Abstracts and Case Studies From the College of American Pathologists 2024 Annual Meeting (CAP24) Open Access

(Poster No. 1)

Muhammad Abdulwaasey, MBBS¹ ([email protected]); Darshil Patel, MBBS²; Jennifer Vazzano, DO, MS.^{1 1}Department of Pathology, Ohio State University, Columbus; ²Department of Pathology, Rush University, Chicago, Illinois.

Intraductal papillary neoplasm (IPN) of the liver and bile ducts is a premalignant condition marked by intraductal papillary or villous growth of biliary epithelium. Although its etiology is often elusive, potential association with clonorchiasis has been seen. IPN exhibits a propensity to spread preferentially along the biliary epithelium, with infiltration into the duct wall in advanced stages. We report a 71-year-old woman with a complex medical history including celiac disease and breast cancer who presented with abdominal pain and constipation. A CT scan revealed multiple cystic lesions, notably a progressively dominant lesion in the left hepatic lobe. A robotic left hepatectomy was performed. Grossly it showed a tan-gray, smooth, serosal surface and a visible 7.0 × 5.2 × 4.5-cm cyst (Figure 1.1, A) with a roughened texture. The cut section showed a fibrous cyst wall and brown fibrous material. Histologically, IPN showed papillary structures with fine fibrovascular cores expressing oncocytic epithelial cells and lacking ovarian-type stroma (Figure 1.1, B and C). Hepatocyte immunostaining was positive in the lesional cells (Figure 1.1, D), Ki-67 stain showed a low proliferative index (10%), and p53 staining showed wild-type staining. Thus, the diagnosis of intraductal papillary neoplasm of bile duct (IPNB) with oncocytic features and low-grade dysplasia was rendered. This case is interesting in terms of its rarity, and the mainstay of treatment is surgical resection, so precise preoperative evaluation is essential. A multifaceted approach is important in diagnosis and creating an optimal treatment plan for patients with IPNB.

(Poster No. 2)

Yuqing Cheng, MD, MSc¹; Xinwen Zhang, MD³; Ting Li, MD⁴; Min Lin, MD, PhD²; Xiaoli Zhou, MD, PhD¹; Qin Huang, MD, PhD⁵ ([email protected]). Departments of ¹Pathology and ²Gastroenterology, the Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, China; ³Graduate School, Dalian Medical University, Changzhou, China; ⁴Graduate School, Nanjing Medical University, Nanjing, China; ⁵Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.

Context: α-Fetoprotein (AFP)–producing colorectal adenocarcinoma (AFPCRA) is rare and its clinicopathologic features and prognosis remain unclear.

Design: Surgically resected colorectal adenocarcinoma (CRA) cases with elevated preoperative serum AFP levels were enrolled as the study group over the study period from 2011 to 2021. Exact sex-, age-, and stage-matched cases served as the control group in a ratio of 1:2. The study group was further divided into low and high AFP-level subgroups at the cutoff of 8.4 ng/mL. Clinicopathologic features and prognosis were compared between AFPCRA and control groups as well as 2 AFPCRA subgroups.

Results: The study group was composed of 49 (2.0%) consecutive APFCRA patients among 2389 CRA cases. No significant difference was found between AFPCRA and control groups in tumor location, size, lymphovascular or perineural invasion, pT or pN stage, PD-L1 immunopositivity, or immunohistochemical mismatch repair protein expression. However, compared to the control group, the AFPCRA group showed a significantly higher frequency of extramural venous invasion, intermediate-/high-grade tumor budding, poor tumor differentiation, distant metastasis, and hepatoid carcinoma. The 5-year overall survival rate was significantly lower in the AFPCRA group (69.2%) than in the control group (87.2%) (P = .002; Table). Compared to the low-AFP-level subgroup, the high-AFP-level subgroup showed a significantly higher prevalence in the left side of the colon, but no significant difference in other clinicopathologic features.

Conclusions: AFPCRA is a rare subtype of CRA associated with aggressive behavior and poor prognosis. Our findings provide pathologic evidence for use of serum AFP testing for screening and surveilling CRA patients.

(Poster No. 3)

Tomilola Agboola, MD ([email protected]); Louis Dehner, MD; Mai He, MD, PhD. Department of Pathology & Immunology, Washington University, Saint Louis, Missouri.

Context: Graft-versus-host disease (GVHD) and posttransplant lymphoproliferative disorder (PTLD) are serious posttransplant complications. This study examined gastrointestinal (GI) pathology in pediatric posttransplant recipients to establish correlations between transplant type and these complications at different sites.

Design: This is a retrospective chart review of pediatric GI biopsies from a single institution with clinical history of hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) from 01/01/1990 to 09/01/2017. Relevant clinical information was obtained, including medication history, such as mycophenolate (MMF) use. The slides were again reviewed for features of GVHD or MMF use.

Results: Chart search revealed 82 HSCT and 132 SOT recipients, with an age range of 5 weeks to 29 years. The frequencies of GVHD post-HSCT and SOT were 46% (38 of 82) and 0.7% (1 of 132), respectively (P < .05). One case (0.7%, 1 of 132) of SOT showed MMF changes. The frequencies of PTLD post-HSCT and SOT were 1.2% (1 of 82) and 5.3% (7 of 132) (P = .16). The colon was the most frequent site for GVHD (56.9%; P = .001), followed by the rectum (52.9%; P = .003). Severe GVHD (grade IV) occurred mostly in the colon (50%; 4 of 8). GVHD grade I was most frequent (47%; 18 of 38). Posttransplant lung, liver, and heart had equal distribution of PTLD (28.6%; 2 of 7).

Conclusions: GI biopsies from about half the HSCT recipients demonstrated features of GVHD affecting mostly the colon and/or rectum. Grade IV GVHD was infrequent but occurred predominantly in the colon. PTLD was rare after SOT and SCT transplantations. Regardless of the transplanted organ, SOT equally predisposed to PTLD.

(Poster No. 4)

Konara Mudiyanselage Maduhasi Bandara, MD ([email protected]); Valerica Mateescu, MD; Amira Hassan, MD. Department of Pathology, University of Missouri Kansas City.

Context: Appendiceal neoplasms are rare, comprising 0.4% to 1% of gastrointestinal malignancies. Most symptomatic tumors present as appendicitis, while some may be encountered incidentally during acute or elective abdominal surgeries. The aim of the study was to audit our institution to provide insight into tumor characteristics and prognosis.

Design: A retrospective analysis was performed using electronic medical records from a single hospital institution. Twenty-six cases of incidental appendiceal malignancies were extracted from 1600 appendectomies performed between 2007 and 2023.

Results: In 20 cases, patients were admitted with acute appendicitis symptoms; 3 cases were diagnosed intraoperatively while performing other surgeries; 1 case was diagnosed after performing routine appendectomy for an ovarian mass; and 2 cases were suspected during screening colonoscopy. The most common appendiceal neoplasm was well-differentiated neuroendocrine tumor (38.5%) followed by low-grade appendiceal mucinous neoplasm (30.8%), goblet cell adenocarcinoma (11.5%), adenocarcinoma (11.5%), small cell lymphoma/chronic lymphocytic leukemia (3.8%), and low-grade serrated dysplasia (3.8%). Histopathologic characteristics, pTNM stage, and management are included in the Table. Patients with stage pT3 or pT4 and selected patients with stage pT2 with positive margins underwent right hemicolectomy. Overall, 83% of patients are alive, while 8.3% have succumbed to other illnesses; survival data are unknown for 8.3%.

Conclusions: Prognosis depended upon stage and tumor grade. Appendiceal adenocarcinomas and goblet cell adenocarcinomas showed more aggressive behavior, and right hemicolectomy did not improve survival in those patients. No recurrence was seen in any appendiceal tumor in patients continuing care at our institution. Larger cohort studies are warranted to further explore appendiceal neoplasms.

(Poster No. 5)

Dr Prachi, MD ([email protected]); Hema M. Aiyer, MD. Department of Surgical Oncopathology, Dharamshila Narayana Superspeciality Hospital, New Delhi, India.

Paragangliomas are rare tumors that arise from the chromaffin cells. They are generally considered to be benign in nature, with malignant carotid body tumor being infrequent. They rarely produce local or distant metastasis, with liver being the rarest distant site of metastasis. We report this rare entity in a 19-year-old man who presented with vomiting, fever, and abdominal pain. On examination he had right-sided neck swelling and hepatomegaly. Contrast-enhanced magnetic resonance imaging (CEMRI) of the face and neck revealed heterogenous soft tissue lesion in the right carotid and parapharyngeal spaces with multiple enlarged cervical lymphadenopathies. CEMRI of the abdomen showed a large heterogeneously enhancing solid mass in the liver suggestive of neoplastic etiology (Figure 1.5, A). Ultrasound-guided biopsy of the liver mass was done for histopathologic correlation. Microscopically, nests of pleomorphic polygonal cells having abundant granular cytoplasm infiltrating the liver parenchyma were seen, and findings were suggestive of neuroendocrine neoplasm (Figure 1.5, B). On immunohistochemistry, neoplastic cells were immunoreactive for INSM-1, synaptophysin, CD56 (Figure 1.5, C), and SSTR2A, with intact cytoplasmic expression in SDH-A and loss of cytoplasmic expression in SDH-B (Figure 1.5, D). Morphologic and immunohistochemistry features were consistent with metastatic SDH-deficient paraganglioma. The patient was given tablet sunitinib, and germline mutational studies were advised because of increased propensity of developing multicentric paragangliomas and pheochromocytomas/gastrointestinal stromal tumor. This case creates an awareness for physicians regarding how paragangliomas metastasize to liver by providing an insight into the diagnostic workup with neuroendocrine markers and molecular immunohistochemical stain to obtain a definitive diagnosis.

(Poster No. 6)

Yazan Al-Othman, MD ([email protected]); Barbara L. Pruetz; Zhenhong Qu, MD; Ping Zhang, PhD, MD; Aqsa Nasir, MD. Department of Pathology, Corewell Health William Beaumont Oakland University Hospital, Royal Oak, Michigan.

Context: Upregulated expression of carbonic anhydrase 9 (CA9) has been used to detect clear cell renal cell carcinoma. However, CA-9 immunostaining is normally present in intrahepatic and intrapancreatic bile ducts and gastrointestinal mucosa. This study seeks to determine if the loss of CA9 expression can correlate with the loss of SMAD4 in pancreatic adenocarcinoma.

Design: SMAD4 and CA9 were immune stained in 26 normal pancreatic tissues and 116 pancreatic ductal carcinomas using tissue microarray sections. The nuclear staining of SMAD4 and membranous staining of CA9 were assigned an intensity from 0 to 4+.

Results: Benign pancreatic ducts revealed positive CA9 staining along the cell membranes and positive nuclear staining for SMAD4. The 116 pancreatic cancer cases included 27 well-differentiated, 50 moderately differentiated, and 39 poorly differentiated ductal adenocarcinomas. SMAD4 staining was lost in 113 cases, 3 cases showed a partial loss, and 3 cases showed retained staining. Eighty-nine cases (75%) of pancreatic ductal adenocarcinoma were positive for CA-IX and 30 cases (25%) were negative (Figure 1.6, A–D). The majority (17 of 30; 57%) of the negative cases were poorly differentiated.

Conclusions: Our data indicate that CA9 expression can be lost in some pancreatic adenocarcinoma cells. Although the etiology of the phenomenon is unclear, CA9 loss appears to be a useful index to support the diagnosis of pancreatic adenocarcinoma in small biopsies, somehow parallel to the SMAD4 losses in the tumor.

(Poster No. 7)

Ali Mokhtari, MD¹ ([email protected]); Wei Chen, MD²; Raul S. Gonzalez, MD.^{1 1}Department of Pathology, Emory University, Atlanta, Georgia; ²Department of Pathology, Duke University Health System, Durham, North Carolina.

Context: Lymphocytic colitis (LC) is histologically diverse, with various potential causes, and identifying the cause based on morphology is challenging.

Design: We reviewed colon biopsies labeled as typical LC or LC-pattern injury, excluding cases with additional significant histopathologic findings. Recorded data included patient demographics, symptoms, colonoscopy findings, clinical impression of LC etiology, and histologic parameters. Comparisons were made between patients with and without diarrhea, abnormal mucosa on colonoscopy, and an apparent cause for LC.

Results: We reviewed 76 cases (59 women, 17 men) with a mean age of 57 (range, 18–84 years). Diarrhea history was present in 63 cases (83%), normal colonoscopy mucosa in 66 (87%). Most lacked LC etiology (64; 84%); others had LC-pattern injury secondary to various causes: drugs (5), Crohn (3), immunodeficiency (2), C difficile infection (1), and autoimmune enteropathy (1). Mean maximum surface intraepithelial lymphocyte (IEL) count was 29 (range, 7–60; Figure 1.7); increased surface IELs diffuse in 31 (41%). Mean maximum crypt IEL count was 15 (range, 4–40); increased crypt IELs diffuse in 23 (30%). Lamina propria (LP) expansion was present in 19 (25%), LP acute inflammation in 7 (9%). Patients with a cause for LC were more likely to exhibit acute LP inflammation (33% versus 5%; P = .01; Figure 1.7) and marginally lower mean maximum surface IELs (24 versus 30; P = .049).

Conclusions: Most LC cases are idiopathic, though etiology assessment may lack robustness. Acute inflammation in LC-pattern injury biopsies may indicate a nonidiopathic cause. Patient symptoms and colonoscopy findings don’t aid in this determination.

(Poster No. 8)

Isairis Peralta, MD ([email protected]); Maria Mayorga, MD; Alan Grindstaff, MD; Laurentia Nodit, MD. Department of Pathology, University of Tennessee Graduate School of Medicine, Knoxville.

Context: Recent studies suggest that obese patients have a higher incidence of gastrointestinal stromal tumors (GISTs) compared to the general population.

Design: Retrospective search of diagnosis of GIST (January 2000 through December 2020).

Results: One hundred forty-eight cases were analyzed (72 males [48.6%] and 76 females [51.4%]); median age was 66 years. Body mass index (BMI) of the patients was categorized according to their nutritional status. The prevalence of obesity in Tennessee is 38.9% in all adults and 35% in White adults. The prevalence of obesity in all GIST cases reviewed was 43.8% (n = 65), higher than the general population, and obesity and overweight combined was 76.2%. GISTs were incidentally found in 4 patients who underwent sleeve gastrectomy for weight loss. The mean preoperative BMI was 43.85 kg/m². A malignant tumor was identified in a patient with a BMI of 25.7 kg/m², and tumors resistant to therapy were found in 2 cases (BMI 35 and 26 kg/m²). Two cases were resistant to treatment and had recurrence to a different location (BMI 34 and 42 kg/m²). C-kit mutation was detected in 8 cases (5 obese, 3 overweight). Metastatic disease was found in 11 patients, of which 5 were overweight, 3 were obese, and 3 had normal weight. Multifocal lesions were found in 2 obese and 2 overweight patients.

Conclusions: At our institution, GISTs are more prevalent in obese (43.8%) and overweight (32.4%) patients compared to the state’s general population. Obese and overweight patients also had more tumor recurrence, treatment resistance, C-kit mutations, and metastatic and multifocal disease.

(Poster No. 9)

Payu Raval, MD¹ ([email protected]); William Watkin, MD.^{2 1}Department of Pathology, University of Chicago (NorthShore), Evanston, Illinois; ²Department of Pathology, NorthShore University Hospital, Evanston, Illinois.

Solid-tubulocystic intrahepatic cholangiocarcinoma is a recently described intrahepatic cholangiocarcinoma variant with distinct histomorphology and inhibin positivity. We present an example arising in a 45-year-old man with a review of the recent literature. A 5.7-cm solitary liver mass was incidentally discovered during cardiac imaging without evidence of disease elsewhere. A subsequent liver resection revealed a well-circumscribed, nonencapsulated, solid, tan-white, lobulated mass with focal necrosis in a background of unremarkable liver parenchyma (Figure 1.9, A). Histologic sections showed variably sized solid nests of epithelial cells with occasional tubules juxtaposed with areas of distinct gland formation (Figure 1.9, C, D). There was mild cytologic atypia and areas of necrosis. On IHC, the tumor cells had CK7, MOC31, and inhibin (patchy) expression (Figure 1.9, B); arginase-1, CDX2, SATB2, TTF-1, CK20, PASD, trypsin, synaptophysin, chromogranin, p40, and CK5/6 were negative. Next-generation sequencing was negative for usual mutations seen for intrahepatic cholangiocarcinoma. These histopathologic and immunohistochemical features are characteristic of the solid-tubulocystic variant of intrahepatic cholangiocarcinoma. Sixteen described cases of this entity in the literature have occurred, predominantly (82%) in females aged 15 to 54, with tumors ranging from 6.9 to 32 cm. In addition to the solid gross appearance, tumors can be multicystic spongiform with hemorrhage and necrosis. A novel recurrent gene fusion NIPBL::NACC1 has been described in 4 cases; the target is not available commercially and was not performed in our case. Recurrence and metastasis have been observed in some patients. Differential diagnosis considerations include sex cord stromal tumors and well-differentiated neuroendocrine tumors. Our patient received 6 months of adjuvant capecitabine, without evidence of the disease 21 months after the initial diagnosis.

(Poster No. 10)

Liubou Kazacheuskaya, MD ([email protected]); James Cotelingam, MD; Ashley Flowers, MD; Kshitij Arora, MD. Department of Pathology, Louisiana State University Health Shreveport.

Context: Hemorrhoids, a common anorectal condition, involve abnormal expansion of anal veins and connective tissue changes. Studies report unexpected histologic findings in 2.15% to 4.5% of hemorrhoidectomy cases, including malignancies (0.16%–1.9%). This study assessed routine histologic examination necessity for hemorrhoid specimens and identified unexpected findings in a high-risk population at a southeastern US teaching hospital.

Design: A retrospective review (January 2010 to October 2023) of pathology specimens labeled “hemorrhoids” was conducted. Exclusions were cases with suspected malignancy. Three pathologists independently reviewed cases.

Results: Results from 361 patients (male to female ratio, 1:1; median, age 46.5 years) showed incidental findings in 41 cases (11.36%). These included low-grade anal intraepithelial lesion (LG-AIN; 1.11%), high-grade anal intraepithelial lesion (HG-AIN; 3.6%), acrochordon (1.94%), squamous cell carcinoma (SCC; 1.39%), and hyperplastic polyp (1.94%; Table). Actionable findings (LG-AIN, HG-AIN, SCC), and tubulovillous adenoma (TVA) were seen in 23 cases (6.37%). Patients with incidental LG-AIN, HG-AIN, and SCC had median ages of 45.5, 49.85, and 43.6 years, respectively. p16 immunohistochemistry was used in 3.04% of cases. The patients were divided into 2 groups: one with high-risk behavior (eg, men who have sex with men, had multiple sexual partners, history of STDs, and HIV-positive individuals) and another without.

Conclusions: Twenty-three cases (6.37%) revealed significant findings such as LG-AIN, HG-AIN, SCC, and TVA. This rate exceeds previous literature reports because of the high-risk patient population within our demographic region and the use of p16 immunohistochemistry. The histopathologic analysis of hemorrhoidectomy specimens has uncovered previously undiagnosed premalignant and malignant conditions, impacting patient care. Continuous microscopic assessment is vital for prompt treatment.

(Poster No. 11)

Abdol Aziz Ould Ismail, MD ([email protected]); Bryceton G. Thomas, MD; Peter P. Seery, PA (ASCP); Juliana Castellano, MD, MDHS, PhD; Louis J. Vaickus, MD, PhD; Mikhail Lisovsky, MD, PhD; Yujun Gan, MD, PhD; Ryland L. Richards, MD; Xiaoying Liu, MD; Charles I. Brown, MD; Michael L. Baker, MD; Bing Ren, MD, PhD. Department of Pathology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire.

Context: Understanding seasonal patterns of Helicobacter pylori infection could help identify potential factors that influence its transmission and prevalence. New Hampshire’s pronounced seasonal variations could influence factors ranging from human behaviors to environmental conditions. As such, identifying seasonal trends would be valuable for public health authorities and healthcare providers to organize resources and efforts to reduce the impact of H pylori–related diseases.

Design: Gastric biopsies taken between November 2022 and October 2023 at Dartmouth Hitchcock Medical Center in Lebanon, New Hampshire, were included in this study. H pylori infection was confirmed on H&E-stained slides and/or immunostains. The χ² test was used for statistical analysis.

Results: A total of 2795 gastrointestinal biopsies were investigated in this study; 184 (6.6%) were positive for H pylori, with 101 of them from females (55.4%). Patients in the 18–60 age group were most frequently tested (Table). The data indicate a seasonal trend in positivity rates, with patients <18 years old seeing higher rates in the winter and fall, the 18–60 age group positivity rate more pronounced in the summer and fall, and those aged >60 showing relatively even rates throughout the year. The χ² test identified a statistically significant difference between males and females during the summer of 2023 (P = .03; F = 4.3).

Conclusions: We revealed notable seasonal variation in H pylori. Specifically, the summer season showed a statistically significant gender-related difference in positive rates, emphasizing the need for targeted public health strategies considering seasonal and gender factors to combat H pylori–related diseases.

(Poster No. 12)

Sara Salehiazar, MD ([email protected]); Komeil Mirzaei Baboli, MD; Amani Minja, MD; Sava Grujic, MD. Department of Pathology, Harbor-UCLA Medical Center, Torrance, California.

MGNETs are extremely rare entities that present as a mass, mostly in the gastrointestinal tract, and are histologically described as clear cell sarcoma-like tumors. However, they lack IHC reactivity for melanocytic markers. We present a case with multiple negative biopsies in a patient who underwent resection. This case involves a 24-year-old man with progressive fatigue, weight loss, and low hemoglobin levels that prompted investigations including endoscopies and colonoscopies because of suspected malignancy to evaluate the source of bleeding, which was nonevident. Given the concern for malignancy, he underwent a PET/CT, which was negative except for focal wall thickening of the jejunum. Segmental small intestinal resection was performed. Gross examination showed an annular mass (5 cm) involving the full thickness of the jejunal wall (Figure 1.12, A). On cross-sectioning the mass was solid tan-white, and the mucosal surface was unremarkable. Histology showed round epithelioid cells divided by fibrovascular bands. The cells had large round nuclei with clear cytoplasm (Figure 1.12, B). Mitotic figures were inconspicuous. Immunohistochemistry showed positivity for S100 and SOX10 (Figure 1.12, C) and patchy membranous staining with CD56, but negativity for melanocyte-specific markers, SALL4, and CD117. FISH study revealed EWSR1(22q12.2) rearrangement (Figure 1.12, D). GNETs are rare malignant tumors that can be mistaken histologically for other nonepithelial gastrointestinal tumors. Awareness of their existence and diagnostic criteria is necessary to avoid misdiagnosis, particularly as a GIST, clear cell carcinoma, or peripheral nerve sheath tumors, as these tumors can only involve the bowel wall with a normal mucosa appearance on endoscopy.

(Poster No. 13)

Amanda C. Gibbs, MD ([email protected]); Edward B. Stelow, MD; Kristen A. Atkins, MD. Department of Pathology, University of Virginia, Charlottesville.

Context: SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily A, member 4–deficient (SMARCA4-d) tumors are rare, clinically aggressive entities. The few reported cases of SMARCA4-d gastroesophageal carcinoma (GEC) have not responded to conventional chemotherapy, necessitating alternative therapeutic approaches. Currently, human epidermal growth factor receptor 2 (HER2) is the only targetable therapeutic biomarker in advanced GEC. To our knowledge, HER2 protein expression and gene amplification in SMACA4-d GEC has not been explored.

Design: GECs with loss of SMARCA4 expression by immunohistochemistry (IHC) were included. HER2 expression and amplification were evaluated by IHC using Ventana 45B antibody and by in situ hybridization (ISH) using Ventana INFORM HER2 Dual ISH DNA probe cocktail. In accordance with current College of American Pathologists GEC HER2 testing guidelines, IHC and ISH were scored using Ruschoff/Hoffman criteria.

Results: Six cases of SMARCA4-d GEC were included in our study. HER2 IHC and ISH were attempted in all cases. HER2 gene amplification was seen in 4 cases. Of these, IHC was positive in 1 case, equivocal in 1 case, negative in 1 case, and unsatisfactory for interpretation in 1 case. Both cases without gene amplification were HER2 IHC negative. Demographics, IHC results, and ISH results are presented in the Table.

Conclusions: We demonstrate HER2 protein overexpression and gene amplification in 20% and 66% of SMARCA4-d GECs, respectively. Our results suggest anti-HER2 therapy may be considered as an alternative therapeutic avenue in these aggressive carcinomas. Importantly, overexpression and amplification are not always concordant, bringing into question the utility of current HER2-testing guidelines in this context.

(Poster No. 14)

Samantha K. Huether, MD ([email protected]); Cristina Fernandez Gonzalez de la Vega, MD; S. Krisztian Kovacs, MD; Whayoung Lee, MD. Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee.

Context: Granular cell tumors (GCTs) and schwannomas are rare mesenchymal tumors in the gastrointestinal (GI) tract with schwannian derivation. When histomorphologic features are ambiguous, distinguishing between them becomes challenging, as both tumors are S100 positive.

Design: Six cases of GCT (all from the GI tract) and schwannomas (1 from GI tract and 5 from soft tissue) were studied. S100 and inhibin α immunohistochemical stains were applied to all cases, and lesion location and histopathology were recorded.

Results: GCTs most commonly originated from the esophagus (4 of 6; 67%) as small nodules. Histologically, GCTs (Figure 1.14, A, B) exhibited either a mixed (spindle and epithelioid, 2 of 6; 33%) or epithelioid (4 of 6; 67%) pattern, characterized by amphophilic granular cytoplasm (6 of 6; 100%). Characteristic features, such as infiltrative growth (4 of 6; 67%) or overlying epithelial change (4 of 6; 67%), were seen in a subset of the cases. Circumscription (1 of 6; 16.7%) and lymphoid cuff (2 of 6; 33%) were also observed. One case of GI schwannoma was found in the sigmoid colon as a polyp, displaying epithelioid cells with abundant amphophilic cytoplasm and an infiltrative border. No Verocay bodies or lymphoid cuffs were observed. Soft tissue schwannomas were mostly spindled (4 of 5; 80%) and more likely to display characteristic features such as Verocay bodies. All GCTs showed diffuse positivity for both S100 (6 of 6; 100%; Figure 1.14, C) and inhibin α (6 of 6; 100%; Figure 1.14, D). All schwannomas were positive for S100 (6 of 6; 100%) but negative for inhibin α (0 of 6; 0%).

Conclusions: Inhibin α serves as a sensitive and specific marker for distinguishing between GCT and schwannoma, particularly in cases where morphologic features are ambiguous.

(Poster No. 15)

Faryal Shoaib, MD, MBBS ([email protected]); Kshitij Arora, MD. Department of Pathology, LSUHSC, Shreveport, Louisiana.

Blue nevus (BN) is a benign pigmented cutaneous lesion caused by abnormal migration of neural crest melanocytes in the dermis. Extracutaneous BN is infrequent, and rectal BN is even rarer. Only 4 cases have been reported in the literature so far. The differentiation between BN and desmoplastic melanoma is challenging, particularly in small mucosal biopsies. Desmoplastic melanoma is characterized by atypical features including enlarged nuclei, hyperchromasia, and high mitotic activity. Immunohistochemistry (IHC) can be notably helpful to distinguish between the 2. Desmoplastic melanoma typically expresses only a few melanocytic markers, S100 and SOX10, and rarely expresses HMB45 and Mart 1. In contrast, blue nevi strongly express HMB45 and Mart 1 and have a low Ki-67 index. We present a case of a 56-year-old man with no significant medical history. Screening colonoscopy revealed abnormal mucosa in the rectum with hyperpigmentation at the level of the anal verge (Figure 1.15, A). A biopsy was performed, and the histologic examination revealed pigmented spindle-shaped cells in an infiltrative pattern in the lamina propria (Figure 1.15, B). IHC showed positive results for SOX10, HMB45, and Mart 1 and was negative for PRAME (Figure 1.15, C, D). Ki-67 indicated a proliferation rate of only 1%. Based on the IHC profile and low Ki-67, spindle cell–type BN was diagnosed. BN, a benign melanocytic proliferation, warrants attention at the extracutaneous site. Awareness of these lesions in the GI tract is crucial. Given the rareness of only 4 reported cases in rectal mucosa, it is essential to remain informed about this entity.

(Poster No. 16)

Nhat-Phuong Nguyen, MD ([email protected]); Abdelsalam Sharabi, MD. Department of Pathology and Laboratory Medicine, Icahn School of Medicine at Mount Sinai West/Morningside, New York, New York.

This study reports the first documented case of concurrent human cytomegalovirus (CMV) infection and intracholecystic papillary neoplasm with high-grade dysplasia in the gallbladder. While CMV, also known as herpesvirus 5, commonly targets the gastrointestinal tract, gallbladder infection has not been reported in the literature. We present a 51-year-old HIV-positive woman with a history of TB and cryptococcal meningitis exhibiting symptoms of diffuse abdominal pain, diarrhea, and intermittent fever. Magnetic resonance imaging revealed a distinctive enhancing gallbladder mass (Figure 1.16, A), measuring 3.0 × 1.6 cm, consistent with neoplasia. The patient underwent cholecystectomy with intraoperative diagnosis of adenocarcinoma in a background of hyperplasia and high atypical cells at the cystic duct margin (Figure 1.16, B). Permanent sections confirmed CMV immunostaining positivity in atypical cells on the cystic margin (Figure 1.16, C), indicating viral effects rather than dysplastic changes. While the primary tumor exhibited small foci of high-grade dysplasia involving Aschoff-Rokitansky sinuses, there was no definite evidence of invasion. Widespread CMV effects throughout the gallbladder complicated the interpretation of dysplastic and invasive processes (Figure 1.16, D), potentially accounting for the discrepancy between frozen and permanent sections. This case underscores the imperative consideration of viral etiologies in gallbladder pathology, enhancing our comprehension of CMV tropism. Importantly, it highlights the necessity of recognizing CMV effects that may mimic dysplastic processes, especially in intraoperative consultation settings.

(Poster No. 17)

Molly Timmerman, DO ([email protected]); Shaima Elgenaid, MD; Lewis Hassell, MD. Department of Pathology, University of Oklahoma, Oklahoma City.

Our patient is a 53-year-old woman with hilar cholangiocarcinoma who subsequently underwent neoadjuvant chemotherapy and radiotherapy and was later put on the liver transplant list. A donor liver was procured from a 21-year-old female donor who died in sickle cell crisis. The patient continues to experience stable liver function tests, bilirubin, and alkaline phosphatase, suggesting tentative success with this graft. On day 0, the transplant liver displayed telltale signs of sickle cell disease, such as sickled cells with hypereosinophilic red blood cells (RBCs), sinusoid congestion, Kupffer cell erythrophagocytosis, and hemosiderosis. Mild periportal fibrosis was also seen. However, a day 5 posttransplant biopsy revealed cleared-out sinusoids without sickled cells and no erythrophagocytosis, cholestasis, or endotheliitis. There was mild residual hemosiderin within the Kupffer cells and mild mixed periportal inflammation consistent with day 5 posttransplant biopsy. Histologically, important features that can commonly be seen on liver biopsy in a patient with sickle cell disease include sickled RBCs, congested sinusoids, erythrophagocytosis, hemosiderosis, iron deposition, and Kupffer hyperplasia. Chronic features of sickle cell disease include portal fibrosis, regenerative nodules, and, rarely, cirrhosis. During a sickle cell crisis involving the liver, more necrosis, anoxic injury, peliosis hepatitis, and extramedullary hematopoiesis can be seen. The lack of crisis findings may be explained by the donor’s bilirubin falling to 1.3 from 6.3 and her transaminases decreasing to the 200s from the 400s. While surgical techniques and clinical management continue to improve transplant outcomes, the increased demand for liver transplants emphasizes the importance for physicians to consider more marginal organ donors (Figure 1.17, A–D).

(Poster No. 18)

Whitney Stolnicki, MD ([email protected]); Bang Tang, MD. Department of Pathology, Allegheny Health Network, Pittsburgh, Pennsylvania.

Acinar cell carcinoma is rare, compromising only 1% to 2% of pancreatic exocrine neoplasms. It is extraordinarily rare for acinar cell carcinoma to arise in the stomach, with only 6 other case reports published to date. Our case involves a 72-year-old woman with a past medical history of breast cancer status post partial mastectomy who presented with anemia and melena. Endoscopic ultrasound revealed a single submucosal nodule on the posterior wall of the proximal gastric body, concerning for gastrointestinal stromal tumor. She underwent partial gastrectomy. The excised lesion measured 2.0 cm. Histologic sections revealed monotonous epithelial cells with finely granular eosinophilic cytoplasm, single prominent nucleoli, and brisk mitotic activity, predominantly located in the submucosa. The tumor displayed acinar, solid, and trabecular growth patterns (Figure 1.18, A, B). The histomorphology closely resembled a neuroendocrine neoplasm. Immunohistochemistry was strongly positive for BCL-10 and trypsin. Synaptophysin and chromogranin showed focal staining; CD117 and DOG1 were negative. Considering the histology and immunohistochemistry, a diagnosis of pure pancreatic-type acinar cell carcinoma arising from the stomach was made. We report this case for the rarity of pure pancreatic-type acinar cell carcinoma of the stomach. As a caution, this entity should be considered as a differential diagnosis when encountering a gastric lesion.

(Poster No. 19)

Keri Janowiak, MD, MEd¹ ([email protected]); Ashton A. Connor, MD, PhD²; Brandee A. Price, PhD³; Sadhna Dhingra, MD¹; Mary R. Schwartz, MD¹; Sudha Kodali, MD²; Ashish Saharia, MD²; Milind Javle, MD⁴; R. Mark Ghobrial, MD, PhD²; Mukul K. Divatia, MD.¹ Department of ¹Pathology and Genomic Medicine and ²J. C. Walter Jr Transplant Center, Houston Methodist Hospital, Houston, Texas; ³Department of Molecular Pathology, Caris Life Sciences, Phoenix, Arizona; ⁴Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston.

NIPBL::NACC1 fusion hepatic carcinoma is a newly described entity predominantly affecting young women and described as thyroidlike, solid tubulocystic, and cholangioblastic cholangiocarcinoma (CCA). We present an index case of this entity in a 17-year-old girl with a 26-cm well-circumscribed, solid-cystic mass in a noncirrhotic liver treated with orthotopic liver transplantation. Multiple growth patterns were noted, including sheets and nests with small, complex tubules (Figure 1.19, A, C); trabeculae of polygonal cells resembling hepatocellular carcinoma (HCC) (Figure 1.19, A, D); back-to-back tubules and microcysts resembling thyroid follicles (Figure 1.19, B); and foci of crowded, hyperchromatic primitive-appearing cells. Macro-vascular invasion of the left hepatic vein by tumor thrombus (Figure 1.19, C) was identified grossly in the explanted liver and not seen preoperatively. Tumor cells were strongly and diffusely positive for inhibin (Figure 1.19, D), pan-cytokeratin (CK), and CK19, with moderate CK7 expression and weak, focal synaptophysin positivity. Immunostains for hepatic and other lineage markers (arginase-1, HepPar-1, α-fetoprotein, glypican-3, nuclear β-catenin, chromogranin, SALL4, PAX8, TTF-1, GATA3, CK20, CDX2, HMB45, Melan-A, ER, PR, SOX10, WT1, calretinin, CD117) were negative. Molecular sequencing demonstrated a NIPBL (exon 8)::NACC1 (exon 2) gene fusion. No driver mutations typically associated with CCA or HCC were detected in this otherwise low tumor mutational burden (2 mutations/Mb) and microsatellite-stable case. After 1 year of follow-up, the patient was disease free. This primary hepatic tumor should be categorized separately from CCA and HCC, as it represents a distinct entity because of significant clinicopathologic differences including presentation, morphology, immunohistochemical profile, and molecular features, thus laying the foundation for treatment development based upon elucidation of its molecular biology.

(Poster No. 20)

Hasan B. Aydin, MD¹ ([email protected]); Maria Faraz, MD¹; Noureldien Darwish, MD¹; Anne Chen, MD²; Hwa J. Lee, MD.^{1 1}Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, New York; ²Department of Pathology & Immunology, Washington University School of Medicine in St Louis, Missouri.

Immunotherapy-induced liver injury is usually mild with favorable outcomes. Past reports mention histologic findings including panlobular hepatitis, perivenular infiltrate, and rarely cholestatic injury with possible necrosis. However, certain hepatic comorbidities such as autoimmunity and chronic viral infection are relative (not absolute) contraindications for immunotherapy because of potential dysregulation of T-cell function. We present the first case of severe immunotherapy-induced liver injury that resulted in a patient’s demise, in a patient with incidental hepatitis C antibody positivity. A 58-year-old woman with type 2 diabetes and metastatic breast cancer without significant hepatitis history underwent bilateral mastectomy followed by immunotherapy with PD-L1 inhibitor atezolizumab. After 1 year, she developed lethargy, generalized itching, unintentional 12-pound weight loss, and hyperglycemia refractory to her typical insulin regimen. Abnormal liver enzyme levels including alkaline phosphatase 419 IU/L (40–129), AST 151 IU/L (8–48), and ALT 224 IU/L (7–55) were found, along with incidental positive antibody for HCV. Subsequent liver biopsy showed primarily cholestatic pattern injury including canalicular and hepatocellular cholestasis with ductular proliferation. Although hepatitis C is known to be capable of mimicking biliary obstruction, typical histologic findings of HCV hepatitis were not present and viral load was undetectable. In the absence of mechanical obstruction, it was likely to represent PD-L1 inhibitor–induced liver injury. The treatment was discontinued; however, the patient deteriorated and expired 3 weeks after the biopsy. Extreme vigilance is essential for patients at risk of viral hepatitis or autoimmunity when using immunotherapy, as their combination may lead to a much worse outcome.

(Poster No. 21)

Chao Fan, MD, PhD¹ ([email protected]); Swan N. Thung, MD²; Aryeh Stock, MD.^{2 1}Department of Pathology, Cooperman Barnabas Medical Center, Livingston, New Jersey; ²Department of Pathology, Molecular and Cell-Based Medicine, Mount Sinai Hospital, New York, New York.

Nuclear protein in testis (NUT) carcinoma (NC) is a rare and aggressive carcinoma, defined by the presence of NUTM1 (15q14) rearrangement or fusion with other genes. NC affects young patients and arises from the midline structures of thorax, the head, and the neck, with rare exceptions. We report a case of NC arising from the bifurcation of hepatic ducts, mimicking perihilar cholangiocarcinoma on preoperative imaging, gross appearance, and initial microscopic examination. A 35-year-old woman presented with acute abdominal pain. Laboratory results were consistent with obstructive jaundice. Abdominal MRI exhibited diffuse intrahepatic duct dilatation and stricture at the biliary confluence. Biopsy revealed invasive carcinoma. The patient underwent an extended right hepatectomy. The resected specimen revealed a 2.5-cm gray-white firm mass at the hepatic duct bifurcation (Figure 1.21, A). The tumor was mass forming and periductal infiltrating. Tumor cells had nested architecture and open vesicular chromatin (Figure 1.21, B, C) and were positive for CK7, CK19, P40, and P63, consistent with cholangiocarcinoma with focal squamous differentiation. Tumor sequencing identified BRD3-NUTM1 fusion. The diagnosis of NC was ultimately made based on combined histology, BRD3-NUTM1 fusion, and the presence of NUT protein (Figure 1.21, D). The patient received chemotherapy but died 9 months later. To our knowledge, this is the first example of NC arising in the biliary tree. This report highlights the importance of recognizing NC in unusual locations, stresses the necessity of a thorough workup in young patients displaying squamous differentiation, and contributes to our understanding of the diagnostic and management challenges associated with biliary NC.

(Poster No. 22)

Olanrewaju Oni, MBChB ([email protected]); Rabia Zafar, MBBS. Department of Pathology, Howard University Hospital, Washington, DC.

Colorectal carcinoma poses a significant health burden worldwide, with metachronous colorectal tumors presenting complex challenges in management. The risk of colorectal carcinoma in HIV patients is debatable. However, there are distinct clinical patterns among HIV patients with colorectal cancer, including increased prevalence, earlier onset, more aggressive tumors, and poorer prognosis. The clinicopathologic features of multiple primary colorectal carcinomas in HIV patients have not been well studied. We present a case of a 64-year-old man who was HIV positive with a low CD4 count and high viral load and who developed 4 separate colonic adenocarcinomas, emphasizing the evolving landscape of cancer risk in this population. The patient’s medical history, clinical presentation, and pathology are described. The patient, who had sigmoid colon adenocarcinoma 3 years prior, underwent multiple biopsies, which revealed adenocarcinoma in the colon. Following total colectomy, gross examination identified 4 exophytic masses, with lymph node involvement. A diagnosis of adenocarcinoma was made with increased tumor-infiltrating lymphocytes and no microsatellite abnormalities. Studies have shown different malignancy profiles in HIV patients, but there is no established correlation between HIV status and colorectal tumors. To the best of our knowledge, metachronous colorectal carcinomas have never been reported in this population. This case underscores the importance of tailored surveillance strategies, early intervention, and vigilance in managing aggressive, multiple colorectal carcinomas in HIV patients. Despite advancements in treatment and survival rates, addressing the complex interplay of genetic variations, environmental exposures, and immunosuppression in CRC development among HIV-positive individuals remains crucial.

(Poster No. 23)

Sonal L. Italiya, MD ([email protected]); Peyman Dinarvand, MD. Department of Pathology, Baylor College of Medicine, Houston, Texas.

Primary hepatic angiosarcoma is an uncommon, aggressive neoplasm and is one of the primary malignant mesenchymal tumors of the liver in adults, accounting for 2% of all primary hepatic malignancies. The tumor has spindle or pleomorphic cells that line or grow into lumina of preexisting vascular spaces in hepatic vessels. We had 2 patients with liver lesions with a history of epithelioid gastrointestinal stromal tumor (GIST) of the stomach. Biopsy of the liver lesions showed a malignant epithelioid neoplasm composed of epithelioid and spindled endothelial cells with strong and diffuse positivity for CD117 and CD34 immunostains. We initially suspected epithelioid GIST, but the tumor behaved very malignantly clinically and grew rapidly. Further immunohistochemistry study showed the tumor was positive for ERG, CD31, p53 (mutated), and high Ki-67, but negative for DOG1, CK7, CK20, CDX2, TTF1, napsin, Hep-Par, glypican, arginase, CD30, CAM5.2, HMB 45, S100, and HHV8. After excluding other differential diagnoses like epithelioid GIST, Kaposi sarcoma, epithelioid hemangioendothelioma, hepatocellular carcinoma, and metastasis, the final diagnosis was reported for both patients as hepatic angiosarcoma. This limited series shows primary hepatic angiosarcoma can be strongly positive for CD117, and that could be a significant pitfall and misleading finding for pathologists. It is necessary to perform both CD117 and DOG1 in such cases to avoid misdiagnosis.

(Poster No. 24)

Lingling Xian, MD, PhD ([email protected]); Xuebao Zhang, MD, PhD; Bin Liu, BS; Guillermo Herrera, MD; Wei Xin, MD. Department of Pathology, University of South Alabama, Mobile.

Context: Goblet cell adenocarcinoma (GCA) is an uncommon and distinct tumor comprising gobletlike mucinous cells and neuroendocrine cells. We present a rare GCA case originating from the residual appendiceal stump following an appendectomy more than a decade prior because of acute appendicitis. A patient with a history of diabetes and appendectomy presented with diarrhea and constipation. Colonoscopy revealed nodular tissue at the appendiceal stump, and biopsy identified poorly differentiated adenocarcinoma with signet cell features. Immunohistochemical (IHC) staining showed tumor cells positive for CK20 and chromogranin and negative for CK7 and synaptophysin, raising the possibility of signet ring carcinoma versus high-grade goblet cell carcinoma. Goblet cell carcinoma arising from nonappendiceal sites is exceedingly rare. Subsequent resection confirmed the tumor’s likely origin from the residual appendix stump (Figure 1.24, A and B). To confirm the diagnosis and elucidate the ultrastructure of the goblet cell carcinoma, electron microscopy (EM) examination was performed, revealing characteristic features of GCA, including mucinous vacuoles and pleomorphic electron-dense granules consistent with neuroendocrine granules that compressed eccentric nuclei into crescentic shapes (Figure 1.24, C, D). GCA predominantly arises in the distal appendix. Instances of GCA originating from a residual appendiceal stump postappendectomy have rarely been documented. Primary signet ring cell carcinoma of the colon may mimic high-grade GCA. Identification of neuroendocrine granules with midgut morphology within carcinoma cells containing mucin aids in accurate diagnosis, particularly in the absence of definitive IHC neuroendocrine markers. EM serves as an adjunctive tool in confirming the diagnosis of GCA, particularly in cases with atypical presentations.

(Poster No. 25)

Gerard Oakley, MD¹ ([email protected]); Jinru Shia, MD³; Chad Vanderbilt, MD³; David Klimstra, MD²; Juan Retamero, MD.² Departments of ¹Biomarker Development and ²Medical Affairs, Paige, New York City, New York; ³Department of Pathology, Memorial Sloan Kettering, New York City, New York.

Context: Microsatellite instability–high (MSI-H)/mismatch repair–deficient (dMMR) tumors in colorectal carcinoma (CRC) are routinely detected by immunohistochemistry (IHC), next-generation sequencing (NGS), and/or polymerase chain reaction (PCR) assays. Paige Colon MSI uses artificial intelligence (AI) on whole slide images (WSI) of H&E-stained CRC to screen for MSI-H (98% sensitivity, 67% specificity). We reviewed histologic and molecular features of CRC cases that were false-positive (FP) and false-negative (FN) for MSI-H by Paige Colon MSI.

Design: A total of 350 CRCs, 50 known to be MSI-H/dMMR by IHC and/or NGS, were screened with Paige Colon MSI. One FN, 93 FP, 9 true-positive, and 9 cases where baseline IHC and NGS were discrepant were found. Expert pathologist (J.S.) review of H&E and IHC and reanalysis of NGS data by MiMSI and SigMA was performed in these cases to investigate the AI performance.

Results: The sole FN had limited metastatic material with poor tumor differentiation and focal high tumor-infiltrating lymphocytes (TILs). FP cases showed TIL mimics, mucinous features, poor tumor differentiation, medullary morphology, and treatment effects as potential AI confounders. Biopsy versus resection and right versus left colon may also have impacted AI accuracy. AI agreed with IHC results in cases where the initial molecular and IHC were discrepant. Two FP cases had POL-E mutations.

Conclusions: Paige Colon MSI showed excellent potential for triaging dMMR/MSI-H testing in CRC. Review of FN and FP cases found histologic mimics of known MSI-H CRC features and some typical morphology of MSI-H, which may account for their detection by the algorithm. This may inform pathologist interpretation using Paige Colon MSI.

Oakley, Vanderbilt, Klimstra, and Retamero are shareholders of Paige.

(Poster No. 26)

Amna Anzar, MD ([email protected]). Department of Pathology, University Hospitals–Cleveland Medical Center, Cleveland, Ohio.

Calcifying fibrous tumor (CFT) is a rare benign mesenchymal neoplasm that has been documented at a variety of anatomic sites. The most common gastrointestinal sites include the stomach, small intestine, and colon, with only 2 cases reported in the pancreatic body. We report the first case of CFT in the pancreatic head in a 30-year-old woman who presented with abdominal pain and was found to have a pancreatic head mass with calcifications on imaging, raising concern for solid pseudopapillary neoplasm. Our patient underwent a Whipple resection showing a 6.4-cm well-circumscribed, solid, tan-white mass in the pancreatic head (Figure 1.26, A). Histologic sections demonstrated hypocellular bland spindle cell proliferation embedded in dense hyalinized collagen (Figure 1.26, B) and associated with dystrophic calcifications (Figure 1.26, C). The spindle cells showed amphophilic cytoplasm, bland vesicular nuclei, and small nucleoli (Figure 1.26, D). Scattered lymphoplasmacytic infiltrates were seen throughout the lesion. CFT has been linked to prior trauma, surgical procedures, IgG4-related diseases, and inflammatory myofibroblastic tumor, among other etiologies; however, the exact pathogenesis remains uncertain. Morphologic examination is generally sufficient to make the diagnosis and immunostains are used to exclude other mimicking lesions in difficult cases. The differential diagnosis includes gastrointestinal stromal tumor, schwannoma, hyalinized leiomyoma, solitary fibrous tumor, desmoid fibromatosis, and sclerosing mesenteritis. CFTs are typically cured by local surgical resection. However, the recurrence rate in the gastrointestinal tract remains unclear, and some authors recommended postoperative follow-up. In our case, the patient had no evidence of recurrence at 15 months of follow-up.

(Poster No. 27)

Ejas Palathingal Bava, MD ([email protected]); Kerem Ozcan, MD; Brian K. Theisen, MD; Qing Chang, MD, PhD; Beena U. Ahsan, MD. Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, Michigan.

Context: The most commonly used scoring systems of tumor response in resected pancreatic cancer after neoadjuvant therapy are from the College of American Pathologists (CAP), MD Anderson, and Evans. Of these, the CAP scoring system is considered the most adequate system for tumor response scoring (TRS). We aimed to evaluate the prognostic value of the CAP scoring system in our patient population at a tertiary care institute.

Design: All consecutive patients who underwent pancreatic resection post–neoadjuvant chemotherapy for pancreatic ductal adenocarcinoma from 2013 to 2023 were included. Clinicopathologic data were collected from pathology and EPIC databases. Overall survival (OS) was calculated from the date of diagnosis to the date of death. Recurrence-free survival (RFS) was calculated from the date of surgery to the date of first recurrence. Kaplan-Meier and log-rank tests were used for survival analysis using GraphPad Prism software.

Results: Of 131 patients, 17 patients (13%) had complete response or minimal residual tumor (CAP grade 0 or 1), 82 patients (62.6%) had moderate response (CAP grade 2), and 32 patients (24.4%) had poor response (CAP grade 3). TRS grade 3 patients had worse OS as compared to those with TRS grade 2 or less (P = .02*; Figure 1.27, A). TRS grade 3 patients had worse RFS as compared to those with TRS grade 2 or less (P = .02*; Figure 1.27, B).

