothelial carcinomas of the bladder are categorized into 2 subtypes, papillary and nonpapillary. It has been suggested that these subtypes have distinct molecular pathways in tumorigenesis. However, further molecular classification is warranted to develop more effective and targeted therapies.

Design: RNA sequencing data from the patients with papillary and nonpapillary urothelial carcinomas were obtained from 2 data sets (Robertson [133 papillary/273 nonpapillary cases] and Weinstein [39 papillary/88 nonpapillary cases]) on cBioPortal for Cancer Genomics. Proteinarium (multisample protein-protein interaction [PPI] analysis and visualization tool) analysis was performed to identify clusters of cases with shared PPI networks in both subtypes for both data sets. The mRNA z-score data for 19 601 genes were used in the analysis.

Results: One significant cluster was identified (P = .01) in the Robertson data set, including 89 papillary (Network A) and 214 nonpapillary (Network B) cases. Another significant cluster with 1 papillary and 14 nonpapillary cases (Network C) was identified (P = .04) in the Weinstein data set. The results revealed that MAPK signaling pathway hub genes (HRAS, SRC, MAPK3, and UBA52) were highly associated in Network A, whereas PI3K/AKT signaling pathway (PIK3R1 and PIK3CA) and TP53 hub genes were significantly associated in Network B. Notable hub genes in Network C were POLR2K, COPS5, DDB1, and ERBB2 in addition to the 12 shared genes with Network B. Survival was significantly higher for papillary than for nonpapillary cases in both data sets (P < .05).

Conclusions: The differences in PPI networks between papillary and nonpapillary urothelial carcinomas indicate unique molecular pathways in tumorigenesis of these 2 distinct subtypes, necessitating the development of distinct targeted therapies.

Complimentary Role of 68Ga-GRPR PET/CT and 68Ga-PSMA PET/CT in Initial Diagnosis of Prostate Cancer

(Poster No. 140)

Xiaomei Gao, PhD1 ([email protected]); Yongxiang Tang, PhD2; Minfeng Chen, MD3; Jian Li, PhD2; Hongling Yin, MS1; Yu Gan, PhD3; Xiongbin Zu, MD3; Yi Cai, PhD3; Shuo Hu, MD.2 Departments of 1Pathology, 2Nuclear Medicine, and 3Urology, Xiangya Hospital, Central South University, Changsha, China.

Context: Prostate-specific membrane antigen (PSMA)–based positron emission tomography/computed tomography (PET/CT) imaging may not be satisfactory for the primary diagnosis of all prostate cancer (PCa). We aimed to evaluate if gastrin-releasing peptide receptor (GRPR) PET/CT is complementary to PSMA PET/CT in the initial diagnosis of PCa.

Design: The study included 207 participants suspected of having PCa who underwent 68Ga-GRPR and 68Ga-PSMA PET/CT. Standardized uptake value (SUVmax) was measured from the dominant lesion and PCa lesions. Visual assessment of PET images was also performed. The comparison of 2 PET/CT imaging methods was accomplished using pathologic specimens as a reference standard.

Results: Of the 207 participants analyzed, 125 had cancer, and 82 received a diagnosis of benign prostatic hyperplasia (BPH). The sensitivity and specificity of 68Ga-GRPR and 68Ga-PSMA PET/CT imaging differed significantly for detecting PCa and clinically significant PCa (P < .001). The AUC was 0.54 for 68Ga-GRPR PET/CT and 0.91 for 68Ga-PSMA PET/CT for detecting PCa (P < .001). 68Ga-GRPR PET/CT imaging had higher sensitivity in PCa, with a Gleason score (GS) of 6 (P =.03), than 68Ga-PSMA PET/CT, but it had poor specificity (20.73%). In the group with PSA <10 ng/mL, the sensitivity, specificity, and AUC of 68Ga-GRPR PET/CT were lower than for 68Ga-PSMA PET/CT (60.00% versus 80.30%, P = .12; 23.26% versus 88.37%, P < .001; and 0.524 versus 0.822, P < .001, respectively). 68Ga-GRPR PET/CT exhibited a significantly higher SUVmax in specimens with GS = 6 (P = .04) and in the low-risk group (P = .01; Table).

Conclusions: Using histopathology as a reference standard and BPH as a negative control in >200 patients, our study showed that PET/CT scans targeting GRPR and/or PSMA could identify PCa with various risks.

RNA Yield of Small Tumor Foci for the 17-Gene Oncotype DX Genomic Prostate Score Assay

(Poster No. 141)

John Abran, MD1 ([email protected]); Megan Roberts, BA2; Amy Lehman, MAS3; Helen Bailey, MD.1 Departments of 1Pathology, 2Clinical Affairs, and 3Clinical Biostatistics & Data Management, Exact Sciences, Redwood City, California.

Context: The 17-gene Oncotype DX Genomic Prostate Score (GPS) assay is a biopsy-based gene expression assay that is validated to predict adverse pathology, distant metastasis, and prostate cancer death. In validation studies, the recommended tumor length was ≥1 mm per pathology report; however, 14% of tumors measured <1 mm on internal pathology review. Here we explore the relationship between tumor length and RNA yield in commercial patient samples.

Design: Included in this study were 5225 commercial specimens processed from 2013 to 2014 meeting pathology, reverse transcription–polymerase chain reaction (RT-PCR), and quality criteria. The submitting practices and laboratories provided pathology reports, NCCN risk group classification, and other clinicopathologic variables relevant to the performance of the GPS assay. Samples were reviewed by pathologists for Gleason score and tumor length. RNA yield was determined during RT-PCR, and a valid GPS result was calculable for all specimens.

Results: For all specimens, median tumor length was 2.3 mm (interquartile range [IQR], 1.2–4.6 mm) and minimum tumor length was 0.4 mm. A total of 732 specimens (14%) were <1 mm, with 19 (0.4%) <0.5 mm. Most specimens (77%) were Gleason 3 + 3. Overall, median RNA yield was 125.6 ng (IQR, 58–262.8 ng), with 0.5% of specimens <5 ng. RNA yield and tumor length were highly correlated (Figure 3.141). For tumor foci <1 mm, median RNA yield was 35.4 ng (IQR, 20.3–53.9 ng), with minimum yield 0.6 ng.

Conclusions: Within the sample cohort a considerable number of patients had tumor foci <1.0 mm. Tumor foci as small as 0.4 mm yielded sufficient RNA to generate a valid GPS score.

Utility of Urinary Comprehensive Genomic Profiling in the Diagnosis, Surveillance, and Molecular Grading of Urothelial Carcinoma

(Poster No. 142)

Brad W. Jensen, MD1 ([email protected]); Vincent T. Bicocca, PhD1; Kevin G. Phillips, PhD1; Daniel S. Fischer, MS1; Vincent Caruso, MS1; Mahdi Goudarzi, PhD1; James Korkola, PhD2; Joe Gray, PhD2; Theresa Koppie, MD3; Trevor G. Levin, PhD.1 1Department of Clinical Research, Convergent Genomics Inc, South San Francisco, California; 2Department of Biomedical Engineering, Knight Cancer Institute, MEP-LINCS Center, Oregon Health & Science University, Portland; 3Willamette Urology, Salem, Oregon.

Context: The standard of care for urothelial carcinoma (UC) relies on suboptimal invasive procedures. Providing actionable information to clinicians about stage, grade, and recurrence risk remains a challenge for pathologists evaluating small biopsies, cauterized curettings, or urine cytology. To enhance the clinical treatment of UC, we developed UroAmplitude, a noninvasive next-generation sequencing–based diagnostic assay that establishes the comprehensive genomic profile of UC from tumor DNA present in urine. To validate the performance of UroAmplitude, we compared the mutation profiles of urine-extracted DNA to those of matched tumor tissue that was present in the bladder at the time of urine collection. We then explored the utility of UroAmplitude in longitudinal case studies to quantify residual disease following bladder-sparing treatments, including transurethral resection (TUR) and intravesical therapy (IVT).

Design: A total of 67 samples from 23 patients were examined retrospectively. Somatic variants were quantified in formalin-fixed, paraffin-embedded tumor samples, matched urine samples, and longitudinal urine samples collected following TUR and between courses of IVT.

