Abstracts and Case Studies From the College of American Pathologists 2022 Annual Meeting (CAP22) Open Access

(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 1}Department 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.

(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.

(Poster No. 3)

Danielle R. Petty, DO¹ ([email protected]); Omer A. Hassan, MD²; Wencheng Li, MD.^{2 1}Department 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.

(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.

(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.

(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.

(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.

(Poster No. 8)

Cherry Pun, MD¹ ([email protected]); Hala Faragalla, MD, MSc²; Jeffrey Mosko, MD, MSc³; Catherine Streutker, MD, MSc.^{2 1}Department 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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(Poster No. 28)

Kusum L. Sharma, MBBS¹ ([email protected]); Ravi B. Singh, MBBS²; Xiaofei Zhang, MD, PhD.^{1 1}Department 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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(Poster No. 38)

Benjamin Gertsen, MD¹ ([email protected]); Tom C. DeRoche, MD²; Aaron R. Huber, DO.^{1 1}Department 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.

(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.

(Poster No. 40)

Xia Qian, MD, PhD¹ ([email protected]); Jinping Lai, MD, PhD.^{2 1}Department 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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(Poster No. 63)

Macy Cummins, BA¹ ([email protected]); Natalie Bhesania, MD²; Neha Varshney, MD.^{3 1}School 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.

(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.

(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.

(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.

(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.

(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).

(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.

(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 1}Department 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).

(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.

(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.

(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.

(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 1}Department 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.

(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.

(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.

(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.

(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.

(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.

(Poster No. 80)

Mark W. McNeely, MD¹ ([email protected]); Yang Zhang, MD.^{2 1}Department 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.

(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.

(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 1}Medical 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.

(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.

(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.

(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.

(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.

(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.

(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.

(Poster No. 89)

Rachel Whitehair, MD¹ ([email protected]); Nadine Aguilera, MD¹; Patcharin Pramoonjago, PhD.^{2 1}Department 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.

(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).

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(Poster No. 101)

Saman S. Karimi, MD, MS¹ ([email protected]); Victoria Angelova, MD²; Shiraz Fidai, MD.^{2 1}Department 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).

(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.

(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.

(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.

(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.

(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 MYD88^L265P-mutated CD5⁺ and/or CD10⁺ LPL.

Design: A 5-year archive search revealed 8 CD5⁺ and/or CD10⁺ MYD88^L265P 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.

(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.

(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).

(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.

(Poster No. 110)

Farshid Kashef, MD, MS¹ ([email protected]); Liang Ding, MD, PhD¹; Sharmila Ghosh, MD¹; Kai Fu, MD, PhD²; Aftab Lalarukh, MD.^{1 1}Department 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.

(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.

(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.

(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.

(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.

(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).

(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.

(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.

(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.

(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 1}Department 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.

(Poster No. 120)

Anup Jnawali, MD¹ ([email protected]); Jacob Bledsoe, MD.^{2 1}Department 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.

(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.

(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.

(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.

(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.

(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.

(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 1}Department 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.

(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.

(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.

(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.

(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 1}Department 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.

(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.

(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.

(Poster No. 133)

Zach Chelsky, DO¹; Meghan White, MD¹ ([email protected]); Amanda Wheeler, MLS²; Richard Hammer, MD¹; Katsiaryna Laziuk, MD.^{1 1}Department 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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(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.

(Poster No. 161)

Matthew C. Donald, BS¹ ([email protected]); Anne C. Kane, MD²; Varsha Manucha, MD.^{3 1}School 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.

(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.

(Poster No. 163)

Christina H. Wiedmer, MD¹ ([email protected]); Kristine Vo, BS²; Kurtis Young, BS²; Daniel Alam, MD.^{3 1}Department 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.

(Poster No. 164)

Tanya Shenoy, BS¹ ([email protected]); Varsha Prakash, MD²; Varsha Manucha, MD.^{2 1}School 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.

(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.

(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.

(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.

(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.

(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.

(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 1}Department 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.

(Poster No. 171)

Yuanzhe Zhu, MBChB¹ ([email protected]); Samantha Jakuboski, BS²; Elnaz Panah, MD¹; Swati Mehrotra, MBBS, MD¹; Vijayalakshmi Ananthanarayanan, MBBS, MD.^{1 1}Department 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.

(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.

(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.

(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.

(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.

(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).

(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.

(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.

(Poster No. 8)

Michelle Lin, MD¹ ([email protected]); Michael Deavers, MD¹; Elvio Silva, MD.^{2 1}Department 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.

(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.

(Poster No. 10)

Tanya R. Lindenmuth, DO, MS¹ ([email protected]); Rubina H. Mattu, MD.^{2 1}Department 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.

(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.

(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.

(Poster No. 13)

Saman S. Karimi, MD, MS¹ ([email protected]); Victoria Angelova, MD.^{2 1}Department 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).

(Poster No. 14)

Allen C. Omo-Ogboi, MD¹ ([email protected]); Michael T. Deavers, MD²; Kathleen M. Schmeler, MD³; Nidhi Tandon, MD, FRCPath.^{1 1}Department 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.

(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.

(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.

(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.

(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.

(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.

(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).

(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.

(Poster No. 22)

Obianuju M. Anelo, MD¹ ([email protected]); Jorge Solares, MSc²; Joel F. Gradowski, MD³; Farhan Khan, MD.^{3 1}Department 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.

(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.

(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.

(Poster No. 25)

Hanae Benchbani, MD¹ ([email protected]); Tara Krishnan, BA²; Emma M. Gloe, BS²; Soheila Hamidpour, MD.^{1 1}Department 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.

(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.

(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.

(Poster No. 28)

Javier A. Baena-Del Valle, MD¹ ([email protected]); Rocio López-Panqueva, MD¹; Paula A. Rodriguez-Urrego, MD.^{2 1}Department 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.

(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.

(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).

(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.

(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.

(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.

(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.

(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 1}Department 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.

(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.

(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.

(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.

(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.

(Poster No. 40)

Amy L. Austin, MD¹ ([email protected]); Michael C. Royer, MD²; Jill I. Allbritton, MD.^{2 1}Department 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.

(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.

(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.

(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.

(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.

(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%).

(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.

(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).