Conclusions: Our results show that patients with TRS grades 2 or less correlated with a more favorable outcome than those with TRS grade 3. Refinements in TRS scoring can further delineate these differences.

(Poster No. 28)

Claire A. Krasinski, DO, MS ([email protected]); Hao Wu, MD, PhD. Department of Pathology & Laboratory Medicine, Yale–New Haven Hospital, New Haven, Connecticut.

Context: Glycogenic acanthosis (GA) is considered a reflux-related histologic change. When seen in the pediatric population or diffusely, it might be associated with Cowden syndrome or tuberous sclerosis, which have mutations in genes encoding proteins involved in insulin signaling pathways. Insulin resistance is a common feature of morbid obesity.

Design: Pediatric patients who underwent prebariatric surgical evaluation from 2022 to 2024 were identified in the pathology database. Age-matched consecutive pediatric for-cause esophageal biopsies from January 2024 were included as the control. Ratios were compared with the Fisher exact test.

Results: Seventeen patients (4 male and 13 female) aged 14 to 20 years (median age 16) were identified. None of the patients had gastrointestinal symptoms or any stigmata of Cowden syndrome or tuberous sclerosis. All but one showed normal endoscopic findings; the other displayed distal esophageal reflux-like changes. GA (Figure 1.28) was seen in 6 as the only histologic finding, and both GA and granulation tissue were present in the patient with endoscopic abnormalities (7 of 17; 41.2%). All 7 had GA distally, while 1 patient also had it proximally. In comparison, GA was observed in 2 of 39 (5%) consecutive for-cause esophageal biopsies in patients aged 12 to 21 years (median age 16; P = .002). Seven patients in the control group had a clinical/endoscopic diagnosis of reflux, including the 2 with GA (28.6%) (P = .67).

Conclusions: GA is prevalent in morbidly obese adolescents without symptomatic or endoscopic correlation, likely related to dysregulated insulin signaling pathways. Further studies are warranted to understand the pathogenic mechanisms.

(Poster No. 29)

Chenchen Niu, MD, PhD ([email protected]); Dong Ren, MD, PhD; Sejal Shah, MD; Vishal Chandan, MD. Department of Pathology and Laboratory Medicine, University of California Irvine, Orange.

Context: The frequency of rectal neuroendocrine tumors (RNETs) has been increasing because of universal screening colonoscopies. A recent paper from South Korea showed chromogranin A (ChrA) protein expression in RNETs to be associated with more aggressive clinical behavior and poor prognosis. The aim of this study was to evaluate the significance of ChrA in RNETs within our patient cohort.

Design: ChrA, synaptophysin, Ki-67 (Roche Diagnostic, Indianapolis, Indiana), and INSM1 (Santa Cruz Biotechnology, Dallas, Texas) expressions were assessed in 102 endoscopically or surgically resected well-differentiated (WD) RNETs (grade 1 = 77; grade 2 = 25). ChrA expression was compared with clinicopathologic factors to identify its clinical and prognostic significance.

Results: Our cohort included 39 Asian, 31 White, 18 Hispanic, 5 Black, 1 Native Hawaiian, 4 mixed, and 4 unknown ethnicities. Synaptophysin and INSM1 were expressed in all 102 cases (100%), while ChrA was detected in only 51 cases (50%). ChrA expression was significantly associated (P < .05) with older age (50 years and older), male sex, perineural invasion, and higher tumor grade (Table). There was no association with ethnicity, vascular invasion, margin status, or overall survival. The plasma ChrA level was higher in the ChrA-positive cases than in the negative cases during follow-up, although this difference was not statistically significant.

Conclusions: Our findings suggest that expression of ChrA in WD RNETs is far less than expression of synaptophysin and INSM1. ChrA expression in RNETs is associated with higher tumor grade and perineural invasion but has no significance on overall patient survival.

(Poster No. 30)

Aditi Tayal, MD ([email protected]); Akram Shalaby, MD. Department of Pathology, Case Western Reserve University/University Hospitals Cleveland Medical Center, Cleveland, Ohio.

Elderberry (Sambucus nigra) supplements are commonly used by the public to treat cold and flu symptoms and boost the immune system. Nevertheless, they have been found to incite autoimmunity through the production of proinflammatory cytokines, and a recent association with the initiation and progression of autoimmune hepatitis (AIH) was suggested. We report a case of a 54-year-old woman with a history of hypothyroidism who presented with acute onset severe liver injury and jaundice. Liver function tests showed aspartate aminotransferase 1202 IU/L, alanine transaminase 2148 IU/L, alkaline phosphatase 214 IU/L, and total bilirubin 5.1 mg/dL. Antinuclear antibody was positive (titer of 1:640), while anti–smooth muscle and anti-mitochondrial antibodies were negative. Viral hepatitis panel was negative. A liver biopsy showed mild to moderate portal and lobular hepatitis, mild interface activity (Figure 1.30, A), and hepatocyte piecemeal necrosis (Figure 1.30, B). Review of the patient’s drug and supplement intake revealed the use of elderberry syrup for 2 months prior to presentation. Limited literature exists regarding the hepatotoxic effects of elderberry supplements, and whether they cause direct hepatic injury or trigger the development of AIH remains unclear. This distinction is clinically relevant, as patients with AIH often require long-term immunosuppressive therapy and close follow-up for disease flares. In our case, the patient showed clinical and biochemical improvement following cessation of elderberry supplements without the need for steroid therapy. To our knowledge, this is the second documented case of autoimmune-like liver injury secondary to elderberry ingestion. Further investigations into the mechanism of elderberry-induced liver injury are warranted.

(Poster No. 31)

Saroja Devi Geetha, MBBS ([email protected]); Amr Ali, MBBCh; Binny Khandakar, MD. Department of Pathology, LIJ/NS Northwell Health, Greenvale, New York.

Context: Inflammatory fibroid polyp (IFP) is a rare benign mesenchymal neoplasm in the gastrointestinal tract (GIT), characterized by submucosal proliferation of vascularized fibromuscular tissue admixed with eosinophils (Figure 1.31, A and B). Our study analyzes comparative clinicopathologic features across the upper (U-GIT) and lower GIT (L-GIT).

Design: A retrospective study was performed with all cases of IFP from 2020 to 2023. Demography, site, and immunohistochemical findings were collected.

Results: Cohort was comprised of 26 cases (14 women and 12 men). IFP was more commonly observed in U-GIT than L-GIT (69% versus 31%; Figure 1.31, C). Stomach was the most common site overall (n = 17; 65%). Ascending colon (n = 3) was the most common location in the L-GIT. Equal male to female distribution was observed in the L-GIT; however, there was a female preponderance in the U-GIT (F:M, 10:8). The average age was 61 years (range, 38–87 years). L-GIT involvement was more common in patients <60 years (88%), while most of the U-GIT patients were >60 years (72%) (Figure 1.31, D). PDGFRA was performed in 2 cases, and both stained positive. CD34 was positive in the rest (Figure 1.31, B). Additional IHC stains were performed in 11 cases to exclude other differential diagnoses: DOG1 (6), SMA (2), CD117 (5), desmin (3), S100 (6), EMA (1), and SOX10 (1); all were negative.

Conclusions: In the current cohort, gastric location and slight female predilection were observed, findings that support the existing literature. Tumors from L-GIT had equal numbers of male and female patients, and most were <60 years. U-GIT involvement was more common in older women.

(Poster No. 32)

Deepa Luitel, MBBS¹ ([email protected]); Lin Cheng, MD, PhD¹; Vijaya Reddy, MD¹; Fabiana Furci, MD²; Paolo Gattuso, MD.^{1 1}Department of Pathology, Rush University Medical Center, Chicago, Illinois; ²Department of Allergy, Provincial Health Care Unit, Vibo Valentia, Italy.

Context: Small bowel neoplastic lesions are rarely encountered during daily sign-out sessions in surgical pathology. We conducted a retrospective clinical-pathologic review to assess small bowel lesions.

Design: Between 1993 and 2021, we performed a retrospective clinical-pathologic review, excluding hematopoietic lesions. The clinical and pathologic data were reviewed in detail.

Results: A total of 128 neoplastic lesions were identified, with 68 in men and 60 in women; age ranged between 22 and 87 (mean, 61 years). Most cases occurred in the small intestine (75), followed by the duodenum (25), jejunum (15), and ileum (13). Among these, 91 of 128 (71%) were primary tumors. The study included 28 gastrointestinal stromal tumors, 21 neuroendocrine tumors, 13 lipomas, 9 adenocarcinomas, 7 leiomyomas, 4 gangliocytic paragangliomas, 2 each of schwannomas and paragangliomas, and single cases of various other tumors. Notably, 8 of 13 neural lesions were in the duodenum. Metastatic tumors constituted 29% (37 cases), with 26 occurring in the small intestine, including 12 melanomas, 6 lung carcinomas, 5 ovarian carcinomas, 4 breast carcinomas, 2 renal cell carcinomas, 2 cervical squamous cell carcinomas, and single cases of the other 6 carcinomas.

Conclusions: Primary small bowel neoplastic processes occur infrequently and encompass a spectrum of usual and unusual lesions, which can pose diagnostic challenges. Among 128 small bowel neoplastic lesions, 29% were metastatic tumors, notably high for a gastrointestinal organ, with melanoma being the most prevalent type. Meanwhile, the duodenum stands out as the primary location for neural differentiation tumors.

(Poster No. 33)

Ziyu Su, MS¹; Wei Chen, MD, PhD²; Muhammad Khalid Khan Niazi, PhD¹; Usama Sajjad, BS¹; Metin N. Gurcan, PhD¹; Wendy L. Frankel, MD² ([email protected]). ¹Center for Artificial Intelligence Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina; ²Department of Pathology, the Ohio State University Wexner Medical Center, Columbus.

Context: Tumor budding (TB), characterized by clusters of ≥4 tumor cells, is a significant prognostic factor in colorectal cancer (CRC). However, manual TB quantification is challenging, leading to labor-intensive efforts and poor interobserver agreement. The Segment Anything Model (SAM) is a powerful artificial intelligence tool that can segment any object from its background in an image or video with high quality and efficiency. Our study proposes adapting SAM for TB segmentation on hematoxylin and eosin (H&E)–stained images.

Design: We used 86 digitalized H&E slides from CRC. Expert pathologists meticulously annotated these slides, focusing on TB at the tumor invasive front. TB-containing regions were extracted and cropped into 512 × 512-pixel images. We trained SAM-Adapter on a dataset of 8606 images specifically for TB segmentation. After predicting TB regions, we refined predictions to minimize potential false positives using morphology transformations.

Results: This model attained an instance-level Dice score of 76% and instance-level recall (sensitivity) of 78% on 176 testing images that were finely annotated by experienced pathologists. Figure 1.33, A–D, showcases our model’s TB predictions (green lines) alongside the pathologist’s annotations (yellow lines). While the model effectively detected TBs, occasional false-positive regions were observed (bottom “TBs” in C and D).

Conclusions: We demonstrated that the adapted SAM model can segment CRC TBs on H&E images with moderate to high accuracy. In addition, finely annotating training images and conducting tumor cell counting on TB predictions helped reduce false positives. Next, we plan to develop a fully automated pipeline for slide-level images to assist pathologists in TB quantification.

(Poster No. 34)

Ifeomachukwu E. Nwosu, MBBS ([email protected]); Jenny Zhang, MD; Alexis S. Elliott, MD; Belinda Sun, MD, PhD. Department of Pathology, Banner-University Medical Center, College of Medicine, University of Arizona, Tucson.

Pancreatoblastoma, a rare pancreatic tumor, exhibits various differentiation pathways encompassing acinar, ductal, and neuroendocrine lineages, often characterized by distinctive squamoid nests. Although the neuroendocrine components typically manifest as well-differentiated neuroendocrine tumors, we present an exceptional instance of pancreatoblastoma entwined with large cell neuroendocrine carcinoma in a 10-year-old boy, heralded by symptoms of abdominal discomfort, weight loss, and intricate solid/cystic lesions in the pancreas, accompanied by splenic and hepatic nodules observed via imaging. Initial biopsy of the hepatic lesion revealed a poorly differentiated carcinoma displaying neuroendocrine features. Conversely, biopsy from the spleen delineated acinar cell differentiation, thereby raising 2 plausible diagnoses: pancreatoblastoma or acinar cell carcinoma. Subsequent surgical resection of liver, distal pancreas, and spleen was performed following neoadjuvant chemotherapy. Gross examination revealed a lobulated tumor infiltrating the distal pancreas and encroaching upon the splenic hilum, alongside a hemorrhagic nodule in the liver. Microscopic examination unveiled diverse differentiated components within the pancreatoblastoma: well-differentiated acinar cells arranged in an acinar formation (Figure 1.34, A), well-differentiated neuroendocrine cells (Figure 1.34, A), squamoid nests (Figure 1.34, B), and a high-grade neuroendocrine carcinoma (Figure 1.34, C) exhibiting a mitotic count of 40 per 2 mm² and Ki-67 proliferative activity of 100% (Figure 1.34, D), thus satisfying the criteria for large cell neuroendocrine carcinoma. Genetic analysis disclosed pathogenic variants in TP53 and SMAD4, seldom detected in pancreatoblastomas. This juxtaposition of large cell neuroendocrine carcinoma and pancreatoblastoma may signify a potential evolution from well-differentiated neuroendocrine tumor to poorly differentiated neuroendocrine carcinomas within the confines of pancreatoblastoma.

(Poster No. 35)

Shubhneet Bal, MD ([email protected]); Oluwole Odujoko, MD; Paul Fiedler, MD. Department of Pathology, Danbury Hospital, Danbury, Connecticut.

Context: The staging of colorectal carcinoma carries room for improvement, as up to 25% of patients deemed early stage (negative for lymph node or distant metastases) develop recurrence following intended curative resections. Immunohistochemical (IHC) markers such as desmin have the potential to greatly impact clinical management of patients with colorectal carcinoma by altering the pathologic stage when used in combination with hematoxylin and eosin stain.

Design: A 2-year institutional data search identified 176 resection specimens for large intestine carcinoma, with adenocarcinoma being the histologic type of interest. The inclusion criteria were defined to include the cases displaying foci of invasive carcinoma in close approximation to 3 borders of interest, namely bottom of muscularis mucosa, top of muscularis propria (MP), and bottom of MP. We performed desmin IHC (Dako D33 monoclonal antibody) on multiple sections of 23 cases.

Results: Three cases (13%), with tumor originating in the rectosigmoid area, were identified where the pathologic stage changed after performing desmin IHC stain as delineated in the Table. One case was upstaged from pT2 (tumor invading MP) to pT3 (tumor invading through MP into pericolorectal fat) and 2 cases were downstaged from pT1 (tumor invades submucosa) to pTis (intramucosal carcinoma) and pT2 to pT1.

Conclusions: Although not performed routinely, desmin IHC in combination with hematoxylin and eosin is strongly suggested for staging invasive colorectal carcinomas. Pathologists should not hesitate in ordering this stain in equivocal cases, even if it delays the case by another day, since it significantly impacts the pathologic staging as witnessed in these cases.

(Poster No. 36)

Chika S. Madu, MBBS ([email protected]); Saroja Geetha, MBBS; Corey Chang, MD; Suganthi Soundararajan, MD; Binny Khandakar, MD. Department of Pathology, Northwell Health, Greenvale, New York.

Severe serous fat atrophy (SSFA) is rare, characterized by the degenerative loss of lipids and deposition of mucopolysaccharides rich in hyaluronic acid within adipocytes. It is usually associated with significant weight loss. Bone marrow is the commonly documented site. Involvement of the omentum is extremely rare. Microscopic examination shows round cells with clear cytoplasm and a small peripheral nucleus without a nucleolus, morphologically resembling signet ring cells (SRCs). Here we describe a case of SSFA in the omentum, mimicking SRC adenocarcinoma. A 64-year-old man presented with history of unexplained weight loss during the preceding year. He also had leukopenia and thrombocytopenia. Initial bone marrow examination was nondiagnostic of hematologic neoplasm. Imaging studies showed omental heterogeneity with possible peritoneal carcinomatosis. Exploratory laparotomy was performed with omental biopsy for concerns for malignancy of unknown origin in the abdomen. Grossly, a uniformly lobulated fat was received. Microscopy showed vacuolated cells with eccentric nuclei and faint myxoid/mucoid changes in the background. Mucicarmine and a battery of immunostains were performed, which showed the cells of interest to be positive for S100 (Figure 1.36, C), while other markers (Claudin4, CAM 5.2, AE1/AE3, CK7, CK20, CDX2, calretinin, D2-40) were negative. Mucicarmine showed a blush in the background (Figure 1.36, D). Very few cases of SSFA in the omentum have been reported. Its rarity, clinical presentation of weight loss, and morphologic resemblance to SRC adenocarcinoma can pose significant diagnostic challenges. Awareness of the unique morphologic features, S100 expression, and clinical presentation would help to achieve an accurate diagnosis of this rare entity.

(Poster No. 37)

Niki Shrestha, MBBS ([email protected]); Bijay Shrestha, MBBS; Akram Shalaby, MD; Navid Sadri, MD; Min Cui, MD. Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, Ohio.

Intraductal tubulopapillary neoplasm (ITPN) is a rare intraductal pancreatic lesion that is commonly associated with invasive carcinoma. We report a case of a 64-year-old man who presented with acute pancreatitis. On further workup, a mass was identified in the distal esophagus and biopsy showed adenocarcinoma (Figure 1.37, A). Additionally, an irregular 3.4-cm mass was identified in the pancreatic head, and cytology showed adenocarcinoma. The patient underwent chemoradiation for esophageal adenocarcinoma and Whipple procedure after chemotherapy for pancreatic adenocarcinoma. The Whipple specimen showed ITPN with extensive high-grade dysplasia (Figure 1.37, B) and associated invasive adenocarcinoma (Figure 1.37, C), stage ypT1c ypN0. Next-generation sequencing identified BRAF p.V600E in the tumor. Five and a half months after surgery, the patient presented with a 1.2-cm liver lesion, and the biopsy showed adenocarcinoma (Figure 1.37, D). Because of overlap of morphology and immunophenotype of esophageal and pancreatic adenocarcinomas, next-generation sequencing was performed on both the liver lesion and the esophageal adenocarcinoma. The liver lesion showed BRAF p.V600E, and the esophageal carcinoma showed TP53 alterations and EGFR amplification. The identical molecular profile of the liver lesion and pancreatic tumor helped to establish the pancreatic adenocarcinoma as the origin of liver metastasis. The patient was started on a chemotherapy regimen using gemcitabine Abraxane. To the best of our knowledge, this is the first case of a patient with synchronous esophageal adenocarcinoma and pancreatic carcinoma associated with ITPN that presented with liver metastasis; the molecular findings were particularly helpful to support the primary origin to be pancreatic tumor.

(Poster No. 38)

Christopher Moroz, MD ([email protected]); Susan L. Haley, MD; Mary R. Schwartz, MD; Mukul K. Divatia, MD; Blythe K. Gorman, MD; Sadhna Dhingra, MD. Department of Pathology & Genomic Medicine, Houston Methodist Hospital, Houston, Texas.

Intraductal papillary mucinous neoplasm (IPMN) colonizing the ampullary mucosa and mimicking an ampullary adenoma has not been previously reported in the US literature. We present 2 such cases of main duct IPMN presenting with obstructive jaundice and an ampullary mass. A 64-year-old man with jaundice had magnetic resonance imaging demonstrating ampullary fullness, biliary ductal dilation, multiple pancreatic cystic lesions in the head of the pancreas, and uncinate process favoring IPMN. Endoscopy showed a 2.5-cm ampullary mass, and biopsy was interpreted as adenoma with high-grade dysplasia. Subsequent pancreatoduodenectomy showed a 6-cm IPMN involving the main pancreatic duct and branch ducts extending into the ampulla (Figure 1.38, A; ampullary component Figure 1.38, B) with associated poorly differentiated adenocarcinoma. A 63-year-old woman with jaundice had a 2-cm ampullary mass and 8-mm dilatation of the main pancreatic duct on imaging. Biopsy of the ampullary mass was interpreted as adenoma with high-grade dysplasia. Pancreatoduodenectomy showed a 2.5-cm IPMN involving the main pancreatic duct extending to the ampulla (Figure 1.38, C; ampullary component Figure 1.38, D), with associated moderately differentiated invasive adenocarcinoma. Awareness of this phenomenon is essential to avoid diagnostic confusion of 2 concomitant primary lesions, that is, ampullary adenoma and IPMN. There is a possibility of missing an underlying IPMN if ampullary adenoma is treated with endoscopic papillectomy. In the setting of an invasive adenocarcinoma infiltrating the ampulla, recognition of the origin of adenocarcinoma is helpful because of significant therapeutic and prognostic differences between ampullary adenocarcinoma and adenocarcinoma arising in an IPMN.

(Poster No. 39)

Roula Katerji, MD ([email protected]); Aaron R. Huber, DO. Department of Pathology, University of Rochester, New York.

Perineurioma is an uncommon benign small intramucosal lesion often seen in the distal colon presenting as a polyp. The lesion is characterized as proliferation of stromal spindled cells that express perineural markers. Usually, they are associated with serrated crypts seen in hyperplastic polyps. We present an unusual case of epithelioid perineurioma in an 82-year-old asymptomatic man with a history of colorectal polyps. Colonoscopy showed multiple polyps in the transverse colon with one 0.5-mm polyp in the sigmoid. H&E sections of the sigmoid polyp showed a serrated hyperplastic polyp, and the lamina propria appeared to be expanded by a vaguely nodular proliferation of epithelioid cells arranged in small clusters with round nuclei, abundant eosinophilic cytoplasm, and occasional nuclear grooves (Figure 1.39, A, B, and C). No cytologic atypia, mitotic activity, or necrosis was identified. The differential diagnosis included granular cell tumor, epithelioid Schwann cell hamartoma, collection of histiocytes, mucosal benign epithelioid nerve sheath tumor, and epithelioid gastrointestinal stromal tumor. Immunohistochemical analysis demonstrated diffuse but weak expression of epithelioid membrane antigen (Figure 1.39, D), while pancytokeratin, GLUT-1, S100, SOX10, HMB45, DOG-1, ERG, CD68, CD163, and SMA were all negative. The overall histologic and immunohistochemical features were consistent with an epithelioid variant of perineurioma. To our knowledge, this is the first reported case of epithelioid perineurioma discovered on colonoscopy. This represents a newly identified and unreported benign mesenchymal colonic polyp that pathologists should be aware of to avoid misinterpretation.

(Poster No. 40)

Arooj Devi, MD ([email protected]); Mohammed Maher, MD; Fnu Poonam, MD; Shoujun Chen, MD. Department of Pathology & Laboratory Medicine, East Carolina University, Brody School of Medicine, Greenville, North Carolina.

Dedifferentiated liposarcoma is not uncommon in limbs and the retroperitoneum. However, primary dedifferentiated liposarcoma of the pancreas is exceptionally rare, with only 11 cases reported. The electronic medical record was reviewed. A 63-year-old man with a history of prostate cancer presented with abdominal pain and significant weight loss. Imaging revealed an 18-cm heterogeneous necrotic mass in the pancreatic tail (Figure 1.40, B). Endoscopic ultrasound fine-needle aspiration (FNA) demonstrated atypical epithelioid to spindle cells within a dense fibrotic tissue background (Figure 1.40, A, C). Immunohistochemical staining was negative for several markers. The initial FNA was diagnosed as an atypical spindle cell neoplasm, prompting surgical resection. The subsequent histopathologic analysis revealed pleomorphic epithelioid neoplasm with abundant mixed inflammation and areas of well-differentiated to dedifferentiated liposarcomatous component (Figure 1.40, D), along with areas of heterologous osteosarcoma differentiation. The neoplastic cells were negative for various markers but positive for MDM2. The final diagnosis was dedifferentiated liposarcoma, FNCLCC grade 2, with heterologous differentiation. Eleven months postsurgery, the patient was disease free on CT scan surveillance. This case highlights the diagnostic challenge posed by atypical spindle cells with mild cytologic atypia in the inflammatory background and low mitotic activity in the FNA specimen. Chronic pancreatitis and other spindle neoplasms were in the differential diagnosis. Imaging study and thorough sampling are important to render the diagnosis of this rare entity in the pancreas. Our findings contribute to the literature by providing rare FNA cytopathology features of pancreatic mass suggestive of liposarcoma and enriching the understanding of this uncommon entity in pancreatic primary cases.

(Poster No. 41)

Amr Ali, MBBCH ([email protected]); Saroja Geetha, MBBS; Chika Madu, MBBS; Binny Khandakar, MD. Department of Pathology, Northwell Health, New York, New York.

Context:Helicobacter heilmannii, a member of the Helicobacter family, is detected in a small portion of gastric biopsies. It primarily affects primates, cats, and carnivorous mammals. It accounts for 0.5% to 6% of human gastric infections. While typically causing mild chronic gastritis, at times it can also lead to peptic ulcers, and in rare cases, gastric carcinoma and lymphoma. Compared to H pylori gastritis, H heilmannii–induced gastritis tends to be milder and more localized, often affecting the antrum with occasional severe inflammation in the body.

Design: This is a retrospective study of cases diagnosed with H heilmannii gastritis (2013–2023). Patient demographics, associated pathology, and the time of the biopsy were analyzed.

Results: Twenty-four cases of H heilmannii infection were identified (2013–2023). A majority of the cases were seen in spring (33%), followed by summer (25%), fall (25%), and winter (17%). The cohort included 5 pediatric cases and 19 adult cases. Median age was 13 years in pediatric patients and 62 years in adults. Male to female ratio was 2:1. Mild to moderate gastritis was seen in all cases, with 4 cases showing intestinal metaplasia (17%). Five cases were diagnosed with H&E stain only. Warthin-Starry stain immunohistochemistry was used to detect the bacteria in the rest (Figure 1.41, A–D).

Conclusions:H heilmannii is a rare cause of infective gastritis. It can affect both children and adults. Incidence of infection in men was twice that seen in women in the current series. Incidence of gastritis also showed seasonal variation, with higher incidences in spring and summer months than the colder months.

(Poster No. 42)

Ritica Chaudhary, MD ([email protected]); Akhila Aravind, MD; Satyapal Chahar, MD. Department of Pathology, UMMC, Jackson, Mississippi.

Context: Endoscopic mucosal resection (EMR) is a minimally invasive procedure effective in treating premalignant and early-stage esophageal malignancies while sparing the organ. We retrospectively analyzed EMR specimens to determine the correlation between endoscopic biopsy, EMR histopathology, and further follow-up.

Design: From our medical center’s database (2017–2023), we reviewed the clinicopathologic features and follow-up of 27 cases of esophageal EMR.

Results: Twenty-seven EMR specimens were identified. Median age was 68 years (age range, 36–86; 85% were men). A relevant medical history of smoking was identified in 70% of the cases (19 of 27). Upon histologic analysis of the EMR specimens, 6 cases had Barrett esophagus (BE) with dysplasia; 5 cases were followed up, and on endoscopy evaluation, 2 cases had no residual BE, whereas 3 cases were treated for BE with endoscopic modalities. There were 13 cases of invasive carcinoma. One case was of invasive squamous cell carcinoma, whereas 12 cases were identified as adenocarcinoma. Nine of 13 cases were followed up endoscopically. Four cases had a follow-up biopsy; 2 cases were negative for BE, while 2 cases were positive for BE with dysplasia. The remaining 5 cases were followed up endoscopically; 2 were treated with further endoscopic modalities, 1 was negative for BE, and 2 had evidence of esophageal stenosis without BE (Table).

Conclusions: EMR is an effective first-line therapy and an alternative to surgery for dysplasia and early carcinoma. However, in our study, 36.8% (7 of 19) of cases showed residual/recurrent BE with dysplasia, and 26.3% (5 of 19) of cases required additional treatment, which highlights the importance of regular follow-up post-EMR.

(Poster No. 43)

Katelyn Moss, DO¹ ([email protected]); Kudakwashe Chikwava, MD²; Sanjeev Vasudevan, MD³; Andras Heczey, MD⁴; Prakash Masand, MD⁵; Dolores Lopez-Terrada, MD²; Kalyani Patel, MD.^{2 1}Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Departments of ²Pathology, ³Surgery, ⁴Hematology-Oncology, and ⁵Radiology, Texas Children’s Hospital, Houston, Texas.

Hepatocellular nodules can arise because of abnormal portal blood flow in the setting of portosystemic shunts (PSS). These nodules include benign entities such as regenerative nodular hyperplasia, focal nodular hyperplasia (FNH), and hepatocellular adenomas as well as malignant neoplasms including hepatocellular carcinoma. We present an otherwise healthy 18-year-old man who presented with 2–3 days of lower abdominal pain and 1-week history of diarrhea. MRI showed multifocal hepatic masses involving the right and left lobes with the largest measuring up to 7.4 cm, favoring FNH or FNH-like lesions (Figure 1.43, A). AFP was 2.2 ng/mL. An ultrasound-guided biopsy of the largest mass showed a proliferation of hepatocytes with monomorphic nuclei and diffuse, predominantly macrovesicular steatosis throughout the lesion, favoring hepatic adenoma. The patient underwent left hepatectomy and resection of 2 right-sided lesions. The left lobe was almost entirely replaced by multiple confluent nodules with mixed histopathologic features (Figure 1.43, B). The nodules included morphology of hepatic adenomas with and without steatosis, FNH, and nodular regenerative hyperplasia (Figure 1.43, C). No significant cytologic atypia or features of malignancy were seen. Molecular testing did not reveal β-catenin (CTNNB1) or any other high-risk mutations, and immunohistochemistry for β-catenin was negative as well (Figure 1.43, D). Peritumor liver showed extensive portal vein abnormalities including thickening, occlusion, dilation, localized cavernoma-like formations, and PSS. This case highlights the rare development of multiple benign hepatocellular lesions in the context of PSS. It also highlights challenges in the surgical management of multifocal lesions with respect to considerations for a transplant.

(Poster No. 44)

Wai Szeto, MD¹ ([email protected]); Yanghee Woo, MD²; Rifat Mannan, MD.¹ Departments of ¹Pathology and ²Surgery, City of Hope, Duarte, California.

Context: Prophylactic total gastrectomy (PTG) is frequently performed in hereditary diffuse gastric cancer patients. The standard practice of examining the entire specimen poses substantial resource challenges. Our objective was to create a grossing protocol that is both efficient and optimal.

Design: We studied 9 PTG specimens. Preprotocol cases were either fully submitted (group 1; n = 2) or partially, randomly submitted (group 2; n = 4). Our targeted 2-step protocol (n = 3) involved gross examination and photography of mucosal surface. Postfixation, mucosa was divided into proximal, middle, and distal thirds. In the first step, ∼75% of proximal third and representative blocks from middle and distal thirds were submitted, with mapping. Signet ring cell carcinoma (SRCC) was assessed on H&E slides. If negative, additional sections were submitted in the second step. Results were compared using a t test.

Results: The new protocol yielded an average of 121 sections (62 blocks) per case (Table). After the initial 59 sections, SRCC was found in 2 cases, in cardia or fundus. In the third case, no SRCC was identified initially, prompting submission of 246 sections (126 blocks). In contrast, group 1 (n = 2) required 375 (129 blocks) and 381 sections (185 blocks). In group 2, SRCC was found in 2 cases, requiring 86 sections (44 blocks). The new targeted protocol detected SRCC with significantly fewer sections compared to the other 2 methods (P = .03).

Conclusions: Our targeted protocol for the proximal stomach successfully identified SRCC using fewer sections, highlighting the efficiency of this approach in saving resources and time. Pending validation, this method could be a valuable option for the optimal histologic evaluation of PTG specimens.

(Poster No. 45)

Anna Nevels, MD¹ ([email protected]); Haiyan Lu, MD, PhD.^{2 1}Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; ²Department of Pathology, Greensboro Pathology Associates, Greensboro, North Carolina.

Gastrocystoplasty can be an indicated treatment for neurogenic bladder in pediatric patients. We report a case of gastric adenocarcinoma in a 35-year-old woman with a history of spina bifida and neurogenic bladder requiring a gastrocystoplasty at the age of 5. She presented with difficult catheterization and hematuria. A cystoscopy with biopsies was performed. Sections demonstrated an invasive, poorly differentiated carcinoma forming small nests and glands with single cell infiltration (Figure 1.45, A and B). Foci of gastric epithelium were seen, composed of predominant foveolar-type epithelium and pyloric glands. Immunohistochemical staining in the neoplastic cells demonstrated weak positivity for CDX2 and negativity for GATA3 (Figure 1.45, C and D). They were also positive for p53, and negative for SATB2, synaptophysin, p63, and racemase. The immunophenotype favored an adenocarcinoma from the gastric mucosa at the gastrocystoplasty anastomotic site, with a urothelial carcinoma or primary bladder adenocarcinoma being less likely. Mismatch repair proteins were intact, and HER2 was positive by FISH. Reporting such cases is important in understanding possible potentiating factors in the earlier onset of gastric adenocarcinoma seen in these patients. It is also imperative to pay careful attention in cases with this clinical context to rule out a gastric carcinoma in an otherwise uncommon location. Although routine surveillance after surgery may not be indicated because of the infrequency with which this occurs, symptomatic patients in this clinical context merit a comprehensive workup to rule out malignancy.

(Poster No. 46)

Patricia Repollet Otero, MD ([email protected]); Elsayed Ibrahim, MD; Saverio Ligato, MD. Department of Pathology, Hartford Hospital, Hartford, Connecticut.

Context: Peroral cholangioscopy-guided direct biopsy is a valuable tool for the investigation of indeterminate lesions in the upper biliary tract. However, obtaining sufficient diagnostic material is challenging, as this technique frequently yields small, crushed fragments of tissue. There are no standard guidelines to assess the adequacy of these biopsies. The purpose of our study is to identify reliable minimal criteria of adequacy for an accurate diagnosis of lesions involving the upper biliary tract.

Design: We searched our database (2016–2023) for cases obtained by SpyBite biopsy of biliary lesions of the upper biliary tract. The cases were organized into benign, nondiagnostic, atypical/suspicious for malignancy, and malignant. Retrospective review of number, size, and quality of fragments per case was performed and tabulated. The statistical significance of each feature was assessed.

Results: A total of 57 samples from 57 patients (30 male, 27 female; average age, 71 years) were included. On average, nondiagnostic/inadequate specimens consisted of ≤2 fragments; benign of ≥4; suspicious of ≥3.5; and malignant of ≥6. For statistical purposes, benign, malignant, and suspicious categories were grouped and compared to the nondiagnostic category to determine the optimal cutoff value for the number of fragments needed for adequacy, which was identified at 3 tissue fragments as the minimum criterion of specimen adequacy (P = .01).

Conclusions: We propose a cutoff value of at least 3 tissue fragments as the minimum criterion of adequacy in SpyBite biopsies obtained from the upper biliary tract. Furthermore, a greater number of tissue fragments correlated with a diagnosis of malignancy.

(Poster No. 47)

Jim C. Lee, MD, MPH ([email protected]); Xiaoyan Liao, MD, PhD; Marisa Jacob-Leonce, MD. Department of Pathology, University of Rochester Medical Center, Rochester, New York.

SMARCA4 (BRG1)-deficient undifferentiated carcinoma (SMARCA4-dUC) is a rare aggressive entity. The diagnosis is often challenging because of the diverse morphology and nonspecific immunohistochemistry profiles. We present an unusual case of gastric SMARCA4-dUC metastatic to liver mimicking hepatocellular carcinoma. The patient was a 68-year-old man with past medical history of rheumatoid arthritis on chronic immunomodulator treatment who presented with dyspnea and subsequent diagnosis of Pneumocystis jiroveci pneumonia. Computed tomography imaging identified multiple liver lesions concerning for abscesses, a biopsy of which demonstrated diffuse infiltrates of malignant epithelioid neoplasm in solid sheets and clusters (Figure 1.47, A). The tumor cells were positive for Hep Par 1 (Figure 1.47, B), but negative for all other hepatocytic markers, cytokeratins, melanoma, and neuroendocrine, as well as lineage markers NKX3.1, CDX2, and TTF-1. Ki-67 labeling index was greater than 70% of neoplastic cells. Unfortunately, tissue was exhausted before a definitive diagnosis could be made, and the patient succumbed shortly after. Autopsy revealed an 11-cm fungating gastric mass and numerous liver lesions. Remarkably, the liver lesions mirrored those observed in the biopsy, while the gastric mass displayed a precursor tubulovillous adenoma transitioning into a poorly differentiated component similar to that in the liver (Figure 1.47, C). Immunostaining highlighted the loss of Brg-1 in the poorly differentiated neoplasm in both liver and stomach (Figure 1.47, D), with the gastric precursor showing partial loss of Brg-1, confirming a diagnosis of gastric SMARCA4-dUC metastatic to the liver. Although exceedingly rare, SMARCA4-dUC has been increasingly reported across various organ systems. Recognizing this entity is crucial to navigate potential diagnostic pitfalls.

(Poster No. 48)

Kasimu U. Adoke, MBBS¹ ([email protected]); Sanusi M. Haruna, MBBS.^{2 1}Department of Pathology, Federal Medical Centre Birnin Kebbi Nigeria, Birnin Kebbi, Nigeria; ²Department of Pathology, Pathology and Forensic Medicine, Usmanu Danfodio University Teaching Hospital Sokoto, Nigeria.

Context: Rhinosporidiosis is a chronic localized granulomatous inflammation caused by Rhinosporidium seeberi. Over the years, it has had different taxonomic classifications, but recently it has been classified under aquatic eukaryote based on genetic sequencing. The causative organism cannot be cultivated in culture media; hence, histopathology of the lesion is the gold standard for diagnosis. It commonly affects nasal mucosa but may have varied presentations. Affectation of extranasal sites is not uncommon, causing a diagnostic dilemma.

Design: Five cases of rhinosporidiosis diagnosed in a period of 3 years were included in the study (December 2020–November 2023). Data were extracted from patient case notes. Special stains PAS and GMS were performed in all cases. Analysis of data was performed using SPSS version 24.

Results: The age range of patients was 5–25 ± 7.7 years with a mean age of 13 years. The male to female ratio was 2:3. The most common site of infestation by rhinosporidiosis was the ileum, causing acute abdomen leading to rupture in some cases. A case of primary infertility was seen with no known etiologic cause after several investigations. All cases of rhinosporidiosis involving the ileum and colon were misdiagnosed by the attending physician as acute abdomen secondary to typhoid perforation until histology showed giant cells and sporangia containing endospores. PAS and GMS were positive in all cases.

Conclusions: Rhinosporidiosis can be deceptive in some instances, and a high index of suspicion may help in the diagnosis of this uncommon entity in the tropics and subtropical regions.

(Poster No. 49)

Dilshad Dhaliwal, MD ([email protected]); Tamadar A. Al Doheyan, MD; Shilpa Jain, MD. Department of Pathology, Baylor College of Medicine, Houston, Texas.

Context: Inflammatory bowel disease (IBD), encompassing Crohn disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal tract characterized by periods of remission and exacerbation. Though vasculitis is primarily autoimmune, its relationship with overlying inflammation is poorly understood.

Design: A retrospective study, aiming to investigate incidence and correlation of vasculitis and degree of inflammation, was performed in 29 colon resection specimens (IBD, 22 specimens; ischemic colitis, 6 specimens; radiation proctitis, 1 specimen) during 6 years (2018–2024). Degree of bowel inflammation was noted using a histologic colitis score. Type, location, size, and cell type associated with vasculitis were noted.

Results: Of 29 resections, 16 (55%) were UC, 6 (20.6%) were CD, and 6 (20.6%) were ischemic colitis. Fourteen (48.2%) specimens showed vasculitis, 11 (38%) showed UC (Figure 1.49, A), and 2 (6.8%) showed CD. All 11 UC cases showed severe inflammation, and 2 had moderate inflammation. Both small and medium arteritis and venulitis in submucosa and serosa were noted (Figure 1.49, A, B, and C). One case of radiation proctitis showed mild vasculitis. Ischemic colitis cases showed neutrophilic margination (Figure 1.49, D). No lymphocytic inflammation was noted.

Conclusions: Our findings revealed a significant correlation between the presence of vasculitis and degree of inflammation. Patients with severe inflammation, as indicated by higher disease activity scores and histologic evidence of active inflammation, were more likely to exhibit concurrent vasculitis. Interestingly, patients with UC tended to demonstrate more pronounced vasculitis as compared to CD, suggesting potential differences in the underlying mechanisms or immune responses between these subtypes of IBD.

(Poster No. 50)

Hasan Basri Aydin, MD¹ ([email protected]); Xin Wang, MD¹, Meng Liu, MD¹, Vaibhav Chumbalkar, MD², Hwajeong Lee, MD¹, Andrea Lightle, DO.^{1 1}Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, New York; ²Department of Pathology, Moffitt Cancer Center, Tampa, Florida.

Vasculitis is an uncommon etiology of acute ischemic/inflammatory conditions in the gastrointestinal (GI) tract. Identification remains challenging because of lack of specific symptoms, variable manifestation, mimicry of other conditions, and limited awareness. We present 2 cases of GI ischemia secondary to vasculitis. Case 1 involved an 8-year-old girl who presented with abdominal pain and diarrhea following streptococcal upper respiratory tract infection. Upper GI obstruction was suspected, prompting exploratory laparotomy and resection of ischemic jejunal segment. Patchy leukocytoclastic vasculitis was identified in mural and serosal vessels in a background of nonspecific ischemic injury (Figure 1.50, C). These findings led to the underlying clinical diagnosis of Henoch-Schönlein purpura, as later confirmed by kidney biopsy. Case 2 involved a 22-year-old man who presented with abdominal pain and hematochezia. CT scan revealed abdominal free air, prompting an exploratory laparotomy. Portions of omentum, small bowel, and right colon were resected. In addition to widespread serosal abscess, leukocytoclastic vasculitis was identified with arterial fibrinoid necrosis and disrupted arterial elastic laminae (Figure 1.50, A, B). The vasculitis was clinically determined to be secondary to infection. These cases illustrate that vasculitis should be suspected in cases of unexplained GI ischemia, particularly in young patients. Helpful histologic features for identification include leukocytoclastic debris, fibrinoid necrosis, and RBC extravasation, which can be obscured by the background ischemic injury/inflammation. While GI vasculitis does occur secondary to ischemia or infection, some cases may be the initial manifestations of systemic vasculitides such as Henoch-Schönlein purpura, eosinophilic granulomatosis with polyangiitis, giant cell arteritis, and polyarteritis nodosum. Timely recognition is crucial to prevent further organ damage.

(Poster No. 51)

Aaron R. Huber, DO¹ ([email protected]); Tom C. DeRoche, MD.^{2 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.

Colitis is a common side effect of programmed cell death protein-1 (PD-1) inhibitors including nivolumab and pembrolizumab. PD-1 inhibitor–induced colitis shows variable histology, but is typically characterized by either an active colitis or inflammatory bowel disease–like chronic active colitis. Twenty-five prior cases of PD-1 inhibitor–induced collagenous colitis (CC) have been reported; to our knowledge, the pseudomembranous variant of CC has not been described in this setting. A 54-year-old woman on nivolumab for conjunctival melanoma with bone metastasis reported 5 months of diarrhea beginning 14 months after starting therapy. Stool calprotectin was elevated. Clostridium difficile toxin and stool gastrointestinal pathogen panel results were both negative. Colonoscopy demonstrated marked cecal inflammation with thick exudates, friability, and cobblestoning; splenic flexure, descending colon, and rectum showed edematous and hyperplastic mucosa. Cecal biopsies showed subepithelial collagen thickening accompanied by surface epithelial detachment and prominent inflammatory pseudomembranes. Splenic flexure and descending colon showed mild crypt distortion and Paneth cell metaplasia without significant neutrophil- or eosinophil-mediated epithelial injury; focal subepithelial collagen thickening was also present in the descending colon (Figure 1.51, A–D). Diarrhea significantly improved after nivolumab was held and steroid treatment was initiated. Colonoscopy performed 5 weeks after the prior study showed fine diffuse nodularity; biopsies revealed classic CC without pseudomembranes. This report further expands the morphologic spectrum of PD-1 inhibitor–induced colitis. Provided that C difficile infection and ischemia are excluded clinically, recognition of pseudomembranous CC in the setting of PD-1 inhibitor therapy will allow for timely treatment including cessation of the medication and possibly steroid therapy.

(Poster No. 52)

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

Immunomodulatory agents, including CTLA-4 and PD-1 inhibitors, are used to treat metastatic melanoma and have been shown to improve survival. There is sparse literature on the morphologic changes seen in immunomodulatory-treated melanoma from gastrointestinal tract mucosal biopsies. Misinterpreting the morphologic findings of treated metastatic melanoma could lead to the erroneous assumption that the tumor has not responded to therapy or has progressed. A 64-year-old man with widely metastatic melanoma at presentation underwent immunomodulatory agent (ipilimumab and nivolumab) therapy with excellent response. His treatment course was complicated by immune-mediated hepatitis, which responded to corticosteroid therapy. He also developed diarrhea and underwent a colonoscopy to exclude immune-mediated colitis. Numerous hyperpigmented black nodules were noted within the colonic mucosa, which were endoscopically believed to represent metastatic melanoma. A biopsy of one of the nodules demonstrated abundant pigment within the lamina propria and erosion. Immunohistochemical stains for SOX10 and S-100 were negative, while CD68 highlighted macrophages within the lamina propria. Fontana-Masson stain was positive within the pigmented cells (Figure 1.52, A–D). The histologic findings were compatible with treated metastatic melanoma without viable malignancy. The morphology of metastatic melanoma treated with immunomodulatory agent chemotherapy within the colon, to our knowledge, has not been well described. We describe a case with residual pigmentation, histiocytic response in the lamina propria, and erosion compatible with treatment response. It is important to recognize this pattern as treated metastatic melanoma and not viable residual tumor to prevent misdiagnosis; ancillary immunohistochemical and histochemical stains can assist to resolve this diagnostic dilemma.

(Poster No. 53)

Sarang Khan, MBBS ([email protected]); Ashbita Pokharel, MBBS; Aqsa Nasir, MBBS; Zhenhong Qu, MD. Department of Pathology, Corewell Health, Royal Oak, Michigan.

Focal nodular hyperplasia (FNH) is increasingly identified as a hepatic lesion post–systemic chemotherapy, notably with agents such as oxaliplatin and cyclophosphamide. This phenomenon poses distinct challenges in diagnosis and management, often mimicking liver metastases. MRI features play a crucial role in differentiating FNH from malignant lesions, thereby avoiding unnecessary interventions. Recognizing the pivotal role of MRI features in distinguishing FNH from malignant lesions becomes crucial, emphasizing the imperative for clinician awareness in accurately discerning these benign lesions from metastatic disease. A 52-year-old woman diagnosed with right-sided colon carcinoma underwent MRI that showed multiple peripherally enhancing lesions scattered throughout the liver consistent with metastasis. Following oxaliplatin chemotherapy, she underwent right-sided hemicolectomy and partial hepatectomy. Gross examination identified 7 separate nodules, with at least 1 exhibiting well-circumscribed, unencapsulated features resembling FNH (Figure 1.53, A). Histologic examination confirmed metastasis and also revealed a nodule with significant atrophy/degeneration of bile ductules but with no typical fibrotic bands (Figure 1.53, B, C). Glutamine synthetase showed pseudomap-like staining (Figure 1.53, D), confirming the diagnosis of FNH. Our report highlights FNH as a postchemotherapy occurrence, particularly with oxaliplatin-based treatments for colorectal cancer. Although de novo FNH is a major differential diagnosis, the morphology on imaging and histology is consistent with posttherapy FNH. The poorly understood pathophysiology of this lesion includes chemotherapy-induced hepatic circulatory abnormalities like sinusoidal obstruction syndrome. Recognition of these potential liver changes, coupled with characteristic MRI appearances, can aid in avoiding incorrect diagnoses of metastasis. Emphasizing conservative treatment strategies, this approach spares patients from unnecessary biopsies or surgeries, underlining the significance of timely and accurate differentiation.

(Poster No. 54)

Harmeet Kharoud, MD, MPH ([email protected]); Michael S. Landau, MD. Department of Pathology, Allegheny General Hospital, Pittsburgh, Pennsylvania.

A 70-year-old man with a history of gastric ulcer status post Billroth II partial gastrectomy underwent upper and lower endoscopy for evaluation of postprandial abdominal bloating. Upper endoscopy showed ulceration of the gastrojejunostomy site. Colonoscopy findings were unremarkable. Histologically, the gastric biopsy demonstrated a lymphoplasmacytic infiltrate involving the entire thickness of the mucosa (Figure 1.54, A), increased intraepithelial lymphocytes (Figure 1.54, C, D), and active chronic gastritis (Figure 1.54, B). No loss of parietal cell mass or enterochromaffin cell–like hyperplasia was seen to suggest autoimmune metaplastic atrophic gastritis. A Helicobacter pylori immunostain was negative. According to the patient’s medical record, he was taking irbesartan, an angiotensin receptor blocker (ARB), pointing to the diagnosis of ARB-induced gastritis. While ARB-induced duodenitis is well described, with villous atrophy and intraepithelial lymphocytosis mimicking celiac disease and sometimes also subepithelial collagen thickening, ARB-induced gastritis has only more recently been described. Histologic findings include full-thickness mucosal lymphoplasmacytic infiltrate, with variable presence of acute inflammation, intraepithelial lymphocytosis, glandular atrophy, and subepithelial collagen thickening. The full-thickness lymphoplasmacytic inflammation in ARB-induced gastritis contrasts with the top-heavy lymphoplasmacytic infiltrate of Helicobacter gastritis. Crohn disease of the stomach can also show similar histologic features. In this case, the normal findings from the patient’s colonoscopy argued against Crohn disease. In summary, ARBs can induce full-thickness active chronic gastritis with intraepithelial lymphocytosis. Subepithelial collagen thickening has also been described but was not seen in this case. Various mechanisms have been hypothesized for the injury induced by this class of drugs, though none have been proven.