Results: Tumor single-nucleotide variants were observed in urine with a median agreement of 91.7%. Genomic profiling of UC tumors from urine DNA revealed common patterns of genomic lesions previously identified in low- and high-grade tumors (Figure 3.142). UroAmplitude detected residual disease in patients receiving bladder-sparing treatment with TUR and IVT.

Conclusions: These findings demonstrate UroAmplitude's ability to identify and track mutations associated with UC at each stage of disease: diagnosis, treatment, and surveillance. Case studies demonstrate clinical utility to inform risk assessment and guide surgical and therapeutic interventions.

B. W. Jensen is a consultant with Convergent Genomics Incorporated. J. Korkola, J. Gray, T. Koppie, and T. G. Levin are Convergent Genomics Incorporated shareholders.

Success of the Oncotype MAP Genomic Assay in Small Tumor Tissue Samples

(Poster No. 143)

Lisa Macera, PhD1 ([email protected]); Josh Routh, MD2; Ariane C. Kemkes, PhD2; Sheelah Changho, MD2; Bingbing Song, MD, PhD2; David W. Hall, PhD1; Jess Hoag, PhD1; Frederick L. Baehner, MD1; Snehal G. Thakkar, MD.2 1Department of Precision Oncology, Exact Sciences, Redwood City, California; 2Department of Precision Oncology, Exact Sciences, Phoenix, Arizona.

Context: Genomic profiling using next-generation sequencing (NGS) is a critical therapy selection tool for cancer. For most commercial assays, profiling requires tumor sample sizes that may necessitate an additional procedure to obtain. Oncotype MAP has differentiated itself by accepting samples as small as 3 mm2 with 15% tumor cellularity. Here we describe the success of Oncotype MAP in small tumor samples.

Design: All samples ≤25 mm2 with tumor cellularity ≥15% submitted for Oncotype MAP testing received after January 1, 2022, and processed by February 22 were examined. The assay sequences 257 genes and reports single base variants, indels, copy number variants, and select structural variants/fusions. Tumor mutational burden (TMB) and microsatellite instability (MSI) are also determined. The number of samples for which NGS results were obtained as a function of sample size is reported. The turnaround time from sample accession to report generation was also calculated for these samples.

Results: A total of 196 samples ≤25 mm2 with ≥15% tumor cellularity were submitted for NGS, and 175 were successfully sequenced. Within these, TMB was determined in all 175 (100.0%) and MSI in 160 (91.4%). NGS performance was not significantly affected by the tissue sample size (Table). The median turnaround time was 5 business days (interquartile range, 4–5 days).

Conclusions: The Oncotype MAP assay is a rapid–turnaround time genomic profiling test that can be performed on very small tumor tissue samples, as low as 1 mm2. As such, in situations where tumor tissue is limited, this assay may be especially useful.

Characterization of the Molecular Features of MUM1+ Peripheral T-Cell Lymphoma

(Poster No. 144)

Jiani N. Chai, MD, PhD ([email protected]); Kevin Kuan, MD; Abul K. Azad, MD, PhD; Xuejun Tian, MD, PhD; Shi Yang, MD, PhD; Yanhua Wang, MD, PhD. Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York.

Context: In peripheral T-cell lymphomas (PTCLs), frequent MUM1 expression has been reported and is associated with poor outcomes. Here, we investigated the genetic mutations in MUM1+ PTCLs and compared them with MUM1− ones using next-generation sequencing (NGS).

Design: Tissue specimens from 7 PTCL cases were collected, including PTCL, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), adult T-cell leukemia/lymphoma (ATLL), primary central nervous system (CNS) mature T-cell lymphoma, and cutaneous T-cell lymphoma (CTCL). Five cases were positive for MUM1 by immunohistochemistry (IHC) stain; 2 cases were MUM1. Genomic DNA was extracted from paraffin-embedded tissue, and mutational status was analyzed by NGS. Mutants with allele frequency ≥5% were included.

Results: Somatic mutations in 20 genes were detected in total. These genes belong to different functional groups that are commonly found in tumor mutations. Most of these mutations (13 of 20) were found in both the MUM1+ and MUM1 PTCL cases. Among these, mutations in PDGFRA, KDR, FGFR3, TP53, and RET were consistently detected in all 7 cases, suggesting their potential pathogenic associations with PTCLs. In addition to these shared mutations, MUM1+ cases showed several gene mutations that were not present in the MUM1 cases: ERBB4, ABL1, BRAF, KIT, KRAS, NRAS, and SMARCB1. These genetic mutations could be involved in the aggressiveness of MUM1+ PTCL.

Conclusions: MUM1+ and MUM1 PTCLs shared many common genetic mutations. Yet, a list of mutations was detected exclusively in the MUM1+ PTCL cases in this limited study. Further investigation will help to understand the genomic landscape of MUM1+ PTCLs.

Genomic Profiling of Brain Tumors and Correlation Between ATRX, IDH1, and TP53 Mutations and Immunohistochemistry Findings

(Poster No. 145)

Eyas M. Alzayadneh, MD; Ramakrishna R. Sompallae, PhD; Natalya V. Guseva, PhD; Aaron D. Bossler, MD, PhD; Deqin Ma, MD, PhD ([email protected]). Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City.

Context: Genomic aberrations are incorporated into the World Health Organization classification of brain tumors. Mutations in ATRX, IDH1, and TP53 are routinely evaluated in gliomas. Immunohistochemistry (IHC) has been used as a surrogate for assessing molecular alternations.

Design: We tested 126 brain tumors by next-generation sequencing (NGS) assay and correlated the molecular findings and IHC results. A custom-designed 214-gene panel was used for detection of mutations and copy number variation (CNV) and the FusionPlex CTL assay (ArcherDx) for gene fusions using formalin-fixed, paraffin-embedded tissue. IHC for ATRX, IDH1 R132H, and p53 was performed using standard protocols.

Results: The tier 1/2 variants detected are shown in Figure 3.145. Mutations in TERT, TP53, and PTEN accounted for 50%, followed by ATRX (18). Fifteen ATRX-mutated cases with available IHC: 12 of 15 (80% concordance) showed loss of ATRX, and 3 had intact ATRX expression (2 variants of uncertain significance and 1 frameshift). Two ATRX mutation (m+)-positive cases were IDH1–wild-type, 1 had a coexisting PTPRZ1::MET fusion, and 8 had CNV, with CDKN2A/2B loss in 5 of 8 cases. The concordance with IHC for ATRXm cases was 50% (11 had retained and 11 had equivocal ATRX staining).

Conclusions: Our results demonstrated that IHC was reliable for determining mutated IDH1 R132H and TP53 but less accurate for single-nucleotide variant of ATRX. However, IHC may define some VUS (case 5). Genomic testing provides additional information and should be included for diagnosis of brain tumors. Moreover, genomic testing also allows identification of targetable genomic aberrations and may ultimately lead to the development of targeted therapy.

Development of a Novel Melanin-Bleaching Reagent and Methodology for Automated IHC Staining of Lymphocyte Activation Gene 3 (LAG3) in Melanoma

(Poster No. 146)

Michael A. Gurney, PhD ([email protected]); Woody Perng, PhD; Zach Bosley, BS; Justin Sinohui, MS; John Palting, PhD; Astin Powers, MD; Laurel McKee, MS; Genevieve LaBahn, MS. Department of Personalized Healthcare Solutions, Roche Tissue Diagnostics, Oro Valley, Arizona.

Context: Melanins are naturally occurring, stable, and insoluble pigments present in neoplastic and nonneoplastic tissues that may impede histopathologic assessment of melanocytic lesions by obscuring cellular morphology and/or immunohistochemical biomarker assessment and may interfere with antibody-antigen interaction. Currently, clinical depigmentation methods use manual bleaching followed by staining on an automated immunohistochemistry (IHC) platform. Our objective was to develop a novel ancillary melanin-bleaching reagent for automated use on BenchMark IHC instruments with LAG3 staining in melanoma.

Design: Multitissue blocks comprising low, moderate, and highly pigmented melanoma cases were subjected to a variety of bleaching formulations and LAG3 staining conditions using DAB detection on the BenchMark ULTRA automated staining platform. Factors such as buffer/diluent composition, pH, bleaching reagent concentration, temperature, and time were optimized. Moreover, selectable instrument parameters and conditions such as antigen retrieval temperatures/times, single versus multiple bleaching reagent applications, and process ordering (eg, antigen retrieval before or after bleaching) were also tested. Melanin intensity and percent coverage (bleaching performance) as well as LAG3 stain intensity and percent immune cell staining (staining performance) were evaluated and compared to unbleached controls.

