The following abstracts and case studies were accepted for the CAP21 Virtual Abstract Program. Shown before each poster session are the subject areas for that session.
POSTER SESSION 1: SUNDAY SEPTEMBER 26, 2021
Gastrointestinal and Liver Pathology: Kidney and Genitourinary Pathology
Disease Anatomic Extent as Part of a Risk Stratification Model That Predicts Survival in Gallbladder Adenocarcinoma
(Poster No. 1)
Haiyan Lu, MD, PhD1 (firstname.lastname@example.org); Breanna Perlmutter, MD2; Robert Naples, MD2; Toms Augustin, MD2; Daniela Allende, MD.1 Departments of 1Pathology and 2General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio.
Context: Gallbladder adenocarcinoma has a poor overall survival (<5% at 5 years). We aim to design a risk-stratification model with novel and traditional features.
Design: We retrospectively identified 57 gallbladder adenocarcinoma resection specimens from January 2009 through December 2017 at Cleveland Clinic Foundation. Clinical data were gathered and histologic features were obtained. Involvement by adenocarcinoma was defined as localized when a single anatomic region; remaining cases were considered diffuse. Kaplan-Meier analysis was used to estimate overall survival (OS) by using XLSTAT. Patients were risk stratified by using 2 prediction models, and receiver operating characteristic curve and area under the curve (AUC) were used to compare the models. P < .05 was considered statistically significant.
Results: Of the 57 cases, 25 patients (43.9%) had localized disease at resection, whereas the rest had diffuse involvement of the gallbladder. The median follow-up was 29.7 months (range, 3.5–122 months). Twenty-six patients (45.6%) were dead from disease, with a median survival of 22.9 months (range, 3.8–61.5 months). Significant predictors of worse OS included diffuse involvement (P < .001), advanced stage (P = .02), and moderate to poor differentiation (P = .02). Lymphovascular invasion (LVI) showed a trend toward significance (P = .08). The risk-stratification model 1 (localized/diffuse extend of tumor, T stage, and tumor grade) provided better prediction for outcome (AUC = 0.721, P = .001) than model 2 (model 1 plus LVI) (AUC = 0.685, P = .009) (Table).
Conclusions: Diffuse involvement, advanced stage, and moderate to poor differentiation are independent prognostic factors of worse outcome in gallbladder adenocarcinoma. Our risk-stratification model (disease extent, T stage, and tumor grade) provides substantial prediction on outcome.
The Impact of Pre-diagnostic Diabetic Status on the Survival of Patients With Pancreatic Ductal Adenocarcinoma
(Poster No. 2)
Haiyan Lu, MD, PhD (email@example.com); Daniela Allende, MD; Xuefeng Zhang, MD, PhD. Department of Pathology, Cleveland Clinic Foundation, Cleveland, Ohio.
Context: Diabetes mellitus (DM) is a risk factor for pancreatic cancer, but its impact on postoperative outcomes remains controversial. It is unknown if prediagnostic diabetic status affects patient survival in tumors with any specific pathologic features.
Design: We retrospectively identified 507 patients with pancreatic ductal adenocarcinoma (PDAC) between January 2008 and December 2018 at Cleveland Clinic Foundation. Clinical data and pathologic features were compared between patients with and without DM prior to the diagnosis. Statistical analysis was performed using IBM SPSS Statistics 19. Overall survival was compared in DM and non-DM groups using Kaplan-Meier analysis in XLSTAT. P < .05 was statistically significant.
Results: In the cohort, 187 patients were diagnosed with DM prediagnostically and 320 patients stayed nondiabetic status prior to the diagnosis. Patients with DM tended to demonstrate worse overall survival (P = .06). In male patients, DM tended to negatively affect patients' overall survival (P = .06). Among the pathologic features, DM status was significantly related to a worse survival in patients with poorly differentiated carcinoma (P = .03), lymphovascular invasion (P = .02), or lymph node metastasis (P = .045). In patients with pT1 tumors defined by AJCC 7th or AJCC 8th edition, DM was significantly associated with a worse survival (AJCC 7th, P < .001; AJCC 8th, P = .04). In patients with AJCC 8th T2 tumor, there was a tendency that DM negatively affected patients' survival rate (P = .06) (Table).
Conclusions: Prediagnostic DM status is associated with worse survival in PDAC patients with poorly differentiated carcinoma, lymphovascular invasion, or lymph node metastasis. DM tends to negatively affect survival rate in male patients and in patients with pT1 and pT2 tumors (AJCC 8th).
Clinicopathological Characteristics and Associations of Traditional Serrated Adenoma
(Poster No. 3)
Subramanya Sakaleshpura Mallikarjunappa, MD (firstname.lastname@example.org); Lin Cheng, MD, PhD; Shriram Jakate, MD. Department of Pathology, Rush University Medical Center, Chicago, Illinois.
Context: Traditional serrated adenomas (TSAs) are the rarest of all the serrated polyps with distinctive endoscopic (“pine cone–like”) and histologic features. However, TSAs are underdiagnosed and the assessment of dysplasia in TSA is disputed. We retrospectively evaluated 62 TSAs to assess their clinicopathologic characteristics and associations.
Design: A review of our database from 2014 through 2020 found 62 patients (32 men, 30 women, ages 34–84 years) diagnosed with TSA. Their clinical presentation, endoscopic/morphologic findings, sizes, multiplicity, distribution, associated other polyps, surveillance frequency, degree of dysplasia, and potential progression to invasive carcinoma were reviewed.
Results: Most cases (59 of 62) were incidentally detected on screening colonoscopies. Polyps were 3–40 mm (mean, 12 mm). TSAs >10 mm were cold or hot snared and showed characteristic endoscopic pine cone appearance. Fifteen patients (24%) had solitary TSA and the rest showed other conventional adenomas and/or SSAs (76%). The majority (85%) of TSAs were in the distal colon: sigmoid (21), rectosigmoid (4), and rectum (28). All TSAs showed typical histologic features including ectopic crypt formation, slitlike serrations, elongated penicillate nuclei, and eosinophilic cytoplasm. Only 1 of 62 cases (1.6%) showed high-grade dysplasia.
Conclusions: TSAs are incidentally detected on screening colonoscopy and are often associated with other conventional polyps than solitary TSA. Most TSAs are located in the sigmoid colon and rectum. High-grade dysplasia appears to be quite rare, even in large TSAs. Multicenter long-term studies are needed to evaluate the true risk of colorectal carcinoma in these unique polyps.
Comparative Analysis of Intra-cholecystic “Pyloric Gland Adenoma” With Luminal Counterparts
(Poster No. 4)
Miao Cui, MD, MS1 (Miao.Cui@mountsinai.org); Isaak Heon, DO2; Binny Khandakar, MD3; Daniel Chung, MD4; Jihong Sun, MD.2 1Department of Pathology, St Luke's-Roosevelt Hospital Center, Icahn School of Medicine at Mount Sinai, New York, New York; 2Department of Pathology, Mount Sinai West, New York, New York; 3Department of Pathology, Mount Sinai St. Luke's Roosevelt Hospital, New York, New York; 4Department of Pathology, Mount Sinai West, Icahn School of Medicine, New York, New York.
Context: Pyloric gland adenoma (PGA) is a rare neoplasm of the gastric mucosa, involved in the gallbladder (GB), main pancreatic duct, and duodenum. Intracholecystic lesions of >1 cm are identified as intracholecystic papillary-tubular neoplasms (ICPNs), and lesions <1 cm are referred to pyloric gland hyperplasia/metaplasia. Our study aims to compare groups of PGA/metaplasia (<1 cm) in the GB and the luminal counterpart.
Design: A retrospective study included cases of PGA or metaplasia at Mount Sinai West, New York, from January 1, 2000, to June 30, 2020. PGA from GB, >1 cm, or ICPN were excluded. Clinicopathologic parameters were analyzed, including age, gender, location of lesion, dysplasia, and the number of lesions (1/>1).
Results: Forty-one cases (Table) were included. Among them, 14 cases were from both GB and duodenum, and 13 were from the stomach only. The mean age of presentation was 73 years. The mean age of GB, stomach, and duodenum groups was 59, 85, and 70 years, respectively. Chronic cholecystitis was present in 85% of cases. All cases involving the GB were >0.3 cm, with 6 cases >0.5 cm and another 4 cases 0.3–0.5 cm.
Conclusions: According to our study, the terminology of “PGA” in the GB could aptly describe the lesions that are purely composed of pyloric glands in the GB, which may represent a true benign tumor rather than an inflammatory metaplastic process. “Adenoma” could be applied for mixed lesions, with overlapping morphology composed of an admixture of pancreaticobiliary and pyloric type, based on size or molecular signature.