(Poster No. 55)

Joseph S. Kim, DO ([email protected]); Shunsuke Koga, MD, PhD; Swachi Jain, MBBS; Kristen M. Stashek, MD. Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia.

Context: In the distal colon, Paneth cell metaplasia (PCM) is one feature used to establish the presence of chronic mucosal injury, usually in the setting of inflammatory bowel disease (IBD). In this study, rectosigmoid adenomas were reviewed to see if PCM could be used as a histologic marker to distinguish IBD-associated from sporadic adenomas.

Design: A database search was performed, and 18 cases of rectosigmoid conventional IBD-associated low-grade dysplasia and 30 cases of rectosigmoid sporadic adenomas with low-grade dysplasia from screening colonoscopies were identified. Exclusions for the control group included history of IBD, graft-versus-host disease, or radiation to the rectum/prostate. H&E slides from both groups were evaluated for the presence of PCM. Fisher exact test was used for comparisons.

Results: In the IBD group, the mean age was 50.9 years (range, 23–74), and there was equal prevalence of Crohn disease and ulcerative colitis (50% each; 9 of 18). Concurrent history of primary sclerosing cholangitis was noted in 28% (5 of 18) of cases. Notably, 78% (14 of 18) of dysplastic lesions were endoscopically visible. PCM was significantly more prevalent in the IBD group (67%; 12 of 18) compared to the control group (10%; 3 of 30; P < .001). All control group adenomas with PCM had adjacent histologically visible prolapse-type changes. In the IBD subgroup analyses, Crohn versus ulcerative colitis, presence versus absence of primary sclerosing cholangitis, and flat versus visible dysplasia showed no significant differences in the presence of PCM.

Conclusions: PCM in rectosigmoid adenomas demonstrated 67% sensitivity and 90% specificity for indicating IBD-associated dysplasia, offering a potentially valuable histologic marker in relevant clinical contexts.

(Poster No. 56)

Ibrahim A. Mohammed, MD ([email protected]); Deepthi Rao, MD. Department of Pathology, University of Missouri, Columbia.

Context: Benign gallbladders are among the common specimens received for pathologic evaluation; however, gallbladder cancer (GBC) is a rare entity. More than half of GBC cases are diagnosed at a late stage. The disease has an aggressive clinical course with a median survival of less than 1 year, yet little is known about its pathogenesis.

Design: We conducted a comprehensive analysis involving 379 patients with confirmed GBC, utilizing the cBioportal platform and Cancer Genome Atlas Firehouse Legacy data. We investigated common genetic mutations associated with GBC and assessed the frequency of mutations in the ErbB signaling pathway.

Results: This study revealed a statistically significant association between TP53 gene mutation and the type of GBC. There was also a statistically significant association between small cell carcinoma and mutation in the SMARCA2 (66.7%, n = 3; P = 1.76 × 10⁻¹²) and RB1 (66.7%, n = 6; P = 2.16 × 10⁻⁸) genes. Further, poorly differentiated neuroendocrine tumor has a significant association with mutation in the PBRM1 (40%, n = 5; P = 6.73 × 10⁻⁷), NTRK3 (40%, n = 5; P = 2.66 × 10⁻⁸), and APLNR (33.3%, n = 1; P = 8.98 × 10⁻¹²) genes (Figure 1.56). Interestingly, ErbB pathway mutations, tested in a subset of patients, were noted in 40.6% of cases tested.

Conclusions: Our findings underscore the significance of TP53 mutations in the histologic diversity of GBC and shed light on the genetic landscape of neuroendocrine neoplasms. The frequent ErbB pathway mutations imply a potential role in pathogenesis. Further studies are warranted to elucidate the clinical implications of these findings.

(Poster No. 57)

Zhengfan Xu, MD ([email protected]); Qing Chang, MD. Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, Michigan.

Distinguishing grade 3 neuroendocrine tumor (NET) from neuroendocrine carcinoma (NEC) is a known diagnostic challenge, and accurate classification is critical. A 76-year-old woman presented with abdominal pain. An upper GI endoscopy showed mucosal nodularity and altered texture in the gastric antrum. Initial outside biopsy reported a high-grade NEN based on a 90% Ki-67 proliferation index. The patient received chemotherapy for 6 months and postchemotherapy PET-CT showed residual disease in the stomach. The rebiopsy specimen demonstrated atypical epithelial cells with fine chromatin, a moderate amount of eosinophilic cytoplasm arranged in nest and trabecular growth patterns, and frequent atypical mitotic figures. Nuclear molding or necrosis was not identified (Figure 1.57, A). Immunophenotypically, the tumor cells were positive for Cam 5.2, mCEA, and synaptophysin (strong and diffuse), while negative for TTF1, PAX8, and CDX2. p53 showed an equivocal null expression pattern (Figure 1.57, B). The Ki-67 proliferation index was 80% to 90% (Figure 1.57, C). Given the lack of unequivocal morphology of NEC, the case was reported as high-grade NEN with a differential diagnosis including NEC and grade 3 well-differentiated NET. Next-generation sequencing study was negative for typical NEC mutations including TP53 or RB. Interestingly, CCNE1 gene amplification, a phenomenon reported in pancreatic NEC, was identified and, in conjunction with the high proliferation rate, favors a NEC diagnosis. This case demonstrated the utility of molecular studies in classification of stomach high-grade NEN with overlapping morphology features and proliferation index between NEC and NET. To our knowledge, this is the first case with CCNE1 amplification in stomach NEN.

(Poster No. 58)

Ibrahim A. Mohammed, MD ([email protected]); Deepthi Rao, MD. Department of Pathology, University of Missouri, Columbia.

Context: Pancreatic ductal adenocarcinoma (PDAC) is a malignant infiltrative epithelial neoplasm with ductal differentiation. Many studies have shown that chronic pancreatitis (CP) is highly associated with PDAC. The International Pancreatitis Study Group conducted a multicenter retrospective study that revealed the cumulative risk of PDAC in patients with CP is 1.8% and 4% at 10 and 20 years, respectively, which indicates a 15- to 16-fold higher risk than the general population.

Design: We gathered 97 patients with confirmed PDAC using the cBioportal platform and Cancer Genome Atlas Firehouse Legacy data. Of the patients studied, 31 cases had a documented background of CP. We analyzed the common driver genetic mutations associated with PDAC, including SMAD4, TP53, KRAS, CDKN2A, and MUC4 in this group of patients. Further, we compared the mutational landscape in patients with CP to those without CP.

Results: This study revealed a significant association between SMAD4 gene mutation and PDAC without background CP (21.21%; 14 of 66) compared to cases with CP (3.23%; 1 of 31). The association is statistically significant (P = .03). Mutations in TP53, KRAS, CDKN2A, and MUC4 genes showed no significant difference between the 2 groups (Figure 1.58).

Conclusions: In PDAC, our study underscores distinct molecular patterns, spotlighting a nuanced role of SMAD4 mutation in the different contexts of CP. Further studies are crucial to explore the exact mechanisms through which CP interacts with SMAD4 mutation to pave the road for potential diagnostic and therapeutic strategies.

(Poster No. 59)

Carley Holmes, DO ([email protected]); Zhenhong Qu, MD, PhD; Aqsa Nasir, MD. Department of Pathology, Corewell Health East, Royal Oak, Michigan.

Type 1 autoimmune pancreatitis (AIP) is a form of pancreatitis associated with IgG4-related disease. Certain clinical and histologic features are classically associated with type 1 AIP. Individuals typically present with elevated serum IgG4 levels (2 times the upper limit of normal) and extrapancreatic involvement. Histologically, the lobular architecture is preserved. Periductal lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis are seen. The plasma cells are characteristically IgG4 positive. Our case involves a 64-year-old woman who presented with elevated liver enzymes, bilirubin, and lipase. Magnetic resonance cholangiopancreatography showed a high-grade stricture of the mid common bile duct with wall thickening and enhancement (suspicious for malignancy); mild pancreatic duct dilation, no discrete masses; and acute interstitial edematous pancreatitis. Atypical cells were present on cytology of the stricture. Pancreaticoduodenectomy was performed. The histologic examination of the pancreas demonstrated preserved lobular architecture and parenchyma with foci of fibrosis, duct-centric lymphoplasmacytic inflammation (Figure 1.59, A), and obliterative phlebitis (Figure 1.59, B). Type 1 AIP was suspected: plasma cells stained positive for IgG (Figure 1.59, C) but negative for IgG4 (Figure 1.59, D), and serum IgG and IgG4 levels were within normal limits. Based on the histologic features, the patient was diagnosed with type 1 AIP. While the presence of IgG4 is thought to be characteristic of type 1 AIP, it is not a requirement to make the diagnosis, and histology alone is sufficient. This case emphasizes the importance of histologic features for making the diagnosis of type 1 AIP.

(Poster No. 60)

Cassandra A. Lamm, DO ([email protected]); Josh A. Wisell, MD; Shyam S. Raghavan, MD. Department of Pathology, University of Colorado, Anschutz Medical Center, Aurora.

A 78-year-old woman presented with painful thrombosed hemorrhoids and perirectal abscesses. During a planned hemorrhoidectomy, an approximately 8-cm mass was found along the left side of the anal canal with ulceration. An incisional biopsy was performed, and the initial diagnosis was a high-grade malignant neoplasm with strong PRAME expression, most consistent with melanoma. The patient received one dose of immunotherapy before the case was rereviewed at our institution. Upon review, the lesional cells strongly expressed PRAME, but showed no expression of any melanocytic markers (SOX10, S100, Melan-A, tyrosinase, HMB45, KBAR), and no expression of cytokeratin. The tumor did, however, express nuclear SATB2, indicating a potential anatomic source (Figure 1.60, A [H&E], B [PRAME], and C [SATB2]; magnification ×400). Molecular testing demonstrated numerous pathologic mutations, including 2 in APC, 1 in KRAS, and 1 in SMARCA4. The constellation of SATB2 expression along with the mutational profile strongly supported a colorectal primary. Ultimately, the tumor was considered to be in the family of SMARCA4-deficient colorectal neoplasms, which have been described in the colorectum. This case highlights the value of molecular testing, and the dangers associated with considering PRAME a melanoma-specific marker, as PRAME can be variably expressed in numerous malignant neoplasms, including certain sarcomas, carcinomas, leukemias, and lymphomas.

(Poster No. 61)

Withdrawn.

(Poster No. 62)

Tanya Ponnatt, MD ([email protected]); Alyssa Krasinskas, MD; Michelle Reid, MD; Haider Mejbel, MD. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.

Context: Follicular dendritic cell sarcomas (FDCS) are rare neoplasms that account for about 0.4% of all soft tissue sarcomas.

Design: A 20-year retrospective study of gastrointestinal FDCS.

Results: Five primary gastrointestinal (GI) FDCS were identified (Table). Patients were 4 men and 1 woman, aged 26 to 77 years (mean, 53). Four cases (80%) were symptomatic, while 1 case (20%) was incidentally detected on radiologic exam. The stomach and colon were the primary site in 2 cases, while the duodenum was the primary site in 1 case. Tumor size ranged from 6.8 to 20 cm (mean, 11.5 cm). Histologically, the tumor cells were epithelioid and/or spindled and arranged in a storiform and/or whorling pattern in all cases. Lymphocytes were sprinkled in between the tumor cells and frequent mitoses were often seen. In all cases, the tumor cells were strongly and diffusely positive for at least 2 follicular dendritic markers (CD21, CD23, CD35). A mean follow-up of 11.8 months (range, 1–24 months) was noted. Neoadjuvant chemotherapy with complete surgical resection was performed on the 2 cases with available clinical data. One case showed stable metastatic disease with no new locoregional recurrence, while the other case showed continued progression and resistance to multiple chemotherapy and immunotherapy agents.

Conclusions: FDCS is a rare tumor with distinct morphology and phenotype. However, because of its rarity, alternative diagnoses are often considered at the initial interpretation. Therefore, awareness of its varied location, morphology, and immunophenotype is essential to arrive at an accurate diagnosis that may alter the disease stage and inform therapy.

(Poster No. 63)

Ning Li, MD, PhD ([email protected]); Lili Lee, MD. Department of Pathology, NYUniversity Langone Long Island, Mineola, New York.

We present the case of a 48-year-old patient who presented with worsening dyspnea on exertion and palpitations. Imaging studies revealed a 5.3 × 4.5 × 4.0-cm left atrial mass, mediastinal lymphadenopathy with multifocal patchy ground glass opacities in the lung, and a 4.9 × 4.1-cm hypodense mass in the right hepatic lobe with irregular margins. The clinical impression was metastatic lung carcinoma, and a liver biopsy was performed. Histologic examination of the liver mass biopsy revealed sheets of epithelioid and spindled cells with granular, eosinophilic to clear cytoplasm and round nuclei with small nucleoli (Figure 1.63, A, B). Some cells showed dense eosinophilic, rhabdoid morphology and some had clear foamy cytoplasm (Figure 1.63, A). Rare intranuclear pseudoinclusions were present. No significant cytologic atypia or mitotic figures were identified. The tumor was diffusely positive for melanocytic markers HMB45 and Melan-A (Figure 1.63, C), with patchy positivity for SMA (Figure 1.63, D). The tumor was negative for desmin, HepPar-1, arginase, glypican-3, S100, CK7, CK20, TTF-1, napsin A, AFP, MOC-31, AE1/AE3, SOX-10, and ER. The overall histology and immunohistochemical profile were consistent with a perivascular epithelioid cell tumor (PEComa). Hepatic PEComas are very rare mesenchymal neoplasms composed of distinctive perivascular epithelioid cells that express both melanocytic and smooth muscle markers. Most hepatic PEComas are sporadic. TSC2 mutations and TFE3 gene rearrangements have been identified in distinctive subsets of PEComas. Multifocal disease may be associated with tuberous sclerosis. Although most hepatic PEComas are benign, the risk of malignant transformation is uncertain.

(Poster No. 64)

Swachi Jain, MBBS ([email protected]); Joseph S. Kim, DO; Kristen M. Stashek, MD. Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia.

Context: Hypermucinous dysplasia (HMD) is a subtype of nonconventional dysplasia that occurs in the setting of inflammatory bowel disease (IBD). It poses a diagnostic challenge, as it is a high-risk lesion, and often shows subtle cytologic atypia. This study assesses the clinical and pathologic findings and outcomes in IBD patients with HMD.

Design: A database search (2013–2023) was performed, and all H&E-stained slides were reviewed to confirm the diagnosis. The presence of high-grade dysplasia, percentage of mucinous morphology, and villous architecture were assessed. Clinical, endoscopic, and follow-up data were obtained from the medical record.

Results: Fifteen IBD patients with 24 distinct HMD lesions were identified. Clinical/endoscopic findings are summarized in the Table. Morphologically, 17 of 24 lesions (71%) showed pure hypermucinous morphology, while 7 were mixed with an adenomatous component. Eleven cases (46%) had a predominant (>80%) villous morphology, while the remaining showed 5% to 50% villous morphology. High-grade dysplasia was identified in 5 lesions. Crypt cell atypia was identified in mucosa adjacent to the HMD in 9 lesions. Follow-up was available for 14 patients (mean, 3.1 years), with 5 developing adenocarcinomas, 1 developing high-grade dysplasia, and 7 developing low-grade dysplasia, all in the same segment of the colon in which the HMD was diagnosed initially.

Conclusions: In this series, HMD occurred in patients with both ulcerative colitis and Crohn disease. It was more common on the left side and endoscopically visible in 58% of cases. Notably, 43% of patients developed advanced neoplasia in the same segment of the colon within 2.1 years of initial biopsy.

(Poster No. 65)

Yan Zhou, MD ([email protected]). Department of Pathology, Boston University, Boston, Massachusetts.

Context: Incidental gallbladder carcinoma (GBC) is a significant clinical phenomenon and perplexing dilemma for surgeons and patients. Clinical implications, prognostic factors, and optimal management strategies are crucial to guide therapeutic interventions and improve survival for affected individuals.

Design: We performed a retrospective study in our institution and identified 20 unexpected GBCs out of 6078 patients (0.33%) who underwent cholecystectomy during the past decade. Demographic data, clinical symptoms, and pathologic and imaging findings were reviewed. Statistical analyses were used for assessing the significant difference of tumor stage and mortality of incident GBC. A P value ≤ .01 was considered statistically significant.

Results: The median age of patients was 64.5 years (range, 31–77 years) including 15 women and 5 men. Eleven patients were African American, 5 Hispanic, 3 White, and 1 Asian. Invasive adenocarcinoma was identified in 95% (19 of 20), while invasive adenosquamous carcinoma was seen in 5% (1 of 20). Most cases (75%) were incidental carcinoma, with higher tumor stage (6.6% T1, 60% T2, 33.3% T3), and required a second surgery of partial hepatectomy and portal nodal dissection after initial cholecystectomy. Five patients (25%) had a radiographically suspected mass; most were lower tumor stage (80% T1, 20% T2). Cancer stage surgery was completed initially. The mortality rate for incidental carcinoma was 20% in our study.

Conclusions: Incidentally identified GBC is rarely seen (less than 1%) at the time of cholecystectomy. Second surgery is required for completion of tumor stage. High suspicion and intraoperative frozen consultation are advised at the time of difficult cholecystectomy in elderly female patients.

(Poster No. 66)

Asad Ur Rehman, MD¹ ([email protected]); Abigail S. Ghorbani, BS¹; John S. Bynon Jr, MD²; Erin Rubin, MD.¹ Departments of ¹Pathology and Laboratory Medicine and ²Transplant and General Surgery, University of Texas Health Science Center, McGovern Medical School, Houston.

Ductal plate malformations (DPM) of the liver occur because of aberrant embryologic ductal plate remodeling, leading to the persistence of early bile duct structures postembryonically. DPM can result in a spectrum of diseases to include Von Meyenburg complexes, congenital hepatic fibrosis, Caroli disease, Caroli syndrome, and polycystic kidney/liver disease, among others. These disorders may occur in isolation or as a component of multisystem syndromes with extrahepatic manifestations, often developmental/genetic in origin. It has been described that the mutation responsible for DPM has been localized in the primary cilia of biliary epithelial cells. We present a case of a 52-year-old man with benign hepatic cysts, innumerable bile duct hamartomas (von Meyenburg complexes), and a perihepatic liposarcoma with MDM2 gene amplification. Microscopic examination of right hepatic lobectomy (Figure 1.66, A) revealed a dedifferentiated liposarcoma (Figure 1.66, B [lower left, red arrow] and C) and bile duct hamartomas (von Meyenburg complexes) (Figure 1.66, B [upper right, yellow arrow] and D). The association of DPM with the extrahepatic manifestation of a perihepatic liposarcoma has not been previously reported. This case underscores the potential to identify extrahepatic disorders that could have a pathogenetic connection with DPM.

(Poster No. 67)

Henrietta O. Fasanya-Maku, MD, PhD¹ ([email protected]); Michael T. Deavers, MD¹; Wade R. Rosenberg, MD²; Mary R. Schwartz, MD.¹ Departments of ¹Pathology and Genomic Medicine and ²Surgery, Houston Methodist, Houston, Texas.

Nesidioblastosis is a disorder of pancreatic islets characterized by islet cell hyperplasia, functional dysregulation of β cells, and resultant hyperinsulinemic hypoglycemia. Nesidioblastosis is most common in infants, where it may be focal or diffuse and is usually associated with genetic mutations. Adult-onset nesidioblastosis is rare and may uncommonly be seen after bariatric surgery. This rare complication is not generally recognized by pathologists and other physicians. We report a case of a 53-year-old woman who 1 year after Roux-en-Y gastric bypass surgery developed severe hypoglycemia with blood glucose levels ranging from 30 to 60 mg/dL, nausea, and syncope. She had lost 188 pounds from her prebypass weight of 393 pounds. CT imaging did not show any pancreatic lesions. Her symptoms were not alleviated with medical management (acarbose, diazoxide) or reversal of the gastric bypass. A distal pancreatectomy was performed, demonstrating diffuse islet cell hyperplasia, enlarged islets up to 550 μm (Figure 1.67, A), and very focal ductuloinsular complexes (Figure 1.67, B). The patient’s symptoms improved after the distal pancreatectomy. She was placed on Ozempic for weight loss management. She has had occasional mild overnight hypoglycemia but is generally euglycemic. The pathogenesis of nesidioblastosis following bariatric surgery is not clear. It has been proposed that it is due to an exaggerated postprandial glucagon-like peptide 1 (GLP-1) response and rapid increase of nutrient delivery into the foregut. In patients with nesidioblastosis and a history of bariatric surgery, use of GLP-1 agonists should be carefully considered. Integrating clinical, biochemical, and histologic findings are crucial to achieving this diagnosis.

(Poster No. 68)

Xing Li, MD ([email protected]); Austin Chan, MD; Adwait Marhatta, MD; Hua-Fang Lin, MD; Kritika Krishnamurthy, MD; Qing Wang, MD, PhD; Yanhua Wang, MD, PhD; Yang Shi, MD, PhD. Department of Pathology, Montefiore Medical Center, Bronx, New York.

Acute myeloid leukemia with plasmacytoid dendritic cell differentiation (pDC-AML) is a recently proposed new type of AML characterized by frequent RUNX1 mutation, clonal expansion of pDCs, and poor outcome. In this report, we present a challenging case of pDC-AML involving both lymph node and skin with different degrees of maturation. A 41-year-old man presented with pancytopenia, enlarged axillary and mediastinal lymphadenopathy, and skin lesions. Peripheral blood flow cytometry study displayed 27.5% myeloblasts that were positive for CD34, CD117 (dim), and CD123. Next-generation sequencing of the bone marrow biopsy unveiled RUNX1/PTPN11/SETBP1 mutations. Lymph node needle core biopsy of the left axilla illustrated proliferation of medium-sized atypical cells with relatively condensed chromatin (Figure 1.68, A) expressing CD4 (diffuse), CD123 (strong) (Figure 1.68, B), TdT (diffuse) (Figure 1.68, C), and CD34 (a very small subset) (Figure 1.68, D), lacking CD56, most compatible with pDCs associated with AML. Furthermore, a skin biopsy demonstrated dermal infiltration by cells with similar morphology and immunophenotypes except rare and weaker TdT expression and complete negativity for CD34, demonstrating more maturation of pDCs. The main differential diagnoses for this challenging case were blastic plasmacytoid dendritic cell neoplasm, which is usually positive for CD56 and negative for CD34; mature plasmacytoid dendritic cell proliferation associated with AML, which is negative for CD34 and TdT; and myeloid sarcoma, which shows blastic morphology in extramedullary tissue. The mechanism underlying the different degree of maturation of pDCs at different anatomic locations in this unusual AML case remains undetermined.

(Poster No. 69)

Sahar Nozad, MD¹ ([email protected]); Julie A. Rosser, DO²; Mina L. Xu, MD³; Jonathan Galeotti, MD⁴; Danielle L. Maracaja, MD⁴; Philipp W. Raess, MD, PhD⁵; Stephanie Salansky, MEd, MS, MT(ASCP)⁶; Olga Pozdnyakova, MD, PhD.^{7 1}Department of Pathology, University of Kentucky, Lexington; ²Department of Pathology, Presbyterian St Lukes Medical Center, Denver, Colorado; ³Department of Pathology, Yale University School of Medicine, New Haven, Connecticut; ⁴Department of Pathology, University of North Carolina, Chapel Hill; ⁵Department of Pathology, Oregon Health & Science University, Portland; ⁶Hematology/Clinical Microscopy Committee, College of American Pathologists, Northfield, Illinois; ⁷Department of Pathology, University of Pennsylvania Hospital, Philadelphia.

Context: Accurate identification of white blood cells (WBC) in peripheral blood smears by laboratory personnel is crucial for clinical diagnosis and patient management. We evaluated the performance of 2 College of American Pathologists (CAP) proficiency testing (PT) programs—blood cell identification photomicrographs (BCP) and BCP virtual (BCPV)—with a goal of identifying laboratory education opportunities.

Design: We reviewed performance for the BCP (2008–2021) and BCPV (2011–2021) PT challenges from ∼5500 and ∼1000 participating laboratories, respectively. The cells of interest included lymphocytes, reactive lymphocytes, large granular lymphocytes (LGLs), lymphoma cells, blasts, granulocytes of varying maturation stages, monocytes, eosinophils, and basophils. We recorded percent of correctly identified cell types, comparing PT results over the years and across both formats.

Results:Figure 1.69 shows the averages of the correct identification rates in BCP and BCPV with <80% as a cutoff for poor performance. For photomicrographs, lymphoma cells, blasts, reactive lymphocytes, and LGLs showed the lowest identification rates (62%, 70%, 78%, and 79%, respectively). For virtual slides, lymphoma cells, LGLs, reactive lymphocytes, toxic neutrophils, and blasts showed the lowest identification rates (48%, 69%, 69%, 74%, and 76%, respectively).

Conclusions: Our study is the first to (1) assess the overall performance of blood cell identification in a large number of clinical laboratories; (2) highlight the specific WBC types presenting significant challenges for morphologic identification for laboratory personnel, with both photomicrograph and virtual formats showing similar trends; and (3) identify the areas that require intervention by committee members to improve laboratory performance.

Nozad received grant or research support from Clarix Imaging Corporation. Xu is a consultant for Treeline Biosciences and Pure Marrow. Maracaja received grant or research support from Beckman Coulter. Raess received grant or research support from Scopio Labs. Pozdnyakova is a consultant for Scopio Labs and Sysmex.

(Poster No. 70)

Withdrawn.

(Poster No. 71)

Tiffany Javadi, MD ([email protected]); Christine G. Roth, MD. Department of Pathology, Emory University School of Medicine, Atlanta, Georgia.

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell lymphoma associated with human T-cell leukemia virus type 1 (HTLV-1) and a wide array of clinical and pathologic presentations that overlap with other T-cell lymphomas. We describe a case of a 30-year-old HTLV-1–positive woman who presented with a nonhealing ulcerated lesion on her left upper inner thigh. Punch biopsy of skin revealed an atypical lymphoid infiltrate within the subcutis characterized by large anaplastic-appearing cells (Figure 1.71, A). The neoplastic cells were positive for CD30 (Figure 1.71, B), CD25 (Figure 1.71, C), and CD4 (partial), and negative for CD7, CD3, CD20, PAX5, CD2, CD5, CD8, ALK-1, and TIA-1. The overall morphology and immunophenotype indicated a CD30-positive T-cell lymphoproliferative neoplasm that was challenging to further subclassify; the main differential diagnosis included the anaplastic variant of ATLL as well as CD30⁺ anaplastic large cell lymphoma (ALCL). To distinguish between these diagnostic considerations, HTLV-1 bZIP factor (HBZ) in situ hybridization (ISH) was performed to evaluate for molecular integration of HTLV-1 within the neoplastic tumor cells. The HBZ ISH negativity (Figure 1.71, D) rendered the diagnosis of ATLL unlikely and favored ALCL. Staging evaluation based on PET/CT was most consistent with a systemic ALCL, informing subsequent treatment decisions. This case highlights the value of HBZ ISH as a diagnostic tool in differentiating HTLV-1–mediated ATLL from other T-cell lymphomas, especially in the setting of overlapping morphologic and immunophenotypic findings and HTLV-1 seropositivity. HBZ ISH studies can help accurately diagnose or exclude ATLL, optimize treatment modalities, and ultimately impact patient outcomes.

(Poster No. 72)

Jack Reid, MD¹ ([email protected]); Gabriella Cardoza-Favarato, MD²; Mark Evans, MD³; Sumayya Aslam, MD⁴; Xiaohui Zhao, MD⁴; Sherif Rezk, MD.^{4 1}Department of Pathology, City of Hope, Duarte, California; ²Department of Pathology, Tri-City Medical Center, Oceanside, California; ³Department of Pathology, Caris Life Sciences, Irvine, California; ⁴Department of Pathology, University of California, Irvine Medical Center, Orange.

Context: CD20 is a membrane-spanning protein expressed on the surface of mature B cells and is frequently employed in the identification of both benign and malignant neoplasms of B lymphocytes by immunohistochemistry (IHC). Specimens with necrosis lose their fidelity and prevent the utility of IHC stains. CD20 positivity is frequently retained in the necrotic areas of lymphoid lesions and can be utilized as a lineage-specific marker, whereas other IHC markers fail to highlight the expected cells within less viable samples.

Design: Eighty-nine patients were diagnosed with lymphoma (n = 35), benign lymphadenopathies (n = 6), carcinomas (n = 23), gliomas (n = 9), sarcomas (n = 10), and melanomas (n = 6), all of which were associated with observable necrosis. Appropriate IHC studies were performed for each specimen’s diagnosis, and all were reviewed for anti-CD20 IHC staining (clone L26, Roche 760-2531) within areas containing >50% necrotic cells.

Results: Preliminary data showed that 30 of 35 lymphoma cases (86%) were positive for CD20 in necrotic areas, as demonstrated by focal to complete membranous staining of ghost cell outlines (Table). All 30 positive cases were of B-cell lineage. None of the carcinomas, gliomas, sarcomas, or melanomas demonstrated positivity for their lineage-specific IHC markers in regions of necrosis.

Conclusions: We found that in aggressive B-cell lymphomas, most B-cell populations within necrotic specimens retained expression of CD20 by IHC. Although sampling additional tissue may be the preferred solution for diagnosing less viable specimens, rebiopsy may not be possible for some patients. In these circumstances, demonstrating CD20 IHC expression within necrotic ghost cells may be sufficient for characterizing lymphoid populations.

(Poster No. 73)

Tsigab B. Hagos, MD ([email protected]); Ramya Gadde, MD; Howard Meyerson, MD. Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, Ohio.

Context: CD1c is an antigen that has been used by immunologists to define marginal zone B cells. A few previous studies of CD1c immunohistochemistry (IHC) expression in B cell lymphoma have been performed. However, expression by lymphoma subtypes using recent classification schemes has never been employed.

Design: CD1c IHC staining was performed on 10 cases each of follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL) and 8 cases of lymphoplasmacytic lymphoma (LPL). IHC staining was correlated with flow cytometry expression.

Results: CD1c IHC was positive in 37.5% of all low-grade B-cell lymphomas. Diffuse positivity was seen in 6.25% of positive cases: 1 FL, 1 MCL, and 1 MZL. Partial positivity was seen in 31.25%: 3 FL, 5 CLL/SLL, 3 MCL, 3 MZL, and 1 LPL. A total of 41.7% did not express CD1c by IHC or only expressed rare scattered positive cells. CD1c was not detected in normal germinal centers, but 4 of 10 FL lymphomas were positive, indicating aberrant CD1c expression may be a feature of subset of FL. Expression by IHC was imperfectly correlated with that seen by flow cytometry (correlation coefficient = 0.32) with many cases positive by flow cytometry but lacking IHC reactivity (n = 11), most notably in LPL cases (5 of 8) (Figure 1.73, A–B).

Conclusions: CD1c IHC staining may be useful in the workup of low-grade B-cell lymphomas because of aberrant expression in germinal center cells in a subset of FL and lack of staining in most LPL, but lacks diagnostic specificity for lymphoma subtype.

(Poster No. 74)

Samir M. Amer, MD, PhD¹ ([email protected]); Nicholas Mackrides, MD²; Reza Nejati, MD.^{2 1}Department of Pathology, Temple University Hospital, Philadelphia, Pennsylvania; ²Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Coexisting clonal plasma cell populations with low-grade B-cell lymphoma (LGBCL) in the bone marrow are uncommon and raise the question of whether these 2 populations are clonally related. This can be a challenging differential diagnosis, and the distinctions are important for proper management. An 82-year-old man presented with progressive anemia, worsening renal function, and an IgM κ monoclonal gammopathy. Bone marrow (BM) biopsy was performed and showed a variable cellular BM (∼40%), with focally clustered CD138-positive, κ monotypic plasma cells representing 15% of the BM cellularity. CD20 showed B cells accounted for approximately 20% of total cells. Flow cytometry detected a plasma cell population that was CD45⁻, CD38⁺⁺⁺, CD138⁺⁺, and cytoplasmic κ light chain restricted and a λ monoclonal B-cell population expressing CD19, CD20, CD22, CD23, CD79b, and FMC7 and negative for CD5, CD10, CD38, and CD103. Based on these findings, the differential diagnosis encompassed plasma cell neoplasm featuring lymphoplasmacytic morphology and/or LGBCL with plasmacytic differentiation. However, the light chain restriction on B cells (λ) contrasted with that of the plasma cells (κ) in our case. Thus, the possibility of a plasma cell neoplasm and a clonally unrelated low-grade B-cell neoplasm emerged as another consideration. Chromosomal microarray analysis and next-generation sequencing performed on samples enriched with CD138 and CD19 microbeads showed loss of Y chromosome in 20% of the cells with MYD88 mutation. By confirming the presence of MYD88 mutation in both populations (Table), we were able to establish the diagnosis of lymphoplasmacytic lymphoma, which is an LGBCL with plasmacytic differentiation.

(Poster No. 75)

Deepak Kumar, MD ([email protected]); Fnu Kiran, MD; Richard D. Hammer, MD. Department of Pathology, University of Missouri Healthcare, Columbia.

A 72-year-old woman presented with 2 months of weakness, weight loss, and multiple enlarged lymph nodes. Retroperitoneal lymph node biopsy showed small lymphocytes and plasma cells with background eosinophilic amorphous material. Flow cytometry showed a CD10⁺ λ light chain restricted B-cell population, with a first impression of follicular lymphoma, sclerosing type. Immunostains showed neoplastic B cells positive for CD10 and Bcl-2 but negative for Bcl-6. The eosinophilic background was positive for Congo red and PAS while negative for trichrome, consistent with amyloid. CD138 showed increased plasma cells bearing monotypic λ light chain, raising consideration of a composite B-cell lymphoma. Plasma cells showed monotypic IgM while negative for IgG and IgA heavy chains, raising suspicion for lymphoplasmacytic lymphoma (LPL) (Figure 1.75, A–D). Additional germinal center B-cell immunostains LMO2 and GCET were negative. Finally, molecular results were positive for MYD88 L265P alteration, were negative for Bcl-2 and Bcl-6 rearrangements, and showed no abnormality in chromosomes 7 and 17, rendering a diagnosis of LPL with amyloid deposition. Review of limited available literature showed CD10⁺ LPL is extremely rare. A handful of such cases are reported, with the latest reported in 2017. One study including 161 patients showed only 7% of LPLs were CD10 expressers. CD10 expression should not exclude a diagnosis of LPL. Amyloid deposition in association with abundant plasma cells is not limited to myeloma, and, though rare, a diagnosis of IgM-producing B-cell lymphoma should also be suspected. Based on the CD10 positivity, clinical frequency, and location, such tumors might be misdiagnosed as follicular lymphoma.

(Poster No. 76)

Patrick Bladek, MD ([email protected]); Carlos Murga-Zamalloa, MD. Department of Anatomic and Clinical Pathology, University of Illinois Hospital & Health Sciences System, Chicago.

Classic follicular lymphoma (FL) is characterized by nodular growth of neoplastic lymphocytes with an IGH-BCL2 translocation. However, rare cases lack this translocation, usually occurring in the inguinal region and harboring a 1p36 deletion. They can be misdiagnosed as large B-cell lymphomas, but feature a distinct clinical course. Follicular lymphomas with diffuse growth and negativity for both the 1p36 deletion and IGH-BCL2 are extremely rare. We present the case of a 55-year-old woman who underwent abdominal wall reconstruction. An incidental 8-cm mass was discovered. Fragments of fibroadipose tissue were sectioned to reveal a nodule. Microscopy demonstrated atypical lymphoid aggregates (Figure 1.76, A) with centrocyte-like morphology, diffuse growth pattern, and no large cell transformation (Figure 1.76, B). Focal areas featured neoplastic nodular patterns. The atypical lymphocytes were positive for PAX-5, CD20, CD10, BCL-6, and MUM-1. They were negative for CD5, BCL-2 (Figure 1.76, C), and cyclin D-1. CD21 highlighted background dendritic follicular meshworks but was downregulated within areas of atypical nodular growth (Figure 1.76, D). The Ki-67 proliferation index was 20%. FISH testing for 1p36 (TNFRSF14) and IGH-BCL2 was negative for rearrangements or deletions. Two years later, the patient reported pelvic swelling. Imaging demonstrated left pelvic/inguinal adenopathy encasing the left external iliac vein, along with right and left para-aortic lymphadenopathy. Biopsy results were consistent with follicular lymphoma with a similar immunophenotype to the original diagnostic biopsy and no definitive morphologic evidence of transformation. Repeat molecular testing revealed the same TNFRSF14 deletion. This case demonstrates the need for vigilance when confronted with an atypical follicular lymphoma.

(Poster No. 77)

Hagar Attia, MD ([email protected]); Elif Yakut, MD; Jenna Zudell, MD; Raavi Gupta, MD. Department of Pathology and Laboratory Medicine, SUNY Downstate Health Sciences University, Brooklyn, New York.

Context: Adult T-cell leukemia/lymphoma (ATLL) is a rare aggressive neoplasm of mature T cells caused by human T-lymphotropic virus type 1 (HTLV-1). ATLL is identified in 2 distinct populations: Japanese (JP) and Caribbean (CP). Disease course could be aggressive (acute and lymphomatous subtypes) or indolent (chronic and smoldering subtypes). Most disease characteristics currently in the literature are derived from large Japanese studies, with limited data available on the CP population. We describe the clinicopathologic and prognostic indicators of ATLL in a CP population.

Design: A cohort of 75 patients with tissue-proven diagnosis of ATLL were classified according to Shimoyama criteria. Demographic, clinical, radiologic, and laboratory findings were noted.

Results: A striking female predominance (M:F 1:2) was noted compared to the JP population (M:F 1.5:1). The median age at diagnosis was 58 years, 10 years earlier than the JP population. Most presented with aggressive subtypes, acute (45.3%) and lymphomatous (34.6%), with fewer nonaggressive subtypes, chronic (9.3%), and smoldering (10.6%). The lymphomatous subgroup had a 73% female majority. Seventy-six percent of patients were classified as stage IV (Lugano classification), and most had elevated calcium and LDH (Table), parameters linked to an aggressive disease course. In contrast, the JP population was reported to exhibit a higher prevalence of smoldering subtype.

Conclusions: To our knowledge, we present one of the largest clinicopathologic studies of ATLL in the CP population. CP ATLL presents at a younger age, with female predominance and higher incidence of aggressive disease as compared to JP population. ATLL in the CP population stands out as a distinct and aggressive entity, emphasizing the need for appropriate diagnosis and management.

(Poster No. 78)

Farhan Hassan, MD¹ ([email protected]); Mohammad Hussaini, MD²; Theresa Boyle, MD²; Nagehan Pakasticali, MD²; Julie Y. Li, MD, PhD.^{2 1}Department of Medicine, School of Medicine, University of Missouri, Kansas City; ²Department of Pathology, Moffitt Cancer Center, Tampa, Florida.

Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm commonly found in extranodal sites, with its pathogenesis remaining unclear. Tumor cells typically exhibit a spindled morphology, while epithelioid morphology is rarely reported. Here, we present a rare biphasic FDCS with distinct immunophenotypic and molecular characteristics. A 63-year-old woman presented with constipation and rectal bleeding. Imaging revealed an 11.4-cm lobulated enhancing soft tissue mass in the posterior pelvis. H&E sections revealed 2 sharply demarcated biphasic neoplastic populations: one population comprised spindled cells (Figure 1.78, A), expressing CD21 (Figure 1.78, B), CD23, CD35, clusterin, EMA, and D2-40 (not shown); the other population consisted of epithelioid cells (Figure 1.78, C) lacking CD21 (Figure 1.78, D) and other FDC-associated markers except for focal weak clusterin expression. Both populations tested negative for CD163, CD68, S-100, langerin, CD1a, ALK-1, CD30, CD117, HMB45, pan-CK, and EBER. Molecular studies revealed a nearly identical mutational profile, confirming clonal identity and ruling out a composite tumor. Additionally, low-level pathogenic mutations (variant allele frequency <10%) were found in GABRA6, ICOSLG, and VEGFA, alongside altered transcript expression in PDGFRB in both populations. While no RNA fusions were detected, we demonstrated a significant increase in PDGFRB expression for the first time using the RNA Salah Targeted Expression panel, with a log2 ratio >2, indicating a more than 4-fold increase compared to a pooled normal control. The absence of FDC antigens poses a diagnostic challenge for FDCS. Investigating the frequency of PDGFRB expression in future studies and its role in the disease will be intriguing.

(Poster No. 79)

Khanh Duy Doan, MD ([email protected]); Muhammad Hussain, MD; Ashish Bains, MD. Department of Pathology, Temple University Hospital, Philadelphia, Pennsylvania.

Acute promyelocytic leukemia (APL) when suspected on blast morphology is considered a hematologic emergency, and patients are usually started on all-trans retinoic acid. The next diagnostic test is generally flow cytometric immunophenotyping, with an expected negativity of blasts for CD34 and HLA-DR in addition to strong myeloperoxidase expression. However, rare cases are known to express CD34 and/or HLA-DR, making it difficult to entirely exclude APL. Even rarer are cases where a T-cell lineage may also be assigned because of concomitant expression of CD3, thus meeting the immunophenotypic criteria of a mixed-phenotype acute leukemia (MPAL). We report a case of a 75-year-old woman with a history of lung adenocarcinoma treated with lobectomy and chemotherapy 4 years prior who presented with a WBC count of 6.4 K/μL with 66% blasts (Figure 1.79, A). Blasts were sparsely granular without Auer rods, though they frequently showed the characteristic bilobed/convoluted nuclei suspicious for APL, microgranular variant. Flow cytometry identified leukemic cells with strong CD34 expression with myeloid (myeloperoxidase, CD117, and CD13) and T-cell lineage–associated markers (cytoplasmic CD3 and CD2), fulfilling the updated immunophenotypic criteria for assignment as MPAL, T/myeloid. However, the final diagnosis of APL was established based on FISH confirming a PML:RARA rearrangement. This case highlights the importance of basic morphologic findings that must be considered in all suspected cases of APL where immunophenotyping may result in a misdiagnosis. It also underscores that the updated 5th edition World Health Organization criteria for immunophenotypic assignment of MPAL are less stringent than previous iterations.

(Poster No. 80)

Yaping Ju, MD, PhD¹ ([email protected]); Imran Siddiqi, MD, PhD¹; Yi Xie, MD, PhD²; Ling Zhang, MD³; Mark C. Lu, MD²; Endi Wang, MD, PhD.^{1 1}Department of Pathology, University of Southern California, Los Angeles; ²Department of Pathology and Laboratory Medicine, University of California San Francisco; ³Department of Pathology, Moffitt Cancer Center, Tampa, Florida.

Context: Lymphoplasmacytic lymphoma (LPL) is a type of small B-cell lymphoma that is usually negative for CD10 expression. CD10 is a follicle center signature antigen, and its expression is conventionally used to define follicular lymphoma (FL) among small B-cell lymphoma. However, CD10 expression has been seen in rare cases of LPL in bone marrow biopsies, which potentially misleads to the diagnosis of FL. We present a series of CD10-positive LPLs compared with FL involving bone marrow to differentiate between these 2 clinically distinctive entities.

Design: The clinicopathologic data for 7 CD10⁺ LPL cases and 11 cases of FL with bone marrow involvement were collected and analyzed.

Results: Median ages of LPL and FL cases were 73 and 66 years, respectively (Table). Three of 7 LPL cases and 9 of 10 FL cases had lymph node involvement. All 7 cases of LPL demonstrated elevated serum IgM by immunoglobulin profiling and clonal IgM paraprotein by immunofixation. Three of 11 FL cases showed circulating lymphoma cells, while none of the LPL cases had them identified. Paratrabecular marrow involvement was seen in 7 of 10 FL cases but 0 of 7 LPL cases. IGH::BCL2 was positive in 5 of 6 FL cases by FISH, while none of 6 LPL cases had it detected. MYD88 L256P mutation was detected in all 7 LPL cases.

Conclusions: CD10-positive LPL involving bone marrow can be easily misdiagnosed as FL. Nonetheless, with clinical/morphologic suspicion, FISH can be used to exclude FL and genomic analysis can be applied to identify signature mutational profile and confirm the diagnosis.

(Poster No. 81)

Ivan De La Riva-Morales, MD ([email protected]); Madina Sukhanova, PhD; Lawrence Jennings, MD, PhD; Hamza Tariq, MD. Department of Pathology, Northwestern University, Chicago, Illinois.

MYD88 hotspot mutations are highly recurrent in primary large B-cell lymphoma of the central nervous system (PCNS-LBCL). Recent studies have shown that MYD88 mutations can be reliably detected in the cell-free DNA (cfDNA) of the cerebrospinal fluid (CSF) of patients with PCNS-LBCL; however, data on serum cfDNA are lacking. We report the case of a 42-year-old woman in whom low-level positivity for MYD88 p.L265P (0.264%) in the serum (Figure 1.81, C) led to an unexpected diagnosis of PCNS-LBCL. She presented with a 2-month history of confusion and was found to have splenomegaly and thrombocytopenia. Extensive workup was negative, including monoclonal protein studies, bone marrow biopsy, and spleen biopsy. Brain imaging revealed multifocal areas of diffusion restriction in the bilateral parietal lobes, raising a broad radiographic differential diagnosis. The patient’s neurologic symptoms worsened, and she eventually underwent a brain biopsy that showed perivascular and infiltrating large lymphocytes (Figure 1.81, A) positive for CD20 (Figure 1.81, B), PAX5, MUM1, BCL6, C-MYC, and BCL2, while negative for CD10, cyclin-D1, and EBER. PCR performed on the brain tissue was positive for MYD88 p.L265P mutation (Figure 1.81, D), confirming the diagnosis of PCNS-LBCL. The patient passed away shortly after the diagnosis because of septic shock. Our case highlights the emerging diagnostic utility of CSF and serum liquid biopsies for the detection of MYD88 mutation in patients with PCNS-LBCL, particularly those with atypical clinical and radiographic presentation. In the future, liquid biopsies for MYD88-mutated cfDNA could eliminate the need for invasive brain biopsies and serve as a tool for monitoring response to therapy in patients with PCNS-LBCL.

(Poster No. 82)

Nagehan Pakasticali, MD ([email protected]); Julie Li, MD; Mohammad O. Hussaini, MD. Department of Pathology, Moffitt, Tampa, Florida.

Blast crisis (BC) (>20%) is a dreaded complication of chronic myelogenous leukemia (CML) with a 7% 10-year risk. BC is usually myeloid but can be lymphoid (one-third), almost invariably B-cell type. We report exceedingly rare T-lymphoblastic blast phase of CML (TLBP-CML). The patient was a 69-year-old man with CML diagnosed in 1992. He received an allogeneic bone marrow transplant (HSCT) in 1993 and was in clinical remission till 2020, when he presented with inguinal lymphadenopathy (LAD), hepatosplenomegaly, and a WBC count of 168 000/L. Bone marrow showed CML–chronic phase (CML-CP). BCR-ABL p210 was 102% IS. The inguinal lymph node was initially misdiagnosed as T-cell lymphoma. Review at our institution showed T-lymphoblastic lymphoma positive for CD3, CD4, CD7, CD5, CD10, CD43, CD34 (subset), and CD117 (subset). FISH for BCR-ABL on tissue showed a 3–BCR-ABL fusion signal pattern in 25% of cells and a 2–BCR-ABL fusion signal pattern in 49% of cells. He was started on dasatanib with reduction in LAD but plateaued with 3-month p210 of 37% IS. Next-generation sequencing showed no ABL1 kinase domain mutation. He was switched to ponatinib, achieving morphologic and cytogenetic remission with partial molecular response (10.9% IS p210). He received HSCT on December 17, 2020, and achieved molecular remission (MMR) on March 17, 2021, and remained in MMR until a recent visit (June 2022) with 100% donor chimerism. In this report, we highlight a rare phenomenon (only a few cases in the literature) and diagnostic pitfall. Our report is the first case of late CML relapse (27 years) after transplant as extramedullary T-lymphoblastic lymphoma with only CML-CP in the marrow.

(Poster No. 83)

Michael B. Stone, DO ([email protected]); Suhalika S. Sahni, MD; Carlos A. Murga-Zamalloa, MD. Department of Pathology, University of Illinois at Chicago.

While BRAF V600E mutations are characteristic of hairy cell leukemia (HCL), other hematologic neoplasms can also harbor the mutation, including Langerhans cell histiocytosis, Erdheim-Chester disease, plasma cell neoplasms, and rarely other B lymphoid neoplasms. We present a case of a 73-year-old man with absolute lymphocytosis of 10 600/μL, extensive lymphadenopathy, and splenomegaly. Peripheral blood flow cytometry identified a κ-restricted B-cell neoplasm with expression of CD5, CD23, CD20 (dim), and CD200 and negativity for CD10, CD25, and CD103, immunophenotypically consistent with chronic lymphocytic leukemia (CLL). Bone marrow biopsy showed diffuse involvement by the neoplasm comprising small lymphocytes with condensed chromatin and scant cytoplasm and occasional large lymphocytes with prominent nucleoli and abundant cytoplasm (Figure 1.83). Cyclin D1 and LEF1 were negative by immunohistochemistry. FISH identified deletion 11q and trisomy 12. Persistent bicytopenia prompted a repeat bone marrow biopsy to exclude a concurrent myelodysplastic syndrome. This revealed involvement by the lymphoid neoplasm and no myelodysplasia. Next-generation sequencing showed a BRAF V600E mutation. The patient ultimately died from the disease despite supportive measures. Although LEF1 expression is present in the majority of CLL cases, its absence does not prevent a diagnosis of CLL/SLL. BRAF V600E mutations are more characteristic of HCL than CLL. In CLL, BRAF mutations are rare, confer a worse prognosis, and mostly do not involve the V600E mutation. The immunophenotype, morphology, chromosomal aberrations, extensive lymphadenopathy, and lymphocytosis were more consistent with a final diagnosis of CLL with BRAF V600E mutation.

(Poster No. 84)

Joshua Nguyen, DO ([email protected]); Michelle Don, MD. Department of Pathology, University of California San Diego.