Results: Our automated bleaching method preserves tissue morphology while substantially reducing or eliminating melanin pigmentation (Figure 3.146). Additionally, nonpigmented melanoma cases, whether bleached or unbleached, displayed similar LAG3-immune cell staining profiles, confirming epitope preservation.

Conclusions: The use of this novel ancillary bleaching reagent and automated methodology has the potential to enhance overall immunostaining performance in melanoma. Further development and optimization may improve melanin removal with minimal clinical burden relative to other common clinical methods.

The Impact of Age-Related Cytosine to Thymine Transition in Myelodysplastic Syndrome: Next-Generation Sequencing Approach

(Poster No. 147)

Yamac Akgun, MD1 ([email protected]); Yigit Baykara, MD2; Ridas Juskevicius, MD1; Laura A. Lee, MD, PhD.1 1Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee; 2Department of Laboratory Medicine and Pathology, Brown University, Providence, Rhode Island.

Context: Myelodysplastic syndrome (MDS) is primarily a disease of old age, although it is unclear whether aging itself contributes to the pathophysiology of the disease. We hypothesized that next-generation sequencing (NGS) data may help to reveal the association between aging and MDS.

Design: NGS was performed on MDS samples to assess the presence of disease-associated variants in a set of 50 genes. The data were analyzed with a focus on base substitutions.

Results: NGS data from 49 MDS patients with an average age of 71 years were analyzed. A total of 124 base substitutions resulting in pathogenic variants were identified. Forty-four (36%) of these substitutions were cytosine (C) to thymine (T) transitions. Twenty-two (50%) of these C to T base changes involved replacement of arginine by a stop codon (73%) or another amino acid (23%) at a hot spot position within multiple genes. Thirty-six de novo acute myeloid leukemia (DN-AML) patients underwent sequencing with the same NGS panel that showed a significantly lower rate of C to T transition in DN-AML even when corrected for age (36% versus 19%, P < .05; Table).

Conclusions: The somatic mutation pattern of MDS revealed a high frequency of age-related C to T transitions. C to T changes were frequently associated with arginine or glutamine replacements by stop codons or well-described hot spot mutations. Investigation of the molecular changes underlying these pathogenic variants may contribute to our understanding of the mechanism of age-associated risk of MDS, with potential for future pharmacologic targeting of the 5-methylcytosine deamination to thymine pathway.

Novel Co-occurrence of HRAS P.G13R and PIK3CA P.H1047R Mutations in Anaplastic Thyroid Carcinoma

(Poster No. 148)

Ali M. Moosvi, MD1 ([email protected]); Udit Naik, MD1; Allison Bellman, MS1; Mauli Shah, MS1; Leomar Y. Ballester, MD, PhD2; Yu Bai, MD, PhD1; Hui Zhu, MD, PhD.3 1Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center at Houston; 2Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston; 3Department of Pathology, HCA North Cypress Medical Center, Cypress, Texas.

Anaplastic thyroid carcinoma (ATC) is an aggressive entity, with RAS and PIK3CA mutations acting as negative prognostic indicators. Molecular aberrations are ill-defined, whereas identification of actionable targetable variants continues to remain a challenge. We present a 73-year-old man who underwent a left hemithyroidectomy and received a diagnosis of follicular thyroid carcinoma with an ATC component. Histopathology revealed a clear distinction between the follicular (Figure 3.148, A) and anaplastic (Figure 3.148, B) morphology from the same tissue block. Targeted genomic analysis was conducted on a formalin-fixed, paraffin-embedded tissue sample through the next-generation sequencing (NGS) platform (Thermo Fisher Scientific, Waltham, Massachusetts). Manual microdissection of the 2 distinct morphologic components was performed, followed by DNA extractions and subsequent NGS analysis to investigate the genomic alterations in each morphologic pattern. The follicular component revealed a HRAS p.G13R (c.37G>C) mutation, whereas the anaplastic component exhibited a rare concurrent HRAS p.G13R (c.37G>C) and PIK3CA p.H1047R (c.3140A>G) mutation. Tumor heterogeneity in thyroid carcinoma may be reflected by genomic alterations, with progression of well-differentiated to poorly differentiated tumors through accumulation of driver mutations predominantly via activation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways. In addition, a genomic database search revealed that these specific mutations in HRAS and PIK3CA are generally mutually exclusive in ATC. This novel finding of cooccurrence with HRAS G13R (c.37G>C) and PIK3CA p.H1047R (c.3140A>G) in ATC provides greater insight into tumorigenesis and may assist in personalized therapeutic implementation.

SARS-CoV-2 RT-PCR Pooled Testing as a Reliable Tool for Mass Testing in Low-Prevalence Areas

(Poster No. 149)

John Basil C. Umali, MD ([email protected]); Francisco P. Tria, MD; Marissa Krizelda D. Santos, MD; Herbert Z. Manaois, MD; Evelina N. Lagamayo, MD; Jhonamari D. David, RMT; Zenith Anne P. Duran, RMT; Daphne C. Ang, MD. Department of Pathology, Chinese General Hospital and Medical Center, Santa Cruz, Manila, Philippines.

Context: Two years into the pandemic, SARS-CoV-2, caused by COVID-19, still continues to spread and affect the susceptible population. Mass testing is necessary to detect, isolate, and prevent its transmission. With limited resources in developing countries, SARS-CoV-2 pooled reverse transcription-polymerase chain reaction (RT-PCR) testing may be done to decrease the cost of testing and save resources.

Design: This was a descriptive prospective study that involved testing for individual and pooled testing samples of SARS-CoV-2 RT-PCR using the Beijing Applied Biological Technologies Co Ltd nucleic acid extraction kit, SLAN-96P Real Time PCR system, and Applied Biosystems QuantStudio 5 Real-Time PCR Instrument. The cohort was taken from a 5% positivity rate from the area of testing.

Results: A total of 200 individual samples were tested in the study. These were grouped into 20 positive pools composed of 1 known positive sample and 4 known negative samples and 20 negative pools composed of 5 known negative samples. Fisher exact testing was performed to analyze the data. Two positive individual samples showed negative results in the pooled sample testing, which yielded a percent positive agreement of 90% from the 5-sample pooled test final results (Table).

Conclusions: There was no significant difference in testing individual and pooled samples for SARS-CoV-2 (P = .86) in areas with low positivity rate. Our data showed overall agreement and comparable performance for pooled and individual sample testing. The study supported the cost-effectiveness and validity of SARS-CoV-2 RT-PCR pooled testing as a means of doing mass testing.

Randomly Collected Saliva-Based RT-PCR Testing for SARS-CoV-2 Detection in Acutely Ill Patients

(Poster No. 150)

David Thomas S. Catapia, MD ([email protected]); Francisco P. Tria, MD; Marissa Krizelda D. Santos, MD; Herbert Z. Manaois, MD; Evelina N. Lagamayo, MD; Jhonamari D. David, RMT; Zenith Anne P. Duran, RMT; Daphne C. Ang, MD. Department of Pathology, Chinese General Hospital and Medical Center, Santa Cruz, Manila, Philippines.

Context: Nasopharyngeal (NPS) and oropharyngeal (OPS) specimens are the current sample of choice in detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although minimally invasive, these techniques are generally considered safe and have often been performed by skilled staff in high-prevalence states. It has been proposed that alternative respiratory samples may be used for SARS-CoV-2 detection. Saliva samples are safe, self-collected, and may be a possible alternative.

Design: This was a prospective cross-sectional study. Mann-Whitney U testing was used for computation and data analysis to calculate the difference between nonreactive and reactive results among the 2 groups. STATA version 13.0 was used for data analysis.

Results: Evaluation of the performance of saliva RT-PCR testing compared with NPS/OPS testing involved the analysis of 133 samples. Our data showed a sensitivity/specificity of 90.32%/99.02% with a positive predictive value of 96.55% and negative predictive value of 97.1% (Table).