Gastric Amyloidosis Presenting as Gastrointestinal Bleeding: Case Report and Concise Review
(Poster No. 5)
Catherine E. Turner, MS (email@example.com); Deepthi Rao, MD; Feng Yin, MD. Department of Pathology and Anatomic Sciences, University of Missouri–Columbia.
Amyloidosis defines a group of disorders characterized by extracellular misfolded protein deposition, such as AL, AA, ATTR, and Aβ2M proteins. Clinical manifestations depend on the biochemical composition and site of deposition. Common sites include kidney, heart, and liver, but gastrointestinal amyloidosis is rare. The overall incidence of primary amyloidosis is 9 new cases per million persons, and involvement of gastrointestinal tract is exceptionally rare, with only an incidence of less than 1 per million. A 62-year-old man with past medical history of diverticulitis and colon resection presented to his physician with blood per rectum, unintentional weight loss, nausea, and vomiting for 1 month. He underwent esophagogastroduodenoscopy and colonoscopy. Biopsies of stomach and colon showed waxy, pale eosinophilic extracellular aggregates on microscopy (Figure 1.5, A), suggestive of amyloidosis, confirmed by Congo red staining (Figure 1.5, B) with apple-green birefringence in polarized light (Figure 1.5, C). These amyloid fibrils had a nonbranching, antiparallel twisted, β-pleated sheet configuration. Additional organ involvement was not found with imaging. This patient had no previous medical history of chronic inflammation, hematologic malignancy, renal disease, or family history, and the absence of risk factors suggested primary amyloidosis. The patient's κ:λ ratio and serum electrophoresis were unremarkable, proving primary amyloidosis. To our knowledge, this was the first ever reported case of gastric amyloidosis at University Hospital (Columbia, Missouri). Recognizing amyloidosis in a differential diagnosis is important, as early recognition of this disorder could prevent further complications for the patient, shorten time to diagnosis, and explore management options in an efficient manner.
Disparity Between Endoscopic Findings and Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation
(Poster No. 6)
Alexander Reese, DO1 (firstname.lastname@example.org); Nushani Jaryatne, MD1; Kun Jiang, MD, PhD.2 1Department of Pathology, University of South Florida, Tampa; 2Department of Pathology, Moffitt Cancer Center, Tampa, Florida.
Context: Gastrointestinal graft-versus-host disease (GVHD) poses a significant clinical and pathologic challenge following allogeneic hematopoietic transplantation. GVHD diagnosis requires clinical, laboratory, and histopathologic confirmation. Endoscopy has been fundamental in ensuring accurate diagnoses in numerous entities; however, an established correlation between endoscopic findings and GVHD remains undetermined.
Design: The endoscopic findings of 185 histopathologically confirmed GVHD and 11 viral enterocolitis cases were reviewed retrospectively.
Results: Among the 185 GVHD cases, 146 were grade 1, 26 were grade 2, 8 were grade 3, and 5 were grade 4. In the grade 1 cases, endoscopy was “normal” in 111 (76%) and abnormal in 35 (24%). Among the grade 2 cases, 21 were endoscopically “normal” (81%) whereas 5 appeared focally abnormal (19%). In the grade 3 cases, 6 (75%) were still considered “normal” and 2 abnormal (25%). Lastly, in the grade 4 cases a “normal” endoscopy was documented for 3 (60%), whereas an abnormal endoscopy was confirmed in only 2 (40%). Overall, endoscopic examination was “normal” in 141 of 185 GVHD cases (76%) and abnormal in only 44 (24%). Notably, in all 11 viral enterocolitis cases (7 cytomegalovirus and 4 adenovirus cases in which GVHD was clinically suspected), endoscopy was “normal.”
Conclusions: To summarize, neither a satisfactory endoscopic sensitivity nor specificity was observed in the 185 GVHD cases; therefore, no correlation can be established between endoscopic findings and histopathologic GVHD. Furthermore, endoscopic abnormities are not only restricted to GVHD, but are also seen with infection, drug, and chemical-related injuries. Astute histopathologic inspection and ancillary tests remain the gold standard for discerning GVHD from its various mimickers.
Langerhans Cell Histiocytosis in Lower Gastrointestinal Tract Polyps With BRAF Testing
(Poster No. 7)
Eric Ollila, MD1 (email@example.com); Abrar Alghamdi, MD1; Sameer Al Diffalha, MD1; Samuel Borak, MD.2 1Department of Pathology, University of Alabama at Birmingham; 2Department of Pathology, University of Alabama at Birmingham, Montgomery.
Langerhans cell histiocytosis (LCH) is a group of idiopathic disorders characterized by an abnormal proliferation of dendritic mononuclear cells that mostly involves the skin and bones. Involvement of the gastrointestinal tract by LCH is exceedingly rare, and few cases have been reported. Here, we present 2 cases of LCH with gastrointestinal involvement and BRAF testing. The first case involves a 51-year-old man who presented with intermittent abdominal pain. Five polyps were found on colonoscopy. Histopathologic examination revealed an infiltrate in the lamina propria consisting of small to intermediatesized cells with variably irregular and focally reniform nuclei, with occasional nuclear grooves and mild amount of cytoplasm (Figure 1.7, A and B). Occasional mitotic figures and scattered eosinophils were present. These cells were immunohistochemically reactive with CD1a (Figure 1.7, C), S-100 (Figure 1.7, D), and CD43. BRAF testing was positive for the V600E mutation. The second case involves a 76-year-old woman who presented with a history of anemia and multiple episodes of C difficile colitis that resulted in gastrointestinal distress and weight loss. Two polyps were found on colonoscopy. Histopathologic examination revealed active inflammation involving surface epithelium and underlying crypts surrounded by prominent histocytes. These cells were reactive with S-100 and CD1a. BRAF testing results were negative. Although involvement of the gastrointestinal tract by LCH is rare, it should be considered in the differential diagnosis when a histiocytic proliferation is present. To our knowledge, these are the first cases of lower gastrointestinal tract involvement in polyps by LCH with reported BRAF testing, which may prove helpful in diagnosis and treatment.
Expression of Enhancer of Zeste Homolog 2 (EZH2) Protein and Its Association With Intracellular Signaling Molecules MYC, P-MAPK, and P-STAT3 in Colorectal Cancer
(Poster No. 8)
Jiani N. Chai, MD, PhD1 (firstname.lastname@example.org); Linlin Yang, MD, PhD2; Shaomin Hu, MD, PhD3; Yanhua Wang, MD, PhD1; Qiang Liu, MD1; Xuejun Tian, MD, PhD.1 1Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York; 2Department of Pathology, The MetroHealth System, Cleveland, Ohio; 3Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio.
Context: EZH2 is a histone methyltransferase associated with a poorer prognosis in several cancers. The regulation of EZH2 in colorectal cancer is unknown. Here we investigated EZH2 expression in colorectal cancer and its association with MYC, p-MAPK, and p-STAT3, potential regulators of EZH2.
Design: One hundred fourteen colorectal cancer cases were collected. Immunohistochemical staining for EZH2, MYC, p-MAPK, p-STAT3, and Ki-67 was performed. EZH2 overexpression was defined if ≥60% neoplastic cells exhibited moderate to strong staining. MYC was positive if ≥40% neoplastic cells displayed moderate to strong staining. Statistical analysis was performed using Fisher exact test and Pearson correlation coefficient by Graphpad Prism (San Diego, California).
Results: Eighty-six of 108 cases (79.6%) overexpressed EZH2. EZH2-overexpressed cases were more abundant in the moderate, moderate to poor/poor groups as compared with the well-differentiated tumor (P < .05) (Figure 1.8, A). Furthermore, EZH2 expression correlated positively with Ki-67 (P < .05) (Figure 1.8, B). We then investigated EZH2 expression in association with MYC, p-MAPK, and p-STAT3. Sixty-three of 103 cases (61.2%) expressed MYC, whereas very few expressed p-MAPK (2 of 104) or p-STAT3 (1 of 106). Among EZH2-overexpressed cases, 59 of 82 (72%) coexpressed MYC. EZH2 expression correlated positively with MYC (P < .001) (Figure 1.8, C). MYC also showed a positive correlation with Ki-67 (P < .01) (Figure 1.8, D).
Conclusions: EZH2 overexpression is associated with more aggressive behavior in colorectal cancer, as indicated by the correlation with Ki-67 and tumor grade. Furthermore, MYC-related signaling, not p-MAPK or p-STAT3, might be involved in EZH2 regulation and correlated with tumor progression. Therefore, EZH2 and MYC could serve as potential prognostic and therapeutic targets for colorectal cancer.