Hairy cell leukemia (HCL) is a mature B-cell lymphoproliferative neoplasm typically negative for CD5 and CD10, rarely presenting with aberrant expression of either of these cell surface markers. Dual CD5 and CD10 expression in HCL has not been reported. This case involves a 68-year-old woman who presented in November 2021 with neutropenia and macrocytic anemia. Bone marrow biopsy showed a hypercellular marrow with 90% involvement by sheets of atypical small lymphocytes with moderate cytoplasm, a so-called “fried egg” appearance, that were positive for CD20 (Figure 1.84, A), CD10 (Figure 1.84, B), and CD5 in a large subset (Figure 1.84, C) that were negative for CD3 (Figure 1.84, D). These cells were also positive for PAX5, CD19, CD20, CD25, CD68, BCL1, BCL2, annexin A1 (focal), and CD103 (rare) and were negative for pankeratin, MUM1, SOX11, BCL6, MYC, CD117, CD34, CD138, CD30, MPO, and TDT by immunohistochemistry. Increased reticulin fibrosis was seen. Flow cytometry of the hemodilute bone marrow aspirate was noncontributory. Molecular testing on the core biopsy identified a BRAF V600E mutation. Fluorescence in situ hybridization testing for t(11;14) was negative. The findings were consistent with HCL with aberrant CD5 and CD10 expression. The patient was treated with cladribine and is currently without significant disease. To our knowledge, this is the first case of HCL with CD5 and CD10 expression by immunohistochemistry in the absence of positive flow cytometric analysis. Aberrant expression of these markers can present a diagnostic pitfall for other CD5- or CD10-positive B-cell neoplasms. Accurate diagnosis is necessary for appropriate treatment.

(Poster No. 85)

Hira Qadir, MD ([email protected]); Yulei Shen, MD, PhD; Wei Liu, MD, PhD; Juan Gomez-Gelvez, MD; Kedar V. Inamdar, MD, PhD; Sharmila B. Ghosh, MD. Department of Pathology, Henry Ford Health, Detroit, Michigan.

Context: Germline mutation in DDX41 genes is associated with late-onset myeloid neoplasms (MNs) and acquisition of a somatic DDX41 mutation as a second hit. Germline DDX41 mutations are present in approximately 1.5% of MNs.

Design: Clinical and pathologic data of DDX41-related acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cases diagnosed between January 2021 and January 2023 were analyzed using electronic medical records, bone marrow morphology, cytogenetics, and gene sequencing studies.

Results: Of 236 cases of AML and MDS reported, 4 cases of AML and 1 of MDS were associated with germline DDX41 mutation (2.1%). The M:F ratio was 4:1 with an average age of 74 years (68–81 years) (Table). The blast count ranged from 15% to 30% in 4 patients. One patient had 69% blasts. All patients had biallelic DDX41 mutations. A germline mutation with high allele frequency was followed by a somatic mutation in the DDX41 gene with low frequency in 4 patients. One patient had a germline mutation with additional mutations in NPM1 (VAF 17%) and FLT3 (VAF 27%). Four patients had normal karyotype, while 1 had del20q. All patients had persistent disease.

Conclusions: In our study, the presumed germline DDX41 mutations correlated with long latency, male preponderance, low blast count, normal karyotype, and persistent disease. No significant family history was present. The germline DDX41 mutation was followed by a secondary missense somatic mutation in the DDX41 gene as a leukemogenic event. Our findings emphasize the increased predisposition of MNs in association with germline DDX41 mutations, advocating for family screening and counseling.

Inamdar is a consultant for Beckman Coulter Inc.

(Poster No. 86)

Zeeshan Ahmed, MBBS, FCPS ([email protected]); Mohammad Shariq Shaikh, MBBS, FCPS; Samra Naz, MSc; Tariq Moatter, MSc, PhD. Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan.

Context: BCR-ABL tyrosine kinase is deregulated in as many as 95% of chronic myeloid leukemia (CML) patients. The most important mechanism that may confer imatinib resistance is point mutation within the BCR:ABL kinase domain. Thus, it is important to perform mutation analysis for effective therapeutic management once patients show imatinib resistance.

Design: This retrospective observational study was conducted at the Section of Molecular Pathology, Aga Khan University Hospital, Karachi, Pakistan, during a period of 2 years (January 2022 to December 2023). In this study, we analyzed for BCR:ABL1 kinase domain mutation by direct sequencing, and the detected mutations along with their percentage prevalence were reported.

Results: Of the 165 patients tested, males comprised 54% of the total, while females comprised 46% included in the full analysis. The median age was 39 years (range, 14–83 years). A total of 165 patients with CML were analyzed for BCR:ABL kinase domain mutation. Fifty-eight patients (35%) had a mutation in at least one of the domains of BCR:ABL conferring resistance to different generations of TKI. Mutations in BCR:ABL kinase domain were observed in different domains of BCR::ABL: ATP-binding P-loop (E255K, Y253H, G250E, L248V, and M244V; 41%), A-loop (A397P; 3%); SH2 contact (F359C, E355G, and F359I/V; 28%); and SH3 contact (T315I, F311I; 28%).

Conclusions: Amino acid substitutions at 7 residues (T315I, G250E, Y253H, E255K, F359V, and F359I) account for 77% of all resistance-associated mutations. The presence of either P-loop or T315I mutations in imatinib-treated patients should warn the clinician to reconsider the therapeutic strategy.

(Poster No. 87)

Veronica Gross, MD, PhD ([email protected]); David Barrera, MD; Sara Beardsley-Eide, DO; Samuel Roush, MD; Kevin Wang, MD; Sunjida Ahmed, MBBS; Riddhish Sheth, MD; Tahmeena Ahmed, MBBS. Department of Pathology, SUNY Stony Brook Medicine, Stony Brook, New York.

Splenic lymphangiomas are benign malformations caused by abnormal proliferation of lymphatic vessels. The cysts are typically lined by a single layer of endothelial cells, but papillary formations have been rarely reported. Splenic lymphangiomas are uncommon, and the papillary variant of splenic lymphangioma is exceptionally rare. This case highlights the importance of recognizing splenic lymphangiomas as an atypical cause of chronic flank pain as well as the unusual morphologic feature of papillary variant. The patient was a 19-year-old woman with Ehlers-Danlos syndrome (EDS) type 3 with aortic dilatation and Chiari malformation status post decompression who reported 4 years of increasing left subcostal abdominal pain. MRIs demonstrated increasing splenomegaly to 14.4 × 8.8 × 7.9 cm with a heterogenous, poorly enhancing lesion of 33 × 35 mm. A minimally invasive total splenectomy was performed. The spleen was 380 g, and a firm, well-circumscribed nodular mass of 6.5 × 3.5 × 3.6 cm with a red homogenous cut surface and central stellate scarring was noted (Figure 1.87, A). Histology demonstrated a splenic lymphangioma with the cyst wall exhibiting occasional papillary projections (Figure 1.87, B) positive for CD34, CD31 (Figure 1.87, C), and D2-40 (Figure 1.87, D). On 6-month follow-up, the patient was well with almost complete resolution of her abdominal pain. Although wandering spleen, spontaneous splenic rupture, and splenic infarction may be associated with EDS, this is the first described case of a splenic lymphangioma with papillary projections in a patient with EDS.

(Poster No. 88)

Jiehao Zhou, MD, PhD ([email protected]). Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Phoenix.

The patient is a 65-year-old man with a history of multiple myeloma. He received lenalidomide/bortezomib/dexamethasone chemotherapy, followed by autologous stem cell transplant and monthly subcutaneous daratumumab/lenalidomide/dexamethasone therapy. His myeloma was well controlled, with low copies on clonoSEQ test. He presented with fever. CBC showed hemoglobin 11.0 g/dL, white blood cell 3.7 × 10⁹/L, and PLTC 88 × 10⁹. Bone marrow evaluation demonstrated sheets of blasts (Figure 1.88, A, B). Immunophenotypic analysis showed blasts were positive for CD19, CD22, CD79a, CD20 (tiny subset), CD10 (tiny subset), CD33 (subset), HLA-DR, CD123, TDT, and surface κ light chain (Figure 1.88, C, D) and negative for CD34, cytoplasmic MPO, and all T cell markers. Additional immunohistochemical stains demonstrated blasts were positive for MYC and BCL-2, and negative for BCL6, MUM1, and EBV. Cytogenetic study showed normal male karyotype. FISH analyses showed no evidence of recurrent genetic abnormalities seen in B-lymphoblastic leukemia (B-ALL) or rearrangement of MYC or BCL2/BCL6. Next-generation sequencing showed 2 pathogenic mutations (KDM6A and KRAS). A diagnosis of B-ALL with surface κ light-chain expression in a patient with previous myeloma treatment was made. This is an interesting case for 2 reasons. The blasts show surface light-chain expression, which is rare in B-ALL. The expression of MYC and BCL2 introduces a differential diagnosis of high-grade B-cell lymphoma with MYC/BCL2 translocation. Negative rearrangement of MYC supports a diagnosis of B-ALL. Also, the patient received chemotherapy for myeloma. Although it is not a WHO-recognized disease entity, previous publications suggest that it may represent a therapy-related B-ALL following myeloma treatment.

(Poster No. 89)

Ashley L. Smith, MD ([email protected]); William P. Morrow, MD; William T. Harrison, MD. Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Oligodendrogliomas are malignant glial neoplasms described as occurring exclusively within the central nervous system. Although local recurrence is common, reports of extraneural metastases are rare. We describe a case of a 60-year-old woman with a history of oligodendroglioma with multiple intracranial recurrences. Treatment included surgical resection, radiation, and adjuvant chemotherapy. She recently presented with worsening neutropenia and anemia requiring transfusion. Subsequent bone marrow biopsy demonstrated marked hypercellularity with dyserythropoiesis and dysmegakaryopoiesis, alongside nonhematopoietic cells with uniform round nuclei and scant clear cytoplasm (Figure 1.89, A). The neoplastic cells formed cohesive clusters focally within a pink proteinaceous background resembling neuropil, morphologically consistent with metastatic oligodendrocytes. Prussian blue stain highlighted the presence of ring sideroblasts. The oligodendroglial cells were strongly positive for IDH1 (Figure 1.89, B), GFAP (Figure 1.89, C), synaptophysin, SOX10, and INSM1 immunohistochemical stains. CD34 confirmed that blasts were not increased. Chromosomal analysis revealed a complex karyotype and fluorescent in situ hybridization detected a 1p/19q codeletion. Next-generation sequencing identified mutations in both TP53 and IDH1 (R132H). Together the IDH1 mutation and 1p/19q codeletion were diagnostic of metastatic oligodendroglioma; however, the TP53 mutation was an unexpected finding. An additional p53 immunostain confirmed that while that the metastatic cells exhibited wild-type expression, the adjacent dysplastic hematopoietic cells had strong positivity (Figure 1.89, D). These overall findings represent metastatic oligodendroglioma with concurrent myelodysplastic syndrome with biallelic TP53 mutation, post–cytotoxic therapy. This is a unique association that emphasizes the need to consider involvement of the primary malignancy in cases of therapy-related myelodysplastic syndrome.

(Poster No. 90)

Xin Wang, MD, PhD ([email protected]); Maria Faraz, MBBS; Rupinder Kaur Brar, MD; Darwish Noureldien, MD; Tipu Nazeer, MD; Xiaoyan Huang, MD. Department of Pathology, Albany Medical Center, Albany, New York.

Follicular lymphoma (FL) is a common type of non-Hodgkin lymphoma. Most patients have indolent clinical courses. Rarely, FL accumulates MYC and BCL2 and/or BCL6 rearrangements and displays a morphology of high-grade B-cell lymphoma (HGBCL). We present a case involving a 42-year-old woman with lymphadenopathy for 4 years. Multiple lymph node biopsies and bone marrow evaluations were performed and showed similar findings. Sections of recent lymph node core biopsy showed dense and diffuse lymphoid infiltrate composed of predominantly small to medium-sized lymphocytes exhibiting centrocytic cytomorphology that were positive for CD20, PAX5, CD79a, CD10, BCL6, BCL2, TDT (rare), p53 (strong, <10%), and c-Myc, with a low to moderate Ki-67-labeled proliferation index (10%–20%), while negative for CD34, CD5, and cyclin D1. Follicular dendritic cell (FDC) meshwork was seen in the background. No features of FL, WHO grade 3B, were present. The overall morphology and immunophenotype were most compatible with low-grade FL. MYC rearrangement and t(14;18) were detected by FISH analysis for non-Hodgkin lymphoma panel in the first marrow biopsy and were also present in lymph node biopsies. Our case represents a morphologically low-grade FL with MYC and BCL2 gene rearrangements detected incidentally by broad FISH studies. These cases were reported to show aggressive features, which drew a question of when a HGBCL FISH study should be initiated on a low-grade FL. Overexpression of c-Myc may give justification of FISH study for MYC gene arrangement. A definitive guideline and future studies are necessary to increase the detection of such challenging cases.

(Poster No. 91)

Vinesh Kumar, MD ([email protected]); Yaqot Baban, MD; Rania Rayes-Danan, MD. Department of Pathology, MetroHealth Medical Center, Cleveland, Ohio.

Intracytoplasmic inclusions can be seen in lymphocytes, histiocytes, and plasma cells in different neoplasms such as chronic lymphocytic leukemia and multiple myeloma. This report highlights a case of large B-cell lymphoma with intracytoplasmic crystals. An older man presented with night sweats, fatigue, weight loss, and abdominal pain. Pancytopenia, inguinal lymphadenopathy, and splenomegaly were noted. Imaging showed extensive retroperitoneal lymphadenopathy, which was biopsied and showed sheets of intermediate to large lymphocytes with cytoplasmic inclusions (Figure 1.91, A) that were positive for CD20 (Figure 1.91, B), MUM1, and BCL-2, with a high Ki-67 proliferation index, and negative for CD5, CD10, and CD138. Diagnosis of large B-cell lymphoma, nongerminal type, was made. Bone marrow biopsy showed extensive involvement by lymphoma; an aspirate smear showed large lymphocytes with intracytoplasmic rhomboidlike inclusions/crystals (Figure 1.91, C). These inclusions were highlighted by the κ immunohistochemical stain (Figure 1.91, D). Flow cytometry analysis on the peripheral blood showed a small CD5- and CD10-negative clonal B-cell population with κ restriction. Cytoplasmic inclusions in lymphomas are uncommon, but have been noted as vacuoles, crystals, and pseudocrystals. They represent immunoglobulin heavy and light chain that precipitate in the cytoplasm. When surface immunoglobulin can be demonstrated on the B lymphocytes, it has been found to be the same as immunoglobulin in the inclusions. Immunoglobulin crystals are not commonly seen in lymphoproliferative disorders and can be rodlike or globular structure. There is no known prognostic significance; however, we are presenting a novel case of large B-cell lymphoma containing intracytoplasmic rhomboidlike crystals.

(Poster No. 92)

Mahreen F. Hussain, MBBS ([email protected]); Faisal Rawas, MS; Liesel Dell’osso, BS; Sri Kavuri, MBBS; Fatima Iqbal, MBBS; Kirill Lyapichev, MD. Department of Pathology, University of Texas Medical Branch, Galveston.

Context: Gelatinous bone marrow transformation is a poorly understood condition linked to severe malnutrition, involving adipocyte atrophy, gelatinous substance deposition, and hematopoietic hypoplasia. Presentation can include unexplained pancytopenia. Therefore, bone marrow biopsies showing gelatinous transformation with ring sideroblasts can be misdiagnosed as myelodysplastic syndrome with ring sideroblasts, leading to inappropriate treatment.

Design: This study analyzes clinical and laboratory data of 3 patients with low body mass indexes (BMIs), persistent severe pancytopenia, ring sideroblasts, and gelatinous bone marrow transformation.

Results: Case 1: A 47-year-old woman (BMI of 16 kg/m²) with unexplained pancytopenia had hypocellular bone marrow (20%–30%), increased iron storage, ringed sideroblasts, and gelatinous transformation (Figure 1.92). Flow cytometry (FC), next-generation sequencing (NGS), and fluorescence in situ hybridization (FISH) myelodysplastic syndrome (MDS) panel results were unremarkable. Case 2: A 35-year-old woman (BMI of 18 kg/m²) with neutropenic fever had hypocellular bone marrow (20%–30%), gelatinous transformation, hemophagocytosis, and ring sideroblasts (10%–20%). FC showed decreased mature neutrophils (low CD10 expression) with increased erythroid population. NGS and FISH MDS panel results were unremarkable. Case 3: A 61-year-old woman with acquired immunodeficiency syndrome (BMI of 15 kg/m²) was admitted for hypoglycemia. FC showed decreased CD10 expression (no mature neutrophils) and elevated erythroid population. Bone marrow biopsy showed gelatinous transformation, ring sideroblasts (5%), hemophagocytosis, and decreased hematopoiesis. NGS and FISH MDS panel results were unremarkable.

Conclusions: Ring sideroblasts may be linked to gelatinous bone marrow transformation in patients with persistent pancytopenia despite negative cytogenetic and molecular studies for MDS aberrations, serving as a potential diagnostic clue. This study appears to be the first to report this association.

(Poster No. 93)

Ahmad F. Alakedi, MD¹ ([email protected]); Monika Pilichowska, MD, PhD²; Ruben Delgado, MD.^{2 1}Department of Medical Diagnostic Laboratories, Dr Sulaiman Al Habib Medical Group, Riyadh, Saudi Arabia; ²Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, Massachusetts.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening syndrome characterized by excessive immune activation, leading to severe inflammation and tissue damage. Infectious triggers for HLH, including viral, bacterial, and parasitic pathogens, are increasingly recognized. Anaplasmosis, caused by Anaplasma phagocytophilum, has emerged as a potential trigger for HLH, with its role in this context still poorly understood. Additionally, the expansion of γ/δ T cells, a subset of unconventional T cells, has been implicated in HLH pathogenesis. We present a compelling clinical case of HLH with γ/δ T-cell expansion secondary to anaplasmosis, illustrating the complex immunologic mechanisms underlying this rare disorder. A 67-year-old man with chronic hepatitis C presented with altered mental status, fever, and characteristic laboratory abnormalities consistent with HLH. Laboratory results revealed leukopenia, thrombocytopenia, hypertriglyceridemia, hypofibrinogenemia, elevated liver enzymes, and markedly high soluble IL-2R/CD25 and ferritin levels. Imaging revealed splenomegaly. BM biopsy confirmed HLH and revealed hemophagocytic forms. Flow cytometry identified an expanded population of γ/δ double-negative T cells. Anaplasma phagocytophilum infection was confirmed via PBS and PCR. Treatment with antibiotics, including doxycycline, led to symptom resolution and discharge after 5 days. Follow-up on day 60 showed resolution of symptoms. Clonal cases resolving after treatment have been documented. With only 7 documented cases of anaplasmosis-induced HLH in the United States, recognition and management of this condition requires vigilance. Early diagnosis and intervention are crucial for improving patient outcomes given HLH’s high mortality rates, including fatalities from anaplasmosis-induced HLH.

(Poster No. 94)

Genti A. Gjyzeli, MD ([email protected]); Taylor Zak, MD, PhD; Kristy Wolniak, MD, PhD; Qing C. Chen, MD, PhD; Yi-Hua Chen, MD; Hamza Tariq, MD. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Aberrant expression of B-cell antigens, including PAX5, can rarely be seen in acute myeloid leukemia (AML), making the distinction from B-cell neoplasms challenging, especially at extramedullary sites. Aberrant B-antigen expression is best documented in AML with t(8;21)/RUX1-RUNX1T1 and has not been reported in AMLs with KMT2A rearrangements. We present the case of a 67-year-old man who presented with multiple skin plaques. A punch biopsy showed a dermal infiltrate of large mononuclear cells with irregular nuclei, open chromatin, and prominent nucleoli (Figure 1.94, A). These cells were diffusely positive for PAX5 (Figure 1.94, B), raising concern for a large B-cell lymphoma, but they were negative for multiple other B-cell markers (CD20, CD19, CD22, and CD79a). Additional immunohistochemical workup showed positivity for CD43, CD4, CD56, CD68-KP1, and lysozyme (Figure 1.94, C), while CD34, CD117, CD123, CD3, and TdT were negative. IGH gene rearrangement studies were negative for clonality. FISH detected a KMT2A (MLL,11q23) rearrangement (Figure 1.94, D). Next-generation sequencing identified ASXL1 p.(D943fs) and NRAS p.(G13V) pathogenic mutations. Therefore, a diagnosis of AML/myeloid sarcoma with KMT2A rearrangement was made. A bone marrow biopsy was negative. The patient received induction per FLAG-IDA, which resulted in complete resolution of the skin lesions. Our case highlights the importance of recognizing the rare event of aberrant diffuse PAX5 expression in AMLs to avoid misdiagnosis as a B-cell neoplasm. PAX5 overexpression in such cases may be reflective of constitutive activation of the RAS/MAPK pathway and possibly serve as a surrogate marker for mutations involving RAS/MAPK genes, such as NRAS in our case.

(Poster No. 95)

Chukwuemeka-Chika C. Iguh, MD, MSc ([email protected]); Julie Kim, DO; Xin Qing, MD, PhD. Department of Pathology & Laboratory Medicine, Harbor-UCLA Medical Center, Torrance, California.

Primary effusion lymphoma (PEL) is a rare, aggressive large B-cell lymphoma variant that is invariably associated with human herpesvirus 8 (HHV8), predominantly in HIV-infected patients, and its oncogenicity is often augmented by coinfection with Epstein-Barr virus. It typically presents as a serous effusion in body cavities without detectable solid tumors. The extracavitary variant of PEL may represent a diagnostic challenge. A 37-year-old man with HIV/AIDS was transferred to our hospital for evaluation of a mediastinal mass with associated clinically diagnosed hemophagocytic lymphohistiocytosis (HLH), fever, pancytopenia, hepatosplenomegaly, retroperitoneal lymphadenopathy, and wasting syndrome. Contrast-enhanced computed tomography showed a large soft tissue mass extending along the middle/posterior mediastinum into the left hilum and a large left pleural effusion. Endoscopic fine-needle biopsy of the lesion showed sheets of large pleomorphic lymphoma cells with prominent nucleoli and abundant cytoplasm (Figure 1.95, A). These cells were also seen on the cytospin smear of pleural fluid (Figure 1.95, B). Immunohistochemical stains showed lymphoma cells positive for CD3 (small subset), CD45, CD138 (Figure 1.95, C), MUM1, and HHV8 (Figure 1.95, D) and negative for CD5, CD20, CD30, ALK1, AE1/3, and PAX-5. The lymphoma cells were also positive for EBER (in situ hybridization). Solid masses in extracavitary PEL have been shown to involve lymph nodes and/or solid organs such as the gastrointestinal tract, lung, liver, spleen, and skin, with a similar phenotype as classic PEL except that they may express B-cell markers with lower expression of CD45 and/or aberrant coexpression of T-cell antigens. This case illustrates the unusual manifestation of PEL as a mediastinal mass with associated HLH.

(Poster No. 96)

Ifeyinwa E. Obiorah, MD, PhD¹ ([email protected]); Chad M. McCall, MD, PhD²; Alexandra Balmaceda, MD³; Stephanie Salansky, MEd, MS, BS, MT(ASCP)⁴; Olga Pozdnyakova, MD, PhD⁵; Archana Agarwal, MD.^{6 1}Department of Pathology, University of Virginia Health, Charlottesville; ²Department of Pathology, Carolinas Medical Center, Charlotte, North Carolina; ³Department of Pathology, Wake Forest University Health, Charlotte, North Carolina; ⁴Department of Hematology and Clinical Microscopy, College of American Pathologists, Northfield, Illinois; ⁵Department of Pathology, University of Pennsylvania Health System, Philadelphia; ⁶Department of Pathology, ARUP Laboratories Inc, Salt Lake City, Utah.

Context: The College of American Pathologists (CAP) Hematology and Clinical Microscopy Committee implemented a hemoglobinopathy proficiency testing (PT) program to allow hematology laboratories to monitor and assess their performance in comparison with a peer group. We aimed to evaluate their performance on hemoglobinopathy PT from 2005 to 2023.

Design: Program participants were sent 2 sets of dry laboratory challenges every year composed of test results from hemoglobin evaluations. The participants were asked to determine the correct hemoglobin disease and what globin chain was affected.

Results: A total of 365 to 676 laboratories were enrolled in the PT program each year. Overall, the error rates for detection of the hemoglobin disorder ranged from 0.5% to 86.5%, and 0.6% to 56.5% for determination of the affected globin chain. Twenty-three of 66 surveyed disorders (34.8%) had an error rate exceeding the consensus threshold of 20%. Furthermore, surveys with >10% error rate showed that the poorest performances were noted in rare Hb variants such as Hb New York (86.5%), Hb δ variants (36.8%–58.8%), and unstable hemoglobin (40.9%). Notably, increased error rates were observed in compound heterozygotes with either Hb C (19.2%–36.2%) or Hb G Philadelphia (10.2%–32.4%) and combinations of α variants and Constant Spring (10.4%–28.8%). In repeat testing of variants, only detection of Hb Lepore worsened over time among participants.

Conclusions: The program participants demonstrated variable performance, with many surveys exceeding a 20% error rate. The increased error rates demonstrated in the compound heterozygote Hb disorders and rare Hb variants suggest the need for an educational review with an algorithmic approach to hemoglobin disorders.

(Poster No. 97)

Jeffrey J. Wang¹ ([email protected]); Weiwei Zhang, PhD²; Xinjie Xu, PhD³; Alessia Buglioni, MD³; Li Peng, MD, PhD⁴; Xueyan Chen, MD, PhD⁵; Min Xu, MD⁶; Jennifer Herrick, MD³; Pedro Horna, MD³; Xiaohui Zhang, MD, PhD⁷; Jinming Song, MD, PhD⁷; Dragan Jevremovic, MD, PhD³; Min Shi, MD, PhD³; Ji Yuan, MD, PhD.^{3 1}Carleton College, Northfield, Minnesota; ²Department of Laboratory Medicine and Pathology, University of Nebraska Medical Center, Omaha; ³Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; ⁴Department of Pathology, Division of Hematopathology, University of Utah Health, Salt Lake City; ⁵Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle; ⁶Department of Pathology, Seattle Children’s Hospital, Seattle, Washington; ⁷Department of Pathology and Lab Medicine, H. L. Moffitt Cancer Center and Research Institute, Tampa, Florida.

Context: PICALM::MLLT10 fusion is a rare but recurrent cytogenetic abnormality in acute leukemia, with limited clinicopathologic and outcome data available.

Design: Clinicopathologic data were collected for 157 acute leukemia patients with PICALM::MLLT10 fusion, including 13 from our institutes and 144 from the literature.

Results: The PICALM::MLLT10 fusion preferentially manifested in pediatric and young adult patients, with a median age of 24 years. T-lymphoblastic leukemia/lymphoma (T-ALL) constituted 65% of cases, acute myeloid leukemia (AML) 27%, and acute leukemia of ambiguous lineage (ALAL) 8%. About half of T-ALL cases were classified as early T-precursor (ETP)-ALL. In our institutes’ cohort, mediastinum was the most common extramedullary site. Eight of 13 patients were diagnosed with T-ALL exhibiting a pro-/pre-T stage phenotype (CD4/CD8-double negative, CD7-positive). Next-generation sequencing revealed pathogenic mutations in 5 of 6 tested cases, including NOTCH1 and genes in RAS and JAK-STAT pathways and epigenetic modifiers. Of 139 cases with follow-up, pediatric patients had a 5-year OS of 71%, significantly better than adults (≥18 years) at 33% (P < .001). The 5-year OS for AML patients was 25%, significantly shorter than ALAL patients at 33% and T-ALL patients at 54% (P < .001). Furthermore, adult but not pediatric ETP-ALL patients demonstrated inferior survival compared to non–EPT-ALL patients (P = .01). Neither karyotype complexity nor transplant status had a discernible impact on OS.

Conclusions: PICALM::MLLT10 fusion is most commonly seen in T-ALL patients, particularly those with an ETP phenotype. AML and adult ETP-ALL patients were associated with adverse prognosis. PICALM::MLTT10 fusion testing should be considered in T-ALL, AML, and ALAL patients.

(Poster No. 98)

Anam Hamid, MD ([email protected]); Wei Xie, MD, PhD. Department of Pathology and Laboratory Medicine, Oregon Health and Science University, Portland.

Angioimmunoblastic T-cell lymphoma (AITL), now classified as nodal TFH cell lymphoma, angioimmunoblastic type in the World Health Organization 5th edition, is characterized by morphology, TFH immunophenotype, and frequent mutations in RHOA, IDH2, DNMT3A, and TET2. The latter 2 mutations occur in clonal hematopoiesis. SRSF2 mutations, typically observed in myeloid malignancies, have not been reported in AITL. We present 2 unique cases of AITL featuring SRSF2 mutations. In case 1, an 84-year-old woman exhibited fatigue, weight loss, and right inguinal lymphadenopathy. Excisional biopsy revealed architectural effacement, with atypical cells positive for T-cell antigens, CD30, ICOS, CXCL13, BCL6, PD-1, and EBER-ISH. The 220-gene next-generation sequencing (NGS) panel detected RHOA mutation with additional mutations in SRSF2 and SETBP1. TCR gene rearrangement confirmed monoclonality. In case 2, a 62-year-old man presented with systemic symptoms and lymphadenopathy. Morphology and immunohistochemical studies were consistent with AITL. NGS identified RHOA, SRSF2, TET2, and DNMT3A mutations in the lymph node. However, in flow-sorted CD33⁺ myeloid cells, only TET2 and DNMT3A mutations were detected, suggesting that SRSF2 mutation was confined to neoplastic T cells in AITL but not present in myeloid cells. Additionally, shared mutations in TET2 and DNMT3A between neoplastic T cells and myeloid cells indicate a possible evolutionary link between T cells and myeloid cells. The patient in case 2 achieved disease-free status 14 months postdiagnosis following an allogeneic hematopoietic stem cell transplant. These 2 rare AITL cases harboring SRSF2 mutation underscore the molecular complexity of AITL and emphasize the importance of molecular methods such as NGS in diagnostic and therapeutic implications.

(Poster No. 99)

Omar Al-Rusan, MBBS ([email protected]); Tanya S. Ponnatt, MBBS; Deniz Peker Barclift, MD. Department of Pathology, Emory University School of Medicine, Atlanta, Georgia.

Context: Diffuse large B-cell lymphoma (DLBCL) is molecularly and genetically heterogeneous. BRME1 (C19orf57), a gene crucial for meiotic double-strand break repair, interacts with the BRCA2:HSF2BP complex. We aimed to study its effects on DLBCL.

Design: The analyzed data were retrieved from the Cancer Genome Atlas Database of the UALCAN. The analysis included 48 patients with DLBCL.

Results: Of 48 patients, 21 (44%) were men and 26 (54%) were women; gender/race information was unavailable for 1 patient. Twenty-seven patients were between 21 and 60 years of age, while 22 patients were older than 61. Patient population breakdown was 28 (58%) White, 18 (38%) Asian, and 1 (2%) African American. Of the 41 patients for whom clinical information was available, no significant difference was noted in BRME1 expression according to stage. Significant overexpression was noted in the female population, likely owing to the sexually dimorphic nature of BRME1. Of the 36 patients for whom the TP53 status was known, 5 were TP53 mutated, while 31 were TP53 unmutated. However, no significant difference in BRME1 expression was noted between the 2 groups. The overall survival was decreased with increased expression of BRME1 (P < .001). Also, a positive correlation was found between the expression levels of BRME1 and ABCB6 (Pearson CC, 0.72), a gene associated with multidrug resistance (Figure 1.99).

Conclusions: Increased BRME1 expression likely contributes to an unfavorable prognosis in DLBCL. Studying BRME1 as a prognostic marker or therapeutic target in DLBCL, particularly in treatment-resistant cases, is justified. Additionally, a deeper understanding of the interrelation between BRME1 and ABCB6 is necessary.

(Poster No. 100)

Zhengchun Lu, MD, PhD¹ ([email protected]); Tyler S. Yeager, BS¹; Yunpeng Lyu¹; Mayu Morita, BS¹; Athena Zhu, BS²; Sophia Wang²; Zhigang Wang, PhD²; Guang Fan, MD, PhD.^{1 1}Department of Pathology and Laboratory Medicine, Oregon Health & Science University, Portland; ²DeepCyto, LLC, West Linn, Oregon.

Context: Manual differentials of bone marrow (BM) remain the gold standard for diagnosing plasma cell neoplasm (PCN). However, manual evaluation of BM is tedious, time-consuming, and highly variable depending on examiners’ experience. Artificial intelligence (AI) has significantly improved the image processing and classification accuracy in the last decade. The objective of this study was to evaluate the correlations of AI-assisted plasma cell differential counts on BM aspirate smear with pathologists’ manual evaluations.

Design: Seventy-two BM aspirate slides were retrieved from the archived diagnostic cases in the pathology department from 2021 to 2023, with 58 positives for PCN and 14 negatives. The DCS-1800 blood cell morphology analyzer (DeepCyto, West Linn, Oregon) was used to scan, classify, and analyze a minimum of 500 nucleated hematopoietic cells from multiple areas of the smear using a proprietary algorithm. The manual differential of plasma cells was retrieved from the final pathology reports. Pearson correlation coefficient was used to determine the correlation of manual and AI-assisted analysis.

Results: The AI-assisted BM differential counts showed strong correlation (r > 0.85) with paired manual analysis (Figure 1.100) in plasma cell differentials. AI tends to count percentages lower than manual and remains to be trained for cases with degenerated cells, pleomorphic plasma cells, and focal plasma cell clusters.

Conclusions: AI-assisted BM differentials show promising potential for accurately classifying plasma cells. Continuous training is necessary to improve recognition of neoplastic plasma cells with various morphologies. Ultimately, AI-assisted BM morphologic evaluation could enhance the standardization, accuracy, and efficiency of the clinical decision-making process.

(Poster No. 101)

Omar Al-Rusan, MBBS ([email protected]); Tanya Ponnatt, MBBS; Deniz Peker Barclift, MD. Department of Pathology, Emory University School of Medicine, Atlanta, Georgia.

Context: Diffuse large B-cell lymphoma (DLBCL) is molecularly heterogenous. CTDNEP1 (DULLARD), implicated in triglyceride biosynthesis regulation, protein dephosphorylation, and nuclear protein localization, has been associated with unfavorable prognoses in MYC-driven medulloblastomas. We aimed to study the impact of CTDNEP1 on DLBCL.

Design: The analyzed data were retrieved from the Cancer Genome Atlas Database of the UALCAN. The analysis included 48 patients with DLBCL.

Results: Of 48 patients, 21 (44%) were men and 26 (54%) were women; gender/race information was unavailable for 1 patient. Twenty-seven patients were between 21 and 60 years of age, while 22 patients were older than 61. Patient population breakdown was 28 (58%) White, 18 (38%) Asian, and 1 (2%) African American. CTDNEP1 expression was significantly higher in Asians compared to Whites (P = .047). No significant difference was noted in CTDNEP1 expression according to stage. Of 36 patients for which the TP53 status was known, 5 were TP53 mutated while 31 were unmutated. CTDNEP1 expression was significantly higher in the TP53 mutated group compared to the unmutated group (P = .02). The overall survival was lower with increased CTDNEP1 expression (P < .001). Additionally, a positive correlation was found between expression levels of CTDNEP1 and RAC2 (Pearson correlation coefficient, 0.71), a gene associated with poor overall survival in DLBCL (P = .03; Figure 1.101).

Conclusions: CTDNEP1 overexpression is associated with an adverse prognosis in DLBCL, prompting exploration of its potential as a prognostic biomarker or therapeutic target. Understanding the interplay between CTDNEP1 and RAC2 is crucial, particularly given ongoing investigations into targeted therapy against RAC2.

(Poster No. 102)

Bo Zhang, MD ([email protected]); Weina Chen, MD, PhD; Mingyi Chen, MD, PhD; Franklin Fuda, DO; Olga Weinberg, MD; Sharon Koorse Germans, MD. Department of Pathology, University of Texas Southwestern Medical Center, Dallas.

Context: Mixed-phenotype acute leukemias (MPALs), a part of ambiguous-lineage leukemias, are rare and account for <4% of all acute leukemias. They remain a diagnostic dilemma, and the inherent plasticity makes it challenging to establish standardized treatment regimens. The clinicopathologic and prognostic features of MPAL have not been fully studied.

Design: We retrospectively identified 52 MPAL patients diagnosed at our institution from August 2010 to February 2024. The medical records were reviewed to analyze the clinicopathologic characteristics of MPAL. Patients with KMT2A rearrangement and with BCR-ABL fusion were both excluded.

Results: The majority of MPAL cases were B/myeloid (80.8%), followed by T/myeloid (11.5%), B/T (5.8%), and B/T/myeloid (1.9%) (clinical data shown in Table). There were 19 adults (median age, 63 years) and 33 pediatric patients (median age, 8.5 years) with a male to female ratio of 2.1:1. Thirty-four biphenotypic (65.4%) and 18 bilineal (34.6%) cases were observed. B-lymphoblastic leukemia/lymphoma–type genetic changes were more common in B/myeloid MPAL, in contrast to T/myeloid MPAL, in which acute myeloid leukemia–driven mutations were more frequent. One B/myeloid and 1 T/myeloid patient progressed to acute myeloid leukemia under the pressure of treatment. A significant difference in overall survival was observed between B-MPAL (B/myeloid, B/T, and B/T/myeloid) and T-MPAL (T/myeloid) (median follow-up: 50 versus 8 months; P = .006).

Conclusions: T-MPAL subset represents a predictor of poorer prognosis in MPAL. Phenotypic switch under therapeutic pressure is an uncommon but distinctive feature of MPAL. This study illuminates the directions in classification and treatment based on the predominant immunophenotype in MPAL.

(Poster No. 103)

Hannah Cutshall, MD ([email protected]); Jeanette Ramos, MD; Soumya Pandey, MD. Department of Pathology, University of Arkansas for Medical Sciences, Little Rock.

The differential diagnosis for skin rashes includes reactive/inflammatory conditions, primary cutaneous lymphomas, and systemic involvement by neoplasms. We present an unusual case of a patient with a rash who was subsequently diagnosed with systemic lymphoma. A 70-year-old woman presented with a 6-month history of a generalized, diffuse, pruritic rash that initially responded to steroid treatments; initial skin biopsy had nonspecific findings. She subsequently presented with worsening rash, fatigue, dyspnea, and acute renal injury. A peripheral smear was reviewed secondary to abnormal lymphocyte morphology, including cleaved forms and forms with irregular nuclear contours (Figure 1.103, A). Flow cytometry confirmed an atypical T-cell population that was positive for CD4 and CD25 and was negative for CD7. Review of medical record revealed a remote history of blood donation deferment because of positivity for HTLV-1 infection. A repeat skin punch biopsy displayed a more prominent and atypical lymphocytic infiltrate with epidermotropism (Figure 1.103, B). A left inguinal lymph node biopsy displayed effaced architecture and diffuse atypical T-cell infiltrate (Figure 1.103, C) with diffuse CD25 positivity (Figure 1.103, D). Bone marrow biopsy also showed involvement. Adult T-cell leukemia/lymphoma was diagnosed. Adult T-cell leukemia/lymphoma is a rare diagnosis in the United States, and the immunophenotype can overlap other T-cell processes. Patients can initially show skin-only involvement, mimicking mycosis fungoides, which is typically CD4 positive and CD7 negative and can also be CD25 positive. Thus, without the correlation with the remote history of HTLV positivity, this diagnosis could have been missed. Early recognition may improve the prognosis of this aggressive lymphoma.

(Poster No. 104)

Jacob Rattin, DO ([email protected]); Genevieve M. Crane, MD, PhD. Department of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio.

Follicular lymphoma (FL) may undergo large cell transformation to aggressive B-cell lymphoma, including diffuse large B-cell or high-grade B-cell lymphoma (“double hit”), with acquisition of MYC translocation. However, in contrast to transformation of other subtypes of low-grade B-cell lymphoma that more often affect underlying immune status (eg, chronic lymphocytic leukemia/small lymphocytic lymphoma), transformation of FL is rarely Epstein-Barr virus (EBV) associated. We present 2 patients with synchronous diagnosis of FL and EBV⁺ aggressive lymphomas. Case 1 involved an elderly woman who presented with paraplegia and paraspinal and pelvic masses, both demonstrating IGH::BCL2 rearrangements. The pelvic mass (Figure 1.107, A, B) demonstrated morphology compatible with classic FL (WHO/ICC grade 1–2), while the paraspinal mass showed large, transformed lymphoid cells (Figure 1.107, C) with a similar immunophenotype, but also EBV⁺ (Figure 1.107, D). Case 2 involved a middle-aged man with history of treated hepatitis C who presented with small bowel wall thickening and mesenteric lymphadenopathy. Both the small intestine and mesenteric lymph node biopsies showed involvement by FL (classic/low grade, IGH::BCL2 present). Adjacent areas in the mesenteric node showed effacement by atypical cells with plasmacytic differentiation consistent with EBV⁺ plasmablastic lymphoma (IGH::BCL2 absent). While EBV⁺ FL has rarely been observed, the underlying FLs here were not EBV⁺. EBV reactivation can decrease the threshold for lymphomagenesis, as seen in patients with immunosuppression and loss of adequate viral control, but case 1 suggests that EBV infection/reactivation in low-grade lymphoma may potentially contribute to transformation, even in the absence of known immunosuppression. EBV⁺-unrelated clonal proliferations may also arise in this setting (case 2).

(Poster No. 105)

Daniel Rivera Delgado, MD ([email protected]); Brenda Mai, MD. Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston.

Myeloid neoplasms (MN) with platelet-derived growth factor receptor β (PDGFRB) gene rearrangement can pose a risk of misdiagnosis. We are the first to report an MN with a rare PDGFRB rearrangement and an ATM germline mutation. The patient was a 36-year-old man without past medical history who presented with weakness, lower extremity edema, and pain. Imaging revealed splenomegaly of 23 cm without lymphadenopathy. Blood work revealed anemia (hemoglobin level of 9.4 g/dL), leukocytosis (61.5 × 10⁹/L) with neutrophilia (29.4 × 10⁹/L), monocytosis (5.1 × 10⁹/L), and eosinophilia (7.2 × 10⁹/L); the platelet count was 190 × 10⁹/L. The bone marrow biopsy (Figure 1.105) was hypercellular (100%) with trilineage hematopoiesis, granulocytic hyperplasia, marked eosinophilia, and less than 5% blasts; dysplasia was not identified. Reticulin stain showed focal mild fibrosis (MF-1). No abnormal immunophenotype was found by flow cytometry. Cytogenetic studies showed a t(5;14)(q33;q32) in 20 metaphases. Fluorescence in situ hybridization testing showed a rearrangement of PDGFRB in 88% of nuclei. Moreover, next-generation sequencing revealed a PDGFRB::CCDC88C fusion and a germline ATM mutation (p.R2034*). The final diagnosis rendered was MN with PDGFRB rearrangement. Evidence on the PDGFRB::CCDC88C fusion t(5;14)(q33.1;q32.11) is scarce. This fusion leads to PDGFRB activation via PI3K/Akt and mTOR pathways. Moreover, it induces cell transformation and sensitivity to imatinib. Germline ATM nonsense mutations disrupt the function of DNA damage response, leading to genomic instability. It has also been associated with second malignancies and a higher risk of myelofibrosis transformation. Further investigation will provide new insight into patient care.

(Poster No. 106)

Zarrin Hosseinzadeh, MD ([email protected]); Wayne Tam, MD; Abdul Hanan, MD. Department of Pathology, Northwell Health, Greenvale, New York.

Anaplastic variant of diffuse large B-cell lymphoma (DLBCL) is a rare subtype that accounts for about 3% of all DLBCL cases. It is characterized by large neoplastic cells, with pleomorphic nuclei, abundant cytoplasm, frequent cohesive sheetlike growth, and extensive sinusoidal involvement. Richter transformation, although a finding frequently seen in long-standing chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), commonly presents with sheets of large cells with centroblastic or immunoblastic features. Anaplastic DLBCL is not typically seen following Richter transformation and we believe this case presents a unique case of this transformation. Our patient was an 82-year-old man who presented with a chief complaint of altered mental status and a mass on his neck. A biopsy of a supraclavicular lymph node was performed that showed effaced lymph node architecture and infiltration by 2 distinct populations of cells. The intrasinusoidal infiltrate consisted of predominantly large cells with bizarre nuclei, prominent nucleoli, and increased eosinophilic cytoplasm, consistent with DLBCL, anaplastic variant. The background constituent was mostly composed of small-sized lymphocytes consistent with CLL/SLL (Figure 1.106, A–C). The presence of DLBCL in the setting of CLL/SLL represents Richter transformation based on immunohistochemical staining pattern (Figure 1.106, D) as well as B-cell gene rearrangement studies supporting clonally related populations.

(Poster No. 107)

Tamar Gomolin, MD ([email protected]); Patricia Arboleda Ezcurra, MD; Matan Kadosh, MD; Mohamed O. Rabie, MD; Alexandra Zara Rozalen, MD; Wen Fan, MD; Abdelsalam Sharabi, MD. Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.

Immunoglobulin G4 (IgG4)–positive marginal zone lymphoma (MZL) is a rare entity, reported in 24 cases as of 2022. We report a 69-year-old man who presented with a right proximal ureteral mass and hydronephrosis (Figure 1.107, A) on imaging, and underwent radical nephroureterectomy. Histology showed interfollicular sheets of atypical lymphocytes and plasma cells, including frequent Mott cells (Figure 1.107, B). The lymphoid cells were positive for CD79a, OCT-2, PAX-5, CD20 (focal), and CD43a, and negative for CD5, CD10, Bcl-1, and Bcl-6. The plasma cells were positive for CD138, MUM-1, and IgG, and showed monotypic expression of λ light chain (Figure 1.107, C) and predominant IgG4 expression (Figure 1.107, D). IgG4-positive MZL primarily occurs in the ocular adnexa and skin. We present a unique case of IgG4-positive MZL occurring in the renal hilum, with only one reported case in this location. Our patient had no clinical evidence of concurrent IgG4-related disease (IgG4-RD), whereas the other case had known IgG4-RD. This suggests that not only can lymphoma occur in relation to IgG4-RD, but IgG4 may be independently produced by neoplastic cells. IgG4-positive MZL can be described by an interfollicular expansion of small lymphocytes and plasma cells with frequent Mott cells. Mott cells are seen in plasma cell dyscrasias and reactive plasmacytoses. We believe the presence of frequent Mott cells could be considered a key diagnostic feature in IgG4-positive MZL, as seen in other reported cases. If frequent Mott cells are identified in a lesion that is concerning for lymphoma, IgG4-positive MZL should be considered.

(Poster No. 108)

Ayesha J. Zaidi, MBBS¹ ([email protected]); Khatcher Margossian, PhD³; Steven Berg, BS²; Sophia Matrov¹; Victoria Angelova, MD²; Shiraz Fidai, MD.^{2 1}University of Illinois at Chicago; ²John H. Stroger Hospital of Cook County, Chicago, Illinois; ³Rush University Medical College, Chicago, Illinois.

The phenomenon of follicular lymphoma transdifferentiating to malignant histiocytosis with Langerhans cell differentiation represents a remarkable rarity. Histiocytic sarcoma (HS) can affect multiple organs, commonly involving the skin, gastrointestinal tract, and soft tissues. Less than 20% of cases present with solitary lymph node involvement. We present a case of a 72-year-old woman who presented with right level II neck/parotid mass on CT scan concerning for malignancy. Biopsy performed showed extensive sinusoidal infiltrate of highly pleomorphic malignant histiocytes, with irregular nuclear contours, prominent nucleoli and pale cytoplasm, and occasionally multinucleated forms. By immunophenotype, these showed Langerhans cell differentiation, positive for CD1a, Langerin, S100, ZBTB46, CD68 (weak), cyclin D1, OCT2 (weak), CD4, CD7 (focal and weak), and CD43. In addition, there were background B-lymphoid follicles composed of CD10- and BCL6-positive germinal center B cells that showed bright aberrant BCL2 expression, highly suggestive of an underlying follicular neoplasm. Interestingly, FISH analysis revealed a BCL2 rearrangement at 18q21 locus in approximately 82% of nuclei (including the histiocytic component). The presence of BCL2 rearrangement within histiocytic sarcoma was consistent with a secondary transdifferentiation of a B-cell lymphoma. Genotype matching primary B-cell neoplasm in a secondary neoplasm with histiocytic immunophenotype supports lineage conversion to histiocytic malignancy. Theories propose mechanisms like dedifferentiation, shared progenitor cells, and transdifferentiation. HS progresses rapidly with a poor response to therapy, emphasizing the importance of distinguishing secondary from primary cases for prognosis. Given its rarity, there is no standardized therapy for malignant histiocytosis. Extensive molecular research is crucial to validate therapeutic implications of these theories (Figure 1.108).

(Poster No. 109)

Pooja Devi, MBBS, MD ([email protected]); Vinodh Pillai, MD, PhD. Department of Hematopathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

Cytomegalovirus (CMV) reactivation is frequent after suppression of the immune system due to therapeutic drugs or disease. We report a CMV lymphadenitis in a patient treated with CAR-T for diffuse large B‐cell lymphoma (DLBCL) mimicking a relapse of DLBCL. A 62‐year‐old man who was diagnosed with DLBCL in 2020 was treated with R-EPOCH. He presented with DLBCL recurrence. He underwent CAR-T therapy and achieved complete metabolic response in 2023. He most recently presented with fever. PET CT showed new diffuse FDG-avid lymphadenopathy. Biopsy of lymph node showed reactive follicular hyperplasia, expansion of interfollicular areas with plasma cells, and necrotizing granulomatous inflammation with scattered large nuclei with eosinophilic nuclear inclusions. Immunohistochemistry revealed CMV‐infected cells. Blood CMV polymerase chain reaction (PCR) was negative. Other infections including HSV, toxoplasmosis, fungi, and mycobacteria were ruled out. Findings were consistent with CMV lymphadenitis. We present a case of CMV lymphadenitis that occurred 1 year after CAR-T therapy. PET‐CT mimicked DLBCL relapse, and biopsy was performed to ascertain a relapse. Although CAR T-cell therapy have been game changing, it does not come without cost. One of the significant complications includes immune suppression and infection. Our case demonstrates 2 important points. Viral blood PCR can help in diagnosis, but negative blood PCR does not exclude viral adenitis and only histologic examination can rule out or confirm the diagnosis. Data on long-term risks of infectious complication after CAR-T are limited. Further studies are required to define post infusion risk factors and guidelines to monitor for infections (Figure 1.109, A–D).