Conclusions: Our study concluded that NPS/OPS and saliva testing for SARS-CoV-2 RT-PCR are comparable in detecting the presence or absence of SARS-CoV-2 infection (P = .88). Saliva testing is a noninvasive method of sample collection for SARS-CoV-2 RT-PCR testing and a simple alternative technique that can be performed by the patients themselves and does not require trained staff for specimen collection.

Bacterial Detection and Pooled Susceptibility Testing by PCR in Catheter-Collected Urine in Patients With Symptoms of Urinary Tract Infection

(Poster No. 151)

Rajan Dewar, MD, PhD1 ([email protected]); Sarah LaSalle, RN2; Dakun Wang, MB, PhD3; Xinhua Zhao, PhD4; Kilian LaFreniere, DO5; Natalie Luke, PhD6; Patrick Cacdac, MD6; David Baunoch, PhD.7 Departments of 1Pathology and 2Infection Prevention and Quality Management, McLaren Greater Lansing, Lansing, Michigan; Departments of 3Writing and 4Statistics, Stat4ward, Pittsburgh, Pennsylvania; 5Department of Critical Care, McLaren Greater Lansing & Michigan State University, Lansing; Departments of 6Medical Research, Education & Outcomes and 7Research and Development, Pathnostics, Irvine, California.

Context: Multiplex polymerase chain reaction (M-PCR) and pooled antibiotic susceptibility testing (P-AST) are equivalents to culture and sensitivity (C&S) in the diagnosis of a urinary tract infection (UTI). This abstract focuses on the technical characteristics of the assay.

Design: Guidance UTI (M-PCR) detected 27 urogenital bacteria/bacterial groups in catheter-collected urine samples from 3442 patients with UTI symptoms. At ≥1000 cells/mL, we defined bacterium as “detected.” This “detection” threshold is a Ct-based equivalent similar to significant bacteriuria/colony counts. The P-AST test detects susceptibilities to 19 antibiotics or antibiotic combinations.

Results: Mean patient age was 69.4 years; 82% of patients were female (2840 of 3442). Positive detection was 63% (2164 of 3442); 28.4% (979 of 3442) were polymicrobial. The M-PCR assay identified all the targeted organisms, with the most common organisms being Escherichia coli (25.4% [873 of 3442]), Enterococcus faecalis (18.4% [631 of 3442]), Actinotignum schaalii (9.9% [342 of 3442]), Aerococcus urinae (7.5% [260 of 3422]), and Viridans Group Strep (7.2% [247 of 3442]). Those commonly assumed to be contaminants were also rarely detected, including Coagulase-Negative Staph Group (4.3% [147 of 3442]) and Corynebacterium riegelii (0.5% [17 of 3442]). Of the positive cases, we obtained susceptibility results for 78.2% (1693 of 2164); we were unable to obtain susceptibility information for 21.8% (471 of 2164). A total of 15.8% (272 of 2166) of the positive cases included exclusively fastidious organisms. The standard urine culture would have reported these cases as negative.

Conclusions: At least 27 different bacteria, including those commonly considered contaminants (erroneously), can be identified, and their susceptibility rapidly tested. This combination is proposed as a superior equivalent to the conventional C&S.

D. Wang and X. Zhao are consultants with Pathnostics.

Characterization of a Complex Case of Myelodysplastic Syndrome With Optical Genome Mapping

(Poster No. 152)

Nivin Omar, MD1 ([email protected]); Nikhil Sahajpal, PhD1; Ashis Mondal, PhD1; Vamsi Kota, MD2; Natasha Savage, MD1; Ravindra B. Kolhe, MD, PhD.1 Departments of 1Pathology and 2Medicine, Medical College of Georgia at Augusta University, Augusta.

Myelodysplastic syndrome (MDS) is a heterogeneous group of hematopoietic neoplasms characterized by abnormal differentiation, dysplasia, and peripheral blood cytopenias. Karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarrays are required to obtain a comprehensive molecular profile for the diagnosis and prognostication of patients with MDS. Herein, we present a case of MDS analyzed using optical genome mapping (OGM), demonstrating the ability of OGM technology to better characterize and delineate structural variants (SVs) previously analyzed with conventional cytogenetic methods. The karyotype analysis demonstrated a simple cytogenetic profile: 46,X,t(X;12)(q13;q24.3),del(20)(q11.2)[14]/46,XX[6], with FISH confirming the loss on chromosome 20. OGM, in addition to identifying all the previously characterized SVs, demonstrated higher sensitivity and resolution for SV analysis in this case. OGM was concordant and refined the breakpoints of the 2 aberrations detected by conventional methods t(12; X)(q24.33;q12)(131825805;65861727), 20q11. 21q13.13(32669677_50729052)x1. Furthermore, OGM detected 7 additional variants that included 6 translocations resulting in 5 potential gene fusions. Also, OGM detected a 2.5-Mb copy number loss on chromosome 13 [13q14.2q14.3(49249067_51832903)x1], which is beyond the resolution of karyotyping, and the region is not included in targeted FISH panels (Figure 3.152). The findings in this case of MDS highlight the clinical utility of OGM for genomic characterization of SVs that are difficult to characterize and resolve by conventional techniques.

R. B. Kolhe is a consultant with Bionano, Agena, QIAGEN, Perkin Elmer, PGDx, and Cepheid, and has received grant or research support from Perkin Elmer and Bionano.

Metaplastic Carcinoma of the Breast With Spindle Cell Features Adjacent to a Phyllodes Tumor: Case Report and Review of Literature

(Poster No. 153)

Azin Mashayekhi, MD ([email protected]); Soheila Korourian, MD. Department of Pathology, University of Arkansas for Medical Sciences, Little Rock.

Spindle cell lesions of the breast show significant biologic and morphologic heterogeneity. Spindle cell carcinoma, a member of this group, is a subtype of metaplastic carcinoma. These tumors are rare, with only a few reported cases. We report a patient who initially was given a diagnosis of at least borderline phyllodes tumor of the left breast, based on the diagnostic core biopsy. Partial mastectomy revealed a spindle cell carcinoma adjacent to a 5-cm phyllodes tumor. The phyllodes component showed typical leafletlike appearance with a prominent cambium layer of spindle cells with marked cytologic atypia and easily identifiable mitotic figures (Figure 3.153, A and B). CK7, p63, CK 5/6, and pancytokeratin did not express in stromal elements of the phyllodes component; however, they showed positivity only within the glandular elements (Figure 3.153, C). The adjacent spindle component showed nuclear expression with p63 as well as focal positivity with pancytokeratin and CK7 (Figure 3.153, C and D). Because of cytokeratin and p63 positivity, the spindle cell component was classified as metaplastic carcinoma. The tumor was negative for estrogen and progesterone receptors and did not show HER2/neu overexpression. All surgical margins were negative. Metastatic workup was negative. The patient later received adjuvant chemotherapy followed by radiation therapy. In the evaluation of any spindle cell lesions of the breast, irrespective of bland or malignant cytomorphology, metaplastic carcinoma must be considered. The distinction between metaplastic carcinoma and malignant phyllodes tumors of the breast is critical because the treatment and prognosis differ. A battery of cytokeratin, including p63, is required to exclude spindle cell carcinoma.

Comparing Oncotype DX With Magee Decision Algorithm: Analysis From an Urban Public Hospital

(Poster No. 154)

Melad N. Dababneh, MBBS ([email protected]); Patrick C. Mullane, MD; Marina B. Mosunjac, MD; George G. Birdsong, MD; Uma Krishnamurti, MD, PhD. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia.

Context: The TAILORx trial concluded that in patients older than 50 years, Oncotype DX (ODX) score 0 to 25 showed excellent response to endocrine therapy, whereas ODX >25 benefited from chemotherapy (CTX). The “Magee Equation 2” (ME2) uses tumor size, Nottingham score, and ER, PR, and HER2 status. The Magee Decision Algorithm (MDA) triages cases for molecular testing (Mtx) using ME2 and mitotic activity (Mit). Here, we compare results using the MDA with TAILORx trial ODX cutoffs.

Design: A total of 133 patients with ER+, node-negative IBC with ODX reports and histopathologic data (2014–2019) were reviewed. ME2 results were calculated using the UPMC calculation. ME2 scores were grouped based on the MDA into: Concordant (IC, IIC, IIIC) to forgo Mtx; Will Test (WT1, WT2) to get Mtx; and Discordant (ID, IID, IIID), where ODX was discordant with ME2 (Table).