Racial and Ethnic Disparities in Molecular Abnormalities and Pathological Findings of Colorectal Carcinoma
(Poster No. 9)
Maria F. Gonzalez, MD1 (email@example.com); Allison L. Kerper, MD.2 Departments of 1Pathology and 2Medicine, College of Medicine, University of Illinois at Chicago.
Context: Although the national incidence of colorectal cancer (CRC) has decreased in recent years, it remains the fourth most common cancer in the United States. The objective of this study is to identify if there is a statistically significant difference in the pathologic and molecular findings of CRC by race and ethnicity at our institution.
Design: Patients with CRC resected from 2016 to 2019 were divided into 4 groups: white/non-Hispanic or Latino (N-HL), black/N-HL, Asian/N-HL, and other/HL. Risk factors, tumor location, grade, stage, size, invasion, and mutations were compared.
Results: A total of 138 patients were included. A higher percentage of the tumors were located in the rectum in Asians/N-HL and others/HLs. In blacks/N-HL and whites/N-HL, CRCs were located in the right and left colon, respectively. CRC was resected earlier in whites/N-HL (60.0) and blacks/N-HL (61.7). Rectal carcinomas were more symptomatic and presented earlier (50s–60s) than colonic carcinomas (60s–70s), especially in whites/N-HL. In contrast, blacks/N-HL and Asians/NH-L showed a later peak in age for rectal cancer (70–79) than colon cancer (50–59). Most cases were diagnosed at early stages in blacks/N-HL and other/HL. Twenty-two patients (15.9%) had young-onset CRC. Most of the CRCs were microsatellite stable. Microsatellite-instable-high CRC (14.5%) presented as advanced well/moderately differentiated rectal carcinomas in blacks/NHL (Table).
Conclusions: Our study demonstrates that the pathologic parameters for the examination of CRC described by the College of American Pathologists do not display statistically significant differences among races/ethnicities. The high percentage of CRC in the rectum in white/NHL, Asian/N-HL, and other/HL has important implications for CRC screening via rectosigmoidoscopy.
Regional Differences in Clinical Management of Patients With a Diagnosis of Chronic Active or Inactive Gastritis and Negative HelicobacterImmunohistochemical Stain
(Poster No. 10)
Xiaobang Hu, MD, PhD1 (firstname.lastname@example.org); Elena Lucas, MD1; Amarpreet Bhalla, MD2; Maria Westerhoff, MD3; ILKe Nalbantoglu, MD4; Nicole Panarelli, MD2; Jerome Cheng, MD3; Suntrea Hammer, MD1; Purva Gopal, MD, MS.1 1Department of Pathology, UT Southwestern Medical Center, Dallas, Texas; 2Department of Pathology, Albert Einstein/Montefiore Medical Center, Bronx, New York; 3Department of Pathology, University of Michigan, Ann Arbor; 4Department of Pathology, Yale School of Medicine, New Haven, Connecticut.
Context: A preliminary study by our group suggested for patients with biopsy diagnosis of active or inactive chronic gastritis (CG) with a pattern that is highly suggestive of Helicobacter pylori (HP) infection but negative HP immunohistochemistry (IHC), a comment raising the possibility of HP infection can change the clinical management.
Design: We conducted a retrospective comparison study of patients from an academic center in the South (group 1) to 3 centers in the Midwest/Northeast (group 2), all with a diagnosis of CG with negative HP IHC.
Results: A total of 19.2% of group 1 patients and 56.8% of group 2 patients were on a nonsteroidal anti-inflammatory drug (NSAID) prior to biopsy (P < .01), whereas 36.4% of group 1 patients and 63.9% of group 2 patients were on a proton pump inhibitor (PPI) prior to biopsy (P < .01). Group 1 patients more frequently had HP history (47.4% versus 21.6%, P < .01). After the diagnosis, 48.7% of group 1 and 11.1% of group 2 received treatment (P < .001). Of those treated, 14.1% and 6.7% received HP treatment, respectively (triple or quadruple therapy; P > .05). In cases with a comment in the pathology report raising the possibility of HP, patients from the South received HP treatment more often as compared with cases without a comment (25.6% versus 2.6%, P < .01). This trend is similar for the Midwest/Northeast institutions (14.3% versus 0%, P = .06) (Table).
Conclusions: Our data suggest a regional difference in patient management after diagnosis of CG with negative HP IHC in that patients from the South were more frequently treated. A comment in the pathology report describing HP-pattern gastritis despite negative HP IHC increased HP treatment, especially in the South.
Colonic Mixed Neuroendocrine Non-neuroendocrine Neoplasm: A Rare Malignant Neoplasm
(Poster No. 11)
Khairya Fatouh, MD (email@example.com); Sulmaz Zahedi, MHSs; Basim Al-Khafaji, MD. Department of Pathology, Ascension St. John and Medical Center, Detroit, Michigan.
Colonic mixed neuroendocrine-nonneuroendocrine neoplasms are a rare entity. The term has evolved with the World Health Organization adopting the current nomenclature in 2017. We present a case of a 59-year-old woman who presented with acute abdomen and a perforated viscus. Explorative laparotomy revealed 2 right colon masses with tumor seeding of multiple peritoneal sites. Histologic evaluation of the tumor identified 2 components, one forming 40%, consisting of sheets of poorly differentiated small hyperchromatic cells with conspicuous nuclei, admixed with a conventional colonic adenocarcinoma; both involved the full thickness of bowel wall and invaded into peri-colonic fibroadipose tissue. Strong positive staining of immunohistochemical markers synaptophysin, chromogranin, CD56, cytokeratin AE1/AE3, cytokeratin 20, and with focal positivity for CDX2 and negativity for TTF-1, was identified in the neuroendocrine component, whereas the conventional adenocarcinoma was positive only for Ber-EP4, CDX2, cytokeratin AE1/AE3, and cytokeratin 20. Additionally, Ki-67 showed 100% positive staining within the entire tumor. Subsequently, the patient developed seizures associated with brain metastasis and expired 2 months later. Mixed neuroendocrine-nonneuroendocrine neoplasms with a poorly differentiated neuroendocrine component are associated with an extremely poor prognosis with an average of 4.5-month survival in patients with stage 4. Mixed neuroendocrine-nonneuroendocrine neoplasm is a rare entity that requires diligent histologic evaluation to identify the neuroendocrine component histologically and immunohistochemically. Although the current criteria suggest a minimal 30% portion of each component, further clinical and histopathologic studies are required to validate these measures and establish appropriate therapy regiments.
Validation of the Current Histology Grading System in Appendiceal Goblet Cell Adenocarcinomas With Advanced Pathologic Stage
(Poster No. 12)
Irene Y. Chen, MD (firstname.lastname@example.org); Xiaoqing Liu, MD, PhD; Sierra Kovar, MS, CT(ASCP); Xiaoyan Liao, MD, PhD. Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York.
Context: Appendiceal goblet cell adenocarcinoma (GCA) is a unique tumor composed of gobletlike cells. The 2019 World Health Organization criteria recommend a 3-tiered grading system based on proportion of low-grade and high-grade patterns. We aim to validate this grading schema with correlation to tumor stage, immunohistochemistry, and patient survival.
Design: All cases of GCA staged pT3 and above were retrieved (2005–2020). P values <.05 were considered significant.
Results: Our cohort consisted of 13 males and 12 females with median age of 62.5 years. Pathologically, 13 were pT3 and 12 were pT4, with 9 cases (36%) demonstrating lymph node and/or distant metastasis. Clinically, 15 (60%) were stage II, 4 (16%) stage III, and 6 (24%) stage IV. Using the 3-tier grading system, 10 (40%) were G1, 7 (28%) G2, and 8 (32%) G3. Immunohistochemically, all cases were mismatch repair proficient. Loss of nuclear SMAD4 expression and abnormal p53 expression occurred at equally low frequencies (n = 3, 12% each). Seven cases (28%) showed nuclear β-catenin positivity. The Ki-67 index (range, 1%–80%) were tiered into low (<5%, n = 8), intermediate (5%–20%, n = 10), and high (>20%, n = 7). Statistically, the histologic grade correlated with clinical stage (P < .001), but not with sex, age, Ki-67 index, or nuclear SMAD4/p53/β-catenin abnormalities. The histologic grade, T stage, lymph, node and distant metastasis were associated with reduced survival (P < .05).
Conclusions: The current grading system for GCA correlated well with clinical stage and disease outcomes. A small percentage of GCA demonstrated nuclear SMAD4, p53, or β-catenin abnormalities, which did not correlate significantly with histologic grade, tumor stage, or patient survival.