(Poster No. 110)

Moyosore Awobajo-Otesanya, MD ([email protected]); Jacob Ritter, MD; Russell Higgins, MD. Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at San Antonio.

Acute promyelocytic leukemia (APL) is a rare subtype of acute myeloid leukemia (AML), a vast majority (∼98%) of which harbors t(15;17)(q24.1;q21.2) resulting in PML::RARA fusion. In a subset of patients (∼2%), RARA fusion with other gene partners is identified, but non-RARA rearrangements are extremely rare. We report a case of a 2-year-old boy with a 2-month history of intermittent fevers, anemia, thrombocytopenia, and leukocytosis. The smear demonstrated 48% blasts with irregular nuclear contours including occasional bilobed forms and abundant cytoplasmic granules (Figure 1.110, A, B). Flow cytometry immunophenotyping revealed expression of CD13, CD33, and MPO, without HLA-DR, CD34, or CD19 (Figure 1.110, C). Diagnostic concern for APL was raised; however, PML::RARA fusion test results by FISH and RT-PCR methods were negative. There was no clinical evidence of coagulation dysfunction, and he was treated on the AAML1831 clinical trial. Comprehensive genomic profiling by DNA/RNA sequencing identified truncation due to a fusion of TBL1XR1 and RARB genes located at 3q26 and 3p24 respectively. Normal karyotype was reported, and no other primary genetic drivers were identified. To date, fewer than 10 cases of variant APL with TBL1XR1::RARB fusion have been reported in the literature, all in patients <4 years of age. The fusion protein TBL1XR1-RARB homodimerizes and suppresses the retinoic acid pathway, with similar oncogenic potency to PML-RARA (Figure 1.110, D). However, the former tends to show resistance to ATRA and increases the risk of induction failure with conventional chemotherapy. Overall, AML with typical APL morphology and immunophenotype but atypical clinical manifestations may confer PML::RARA-negative APL variant, and, particularly in young patients, the presence of TBL1XR1::RARB fusion.

(Poster No. 111)

Suhalika S. Sahni, MD ([email protected]); Michael Stone, DO; Carlos A. Murga-Zamalloa, MD. Department of Pathology, University of Illinois at Chicago.

Large B-cell lymphomas that coexpress SOX11 and CD5 pose a difficult diagnostic conundrum between blastoid/pleomorphic mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL). Blastoid variant of MCL comprises 10% to 20% cases of MCL, and these cases can be negative for cyclin D1 expression; however, positive expression of SOX11 is ubiquitous. This is a report of a 48-year-old man with a 1-month history of 20-lb weight loss, constipation, oliguria, and a new deep venous thromboembolism. Imaging studies showed a 20-cm retroperitoneal mass, abdominal lymphadenopathy, and lymphocytosis. Review of the peripheral blood smear demonstrated numerous medium to large atypical lymphocytes. Core biopsy of the abdominal mass revealed sheets of atypical intermediate- to large-size lymphoid cells with oval or irregular nuclear contours, vesicular chromatin, conspicuous central nucleoli, and little cytoplasm (Figure 1.111, A). Immunohistochemistry revealed that the atypical cells were positive for CD20, PAX5, CD5, MYC, SOX11 (∼70%), MUM-1, and BCL2 (Figure 1.111, B–D), and were negative for CD10, BCL6, and cyclin D1. Ki-67 positivity was ∼70%. Flow cytometry performed on the peripheral blood revealed a λ-restricted mature B cell neoplasm. FISH was positive for MYC rearrangement, while negative for IGH:BCL2 and BCL6 rearrangements. This case emphasizes that SOX11 should be routinely performed to rule out cyclin-D1–negative MCL, as this marker is highly specific for MCL.

(Poster No. 112)

Sonu Kalyan, MD¹ ([email protected]); Xiaojun Feng, PhD²; Derek Jones, MD.^{2 1}Department of Pathology, New York University Grossman Long Island School of Medicine, Mineola; ²Department of Pathology, New York University Grossman School of Medicine, New York, New York.

Hairy cell leukemia (HCL) is a B-cell neoplasm characterized by pancytopenia, massive splenomegaly, characteristic leukemic cells with hairy projections infiltrating the bone marrow, and other hematopoietic organs and unique immunophenotypic features. Numerous studies in the literature have demonstrated the presence of BRAF (V600E) mutation in nearly all cases of hairy cell leukemia and thus identified it as a hairy cell leukemia–defining mutation, which in turn formed the basis of targeted therapy. However, a minority of the cases may lack this defining mutation and have alternative mechanisms involved in the pathogenesis. We report a case of a 60-year-old man who presented with pancytopenia with more pronounced decline in the platelet count. Bone marrow biopsy revealed increased interstitial lymphoid infiltrate and ill-defined aggregates, staining positive for CD20. Concurrent flow cytometry confirmed the diagnosis of hairy cell leukemia. Cytogenetic analysis of bone marrow specimen suggested the presence of trisomy 5. DNA sequencing was negative for the BRAF V600E mutation. Targeted RNA sequencing of bone marrow specimen revealed intragenic fusion of BRAF gene between exons 1 and 9 [BRAF(1)-BRAF(9)]. The BRAF intragenic fusion in silico demonstrates an intact kinase domain. This may potentially serve as an alternative mechanism for BRAF activation. BRAF intragenic fusions have been noted as a resistance mechanism to BRAF inhibitor therapies in various malignancies such as melanoma. Recognition of such alternative mechanisms is crucial for optimizing targeted therapy decisions in hairy cell leukemia and underscores the importance of comprehensive molecular profiling in guiding therapeutic strategies.

(Poster No. 113)

Nourhan Ibrahim, MD ([email protected]); Zubaidah Al-Jumaili, MD; Sibel AK, MD; Phuoc T. Christie-Nguyen, MD; Brenda Mai, MD. Department of Pathology and Laboratory Medicine, University of Texas Health Science Center, Houston.

Mixed phenotype acute leukemia (MPAL) occurs when blasts exhibit characteristics of multiple lineages; they are usually biphenotypic. We present an exceedingly rare case of a triphenotypic MPAL in a 65-year-old HIV-positive man with a history of multiple malignancies, post–cytotoxic therapy, who presented with leukocytosis. Peripheral blood smear revealed approximately 50% blasts, normocytic anemia, and thrombocytopenia. Bone marrow aspirate smears showed more than 90% blasts and the megakaryocytes were dysplastic. Flow cytometry analysis showed a distinctive immunophenotype including positivity for immature markers (CD34, CD117, Tdt), B-cell markers (CD10, CD19, CD20, cCD22, cCD79a, Tdt), T-cell markers (cCD3, CD7), and monocytic markers (CD13, CD33, CD11b, CD11c, CD64), indicating a mixed-lineage composition. Karyotype analysis showed a complex composite male karyotype. Fluorescence in situ hybridization (FISH) detected a loss of chromosome 3q, del(5q), trisomy 6, trisomy 7, trisomy 10, amplification/gain of chromosome 11/11q, gain of chromosome 9/9q, trisomy 17, del17p, and gain of chromosome 22/22q. Next-genome sequencing detected a TP53 missense mutation. The bone marrow was hypercellular, ∼80% to 90%, with extensive involvement by acute leukemia. This is the first reported case of a triphenotypic MPAL with monocytic differentiation as the myeloid component according to a literature review. The case presents a diagnostic challenge because of its dysplastic morphology, FISH abnormalities, and complex karyotypes, suggesting a possible classification as “acute myeloid leukemia, myelodysplasia related,” particularly considering the patient’s history of cytotoxic therapy. However, the presence of B and T lineage markers in the blasts complicates classification, rendering a diagnosis of a MPAL, B/T/M (triphenotypic) (Figure 1.113).

(Poster No. 114)

Akshita Yadav, MD ([email protected]); Rozeen Badeel, MD; Karen Ferreira, PhD; Elena Puscasiu, MD; Diana O. Treaba, MD. Department of Pathology, Rhode Island Hospital, Providence.

Myeloid neoplasms with mutated TP53 include AML, MDS, and MDS/AML. A 72-year-old man developed massive left pleural effusion with associated pleural nodularity 17 years following mastectomy for left breast ductal carcinoma in situ (DCIS). His pleural fluid had 8% blastlike cells, neutrophils with shift toward immaturity and in a subset with erythrophagocytosis, monocytes/macrophages, nucleated erythroid precursors with dyserythropoiesis, eosinophils, basophils, and small lymphocytes. The blasts were CD117, CD13/CD33, HLA-DR, CD36, and CD45 positive. A small κ-restricted B-lymphoid population, chronic lymphocytic leukemia (CLL)–like, was also detected. A second pleural fluid found 80% HLA-DR, CD13-, CD33- (dim), CD123-, CD36-, CD4-, CD38-, and CD30-positive blasts, and the pleural mass biopsy had dense CD4-, CD99-, p53-, c-myc-, bcl-2 CD117-, CD30-, CD31-, and CD45-positive lesional cells, with high proliferation rate (100%). FISH studies were reported low positive for TP53 deletion and negative for BCR::ABL1 and MYC rearrangements. Peripheral blood had leukocytosis (WBC 19.6 × 10⁹/L) with neutrophilia (10.8 × 10⁹/L), lymphocytosis (7.3 × 10⁹/L), monocytosis (1.2 × 10⁹/L), mild thrombocytopenia (137 × 10⁹/L), and anemia (hemoglobin 9.2 g/dL) without blasts. The bone marrow biopsy had 50% cellularity, increased reticulin (MF2 of 3), and lymphoid aggregates comprising 50% of the interstitium. The hemodiluted aspirate had 0.7% blasts; <5% CD34- and CD117-positive cells were identified on the biopsy. Next-generation sequencing studies of the bone marrow aspirate detected 3 distinct pathogenic TP53 mutations, JAK2, DNMT3a, and TET2 mutations. Our case may suggest the inclusion of myeloid sarcoma in the TP53-mutated myeloid neoplasms group, also raising the clinical consideration of progression from an underlying JAK2-positive chronic myeloid neoplasm.

(Poster No. 115)

Vinay Sakaleshpura Mallikarjuna, MD¹ ([email protected]); Divya Salibindla, MD¹; David D. Grier, MD.^{2 1}Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio; ²Department of Pathology and Laboratory Medicine, Cincinnati Childrens Hospital Medical Center, Cincinnati, Ohio.

The concept of “in situ” lesions for mantle cell lymphoma and lymphomas of germinal or marginal zone origin is part of the 4th and 5th versions of the WHO classification and the International Consensus Classification. Outside of these classifications, there is literature that references the concept of another germinal center–derived lymphoma, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). The recognition of intrafollicular neoplasia is based on the immunohistologic pattern of intrafollicular atypical cells and appropriate immunohistochemical staining resembling lymphocyte-predominant (LP)–like cells within a microenvironment of altered follicles. We report a case of a healthy 6-year-old boy presenting with a painless neck mass. The node had histologic features of follicular hyperplasia with expanded mantle zones, focal Castleman-like morphology, and progressive transformation of germinal center with large, atypical cells (Figure 1.115, A [H&E]). The larger atypical cells expressed CD79a, CD20 (Figure 1.115, B), and OCT-2 (Figure 1.115, D) with CD 21 (Figure 1.115, C) highlighting follicular dendritic cell meshwork. The immunohistologic pattern fit an in situ lesion or intra follicular neoplasia as described by Carbone and Gloghini. This case highlights the importance of recognizing possible early lesions of NLPHL and a potential diagnostic pitfall, especially in limited biopsies. Further clinicopathologic correlation is required to define the frequency of association and risk of progression to NLPHL.

(Poster No. 116)

Maira Alejandra Forero Rivera, MD ([email protected]); Angie Lucia Rozo Cruz, MD; Karen Tatiana Galvis Castro, MD. Department of Pathology and Laboratory, Fundación Santa Fe de Bogotá, Bogotá DC, Colombia.

ALK-positive anaplastic large cell lymphoma (ALK⁺ ALCL) constitutes a notable portion of non-Hodgkin lymphomas in the pediatric population, accounting for approximately 10% to 15% of cases. While pericardial involvement is rare, its occurrence is associated with rapid dissemination and worse prognosis. The diagnostic challenges in such cases are related to the difficulty in distinguishing between reactive and neoplastic lymphoid infiltrates based on morphology, as well as unusual presentation. Consequently, there arises a critical need for complementary tools, with flow cytometry (FC) emerging as one of them, reducing the frequency of indeterminate diagnoses and the opportunity for intervention. We report the case of an 8-year-old girl under surveillance for ALK⁺ ALCL who presented to the emergency department with cardiologic symptoms. Clinical evaluation revealed severe pericardial effusion, focal thickening of the interventricular septum, and hemodynamically significant arrhythmias. Initial assessment by FC demonstrated the presence of a pathologic cell population expressing CD30, CD45, CD4, and partial loss of CD7 and negativity for CD3 (Figure 1.116, A). These findings were corroborated by cytologic (Figure 1.116, B) as well as immunocytochemical analysis showing expression of ALK and CD30 (Figure 1.116, C). All findings confirmed an early relapse of ALK⁺ ALCL. Despite ALK⁺ ALCL being a relatively common hematolymphoid malignancy in children, pericardial involvement is infrequent and sparsely documented in medical literature. Our case highlights the utility of FC in the diagnostic evaluation of pericardial effusions and the importance of considering unusual sites of dissemination in ALK⁺ ALCL, which necessitates a precise and rapid diagnosis for intervention.

(Poster No. 117)

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

Plasma cell myeloma with paraneoplastic POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is a rare occurrence with a variety of possible different clinical presentations that can lead to a delayed final diagnosis. We present the case of a 41-year-old woman who had been recently diagnosed with Guillain-Barré syndrome with subsequent weight loss, ascites, neuropathy, polycythemia, and thrombocytosis. Computerized tomography (CT) showed bilateral breast lesions measuring 3.1 cm and 2.7 cm in the right and left breast, respectively, and axillary and inguinal lymphadenopathy. Widespread sclerotic osseous lesions were also seen. The overall findings were highly concerning for metastatic breast carcinoma. Core biopsies of the axillary and inguinal lymph nodes showed reactive changes with polytypic plasmacytosis, which were negative for carcinoma, hematolymphoid malignancy, IgG4 disease, and syphilis. Serum immunofixation (IFE) detected an IgG λ monoclonal protein. Finally, a bone marrow biopsy showed 10% λ restricted plasma cells. As 3 major criteria and 4 minor criteria were met, a diagnosis of plasma cell neoplasm with POEMS syndrome was reached. Our case highlights the variable clinical presentation of plasma cell neoplasms with paraneoplastic POEMS syndrome, which is further obscured by other cofounding factors, and which requires a high level of suspicion for definitive diagnosis.

(Poster No. 118)

Kirk Bourgeois, MD¹ ([email protected]); Bryan Dangott, MD¹; Zeynettin Akkus, PhD¹; Trynda Kroneman, SCT(ASCP)²; Lucas Stetzik, PhD.^{3 1}Department of Laboratory Medicine and Pathology, Mayo Clinic Jacksonville, Florida; ²Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; ³Aiforia Inc, Cambridge, Massachusetts.

Context: Plasma cell disease diagnosis relies on the percent of clonal bone marrow plasma cells, traditionally from the 500-cell manual differential. However, atypical plasma cells are known to be highly variable in distribution within bone marrow, which increases risk of sampling bias. The bone marrow biopsy and clot section with specific immunohistochemical (IHC) stains (such as CD138 for plasma cells) provide much larger sampling of cells and increased accuracy. We test the hypothesis that pathologist-trained artificial intelligence (AI) for image analysis could augment manual evaluation.

Design: The AI model was developed using Aiforia Create, which includes multiple layers (specimen versus control, tissue versus nontissue, marrow space versus nonmarrow space, cellular versus fat, and positive versus negative), to narrow down the specimen into a cellular marrow layer allowing determination of positive and negative staining. Prior plasma cell disorder cases evaluated for estimated percentage of plasma cells by pathologists using CD138 IHC were scanned to create digital images. Twenty-five slides were used for annotation by a pathologist to create an AI model by image analysis (AIFORIA) for each layer. Forty separate slides were used for analysis by the composite multilayered AI model.

Results: Representative images of a case with prediction maps are shown in Figure 1.118, A–D. At current development, the combined layer model has a Pearson correlation between automated AI counting and pathologist estimation of 0.90 (R² = 0.81).

Conclusions: Preliminary development of an AI-layered model shows promise for providing accurate plasma cell percentage for use by pathologists in cases of plasma cell disease.

Dangott is a consultant with Philips Digital Pathology and Sectra.

(Poster No. 119)

Neel Patel, MBBS, MPH¹; Divya Salibindla, MD² ([email protected]); Fnu Kiran, MD³; Sanket Choksi, MD⁴; Matan Kadosh, MD⁵; Matthew S. Shapiro, MD⁵; Christian Salib, MD⁵; Bruce Petersen, MD⁵; Shafinaz Hussein, MD.^{5 1}Department of Pathology, Massachusetts General Hospital, Boston; ²Department of Pathology, University of Cincinnati Medical Center, Cincinnati, Ohio; ³Department of Pathology, Staten Island University Program, Staten Island, New York; ⁴Department of Pathology, Boston University Medical Center, Boston, Massachusetts; ⁵Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.

Context: In the context of the COVID-19 pandemic, understanding its impact on patients with plasma cell disorders, particularly multiple myeloma (MM), is crucial. We conducted a comprehensive nationwide study to assess the prevalence and outcomes of COVID-19 in hospitalized adults with MM.

Design: Using the Nationwide Inpatient Sample data for the year 2020, we conducted a population-based retrospective analysis of adult hospitalizations with primary diagnoses of MM and plasma cell malignancies. Sociodemographic factors and outcomes, including end-stage renal disease, mortality, and discharge disposition, were compared between COVID and non-COVID hospitalizations using ICD-10 codes. Weighted analyses, χ² tests, unpaired t tests, and multivariate regression models were employed to assess the prevalence and role of COVID in predicting outcomes.

Results: Among a total of 20 255 myeloma hospitalizations, 175 patients (0.86%) were diagnosed with COVID-19 after excluding those with age less than 18 years. COVID-19–positive MM patients exhibited a younger mean age at presentation (65 versus 66 years) and a longer length of hospital stay (12 versus 10 days) compared to non-COVID patients. Compared to non-COVID, MM was predominant in the 18–49 age group (20% versus 7.35%), in the >70 age group (42.86% versus 36.78%), and among Hispanics (25.71% versus 10.35%) and Asians (5.71% versus 2.95%; P < .001] in COVID hospitalizations. There was no impact of COVID on gender in MM prevalence (P = .20).

Conclusions: Our study found the substantial impact of COVID-19 on the prevalence and outcomes of plasma cell disorders including higher morbidity, mortality, functional decline, and poor discharge disposition.

(Poster No. 120)

Farhan Hassan, MD; Elizabeth Hyjek, MD, PhD; Hailing Zhang, MD; Mohammad Hussaini, MD ([email protected]). Department of Pathology, Moffitt Cancer Center, Tampa, Florida.

Histiocytic sarcoma (HS) is a rare malignant neoplasm (0.17/million). We present the first case of secondary HS with indeterminate dendritic cell (IDC) features developing in a patient with CLL and discuss the potential molecular mechanisms. A 77-year-old man with CLL infiltrating the liver presented with a right-sided oropharyngeal mass. Biopsy of the mass revealed infiltrate of large atypical histiocytic cells with oval to irregular indented nuclei. The neoplastic cells were positive for CD33, CD4, CD68 (subset, weak), CD163 (subset, weak), BCL6, S100 (subset), CD1a, and cyclin D1 (subset), but were negative for Langerin, BRAF V600E, CD21, CD23, CD35, CD123, TCF4, TCL1, MPO, lysozyme, CD20, CD79a, CD10, MUM1, and BCL2. The patient was also diagnosed with concurrent chronic myelomonocytic leukemia (CMML) on bone marrow biopsy. Careful genomic evaluation and dissection of all 3 cancers showed that SF3B1 p.E622D was present in both CLL and HS but not CMML; in addition, the HS acquired KRAS p.G13D, which we hypothesize drove the transdifferentiation of CLL to HS. Moreover, clonotypic evaluation of VDJ rearrangements by next-generation sequencing (NGS) in both the HS and CLL confirmed that these were clonally related, but not the CMML. Ours is the first report of secondary HS with IDC features arising from CLL. We established by both IGH NGS analysis and mutational analysis that the CLL and HS were clonally related and posit that acquisition of KRAS p.G13D drove transdifferentiation. This has potential therapeutic implications for targeting the RAS-BRAF-MAPK-ERK pathway.

(Poster No. 121)

Kelly S. Kim, BA¹ ([email protected]); Shuyue Ren, MD, PhD²; Gord Zhu, MD.^{2 1}Cooper Medical School of Rowan University, Camden, New Jersey; ²Department of Pathology, Cooper University Hospital, Camden, New Jersey.

Ewing sarcoma is a small round cell sarcoma that usually presents as a malignant bone tumor with locoregional pain and a palpable mass in pediatric patients. EWSR1-FL1 (85%) and EWSR1-ERG fusions (10%) are the most common translocations. We report a 38-year-old White man who presented with 2 months of progressive nasal congestion and edema of the medial canthus/upper eyelid secondary to an obstruction caused by a nasal mass. MRI and PET scan showed a left nasal cavity lesion extending to the maxillary, ethmoid air cells, and frontal sinuses with adjacent bony erosion. A left sinonasal mass biopsy revealed hypercellular sheets of relatively uniform small round cells with scant cytoplasm, indistinct cytoplasmic borders, round to oval nuclei, mild nuclear pleomorphism, and small nucleoli. The tumor was diffusely positive for vimentin, CD99, ERG, and NKX2.2; positive for INI1; and focally positive for CK Oscar, CAM5.2, desmin, and S100 immunohistochemical stains. The tumor was negative for claudin-4, pancytokeratin, CK19, CK7, CK20, CK5/6, p40, TTF-1, CD56, synaptophysin, chromogranin, INSM1, SOX10, HMB45, NKX3.1, TdT, CD43, CD45, CD34, CD31, WT1, TLE1, SALL4, and in situ hybridization for EBER (Figure 1.121, A–D). Ki-67 showed a proliferative rate of ∼20%. Next-generation sequencing testing of the tumor revealed EWSR1-ERG and PMM1-EWSR1 fusions. These findings supported a diagnosis of Ewing sarcoma. He was started on chemotherapy (vincristine, Adriamycin, cyclophosphamide, ifosfamide, etoposide, and mesna) and continues to be followed. This is the first case, to our knowledge, in which Ewing sarcoma occurred in the sinonasal cavity of a nonpediatric patient with both EWSR1-ERG and PMM1-EWSR1 fusions.

(Poster No. 122)

Grace J. Kwon, MD, PhD ([email protected]); Diana M. Cardona, MD, MBA; Kristen L. Deak, PhD; Jadee L. Neff, MD, PhD; William R. Jeck, MD, PhD. Department of Pathology, Duke University Medical Center, Durham, North Carolina.

A 16-year-old girl presented with a 2-month progressively growing left middle finger mass. MRI demonstrated an enhancing mass extending deep to the flexor tendon (Figure 1.122, A). A biopsy demonstrated epithelioid morphology (Figure 1.122, B) with negativity for SOX10, S100, p63, and p40. Myogenic markers (SMA, desmin) were also negative. MyoD1 was also negative. TLE1 was patchy positive, while INI1 was retained. Pan-CK was diffusely positive (Figure 1.122, C), while CK5/6 was focally positive. A solid tumor next-generation sequencing fusion panel demonstrated a novel EWSR1::KLF5 fusion at exon 9 of EWSR1 and exon 2 of KLF5. Interestingly, 8 cases have been reported in the literature of an EWSR1 fusion with a different KLF member (KLF15 in 7, KLF17 in 1), and all were described as myoepithelial carcinomas occurring in children/adolescents (7 weeks to 20 years). Of 3 cases that reported the breakpoint, all were at exon 2 of KLF15. The resection specimen demonstrated increased mitotic activity (up to 11/10 high-power fields), and redemonstrated negativity for SOX10, S100, p63, and SMA. Unexpectedly, preoperative workup revealed the patient had elevated β-HCG levels that precipitously decreased following resection; immunohistochemistry for β-HCG in the resection specimen was positive in tumor cells (Figure 1.122, D). To our knowledge, β-HCG has never been examined in reported KLF-fused tumors of soft tissue. Further investigation of these KLF-rearranged neoplasms will be helpful in clarifying whether they comprise a family of fusion tumors, a shared oncogenic event in numerous tumor types, or whether our case of an epithelioid neoplasm is a coherent, independent entity.

(Poster No. 123)

Xi Wang, MD, PhD ([email protected]); William Laskin, MD; Hao Wu, MD, PhD. Department of Pathology and Lab Medicine, Yale New Haven Hospital, New Haven, Connecticut.

Sarcoidosis is a multisystem granulomatous disorder that most commonly presents as bilateral hilar adenopathy and nodular pulmonary opacities with or without involvement of other organ systems. Presentation as an isolated osseous lesion is rare. We report 2 cases of granulomatous osteomyelitis that led to the diagnosis of systemic sarcoidosis. Case 1 involved a 74-year-old woman who was found to have pulmonary nodules during breast cancer surveillance. Further diagnostic workup showed extensive diffuse mixed lytic/sclerotic changes in the bilateral femurs, thoracic ribs, pelvis, and spine. Biopsy of the iliac lesion showed granulomatous osteomyelitis (Figure 1.123, A) with negative histochemical stains for infectious organisms (PAS, GMS, and AFB) (Figure 1.123, B), negative universal polymerase chain reaction (PCR) for an infectious cause, hypercalcemia, and bilateral hilar lymphadenopathy. She was diagnosed with sarcoidosis. Patient 2 was a 30-year-old woman who complained of intermittent right foot/ankle pain for 5 years with increased intensity for 2 months. Imaging showed multiple lytic lesions in the medial malleolus as well as the bone of the mid and hindfoot. Biopsy of the right ankle lesions showed necrotizing granulomatous inflammation (Figure 1.123, C). Histochemical stains for an infectious organism (GMS, AFB, Gram, and Warthin-Starry) and universal PCR for an infectious cause were negative. At the 11-month follow-up, she was found to have bilateral hilar soft tissue densities, mediastinal lymphadenopathy, and biopsy of the mediastinal lymph nodes showed nonnecrotizing sarcoidal-like granulomas (Figure 1.123, D), confirming a diagnosis of sarcoidosis. Our 2 cases show that osseous sarcoidosis can be asymptomatic and may precede systemic manifestation of sarcoidosis.

(Poster No. 124)

Xi Wang, MD, PhD ([email protected]); Raffaella Morotti, MD; William Laskin, MD; Hao Wu, MD, PhD. Department of Pathology and Lab Medicine, Yale New Haven Hospital, New Haven, Connecticut.

Rosai-Dorfman disease (RDD) is a rare non–Langerhans cell histiocytosis. Most patients present with painless cervical lymphadenopathy, but the clinical manifestations can be variable. Isolated osseous RDD can be especially challenging, mimicking more common osseous lesions clinically and radiologically. We report 2 cases of primary bone RDD. Case 1 involved a 4-year-old boy with a 2-week history of foot pain. Plain radiograph showed a lytic lesion in the distal tibia metaphysis with cortical thinning/breaching. Pathologic examination of the curettage specimen showed aggregates of enlarged histiocytes (Figure 1.124, A), which were diffusely S100 positive and negative for CD1a (Figure 1.124, B), establishing a diagnosis of RDD. The child was symptom free at the 8-year follow-up examination. Case 2 involved a 14-year-old girl who presented with a 1-year history of intermittent right knee pain. Radiology showed an aggressive-appearing distal femoral mass. Initial core biopsy showed a dense lymphohistiocytic infiltrate, and the patient was diagnosed with chronic osteomyelitis. A month later, she underwent curettage with placement of antibiotic beads and bone graft. This additional specimen showed a dense mixed inflammatory infiltrate with characteristic emperipolesis. The histiocytes were strongly immunoreactive for S100 (Figure 1.124, C), cyclin D1, and Oct2 (Figure 1.124, D), while negative for CD1a. The radiographs showed no evidence of disease progression at 2-month follow-up. No other FDG-avid lesion was seen on PET-CT in either of the 2 patients. Our cases illustrate the variable clinical presentation and nonspecific radiologic findings of RDD and highlight the importance of adequate sampling for a correct tissue diagnosis.

(Poster No. 125)

Jasmeen Kaur, MD ([email protected]); Alessandra Nascimento, MD. Department of Pathology, University Hospitals, Cleveland, Ohio.

Myoepithelial neoplasms of soft tissues are heterogenous and genetically different from salivary gland myoepitheliomas. Because of their rarity and variable morphologic features, ancillary studies are required for diagnosis. We present a case of a 12-year-old boy who presented with a 10-cm heterogeneously enhancing mass at the plantar aspect of the midfoot. Microscopically the neoplasm was composed of fascicles of spindle cells arranged in an alternating hypocellular and hypercellular pattern, with a delicate capillary-sized background vascular network. The tumor cells showed ovoid to spindled nuclei, hyperchromatic chromatin, variably conspicuous nucleoli, and moderate amounts of palely eosinophilic cytoplasm (Figure 1.125, A, B). Foci of necrosis were identified. Focally, the tumor fascicles appeared to infiltrate native tendinous tissue. By immunohistochemistry, neoplastic cells were positive for AE1/AE3, desmin (Figure 1.125, C and D), EMA, and pan-TRK (rare). INI1 and SMARCA4 showed intact nuclear positivity. The Ki-67 staining was 40.8% by automated 500-cell count. Next-generation sequencing demonstrated a EWSR1::KLF5 gene fusion, consistent with myoepithelial carcinoma. Two months later, a PET CT revealed multiple pulmonary nodules. A left lower lobe wedge resection was done and microscopically revealed metastatic myoepithelial carcinoma. This novel fusion has never been described in the literature in association with a specific tumor type. Myoepithelial neoplasms have been shown to harbor fusions involving EWSR1/FUS genes and other members of the KLF family of genes, namely KLF15 and KLF17. The novel fusion gene identified in these tumor cells expands the molecular spectrum of myoepithelial tumors. Further studies could help determine the clinical significance of these findings and identify potential targeted therapies.

(Poster No. 126)

Reba E. Daniel, MBBS ([email protected]); Alessandra F. Nascimento, MD. Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, Ohio.

Solitary fibrous tumors (SFTs) are fibroblastic mesenchymal tumors known to occur at any anatomic location. However, primary SFTs of bone are rare. We present a case of a 77-year-old White man, status post total right hip arthroplasty, with the complaint of right hip pain for 1 year that had worsened since a fall. Imaging showed a stable hip implant with significant osteolysis of the proximal femur with complete cortical breakthrough and extension into the soft tissues. A core biopsy showed atypical cells, some with large irregular hyperchromatic nuclei, positive for STAT6, CAM5.2, and CD99 (weakly). CD34 was negative. Next-generation sequencing showed NAB2::STAT6 gene fusion, supporting the diagnosis of SFT. Atypical morphology and loss of CD34 expression suggested dedifferentiation. The patient underwent a wide excision of the right proximal femur. Histologic examination of the resection specimen revealed a multinodular spindle cell neoplasm arising from bone and extending into soft tissue. The tumor had a haphazard pattern with focal areas of nuclear palisading, and diffuse CD34 and STAT6 expression (Figure 1.126, A, B). Hypocellular foci with adipocytic differentiation, slight myxoid background, and weak CD34 and STAT6 were present, suggestive of lipomatous variant of SFT. A dedifferentiated component was also noted with a fascicular proliferation pattern, scattered large atypical hyperchromatic cells without CD34 or STAT6 expression (Figure 1.126 C, D), numerous giant cells, and increased mitotic activity. To our knowledge, this is the first reported primary dedifferentiated SFT of bone. In core biopsy specimens with dedifferentiated morphology, immunohistochemistry along with molecular studies is vital for accurate diagnosis.

(Poster No. 127)

Hatem Kaseb, MD, PhD, MPH¹ ([email protected]); Jeffrey P. Townsend, PhD²; Jose Costa, MD³; William Laskin, MD.^{3 1}Department of Clinical Sciences, Pathology, University of Central Florida, Orlando; ²Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut; ³Department of Pathology, Yale School of Medicine, New Haven, Connecticut.

Context: Undifferentiated pleomorphic sarcoma of bone (UPSb) is a rare bone sarcoma with a poorly defined mutation lineage. These tumors usually present as high grade and have high metastatic rates of roughly 50%. There are limited data on molecular characteristics of UPSb. TP53 mutations have been identified as the most common mutation in USPb.

Design: We searched the electronic medical records system of Yale School of Medicine for archived pathology cases from 1980 to 2019. Four cases were retrieved. Whole-exome sequencing was used to identify significant mutations that exist in the UPSb patient cohort. We assessed the contribution of each mutation to cancer cell survival and proliferation using cancer effect size R. We also analyzed the influence that endogenous and exogenous mutagenic processes defined by trinucleotide mutational signatures have on formation of oncogenic driver mutations.

Results: Assessment of genetic mutations in our cohort revealed many somatic mutations affecting diverse signaling pathways, including cell cycle/apoptosis pathways, the DDR pathway, and histone and chromatin modifier pathways. Consistent with historical data, the most commonly identified mutation was in TP53. We and others believe that TP53 alterations are likely early events in sarcoma pathogenesis and facilitate genomic instability. The mutational processes with the largest tumor mutation burdens were unknown/nonspecific aging process, thiopurine chemotherapy treatment effect, and deamination aging signature.

Conclusions: The identification of these molecular characteristics is crucial not only for clearer diagnostic process, but also because it may lead to more efficient and targeted immunomodulatory therapies.

(Poster No. 128)

Reba E. Daniel, MBBS ([email protected]); Alessandra F. Nascimento, MD. Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, Ohio.

Giant cell tumor (GCT) of bone is a benign tumor with locally aggressive behavior and predilection for metaphyses of long bones. It most often arises in the third to fifth decades of life. GCTs account for only 5% of all primary bone tumors. These tumors are characterized by the presence of osteoclast-like giant cells in a background of bland mononuclear cells with variable cytomorphology. However, there are a small handful of reported cases in the literature describing a giant cell–poor variant of GCT of bone. While morphologically these cases prove to be difficult because of a lack of diagnostic giant cells, appropriate classification is aided by availability of H3.3 G34W mutation–specific monoclonal antibody and molecular studies. We report a 19-year-old man who presented with history of left hip pain for 5 months exacerbated by playing sports. X-ray showed a lytic lesion in the left proximal femoral head and neck (Figure 1.128, A). Biopsy of the lesion showed a cellular proliferation of uniform spindle cells with ovoid nuclei and sparse cytoplasm within a fibrous stroma and interspersed calcifications. Immunohistochemistry demonstrated nuclear expression of G34W and absence of K36M expression. Histone gene mutation analysis confirmed H3F3A gene mutation, consistent with the diagnosis of GCT. The resection specimen showed similar morphology with G34W expression and scattered giant cells in a few areas (Figure 1.128, B–D). Only a few cases of this variant of GCT of bone have been described. It is unclear if this morphology represents a histologic variant of the lesion or an attempt at tumor regression.

(Poster No. 129)

Michael Lack, DO ([email protected]); Robert Foucart, DO; Lauren Edwards, BA; Robert Hoyt, MD; Ameer Hamza, MD; Anders Meyer, MD. Department of Pathology, University of Kansas Medical Center, Kansas City.

Nested glomoid neoplasm is a recently described subset of mesenchymal neoplasm defined by alterations and rearrangements in the gene for glioma-associated oncogene 1 (GLI1). Histologically they are composed of nests of round to ovoid cells with scant, palely eosinophilic cytoplasm and monomorphic nuclei with vesicular chromatin and small nucleoli. These tumors can show STAT 6 positivity, and therefore can be misdiagnosed as solitary fibrous tumor. The purpose of this report is to describe a case of solitary fibrous tumor mimicking this new entity. A 76-year-old man presented with a lesion on the posterior neck, initially noted incidentally on a CT scan performed because of a fall. MRI demonstrated a T1 hypointense, T2 heterogeneously hyperintense enhancing mass in the paraspinous musculature in the suboccipital region, 6.2 cm in greatest dimension. Because of a concern that this was a soft tissue sarcoma, an initial biopsy was performed, which was morphologically consistent with a mesenchymal neoplasm without high-risk histologic features. CD34 and STAT6 were positive, while S100, SOX10, SMA, and desmin were negative. The mass was subsequently resected. Histologically, the tumor was composed of epithelioid to spindled cells in nests and rosettes, mimicking the nested glomoid neoplasm. Next-generation sequencing demonstrated NAB2::STAT6 fusion, clinching the diagnosis of solitary fibrous tumor. With incorporation of molecular data, the pathologic classification of tumors in general and soft tissue tumors in particular is rapidly evolving. Pathologists need to stay up-to-date and include molecular studies in addition to immunohistochemical stains to avoid potential diagnostic pitfalls.

(Poster No. 130)

Saad Abdul Quddus Gandhi, MD ([email protected]); Soheila Hamidpour, MD. Department of Pathology, University of Missouri Kansas City–School of Medicine, Kansas City.

A 71-year-old man, a nonsmoker with past medical history of hypertension and hyperlipidemia, presented to the emergency department with a 1-week history of worsening shortness of breath associated with orthopnea, paroxysmal nocturnal dyspnea, and chronic lower limb swelling. Chest x-ray and CT chest showed large right-sided pleural effusion; workup showed bloody pleural fluid negative for malignancy on cytology. Video-assisted thoracic surgery for pleural biopsy was performed, which showed white pleura with punctate hemorrhages and multiple adhesions between lung and parietal pleura. Biopsies were taken from the pleura and adhesions. The pleural fluid tested negative for asbestosis. Histologic sections of the pleural biopsy showed a cytologically atypical population of epithelioid cells infiltrating a reactive soft tissue. The cells infiltrated in single cell cords and nests. Many of the cells had intracytoplasmic lumina (Figure 1.130, A). Immunohistochemical stains for CAMTA-1 (Figure 1.130, B) showed diffuse nuclear positivity that confirmed the diagnosis of epithelioid hemangioendothelioma. Immunohistochemical stains showed that the tumor cells were diffusely positive for CD31 (Figure 1.130, C), CD34, and FLI-1, while they were negative for TFE3, pancytokeratin, calretinin, TTF-1, SOX10, Mart 1, and CK5/6. This is a rare low-grade cancer with an incidence of 1 in 1 000 000 that arises from endothelial cells and affects veins, arteries, and capillaries anywhere in the body, although the most common locations include lungs, bones, and liver. It appears in all ages but is slightly more prevalent in young adults and is more frequent in females. The management and prognosis depend upon location and extent of disease.

(Poster No. 131)

Andrew Horton, DO ([email protected]); Palak Parekh, MD; Debby Rampisela, MD. Department of Pathology, Baylor Scott and White, Temple, Texas.

Context: Tenosynovial giant cell tumor (TGCT) encompasses a group of lesions that involves the synovium, tendon sheath, and bursae. This entity can be subclassified into diffuse or localized. A rare subtype known as the chondroid TGCT has been reported to have a predilection for the temporomandibular joint. We report 4 cases of chondroid TGCT occurring in the fingers, a location in which chondroid TGCT has been rarely reported.

Design: We reviewed cases in our institutional records involving finger lesions with findings suggestive of chondroid TGCT such as calcifications, giant cells, and/or mononuclear cells (Figure 1.131). Four cases that were diagnosed descriptively after further review were determined to likely be chondroid TGCT. The 4 cases were stained with clusterin and D2-40 immunostains, which are known to be expressed in TGCT.

Results: All 4 cases involved the fingers at the proximal interphalangeal, distal interphalangeal joint, and shaft of the first metacarpal. The ages of the patients ranged from 34 to 74 years. The ratio of male to female was 1:1. The tumors’ gross measurements ranged from 0.7 cm to 1.2 cm. All cases had focal chondroid features and positive staining for clusterin and D2-40.

Conclusions: This case series reports chondroid TGCT occurring in the fingers as opposed to its more known location of the temporomandibular joint. Therefore, chondroid TGCT is an important differential diagnosis to consider in finger lesions with calcifications and giant cells. Microscopic examination to find the chondroid features and mononuclear cells is recommended. In addition, performing clusterin and D2-40 immunostains can aid in its diagnosis.

(Poster No. 132)

Julie M. Pham, DO ([email protected]); Hebatullah Elsafy, MBBCh; Michael Lack, DO; Ameer Hamza, MD. Department of Pathology, University of Kansas Medical Center, Kansas City.

Myxoid pleomorphic liposarcoma is an exceedingly rare and aggressive adipocytic neoplasm. Patients are predominantly children and adolescents with a female predominance. Common sites of involvement include mediastinum, head and neck, thigh, perineum, abdomen, and back. Visceral involvement is exceptionally rare. The purpose of this report is to describe a case of a primary pulmonary myxoid pleomorphic liposarcoma. A 33-year-old man with a history of osteochondroma and anaplastic astrocytoma presented for evaluation of a pleural-based mass of the left lower lung lobe that measured 8.5 × 5.1 cm by CT imaging. A biopsy showed a pleomorphic and sarcomatoid neoplasm with areas of lipoblastic differentiation. Immunohistochemical stains showed positivity for S100 (lipoblasts) and p53 (mutant pattern). ERG, SMA, calretinin, D2-40, and GATA3 showed weak, focal positivity. Immunohistochemical stains for pancytokeratin, CAM 5.2, CK5/6, CK7, CK20, MOC-31, p40, NUT, desmin, SOX10, WT1, GFAP, Olig 2, Myo D1, and STAT6 were negative. INI1, BAP1, and MTAP stains showed retained expression in the tumor cells. Results of FISH study for MDM2 were negative. Diagnosis of myxoid pleomorphic liposarcoma was rendered after expert consultation. The patient received induction chemotherapy with doxorubicin and subsequently underwent resection. The patient is alive without recurrent or metastatic disease 5 months after surgery. Primary visceral myxoid pleomorphic liposarcoma is rare, with a handful of cases reported in the literature. Diagnosis is challenging, especially on a biopsy specimen. Apart from essential diagnostic criteria based on morphology, desirable diagnostic criteria include absence of FUS/EWSR1-DDIT3 gene fusions and MDM2 amplifications in selected cases. Expert opinion is also advisable.

(Poster No. 133)

Mahalia T. Robinson, DO, MS ([email protected]); John Gross, MD. Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare translocation sarcoma characterized by alternating collagenous and myxoid areas, deceptively bland spindle cells with a whorling growth pattern, and arcades of small vessels. LGFMS commonly involves the deep soft tissues of the proximal extremities, with unusual presentations in visceral sites. To our knowledge, there is one case of an LGFMS of the penis in the literature; however, immunohistochemistry and molecular genetics were not performed. Herein, we report the case of a 23-year-old man who presented with a nodular mass at the base of the penis. An excisional biopsy showed a cellular mesenchymal tumor composed of bland spindled cells growing in alternating zones set within a background fibromyxoid stroma (Figure 1.133, A–C). Nuclear pleomorphism, mitotic activity, and necrosis were not identified. MUC4 immunohistochemistry was strong and diffusely positive (Figure 1.133, D). Subsequent molecular analysis detected a FUS::CREB3L2 fusion, further supporting this diagnosis. While the behavior of LGFMS is fully malignant with local recurrence and metastatic potential, the histologic differential diagnosis typically includes less sinister neoplasms such as intramuscular myxoma, soft tissue perineurioma, and PRRX1-rearranged tumors. Therefore, careful morphologic correlation and judicious application of ancillary studies (MUC4 immunohistochemistry and RNA-fusion panels) can aid tumor classification and avoid potential pitfalls, including when LGFMS presents in extraordinarily rare anatomic sites.

(Poster No. 134)

Jessica Maupin, DO ([email protected]); Swati Satturwar, MD; O. Hans Iwenofu, MD. Department of Pathology, Ohio State University, Columbus.

Primary cutaneous spindle cell malignant peripheral nerve sheath tumor (CS-MPNST) is a rare subset of MPNST located in the dermis or subcutis. While they share a similar morphologic phenotype with their deep soft tissue counterparts, they tend to be smaller, have infrequent association with neurofibromatosis 1 (NF1), and tend to have better prognosis. Notably, conventional MPNST has been molecularly characterized by mutations of CDKN2A/CDKN2B, loss of EED and SUZ12, and H3K27 trimethylation; the molecular underpinnings of CS-MPNST are not known. We present the comprehensive genomic profiling of CS-MPNST with novel predominant SETD2 inactivating mutation. A 32-year-old man with no significant PMH presented with a mass in the left leg. Imaging studies showed a 2.0 × 1.0 × 0.8-cm well-circumscribed, thin-walled cystic mass within the subcutis. The initial biopsy was presumed to be benign, prompting an intralesional excision. Sections revealed a malignant neoplasm composed of spindle cells exhibiting herringbone pattern, nuclear hyperchromasia, and brisk mitosis. By immunohistochemistry, the cells were positive for CD56 and negative for p16, desmin, S100, SOX10, and H3K27me3, consistent with CS-MPNST. Comprehensive genomic profiling revealed an inactivating mutation in SETD2 with variable allele frequency of 81.7%. SETD2 is an RNA polymerase II–associated histone methyltransferase involved in the transcriptional methylation of H3K36me3, critical in DNA repair and the maintenance of genomic stability. Mutations of SETD2 are associated with tumorigenesis involving several solid tumors. Identification of this mutation may offer diagnostic and therapeutic strategies. Further studies on CS-MPNST are warranted to fully elucidate the biological/translational significance of this mutation (Figure 1.134, A–D).

(Poster No. 135)

Jack Reid, MD¹ ([email protected]); Elyssa Rubin, MD²; Amirhossein Misaghi, MD³; Ali Nael, MD.^{4 1}Department of Pathology, City of Hope, Duarte, California; Departments of ²Pediatric Oncology, ³Orthopedic Surgery, and ⁴Pathology, Children Hospital of Orange County, Orange, California.

Desmoplastic small round cell tumor (DSRCT) is an extremely rare malignant mesenchymal neoplasm that preferentially affects children and young adults. Patients usually present with widespread abdominal and peritoneal involvement. Exceedingly rare cases of DSRCT in the limbs, head and neck, kidney, and brain have been reported. Grossly, DSRCT typically shows multiple tumor nodules studding the peritoneal surface. Histologic findings include nests of small round blue cells embedded in desmoplastic stroma. By immunohistochemistry, DSRCT shows expression of cytokeratin, EMA, desmin, and WT1. Molecular studies show EWSR1-WT1 gene fusion. We present a case of a 15-year-old boy who presented with a mobile, painful left shoulder mass for the previous 2 years. The patient was admitted for metastatic evaluation. Radiologic imaging results showed a well-defined enhancing solid mass in the left trapezius muscle measuring 2.8 × 6.5 × 6.9 cm. No bony abnormality was identified. The biopsy of the lesion showed nests of small round cells (Figure 1.135, A, B) expressing desmin (Figure 1.135, C), synaptophysin (Figure 1.135, D), and FLI-1 and negative for S100, myogenin, pancytokeratin, SALL4, TLE1, SATB2, ERG, chromogranin, WT-1, NKX2.2, and CD99. Next-generation sequencing was performed and detected EWSR1-WT1 gene fusion. DSRCT is a rare aggressive mesenchymal tumor affecting children and young adults with a poor median overall survival. Our case highlights the unique clinical presentation of a solitary DSRCT of the left trapezius muscle without peritoneal involvement, underscoring the necessity for comprehensive histologic analysis and cytogenetic and molecular testing to guide specific clinical treatment strategies.

(Poster No. 136)

Chukwuemeka-Chika C. Iguh, MD, MSc ([email protected]); Joshua Lee, MD; Parisa Davoodi, MD; Manuel Enrique Lores Gonzalez, MD; Caroline Yap, MD; Sava Grujic, MD. Department of Pathology & Laboratory Medicine, Harbor-UCLA Medical Center, Torrance, California.

Myxoid liposarcoma is a rare malignant mesenchymal tumor that typically arises in the lower extremities of young adults, with a high potential for metastasis. Common areas of spread include the lungs, bone, retroperitoneum, and other soft tissue sites. We present a case of a 34-year-old woman who presented with a 1-week history of epigastric pain, vomiting, and melena. A year prior to presentation, she was diagnosed at our institution with left anterior thigh myxoid liposarcoma and treated with wide local excision, neoadjuvant chemotherapy (doxorubicin, ifosfamide, and mesna), and radiation. Contrast-enhanced computed tomography of the abdomen revealed a complex solid and cystic mass in the pancreatic head, and this heterogeneously enhancing mass was also seen on endoscopic ultrasound. Fine-needle biopsies of the mass were performed with histologic evaluation showing admixed, variably sized aggregates of proliferating stellate to fusiform spindled cells that were haphazardly embedded within an abundant myxoid stroma and separated by an arborizing or plexiform “chicken wire” or “crow’s feet” capillary network (Figure 1.136, A). Immunohistochemical stains of the tumor cells were positive for vimentin (Figure 1.136, B) and negative for pancytokeratin (AE1/AE3), CK7 (Figure 1.136, C), CK20, and S100 (Figure 1.136, D), supporting a diagnosis of metastatic myxoid liposarcoma. The patient died approximately 6 months following this diagnosis despite subsequent neoadjuvant chemotherapy and radiation. Solitary metastasis of extremity myxoid liposarcoma to the pancreas is exceptionally unusual. The present case adds significantly to the current understanding of the metastatic behavior of this entity.

(Poster No. 137)

Zhengchun Lu, MD, PhD ([email protected]); Sintawat Wangsiricharoen, MD. Department of Pathology and Laboratory Medicine, Oregon Health & Science University, Portland.