Results: Of the patients, 102 of 133 were older than 50 years. In this group, by MDA, 63.7% could forgo Mtx and 29.4% could undergo Mtx (Table). Of 7 patients with discordant results, 3 of 7 received CTX, and 6 of 7 received endocrine therapy. In group ID, 2 received CTX and 2 refused. The 1 patient in group IID got CTX and 0 of 2 patients in IIID received or were offered CTX. The results in patients younger than 50 years were similar.

Conclusions: By the recent MDA, 63.7% of cases were concordant with ODX and could forgo Mtx. A total of 29.4% could undergo further Mtx. A total of 6.9% patients had discordant results, and clinical decision was based on the ODX score. Screening using the MDA prior to ODX testing would be cost saving without compromising clinical care.

Protein Expression of Lysine-Specific Demethylase-1 Correlates With Poor Survival Outcomes in Triple-Negative Breast Cancer

(Poster No. 155)

Jabed Iqbal, MD, PhD1 ([email protected]); Dong Lee, BSc2; Bernett Lee, PhD3; Puay Hoon Tan, FrCPath.1 1Department of Anatomical Pathology, Singapore General Hospital, Singapore; 2Department of Biological Science, Nanyang Technological University, Singapore; 3Department of Bioinformatics, ASTAR, Singapore.

Context: Clinical outcomes remain poor in triple-negative breast cancer (TNBC). An epigenetic modulator, lysine-specific demethylase-1 (LSD1), plays an important role in altering the immune landscape in cancers including TNBC. We aimed to investigate the association of LSD1 with clinicopathologic parameters and immune cells and its role in predicting survival outcomes in TNBC.

Design: Tissue microarrays were constructed from 389 TNBC cases from Singapore General Hospital (2003–2014). Immunohistochemistry was performed using LSD1 antibody, whereas transcripts were quantified using Nanostring. Nuclear expression was correlated with clinicopathologic parameters using the χ2 or Fisher exact tests. Overall survival (OS) was estimated using Kaplan-Meier analysis and compared between groups with the log-rank test. Positively correlated genes with KDM1A in TCGA TNBC patients were identified using LinkedOmics, where a PPI network was constructed to identify hub genes.

Results: Approximately 45% of the TNBC tumors expressed LSD1 protein and reported a significant association with worse OS on multivariate analysis (HR, 1.353; 95% CI, 1.053–1.740; P = .02). LSD1+ tumors showed a significant correlation with FOXP3+ T-regulatory cells (P = .04) and hypoxia regulator HIF1a (P = .04). Among the differentially regulated genes, 10 hub genes were identified, and higher expression of 8 genes (WRAP73, PITHD1, LYPLA2, DNAJC11, CEP85, EMC1, ENO1, and SDHB) showed significantly worse TNBC survival.

Conclusions: Our results demonstrate the prognostic significance of increased LSD1 protein expression and KDM1A-linked gene signatures in TNBC. Significant LSD1 correlation with HIF1a and T-regulatory cells suggests a potential role in tumor progression as well as a putative target to enhance antitumor immunity.

Comprehensive Analysis of Clinicopathologic Features and p53 Mutation in Neuroendocrine Neoplasms of the Breast

(Poster No. 156)

Saba Shafi, MD1 ([email protected]); Yan Hu, MD1; Anil V. Parwani, MD, PhD, MBA1; Qingqing Ding, MD, PhD2; Zaibo Li, MD, PhD.1 1Department of Pathology and Laboratory Medicine, The Ohio State University Wexner Medical Center, Columbus; 2Department of Pathology and Laboratory Medicine, MD Anderson Cancer Center, Houston, Texas.

Context: The recent World Health Organization 5th edition classifies breast carcinoma with neuroendocrine (NE) differentiation into 2 categories: (1) invasive breast carcinoma, no specific type (NST) with NE features (IBC-NE; ≤90% NE histologic features), and (2) NE neoplasm (NEN; >90% NE features), which is further separated into NE tumor (NET) or NE carcinoma (NEC). p53 mutation has been frequently identified in NEC of other sites, but very little has been published about p53 mutation in NEN of the breast. Here, we examined p53 expression and other clinicopathologic characteristics in 3 types of breast carcinomas with NE differentiation.

Design: In this study, 63 breast carcinomas were included (IBC-NE: n = 45; NET: n = 10; and NEC: n = 8). p53 mutation status was examined using p53 immunohistochemistry (IHC).

Results: No significant difference was observed between NET and IBC-NE regarding tumor grade, breast biomarkers, p53 mutation, and survival. However, NEC had a significantly higher frequency of p53 mutation than NET or IBC-NE (75% versus 0% or 11.1%). In addition, NEC showed significantly higher tumor grade and less ER/PR positivity. Patients with NEC received chemotherapy more frequently than patients with IBC-NE, but they showed more distant metastasis than IHC-NE patients. No statistical significance was observed regarding overall survival between NEC and IBC-NE patients because of a small sample size and short follow-up period (Table).

Conclusions: This is one of the first exploratory studies highlighting p53 mutation in neuroendocrine cancers of the breast. NEC was significantly associated with p53 mutation compared with IBC-NE or NET. Our data have also demonstrated that NECs exhibit different clinicopathologic features from those of IBC-NE or NET.

Adenomyoepithelioma of the Breast: Molecular Profile of 6 Cases

(Poster No. 157)

Zena Jameel, MD ([email protected]). Department of Pathology, H. Lee Moffitt Cancer Center, Tampa, Florida.

Context: Adenomyoepithelioma of the breast is a rare, biphasic neoplasm characterized by proliferation of epithelial and myoepithelial cells. Adenomyoepitheliomas can be benign, atypical, and malignant (adenomyoepithelioma with carcinoma). Malignant transformation of one or both cellular components may occur. Most adenomyoepitheliomas have a benign clinical course and can be treated by local excision; however, local recurrence and distant metastasis have been reported.

Design: After Institutional Review Board approval, we searched our archives for adenomyoepithelioma diagnosed in our department in the last 10 years. Cases were included if material was available for testing. The cases were subjected to estrogen receptor (ER) testing and targeted next-generation sequencing using the MOFFITT STAR (Illumina TST170) 170 gene panel.

Results: Six cases were identified and reviewed. The age at diagnosis ranged from 35 to 85 years, and all patients were female. Five cases were benign (83%), 1 was malignant. Three cases were positive for ER and 3 were negative. All 3 ER-negative cases showed MYC and FGFR1 amplification. A total of 2 of the 3 ER-negative cases showed NRG1 amplification. A total of 5 of our 6 cases (83%) showed molecular change in the PI3K/AKT/mTOR pathway to include: 2 with PIK3R1 mutation, 2 with PIK3CA mutation, and 1 with AKT1 mutation. Only 1 case had an HRAS mutation, and 1 case had an FGFR2 deletion. The malignant case showed PIK3R1 mutation, MYC, FGFR1, and NRG1 amplification (Figure 3.157).

Conclusions: Breast adenomyoepitheliomas are rare tumors. They represent a heterogeneous group morphologically, clinically, and genetically. Identification of recurrent genetic alterations may have diagnostic and therapeutic applications.

Pathologic Features of Invasive Carcinomas Presenting as Asymmetry on Mammographic Screening

(Poster No. 158)

Mohamed M. Kahila, MBBCH1 ([email protected]); Catherine S. Giess, MD2; Allyson L. Chesebro, MD2; Esther Rhei, MD3; Xuefei Hong, MD4; Susan C. Lester, MD, PhD.1 Departments of 1Pathology and 2Radiology, Brigham and Women's Hospital, Boston, Massachusetts; 3Department of Surgical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; 4Department of Pathology, Brigham and Women's Faulkner Hospital, Boston, Massachusetts.

Context: Breast carcinomas are rarely detected as mammographic asymmetry. Asymmetry is defined as increased breast density without mass features when compared with other areas. Little has been reported about the pathologic features of cancers and why these features result in this unusual appearance.

Design: This study was undertaken to identify carcinomas associated with asymmetry from 2015 to 2021. Radiology and pathology reports were reviewed. Single-feature asymmetry was defined as lesions not associated with other findings on mammography, ultrasonography, or magnetic resonance imaging. Multiple-feature asymmetry included all other cases.