Primary Pancreatic Signet Ring Cell Carcinoma in Patient With Lynch Syndrome
(Poster No. 13)
Abdullah Osme, MD (email@example.com); Wei Xin, MD, PhD. Department of Pathology, University Hospitals Cleveland Medical Center/Case Western University, Cleveland, Ohio.
Primary pancreatic signet ring cell carcinoma (PPSRCC) is a rare histologic variant of pancreatic ductal adenocarcinoma. We report a case of PPSRCC in a 52-year-old woman with a confirmed personal history of hereditary nonpolyposis colorectal cancer with MSH2 germline mutation. The patient had abdominal pain, and computed tomography showed a pancreatic body mass. Ultrasound-guided fine-needle aspiration (FNA) biopsy of the pancreas was nonconclusive. Eventually, the patient underwent distal pancreatosplenectomy. Gross examination revealed a tan-white, poorly demarcated and unencapsulated mass located at the body, measuring 1.9 × 1.4 × 1.0 cm, and obstructing the pancreatic duct. Hematoxylin-eosin sections showed a polypoid mass occupying the pancreatic duct consisting of a predominant signet ring cell carcinoma. There was also some well-differentiated ductal adenocarcinoma component (20%). Because of the tumor obstruction of the pancreatic duct, distal pancreas showed extensive chronic pancreatitis. Immunostains showed the loss of MSH2 and MSH6 in the signet ring cell carcinoma with proper positive background staining. The patient did not have signet ring cell carcinoma in other parts of the gastrointestinal (GI) tract. Therefore, this is a primary signet ring cell carcinoma in a Lynch syndrome patient. The most common signet ring carcinoma site is the stomach and occasionally can be found in other parts of the GI tract, but pancreas is a rare place for the primary signet ring cell carcinoma. Lynch syndrome tends to be associated with poorly differentiated carcinoma, including signet ring cell carcinoma in colon, but has not been reported in pancreas. It imposes a diagnostic challenge for FNA cytology and frozen section if not aware of this rare variant.
Appendiceal Mucinous Neoplasia: Reflection on 20 Years of Experience at a Single Institution
(Poster No. 14)
Yan Wang, MD (firstname.lastname@example.org); Ali Shahabi, MD; Agnes Loeffler, MD, PhD. Department of Pathology, Metrohealth Medical Center, Cleveland, Ohio.
Context: During the past 3 decades, multiple diagnostic terms have been applied to the entity we now call low-grade or high-grade appendiceal mucinous neoplasm (LAMN/HAMN). We undertook this study to understand the rate of adoption of World Health Organization guidelines regarding the reporting of this entity in a community practice setting.
Design: We conducted a retrospective study of all the neoplastic appendiceal cases in a county hospital in Cleveland from 1999 to 2019. The cases were reviewed by 3 pathologists, including 1 gastrointestinal pathologist. In the cases of appendiceal mucinous neoplasm, we compared the terminology used at the time of diagnosis with contemporary nomenclature and grading.
Results: A total of 32 patients with appendiceal mucinous neoplasia were identified (LAMN [n = 30] and HAMN [n = 2]), 13 of these since 2010. Twenty-six of the cases (81.2%) would now receive another name, and of these, there were diagnostic discrepancies in 5 cases (19.2%) (Table). Anachronistic terminology continued to be used at least until 2019 (7 of 13 cases; 53.8%). None of these changes would have had an impact on the further management or clinical follow-up of the patients.
Conclusions: Despite frequent updates and consensus guidelines for pathologic assessment of appendiceal mucinous lesions, in the past 2 decades there has been considerable confusion around how these entities should be named and graded. Our findings suggest that pathologists should consider a second opinion in these unusual cases, especially since a history of terminologic abundance has created inconsistency in the diagnostic approach to the entity.
Cokeromyces recurvatus Incidentally Found in a Patient With Gastric Outlet Obstruction
(Poster No. 15)
Bitania Wondimu, MD (email@example.com); Benjamin Bradley, MD, PhD; Joshua Lieberman, MD, PhD; Seth Cohen, MD, MSc; Lynda Bui, MLS; Deepti Reddi, MD. Department of Pathology, University of Washington Medical Center, Seattle.
Isolation of Cokeromyces recurvatus, a dimorphic fungus in Zygomycete family, is equivocal because it is uncertain whether the organism is a pathogen or a tissue contaminant/colonizer. We report a case of C recurvatus present in a circumferential duodenal lesion. The patient is a 64-year-old man with medical history notable only for heavy consumption of edible marijuana, admitted with a 3-week history of left upper quadrant abdominal pain. Computerized tomography scan identified duodenitis with significant gastric outlet obstruction, confirmed by a partially obstructing nonbleeding duodenal ulcer on upper endoscopy (Figure 1.15, A). The histology showed variably sized spherical structures with bubbly internal contents and no nuclei, reproductive tracts, or alimentary tracts. Small, clustered spherules representing putative endospores were observed within the larger structures and in the exudate (Figure 1.15, B). Based on the histology, the differential diagnosis included Coccidioides, Emmonsia, or Chrysosporium species. Additionally, gastric biopsies revealed concurrent Helicobacter pylori gastritis. The fungus was identified as C recurvatus by broad-range fungal polymerase chain reaction performed on formalin-fixed, paraffin-embedded biopsy tissue, as well as morphology, DNA sequencing of the isolate, and cultures (Figure 1.15, C and D). The fungus was susceptible to a wide variety of antifungals; however, in the context of the H pylori infection, the patient was treated with amoxicillin and clarithromycin with improvement in his symptoms before hospital discharge. In literature review, 2 cases of C recurvatus were isolated from the colon in myeloma patients; this case highlights the unique clinical presentation in the small bowel in a patient with no underlying medical conditions.
Metastatic Colonic Adenocarcinoma in a 12-Year-Old Female
(Poster No. 16)
Sepideh Madahian, MD (Sepideh.firstname.lastname@example.org); Richard Judelson, MD; Salwa Khedr, MD; Xiaoqin Zhu, MD. Department of Pathology, UMass Memorial Health Care, Worcester, Massachusetts.
Pediatric colorectal carcinoma is rare, comprising approximately 1% of pediatric neoplasms. Nonspecific symptoms and low awareness of the disease usually delays diagnosis, resulting in poor prognosis. We report a rare case of a 12-year-old female who presented with acute abdominal pain, bowel habit change, weight loss, and anemia. Abdominal computed tomography (CT) scan showed a 4.4-cm mass in the ascending colon, heterogeneous mass in the second/third portion of the duodenum, multiple liver hypodensities, stranding, and soft tissue thickening within the lower abdomen and scattered peritoneal nodules. During endoscopic ultrasound examination, a mass lesion was identified in pancreatic uncinate. Fine-needle aspiration of the pancreatic mass showed tumor cells positive for CK20 and CDX2 and negative for CK7 and HNF1b, most compatible with metastasis from a lower gastrointestinal primary. The colonic mass biopsy showed adenocarcinoma, arising in a background of tubular adenoma with high-grade dysplasia, positive for CK20 and CDX2 and negative for CK7 and HNF1b, consistent with colonic primary. Immunohistochemistry for DNA mismatch repair proteins was negative. Next-generation sequencing (NGS) detected TP53 mutation. Gene copy number analysis showed gain (6 to 9 copies) of the KRAS (12p12.1) oncogene and deletion of the TP53 (17q13.1) tumor suppressor. She started chemotherapy protocol (FOLFOXIRI + Bevacizumab) with interval improvement in disease on abdominal/pelvis CT scan. Because of nonspecific symptoms of pediatric colorectal carcinoma, clinicians should have a high index of suspicion to avoid diagnosis at an advanced disease stage with poor prognosis and outcomes.
Recurrent Mucosal Schwann Cell Hamartoma: A 10-Year Follow-up Case Study
(Poster No. 17)
Kevin Kuan, MD (email@example.com); Amarpreet Bhalla, MD. Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York.
Mucosal Schwann cell hamartoma (MSCH) of the gastrointestinal tract is an uncommon entity that is usually an incidental finding from routine colonoscopy. It is a benign mesenchymal lesion that consists of poorly circumscribed spindle cells proliferation in the lamina propria. Hitherto, all the available literature suggests that the occurrence of MSCH is incidental, sporadic, and nonsyndromic, and that polypectomy is curative. We present the first case of recurrent MSCH with a 10-year follow-up period. The patient is a 50-year-old woman who had a history of hypertension, obesity, and pituitary adenoma, Cushing syndrome, and Wolf-Parkinson-White syndrome status post ablation. The family history was noncontributory. The initial diagnosis of MSCH was made from colonoscopy procedure performed for abdominal pain. Subsequently, she has had 4 additional follow-up colonoscopy procedures and a total of 20 MSCH polyps were identified. These polyps were located from transverse to rectal sigmoid colon. They were all small sessile lesions (Figure 1.17, A) that range from 4 to 7 millimeters. On histologic examination, these polyps were composed of bland spindle cells within the lamina propria (Figure 1.17, B and C). Immunohistochemically, they were positive for S100 (Figure 1.17, D) and CD56, and negative for EMA, GFAP, CD117, chromogranin, and CD34. Although it is uncertain that the combination of the patient's unusual clinical presentation is part of syndromic manifestation, the recurrence of multiple MSCH warrants further testing and close follow-up.