Dermatofibrosarcoma protuberans (DFSP) is a superficial, locally aggressive, fibroblastic soft tissue tumor that has a unique cellular storiform appearance. Although most tumors harbor COL1A1::PDGFB gene fusions, 2% of cases harbor alternative fusions involving PDGFD. We present a case of a 40-year-old woman who presented with a small mass present on her left ankle for 10 years that recently had increased in size, prompting surgical excision. Histologic sections showed a monotonous, low-grade, spindle cell neoplasm that consisted of fascicles of mildly atypical spindle cells in a variably collagenous stroma, giving a vague biphasic appearance (Figure 1.137, A–C). Typical areas of DFSP were not identified. Mitotic rate was 3/10 high-power fields. Tumor necrosis was absent. The tumor cells were diffusely positive for CD34 (Figure 1.137, D), focally positive for SMA and caldesmon, and negative for desmin, CD31, ERG, S100, SOX10, EMA, β-catenin, p63, STAT6, MUC4, and SS18-C-terminus. H3K27me3 expression was retained. We reviewed this case as a confirmatory consultation with an initial diagnosis being a CD34-positive low-grade spindle cell sarcoma. No gene fusion was identified; however, the fusion panel did not cover PDGFD. Given the monotony and diffuse CD34 expression, we performed whole-transcriptome sequencing, which identified an EMILIN2::PDGFD fusion. This case highlights the importance of considering alternative fusions when the diagnostic consideration includes DFSP but PDGFB rearrangement is not identified by FISH or targeted fusion panel. Whole-transcriptome sequencing can identify rare gene fusions to confirm the diagnosis. Cases with EMILIN2::PDGFD fusions tend to be deep-seated in the subcutis and display fibrosarcomatous transformation.

(Poster No. 138)

Hehua (Hannah) Huang, MD, MS ([email protected]); Shi Kaung Peng, MD, PhD. Department of Pathology, Harbor-UCLA Medical Center, Torrance, California.

Context: Retroperitoneal liposarcoma (RLS) stands out as a rare tumor in an uncommon location, presenting unique challenges because of its heterogeneity and the array of histopathologic subtypes affecting outcomes. This study delves into these subtypes, particularly contrasting well-differentiated and dedifferentiated/mixed types, enriched by an analysis of patient demographics and the MDM2 molecular marker. It aims to deepen the understanding of RLS’s prognostic factors, contributing to improved care for this challenging condition.

Design: We conducted a detailed retrospective analysis from 2014 to 2024, reviewing 10 RLS cases for demographic information, histopathologic classification, treatment modalities, and follow-up outcomes.

Results: The cohort’s median age was 52 years, with a male predominance (80%; Table). Tumor size varied significantly, ranging from 10.5 cm to 38 cm, indicating the aggressive potential of RLS. All cases exhibited MDM2 amplification, affirming its diagnostic relevance. Importantly, purely well-differentiated liposarcomas (3 cases) demonstrated no recurrence during a 3-year or 5-year follow-up, signaling a comparatively favorable prognosis. In stark contrast, dedifferentiated/mixed types (7 cases) were associated with a higher recurrence rate, even with surgical resection and negative margins, highlighting their inherently aggressive behavior.

Conclusions: This research highlights the prognostic differences in RLS based on histopathologic subtypes. Well-differentiated liposarcomas show a favorable prognosis with low recurrence, while dedifferentiated/mixed types suggest a worse prognosis, requiring intensive management and careful monitoring after surgery. These insights underline the critical role of identifying subtypes to improve prognostic precision and tailor patient management in RLS.

(Poster No. 139)

Xinrui Bao, BS ([email protected]); Brittni Plummer, BS; Christian Heck, PhD; Ronald Walser, DPT. Department of Anatomy, Pacific Northwest University of Health Sciences, Yakima, Washington.

Diffuse idiopathic skeletal hyperostosis (DISH) is a diffuse spinal arthritic disease that commonly presents asymptomatically in the eighth decade of life. Classic presentation of DISH involves bridging ossifications on the anterior and right anterolateral aspects of the cervical and thoracic vertebrae, respectively. Here we present unique gross anatomical findings supported by a radiographic X-ray series conducted on a dissected cadaver showing anomalous morphologies of DISH. During a routine medical education dissection, evidence of ossifications characteristic to DISH were found on a 75-year-old deceased man who suffered from chronic obstructive pulmonary disease and cardiovascular disease of unknown etiology. Further examination revealed lesions spanning from C2 through L4, including unique involvements on the bilateral thoracic vertebrae, and posterior facets and spinous processes of the cervical spine that are otherwise undescribed in association with DISH. Gross isolation of the vertebrae was performed with removal of the supraspinous ligament, musculature, soft tissue, and organs. Postdissection x-ray imaging, after resection of the ribs and thoracolumbar lamina, was interpreted by a board-certified radiologist who confirmed the diagnosis of DISH. Severe DISH is rarely described clinically. However, extensive ossifications in the cervical vertebrae as seen in this study implicate physiologic deglutition and neuropathies through mass effects, while bilateral thoracic growths potentiate the formation of atherosclerotic plaque through disruption of aortic laminar flow. Studying the pathologic anatomical relationships and radiologic manifestations of this unusual severe DISH presentation can inform targeted interventional therapies aimed at diagnosing and managing the condition and aid in the understanding of related histopathologies.

(Poster No. 140)

Tania M. Platero Portillo, MD¹ ([email protected]); Haneen T. Salah, MD²; Kalyani R. Patel, MD¹; Kevin E. Fisher, MD, PhD.^{1 1}Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas; ²Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas.

Myxomas are rare, benign neoplasms originating from primitive mesenchymal cells. They commonly occur in adulthood and are rarely found in the orbit. In this report, we present 2 unusual cases of infantile orbital myxoma, both associated with a rare MN1::TAF3 fusion. Case 1 involved a male infant with a right orbital mass first noticed by his parents at 5 months of age and thought to be a dermoid cyst. Clinical monitoring over 10 months revealed progressive growth leading to excision. Pathologic examination showed a cellular spindle cell lesion morphologically resembling nodular fasciitis. Case 2 was a 3-month-old male infant with intermittent left eye drainage and swelling of eyelid with a rapidly growing orbital mass. MRI showed a 1.7-cm extraocular enhancing mass lesion involving the left superior medial preseptal and postseptal orbital soft tissues. Biopsy showed a tumor composed of mildly atypical spindle cells arranged in short fascicles and focal whorls, and scattered cells with large hyperchromatic nuclei and absent nucleoli and infrequent mitosis. In both cases, targeted next-generation RNA sequencing revealed MN1::TAF3 fusion that was confirmed by reverse transcriptase PCR and Sanger sequencing. Case 1 did not exhibit USP6 and ETV6 fusions. No other fusions were detected. These cases highlight the rarity of infantile orbital myxoma and underscore the significance of broad fusion analysis to identify rare MN1::TAF3 fusions. The absence of common fusions linked to other neoplasms suggests distinct molecular mechanisms in the pathogenesis of infantile orbital myxoma, prompting the need for further research and exploration of potential targeted therapeutic strategies.

(Poster No. 141)

Troi Lake, MD, MS ([email protected]); John Gross, MD. Department of Pathology, the Johns Hopkins Hospital, Baltimore, Maryland.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare translocation sarcoma (commonly harboring FUS::CREB3L2 or FUS::CREB3L1 fusions) characterized by alternating collagenous and myxoid areas and deceptively bland spindle cells. Although LGFMS shows low rates of recurrence and metastasis in the first 5 years after primary excision, rates are much higher with long-term follow-up, including metastases occurring as long as 45 years after primary excision (1 patient). The median interval to tumor-related death is 15 years. We present a 40-year-old woman who had a “benign” tumor removed from her arm in 1983. Now, as an 80-year-old, she presented with a 10-cm mass arising within the prior surgical bed. Histology revealed a bland myxoid spindle cell neoplasm growing in intersecting fascicles and whorls with a prominent arcadelike background vasculature (Figure 1.141, A–C). Immunohistochemistry was positive for MUC4 (Figure 1.141, D). While LGFMS is notorious for late recurrences and metastases, to our knowledge, this is possibly the longest interval of local recurrence (40 years) ever described. There is a report of 1 patient developing metastatic disease at 45 years after primary excision, but that was after multiple prior local recurrences at 13, 19, 25, and 30 years before ultimately developing lung metastases at 45 years. Thus, we emphasize that patients with LGFMS need to be followed indefinitely by an oncologist. While her tumor was originally misclassified as “benign” in 1983, improved tumor classification, including judicious application of ancillary studies (MUC4 IHC and/or RNA fusion analysis), can help avoid diagnostic pitfalls.

(Poster No. 142)

Reem Youssef, MBBCh ([email protected]); Laura Warmke, MD; Carina Dehner, MD, PhD. Department of Pathology, Indiana University School of Medicine, Indianapolis.

Context: Perivascular epithelioid cell neoplasms (PEComas) are mesenchymal tumors that typically have TSC1 or TSC2 alterations and occasionally TFE3 fusions. While large case series involving the GYN tract have been reported, the data on nonuterine tumors remain scarce.

Design: The institutional archive was searched for “malignant perivascular epithelioid cell neoplasm (PEComa)” while excluding uterine tumors. Data were collected from electronic medical records. Slides were reviewed for morphologic features.

Results: Twelve tumors occurred in 6 males and 6 females with a median age of 52 years. Primary sites included genitourinary tract (7), gastrointestinal tract (3), lung (1), and soft tissue (1). Median tumor size was 9.6 cm. Follow-up for 10 of 12 patients (median, 28.5 months; range, 1.5–144 months) showed 3 with no evidence of disease, 2 died of disease, 4 alive with distant metastasis, and 1 alive with residual tumor. On histology, all tumors were classified as malignant based on necrosis (5 of 12), nuclear atypia (12 of 12), and increased mitotic activity (7 of 12). Interestingly, most tumors displayed epithelioid features (11 of 12) either complete or at least partial. Positive immunohistochemistry was observed for cathepsin K (7), HMB45 (6), MITF (2), Melan-A (4), TFE3 (4), actin (7), and desmin (3) (Figure 1.142, A-D). Fluorescence in situ hybridization demonstrated TFE3 gene translocation in 2 cases. Molecular analysis revealed genetic alterations to include (1) TSC2 and ATRX, (1) TSC1, and (1) PDGFRB W566R, MTOR C1483F, CDKN2A/B.

Conclusions: Herein we studied the clinicopathologic features of a large series of nonuterine malignant PEComas. Predominance of epithelioid morphology, prominent nuclear atypia, and diffuse cathepsin K expression were noted. Further studies regarding molecular landscape and comparison with uterine tumors are ongoing.

(Poster No. 143)

Azadeh Samiei, MD; Mohammed Saad, MBBS; Ahmet Surucu, MD; Katrina Collins, MD ([email protected]); Muhammad T. Idrees, MD; Andres M. Acosta, MD; Thomas M. Ulbright, MD; Varsha Nair, MD. Department of Pathology, Indiana University, Indianapolis.

Since the widespread adoption of next-generation sequencing, rare mesothelial neoplasms driven by EWSR1 fusions (including EWSR1::CREM, EWSR1::ATF1, and EWSR1::YY1) have been identified in mesothelial-lined cavities of patients without significant exposure to asbestos. Tumor resection has shown promise as a treatment modality. A 42-year-old man, previously treated for metastatic seminoma, presented with a perirectal mass. Prior radical orchiectomy showed a testicular scar consistent with a regressed germ cell tumor. After chemotherapy and surveillance, a follow-up PET/CT scan revealed a new pelvic cavity mass with fludeoxyglucose activity. Fine-needle aspiration confirmed an epithelioid neoplasm with mesothelial differentiation, positive for mesothelial markers and androgen receptor. On resection, the tumor showed a monotonous population of epithelioid cells arranged in nests and tubules with mild nuclear atypia. Scattered mitotic figures were seen. The periphery of the lesion showed a lymphoid cuff. Mesothelial differentiation was confirmed with positive immunostaining for WT1, D2-40 (focal), and AE1/AE3, while calretinin, OCT4, SALL4, AFP, glypican-3, CD30, ER, MOC31, and synaptophysin were negative. A FISH study for isochromosome 12p was negative. RNA sequencing analysis identified a EWSR1::YY1 rearrangement, a finding consistent with this rare subtype of mesothelioma. Peritoneal mesothelioma with EWSR1::YY1 fusion is a distinct entity, typically occurring in the peritoneal cavity of middle-aged patients unrelated to asbestos exposure. Notably, no recurrence occurred in cases where complete surgical excision was achieved. The clinical significance of this fusion remains to be fully elucidated.

(Poster No. 144)

Veronica Gross, MD, PhD ([email protected]); Maoxin Wu, MD; Brendan Boyce, MD. Department of Pathology, SUNY Stony Brook Medicine, Stony Brook, New York.

Secondary malignancy due to treatment for non-Hodgkin lymphoma (NHL) is well documented, with an increased absolute excess risk for developing any malignancy regardless of treatment modality. Primary leiomyosarcomas of the inferior vena cava (IVC) are rare solitary tumors arising from the smooth muscle of the intima. A history of radiotherapy is a significant factor in development of any sarcoma. This case highlights an exceptionally rare secondary malignancy of an IVC leiomyosarcoma. A 69-year-old woman was treated for retroperitoneal NHL in 1968 with high-intensity radiotherapy and lumbar laminectomy. She experienced complete remission without subsequent known malignancies. She presented in 2024 with pain and swelling at the site of her surgical incision at L1–L3. An MRI demonstrated a new 1.5-cm enhancing lesion in the L3 vertebral body. CT showed a 1.3 × 1.0 × 2.5-cm infrarenal IVC thrombus (Figure 1.144, A). Interventional radiology removed gelatinous white material concerning for tumor thrombus. Histology demonstrated a spindle cell neoplasm with significant nuclear pleomorphism (Figure 1.144, B), extensive necrosis, and >7 mitoses per 10 high-power fields. Immunohistochemistry showed the tumor cells were positive for desmin (Figure 1.144, C), calponin (Figure 1.144, D), smooth muscle myosin heavy chain, and vimentin, consistent with a leiomyosarcoma. Biopsies of the soft tissue swelling and L3 vertebral lesion demonstrated nonmalignant soft tissue, and bone and cartilage fragments. To our knowledge, this is the first report of an IVC leiomyosarcoma in a patient treated for NHL. Though sarcomas are rare secondary malignancies, the tumor’s location within the area of treatment suggests radiation was a contributing factor.

(Poster No. 145)

Serene A. Mostafa, MD ([email protected]); Evita Henderson-Jackson, MD. Department of Pathology, University of South Florida, Tampa.

Chordomas are malignant notochordal neoplasms typically occurring in the clivus, spine, and sacrum, which are difficult to treat with a poor prognosis. Extra-axial chordomas are increasingly rare and are usually found in the extremities. This is the first report of a chordoma occurring in the phalanges. A 34-year-old woman presented with a 2-year history of a slow-growing mass on her left fourth digit that began to increase in size as she was pregnant. Imaging noted a circumferential mass with and around the fourth metacarpophalangeal joint. An ultrasound-guided core needle biopsy was performed. Cytology demonstrated individual bland epithelioid to spindled cells with a fibrillary stroma. The tissue biopsy had cords and clusters of epithelioid cells with eosinophilic to clear cytoplasm with occasional bubbly cytoplasm in an abundant myxoid stroma. Immunostains were performed with expression of pancytokeratin and brachyury. The differential diagnosis included extraosseous chordoma versus extraosseous benign notochordal tumor. CT of thorax, abdomen, and pelvis to evaluate for an axial lesion was negative. She subsequently underwent an open biopsy, followed by a treatment with a radical resection with digital amputation. The tumor demonstrated similar histologic findings to the biopsy and was noted to originate from the soft tissue of the metacarpophalangeal joint with focal invasion into the phalanx bone. Given the destructive nature of this entity, it is important to suspect extra-axial chordomas when considering other common chondromyxoid entities and confirm the diagnosis with brachyury expression (Figure 1.145, A–D).

(Poster No. 146)

Kimberly C. Brimhall, PhD¹; Yael K. Heher, MD²; Diana M. Cardona, MD³ ([email protected]). ¹Department of Health Law, Policy and Management, Boston University, Boston, Massachusetts; ²Office of the Chief Medical Officer, Beth Israel Lahey Health, Cambridge, Massachusetts; ³Department of Pathology, Duke University School of Medicine, Durham, North Carolina.

Context: The 21st Century Cures Act Final Rule granted patients immediate access to their medical records, including pathology results. In 2015, the National Academy of Medicine included communication of pathology results as one source of diagnostic errors. Pathologists have an opportunity to improve the clarity and utility of their reports; however, more research is needed on how to improve these reports to meet the needs of patients, treating clinicians, and other stakeholders.

Design: Patients diagnosed with colorectal cancer were invited via patient advocacy groups and Katie Couric Media to participate in a survey and interviews seeking their perspective on current pathology reports and ideas for improvements. These data were used to create prototype patient-centered pathology reports. Patient focus groups evaluated and refined the prototyped reports, and an expert panel of pathologists provided a final review.

Results: Of the 32 participants, 87% found their current pathology reports difficult to understand, while 43% were dissatisfied with the amount and organization of information in the report. More than 75% of participants recommended adding an explanation of the diagnosis or a glossary of terms in the report. The expert pathologist panel reviewed the resulting patient-centered pathology reports and recommended inclusion of a glossary or links to institution-specific patient resources. At this time, additional changes were not recommended because of the added burden.

Conclusions: Currently, pathology reports are difficult for patients to understand. This study engaged patients in the process of creating a prototype patient-centered pathology report; however, the feasibility and practical implementation of these recommendations need to be explored further.

Cardona is a consultant with Leica.

(Poster No. 1)

Aidan Clement, BA ([email protected]); Art Mendoza, MD; Omid Bakhtar, MD; Chris Wixom, MD; Stephanie Muller, MD; Lana Kabakibi, BS; Madeleine Schwab, BS; Peilin Zhang, MD, PhD. Department of Pathology, Sharp Healthcare Laboratories, San Diego, California.

Context: Low-grade endometrial carcinoma is the most common gynecological malignancy. The risk factors include genetics and environmental factors influencing hormonal levels. Race/ethnicity and social determinants in low-grade endometrial carcinoma are less studied, and the relationship between the social determinants and biomarker expressions is unknown.

Design: We collected 459 hysterectomy specimens with low-grade endometrial carcinoma with information including race/ethnicity, marital status, religion, body mass index (BMI)/obesity, and staging information as well as mismatch repair protein (MMRP) expression status. Statistical analysis was performed by using baseline characteristic table and χ² programs in an R package.

Results: A total 459 hysterectomy specimens of low-grade endometrial carcinoma (FIGO grades 1 and 2) were examined. Race/ethnicity and marital status were significantly associated with patients’ age (P < .01), BMI/obesity (P < .01), and tumor pathology (FIGO grade 1 versus grade 2) (P = .02). Tumor MMRP status was available in 333 cases: MMRP-deficient tumor was found in 79 cases, and MMRP-proficient tumor in 254 cases. MMRP status was not only significantly associated with tumor pathology/histologic grade (P < .01), nodal metastasis (P < .01), and FIGO stages (P < .01), but also associated with patients’ marital status (P = .02). Religious belief was not associated with other social determinants, environmental factors, or tumor pathology (Table).

Conclusions: Race/ethnicity and social determinants appear important in low-grade endometrial carcinoma, and these factors not only presented as risks for pathogenesis, but also affect the tumor grade and MMRP expression, which in turn affect the stage, nodal metastasis, and tumor pathology. These social determinants should be incorporated into patients’ counseling before and after surgery.

(Poster No. 2)

Ying Ma, MD, PhD¹ ([email protected]); Rujia Fan, MD, PhD²; Yiying Wang, MD, PhD³; Wanrun Lin, MD, PhD.^{4 1}Department of Obstetrics and Gynecology, Mianyang People’s Hospital, Mianyang, China; Departments of ²Pathology and ³Obstetrics and Gynecology, Henan Provincial People's Hospital, Zhengzhou, China; ⁴Department of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Context: Progestin's role in treating atypical endometrial hyperplasia is pivotal but evaluating its effect on residual disease (RD) presents challenges due to induced morphologic variations. This study, referencing previous University of Texas Southwestern Medical Center research, categorizes these changes into nonresponse (NR), partial response (PR), and complete response (CR). It explores the connection between these morphologic shifts and RD, particularly how PTEN, Pax2, and β-catenin biomarkers (PPB) assist in diagnosing atypical endometrial hyperplasia in both pretreatment and posttreatment scenarios.

Design: The study involved 120 patients from 2018 to 2021. Immunohistochemistry staining for PTEN, Pax2, and β-catenin was conducted on biopsies post–progestin treatment. Morphologic responses were categorized and related to PPB marker expression, considering any aberrancy as indicative of RD.

Results: Of the 120 cases, there were 348 defined areas studied. Morphologic analysis showed 76 NR, 132 PR, and 140 CR cases. Aberrant PPB markers were prominent in NR (89.4%) and PR (48.5%) but absent in CR. PR cases with complex architecture correlated with higher marker aberrancy, especially β-catenin in glands with morules. Overall, RD was noted in 58 (48.3%) of the 120 cases studied. Detailed data are summarized in the Table.

Conclusions: NR generally signifies RD presence, while PR includes a blend of residual and nonresidual diseases. PPB markers are very useful to help recognize RD in cases showing PR. CR indicates optimal treatment with no RD. For accurate diagnosis, quantifying progestin's diverse morphologic impacts is essential, especially when biomarker guidance is unavailable.

(Poster No. 3)

Wanrun Lin, MD, PhD¹ ([email protected]); Wenxin Zheng, MD.^{2 1}Department of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; ²Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.

Context: High-grade serous carcinoma (HGSC) is a leading cause of ovarian cancer deaths, often diagnosed at an advanced stage. Folate receptor α (FRα) has been identified as frequently upregulated in HGSC and targeted by the drug mirvetuximab soravtansine (MIRV). This study evaluates the expression of FRα in HGSC and its precursor lesions by focusing on lesions of serous tubal intraepithelial carcinoma (STIC) to assess its potential as a therapeutic target.

Design: Immunohistochemical analysis was conducted on samples from normal fallopian tubes, HGSC, and precursor lesions (including secretory cell expansion, secretory cell outgrowth, serous tubal intraepithelial lesions, and STIC). The expression levels of FRα were assessed and compared.

Results: FRα showed significantly elevated expression in STIC (53.8%) and HGSC (73.9%) compared to normal fallopian tubes and other precursor lesions. The expression did not differ significantly between STIC and HGSC or between BRCA1/BRCA2 mutation and wild-type groups. Representative pictures of FRα are presented in Figure 2.3, A–D.

Conclusions: The observed increase in FRα expression in STIC and HGSC highlights the potential for MIRV, an antibody-based targeted therapy, to be effective for treating not only HGSC but also isolated STIC. This is of particular clinical importance given that isolated STIC, often identified during prophylactic bilateral salpingo-oophorectomy in BRCA mutation carriers, currently lacks a definitive therapeutic strategy.

(Poster No. 4)

Sydney S. Kenney, BS ([email protected]); Sean K. Lau, MD; Jason V. Scapa, MD. Department of Pathology, Kaiser Permanente Orange County, Anaheim, California.

Endometrial stromal tumors, ranging from benign nodules to malignant sarcomas, are classified as low-grade or high-grade based on morphologic, immunophenotypic, and genetic features. The majority of low-grade endometrial stromal sarcomas of the uterus are characterized by recurrent chromosomal translocations, producing specific gene fusions, with JAZF1::SUZ12 being the most common. Though typically arising in the uterine corpus, they can rarely manifest as extrauterine endometrial stromal sarcomas (EESS) in the absence of uterine involvement. Here, we present a case of a 55-year-old woman with an intra-abdominal mass incidentally found on renal ultrasound for chronic kidney disease. Resection revealed irregular nodules of tumor permeating mesenteric soft tissue, composed of spindle cells immunohistochemically positive for CD10, estrogen receptor, and WT-1. Careful gross and microscopic evaluation of the accompanying hysterectomy specimen showed no uterine involvement by the tumor. Fluorescent in situ hybridization testing on the mesenteric mass demonstrated the presence of a JAZF1 gene rearrangement. The patient was diagnosed with EESS and placed on adjuvant hormone therapy without clinical or imaging recurrence at the 18-month follow-up. Diagnosis of EESS can be challenging since tumors of endometrial stromal origin are often not considered when encountered outside the gynecologic tract and without a uterine mass. The presented case of low-grade EESS with JAZF1 gene rearrangement provides additional evidence that this particular genetic alteration can affect tumors in an extrauterine setting and supports the potential use of FISH as an emerging confirmatory diagnostic tool in cases of suspected EESS.

(Poster No. 5)

Whitney Stolnicki, MD¹ ([email protected]); John Nakayama, MD²; Alexander Strait, MD¹; Sharon Liang, MD.¹ Departments of ¹Pathology and ²Obstetrics and Gynecology, Allegheny Health Network, Pittsburgh, Pennsylvania.

Aggressive angiomyxoma is a rare, locally aggressive mesenchymal neoplasm typically arising from the vulvovaginal tissue in reproductive-age women, with approximately 500 cases reported since the discovery of this entity. In our case, a 41-year-old woman presented with edema of the buttock and was found to have a large retroperitoneal mass centered around the left pelvis and extending to the pelvic soft tissue. She underwent radical hysterectomy, left salpingo-oophorectomy, and lower anterior resection. The excised mass measured 22.0 × 5.0 × 3.5 cm and consisted of a gelatinous and myxoid mass intimately involving the left broad ligament (Figure 2.5, A). Histologic sections showed a lesion composed of bland, stellate, and spindle cells embedded in a collagenized myxoid matrix with a prominent vascular pattern consisting of dilated vessels of varied caliber (Figure 2.5, B–D). There are entrapped mature adipocytes and nerves within the lesion and notably, no mitoses or necrosis. A diagnosis of aggressive angiomyxoma arising from the broad ligament was made. The patient is without evidence of recurrence at the 26-month follow-up. To our knowledge, there is only 1 other report of aggressive angiomyxoma arising from the broad ligament. We report this case for the unique origin of this lesion from the broad ligament and so aggressive angiomyxoma should be among the differential diagnoses for lesions arising from the broad ligament when the radiologic and histologic features align. Of interest, comprehensive molecular profiling of the tumor identified a pathologic variant in ATM which has not yet been linked to aggressive angiomyxoma.

(Poster No. 6)

Huma Asif, MBBS ([email protected]); Josephine K. Dermawan, MD, PhD; Karen J. Fritchie, MD; Natalie Banet, MD. Department of Pathology and Laboratory Medicine, the Cleveland Clinic, Cleveland, Ohio.

Extraskeletal myxoid chondrosarcoma (EMC), a rare tumor more common in men during the fifth and sixth decades in the deep soft tissue of proximal extremities/limb girdles, has not been reported involving the uterus. EMC diagnosis often depends on molecular testing, with translocations involving the NR4A3 gene, which can be fused in-frame with different partners, most often EWSR1 or TAF15. Herein is a case of EMC presenting as a pelvic mass with a novel gene fusion. Imaging revealed a 4.5-cm retroperitoneal mass attached to the outer posterior lower uterine segment in a 44-year-old woman who presented with pelvic pain for 5 months. A hysterectomy showed a 4.5-cm tan-purple mass growing on the uterine serosa (Figure 2.6, A). Histology showed uniform ovoid to epithelioid cells in cords and nests with eosinophilic cytoplasm (Figure 2.6, B) in myxoid stroma (Figure 2.6, C) with rare mitotic figures. Immunohistochemical stains were positive for ER (Figure 2.6, D) and focally for calretinin, and negative for desmin, S100, EMA, myogenin, cytokeratin Cam 5.2, CK7, synaptophysin, inhibin, CK20, ERG, CD34, SOX10, PAX8, and ALK. Targeted RNA sequencing revealed an ACTB::NR4A3 fusion. This case highlights the broad differential diagnosis of mesenchymal neoplasms of the uterus, which in this case was a sarcoma which does not commonly involve the female reproductive organs. Additionally, it reinforces the ability of nongynecologic sarcomas to demonstrate ER positivity. While NR4A3 is typically rearranged in EMC, this specific variant is novel, thus highlighting the importance of application of molecular techniques to correctly identify and expand our knowledge of such cases.

(Poster No. 7)

Margarita Consing Gangelhoff, MD ([email protected]); Paul Weisman, MD; Jin Xu, MD, MS. Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison.

Vulvar microcystic adnexal carcinoma (MAC) is extremely rare and may not enter the differential diagnosis for gynecologic pathologists. Here, we describe a case of vulvar MAC in a 67-year-old woman. She presented with a 3.5-cm raised, erythematous vulvar plaque. Sections revealed an infiltrative lesion (Figure 2.7, A) with sweat-duct–like dual luminal/abluminal morphology (Figure 2.7, B). Ventana immunohistochemistry was performed confirming this morphology as evidenced by an inner p40⁻/epithelial membrane antigen (EMA)⁺ cell population (Figure 2.7, C) and an outer p40⁺/EMA⁻ cell population (Figure 2.7, D). The lesion focally connected to the overlying epidermis and showed a variably chondromyxoid matrix. Despite their bland cytology (Figure 2.7, B), the tumor cells were mitotically active. Expression of p16 was patchy, militating against a human papilloma virus–related carcinoma. In keeping with true sweat duct differentiation, the aforementioned abluminal p40⁺ cells were completely negative for the myoepithelial marker SOX10. The discordant p40⁺/SOX10^- pattern helped to exclude MAC mimickers with dual luminal/abluminal morphology including cutaneous malignant mixed tumor and the tubular variant of adenoid cystic carcinoma, both of which have a component of myoepithelial cells that would be expected to coexpress p40 and SOX10. We underscore the diagnostic utility of discordant p40⁺/SOX10⁻ expression in human papilloma virus–independent vulvar carcinomas with dual luminal/abluminal morphology and endorse the use of a limited panel of p40, SOX10, and EMA in this context.

(Poster No. 8)

Pierre Tran, BA ([email protected]); Terry K. Morgan, MD, PhD. Department of Pathology, Oregon Health & Science University, Portland.

Context: Endometrial adenocarcinoma is the most common gynecologic malignancy with 10% of cases arising in reproductive-age women. Endometrial intraepithelial neoplasia (EIN) is a precursor lesion based on a histopathologic diagnosis. Depending on the classification of EIN, about 50% of cases fail to respond to progestin therapy. Histology fails to predict this response. We hypothesized that nonresponders may have mutations in PTEN that affect function and machine deep-learning may better predict response.

Design: Retrospective case-control study of 49 de novo endometrial biopsies diagnosed with EIN (41 CAH and 8 simple hyperplasia). Included cases required diagnoses confirmed by 2 pathologists and a history of progestin therapy combined with at least 3–6 months of hysteroscopic evaluation and biopsies. Regions of interest containing EIN were sampled for DNA analysis using histologic sections and the commercially available GeneTrails solid tumor panel. Data were analyzed by χ² and unsupervised clustering with adjusted P values. The computer model was trained using scanned slides annotated by a pathologist with known outcomes (+/− responder).

Results: Clinical follow-up revealed 24 responders and 25 progestin nonresponders with either progression to adenocarcinoma, or no response by 6 months. PTEN mutations above the variable allele frequency were identified in 19/25 nonresponders and 2/16 responders (likelihood ratio = 6.0 [2–23], P < .001). Deep machine learning based on 73 948 patches provided no insight into +/− responders (DeepMIL AUC 0.53).

Conclusions: Histopathologic diagnoses by pathologists and machine deep learning do not distinguish EIN progestin responders from nonresponders. However, there is a significantly increased frequency of PTEN functional mutations in non-responders.

(Poster No. 9)

Leslie Lopez-Calderon, MD¹ ([email protected]); Rishika P. Sakaria, MD²; Kan Gaston, PharmD³; Divya Rana, MD²; Massroor Pourcyrous, MD.² Departments of ¹Pathology and ²Pediatrics, University of Tennessee Medical Science Center, Memphis; ³Department of Pharmacy, Regional One Health Hospital, Memphis, Tennessee.

Context: In our center, the incidence of neonatal opioid withdrawal syndrome (NOWS) is significantly lower in infants born to mothers with sickle cell disease (SCD) who are on prescribed opioids for vaso-occlusive pain crises compared with mothers who have opioid use disorders. The transport of opioids to the fetus can be limited in SCD due to placental maternal vascular malperfusion (MVM). We aimed to describe the placental pathology findings of infants born to mothers with SCD and study their relationship with MVM and NOWS.

Design: This is a descriptive study. Data were collected over 9 years (2013–2022). Mothers with SCD, infant and maternal demographics, delivery data, maternal opioids (prescribed and/or illicit), placental pathology, and infants’ withdrawal symptoms and needs for treatment were recorded.

Results: We identified 65 mothers with SCD who delivered 85 infants. Placental pathology reports were available for 42 infants. Significant placental abnormalities consistent with MVM were found, including increased syncytial knots, accelerated villous maturation, placenta small for gestational age, and altered villous architecture. Three of 42 infants had NOWS requiring treatment. No obvious correlation was noted in the placental pathology findings and the development of NOWS (Table).

Conclusions: MVM is the predominant lesion in placentas of women with SCD which can limit the transport of opioids to fetus. The results of this study are limited by the small sample size of infants who developed NOWS. This is an ongoing trial, and we plan to ensure that all placentas from mothers with SCD will be investigated.

(Poster No. 10)

Jesse Champer, MD ([email protected]); Natalie Banet, MD. Department of Pathology and Laboratory Medicine, the Cleveland Clinic, Cleveland, Ohio.

Amyloidosis is characterized by extracellular deposition of an insoluble fibrillary protein and is classified based on the identity of the precursor protein. The most common form is primary amyloidosis, caused by the deposition of immunoglobulin light chains and is associated with plasma cell dyscrasias. Though involvement of the gastrointestinal tract is common, isolated amyloidosis of the omentum and peritoneum is an unusual presentation. We present a case study of a 68-year-old woman with abdominal pain and found on imaging to have diffuse omental thickening and nodularity with poorly visualized adnexa. She was scheduled for surgery for confirmation of suspected carcinomatosis. Intraoperatively, she was found to have ill-defined omental thickening without discrete adnexal tumors. Histologically, the omentum showed amorphous eosinophilic deposits (Figure 2.10, A, ×4; and Figure 2.10, B, ×40) which demonstrated apple-green birefringence on Congo red stain (Figure 2.10, C, ×40) and fluorescence with thioflavin D stain (Figure 2.10, D, ×40). Mass spectrometry showed λ immunoglobulin light chains. The case was presented at a gynecologic oncology tumor board and referred to a hematologist/oncologist. Urine electrophoresis and immunofixation assay determined the amyloid fibril to be immunoglobulin λ light chains. This prompted the patient to undergo a bone marrow biopsy, which showed a plasma cell neoplasm, with greater than 20% plasma cells. This case highlights the broad differential diagnosis of patients presenting with presumed carcinomatosis, especially in a time of subspecialization within pathology. Cooperative interworking between multiple clinical, laboratory, and anatomic pathology teams were necessary to provide this patient with an accurate diagnosis prior to being triaged to appropriate therapy.

(Poster No. 11)

Dina Zenezan, MD ([email protected]); Kassaye Firde, MD; Israh Akhtar, MD. Department of Pathology, Temple University, Philadelphia, Pennsylvania.

Context: Dedifferentiated (DDC) and undifferentiated endometrial carcinomas (UDC) are aggressive and constitute 1%–2% of endometrial malignancies. It is crucial to identify these tumors and differentiate them from high-grade endometrioid carcinoma (HGEC) for prognostication.

Design: A retrospective study was conducted at our safety net hospital to compare histopathologic, immunohistochemical, and molecular results of both.

Results: Six DDC and 4 UDC were collected over a 4-year period (2020–2023) with a mean age of 62 years (range: 54–72). Imaging revealed heterogenous uterine/ovarian masses. Five DDC cases originated from the endometrium and 1 from the ovary. All patients had family history of cancer. Myometrial invasion was <50% in 3 out of 6 cases. Immunohistochemical (IHC) stains were positive for AE1/AE3 in differentiated and solid components, while ER, PR, P16, PAX-8, E-cadherin, and vimentin were positive in the well differentiated component. P53 was wild type in 4 cases and mutated in 2 cases. Molecular studies revealed MLH1 methylation in 4 out of 6 cases and 1 had POLE mutation. One had loss of SMARC-A4 and SMARCB1. Four cases of UDC had >50% of myometrial invasion, and 3 out of 4 cases showed lymphovascular invasion. IHC stains were positive for AE1/AE3, CAM5.2, EMA, E-cadherin, and vimentin. P53 was wild type in 3 cases and mutated in 1 case, which also showed PTEN mutation (Table).

Conclusions: Morphology and ancillary tests are crucial for identifying UDC and DDC, given their unfavorable prognosis compared to HGEC. p53 and POLE mutations determine prognosis, while MMR, p16, and ER/PR aid in the differential diagnosis, guiding targeted therapy.

(Poster No. 12)

Briana Wilson, PhD¹ ([email protected]); Anne M. Mills, MD²; Megan Dibbern, MD.^{2 1}Department of Pathology, University of Virginia School of Medicine, Charlottesville; ²Department of Pathology, University of Virginia Medical Center, Charlottesville.

Context: Pembrolizumab is US Food and Drug Administration (FDA)–approved for recurrent/metastatic cervical carcinomas with programmed death ligand-1 (PD-L1) combined positive score (CPS ≥ 1). However, approval is contingent on PD-L1 evaluation using a specific companion diagnostic assay, 22C3 pharmDx, which is not routinely available in many pathology labs. We assessed interchangeability of 3 commercially available PD-L1 antibodies in cervical/vulvovaginal carcinomas (CVCs) to ascertain whether an alternate assay may be acceptable for identifying pembrolizumab candidates in clinical practice.

Design: A tissue microarray (TMA) was constructed with 41 CVCs (38 squamous cell, 2 small cell, 1 adenocarcinoma), each represented on 4 replicate 0.6-mm cores. TMAs were stained with 3 antibodies: 22C3 (Dako Autostainer Link 48), and SP263 and SP142 (Ventana Benchmark Ultra). PD-L1 CPS was manually determined by consensus read with blinding to alternate assay scores.

Results: At the threshold of CPS ≥ 1, each antibody met expression criteria for pembrolizumab candidacy in a proportion of cases: 22C3 78%, SP263 78%, and SP142 61%. Using the 22C3 as a gold standard, SP263 results agreed in 90% of cases (37 of 41), while SP142 agreed in only 73% (30 of 41). SP263 versus 22C3 discrepancies showed no trend, whereas SP142 versus 22C3 discrepancies were most often negative on SP142. This was attributable to limited tumor staining in the majority of cases with SP142. Most discrepancies occurred near the CPS = 1 border.

Conclusions: These data suggest that the Ventana SP263 assay may be a reasonable surrogate for 22C3 pharmDx in aggressive CVCs being considered for anti-PD-1 therapy, but the Ventana SP142 is unlikely to be a reliable surrogate in this setting. Larger studies are needed to prove reproducible interchangeability based on College of American Pathologists recommendations.

(Poster No. 13)

Fatma L. Emiroglu, MD ([email protected]); Ediz Cosar, MD; Lisa Cole, MD; Olga Krasnozhen-Ratush, MD. Department of Pathology, UMass Chan Medical School Baystate Medical Center, Springfield, Massachusetts.

Mesonephric hyperplasia is an uncommon entity that originates from the Wolffian (mesonephric) duct remnants. It is usually an incidental finding that can mimic an adenocarcinoma. We present a case of a 45-year-old woman who underwent a total hysterectomy for menorrhagia. On gross examination the cervix was unremarkable. Microscopic examination revealed a florid glandular proliferation with mixed lobular and pseudoinfiltrative pattern, raising the concern for adenocarcinoma (Figure 2.13, A). The glands were composed of small cuboidal cells with uniform nuclei, scant eosinophilic cytoplasm, and PAS-positive luminal secretions (Figure 2.13, B). The immunohistochemical studies showed positive staining with GATA3 (Figure 2.13, C), HNF1B, and PAX8 (Figure 2.13, D). Calretinin, TTF-1, ER, and PR were negative. Absence of architectural complexity, cytologic atypia, desmoplastic stromal response, and mitotic figures helped to exclude mesonephric adenocarcinoma of the cervix. Florid mesonephric hyperplasia may mimic mesonephric adenocarcinoma of the cervix by morphology and immunohistochemistry. Both entities arise from the mesonephric remnants, and can have infiltrative glands with a tubular pattern, PAS-positive luminal secretions, inconspicuous stromal response, and positive immunohistochemical staining with PAX8, GATA3, and HNF1B. However, mesonephric adenocarcinoma differs from mesonephric hyperplasia with the presence of nuclear atypia, mitotic activity, and architectural complexity, and typically presents with a mass lesion. It is important for pathologists to differentiate florid mesonephric hyperplasia and mesonephric adenocarcinoma of the cervix, as the former entity is benign and requires no further treatment, and the latter entity is malignant and prompts aggressive treatment such as radical hysterectomy, chemotherapy, and radiotherapy.

(Poster No. 14)

Fitra Rianto, MD ([email protected]); Mark J. Suhrland, MD; Amarpreet Bhalla, MD; Tiffany M. Hébert, MD. Department of Pathology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York.

Ovaries are frequently metastatic sites for primary malignancies. However, instances of pancreatic cancer metastasizing to the ovaries are exceedingly rare and are frequently challenging to differentiate from primary ovarian cancer. We present one such case. A 72-year-old patient presented with a new 7.2-cm multiseptated right adnexal mass, 2 years following a diagnosis of stage IV pancreatic ductal carcinoma that was responding to chemotherapy. At intraoperative consultation, the mass was deemed grossly benign due to its smooth appearance with no solid growth or excrescences. No frozen section was performed. On histology, the bilateral masses showed multiple cysts, mostly lined by single layers of mucinous epithelium (Figure 2.14, A) with cytology that seemed out of sync with the architecture. The cytology ranged from bland (Figure 2.14, B) to markedly atypical, resembling intraepithelial carcinoma (Figure 2.14, C). The immunostaining results were CK7 (+)/CK20 (+), CDX2 (+), P504S (+), CK19 (+), Ki-67 increased proliferation, p53 overexpressed, and Napsin a (+). Given the unusual histology, testing for SMAD4 was performed, showing loss of expression in the tumor cells (Figure 2.14, D). Therefore, we favored metastasis from the pancreaticobiliary primary. In the setting of known pancreatic carcinoma primary, an adnexal mass may be deceptively bland, even on gross examination. These cases should be frozen at the time of the intraoperative evaluation, even if they appear grossly benign. This case also illustrates the need to recognize bland histological architecture combined with atypical cytology as a potential metastatic tumor and the utility of SMAD4 testing in identifying pancreaticobiliary metastases in this setting.

(Poster No. 15)

Paula D. Binsol, MD¹ ([email protected]); Jaya Ruth Asirvatham, MD²; Douglas A. Larsen, MD.^{2 1}Department of Pathology, Baylor Scott and White, Temple, Texas; ²Department of Pathology, Baylor Scott and White, Temple West Campus, Temple, Texas.

A 78-year-old woman was referred to our institution with a diagnosis of endometrial adenocarcinoma and underwent total hysterectomy with bilateral salpingo-oophorectomy. There was a 3.5-cm tumor involving the entire endometrial cavity. Microscopic examination of the uterine tumor revealed areas composed predominantly of a complex glandular architectural growth pattern with only focal and superficial papillary-like features. Deeply invasive tumor was also identified in the cervix; however, the glands within the cervical stroma appeared distinctly different from those in the endometrium, composed of simple glands with a single layer of tall cells with basally oriented nuclei. Focally, there was blending of these 2 patterns in the myometrium appearing as a band of simple glands below the more complex glandular pattern (Figure 2.15, A–D). In the latter areas, there was a differential staining pattern, suggestive of a collision tumor, which on further evaluation and investigation was consistent with poor/delayed fixation. However, in better preserved areas, the tumor cells were positive for vimentin, estrogen receptor (strong intensity, 70%–80%), progesterone receptor (strong intensity, 70%–80%), with wild-type p53 staining and patchy p16. There was no significant staining with napsin A, GATA-3 or CD10, and no loss of nuclear expression of mismatch repair proteins, confirming that the cervical tumor was not a separate endocervical primary, but rather an extension of the endometrial neoplasm within the uterine corpus. As a result of the above findings, a diagnosis of invasive endometrioid adenocarcinoma, FIGO grade 2 with an adenoma-malignum type of invasion was rendered.

(Poster No. 16)

Azin Mashayekhi, MD ([email protected]); Krisztina Hanley, MD; Elizabeth M. Genega, MD; Gulisa Turashvili, MD, PhD. Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, Georgia.

Context: Gynecologic carcinosarcomas are uncommon carcinomas with biphasic morphology comprising high-grade epithelial and sarcomatous components. Ovarian and uterine carcinosarcomas frequently share mutations in genes such as TP53, PIK3CA, FBXW7, PTEN, and ARID1A. We aimed to analyze clinical-pathologic features and molecular alterations in these rare tumors.

Design: After obtaining institutional review board approval, the institutional archive was searched for carcinosarcomas diagnosed in 2011–2023, with available molecular data using Caris Life Sciences platform (next-generation sequencing, tumor mutational burden [TMB], loss of heterozygosity [LOH] and microsatellite instability). Clinical-pathologic and immunohistochemical data were reviewed

Results: A total of 20 cases were identified, including 14 uterine and 6 ovarian carcinosarcomas. The median patient age was 66.5 years (41–82). The most common carcinomatous component was serous (45%). Heterologous differentiation was present in 65%, including rhabdomyosarcoma (46%), chondrosarcoma (38%), liposarcoma (8%), and other (8%). All tumors were proficient for DNA mismatch repair (MMR) proteins and negative for HER2 protein overexpression or gene amplification, with expression of estrogen receptor in 30%, and progesterone receptor in 20%. The most common gene mutation was TP53 (90%), followed by PTEN (40%), PIK3CA (25%), PPP2R1A, TOP2A, and RRM1 (20% each), TS (15%), BRCA, SOS, Rb and VDR (10% each), FBXW7 and ARID1A (5% each). Most tumors (65%) had low TMB, while 50% had low LOH. Amplification of MYCN, FGFR1, MCL, and CCNE1 genes was present in 5% of cases.

Conclusions: Most gynecologic carcinosarcomas are MMR-proficient, and exhibit TP53 mutations and low TMB. Elucidating the significance of uncommon gene alterations warrants larger studies.

(Poster No. 17)

AlBatool A. Abdelghaffar, MD ([email protected]); Lisa L. Cole, MD. Department of Pathology, UMass Chan Medical School-Baystate, Springfield, Massachusetts.

Mesonephric-like adenocarcinoma (MLA) of the uterus is a rare subtype of endometrial carcinoma with histological features resembling mesonephric remnants. Accurate diagnosis from biopsy specimens poses significant challenges due to its histomorphologic and immunophenotypic heterogeneity. A hysterectomy specimen from a 67-year-old woman with an endometrial mass and postmenopausal bleeding was evaluated histologically and a panel of immunohistochemical (IHC) stains were performed in order to confirm the diagnosis of a neoplasm with mesonephric differentiation. Histology revealed different architectural patterns including retiform, papillary, glomeruloid, and yolk sac–like, mimicking other uterine and nonuterine malignancies (Figure 2.17, A). IHC stains revealed CD-10: diffusely positive in the retiform, patchy positive in the yolk sac-like and negative in the papillary and glomeruloid patterns (Figure 2.17, B), mPAX-8: diffuse weakly positive in all 4 patterns (Figure 2.17, C), and TTF-1: nuclear staining in all patterns, most intense in retiform pattern (Figure 2.17, D). Recognizing the staining patterns is essential for confirming the mesonephric lineage and differentiating MLA from other entities. Biopsy specimens may provide limited tissue for histologic evaluation, increasing the risk of misdiagnosis of MLA. Use of an IHC panel is important in establishing an accurate diagnosis due to the heterogeneity in both morphology and immunohistochemistry. Pathologists must realize these challenges and utilize careful histopathological evaluation and an appropriate panel of IHC stains to appropriately recognize the mesonephric lineage to achieve accurate diagnosis for appropriate management of this rare subtype of endometrial carcinoma.

(Poster No. 18)

Joyce Opara, MD ([email protected]); Leah Geiser Roberts, DO; David Zagzag, MD, PhD; Christopher M. William, MD, PhD; Amir Dehghani, MD. Department of Pathology, New York University, New York.

In this case study, we present the clinical and pathological findings of a 37-year-old woman who underwent a robotic hysterectomy, right salpingo-oophorectomy, and omentectomy for pelvic masses. The patient's clinical history revealed a previous left oophorectomy for an immature teratoma diagnosed in an outside hospital. Computed tomography of the abdomen and pelvis with IV contrast revealed peritoneal thickening and omental nodularity, suspicious for peritoneal carcinomatosis or posttreatment changes. Gross examination showed fragments of yellow-tan fatty tissue with a fibrotic and nodular appearance. Microscopic examination of omental nodules revealed mature, reactive, neuroglial tissue, highlighted by diffuse glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) immunopositivity. The neuroglial tissue was negative for BRAF V600E, IDH-1 R132H, OCT-4, CD34, and SALL4 by immunohistochemistry, ruling out a malignant transformation of the tissue. The Ki-67 proliferation index was vanishingly low, focally up to 3%. These findings are consistent with the diagnosis of gliomatosis peritonei (GP), a rare entity linked to <1% of ovarian teratoma cases. The pathogenesis of GP remains unclear; while earlier theories suggest the transcoelomic spread of glial implants with subsequent partial or total differentiation, current understanding leans towards a metaplastic process of submesothelial mesenchyme towards a glial phenotype, likely induced by teratoma in a paracrine fashion. This case underscores the importance of comprehensive histopathological examination and vigilant follow-up in patients with a history of ovarian teratomas. Additionally, it highlights the significance of considering GP in the differential diagnosis of peritoneal nodules. Continued research will enhance our understanding and guide optimal management strategies for this rare condition (Figure 2.18, A–D).

(Poster No. 19)

Ivan Ogloblin, MD ([email protected]); Karen Fritchie, MD; Natalie Banet, MD. Department of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio.