Results: During the study period, 15 319 core needle biopsies were performed and 620 (4%) described the lesion as associated with asymmetry. Of these, 30 (4.8%) revealed invasive carcinoma and 8 (0.1%) ductal carcinoma in situ. Almost half (46%) of the invasive carcinomas were either lobular in type or had lobular features. More than half (61%) were ≤1 cm in size, and 83% (19 cases) were node negative. All but 1 cancer was AJCC stage I when stage could be assigned. All but 2 carcinomas were either favorable biologic type or stage, and most were both. Only 6 cases presented as single-feature asymmetry, and these carcinomas tended to have more favorable features (Table).

Conclusions: This is the largest series of carcinomas presenting as asymmetry. The major correlates for presenting as asymmetry rather than a mass were the frequent presence of lobular features and/or small size in more than 80% of cases. Although most had very favorable biologic features and were stage I, carcinomas with less favorable features were also detected.

A Rare Benign Breast Lesion Masquerading Atypically Radiologically and Clinically: A Case of Lymphocytic Mastitis Carrying a Diagnostic Dilemma

(Poster No. 159)

Prachi, MD ([email protected]); Neerja Gupta, MD; Gaurav Sharma, MD. Department of Anatomic Pathology and Laboratory Medicine, Dharamshila Narayana Superspeciality Hospital, New Delhi, India.

Lymphocytic mastitis or fibrotic mastopathy is usually associated with insulin-dependent diabetes or an autoimmune disease. It is a benign clinicopathologic entity, forming a main differential diagnosis of breast carcinoma radiologically. Herein, we present a 31-year-old hypertensive woman with a 2-year history of a left breast lump. She was nondiabetic. Clinically, the lesion was a nontender, immobile, firm mass. Ultrasonography revealed a large, round circumscribed mass with posterior acoustic shadowing, categorized as BI-RADS IV (Figure 3.159, A). Cytology was suggestive of a fibroepithelial lesion. Wide local excision of the lump was performed. Intraoperatively, it was a cystic mass in the left upper outer quadrant filled with necrotic puslike material, raising the suspicion of tuberculosis (Figure 3.159, B). Genexpert for Mycobacterium tuberculosis was not detected. Grossly, the lump was 6.5 × 5.5 × 2.5 cm. The cut surface showed a cystic cavity filled with necrotic material. Microscopically, dense collagenous keloid-like fibrosis with periductal, perilobular, and perivascular lymphocytic infiltrate with focal palisading plump histiocytes around the cystically dilated spaces was observed, and the final diagnosis of lymphocytic mastitis was rendered (Figure 3.159, C and D). Lymphocytic mastitis pathogenesis is believed to be multifactorial. The relevant history of diabetes or autoimmune disease may or may not present, as in this case. This entity carries variable appearance on mammography and ultrasound; hence, the constellation of findings on clinical examination, medical history, radiologically, and pathologically is mandatory to come to a definitive diagnosis of such rare benign entities, and to distinguish them from breast carcinoma.

Size Measurement of Breast Mucinous Carcinomas: A Survey Report

(Poster No. 160)

Amir H. Samani, BSc1; Samieh Khosravinia, MD1; Amir A. Samani, MD, PhD2 ([email protected]). 1Department of Research, Dr Amir Samani Medicine Professional Corporation, Toronto, Ontario, Canada; 2Department of Pathology, Humber River Hospital, Toronto, Ontario, Canada.

Context: Mucinous carcinomas are composed of floating nests of tumor cells in mucin pools. As of the date of this report, there is no guideline or agreed-upon method on how to measure the size of mucinous carcinomas.

Design: Microphotographs of a mucinous carcinoma were emailed to 11 breast pathologists in the United States and Canada with the following question: Should this tumor be staged as pT1a (2.8 mm; considering whole surface area with mucin pools [Figure 3.160, A]) or pT1mi (0.4 mm; considering only floating cancer cells [Figure 3.160, B])?

Results: The tumor was staged as pT1a by 7 pathologists (64%). However, 2 pathologists (18%) deemed it pT1mi, using floating tumor cells for measurements. The other 2 pathologists (18%) called it pT1mi because they believed that the acellular mucin pools not connected to the mucin pool with floating cells likely represented mucocele-like lesions and should not be considered as a component of a malignant process.

Conclusions: Determining the size of mucinous carcinomas is a controversial issue. This may affect tumor staging (pT), margin status (when only acellular mucin presents at margin [Figure 3.160, C]), lymph node involvement (when only acellular mucin present [Figure 3.160, D]), and size of metastasis (micrometastasis versus macrometastasis) and extranodal extension assessment (when only acellular mucin is present) in mucinous carcinoma. Postneoadjuvant assessment of mucinous carcinomas with pools of acellular mucin is another controversial issue. This survey shows that there is a need for consensus criteria to settle on a standardized method of measurement.

Correlation of Ki-67 Proliferation Rate With Oncotype DX Score in Early-Stage Lymph Node–Negative and Lymph Node–Positive Breast Cancer

(Poster No. 161)

Suzanne Iwaz, MD ([email protected]); Sharlene See, MD; Luis Blanco, MD; Kalliopi P. Siziopikou, MD, PhD. Department of Pathology, Northwestern University, Chicago, Illinois.

Context: Oncotype DX provides prognostic and predictive information in early breast cancer. Although initially used in early-stage lymph node–negative (LN) ER+/HER2 breast cancer patients, its use recently expanded to include early-stage LN+ patients. We evaluated Ki-67 proliferation rates and correlated these results with the Oncotype DX score in breast cancer patients with and without LN involvement.

Design: Our patient population consisted of 212 breast cancer patients (age range, 32–80 years) with known Oncotype DX results (2016–2021). Clinicopathologic characteristics, such as tumor size, grade, LN status, ER/HER2 expression, and Ki-67 proliferation index, were correlated with Oncotype recurrence scores (RS: low, 0–10; intermediate, 11–25; high, >26).

Result: A total of 141 patients were LN negative and 61 were LN positive. All patients were ER+/HER2. Our LN cases had an average tumor size of 2.1 cm. A total of 31 had low RS, 84 had intermediate RS, and 26 had high RS. Our LN+ cases had an average tumor size of 2.3 cm; 15 had low RS, 36 intermediate RS, and 10 high RS. The average Ki-67 index correlated with RS in all groups and was statistically significant (P = .03) in the high RS in LN+ cases (Table).

Conclusions: Our findings add to the understanding that Ki-67 proliferation rates correlate with the Oncotype scores in both LN and LN+ early-stage breast cancer patients and support the possibility of reliably using Ki-67 proliferation rates as an initial tool for making therapeutic decisions in early-stage breast cancer patients.

Validation of a New Prognostic Breast Cancer Index Based on Classical Clinicopathologic Information

(Poster No. 162)

Anne-Sophie Wegscheider, MD1 ([email protected]); Anna Catharina Richter1; Bernhard Ulm1; Dimitrij Tschodu, MSc2, Kay Friedrichs, MD3; Christoph Lindner, MD4; Josef Käs, PhD2; Axel Niendorf, MD.1 1Department of Pathology, MVZ Prof. Dr. Med. A. Niendorf Pathologie Hamburg-West GmbH, Hamburg, Germany; 2Department of Faculty of Physics and Earth Science, University Leipzig, Peter Debye Institute of Soft Matter Physics, Leipzig, Germany; 3Department of Gynecology, Mammazentrum Hamburg MVZ GbR, Hamburg, Germany; 4Department of Gynecology, Agaplesion Diakonieklinikum Hamburg, Frauenklinik, Hamburg, Germany.

Context: The Altona prognostic index (API) has previously been constructed in a cohort of 6654 breast cancer patients on the basis of clinicopathologic variables (ie, tumor grade, tumor size, nodal status, and age). To reduce confounding bias, the API has been intentionally addressed to predict progression-free survival in a situation of primary, unilateral, unifocal estrogen receptor–positive and HER2 breast cancer of no special type (NST, World Health Organization 8500/3) in patients not older than 70 years at the time of diagnosis. When compared to the Nottingham Prognostic Index (NPI), which is generally accepted to represent the gold standard, API showed a superior prediction of outcome.