Recurrence of Granular Cell Tumor in the Esophagus With Multiple New Liver Lesions: Multifocal Disease Versus Metastasis?
(Poster No. 18)
Ayaz G. Kalsekar, MD (firstname.lastname@example.org); Ahmed Shehabeldin, MD; Charlotte F. Kim, MD; Erin N. Vicknair, MD; Mary R. Schwartz, MD; Jae Y. Ro, MD, PhD. Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas.
Granular cell tumor (GCT) is an uncommon soft tissue tumor derived from Schwann cells that usually behaves in a benign fashion. GCT most commonly arises in skin, tongue, and gastrointestinal (GI) tract, with esophagus as the most common GI site. Hepatobiliary involvement can occur, although it is rare. Multifocal GCTs occur in about 10% of the cases; however, malignant GCTs are rare, accounting for approximately 0.5% to 2% of all GCTs. We present a 67-year-old woman who underwent a complete endoscopic resection of an esophageal GCT (Figure 1.18, A). Four years later, she presented with multiple liver lesions and a mass in an esophageal diverticulum that were biopsied and diagnosed as GCTs. Histologic examination of the previous resection specimen and the subsequent esophageal and liver biopsies (Figure 1.18, B) showed GCT with benign features (well demarcated, no nuclear atypia or tumor necrosis, and a mitotic count of <1/10 high-power fields). Immunohistochemical stains for S-100 (Figure 1.18, C) and CD68 (Figure 1.18, D) were immunoreactive in all the lesions, supportive of the diagnosis of GCT. Based on the benign histopathologic features, the presence of multiple liver lesions, and the rare occurrence of primary GCT in the hepatobiliary system, the liver lesions were interpreted as benign metastasizing GCT. We believe that the initial endoscopic resection may have inadvertently created iatrogenic spread of GCT via lymphovascular spaces to the liver. This phenomenon has been described in other tumors including benign metasta-sizing leiomyoma of uterus, giant cell tumor of bone, and pleomorphic adenoma of salivary glands.
Groove Pancreatitis Due to Periampullary Gangliocytic Paraganglioma With Lymph Node Metastasis
(Poster No. 19)
Dongwei Zhang, MD, PhD (email@example.com); Xiaoyan Liao, MD, PhD. Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York.
Groove pancreatitis is a rare form of segmental pancreatitis affecting the “groove” space located between the pancreatic head, duodenum, and common bile duct. It may be indistinguishable from pancreatic malignancy clinically and radiographically. Gangliocytic paraganglioma is a rare benign tumor occurring most frequently in the second portion of duodenum, near the ampulla of Vater. Here we report an extremely rare case of groove pancreatitis due to periampullary gangliocytic paraganglioma. A 55-year-old man was noted to have a cystic lesion in the head of the pancreas by computed tomography (CT) scan and was given a radiographic diagnosis of branch-duct intraductal papillary mucinous neoplasm. Two years later, he developed abdominal pain and 20-pound weight loss with CT scan showing a heterogeneous 4.1-cm low-attenuation mass at the level of the pancreatic head/uncinate process (Figure 1.19, A), highly concerning for malignancy. His CEA was slightly elevated, and he underwent pancreaticoduodenectomy. Macroscopic examination revealed a 4.2-cm ill-defined fibrous lesion at the head of pancreas, and a 1.1-cm periampullary nodule compressing the ampulla of Vater (Figure 1.19, B). Histologically, no pancreatic malignancy was identified. The periampullary nodule demonstrated a classic gangliocytic paraganglioma with metastasis in one lymph node (Figure 1.19, C). Background pancreas demonstrated fibrosis, pancreatic duct dilation, and inflammatory pseudocysts, consistent with groove pancreatitis (Figure 1.19, D). The patient recovered well from the surgery with no evidence of recurrence or metastasis 4 months later. Overall, our findings suggest that gangliocytic paraganglioma, as well as other periampullary tumors, can be a rare cause of groove pancreatitis that mimics malignancies.
Malignant Gastrointestinal Neuroectodermal Tumor With EWSR1Gene Amplification: A Rare Case of a Rare Entity Lacking the Signature Gene Translocation
(Poster No. 20)
Omer A. Saeed, MBBS1 (firstname.lastname@example.org); Christopher Quinn, MD1; Gail H. Vance, MD2; Chen Zhang, MD, PhD.1 Departments of 1Pathology and Laboratory Medicine and 2Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis.
Malignant gastrointestinal neuroectodermal tumor (MGNECT) is a rare aggressive neoplasm with a dismal prognosis. There are fewer than 100 cases reported in the literature and most of them demonstrate translocation involving a ESWR1 gene with fusion partners of either ATF1 or CREB1. Here we report a case of MGNECT lacking a EWSR1 gene translocation or rearrangement. The patient was a 43-year-old man who presented with symptoms of intestinal obstruction. An abdominal computed tomography scan showed findings compatible with proximal small bowel obstruction secondary to an enhancing mass measuring 3.9 cm and a left hepatic lobe mass measuring 4.6 cm. Exploratory laparotomy with small bowel resection and partial hepatectomy was performed. Grossly multiple submucosal masses, up to 3.5 cm, were identified in the small bowel, in addition to a 6-cm liver mass. Histologic examination showed a proliferation of malignant epithelioid and spindle cell cells with open chromatin and prominent nucleoli. The neoplastic cells were positive for SOX-10, S100, and synaptophysin, and focally positive for smooth muscle antigen. Stains for CD117, DOG-1, HMB45, Melan-A, and cytokeratin AE1/AE3 were negative. Fluorescence in situ hybridization testing with an EWSR1 break-apart probe showed EWSR1 gene amplification with no evidence of rearrangement. Although the current World Health Organization classification of gastrointestinal tumors indicates translocations involving EWSR1 gene as essential for the diagnosis of MGNECT, our case shows typical clinical, histologic, and immunohistochemical features of MGNECT, with unusual molecular findings involving the EWSR1 gene. To our knowledge, only one case of MGNECT with EWSR1 gene amplification has been previously reported.
Differences in Vascular Patterns and Reticulin Staining Aid the Distinction Between Hepatoid Adenocarcinoma and Metastatic Hepatocellular Carcinoma
(Poster No. 21)
Yan Huang, MD1 (email@example.com); Carlos Castrodad-Rodríguez, MD1; Kevin Kuan, MD1; Preeti Malik, MBBS, MPH2; Sun Chung, MD1; Qiang Liu, MD1; Nicole Panarelli, MD1; Amarpreet Bhalla, MD.1 1Department of Pathology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York; 2Department of Neurology, Harvard Medical School/Massachusetts General Hospital, Boston.
Context: Hepatoid adenocarcinoma (HAC) is a challenging diagnosis and is difficult to differentiate from metastatic hepatocellular carcinoma (mHCC). There is significant overlap in radiologic, serologic, and immunohistochemical profiles of the 2 tumors. Primary hepatocellular carcinomas often display reduced reticulin framework and diffuse positivity for CD34 within sinusoids. We hypothesized that these features would be retained in mHCC, but absent in HAC.
Design: The study included previously diagnosed mHCCs and HACs in our institution from 2018 to 2020. The clinical, radiologic, and follow-up data were documented. The hematoxylin-eosin and immunostained slides were reviewed. Reticulin and CD34 stains were performed. The patterns of both stains were analyzed in the 2 groups (Table).
Results: Six mHCCs and 5 HACs were identified. The architectural pattern in the mHCCs was solid, trabecular, and pseudoglandular. Reticulin stain outlined trabeculae and pseudoglands and was focally retained in the solid areas. CD34 immunostain revealed diffuse orderly positivity in the sinusoidal endothelium. HACs showed variable architectural patterns consisting of solid, glandular, cribriform foci, and single cells. Reticulin stain highlighted large vessels within the tumor but was absent amidst the tumor tissue. CD34 immunostain showed haphazardly arranged stromal blood vessels but lacked regular sinusoidal pattern.
Conclusions: Utilization of reticulin and CD34 stains is an economical and simple method, available in most laboratories, to differentiate mHCC from HAC. Retained delicate reticulin framework and organized sinusoidal CD34 staining are characteristic of mHCC but absent in HAC.