Context: Benign metastasizing leiomyoma (BML) of the lung is rare. Molecular diagnostic advances have altered classification of uterine mesenchymal neoplasms. Inflammatory myofibroblastic tumor (IMT) of the uterus is a neoplasm of uncertain malignant potential defined by recurrent translocations, mostly involving the anaplastic lymphoma kinase (ALK) gene. Recent publications have highlighted cases with morphologic overlap between leiomyoma and IMT. In this series we sought to characterize BML at our institution and verify that no previously diagnosed cases were IMT.

Design: We searched for cases of leiomyoma involving the lung over a 12-year period. Clinical and pathologic information was collected. Cases were subjected to immunostaining (IHC) for ALK (clone D5F3).

Results: Clinical and pathologic features are noted in the Table. All patients had at least 1 sample of the lung, and 3 of 15 had sampling at other anatomic locations, including pelvic wall, periaortic tissue, lymph nodes, omentum, pleura, scalp, brain, and clavicle. Review of the uteri in available cases showed conventional leiomyoma. IHC was positive in all cases where it was performed for desmin (11 of 11), smooth muscle actin (9 of 9), and ER (12 of 12). In all cases ALK (15 of 15) and S100 (8 of 8) were negative. The single patient who did not survive on follow-up had progression of her disease versus a separate primary diagnosed as leiomyosarcoma metastatic to the skull.

Conclusions: BML of the lung at our institution does not contain ALK-positive IMTs. The clinical course of these patients seems indolent with the rare exception of the patient who had subsequent disease at a distant site.

(Poster No. 20)

Faye Oakes, MD ([email protected]); Jain Zhou, MD PhD; Joshua A. Hanson, MD; Nadja K. Falk, MD. Department of Pathology, University of New Mexico, Albuquerque.

United States congenital syphilis cases increased 755% from 2012 to 2021. In 2022, New Mexico had the highest rate of congenital syphilis nationwide. Congenital syphilis is a preventable cause of miscarriage, stillbirth, and maternal and infant morbidity. This case highlights congenital syphilis’ key histopathologic alterations both in the placenta and the infant that should be recognized in this increasingly common infection. A pre-eclamptic 34-year-old woman with late latent syphilis presented at 33 weeks, 6 days for cesarean section. Due to noncompliance, she had incomplete syphilis treatment (only 1 of 3 doses of penicillin G). Histologic examination of the placenta revealed necrotizing funisitis (Figure 2.20, A) and severe acute chorioamnionitis (Figure 2.20, B). Spirochete immunochemical stain showed numerous spirochetes in the umbilical cord (Figure 2.20, C). The infant contracted congenital syphilis and demonstrated persistent transaminitis (AST 144 U/L, ALT 154 U/L), hyperbilirubinemia (total bilirubin 5.0 mg/dL), and cholestasis despite treatment. A liver biopsy at 5 weeks showed neonatal hepatitis with diffuse hepatocanalicular cholestasis and hepatocellular giant cell change (Figure 2.20, D). Spirochete immunochemical stain did not demonstrate liver organisms, and the hepatitis resolved after 4 months of supportive care. Although congenital transmission is significantly lower with late latent syphilis than with primary or secondary syphilis, as congenital syphilis surges in the United States, it is imperative to understand its pathologic manifestations. Necrotizing funisitis is characteristic of congenital syphilis and should be in the differential diagnosis when seen in an umbilical cord. Although neonatal hepatitis with cholestasis is a rare complication of congenital syphilis, this could be considered when diagnosed.

(Poster No. 21)

Adriana Garrison, MD ([email protected]); John D. Andersen, DO. Department of Pathology, New York University Grossman School of Medicine, New York.

Malignant perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors involving the uterus that typically harbor TSC1/2 mutations. This uniformly epithelioid malignant PEComa has an additional JAZF1::SUZ12 fusion. POLE-mutated well-differentiated endometrioid carcinomas harbor numerous mutations. This case study is increasing the genomic landscape of uterine mesenchymal tumors and highlighting the extremely rare collision between a malignant PEComa and a POLE-mutated endometrioid carcinoma in a 60-year-old woman presenting with postmenopausal bleeding. Imaging revealed an enlarging heterogeneously complex intramural fibroid within the uterine body. Initial biopsy studies demonstrated an atypical mesenchymal tumor with diffusely positive CD10 immunohistochemistry. The resection specimen demonstrated a malignant PEComa colliding with a well-differentiated endometrioid carcinoma (Figure 2.21, A) with metastatic PEComa deposits identified in paratubal and pelvic lymph nodes. Immunohistochemical studies showed an HMB-45, cathepsin-K, and CD10–positive tumor (Figure 2.21, B-D). Malignant status was determined by a mesenchymal tumor size greater than 5 cm, high-grade atypia, necrosis, increased mitotic activity, and presence of lymphovascular space invasion. Next-generation sequencing results demonstrated TSC1/2 and estrogen receptor 1 (ESR1) mutations along with a JAZF1::SUZ12 fusion along with a hypermutated POLE endometrioid carcinoma with a different TSC2 mutation site. We are the first to report the collision between a malignant mesenchymal tumor with both TSC1/2 mutation and JAZF1::SUZ12 fusion with a POLE-mutated endometrioid carcinoma with different TSC2 mutation site. This unique collision tumor has a favorable prognosis with a treatment modality including an mTOR inhibitor. This case increases the genomic landscape of potential uterine collision tumors.

(Poster No. 22)

Rayan Sibira, MD ([email protected]); Mahmoud Khalifa, MD, PhD; Molly Klein, MD; Minghao Zhong, MD, PhD; Sandhyarani Dasaraju, MD. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis.

Context: Morphologic criteria for diagnosing uterine leiomyosarcomas (ULMS) include tumor necrosis, cellularity, nuclear atypia, and mitotic activity. Despite established criteria, diagnosing uterine smooth muscle tumors remains challenging. We aim to validate a small immunohistochemical panel based on recent molecular studies to aid in ULMS diagnosis.

Design: We identified 26 consecutive ULMS cases diagnosed at our institution from 2018 to 2023. A representative block from each case was chosen for immunohistochemical studies. Additionally, 5 leiomyomas were included as controls. Sections were immunostained for p16, p53, and ATRX.

Results: Of the 26 cases, p16 immunohistochemical staining was strongly and diffusely positive in 19 (73%) and negative in 7 (27%) cases. ATRX showed loss of staining in 14 (53.8%) and was retained in 12 cases (46.1%). p53 positivity was strongly and diffusely positive in 2 (7.6%), showed wild-type staining in 10 (38.4%), and was negative/nonspecific in 14 cases (53.8%). All control leiomyomas demonstrated patchy staining of p16, wild-type staining of p53, and intact expression of ATRX. Examples of the immunostaining profile of a leiomyosarcoma are shown in Figure 2.22, A (H&E), B (p16), C (p53), and D (ATRX). We also had evidence that strongly and diffusely positive p16 was due to loss or reduced RB1 protein expression.

Conclusions: Our study shows that a considerable proportion of ULMS cases exhibit strong p16 staining and loss of ATRX. This small immunohistochemical panel can aid in differentiating ULMS from leiomyoma, especially with p16 staining, even in necrotic areas. We are currently evaluating this panel in smooth muscle tumor of uncertain malignant potential (STUMP) and other atypical leiomyoma cases.

(Poster No. 23)

Linnette Arroyo Roldan, MD ([email protected]); Alexandra Bryson, PhD; Sadia Sayeed, MD. Department of Pathology, Virginia Commonwealth University, Richmond.

We report an unusual case of a 76-year-old woman with a travel history to Mexico and multiple admissions for dyspnea, chest pain, and abdominal pain. The patient had a positive Coccidioides IgG antibody testing with a 1:1024 complement fixation and IgG immunodiffusion precipitating bands. However, fungal cultures revealed no organism growth. Magnetic resonance imaging demonstrated a thickened endometrial stripe measuring 29 mm, concerning for endometrial hyperplasia or neoplasm. An endometrial biopsy showed necrotic tissue. A follow-up hysteroscopy with dilation and curettage showed necrotizing granulomas (Figure 2.23, A) with multiple thick-walled, 10- to 19-μm spherules morphologically consistent with Coccidioides spp. (Figure 2.23, B). A Grocott methenamine silver stain highlighted the Coccidioides spp. spherules with multiple internal endospores (Figure 2.23, C). The patient was called back to the hospital for inpatient administration of amphotericin B. Coccidioidomycosis is caused by the dimorphic fungi Coccidioides spp. Coccidioides is known to exist in the southwestern part of the United States, Central America, and South America. The Coccidioides mycelium fragments into arthroconidia that deposit in the lung alveoli and morph into spherules. The spherules contain multiple internal endospores that are released and cause an inflammatory response. Although rare, coccidioidomycosis can disseminate to other tissues, including the female reproductive tract. The identification and notification of this dimorphic fungi is imperative to determine appropriate antifungal treatment. While more commonly found in the context of granulomatous inflammation of the lung, this case demonstrates the importance of a microbial workup in findings of granulomatous inflammation regardless of site.

(Poster No. 24)

Krisztina Lengyel, MD ([email protected]); Gulisa Turashvili, MD, PhD; Elizabeth Genega, MD; Krisztina Hanley, MD. Department of Pathology, Emory University, Atlanta, Georgia.

Context: Recognition of fumarate hydratase (FH)–deficient leiomyomas (FHDL) is important due to association with germline FH mutations and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. Although FHDLs have characteristic morphology, misinterpretation of cytologic atypia may lead to misclassification as smooth muscle tumor (SMT) of uncertain malignant potential (STUMP) or leiomyosarcoma. Immunohistochemical stains for FH and S-(2-succino)-cysteine (2SC) may be used for confirmation of FHDL diagnosis.

Design: The institutional archive was searched for uterine SMTs diagnosed as FHDL, STUMP, and leiomyoma with bizarre nuclei (LBN) in 2014–2022. Immunohistochemical studies for FH and 2SC were performed. Two pathologists blinded to the original diagnosis assessed the hematoxylin-eosin and immunostained slides. Diagnostic features of FH deficiency included staghorn vasculature, alveolar-type edema, scattered bizarre nuclei, eosinophilic cytoplasmic inclusions, and prominent eosinophilic nucleoli with perinucleolar haloes. FH stain was assessed as lost or intact, while 2SC was assessed as positive or negative.

Results: A total of 50 cases were identified, including 23 LBNs, 13 FHDLs, 10 STUMPs, and 4 leiomyomas. The specimens consisted of 38 hysterectomies 10 myomectomies, and 2 curettings. The median patient age was 44 years (29–73). The results are summarized in the Table.

Conclusions: Of 50 uterine SMTs, only 12 FHDLs were diagnosed with the use of FH immunohistochemistry alone, whereas the addition of 2SC identified 6 additional cases of FHDL. The combined use of FH and 2SC improves the diagnostic accuracy and ensures optimal clinical management.

(Poster No. 25)

Meena Kashi, MBBS ([email protected]); Seema Khutti, MD; Sudarshana Roychoudhury, MD. Department of Pathology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Greenvale, New York.

Uterine leiomyomas are the most common tumors of the uterus. In rare scenarios when morphological features are not classic, molecular tools may aid the diagnosis and provide clues to their treatment. We describe detailed clinicopathologic features of 2 cases of uterine mesenchymal neoplasms with unique molecular alteration CEP170::RAD51B,t(1;14)(q43;q24.1) fusion and unusual morphologic features. The first case was a 53-year-old woman who presented with irregular bleeding. Microscopically, the tumor displayed sheets and cords of epithelioid cells with round to ovoid nuclei, vesicular chromatin, and scant to moderate cytoplasm (Figure 2.25, A). There was no nuclear atypia or tumor necrosis. On immunohistochemistry (IHC), the tumor cells were diffusely positive for desmin and H-caldesmon, while negative for AE1/AE3, calretinin, S100, and Melan-A. A second case, an 81-year-old woman, presented with abnormal bleeding. Microscopically, the tumor displayed epithelioid to focally spindle cells with mild nuclear atypia and scattered sheets of macrophages (Figure 2.25, B). On IHC, tumor cells were focally positive for desmin and SMA, while negative for HMB-45, S100, ALK, CD34, and CD10. CD163 highlights the macrophages. Due to unusual morphologic features, molecular testing was performed. We describe 2 cases of uterine mesenchymal neoplasms with different morphologic features. Both cases demonstrated CEP170::RAD51B,t(1;14)(q43;q24.1) fusion. RAD51B may be a fusion partner of HMGA2 and HMGA1 but can occur in fusion with other genes including CEP170. The knowledge about molecular features of uterine leiomyoma can be of practical value in differential diagnoses, especially in tumors with unusual morphologic features, such as epithelioid leiomyoma and leiomyoma with multiple scattered sheets of foamy macrophages.

(Poster No. 26)

Andrea Mladenovic, MD ([email protected]); Alaaeddin Alrohaibani, MD; Krisztina Hanley, MD; Gulisa Turashvili, MD, PhD. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.

Context: The depth of invasion (DOI) determines prognosis and extent of surgery in vulvar squamous cell carcinomas (vSCCs). DOI is assessed using the conventional and alternative methods, the latter down-staging some tumors from IB to IA. We evaluated interobserver agreement (IA) for measuring DOI using both methods.

Design: vSCCs diagnosed in 2017–2023 were identified. DOI was reassessed by 2 gynecologic pathologists using the conventional (DOI-1-conv, DOI-2-conv) and alternative (DOI-1-alt, DOI-2-alt) methods, and compared with the original DOI (DOI-3-conv). IA was assessed using κ statistics.

Results: The cohort comprised 42 cases, including 19 (45%) biopsies and 23 (55%) resections, with a median patient age of 70 years (26–98) and median tumor size of 1 cm (0.1–7.2). Lymphovascular invasion was seen in 11 of 42 (26%) tumors. Of 6 of 42 (14%) cases with lymph nodes assessed, 3 were positive. DOI-3-conv was originally measured in 33 of 42 (79%) specimens, versus 27 of 42 (64%) for DOI-1-conv, 31 of 42 (74%) for DOI-1-alt, and 34 of 42 (81%) for DOI-2-conv and DOI-2-alt. In the remaining cases, invasion was present but DOI was deemed unassessable. With binarized DOI (≤1 versus >1 mm), IA was moderate for each method and the conventional versus alternative methods (Table). The proportion of patients requiring nodal assessment (DOI >1 mm) was 21 of 42 (50%) for DOI-3-conv, 20 of 42 (48%) for DOI-1-conv and 26 of 42 (62%) for DOI-2-conv, versus 18 of 42 (43%) for DOI-1-alt and 16 of 42 (38%) for DOI-2-alt.

Conclusions: IA was moderate for DOI assessment in vSCC, irrespective of the measurement method. Additional validation studies are warranted to establish the prognostic value of the alternative method.

(Poster No. 27)

Dorsay Sadeghian, MD¹ ([email protected]); Maryam Shahi, MD.^{2 1}Department of Pathology, Baylor College of Medicine, Houston, Tex; ²Department of Pathology, Mayo Clinic, Rochester, Minnesota.

Alveolar soft-part sarcoma (ASPS) is a malignant mesenchymal tumor primarily arising in extremities. Its manifestation in the female genital tract poses a significant diagnostic challenge due to extreme rarity of ASPS in this location, in addition to histomorphologic similarities with various primary and metastatic tumors, including perivascular epithelioid cell tumors (PEComa). A gene fusion, including alveolar soft part sarcoma chromosome region, candidate 1 (ASPSCR1) and transcription factor E3 (TFE3), is specific for ASPS. We present a 23-year-old woman, presenting with vaginal bleeding. Endometrial biopsy was performed. Microscopic evaluation revealed a neoplasm characterized by large polygonal cells with abundant eosinophilic cytoplasm, eccentric nucleus, and occasional prominent nucleoli. The tumor was focally arranged in nests, separated by fibrous septa. Immunohistochemical evaluation exhibited diffuse TFE3 positivity, with negative staining for HMB45, Melan A, SOX10, cytokeratin, and smooth muscle markers. Periodic acid-Schiff stain highlights the presence of cytoplasmic eosinophilic crystalline. Genetic testing confirmed the presence of ASPSCR1::TFE3 gene fusion. Although TFE3 immunostaining serves as a strong surrogate marker for TFE3 gene fusions, a subset of PEComas may harbor various TFE3-associated gene fusions, followed by positive immunostaining. However, since the specific rearrangement of ASPSCR1::TFE3 has been rarely reported in PEComa, in addition to negative staining for melanocytic markers, the tumor was finally diagnosed as ASPS. Utilization of a comprehensive diagnostic approach, including a panel of immunohistochemical stains, coupled with genetic testing to specify the exact type of TFE3 gene rearrangement, can be beneficial for more accurate classification of these tumors (Figure 2.27, A–D).

(Poster No. 28)

Annie A. Wu, MD, PhD¹ ([email protected]); Efrain A. Ribeiro, MD, PhD¹; Ying S. Zou, MD, PhD¹; Michael Michal, MD, PhD²; Deyin Xing, MD, PhD¹; John M. Gross, MD, MS.^{1 1}Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland; ²Department of Pathology, Charles University, Plzen, Czech Republic.

Sarcomas with RAD51B fusions seem to represent a rare and heterogenous family of sarcomas with a predilection for the uterus. To date, 14 cases have been described (all cases were female; 13 involving the gynecologic tract, and 1 sarcoma of the knee) and demonstrate aggressive behavior, heterogenous morphology, with varied fusion partners. The histologic spectrum is generally spindled or epithelioid, often with fibrous or myxoid stroma. In keeping with a high-grade sarcoma, all had brisk mitotic activity and frequent necrosis. Focal nuclear pleomorphism was common. Herein, we present an unusual case of a 66-year-old woman who underwent a radical hysterectomy for a 29-cm uterine mass which was adherent to the sigmoid colon. Histologic sections revealed a constellation of morphologic features including a low-grade phyllodes-like pattern suggestive of an adenosarcoma (Figure 2.28, A), uniform round to spindle cells with extensive perivascular hyalinization reminiscent of a kinase (NTRK) fusion tumor (Figure 2.28, B), biphasic glandular components (Figure 2.28, C), and scattered spindle cells growing in intersecting fascicles with anaplasia suggestive of leiomyosarcoma (Figure 2.28, D). Mitotic activity was variable but focally brisk and tumor necrosis was also present. Immunohistochemistry was weakly positive for SMA but negative for desmin, S100, and CD34. CK AE1/AE3 highlighted the glandular components. Molecular analysis revealed a novel RAD51B::TERT fusion. The patient received adjuvant chemotherapy and is alive with disease (peritoneal metastases) 6 months after surgical exploration. We describe a novel case of a RAD51B::TERT high-grade uterine sarcoma with biphasic morphology supporting the current conceptualization that RAD51B-sarcomas are morphologically heterogeneous with aggressive behavior and poor outcomes.

(Poster No. 29)

Jianhua Liu, MD¹ ([email protected]); Suyeon Yeon, MD¹; Suhalika Sahni, MD¹; Priyanka Gokhale, MD²; Vikas Mehta, MD.³ Departments of ¹Pathology and ²Obstetrics & Gynecology, University of Illinois at Chicago; ³Department of Pathology, Northwestern Medicine, Chicago, Ill.

Context: Excisional procedures are the standard care for treating high-grade squamous intraepithelial lesions (HSIL). However, discordant results between excision and biopsy specimens are quite frequent, and the reason is not fully understood. This study reviewed the cervical biopsy specimens with discordant results on excision and aimed to identify possible histological factors associated with discordancy.

Design: All cases with discordant results showing HSIL biopsy followed by low-grade or normal on excision specimens at an urban academic hospital between October 1, 2020, and September 30, 2023, were included. Biopsy slides of discordant cases were reviewed by a pathologist practicing subspecialty gynecologic pathology sign-out.

Results: Among 57 discordant cases where initial biopsies were performed at our institution, slides from 51 cases were available for review. Twenty of 57 cases were found to be overdiagnosed as HSIL on biopsy. Twelve (60%) of these 20 cases had no immunohistochemical (IHC) stains ordered while 8 of 20 cases (40%) were overdiagnosed due to misinterpretation of p16 in tangential sections and would have benefited with Ki-67 stain. Three of 20 cases (15%) were misdiagnosed due to immature squamous metaplasia and atrophy with IHC stains ordered in 1 case. Thirteen of 20 cases (65%) had fragmented biopsy specimens.

Conclusions: This study reveals significant overdiagnosis in discordant cases. Issues such as lack of p16 and Ki-67 staining, misinterpretation of p16 staining in tangential sections, immature squamous metaplasia, atrophy, and tissue fragmentation contribute to discordance. Special care should be taken in cases with scant, fragmented tissue, and liberal use of IHC and even in situ hybridization for human papillomavirus could be undertaken to avoid this pitfall.

(Poster No. 30)

Hadeel Altameemi, MD ([email protected]); Mohammed Aldahan, MD; Basim Al-Khafaji, MBChB, MHPE. Department of Pathology, Ascension St. John Hospital, Detroit, Mich.

Uterine cervix small cell neuroendocrine carcinoma (SCNEC) accounts for 3% of cervical cancers and most are associated with high-risk human papillomavirus (HPV). Here we report the case of a 91-year-old woman who presented with abnormal postmenopausal bleeding. Transvaginal ultrasound showed a 2.4-cm prominent nonuniform mass, and subsequent cervical biopsy identified sheets of pleomorphic cells (Figure 2.30, A), with minimal cytoplasm, nuclear molding, a fine salt-and-pepper–like nuclear chromatin pattern, inconspicuous nucleoli, brisk mitotic activity, abundant nuclear karyorrhexis, and focal necrosis. Immunohistochemical stains performed were as follows: tumor cells were positive for cytokeratin cam 5.2, synaptophysin (Figure 2.30, B), and p16 (Figure 2.30, C), with a Ki-67 proliferation index of almost 100% (Figure 2.30, D), while negative for cytokeratin (AE1/AE3), estrogen receptor, p40, p53, PAX8, vimentin, and chromogranin. SCNEC of the cervix usually presents at a median age of 48.1, unlike in this postmenopausal patient. Awareness of the histopathology plus appropriate immunostains to include p16, which when positive confirms the HPV association, aids in identifying the cervix as the primary origin. While multimodal treatment can improve tumor-free survival, the prognosis is poor.

(Poster No. 31)

Lidys Rivera Galvis, MD ([email protected]); Yong Zhang, MD, PhD; Eman Sallan, MD; David Haddock, MD; Bohdan Zoshchuk, MD; Julie Fanburg Smith, MD; Erick Washburn, MD. Department of Pathology, Penn State Health Hershey Medical Center, Hershey, Pennsylvania.

Context: Germline fumarate hydratase (FH) mutations cause hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC), with similar histopathological findings in germline and somatic mutations. We assessed morphologic features to screen for FH-deficient leiomyoma (FHD-LM) in uterine smooth muscle (SM) tumors, including leiomyosarcomas (LMS), smooth muscle tumors of uncertain malignant potential (STUMP), and leiomyomas with bizarre nuclei (LM-BN), correlating them with FHD-LM.

Design: Cases diagnosed as FHD-LM, LMS, STUMP, LM-BN from 2003 to 2023 were retrieved, clinicopathologically reviewed, and assessed for morphologic features of FH deficiency: macronucleoli with perinucleolar halos (MN-PNH), alveolar-pattern edema (APE), chain-like nuclear arrangement (CLNA), staghorn-type vessels (SHTV), and eosinophilic cytoplasmic inclusions (ECI), and submitted for FH mutation analysis.

Results: There were 3 FHD-LM, 6 LM-BN, 4 STUMP, and 12 LMS. Macronucleoli with perinucleolar halos were identified in 100% of FHD-LM, 33% of LM-BN, 50% of STUMP, and 17% of LMS. APE was present in 67% of FHD-LM. CLNA was found in 67% of FHD-LM, 17% of LM-BN and LMS, and 0% of STUMP. SHTV was present in 100% of FHD-LM, 50% of LM-BN, 75% of STUMP, and 42% of LMS. ECI was present in 67% of FHD-LM. LMS with macronucleoli and perinucleolar halos had a median age of 76 years and a worse outcome compared to those without these features.

Conclusions: On retrospective review of atypical uterine SM tumors, the presence of macronucleoli with perinucleolar halos appears to predict FHD in LM-BN and STUMP and separates LMS into a subset of older patients with higher mitotic rate and worse outcome.

(Poster No. 32)

Mahsa Chitsaz, MD ([email protected]); Atousa Ordobazari, MD. Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida.

A somatic neoplasm arising from a mature teratoma (MT) is very rare. We report a patient with spiradenocylindroma arising in an MT and discuss its histopathologic and immunohistochemistry features. A 65-year-old postmenopausal woman presented with pelvic pain. The patient, with a past medical history of recurrent squamous cell carcinoma of the neck and status post excision and radiation therapy, underwent a comprehensive evaluation revealing an 8.5-cm complex left adnexal cystic and solid mass with mural calcifications and internal septations. Serum tumor markers were normal. Histologic examination showed a mature teratoma in the left ovary including 2 large lobular neoplastic components, intermingled side by side. The first component was a partially encapsulated lobule that was biphasic containing 2 cell types: small cells with scant cytoplasm and small, hyperchromatic nuclei located mostly at the periphery of tumor lobules, and larger cells with eosinophilic cytoplasm and oval, vesicular nuclei located in the centers of tumor lobules. The second component was an unencapsulated lobule of basaloid cells with a jigsaw puzzle pattern, surrounded by dense eosinophilic basement membrane material and focal ductal formation. The initial consideration was adenoid cystic carcinoma (ACC); however, both components were diffusely positive for p63 and negative for CD117. Notably, the absence of classical biphasic differentiation challenged the initial consideration of ACC. This case emphasizes the significance of a multidisciplinary approach in diagnosing and managing atypical presentations of neoplastic entities within teratomas and highlights the importance of follow-up assessments for such rare lesions (Figure 2.32, A-D).

(Poster No. 33)

Andrea Mladenovic, MD ([email protected]); Geetha Jagannathan, MD; Elizabeth Genega, MD; Azin Mashayekhi, MD; Krisztina Hanley, MD; Gulisa Turashvili, MD, PhD. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.

Context: Binding of programmed death ligand-1 (PD-L1) to its ligand programmed death receptor-1 (PD-1) hinders the activation of T cells. Pembrolizumab is a monoclonal antibody that blocks the PD-1/PD-L1 pathway and is recommended for first-line combination therapy or second-line monotherapy for recurrent/metastatic cervical cancer. Vulvar carcinomas may also be treated with this immune checkpoint inhibitor.

Design: Our institutional archives were searched for cervical/vaginal and vulvar carcinomas tested for PD-L1 by immunohistochemistry. Clinical-pathologic data was reviewed, and PD-L1 immunostains were reassessed. The combined positive score (CPS) was calculated by dividing the number of PD-L1-positive cells (tumor cells, lymphocytes, macrophages) by the total number of viable tumor cells, multiplied by 100. Tumors with ≥1 CPS were considered PD-L1–positive.

Results: Of 30 patients, most were African American (20, 66.6%) diagnosed with squamous cell carcinoma (28, 93.4%). The median age was 51 (35–78) years. Most patients (11 of 30, 36.7%) were at FIGO stage III. The median tumor size was 0.4 cm (0.1–3.2). PD-L1 was positive in 28 (93.4%), with a median CPS of 31 (2–100). The most common treatment regimen was chemoradiation (14 of 30, 46.7%), followed by chemoradiation and pembrolizumab (8 of 30, 26.7%). For 28 patients with available follow-up (median 12 months, 2–171), 10 (35.7%) had no evidence of disease, 13 (46.4%) were alive with disease, and 5 (17.8%) were deceased. No statistically significant differences were observed among clinical-pathologic variables based on pembrolizumab therapy (Table).

Conclusions: Our results suggest that most patients with cervical/vaginal and vulvar carcinomas express PD-L1. However, elucidating the prognostic and predictive significance of the PD-L1 expression levels requires larger studies.

(Poster No. 34)

Li He, MD, PhD ([email protected]); Zhongxin Yu, MD; Anand Annan, MD, PhD; Lewis Hassell, MD; Doaa Atwi, MD. Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City.

Apocrine carcinoma (AC) is characterized by apocrine morphology and an estrogen receptor–negative and androgen receptor–positive immunoprofile. Most cases occur in skin adnexa and breast. No cases of primary AC in the ovary arising from Brenner tumor (BT) have been reported. Herein we report a unique case of primary low-grade AC arising from borderline BT of the ovary. The patient was an 84-year-old woman with no history of malignancy who presented with a left adnexal cystic mass detected by ultrasound 4 years prior. She underwent bilateral salpingo-oophorectomy. Grossly, the left ovary measured 24 cm in greatest dimension and had a tan-white smooth external surface. Cut surfaces revealed solid and cystic areas with multiple white to yellow excrescences. Microscopically, the tumor was composed predominantly of apocrine type glands showing complex papillary and cribriform architecture invading the underlying cyst wall (Figure 2.34, A). The apocrine cells were positive for androgen receptor, CK7, GATA3 and GCDFP-15, and negative for S100, PAX8, and estrogen and progesterone receptors. Ki-67 proliferative index was increased and p63 was negative around the glands. Areas of borderline Brenner type tumor were seen (Figure 2.34, B) and were closely intermingled with the apocrine tumor cells, suggesting that the AC is arising from the BT (Figure 2.34, C and D). The specimen was extensively sampled with no demonstrable normal breast tissue or skin adnexal structures. Molecular profiling of the apocrine areas revealed PIK3CA, KRAS, and CDKN2A mutations, which is typically associated with BT, and further supports that AC is arising from borderline BT in our case.

(Poster No. 35)

Isha Khanduri, MD ([email protected]); Dorsay Sadeghian, MD; Ramya Masand, MD. Department of Pathology, Baylor College of Medicine, Houston, Texas.

Sarcomas of the cervix constitute less than 1% of all cervical malignancies, with rhabdomyosarcomas being the most reported sarcomas. Most patients present with vaginal bleeding and a bulky cervical mass at diagnosis. Due to their diverse and overlapping histology, ancillary techniques are necessary for definitive diagnosis. We report a case of TPM3::NTRK1 fusion cervical sarcoma in a 50-year-old postmenopausal woman who presented with postmenopausal bleeding. Ultrasonography revealed a leiomyomatous uterus. The patient underwent hysterectomy with bilateral salpingo-oophorectomy. On microscopy, an incidental tumor circumferentially replacing cervical stroma with pushing and focally infiltrative borders with entrapped endocervical glands was identified (Figure 2.35, A–C). The tumor was composed of haphazardly arranged uniform spindle cells in a vague myxoid background with low mitotic index and brisk lymphocytic infiltrate (Figure 2.35, D). Differential diagnosis of adenosarcoma and inflammatory myofibroblastic tumor was considered. The tumor cells were negative for smooth and skeletal muscle markers, and ALK1, with patchy positivity for CD10 and cyclin D1. Given the nonspecific low-grade morphology, next-generation sequencing was performed and revealed a TPM3::NTRK1 fusion. NTRK-rearranged uterine sarcomas are recently described with activating mutations of NTRK, TPM3::NTRK1 being the most common fusion. Unusual adenosarcoma-like/fibrosarcoma-like spindle cell neoplasms of the cervix may represent an NTRK fusion sarcoma, which can be detected by S100 and pan-Trk staining and confirmed by NTRK molecular testing. This entity must be differentiated from malignant peripheral nerve sheath tumors, inflammatory myofibroblastic tumor with ETV6::NTRK3 fusion and COL1A1::PDGFB fusion sarcomas due to availability of targeted therapy.

(Poster No. 36)

Berkeley Sheppard, BS¹ ([email protected]); Dylan V. Miller, MD²; Jeremy C. Wallentine, MD.^{2 1}Rocky Vista University, Ivins, Utah; ²Department of EM Lab, Intermountain Central Lab, Murray, Utah.

Context: Testing for FOLR1 expression in ovarian high-grade serous carcinoma has emerged as an important predictive marker for patients being considered for treatment with mirvetuximab. Interpretive criteria include a 75% positivity threshold. Validation has been based on tissue section staining but testing of peritoneal fluid samples (cell blocks) is often requested as well in our laboratory. This study compares results of FOLR1 expression immunohistochemistry between paired tissue and peritoneal fluid samples from the same patients.

Design: Patients who had both surgical tissue biopsies and peritoneal fluid samples that were positive for high-grade serous ovarian cancer were identified in our pathology lab information system. FOLR1 staining was performed using the Ventana FOLR1 (FOLR1-2.1) RxDx Assay. The percentage of positive staining cells was assessed and recorded for both samples.

Results: A total of 21 paired samples were obtained and stained for FOLR1. Five patients had multiple peritoneal fluid samples (compared to a single tissue sample). In tissue sections, FOLR1 expression ranged from 0% to 100% (mean 63%). For peritoneal fluid samples, FOLR1 expression ranged from 0% to 65% (mean 10%). Among the tissue cases, 8 showed >75% staining. None of the cell block cases showed >75% staining (Figure 2.36).

Conclusions: Cell block samples show significantly less staining for FOLR1 compared to tissue sections from the same patients. Pathologists should be aware of this limitation.

(Poster No. 37)

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

Context: Adult granulosa cell tumors (AGCTs), a type of ovarian sex cord stromal (SCS) tumor, are distinguished from the more common benign neoplasms, such as fibroma/thecoma, using a number of histologic features (eg variable architecture and reticulum staining pattern) and molecular characteristics. Challenges may arise when the presumed AGCT exhibits features of fibromas, such as increased collagen, hyalinized stroma, and indeterminate reticulum staining pattern.

Design: Here we report a series of 5 tumors demonstrating uniquely ambiguous features. These came from 5 female patients (age 55–69 years; median 66 years) who underwent resections for adnexal mass (n = 2), postmenopausal bleeding (n = 2), and uterine clear cell carcinoma (n = 1).

Results: Pathologic examination revealed unilateral ovarian SCS tumors (size, 1.0–7.0 cm; median, 2.2 cm). All tumors displayed multiple variably sized solid nodules of predominantly epithelioid cells, surrounded by fibrous stroma. These epithelioid nodules had increased collagen deposition, ranging from wisps of hyalinized stroma (Figure 2.37, A) to hyaline plaques (Figure 2.37, B). Reticulum staining revealed that all cases showed a mixed pattern, comprising vague nodules with sparse reticulum staining, closely associated with areas of individual cell investing. The loss of reticulum staining in 2 tumors was in focal areas at the periphery of the nodules while the predominant central component showed individual reticulum wrapping (Figure 2.37, C). Three tumors had associated classical fibromas (Figure 2.37, D). All epithelioid tumors demonstrated FOXL2 C134W mutation, supporting the diagnosis of AGCTs

Conclusions: In summary, these 5 cases bring attention to the particular collagen-rich, reticulum-indeterminate patterns that may be mistaken for fibroma/thecoma and emphasize the use of molecular testing when faced with such challenging features.

(Poster No. 38)

Sibel Ak, MD¹ ([email protected]); Hula Taha, MD²; Hongxia Sun, MD, PhD³; Zhenjian Cai, MD, PhD⁴; Hui Zhu, MD, PhD⁴; Helen Zhang, MD¹; Tianhua Guo, MD.^{1 1}Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston; ²Department of Pathology and Laboratory Medicine, Baylor College of Medicine, Houston, Texas; ³Department of Pathology and Laboratory Medicine, MD Anderson Cancer Center, Houston, Texas; ⁴Department of Pathology and Laboratory Medicine, Clinical Pathology Laboratories, Austin, Texas.

Context: Cervical neuroendocrine carcinoma (CNC) is a rare and highly aggressive malignant neoplasm of the cervix, comprising 0.9% to 1.5% of uterine cervical tumors. Most cases involve lymphovascular invasion and distant metastasis at first presentation, leading to a poor prognosis and presenting clinical and therapeutic challenges.

Design: This retrospective case series included 6 patients who underwent cervical biopsy between 2020 and 2023. The pathology and patient medical records were reviewed for clinicopathologic evaluation.

Results: The average age of the 6 patients was 56 years. At the initial presentation, 5 out of 6 patients (83.3%) exhibited metastasis, including involvement of the lung, liver, and lymph nodes. Within 14 months following diagnosis, 3 out of 6 patients (50%) succumbed to the disease. The histomorphologic features were highly overlapping with human papillomavirus (HPV)–associated squamous cell carcinoma. Immunohistochemical analysis revealed that tumor cells were consistently positive for pancytokeratin and synaptophysin in all 6 cases. Five cases were tested for high-risk HPV by mRNA-ISH, and all turned out to be positive. p16 exhibited block-like positivity in 4 cases out of the 5 cases tested. p40 or p63 were negative in all 5 cases tested.

Conclusions: Cervical neuroendocrine carcinoma poses a considerable clinical and therapeutic challenge due to its aggressive behavior and lack of standardized treatment protocols. In this small case series, we explore the histopathologic features and clinicopathologic characteristics of CNC, which are vital and time-sensitive for clinicians in the accurate diagnosis and effective treatment of patients afflicted with this uncommon and aggressive malignancy.

(Poster No. 39)

Andrea Mladenovic, MD ([email protected]); Ekaterina Menshikova, MD; Elizabeth M. Genega, MD; Krisztina Hanley, MD; Gulisa Turashvili, MD. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.

Context: Overexpression of TRPS1, a member of the GATA transcriptional factor family, has been described in HER2-positive and triple-negative breast carcinomas (including metaplastic carcinoma), chondrosarcomas, and osteosarcomas. Limited data are available on TRPS1 staining in gynecologic cancers.

Design: The institutional archive was searched for uterine tumors diagnosed as clear cell, serous and undifferentiated/dedifferentiated carcinomas, mixed carcinomas, carcinosarcoma, and leiomyosarcoma from 2015 to 2023. Immunohistochemistry for TRPS1 was performed. Only nuclear staining was considered specific, and percentage of positive cells and staining intensity (weak versus moderate/strong) were assessed. The cut-off for positive staining was 1%.

Results: A total of 115 cases were identified. The median patient age was 68 years (37–90). The specimens included 62 (54%) biopsies, 38 (33%) hysterectomies, 13 (11%) curettings, and 1 (1%) myomectomy. The most common diagnosis was carcinosarcoma (33 of 115, 29%), followed by serous carcinoma (30, 26%), leiomyosarcoma (15, 13%), clear cell carcinoma, mixed serous and clear cell carcinoma (14 each, 12%), and others. TRPS1 was only positive in 20 (17.4%) tumors, in which the median percentage of positive cells was 10% (1–60), while staining intensity was weak in 11 (55.0%) and moderate/strong in 9 (45.0%). Expression of TRPS1 was higher in pure or mixed clear cell carcinomas compared with other subtypes (40% versus 8.4%; P < .001) (Table).

Conclusions: TRPS1 was only expressed in 17.1% of uterine high-grade carcinomas and sarcomas. TRPS1 expression in clear cell carcinoma may cause diagnostic confusion with breast carcinomas, warranting further studies.

(Poster No. 40)

Isha Khanduri, MD ([email protected]); Dorsay Sadeghian, MD; Ramya Masand, MD. Department of Pathology, Baylor College of Medicine, Houston, Texas.

STK11-mutated adnexal tumors represent a recently described, distinct category of locally infiltrative neoplasms, predominantly in the para-tubal region with an aggressive clinical course. They manifest diverse morphologic patterns and harbor characteristic STK11 gene mutations, loss of heterozygosity being the most common. Considering overlapping histologic features with sex-cord stromal tumors and tumors of Wolffian origin, morphologic categorization of these tumors poses significant diagnostic challenges. We describe a case of a 45-year-old woman with acute lower abdominal pain with the clinical suspicion of ovarian torsion. The patient underwent right salpingo-oophorectomy showing a 14-cm hemorrhagic para-tubal cystic mass. On microscopy, epithelioid neoplastic cells were arranged in diverse architectural patterns including glandular and tubular structures along with anastomosing corded, reticular, and solid patterns (Figure 2.40, A–D). Moderate mitotic activity was noted with proliferation index of 20%. Immunohistochemical staining exhibited patchy positivity for sex cord markers calretinin, CD56, as well as ER, PR, and CD117. Inhibin, cytokeratin, PAX8, EMA, WT-1, synaptophysin, chromogranin, GATA-3, SALL4, SF-1, and PAX2 were negative. Differential diagnosis of female adnexal tumor of Wolffian origin and sex-cord stromal tumors were considered. Subsequent evaluation by next-generation sequencing identified a possible germline STK11 mutation. This case highlights the significance of adopting a comprehensive approach, including integration of genomic analysis, to reveal the presence of STK11 gene alterations, in unclassified adnexal tumors demonstrating heterogeneous histologic patterns. Identification of STK11 mutation, despite overlapping immunohistochemical profiles with other tumors aids in accurate classification and patient management, given the aggressive behavior of these tumors.

(Poster No. 41)

Carol N. Rizkalla, MBBS¹ ([email protected]); Ankur R. Sangoi, MD.^{2 1}Department of Laboratory Medicine and Pathology, University of Washington, Seattle; ²Department of Pathology, Stanford Medical Center, Stanford, California.

Context: Despite the College of American Pathologists’ recommendation against diagnosing “fat invasion” in urinary bladder biopsy/transurethral resection of bladder tumor specimens (Bx/TURBT), some pathologists still consider this scenario as pathologic stage pT3. However, a formal evaluation of fat in Bx/TURBT has not been performed. Herein, we analyze adipose tissue incidence/distribution, cancer invading into fat, staging ramifications, and clinical outcomes in a large series of Bx/TURBT.

Design: Among a series of 383 Bx/TURBT cases, data on adipose tissue presence, location, and quantity were analyzed. Adipose tissue mimics such as lymphovascular spaces and cautery artifacts were excluded. Of the cancer cases involving fat (putative “pT3”) Bx/TURBT, clinical follow-up was obtained.

Results: Of the 200 consecutive Bx/TURBT (including benign/cancer), adipose tissue was identified in 37% of 200 cases (22% Bx, 78% TURBT), primarily in the lamina propria (57%) or both lamina propria/muscularis propria (32%). Of 183 Bx/TURBT pT1/pT2 cases, adipose tissue was present in 40%, predominantly within both lamina propria and muscularis propria (Table). Among pT1/pT2 cases, 26% (23/88) had cancer involving fat. Clinical follow-up on these putative “pT3” cases revealed 10 patients who underwent radical cystectomy of which only 1 of 10 remained pT3/pT4 (although 8 patients had neoadjuvant therapy).

Conclusions: Adipose tissue, while more prevalent in TURBT, is not uncommon in Bx specimens and is often located in the lamina propria. In this regard, when there is invasive urothelial carcinoma present, there is a potential for overstaging cases as pT3 when cancer is present in fat.

(Poster No. 42)

Tung Nguyen, MD ([email protected]); Melissa Tjota, MD, PhD; Peng Wang, MD, PhD; Tatjana Antic, MD. Department of Pathology, the University of Chicago Medical Center, Chicago, Illinois.

The 2022 World Health Organization classification identifies succinate dehydrogenase-deficient (SDHD) renal cell carcinoma (RCC) as a malignant epithelial tumor characterized by bland cells with eosinophilic cytoplasm and loss of succinate dehydrogenase B (SDHB) immunostaining. We present the first case of a widely metastatic SDHD RCC in a 39-year-old woman with a history of germline SDHB gene mutation. Macroscopically, the tumor presents as a singular, tan-brown mass with hemorrhagic areas, encompassing the entire kidney. It extensively infiltrated the renal sinus and perinephric adipose tissue. Microscopically, the tumor displayed heterogeneous morphology (Figure 2.42, A), including a predominantly solid tumor with focal tubular and pseudopapillary architecture and areas bordering on sarcomatoid histology. The predominant portion of the tumor consists of cells displaying eosinophilic cytoplasm with a moderate amount of cytoplasm that is occasionally vacuolated, and nuclei that exhibit INI-1 retention on immunohistochemistry (Figure 2.42, B). In a separate area, cells exhibit a small amount of amphophilic to clear cytoplasm, and their nuclei are negative for INI-1 immunohistochemical stain (Figure 2.42, B inset, C). The stroma is sclerosed and hyalinized with bony metaplasia and focal necrosis. Despite nonclassical cytomorphology for SDHD RCC, the entire tumor lacked SDHB immunostaining (Figure 2.42, D). Next-generation sequencing revealed a pathogenic SDHB variant (p.C191Y, VAF 77%) and SMARBC1 variant (p.P146Mfs*33, VAF 46%). We propose that, similar to other RCCs, the morphological and immunohistochemical variations in this tumor may be influenced by additional gene mutations, akin to BAP1-mutated clear cell RCC, or determined by partner genes, as observed in translocation RCCs.

(Poster No. 43)

Margaux M. Canevari, DO¹ ([email protected]); Isabell A. Sesterhenn, MD¹; Adina Paulk, MD¹; Allen P. Burke, MD¹; Sean Kern, MD²; Joel T. Moncur, MD, PhD, MS¹; Justin M. Wells, MD.^{1 1}Department of Pathology, Joint Pathology Center, Silver Springs, Maryland; ²Department of Urology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

Context: Testicular germ cell tumors (TGCT) are rare and complex. There is a 95% 5-year survival across all stages at presentation; however, the treatments required beyond orchiectomy come at a cost. It has been shown that the chemotherapy or radiation for TGCT leads to an increased risk of subsequent malignancies such as mesothelioma. Attention has turned to fine tuning algorithms to help limit exposure to those for whom it is necessary. Centered in these efforts are pathologists’ diagnostics.

Design: We reviewed the 304 TGCT consultative cases received at the Joint Pathology Center (JPC) from 2018 to 2023. Fifteen percent received diagnostic concordance (category 1), 27% received diagnostic discordance (category 2), and 58% (category 3) were submitted with diagnostic deferral to the JPC.

Results: For category 2, they reclassified testicular cancer subtypes (69 events), added or removed pathologic staging and prognostic variables such as disease extent or lymphovascular invasion (43 events), reclassified the malignant or benign diagnostic category (10 cases), and changed TGCT to metastatic disease (1 case).

Conclusions: Continuity of care cases at another high testicular volume institution are reported in the literature with a similar pattern of findings of category 2. National Comprehensive Cancer Network guidelines for sarcomas, another challenging specimen, recommend an expert pathologist review with sarcoma experience prior to treatment. The combined findings of our review and the literature are evidence to institute a similar policy for testicular cancer.

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

(Poster No. 44)

Tengfei Wang, MD ([email protected]); Bing Leng, MD, PhD; Lina Liu, MD. Department of Pathology, Baylor Scott and White Health, Temple, Texas.

Context: Early-onset (age <47) clear cell renal cell carcinoma (ccRCC) represents 3%–7% of all RCC cases, demonstrating an increasing trend. However, understanding the clinicopathologic characteristics and survival of early-onset ccRCC is limited.

Design: To investigate the characteristics and survival in early-onset ccRCC, a cohort study examining early-onset ccRCC was conducted using the Texas Cancer Registry anonymous dataset with 3–5 years of follow-up. Survival estimation was performed with log-rank (Mantel-Cox) tests and Kaplan-Meier survival curve plots.

Results: A total of 1115 early-onset ccRCC cases were identified (ages 19–46, mean 40). Most cases were male (60.1%), white (90.9%), Hispanic (44.6%), and overweight/obese (87.5%). Additionally, 48.3% never used cigarettes, 89.0% lived in metropolitan counties, and 28.0% resided in high-poverty areas. Of these cases, 92.1% had a single primary tumor, with 81.4% ≤7 cm in tumor size, and 4.5% with distant metastasis. At the last visit, 3.8% of patients had died, and 57.4% were American Joint Committee on Cancer (AJCC) clinical stage 1. Interestingly, Mexican Hispanic ethnicity (P < .001) significantly correlated with poor prognosis. Overweight/obesity (body mass index [BMI] ≥ 25, P = .045) and metropolitan area residence (P = .006) were related to a better prognosis (Figure 2.44). AJCC stages, distant metastasis, age, and tumor size also served as prognostic factors. But race, sex, smoking status, and poverty level were not associated with prognosis.

Conclusions: This population-based study of early-onset ccRCC revealed several notable findings. Surprisingly, Mexican Hispanic ethnicity, BMI, and metropolitan area emerged as significant prognostic factors for early-onset ccRCC. This finding is reported for the first time and not found in the literature.

(Poster No. 45)

Hebatullah Elsafy, MD ([email protected]); Robert Foucart, DO; Farhan Sami, MBBS; Ameer Hamza, MD. Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City.

There is growing recognition of SARS CoV-2 (COVID-19) virus impact on all organ systems, including the urinary tract. The exact mechanism underlying many of these manifestations remains underexplored, with hypotheses ranging from direct viral involvement to secondary effects of the inflammatory response. This case describes a patient who developed severe and refractory urinary symptoms post-COVID-19. We report the case of a 58-year-old woman diagnosed with SARS-CoV-2 infection lasting a week who did not require hospitalization. However, concurrently the patient started experiencing intractable lower urinary tract symptoms that kept getting worse even after COVID-19 was completely resolved. Urodynamic studies showed normal bladder pressure with no sign of outlet obstruction. Abdomen and pelvic CT scans did not show any concerns for malignancy. Multiple cystoscopies showed no lesions or abnormalities. Antibiotic trials never resulted in adequate response and trials of catheterization, although helping with her symptoms, caused irritation and discomfort over time. After extensive discussion, the patient elected to proceed with cystectomy and urinary diversion with ileal conduit. Grossly, the bladder mucosa was unremarkable. Microscopic examination showed patchy urothelial denudation, squamous metaplasia, acute and chronic inflammation, transmural dense chronic inflammatory infiltrate, fibrosis, and reactive changes. This case highlights the challenges in management of post-COVID-19 lower urinary tract symptoms. The enigmatic nature of the patient's symptoms emphasizes the importance of continued research and collaboration to unravel the intricacies of postviral urinary complications. This case contributes to the evolving narrative surrounding the long-term impact of COVID-19, urging healthcare professionals to approach cases with diligence and a multidisciplinary approach.

(Poster No. 46)

Hebatullah Elsafy, MD ([email protected]); Jwan Alallaf, MD; Katie Dennis, MD. Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City.