Design: To validate this new index in a retrospective study, we calculated progression-free survival in an independent cohort (n = 2408; mean age, 63 years; observation period between January 2015 and December 2021), including female patients with the same filter criteria as they were set in the development of the API (see above). Both indexes were compared using iAUC value and C-index. All patients gave written informed consent after the study design was approved by the ethics committee of the Aerztekammer Hamburg.

Results: The API showed significantly higher iAUC (0.627 versus 0.547, P < .001) and concordance (0.625 versus 0.581, P = .01) values compared with the NPI (Figure 3.162).

Conclusions: In this study we could validate the prognostic power of the API in a large independent cohort of breast cancer patients. This corroborates the significance of classical clinicopathologic parameters and especially underlines the importance of the histopathologic tumor type.

Impact of the 2018 ASCO/CAP HER2 Guideline in the Clinical Management of Filipinos With Invasive Breast Cancer

(Poster No. 163)

Anna Carissa Mariano, MD ([email protected]); Daphne Ang, MD. Department of Pathology and Laboratories, Makati Medical Center, Makati, Philippines.

Context: Human epidermal growth factor receptor 2 (HER2) is a glycoprotein that is amplified and/or overexpressed in breast cancer and has a 24.4% positivity rate in Filipinos. HER2-targeted therapy has significantly improved survival in HER2+ cases. Thus, guidelines for HER2 testing are constantly updated to reflect clinical response.

Design: A total of 152 breast cancer cases from January 2014 to March 2019 with HER2 immunohistochemically equivocal 2+ and reflex fluorescence in situ hybridization results using the 2013 guideline were reviewed. Cases were reevaluated using the 2018 update, and the overall HER2 status was compared using both guidelines.

Results: Using the 2013 guideline, 33 (21.71%) were HER2+, 6 (3.95%) were HER2-equivocal, and 113 (74.34%) were negative. Applying the 2018 guideline decreased the HER2+ cases to 30 (19.74%), increased the HER2 cases to 122 (80.26%), and eliminated the HER2-equivocal category. There was a 94.08% level of agreement between the 2013 and 2018 guidelines. All cases that were reclassified into a different category using the 2018 guideline were from in situ hybridization groups 2 (3 of 152) and 4 (6 of 152).

Conclusions: Implementation of the 2018 guideline increased number of HER2 cases due to the reclassification of cases from in situ hybridization groups 2 and 4. Patient management would be different in 9 cases (6%) in our cohort. More importantly, in a third-world country like the Philippines, reducing the number of cases in the equivocal category will be of financial benefit to the patients.

Diffuse Sarcoidosis-like Granulomatous Change in Breast Cancer Tumor Bed After Neoadjuvant Chemotherapy

(Poster No. 164)

Haval Ali, MD ([email protected]); Zhihong Hu, PhD, MD; Hongxia Sun, PhD, MD. Department of Pathology and Laboratory Medicinej, UTHealth, Houston, Texas.

Granulomatous change is not commonly seen in the breast cancer tumor bed after neoadjuvant chemotherapy (NAC). Currently all reported cases of therapy-induced granulomas were either in the axillary lymph nodes only or were described as xanthogranuloma in breast tissue. We present a case of diffuse sarcoidosis-like granulomatous change that developed in both the breast tumor bed and axillary lymph nodes after NAC. The patient was a 59-year-old Hispanic woman with a past medical history of hypertension who presented with a large heterogeneous left breast mass measuring 11.4 × 6 cm. Biopsy of the mass showed triple-negative invasive ductal carcinoma, combined Nottingham histologic grade 3 with brisk lymphoplasmacytic infiltrate and necrosis. The patient received doxorubicin hydrochloride and cyclophosphamide, followed by paclitaxel as NAC. She subsequently underwent left modified radical mastectomy. Histologic examination of the treated tumor bed revealed multifocal residual invasive ductal carcinoma with frequent nonnecrotizing sarcoidosis-like granulomatous change. The granulomatous reaction was also seen in several axillary lymph nodes, one of which had residual metastatic cancer cells. The granulomas were negative for microorganisms by GMS and AFB special stains. Idiopathic granulomatous mastitis, sarcoidosis, and infective etiologies were excluded based on the history, imaging, and histologic findings. To the best of our knowledge, this is the first report of diffuse granulomatous change in response to NAC in breast cancer.

An Aggressive and Advanced-Stage Encapsulated Papillary Breast Carcinoma in a Male Patient

(Poster No. 165)

Mary Torrez, MD1 ([email protected]); Michaela L. Granados, BS1; Stephanie Fine, MD2; Jain Zhou, MD, PhD1; Nadja K. Falk, MD.1 Departments of 1Pathology and 2Surgery, Division of Surgical Oncology, University of New Mexico, Albuquerque.

Male breast cancer is rare, representing 1% of male cancers and 1% of all breast cancers. Male breast papillary lesions are uncommon and consist of a heterogeneous group including benign, carcinoma in situ, and invasive carcinomas; 4% of breast carcinomas in men are of papillary subtypes. Encapsulated papillary carcinoma (EPC) is uncommon, particularly in males, and generally behaves indolently. A 61-year-old man presented emergently with pain, swelling, and erosion of left chest. Computed tomography and ultrasound revealed a 7.1-cm solid mass with suspicious left axillary lymph nodes. Biopsies of the left chest and left axillary lymph node showed invasive carcinoma with papillary features (Figure 3.165, A), grade 1, estrogen receptor/progesterone receptor positive (both 100%), HER2 immunohistochemical stain negative (1+) (Ventana Medical Systems, Tucson, Arizona), with lymph node metastasis (Figure 3.165, B), respectively. The patient underwent neoadjuvant chemotherapy followed by left radical mastectomy and axillary dissection, revealing EPC (Figure 3.165, C), confirmed by lack of myoepithelial cells (p63 negative [Biocare Medical, Concord, California]) within and surrounding the tumor (Figure 3.165, D) and by the lack of neuroendocrine differentiation. Advanced stage at presentation for EPC is highly unusual. Skin ulceration and no definitive response to presurgical therapy were seen. Although guidelines for male patients are not clearly delineated, the patient subsequently underwent radiation and tamoxifen therapy. Even with advanced presentation and metastasis, the tumor is behaving indolently, as its subtype implies, and the patient is doing well 1 year after surgery.

Cell and Nucleus Shape as Static Indicators of Cell Motility in Histologic Images

(Poster No. 166)

Pablo Gottheil, MSc1 ([email protected]); Jürgen Lippoldt, PhD1; Steffen Grosser, PhD1; Frédéric Renner, MSc1; Benjamin Wolf, PhD2; Bahriye Aktas, PhD2; Axel Niendorf, MD, PhD3; Josef Käs, PhD, Dr. rer. nat.1 1Department of Physics, University of Leipzig, Germany; 2Department of Gynecology, University Hospital Leipzig, Germany; 3Department of Histology, Cytology, MVZ Prof. Dr. Med. A. Niendorf Pathologie Hamburg-West GmbH Institute for Histology, Cytology and Molecular Diagnostics, Leipzig, Germany.

Context: Distant metastasis can be considered the most lethal hallmark of cancer. Nevertheless, because of a lack of suitable markers, the motility of cancer cells only has an insignificant impact on current diagnosis and prognosis. Cancer cell motility is an emergent biophysical phenomenon that provides crucial information for the development of a motility signature.

Design: Cultivated cell spheroids from malignant and healthy breast cells as well as vital primary breast and uterine cervical cancer samples were biomechanically evaluated regarding motile and nonmotile behavior using nucleus tracking and cell and nucleus segmentation.

Results: Three-dimensional evaluation of the samples showed a high correlation of cell motility with elongated cell and nucleus shapes. These variables were also associated with the collective ability of cells to move in cancer clusters. Single cells elongated to squeeze through the dense matrix of neighboring cells (Figure 3.166, A), where nuclei were stained with a vital DNA stain.

Conclusions: Because cell and nucleus elongation are static representatives of dynamic motility behavior, they may be used as a pathologic assessment of metastatic risk. Modern image quality and analysis techniques make nucleus and approximated cell shapes available on histologic slides (Figure 3.166, B and C). We already initiated a promising retrospective study on breast cancer and hope to trigger more studies on this topic.