A Pilot Study of a Universal Fibrosis Scoring System in Medical Liver Disease
(Poster No. 22)
Gabriel Lerner, MD1 (firstname.lastname@example.org); Sanjay Kakar, MD2; Michael Torbenson, MD3; Matthew Yeh, MD, PhD4; Tsung-Teh Wu, MD3; Dhanpat Jain, MD.1 1Department of Pathology, Yale University, New Haven, Connecticut; 2Department of Pathology, University of San Francisco, California; 3Department of Pathology and Laboratory Medicine, Mayo Clinic Hospital–Rochester, Minnesota; 4Department of Pathology and Laboratory Medicine, University of Washington, Seattle.
Context: Evaluation of fibrosis is important for prognostication in medical liver pathology. Currently, many etiology-specific fibrosis scoring systems exist, making comparisons difficult. Thus, a need exists for a universal fibrosis scoring system (UFS). Our goal was to evaluate such a UFS.
Design: Ten biopsies from 8 diseases were selected, including viral hepatitis B (HBV), viral hepatitis C (HCV), autoimmune hepatitis, primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), congestive hepatopathy, nonalcoholic steatohepatitis (NASH), and NASH with concurrent HBV or HCV. A UFS was designed using etiology-specific systems, including Batts and Ludwig (viral, autoimmune hepatitis), Kleinermodified Brunt (NASH), Dai (congestive hepatopathy), and Ludwig (PBC, PSC; Table). Hematoxylin and eosin, trichrome, and reticulin stains from liver biopsies (>1 cm in length) were reviewed by 2 pathologists and scored by UFS and etiology-specific systems. In discrepant cases, consensus was achieved by second morphologic review.
Results: Fibrosis grading by UFS and etiology-specific systems showed high concordance across all entities, with 100% concordance (10 of 10 cases) in congestive hepatopathy, autoimmune hepatitis, NASH, PSC, HBV, and HCV. Concordance was lower in PBC (0.9; 9 of 10 cases) and NASH with concurrent HBV or HCV (0.9; 9 of 10 cases). The 2 discordant cases included HCV with concurrent NASH (Batts-Ludwig: 1; UFS: 2), and PBC (Ludwig: 1, UFS: 2).
Conclusions: Using UFS and etiology-specific systems, fibrosis grade shows high concordance across diverse hepatic disorders. Larger, prospective UFS studies are needed to assess observer variability and validate against clinical outcomes.
Expression of Aspartate B Hydroxylase in Gallbladder Adenocarcinoma
(Poster No. 23)
Mehran Najibi, MD1 (email@example.com); Rolf I. Carlson, BS2; Jack Wands, MD2; Dongfang Yang, MS1; Weibiao Cao, MD, PhD.1 Departments of 1Pathology and 2Medicine, Rhode Island Hospital–Brown University, Providence.
Context: Aspartate-β-hydroxylase (ASPH) is a transmembrane protein that catalyzes the hydroxylation of aspartyl and asparaginyl groups in the epidermal growth factor–like domains of membrane molecules. Previous studies revealed that ASPH is upregulated in several malignant neoplasms. However, the expression of ASPH in gallbladder adenocarcinoma remains unknown. In this study, we examined ASPH expression in gallbladder adenocarcinoma.
Design: Forty-one cases diagnosed from 2001 to 2017 were included. Slides were reviewed to select 3 cores for tissue microarray. Immunohistochemical staining for ASPH, PD1, PD-L1, CD3, and CD8 was performed. A combined score of intensity and extent was calculated and categorized as weak or strong staining (Figure 1.23, A and B).
Results: Strong ASPH staining was observed in 75.6% (31 of 41) of adenocarcinomas (P < .001), whereas only 18.8% (3 of 16) of adjacent benign tissues had strong staining. Eighteen of 20 poorly differentiated adenocarcinomas (90%) exhibited strong ASPH staining (P < .02), whereas 55% (11 of 20) of moderately and well-differentiated tumors showed strong staining. Seventeen of 31 high-stage tumors (stages 3 and 4) (54.8%) showed strong ASPH staining, which was significantly higher than that (10%, 1 of 10, P < .02) in low-stage (stages 1 and 2) tumors. Twenty-eight of 34 tumors with PD-L1–positive tumor-infiltrating lymphocytes (TILs) (82.4%) showed strong ASPH staining, which was significantly higher than that (42.8%; 3 of 7; P < .05) seen in tumors with PD-L1–negative TILs. However, there was no survival difference between weak and strong ASPH staining.
Conclusions: ASPH is highly expressed in gallbladder adenocarcinomas. Strong expression of ASPH is associated with higher tumor grade, tumor stage, and PD-L1–positive TILs. Our findings imply that ASPH may be a potential diagnostic and prognostic marker for gallbladder adenocarcinoma.
Follicular Cholecystitis: A Rare Subtype of Chronic Cholecystitis Presenting as Mucosal Polyps of the Gallbladder
(Poster No. 24)
Ahmed M. Alhusseiny, MD (firstname.lastname@example.org); Rahul Jawale, MD. Department of Pathology, Baystate Medical Center, Springfield, Massachusetts.
Follicular cholecystitis is a poorly characterized entity seen in approximately 2% of cholecystectomies. Since its initial description in the early 1900s, a limited number of cases have been analyzed to characterize this entity. We present a case of follicular cholecystitis presenting as multiple polypoid lesions of the gallbladder. A 71-year-old obese woman presented with 5 weeks of right upper quadrant abdominal pain. Ultrasound showed dilatation of the common bile duct, cholelithiasis without cholecystitis, and an 8-mm mucosal polyp. Computed tomography revealed dilation of the common bile duct without distal obstruction. Laparoscopic cholecystectomy was performed that showed multiple mucosal polyps, the largest measuring 9 mm, with normal intervening mucosa. No choleliths were identified. The polyps were associated with well-formed lymphoid follicles; the follicles involved the gallbladder wall full thickness. In areas of concern for involvement by lymphoma, a workup demonstrated a mixed population of CD20-positive B cells and CD3-positive T cells (Figure 1.24, A through D), without aberrant expression of CD5 or CD43 on B cells. Germinal centers were highlighted by CD10 and were negative for bcl2. A review of the patient's history, symptoms, and clinical findings did not reveal evidence of findings associated with follicular cholecystitis, as characterized in the literature. Follicular cholecystitis may be an underrecognized diagnosis that occurs with a greater frequency than initially thought. Given that gallbladder has become a frequent surgical specimen with the advent of laparoscopic surgery, there should be an increased awareness for diverse microscopic findings such as follicular cholecystitis that can histologically mimic a lymphoma.
A Rare Case of Disseminated Histoplasmosis Presenting With Widespread Gastrointestinal Tract and Soft Palate Involvement
(Poster No. 25)
Sanobar Yasmeen Mohammed, MD (email@example.com); Qandeel Sadiq, MD; Farhan Khan, MD. Department of Pathology, University of Tennessee Health Science Center, Memphis.
Histoplasma capsulatum, a thermally dimorphic fungus, is primarily found in Midwestern states. Immunocompromised patients are at risk of disseminated disease. Diagnosis of disseminated histoplasmosis requires a high index of suspicion. We report a case of disseminated histoplasmosis in an immunocompromised patient. A 59-year-old man presented with jaw pain, difficulty in swallowing, and weight loss for few months. HIV antibody was negative and CD4 count was 36. Computed tomography scan of the head showed thickening of the soft palate, near the uvula, concerning originally for squamous cell carcinoma. Patient also complained of diarrhea and black stools. Multiple gastrointestinal (GI) biopsies including duodenum and colon showed expansion of lamina propria by macrophages infected with fungal organisms. GMS special stain highlighted fungal organisms most compatible with histoplasma. Cytomegalovirus immunostain was negative and no microorganisms were identified on AFB special stain. The biopsy of the soft palate was negative for malignancy but showed histoplasmosis. The patient's immunocompromised status predisposed to disseminated histoplasmosis in the soft and hard palate and the GI tract. This case study highlights the importance of a high index of suspicion for disseminated histoplasmosis in unusual sites, especially in immunocompromised patients without a prior history of pulmonary histoplasmosis.
Lymphocytic Gastritis: Clinical and Pathologic Presentation Vary With Age
(Poster No. 26)
Katherine A. Weng, MD, PhD (firstname.lastname@example.org); Ateeqa Mujeeb Ullah, MD; Mona Deerwester, MD; Suparna Sarkar, MD, PhD. Department of Pathology, NYUniversity Langone Health, Mineola, New York.