Context: Composite pheochromocytoma (CP) is a rare neoplasm fusing elements of pheochromocytoma (PCC) and tumors of neuroblastic origin like ganglioneuroma (GN), neuroblastoma (NB), and ganglioneuroblastoma (GNB). From 2015 to 2023, we report the characteristics and outcome of 4 cases of CP (PCC and GN components).

Design: Case 1, a 64-year-old woman presented with long-standing resistant hypertension and CT imaging revealed a large left adrenal mass. A left adrenalectomy was performed, revealing a CP with a minor component of GN (Figure 2.46, A). Case 2, a 57-year-old asymptomatic woman presented with an incidentally discovered right adrenal mass. A right adrenalectomy revealed CP with GN element (Figure 2.42, B). Case 3, a 40-year-old woman, presented to the emergency room with chest pain and hypertension. CT showed a left adrenal mass. Left adrenalectomy revealed CP with 50%–60% of primitive neurogenic/neuroblastic features (Figure 2.42, C). Case 4 was a 15-year-old male who presented with elevated blood pressure. CT scan showed a right hilum kidney mass. A partial nephrectomy revealed a CP with a small NB component (Figure 2.42, D).

Results: Three patients were females. Heterozygosity for SDHB was found in 1 case. Tumors were unilateral and large, measuring 7.2, 4.9, 13.5, and 3.2 cm on greatest dimension, respectively. There was no recurrence, metastasis, or development of a contralateral tumor during follow-up.

Conclusions: CP can present without hypertension and classic symptoms; therefore, it is vital to identify the rare presentations of CP. By shedding light on these specific cases, we hope to enhance fostering advancements in clinical management and diagnosis.

(Poster No. 47)

Cullen M. Lilley, MD, MS, MA ([email protected]); Jonathan E. Zuckerman, MD, PhD. Department of Pathology and Laboratory Medicine, UCLA Health, Los Angeles, California.

Context: Pathologic connection between the kidney tubules and veins is known as a microscopic tubulovenous fistula (TVF). This finding has been reported in a few small case reports but no systematic examination of cases across various clinical settings detailing their histologic spectrum and associated clinical/pathologic findings has been performed.

Design: Nonneoplastic kidney pathology reports from an academic medical center (February 1, 1990–February 1, 2024) were queried for mention of TVF. Pathology reports and clinical data were gathered from the electronic medical record. TVFs were defined as histologic continuity between a tubule and vein lumen associated with uromodulin, fibrin, and a cellular reaction within the vein lumen.

Results: A total of 30 537 nonneoplastic kidney reports were queried; 22 cases of TVF were identified, of which 72.7% were from native kidneys. Median patient age was 66 (range: 25–84) with a male predominance (68.2%). Microscopic hematuria was found in 76.5%, and 11.8% had gross hematuria. TVFs were usually singular and involved arcuate veins. Acute tubular injury was found in 95.5% of cases and 73.3% had pathologic intratubular casts/calcium crystals (Table). Of native cases, 56.3% exhibited interstitial nephritis. Of the transplant cases (n = 6), 66.7% exhibited rejection.

Conclusions: This is the largest case series exploring the clinical and histologic features associated with TVFs in the kidney. While rare in our repository, this is likely an underreported finding. Our findings support the assertion that TVFs are associated with hematuria without glomerulonephritis and occur in the setting of significant tubular injury, intratubular casts/crystals, and obstructive phenomena likely due to disruption of tubular basement membranes adjacent to veins.

(Poster No. 48)

Zhengfan Xu, MD ([email protected]); Khaleel Al-Obaidy, MD; Nilesh Gupta, MD; Oudai Hassan, MD. Department of Pathology and Lab Medicine, Henry Ford Hospital, Detroit, Michigan.

Context: Genomically unstable urothelial carcinoma (UC) tends to have cell cycle expression aberrancy and tendency of muscle invasion. We studied relationship between the immunohistochemical expression of cell cycle protein (p16 and cyclin-D1) and muscle invasion in UC.

Design: We included consecutive transurethral resection of bladder tumors (TURBTs) at our institution from 2016 to 2021 with marked lamina propria invasion, defined as ≥2 invasion foci measuring ≥0.5 mm. Cases with variant histology were excluded. All cases were double-reviewed by urologic pathologists. Positive p16 was defined as strong diffuse nuclear and cytoplasmic staining. Cyclin-D1 loss was defined as complete loss of nuclear staining. Tissue microarrays were created from the cases with marked lamina propria invasion and stained for p16 and cyclin-D1. Statistical analysis was performed using the Fisher exact test.

Results: A total of 44 cases were included. Median age at diagnosis was 69 (47–91). Eleven patients were female and 33 were male. Median follow-up was 34 months (2–89). Of 44 cases, 10 progressed to muscle invasion. p16 positivity was seen in 7 of 10 (70%) progressed cases compared to 9 of 34 (26%) nonprogressed cases. There was significant difference in p16 expression between the 2 groups (P = .02). Cyclin-D1 loss was seen in 4 of 10 (40%) progressed cases compared to 8 of 34 (23.5%) nonprogressed cases, and the difference was not significant (P = .4) (Table).

Conclusions: Positive p16 in UC with marked lamina propria invasion was significantly associated with future muscle invasion. Cyclin-D1 loss, although more frequent, was not significantly associated with progression. Our findings are exciting in pursuit of potential markers to predict future muscle invasion in UC.

(Poster No. 49)

Sujani C. Madabhushi, MD¹ ([email protected]); Manita Chaum, MD²; Simon B. Chen, MD⁴; Franz Fogt, MD, PhD¹; Priti Lal, MD.^{3 1}Department of Pathology and Laboratory Medicine, Pennsylvania Hospital of the University of Pennsylvania Health System, Philadelphia; Departments of ²Precision and Computational Diagnostics and ³Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia; ⁴Department of Precision and Computational Diagnostics, Perelman School of Medicine University of Pennsylvania, Philadelphia.

We present molecular findings of a case of primary seminal vesicle adenocarcinoma (PSVA), a rare primary malignancy, not well characterized genetically. A 38-year-old man presented with bilateral testicular pain and left supraclavicular node enlargement. Imaging showed a large soft tissue mass involving the left prostate gland and left seminal vesicle with extensive retroperitoneal lymphadenopathy. No other organ systems, including the gastrointestinal tract, revealed additional lesions. Given the location, our top differential included prostatic adenocarcinoma. The serum prostate-specific antigen (PSA) level was normal. Biopsy of the supraclavicular lymph node and the mass revealed a tubuloglandular and papillary architecture with pleomorphic nuclei, scant clear cytoplasm, hob nailing (Figure 2.49, A) with Ki-67 proliferation index of 10%–15%. Immunohistochemical analysis demonstrated positivity for CK7 (Figure 2.49, B), CA125 (Figure 2.49, C), PAX8 (Figure 2.49, D), napsin A, CEA, with focal positivity for glypican 3 and CD10. Additionally, the carcinoma was negative for SALL4, OCT4, AFP, TTF1, CDX2, SATB2, racemase, PSA, NKX3.1, and PLAP. Based on the combined radiology-pathology findings a diagnosis of exclusion of PSVA was suggested. Next-generation sequencing (NGS) revealed an ASXL1 c.1934dupG (p.G646fs) mutation, an alteration typically found in myeloid neoplasia, at a variant allele frequency (VAF) of 26%; a TERT promoter mutation (c.-124C>T), which is commonly found in urothelial carcinoma, gliomas, melanoma, and hepatocellular carcinoma, was also identified (at 21% VAF). Both mutations were classified as pathogenic. We did not identify driver molecular alterations characteristic of the differential diagnostic considerations of metastasis from a colorectal or prostatic primary. Further studies are warranted to unravel the genetic profile of PSVA.

(Poster No. 50)

Ping Shi, MD ([email protected]); Sohira Malik, MD; Yong Zhang, MD, PhD; Tiane Chen, MD, PhD; Qingqing Wu, MD, PhD; Guoli Chen, MD, PhD. Department of Pathology, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania.

Context: Upper-tract urothelial carcinoma (UTUC) poses diagnostic challenges due to the typically low-yield, artifact-prone biopsy specimens. This study aims to improve UTUC diagnosis through immunohistochemical profiling of p16, p53, and Ki-67 markers using tissue microarray (TMA) analysis.

Design: A retrospective analysis encompassed 149 UTUC patients post-nephroureterectomy at Hershey Medical Center, spanning 2000–2020. TMAs were constructed to differentiate between low-grade (LG) and high-grade (HG), noninvasive and invasive tumors. The expression levels of p16, p53, and Ki-67 were scored (0–3) via a semiquantitative method and correlated with clinical and histologic data. Statistical analyses were conducted using 1-way ANOVA and Student t test.

Results: p53 and Ki-67 expressions were significantly higher in HG UTUC than in LG or normal tissues (P < .01). p16 was more abundant in malignant lesions (P < .05), without distinction between HG and LG. Within the same patients, increased expression of all 3 markers was associated with invasive HG carcinoma compared to normal tissues (P < .05). Stratifying by tumor stages, Ki-67 expression was notably elevated in stage 3 and 4 compared to stage 0 (P <.005). Strong p53 expression (IHC = 3) was present from stage 2 onward but absent in stages 0 and 1. However, p16 strong expression can be displayed across all stages.

Conclusions: Aberrant p53 and Ki-67 expression intensify with UTUC grade and stage progression. p16 expression distinguishes malignant from benign tissues but lacks prognostic value for tumor grading. Our findings suggest that combining p53, p16, and Ki-67 immunostains strategically may be valuable in the diagnosis and characterization of UTUC, particularly when the specimens are limited.

(Poster No. 51)

Issa Al-kharouf, MD ([email protected]); Hebatullah Elsafy, MBBCh; Farhan Sami, MD; Ameer Hamza, MD. Department of Pathology, Kansas University Medical Center, Kansas City, Missouri.

Context: The population of gender nonbinary is growing in the United States. Specifically, considerable increase in individuals seeking male to female physical adaptation is noted. The purpose of this study is to identify trends in the number and age of patients who presented to our institution for male-to-female physical adaptation.

Design: Data were collected for the patients who had orchiectomy for gender transition at our institution from January 2018 to March 2023.

Results: A total of 190 patients underwent orchiectomy for gender transition. Patients’ ages ranged from 18 to 81 years with a mean of 35.6 ± 13.5 years. Two-thirds (126 of 190) were 21 to 40 years old. A steady increase was seen in the number of cases from 13 patients in 2018, to 52 in the year 2022 and a projected 80 patients the subsequent year. The mean age of the patients predominantly showed a downwards trend (Figure 2.51). From a pathologic standpoint, all patients demonstrated a variable degree of hormone therapy–related changes. More prevalent changes included fibrosis/hyalinization of seminiferous tubules and diminished or absent spermatogenesis, present in 97% of the specimens. Reduction or complete absence of Leydig cells was seen in 63% of the specimens. Periepididymal fibrosis was identified in 59% and hyperplastic epididymal epithelium was seen in 15%.

Conclusions: Individuals in a wide age range seek transition; however, the mean age continues to show a downwards trend, meaning more younger individuals are seeking male-to-female physical adaptation. Pathologically, all patients consistently demonstrate a variable degree of hormone therapy–related changes.

(Poster No. 52)

Rodrigo Tavares-Macedo, MD¹ ([email protected]); Ross S. Liao, MD²; Nima Almassi, MD²; Erick Remer, MD³; Jane Nguyen, MD, PhD¹; Christopher G. Przybycin, MD¹; Sean R. Williamson, MD¹; Christopher Weight, MD²; Samuel Haywood, MD²; Mohamed Eltemamy, MD²; Georges-Pascal Haber, MD, PhD²; Reza Alaghehbandan, MD.¹ Departments of ¹Pathology and Laboratory Medicine, ²Urology, and ³Diagnostic Radiology, Cleveland Clinic Foundation, Cleveland, Ohio.

Context: Paraganglioma of the urinary bladder is a rare neoplasm that can clinically and pathologically mimic urothelial carcinoma. The aim of this study was to assess the histopathologic spectrum of paraganglioma of the urinary bladder, with emphasis on risk stratification.

Design: The laboratory information system was searched (1992–2023), yielding 8 confirmed bladder paragangliomas after pathological rereview. Clinical information was obtained from medical charts and available images were reviewed by an expert radiologist.

Results: Eight cases were identified (3 males and 5 females), ranging from 32 to 83 years (mean 64.1). All tumors were unifocal, ranging from 0.4 to 3.6 cm (mean: 1.9 cm). Imaging demonstrated 1 polypoid, 1 polypoid with mural involvement, and 5 submucosal/intramural tumors. Six cases (6 of 8) showed classic zellballen nested pattern, 1 with large/irregular nested architecture, and 1 with pseudorosette growth pattern. Necrosis or vascular invasion were not identified (0 of 8). Muscularis propria invasion was identified (5 of 8). Focal nuclear atypia (4 of 8) and cytoplasmic clearing (6 of 8) were observed. Urine cytology demonstrated 2 negative and 1 “atypical” case with negative fluorescence in situ hybridization. Immunohistochemically, tumors were negative for CAM5.2, diffusely positive for chromogranin and GATA3, and retained SDHB. Using the Grading of Adrenal Pheochromocytoma and Paraganglioma scoring system moderately differentiated (5 of 8) and well-differentiated (3 of 8) types were present. Three patients died of causes other than bladder paraganglioma and the remaining 5 were alive without disease (mean follow-up 54.6 months).

Conclusions: Bladder paraganglioma remains an uncommon neoplasm, presenting in a broad age range with features mimicking urothelial neoplasms. The majority of bladder paragangliomas are sporadic and behave in an indolent fashion.

(Poster No. 53)

Omar Abbas, MD ([email protected]); Sarah Kisha, MD; Oudai Hassan, MD; Nilesh S. Gupta, MD; Khaleel I. Al-Obaidy, MD. Department of Pathology, Henry Ford Health, Detroit, Michigan.

Context: Renal cell carcinomas (RCC) in patients younger than 45 years represent a distinct subset with unique clinicopathologic features. While the characterization of RCC in older populations is well established, comprehensive insights into this younger age group are limited. Our study aims to bridge this knowledge gap by examining a cohort of 173 RCC cases diagnosed in individuals aged under 45 at our health system between 2011 and 2023. This study explores the prevalence of RCC subtypes, clinicopathologic parameters, and demographic characteristics within this specific age range.

Design: We searched the pathology electronic archive from the department of pathology at our institution for cases diagnosed as RCC in patients under the age of 45 years between 2011 and 2023.

Results: We identified 173 cases within our health system. The average age at diagnosis was 38 years (range, 22–44 years) and sex distribution revealed a male predominance (59%, n = 102). Clear cell RCC (66%, n = 115) was the most prevalent subtype, followed by papillary (15.6%, n = 27) and chromophobe RCC (11.6%, n = 20). Other subtypes included multifocal clear cell RCC (1.2%), multifocal papillary RCC (2.3%), TFE3-rearranged RCC (1.7%), acquired cystic disease-associated RCC (1.2%), SMARCB1-deficient renal medullary carcinoma (0.6%), FH-deficient RCC (0.6%), and RCC-not otherwise classified (Table).

Conclusions: Our study provides an overview of RCC in patients aged under 45, emphasizing the significance of recognizing diverse histologic subtypes within this population. Clear cell RCC remains the most common subtype, but the presence of rare variants underscores the complexity of RCC in younger individuals.

(Poster No. 54)

Angelle L. Jolly, MD ([email protected]); Haibo Wang, MBBS, PhD; Michael Webber, DO; Ritu Bhalla, MD. Department of Pathology, Louisiana State University, New Orleans.

Biphasic squamoid alveolar renal cell carcinoma (BSARCC) is a newly described histologic variant of papillary renal cell carcinoma that has not yet been added to the World Health Organization (WHO) classification as a distinct entity. This variant is characterized by a unique biphasic growth pattern with nests of large squamoid cells surrounded by smaller cuboidal to flattened cells reminiscent of glomeruloid structures. Immunohistochemically, BSARCC shows diffuse positivity for cytokeratin 7, vimentin, PAX-8 and alpha-methylacyl-CoA racemase (AMACR), with cyclin D1 positivity limited to the squamoid cells. We present 2 cases of BSARCC diagnosed at our institution that unveil a novel immunohistochemical staining pattern not yet described in the literature. The patients, a 61-year-old woman and a 49-year-old man, presented with renal masses (4.1 and 6.3 cm, respectively). Microscopic examination revealed 2 distinct cell populations within alveolar structures comprised of peripheral cuboidal cells surrounding larger squamoid cells (Figure 2.54, A). Immunostaining demonstrated diffuse positivity for CK7, PAX-8, and AMACR, while cyclin D1 positivity was limited to the squamoid cells (Figure 2.54, B), consistent with BSARCC. Interestingly, despite negativity for p63, high-molecular-weight cytokeratin (HMWCK) was found to stain the squamoid cells in both cases, a characteristic not yet described for this entity (Figure 2.54, C and D). Our study suggests that the immunostaining profile, particularly this novel and unique expression of HMWCK, may hold significant diagnostic value in differentiating BSARCC from other variants of renal cell carcinoma. This finding is crucial as we anticipate future recognition of BSARCC as a distinct entity in the WHO classification.

(Poster No. 55)

Akhila Aravind, MD ([email protected]); Philip Carithers, MD; Varsha Manucha, MD; Ramya Velagapudi, MD. Department of Pathology, University of Mississippi Medical Center, Jackson.

The occurrence of primary retroperitoneal cystic teratoma in adult males is exceedingly rare, with only a few case reports in the English literature. We present the case of a 48-year-old man who was discovered incidentally to have a mass in the left retroperitoneum during diagnostic evaluation for low back pain. Imaging revealed a 6.9-cm heterogenous mass (Figure 2.55, A) felt to be originating from the left adrenal gland with extension to the left kidney. Subsequently, the patient underwent a left nephrectomy-adrenalectomy. Gross examination revealed a cystic mass in the renal hilum discreet and separate from kidney and adrenal gland. On sectioning, the mass was filled with yellow greasy material and hair (Figure 2.55, B). Microscopic analysis showed a fibro-collagenous cyst wall lined with keratinizing squamous epithelium and the presence of pilosebaceous units, apocrine gland, mature fat, nerve bundles, and cartilage in the cyst wall (Figure 2.55, C and D) with no immature neural epithelium or mesenchyme. The patient’s young age prompted the consideration of primary and metastatic germ cell origin postpubertal teratoma. Testicular ultrasound and analysis of germ cell tumor markers yielded normal results, with a negative isochromosome 12p test. A final diagnosis of a benign cystic teratoma was rendered. Per last follow-up, the patient is doing well. Retroperitoneal primary cystic teratoma in an adult male is rare, most often incidentally detected, and should be considered in the differential diagnosis of retroperitoneal cystic mass. The diagnosis should, however, be rendered only after excluding a metastatic gonadal postpubertal teratoma because of the difference in management and prognosis.

(Poster No. 56)

Elie Tannous, MD¹ ([email protected]); Reza Hosseini, MD¹; Dilek Ertoy Baydar, MD²; Kemal Kosemehmetoglu, MD³; Yasemin Yuyucu Karabulut, MD⁴; Laurence Galea, MD⁵; Mahmut Akgul, MD.^{1 1}Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, New York; ²Department of Pathology and Laboratory Medicine, Koç University Hospital, Istanbul, Turkey; ³Department of Pathology and Laboratory Medicine, Hacettepe University School of Medicine, Ankara, Turkey; ⁴Department of Pathology and Laboratory Medicine, Mersin University Hospital, Mersin, Turkey; ⁵Department of Pathology and Laboratory Medicine, Melbourne Pathology, Sonic Healthcare, Collingwood, Australia.

Context: Renal lesions with a prominent cystic component can be challenging. Localized cystic disease of the kidney (LCDK) is a rare nonhereditary, nonprogressing cystic disease. LCDK is a poorly understood lesion, with rare representation in the literature.

Design: The study includes 10 multinational, previously unreported cases.

Results: Nine adults and 1 pediatric patients were identified (M:F = 7:3; median 59 years [range: 9–79]). Most common presentation was flank pain (n = 4), followed by incidentally identified lesions by imaging, which was mostly computed tomography. The right kidney was slightly more affected than the left, and contralateral kidney was mostly normal (n = 6). No family history of polycystic kidney disease was present. No cases had bilateral disease, and none had extrarenal solid organ cysts. Radical and partial nephrectomy were performed in 6 and 4 cases, respectively. All cases were grossly macroscopically multilocular, ranging from 1.8 to 20 cm. Diffuse involvement was not present. Microscopically, frequent nonneoplastic elements of kidney parenchyma, including renal tubules and mostly cystic glomeruli, were present in the cystic septa without any primitive epithelial cellular elements, blastema, or immature stromal cells (Figure 2.56, A–D).

Conclusions: LCDK should be considered as a differential in unilateral cystic kidney disease.

(Poster No. 57)

Mary M. Torrez, MD ([email protected]); Eman Abdulfatah, MD. Department of Pathology, University of Michigan, Michigan Medicine, Ann Arbor.

Cellular angiofibroma (CAF) is a rare benign, moderately cellular mesenchymal neoplasm that typically arises in genital sites, including the vulvovaginal and inguinoscrotal/paratesticular regions, and rarely occurs in extragenital sites. We report the case of a 72-year-old man with longstanding urinary retention and benign prostatic hyperplasia who underwent transurethral resection of the prostate. Gross examination revealed numerous fragments of tan-pink fibrous tissue without any discernible masses. Histologic sections showed a spindle cell proliferation with an associated vascular component comprised of hyalinized small to medium-sized blood vessels (Figure 2.57, A). Cytologically, the cells were normochromatic with evenly distributed chromatin with no significant atypia or brisk mitotic activity. Based on the histomorphologic features, the differential diagnosis included solitary fibrous tumor, prostatic stromal nodule, prostatic stromal tumor of undetermined malignant potential, and CAF. Immunohistochemical stains showed the neoplastic cells were positive for CD34 (Figure 2.57, B), PR (Figure 2.57, C), desmin, and SMA, and negative for STAT6, DOG-1, CD117, ALK, S100, myogenin, and myoD1; there was patchy loss of Rb1 expression (Figure 2.57, D). Overall, these features, including the patchy loss of RB expression, represent CAF arising in the prostate. To our knowledge, this is the second reported case in the literature of CAF arising in the prostate, and the first to be established using Rb1 immunohistochemistry, the previous supported by loss of RB1/13q14 region by fluorescence in situ hybridization. This case illustrates the importance of maintaining a high level of suspicion for rare mesenchymal neoplasms in unusual locations as well as the utility of immunohistochemistry for Rb1 in routine clinical practice.

(Poster No. 58)

Reem Youssef, MBBCh ([email protected]); Andres Acosta, MD. Department of Pathology, Indiana University School of Medicine, Indianapolis.

Pseudomyogenic hemangioendothelioma (PHE) is a rare soft tissue vascular tumor that typically occurs in the distal extremities of young men and is often multifocal. It is classified as an intermediate-type tumor that tends to recur locally but rarely metastasizes. Recurrent FOSB rearrangements are characteristic molecular alterations, with SERPINE1::FOSB and ACTB::FOSB fusions being the most common. We present the case of a 47-year-old man who presented with a painful penile plaque at the glans penis that began to increase in size with occasional drainage. Mass excision was performed, and pathology results revealed a nodule composed of epithelioid neoplastic cells with irregular nuclei and small, visible nucleoli, with foci of perineural invasion. The tumor cells were arranged as single cells or single-cell files, diffusely infiltrating the dermis with scattered cells demonstrating a rhabdoid (“pseudomyogenic”) morphology. Immunohistochemistry demonstrated that the lesional cells were positive for keratin (AE1/AE3), ERG, CD31, and INI1 (with retained expression), and FOSB while CD34, CAMTA1, factor XIIIa, SOX10, CD163, and ALK were negative. The morphologic and immunohistochemical staining pattern supported the diagnosis of PHE. Two months later, he developed a second penile nodule suggestive of local recurrence and was started on a rapamycin kinase (mTOR) inhibitor. We report an exceedingly rare case of penile PHE; to date, only 1 case has been reported in the literature. PHE is a rare entity that could be easily misdiagnosed based solely on histomorphology and needs to be confirmed with immunohistochemistry for prompt differentiation of this tumor from its mimickers (Figure 2.58, A–D).

(Poster No. 59)

Christina A. Hansen, MD ([email protected]); Sara E. Wobker, MD, MPH. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill.

Context: Immune checkpoint inhibitors (ICI) are increasingly used for treatment of renal cell carcinoma (RCC) and can result in complete eradication of tumor in the resection. Understanding the spectrum of histologic changes following treatment with ICI is paramount for accurate diagnosis and avoiding pitfalls in staging.

Design: We performed a retrospective search of our institutional database from January 2023 to March 2024 for RCC treated with neoadjuvant ICI. Clinicopathologic, gross, and microscopic features were reviewed. We present 3 illustrative cases of clear cell RCC treated with ICI to demonstrate the range of findings seen post-neoadjuvant ICI.

Results: The 3 selected cases showed extensive treatment effect following therapy with pembrolizumab and axitinib. Two cases were classified as ypT0 with no residual viable carcinoma identified. The third case was classified as ypT3a with focal residual carcinoma involving the renal sinus. Histologic features after ICI therapy included abundant fibrosis (Figure 2.59, A), myxoid change, macrophages (Figure 2.59, B), hemosiderin deposition, and siderophages (Figure 2.59, C). Macrophages represent a potential diagnostic pitfall by mimicking the clear cell cytology of RCC, which may necessitate confirmation with immunohistochemistry (IHC) for keratin, PAX-8, and CD68. Some ICI-treated specimens also showed extensive granulomatous reaction in lymph nodes mimicking sarcoidosis, which has been described following ICI treatment (Figure 2.59, D).

Conclusions: As neoadjuvant treatment is increasingly utilized for RCC, awareness of histologic features associated with ICI is critical for the pathologist. Best practices for the gross and microscopic examination have not been determined but should take into account the extensive treatment changes occurring in this setting.

(Poster No. 60)

Bashar Aldaraiseh, MD¹ ([email protected]); Minghao Zhong, MD, PhD¹; Haiying Zhan, MD, PhD²; Peter Humphrey, MD, PhD²; Paari Murugan, MD.^{1 1}Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis; ²Department of Pathology, Yale School of Medicine, New Haven, Connecticut.

Context: The study focuses on understanding the morphology spectrum of prostatic intraductal urothelial carcinoma (PID-UC), the counterpart of intraductal carcinoma of the prostate (IDC-P). The goal is to distinguish PID-UC from high-grade prostatic intraepithelial neoplasia (HGPIN) or atypical intraductal proliferation (AIP), particularly in biopsy specimens, where differentiation can be challenging.

Design: The collection of cases involving urothelial carcinoma in the prostate, focused on those featuring intraductal spreading of urothelial carcinoma. Morphology features of PID-UC were analyzed, including the examination of early and late stages of IDC-P. Utilization of immunohistochemistry stains such as PIN 4, GATA3, and NKX3.1 aided in the characterization of the cases.

Results: Review of 86 cystoprostatectomy cases with urothelial carcinoma involving the prostate revealed 52 cases of PID-UC. PID-UC demonstrated a wide morphologic spectrum, classified into 2 stages and 4 subtypes: early stage: pagetoid and pseudo-glandular/pseudo-HGPIN; late stage: classical and reinvasion from PID-UC. Late-stage PID-UC consistently showed association with urothelial carcinoma stromal invasion.

Conclusions: Due to clinical and biologic similarities between PID-UC and IDC-P, the study aimed to predict the potential morphology of IDC-P by studying the spectrum of PID-UC. Results suggested that early stages of IDC-P might not be reliably distinguishable from HGPIN or AIP. Late stages of PID-UC consistently exhibited stromal invasion. This study emphasized the importance of maintaining high-threshold morphologic criteria for IDC-P in biopsy specimens, indicating a need for careful differentiation between benign and malignant intraductal lesions (Figure 2.60, A-D).

(Poster No. 61)

Ebubekir Ucar, MD ([email protected]); Dmitriy Milkis, MD; Busra Uzun Ucar, MD; Oksana Yaskiv, MD. Department of Pathology, Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Northwell, Greenvale, New York.

Clear cell sarcoma (CCS) is an uncommon aggressive sarcoma showing melanocytic differentiation and a distinct molecular profile. It commonly manifests as a small, deep-seated tumor in young adults, predominantly originating in the lower extremities. It is very rare in the genitourinary system. We report the first known case of a primary CCS arising in the bladder. A 56-year-old woman presented with gross hematuria and imaging revealing a bladder mass. A transurethral biopsy was performed, and pathologic examination showed a bladder-centric tumor consisting of spindled pleomorphic cells with plump ovoid nuclei and prominent macronucleoli (Figure 2.61). Foci of necrosis and scattered mitoses were noted. Immunohistochemically, the tumor cells were positive for S-100, Melan-A, HMB-45, and SOX10, supporting melanocytic differentiation. Immunostains for AE1/3, Cam5.2, SMA, desmin, ALK-1, DOG-1, and CD117 were negative. The Ki-67 proliferative index was up to 10%. The initial morphologic and immunohistochemical profile suggested the diagnosis of malignant melanoma. However, further analysis by next-generation sequencing analysis revealed a EWSR1::ATF1 fusion, supporting the diagnosis of clear cell sarcoma, which has also been termed “malignant melanoma of soft parts.” CCS shows an immunohistochemical profile identical to that of melanoma. This case emphasizes the importance of considering CCS in the differential diagnosis of lesions with a melanocytic phenotype and the need for ancillary studies to target the EWSR1::ATF1 fusion. This is an important finding in differentiating CCS from melanoma with subsequent clinical and therapeutic implications.

(Poster No. 62)

Lukman Cheraghvandi, MD ([email protected]); DongHyang Kwon, MD; Joeffrey J. Chahine, PhD; Bhaskar V. Kallakury, MD. Department of Pathology, Georgetown-Medstar University Hospital, Washington, DC.

Context: Renal allograft BK virus nephritis and antibody-mediated rejection pose diagnostic challenges, often necessitating tissue biopsy and routine immunohistochemical (IHC) staining, such as BK polyoma virus immunostaining and complement C4d fragment immunostaining. The C4d IHC stain is believed to be specific for the C4d component of the complement system, typically reactive in peritubular capillaries in patients with antibody-mediated rejection.

Design: Formalin-fixed, paraffin-embedded (FFPE) samples from 4 post–renal allograft transplant patients with an established diagnosis of BK virus nephritis were analyzed. Patients with diffuse positive BKV IHC FFPE were compared with the same patients' FFPE blocks stained with C4d rabbit polyclonal antibody by Cell Marque and C4d monoclonal (720-MSM1-P1ABX) by Neo Biotechnologies. The IHC pattern was examined for cross-reactivity by 3 pathologists (not blinded).

Results: All polyclonal C4d-stained biopsies showed at least 1 or more tubules with strong nuclear cross-reactivity with BK virus–positive nuclear immunostaining in the same tubule. In contrast, monoclonal C4d stain did not show any cross-reactivity (Figure 2.62).

Conclusions: To our knowledge, this is the first report of such a cross-reactivity. Such cross-reactivity, while it may represent a manufacturing contamination, antigen mimicry, or an unreported complex interaction of complement fragments and virus-infected nucleoli, remains elusive but represents a potential pitfall for the use of IHC in different diagnostic settings.

(Poster No. 63)

Andrea Mladenovic, MD ([email protected]); Faisal Saeed, MD; Jatin S. Gandhi, MBBS, MD. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.

Context: Translocation-associated (TFE3/TFEB-altered) renal cell carcinomas (RCCs) are morphologically distinct tumors, which have a well-characterized and disease-defining underlying molecular alteration. Their incidence in the setting of end stage renal disease (ESRD) has been reported rarely. This study was undertaken to assess the incidence of TFE3/TFEB-altered RCCs in ESRD setting.

Design: By retrospective review, we searched our pathology database for translocation-associated RCC in ESRD during the past 12 years. We analyzed and documented the clinical, histopathologic, immunohistochemical, and molecular findings in these tumors.

Results: Out of 246 ESRD-associated RCCs, we found 4 cases of TFE3/TFEB-altered RCCs (4 of 246; 1.6%). The age range was from 36 to 74 years (median 51 years) with a female predominance (F:M = 3:1). Tumor size ranged from 1.6 to 4.7 cm (median 2.1 cm). Tumors in all 4 cases were confined to the kidney (pT1) and did not exhibit any necrosis or small vessel invasion. The tumors exhibited characteristic morphology (clear and papillary architecture in TFE3-overexpressed/TFE3-rearranged RCCs; and biphasic morphology with basement membrane–like material in TFEB-altered RCCs). On immunohistochemistry, tumors consistently expressed cathepsin-K (3 of 3) and Melan-A (3 of 3). Three cases were molecularly confirmed (fluorescence in situ hybridization and or Fusionplex). On median follow-up of 32 months (range 1.5 to 84 months), the patients were alive with no recurrence/metastasis (Table).

Conclusions: TFE3/TFEB-altered RCCs can be rarely encountered (incidence 1.6%) in ESRD. Morphological and immunohistochemical findings of translocation-associated RCC in ESRD replicate those found in non-ESRD. To the best of our knowledge, this study is the first to identify TFEB-altered RCCs in ESRD setting.

(Poster No. 64)

Heather Kirkham, DO ([email protected]); Maria Tretiakova, MD. Department of Pathology, University of Washington, Seattle.

Context: Identifying fumarate hydratase (FH)–deficient renal cell carcinoma (RCC) can be challenging due to the morphologic overlap with other renal cell carcinomas and false negativity of FH by immunohistochemistry (IHC). Aldo-ketoreductase family 1 member B10 (AKR1B10) has been proposed as a potential IHC screening marker for FH-deficient RCC.

Design: A total of 336 cases were evaluated for quantitative expression of FH and AKR1B10 by IHC on tissue microarrays that included 12 renal tumor types, urothelial carcinoma, and benign tissue. A 4-tier scoring system was used for quantifying staining intensity (0–3+) and then stratified into weak (0/1+) and strong (2/3+) expression.

Results: AKR1B10 was strongly expressed in all 6 cases of FH-deficient RCC (molecularly confirmed), with 1 case demonstrating retained FH expression (false negative). Of the renal tumors with distinct subtypes, FH IHC had a specificity of 97% while AKR1B10 specificity was 87%, and none of these cases demonstrated both loss of FH with strong expression of AKR1B10. AKR1B10 was negative across a wide spectrum of benign tissue types except for adrenal, kidney, and gastrointestinal tract.

Conclusions: We propose that when used in conjunction with FH IHC, AKR1B10 IHC may assist the pathologist in identifying tumors that are highly suspicious for FH deficiency in the setting of potential false negative FH results and when the tumor cannot otherwise be classified.

(Poster No. 65)

Liz Yang, MD ([email protected]); Tracy Dewenter, MD; Ritu Bhalla, MD. Department of Pathology, Louisiana State University Health Sciences Center, New Orleans.

Ewing sarcoma (ES) is an undifferentiated tumor of bone and soft tissue, observed in children and young adults. Although extraskeletal ES involves about 12% of patients, primary renal involvement is extremely rare. We present a challenging case of primary renal ES (RES) in a 36-year-old man manifesting with right flank pain and painless gross hematuria over a short 3-week period. A right renal mass (9.2 cm), identified on imaging, prompted an ultrasound-guided biopsy, demonstrating sheets of monomorphic neoplastic cells possessing hyperchromatic, mitotically active nuclei with high nucleocytoplasmic ratios and focal nuclear molding (Figure 2.65, A). Foci of necrosis were observed. Although neuroendocrine tumor was in the top differential, a broad panel of immunostains was performed, demonstrating positive diffuse synaptophysin (Figure 2.65, B), weak NSE, and negative TTF1, pan-cytokeratin, WT1, and desmin. Young age of presentation and nonconclusive stains prompted additional studies including CD99 and FLI1 stains (Figure 2.65, C, D; both diffusely positive) and fluorescence in situ hybridization analysis revealing 22q12, EWSR1 gene rearrangement. Diagnosis of RES was rendered. Primary RES is a rare lethal disease. Because of prognostic and therapeutic implications of RES, awareness and pertinent evaluation is critical. It uniformly manifests aggressive clinical behavior, but accurate diagnosis facilitates appropriate therapy with prolongation of survival. Although rare, 150 RES cases have been reported in the literature. Currently RES is not included in 2022 World Health Organization classification of renal tumors; its addition in the renal tumor classification will promote awareness and early consideration in differential diagnosis during evaluation of small-round-blue-cell renal neoplasms to prevent misdiagnosis and to ensure timely accurate treatment.

(Poster No. 66)

Charu Shastri, MD¹ ([email protected]); Jatinder Kumar, MD²; Sarabjeet K. Sudan, PhD¹; Guillermo A. Herrera, MD¹; Ajay P. Singh, PhD.¹ Departments of ¹Pathology and ²Urology, University of South Alabama, Mobile.

Context: Incidental prostate cancer (IPC) is a clinically inapparent tumor detected upon histopathology. Its incidence can vary from 1.4% to 13.3% in transurethral resection of prostate (TURP) specimens. Because the Gulf Shore serves a unique mix of patient population, we studied racial disparities of IPC at a tertiary care institution.

Design: A retrospective review was done on TURP specimens from January 2019 to December 2023. Data were collected on age, prostate-specific antigen (PSA), stage, grade group (GG), perineural invasion (PNI), and stromal inflammation and were subjected to descriptive statistical and correlation analyses.

Results: Of 248 TURP cases, IPC was detected in 42 (16.9%). White patients comprised 66.7% of cases, while African Americans (AA) were 33.3%. No cases were reported in other races. The incidence of IPC in White patients was 16.7%, and in AA patients, 21.9%. The overall incidence of IPC in smokers was 19.6%, in nonsmokers it was 14.9%. The percentage of tumor area varied (mean, 14.4%; IQR, 2.1%–17.0%) and correlated positively with Gleason score (r = 0.61, P < .001) and PSA (r = 0.46, P = .004). Mean PSA level in IPC was 2.8 ng/mL (IQR, 1.1–3.2 ng/mL). PNI was seen in 47.6% of IPC. Stromal inflammation was present in 73.8% of IPC versus 47.6% of BPH. Mean PSA in IPC with inflammation was 3.3 ng/mL and 1.7 ng/mL in IPC without inflammation (Table).

Conclusions: This study shows a higher incidence of IPC than reported previously, along with a higher incidence of T1b and PNI in GG1 tumors. Further, AA men had higher incidence of IPC in both smoker and nonsmoker categories, higher tumor grade, and increased PSA levels compared to White patients.

(Poster No. 67)

Kayli A. Roth, DO¹ ([email protected]); Ariel Kleydman, DO¹; Adina Paulk, MD⁴; Michael A. Pavio, MD²; Brandon Garren, MD³; Vladimir Mezhiritsky, DO³; Katie Louka, MD⁵; Margaux M. Canevari, DO, MS.¹ Departments of ¹Pathology, ²Radiology, and ³Urology, Walter Reed National Military Medical Center, Bethesda, Maryland; Departments of ⁴Genitourinary Pathology and ⁵Soft Tissue Pathology, the Joint Pathology Center, Silver Spring, Maryland.

Hemangioblastoma-like renal cell carcinoma (HB-RCC) is a rare, emerging diagnostic entity since 2015. We present the case of a woman in her thirties with a solid and cystic left kidney mass involving multiple renal veins, parasitic vessels, and a direct tumor-feeding hilar artery (Figure 2.67, A). Histology revealed clear cells scattered amongst delicate vessels (Figure 2.67, B), larger atypical-appearing cells (Figure 2.67, C), and areas of prominent vasculature and fibrosis. Inhibin (Figure 2.67, D), PAX8, S100, and CKAE1/3 were variably positive. Despite resemblance to hemangioblastoma, regions were more consistent with RCC, leading to a diagnosis of a pT1 HB-RCC. Next-generation sequencing revealed mutation in TSC2c.600_603delGATG, with variants of unknown significance in SDHC, PRKC1, EPHA3, FAT1, PIK3CG, and RECQL4. Our patient was offered genetics consultation and follow-up imaging. HB-RCC demonstrates low-grade RCC behavior with only 1 of the now 6 cases identified having renal vein involvement. Delineation from the more common clear cell RCC, given its well-characterized malignant potential, is crucial. The absence of VHL mutation with positive inhibin and S100 staining is more consistent with HB-RCC. The boundary between hemangioblastoma and HB-RCC is loosely defined, with the possibility of them representing a morphologic spectrum of 1 entity not being excluded. This case and 1 other have identified TSC2 alteration, which has not been identified in hemangioblastomas. Further studies for improved diagnostics and management are necessary.

Disclaimer: 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. 68)

Katrina Collins, MD ([email protected]); Joshua Kocemba, DO; Sheila E. Segura, MD; Tieying Hou, MD; Andres M. Acosta, MD; Varsha Nair, MD. Department of Pathology, Indiana University, Indianapolis.

Extrarenal renal cell carcinoma, a rare phenomenon lacking a discernible origin in the kidney, presents unique diagnostic challenges. Approximately 12 cases have been previously reported. Here, we describe a 54-year-old woman with primary biliary cirrhosis who, during liver screening, was incidentally found to have a soft tissue tumor measuring 2.8 cm in the suprarenal space of the right retroperitoneum, distinctly separate from the kidney and adrenal gland. Further investigations, including a heat-damaged red blood cell scan, ruled out ectopic splenic tissue. Attempts at a computed tomography–guided biopsy were deferred due to inability to identify a safe window, leading to the decision for resection. Gross examination revealed an encapsulated mass with a pink-tan to red-brown, lobulated, and hemorrhagic cut surface (Figure 2.68, A). No identifiable renal or adrenal tissue was identified. Histologic analysis demonstrated tumor cells with clear cytoplasm and a rich vascular network (Figure 2.68, B). Immunohistochemical stains performed showed the tumor cells were positive for PAX8, CA9, and CD10, while negative for CK7 and SF-1. The overall morphology and immunoprofile were consistent with clear cell renal cell carcinoma. Greater awareness of this unusual clinical scenario is warranted, as correct diagnosis may facilitate treatment with more specific targeted therapies available.

(Poster No. 69)

Susan Karki, MD¹ ([email protected]); Li Qiang, MD²; Dongbo Xu, PhD³; Bo Xu, MD.¹ Departments of ¹Pathology & Laboratory Medicine, ²Urologic Oncology and ³Urology, Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Context: Special AT-rich sequence-binding protein 2 (SATB2) is a transcriptional factor expressed in the lower gastrointestinal tract. Recently, positive staining of SATB2 has been reported in neuroendocrine carcinoma (NEC) of various organs. The aim of this study is to investigate SATB2 expression and its clinical significance in NEC of the urinary bladder and prostate.

Design: Twenty-eight NEC cases (13 bladder, 15 prostate) were retrieved from the institutional archive. Representative sections were immunostained with a monoclonal antibody against SATB2. Nuclear staining of tumor cells was evaluated by 2 pathologists. The percentage of positive tumor cells and staining intensity were semiquantitated. Kaplan-Meier method and log-rank test were used to compare overall survival between patients with SATB2 expression status.

Results: Among 13 bladder NEC, 62% (8 of 13) of cases displayed moderate to strong SATB2 expression, and 8% (1 of 13) of tumors showed weak expression. In prostatic NEC, 33% (5 of 15) of cases with moderate to strong SATB2 expression and 13% (2 of 15) of tumors with weak SATB2 expression were observed. Prostatic adenocarcinoma, bladder urothelial carcinoma, and adenocarcinoma were negative for SATB2. Positive expression of SATB2 in the prostatic NEC tumors was associated with a worse overall survival (median survival 21 versus 127 months, P < .001). However, this association was not found in patients with bladder NEC tumors (P = .61).

Conclusions: This is the first report of SATB2 expression in urinary tract NEC with high sensitivity and specificity by immunohistochemical study. Positive expression of SATB2 can be used as a prognostic marker for patients with prostatic NEC.

(Poster No. 70)

Daniel L. Shen, MD¹ ([email protected]); Jihee Choi, MD¹; Kirill E. Medvedev, PhD²; Daniel N. Costa, MD³; Liwei Jia, MD, PhD.¹ Departments of ¹Pathology, ²Biophysics, and ³Radiology, University of Texas Southwestern, Dallas.

Context: Patients with prostate cancer often exhibit multiple foci of tumors, with distinct morphologic and molecular features. Morphologic heterogeneity is commonly seen even within the same tumor focus. Deeper understanding of the extent and effect of intratumoral heterogeneity is needed.

Design: Hematoxylin-eosin slides were reviewed to select sufficient tumor tissue with spatially close but well-delineated low-grade (LG, Gleason pattern 3 only) and high-grade (HG) areas (Gleason pattern 4 only, with or without cribriform pattern) within the same tumor focus. Paired LG, HG, and normal tissue samples were obtained from all cases. Mutational analysis was performed using a 1425-gene next-generation sequencing platform. RNA expression profile across 1331 genes was also investigated.

Results: DNA sequencing revealed remarkable intertumoral genomic heterogeneity, without any recurrent gene mutations across 5 tumors. Intratumorally, LG and HG areas of 4 individual tumors demonstrated significant overlapping somatic gene alterations, including some known oncogenes (SPOP, CUL3, FOXA1, MSH2). One tumor showed low-input DNA quality without shared variants. Copy number alterations (CNAs) were mostly involved in chromosomes 2 (n = 4) and 8 (n = 4). Most of the CNAs were shared by the distinct LG and HG pairs in each case. Notable RNA expression alterations were detected in TAFA5, FASLG, DACH2, DUSP26, and FRMPD4, which were downregulated in HG areas as compared with LG areas.

Conclusions: Shared gene alterations and CNAs between LG and HG regions were detected. Five genes were downregulated in HG areas, some of which were reportedly involved in tumorigenesis or progression. These findings are preliminary and need further validation in larger cohorts (Table).

(Poster No. 71)

Abdelrahman Dabash, MD ([email protected]); Maher Ali, MD; Zoon Tariq, MD; Ali Alzeer, MD; Andrew Hall, MD; Mohadese Behtaj, MD; Elham Arbzadeh, MD. Department of Pathology, George Washington University, Washington, DC.

Sarcomatoid carcinoma is a rare primary tumor of the urinary bladder (0.1%–0.3% of cases) with a poor prognosis (median overall survival 14 months) compared to conventional urothelial carcinoma. We report the case of a 72-year-old man with a history of prostate cancer, paraplegia with suprapubic catheterization, diabetes, and cardiovascular disease, presenting with pain around his suprapubic catheter. Computed tomography imaging demonstrated a homogeneous mass surrounding the catheter and a biopsy revealed a spindle cell neoplasm compatible with sarcoma with fibroblastic/myofibroblastic differentiation. Subsequently, partial cystectomy with resection of the mass with pelvic lymph node dissection was performed. Macroscopically, an 18-cm tan exophytic ulcerated mass was identified within the bladder, abutting the soft tissue and bladder wall margin. Microscopic examination revealed a highly proliferative tumor with mesenchymal and epithelial (squamous) differentiation with palisading necrosis. The immunohistochemistry revealed the mesenchymal component to be patchy positive for smooth muscle actin exclusively (negative for cytokeratins, melanocytic and neuroendocrine markers, CD34, desmin, NKX3.1, and beta-catenin). Conversely, the epithelial component demonstrated positive staining for cytokeratins. The final histopathologic diagnosis rendered was pT4b sarcomatoid carcinoma (high-grade sarcomatoid component 90%; well-differentiated squamous cell carcinoma 10%), involving bladder, dermis, and invading the anterior pelvic wall. All lymph nodes were negative for sarcomatoid carcinoma; however, 4 lymph nodes were positive for concurrent metastatic prostate carcinoma. Within a month of diagnosis, the patient expired due to sepsis related to hydronephrosis. No postoperative chemotherapy or radiotherapy was administered. Early detection and establishing histopathologic diagnosis with tumor staging can be used to guide management.

(Poster No. 72)

Faryal Shoaib, MD, MBBS ([email protected]); Rusella Mirza, MD, PhD. Department of Pathology, Louisiana State University, Shreveport.

Renal cell carcinoma (RCC) is a rare renal manifestation in tuberous sclerosis patients, with an estimated incidence of 2%–4%. RCC with tuberous sclerosis complex ([TSC]/mammalian target of rapamycin [MTOR] pathway) genomic alterations have been classically described in hereditary TSC syndrome involving germline mutations, with heterogenous histologic appearance. Most identified as clear cell RCCs, others include papillary, chromophobe, unclassified RCC, and benign renal oncocytoma. Recently, a similar morphologic spectrum has been recognized in emerging entities characterized by somatic mutations in the TSC1/2 and MTOR in patients who do not suffer from TSC. TSC1 mutations are rare and reported in only 0.0%–3.1% of RCC samples. Herein, we present the case of a 49-year-old woman who presented with flank pain and gross hematuria. Imaging revealed a 3.5-cm right endophytic renal mass. Following radical nephrectomy, histologic examination revealed a tumor composed of tubular papillary architecture with thick fibromuscular transecting bands. Tumor cells demonstrated clear voluminous cytoplasm, prominent cell membranes, and low nuclear grade. Immunohistochemistry revealed positivity with CK7 (patchy), CAIX (both cup shape and box type), and CD10 (patchy). Molecular testing reported TSC1 (c2145 del and c.663 + 1G>A) inactivating mutation. The tumor mutation burden was low. The frameshift alteration reported here is expected to effectively truncate the hamartin protein within C-terminal domain reported to be important for tuberin interaction. TSC1-mutated RCC has histologic overlapping with TCEB-1–mutated RCC. Molecular testing is required for the correct diagnosis. The mutation site noted in our case has not been reported before (Figure 2.72, A–D).

(Poster No. 73)

Manasa Morisetti, MD¹ ([email protected]); Angela C DiPoto-Brahmbhatt, MD²; Raynor Morant, MD¹; Catherine Chaudoir, MD²; Anthony Tanner, PA²; Michael Constantinescu, MD²; Yunshin Albert Yeh, MD.^{2 1}Department of Anatomic and Clinical Pathology, Louisiana State University Health, Shreveport; ²Department of Pathology and Laboratory Medicine Service, Overton Brooks VA Medical Center, Shreveport, Louisiana.