Quantitative Image Analysis of HER2 Fluorescence In Situ Hybridization: Need for Standardization

(Poster No. 167)

Diane M. Wilcock, MS1 ([email protected]); Kristina Moore, MS2; Leslie R. Rowe, MS1; Evin H. Gulbahce, MD3; Deepika Sirohi, MD.3 Departments of 1Research & Development and 2Immunohistochemistry, ARUP Laboratories, Salt Lake City, Utah; 3Department of Pathology, University of Utah School of Medicine, Salt Lake City.

Context: The College of American Pathologists (CAP) released a guideline in 2019 for quantitative image analysis (QIA) of Human Epidermal Growth Factor Receptor 2 (HER2) immunohistochemistry for breast cancer. No equivalent guidelines exist for the QIA of HER2 fluorescence in situ hybridization (FISH) in breast carcinoma.

Design: The CAP QIA guideline for HER2 IHC was extrapolated to HER2 FISH combined with Clinical and Laboratory Standards Institute guidelines for FISH and industry best standards. QIA validation was performed on GenASIs Scan & Analysis instrument (Applied Spectral Imaging, Carlsbad, California). A minimum of 40 samples for groups 1, 4, and 5 and all available group 2 and 3 samples (n = 14 and 23) were used. Discordances between manual and digital scores were addressed by blinded review by 2 pathologists.

Results: Digital and manual accuracy results for HER2 and CEP17 correlated well (r = 0.82, 0.77; Figure 3.167, A through D). Intrarun, interrun instrument precision and operator precision done in triplicate for all groups were 100%, 100%, and 88% concordant. Reference range studies on digital and manual analysis were concordant. Optimal margin of error was obtained with 100-cell enumeration. Additional parameters evaluated included optimization of settings for fluorescence filters, cellular variables, z-stacking, and monitors. Digital QIA has the advantage of accurate mapping of the highest areas of IHC staining to the FISH slides, enumeration of greater number of cells, unbiased scoring, and better documentation.

Conclusions: In this study we report assay parameters that can be adopted for standardization of QIA FISH and provide a tool for more accurate HER2 status determination, especially for equivocal cases.

The Arrangement of Polarizable Collagen in Breast Tissue Can Be Seen With Polychromatic Polarization Microscopy During Diagnostic Microscopy

(Poster No. 168)

Raja, MD1 ([email protected]); Kevin Eliceiri, PhD2; Bin Li, PhD2; Adib Keikhosravi, PhD3; Agnes Loeffler, MD, PhD.1 1Department of Pathology, Metrohealth Medical Center, Cleveland, Ohio; 2Department of Pathology, Laboratory for Optical and Computational Instrumentation, Madison, Wisconsin; 3Department of Pathology, National Cancer Institute, Bethesda, Maryland.

Context: Studies using second harmonic generation (SHG), the gold standard methodology for evaluating collagen, have shown changes in the malignant stroma that correlate with survival in a variety of cancers. SHG is not conducive for use in routine diagnostic practice. The polychromatic polarization microscope (PPM), attached to a conventional microscope, highlights polarizable collagen fibers (PCFs) from hematoxylin-eosin–stained slides. We tested the ability of PPM to highlight the arrangement of PCFs in benign and malignant breast tissue.

Design: PPM was used to qualitatively assess the arrangement of PCFs in 10 slides each of: normal breast tissue, fibroadenoma, ductal carcinoma in situ (DCIS), and invasive ductal adenocarcinoma (IDC). PCF was characterized at 2 magnifications in relationship to the benign or malignant epithelium and by the length, width, and straightness of the PCF.

Results: Normal breast tissue, fibroadenoma, and DCIS were notable for a PCF-free space immediately around the basement membrane of ducts and acini (Figure 3.168, A through C). Rare, thin, and short slips of PCF were present within lobules. Stroma in benign breast tissue, fibroadenoma, and DCIS shows polychromatic (corrugated), thin, and delicate PCF. In contrast, in IDC, PCF is monochromatic, thick, and straight, and directly adjacent to the malignant epithelium (Figure 3.168, D).

Conclusions: PPM highlights the topology of collagen in benign and malignant breast stroma and reproduces findings originally described with SHG. Unlike SHG, PPM can easily be used during routine diagnostic workflows. Future studies using PPM will investigate the orientation of PCF in IDC to correlate stromal changes with an outcome.

Tall Cell Carcinoma of Breast With Reverse Polarity: Report of 2 Cases, 1 With 7-Year Follow-Up

(Poster No. 169)

Bing Han, MD ([email protected]); Saeed Bajestani, MD. Department of Pathology, Moffitt Cancer Center, Tampa, Florida.

Two cases of tall cell carcinoma of breast with reverse polarity (TCCRP) are reported. Case 1: An 86-year-old woman presented with a right breast mass in 2014, which after biopsy was interpreted as intraductal papilloma. Clinical follow-up showed increase in tumor size, and a rebiopsy was performed. The rebiopsy and retrospective review of the biopsy from 2014 showed TCCRP. The lesion was excised with sentinel lymph node biopsy. In the 7-year interval, the lesion only slightly enlarged (from 0.8 to 1.5 cm) without metastasis. Case 2: A 49-year-old woman presented with right breast mammographic focal asymmetry, for which an excision showed TCCRP without lymph node involvement. In both cases, histopathology showed malignant papillary structures composed of tall columnar cells with apical nuclei. Immunohistochemical stains demonstrated an absence of myoepithelial cells. Malignant cells were positive for low–molecular-weight and high–molecular-weight cytokeratin. Hormone receptors were negative/low-positive, and HER2/neu was negative in both cases. Next-generation sequencing identified PIK3CA and IDH2 hotspot mutations. TCCRP is a rare type of invasive breast carcinoma. Given its rarity, there is no standard guideline regarding its treatment. In the first case, the tumor did not metastasize in a 7-year interval between the first biopsy and eventual excision, supporting its indolent behavior. To our knowledge, this is the longest clinical follow-up available for TCCRP (Figure 3.169, A: carcinoma with papillary pattern [×20]; Figure 3.169, B: carcinoma showing tall cell morphology and reversed polarity [×200]; Figure 3.169, C: absence of myoepithelial cells [calponin, ×100]; Figure 3.169, D: positivity for high–molecular-weight cytokeratin [CK5/6, ×100]).

Two Cases of Tall Cell Carcinoma With Reverse Polarity: A Unique Subtype of Invasive Breast Cancer

(Poster No. 170)

Jessica N. Cole, DO1 ([email protected]); Justin Wells, MD1; Rubina Mattu, MD.21Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland; 2Department of Pathology, Joint Pathology Center, Silver Spring, Maryland.

Tall cell carcinoma with reverse polarity (TCCRP) is a distinct subtype of invasive breast cancer histologically resembling tall cell variant papillary thyroid carcinoma. This report of 2 cases includes histologic, immunohistochemical, and molecular findings of this rare carcinoma. Both cases displayed fibrovascular cores lined by tall columnar epithelium with abundant eosinophilic cytoplasm and apically placed nuclei, imparting the reversed polarity. The nuclei were round to oval, and some had nuclear grooves (Figure 3.170, A and B). Both cases were positive for GATA 3 (Figure 3.170, C) and CK 5/6 (Figure 3.170, D) and negative for thyroid markers TTF-1 and thyroglobulin. Myoepithelial markers (p63 and SMMHC), ER, PR, and HER2 were negative. Molecular studies done in 1 of the cases showed IDH2, PIK3CA, and NOTCH1 mutations. TCCRP is an invasive breast cancer with an indolent course. The differential includes metastatic papillary thyroid carcinoma and breast papillary lesions including solid papillary carcinoma, encapsulated papillary carcinoma, and intraductal papilloma with usual ductal hyperplasia. Despite histologic similarities with papillary thyroid cancer, this malignancy neither exhibits the immunohistochemical profile of papillary thyroid cancer nor harbors the typical BRAF, RET/PTC mutations. The distinct reverse polarity of the nuclei is not seen in any of the breast lesions on the differential, and these can also be differentiated with ER, CK 5/6, and myoepithelial markers. TCCRP should be considered in the differential diagnosis for a triple-negative invasive breast cancer presenting with bland histologic features. The diagnosis can be confirmed by molecular studies for IDH2 hot spot mutations, which are present in most cases.