Context: Lymphocytic gastritis (LG) is an unusual pattern (present in less than 0.3% of gastric biopsies) of gastric mucosal damage characterized by increased intraepithelial lymphocytes (IELs; >25 per 100 epithelial cells in the gastric mucosa) and increased chronic inflammation in the lamina propria. LG is commonly associated with gluten-sensitive enteropathy, Helicobacter pylori gastritis, and nonsteroidal anti-inflammatory drugs. The clinical presentation of LG is variable, and the pathophysiology has yet to be elucidated. The aim of this study is to review and correlate the morphology of LG with the presence of comorbidities along with pathologic findings and age of presentation.
Design: We conducted a retrospective observational study of all patients diagnosed with LG via gastric biopsy at our medical center from 2002 to 2019. Thirty-eight patients with LG were identified and the data were stratified by age (<21 years, 22–59 years, and >60 years). Fisher exact tests were used to identify which categorical variables may correlate with increased IELs in the gastric mucosa. P < .05 was considered statistically significant.
Results: Increased IELs in patients >60 years were associated with a significantly higher probability of anemia/gastric bleeding, whereas increased IELs in patients <21 years were associated with a significantly higher probability of increased duodenum IELs and villus blunting.
Conclusions: Increased gastric IELs have significantly different clinical and pathologic associations dependent on age. These findings suggest that LG may have different etiologies dependent on age. Hence, morphologic diagnosis of LG should prompt different clinical and pathologic workup dependent on age.
Two Case Reports of Primary Anaplastic Large Cell Lymphomas of the Pancreas
(Poster No. 27)
Ling Chen, MD, PhD (email@example.com); Haiying Zhang, MD; John R. Krause, MD. Department of Pathology, Baylor University Medical Center, Dallas, Texas.
Primary pancreatic lymphoma is rare, and primary pancreatic anaplastic large cell lymphoma (ALCL) is extremely rare with fewer than 20 cases reported to our knowledge. ALCL is a type of T-cell lymphoma that can be divided into 2 subtypes based on anaplastic lymphoma kinase (ALK) expression: ALK-positive (ALK+) ALCL and ALK-negative (ALK−) ALCL. We report 1 case each of ALK+ and ALK−ALCL of primary pancreatic lesions. A 34-year-old woman presented with rapid-onset ascites and magnetic resonance imaging finding of illdefined fullness in pancreatic head and neck. Fine-needle aspiration of the pancreatic mass (Figure 1.27, A) and subsequent small bowel biopsy (Figure 1.27, B) revealed large malignant cells with abundant cytoplasm and pleomorphic nuclei. Immunohistochemically, the tumor cells were CD30, CD4, and ALK positive but CD20 negative. Diagnosis of ALK+ ALCL was made. In another case, a 66-year-old woman presented with abdominal pain and jaundice. Computed tomography showed locally invasive hypoenhancing lesion in the pancreatic head. Fine-needle aspiration of the pancreatic lesion (Figure 1.27, C and D) revealed large malignant cells with abundant cytoplasm and pleomorphic, eccentric nuclei. Immunohistochemically, the tumor cells were positive for CD30 and CD4 but negative for CD20 and ALK. Diagnosis of ALK−ALCL was made. ALK+ ALCL is more prevalent in young patients. In contrast, ALK−ALCL occurs most commonly in older adults. The clinical outcome of ALK−ALCL with conventional therapy is generally poorer than that of ALK+ ALCL.
Hepatic Calcifying Nested Stromal Epithelial Tumor With Recurrence in a Transplanted Liver
(Poster No. 28)
Maria Kamal, MD (firstname.lastname@example.org); Doaa Atwi, MD; Sara Abu Mehsen, MD; Wenyi Luo, MD, PhD. Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City.
Calcifying nested stromal-epithelial tumor (CNSET) is a rare liver neoplasm of debatable pathogenesis. It is primarily a pediatric tumor with female preponderance. An association of ectopic ACTH production, Cushing syndrome, Beckwith-Weidmann, and Klinefelter syndrome has been demonstrated in prior literature. We report a CNSET case with unique clinical, microscopic, and molecular features in a 17-year-old female who initially presented with liver failure and ultimately underwent liver transplantation. Gross examination of the resected native liver revealed a circumscribed calcified mass in the right lobe. Microscopic examination revealed a nested biphasic appearance composed of an epithelial and a stromal component (Figure 1.28, A) with calcification (Figure 1.28, B) and necrosis. A unique finding of the water-silk pattern of small blue cells (Figure 1.28, C) was identified in some tumor nests that was never described previously. The patient presented 3 years later with tumor recurrence in the transplanted liver and extensive metastasis. Recurrence in the transplanted liver has never been reported in previous literature. Biopsy from the recurrent tumor revealed similar morphologic findings. Immunohistochemistry revealed CD56, CDX2, β-catenin (cytoplasmic and nuclear) (Figure 1.28, D), WT-1 (nuclear), neuron-specific enolase (patchy), and CD99 positivity in the epithelial component and smooth muscle actin in the stromal cells, supporting our diagnosis. Our case also had a distinctive mutation profile involving CTNNB1, PIK3CA, and TERT promoter genes. The occurrence and accumulation of multiple mutations in our case may have contributed to the aggressive nature of this case.
Sarcina Ventriculi in the Upper Gastrointestinal Tract: A Multicentric Study of 13 Cases
(Poster No. 29)
Mark Ettel, MD1 (email@example.com); Zhenjian Cai, MD, PhD2; Xiaoyan Liao, MD, PhD.1 1Department of Pathology, University of Rochester Medical Center, Rochester, New York; 2Department of Pathology, The University of Texas Health Science Center, Houston.
Context: Although the pathogenicity of Sarcina ventriculi (SV) in humans is still unproven, it has been associated with gastric outlet obstruction and emphysematous gastritis. We aim to further characterize the clinicopathologic features of SV in the largest yet reported case series.
Design: We searched for surgical pathology specimens carrying a diagnosis of SV from 2010 to 2020 at 2 institutions. Clinical and endoscopic findings were collected from medical records.
Results: Twelve upper gastrointestinal biopsies and 1 gastrectomy specimen were identified. The patients included 7 females and 6 males, with a mean age of 57 years. The most common symptoms were abdominal pain (n = 4, 31%), diarrhea (n = 3, 23%), nausea/vomiting (n = 2, 15%), dysphagia (n = 2, 15%), and reflux symptoms (n = 2, 15%). Most SVs were identified in the stomach or gastroesophageal junction (n = 10, 86%), with 2 (7%) in the esophagus and 1 (7%) in the duodenum. Endoscopically, the most common finding was retained food debris (n = 4, 31%), followed by erythema/gastritis (n = 3, 23%) and ischemia/necrosis (n = 2, 15%). The most common clinical associations were gastroparesis (n = 8, 62%), diabetes mellitus (n = 8, 62%), gastroesophageal reflux disease (n = 5, 38%), and gastric outlet obstruction (n = 2, 15%). Two cases (15%) had concomitant Candida. Upon follow-up, 1 patient with gastric necrosis and suspected ischemia died of septic shock shortly after resection; the remaining 12 patients were alive.
Conclusions: Our study confirmed the frequent association of SV with gastroparesis and many other comorbidities, suggesting that it could be pathogenic. SV should be diligently searched for in upper gastrointestinal biopsies, particularly in those with ischemia or necrosis.
Metastatic Colon Cancer to the Stomach: Report of a Rare Case
(Poster No. 30)
Hossein Hosseini, MD1 (firstname.lastname@example.org); Jordan M. Steinberg, MD1; Elliot Newman, MD2; Barry Pearson, MD.1 Departments of 1Pathology and Laboratory Medicine and 2Surgery, Lenox Hill Hospital, New York, New York.
Colorectal cancer (CRC) is the most common malignancy arising from the gastrointestinal tract. Liver and lung are the most common sites of metastasis. Stomach is an exceedingly rare target for CRC. To our knowledge, there are only 5 cases of gastric metastasis from CRC published in the English literature. We present a 54-year-old man with a past medical history significant for colon adenocarcinoma (Figure 1.30, A), for which he underwent left hemicolectomy and received adjuvant chemotherapy. Immunohistochemically, the adenocarcinoma was positive for CK7 and CDX2 and negative for CK20. Molecular studies showed that the tumor cells harbored BRAF and PIK3CA mutations and did not have loss of mismatch repair proteins. Twelve months after the hemicolectomy, imaging studies revealed a 6-cm mass in the body of the stomach. Biopsy of the gastric mass showed that the tumor cells were morphologically similar to the colon adenocarcinoma. Notably, the tumor cells in the gastric mass displayed an immune-phenotyping profile similar to the colon adenocarcinoma (CK7+, CK20−, CDX2+). The patient underwent partial gastrectomy. Gross examination of the gastrectomy specimen showed a 7-cm tan exophytic mass with central ulceration. Histology revealed an unremarkable gastric mucosa overlying the tumor (Figure 1.30, B). Morphologically, the tumor was identical to the colon cancer. SATB2, a highly specific nuclear marker for CRC, stained both colonic (Figure 1.30, C) and gastric (Figure 1.30, D) tumors strongly and extensively. This is a rare case of CRC metastatic to the stomach, in which the diagnosis is supported by SATB2 staining.
Lanthanum-Induced Gastrointestinal Histiocytosis in the Setting of Recurrent Gastric Ulcers: Case Report and Review of the Literature
(Poster No. 31)
Tolson Nichols, MD (email@example.com); Michael D. Black, MD. Department of Pathology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii.
Lanthanum carbonate is a potent binder of dietary phosphate used to prevent hyperphosphatemia in patients with end-stage renal disease (ESRD). The resulting lanthanum-phosphate complex is highly insoluble and passes through the gastrointestinal (GI) tract with little absorption. However, recent case reports have described upper GI histiocytosis with intracellular lanthanum and phosphate accumulation in varied clinical and endoscopic settings. Here, we report a unique case of lanthanum-induced histiocytosis associated with recurrent gastric ulcers in a 62-year-old man with ESRD. Initial endoscopy for epigastric pain and melena revealed small nonbleeding gastric ulcers. Biopsies of the ulcer margin (Figure 1.31, A) and endoscopically normal duodenum (Figure 1.31, B) revealed histiocytic aggregates containing eosinophilic crystalloid material consistent with lanthanum. Following standard treatment, repeat endoscopy and gastric biopsies showed resolution of the ulcers and, interestingly, showed no evidence of lanthanum deposition. However, the patient subsequently presented with recurrent upper GI bleeding and multiple endoscopies revealed a large bleeding ulcer. Biopsies again showed lanthanum deposition at the ulcer margin (Figure 1.31, C) and in endoscopically normal mucosa (Figure 1.31, D). Of note, the patient reported avoiding nonsteroidal anti-inflammatory drugs after his initial presentation but remained on his original dose of lanthanum throughout this period. Gastric biopsies and serology were negative for Helicobacter pylori. This case highlights a rare cause of GI histiocytosis and suggests a potential association between lanthanum deposition and formation of gastric ulcers. Although rare, recognition of lanthanum-induced histiocytosis is important as a reversible cause of GI injury in ESRD patients receiving lanthanum carbonate therapy.
What Is It? Glomus Coccygeum, the Little-Known Structure Mimicking Malignancy
(Poster No. 32)
Jacob C. Kinskey, MD (firstname.lastname@example.org); Ziad M. El-Zaatari, MD; Tracie Koen, MD; Mary R. Schwartz, MD. Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas.
Glomus coccygeum (GC) is an underrecognized vestigial glomus near the tip of the coccyx with unknown function. Our case illustrates the importance of recognizing this enigmatic structure and provides the first description post–neoadjuvant therapy. A 76-year-old woman with rectal bleeding and severe anemia was found to have synchronous invasive distal rectal adenocarcinoma and invasive anal squamous cell carcinoma with gluteal extension. Following neoadjuvant chemoradiation, she underwent abdominoperineal resection with extended resection of skin. There was a small focus of residual rectal adenocarcinoma with treatment effect, one lymph node with treatment effect, and no residual anal squamous cell carcinoma. One section of the entirely submitted anal soft tissue radial resection margin showed a small focus of epithelioid cells arranged in nests (Figure 1.32, A), faint intercellular bridges, and focal mild atypia (Figure 1.32, B). The initial histologic differential diagnosis included focal residual carcinoma with treatment effect, neuroendocrine tumor, and paraganglioma. The cells were not immunoreactive for pancytokeratin, p40 (Figure 1.32, C), chromogranin, or synaptophysin, militating against the initial diagnostic considerations. Additional immunohistochemical studies demonstrated that the cells expressed smooth muscle actin (Figure 1.32, D) and were surrounded by an S-100–positive neural sheath. Based on location, presence of epithelioid cells in vessel walls, and immunohistochemical profile, the overall findings were interpreted as GC with focal treatment-related changes. In an era of increasing use of neoadjuvant therapy and extensive sampling required to assess response to therapy, it is important that pathologists recognize GC to avoid misinterpretation as residual carcinoma, which could lead to unnecessary postoperative adjuvant therapy.
Unusual Giant Gastric Polyp in Juvenile Polyposis Syndrome
(Poster No. 33)
Yalda Soleimanifard, MD (email@example.com); Dalia Ibrahim, MD; Surendra Singh, MD. Department of Pathology, University of Toledo, Ohio.
Juvenile polyposis syndrome (JPS) is a rare autosomal-dominant syndrome associated with mutations in the SMAD4 or BMPR1A genes. JPS is characterized by multiple hamartomatous polyps in the gastrointestinal (GI) tract, mainly in the colon and stomach; patients are at increased risk of colon and stomach cancer. Clinically, JPS presents with hematochezia, diarrhea, and abdominal pain. Endoscopically, polyps range from small sessile nodules to pedunculated lesions large enough to prolapse rectally. Diagnosis of JPS requires at least 1 of the following: a minimum of 5 juvenile polyps (JPs) in the colon and/or rectum, multiple JPs in other parts of the GI tract, or a JP in a person with known family history of JPS. We present a 34-year-old woman who presented with abdominal pain and distension, and severe GI bleeding requiring transfusion. She was status post colectomy at age 11 because of her known SMAD4 mutational status and JPS family history. Imaging revealed a giant gastric mass and she underwent gastrectomy. Hundreds of polyps were present, the largest pedunculated and 17 cm in greatest dimension (Figure 1.33, A). Microscopically these were hyperplastic polyps with multiple cystically dilated crypts of foveolar-type epithelium and a milder degree of smooth muscle hyperplasia (Figure 1.33, B and C). The lamina propria was edematous with lymphoplasmacytic infiltrate and a few neutrophils. Focal low-grade dysplasia was identified (Figure 1.33, D) with elongated hyperchromatic pseudostratified nuclei. Our case highlights the importance of continued surveillance in JPS patients and necessity of extensive polyp sampling to identify dysplasia or carcinoma.
Postinfantile Giant Cell Hepatitis: A Rare Complication of Epstein-Barr Virus Infection
(Poster No. 34)
Kevin Kuan, MD (firstname.lastname@example.org); Raquel Yokoda, MD; Nicole Panarelli, MD. Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York.
Postinfantile giant cell hepatitis (PIGCH) is a rare and enigmatic inflammatory disease of the liver, characterized by the presence of enlarged, eosinophilic, and multinucleated hepatocytes in a background typically consisting of severe necroinflammatory stroma. Although only a handful of case reports are available in the literature, its exact pathogenesis remains elusive. Numerous factors, including various viral infections, medications, and even autoimmune conditions, have been associated and postulated as etiologic agents of PIGCH. Herein, we present an unusual case of PIGCH that is believed to be caused by autoimmune hepatitis secondary to a newly acquired Epstein-Barr virus (EBV) infection. The patient was a 56-year-old man with a history of HIV and HCV coinfection on antiviral therapy, HPV-associated squamous cell carcinoma of the tonsil, genital warts, and active cocaine user who presented to the emergency department because of abdominal pain and vomiting for several days. Preliminary test results revealed markedly elevated liver enzymes (ALT and AST >2000 U/L) and positive EBV serology, but HIV RNA was not detected. He was admitted for further evaluation and liver biopsy procedure was performed. Histologic examination of the collected liver tissue showed remarkable giant cell transformation of most hepatocytes, with associated active, chronic inflammation, florid ductular reaction, and bridging necrosis (Figure 1.34). Further serology testing also revealed elevated anti–liver-kidney-microsome antibody, supporting the diagnosis of autoimmune hepatitis with extensive giant cell transformation.
Clinical Implications of Microscopic Colitis–like Polyps
(Poster No. 35)
Caroline Miller, MD (Caroline_Miller@URMC.Rochester.edu); Christa Whitney-Miller, MD; Mark Ettel, MD. Department of Pathology, University of Rochester Medical Center, Rochester, New York.
Context: Microscopic colitis (MC) is generally identified on random colon biopsies performed for chronic diarrhea, but rarely incidental polyps have histologic features of MC. We compared patients with MC-like polyps (MCLPs) with control patients with conventional polyps to determine the implications of MCLPs.
Design: We searched medical records for patients without prior or concurrent MC who were found to have MCLPs. For each patient with MCLPs, 1 patient with conventional polyps was selected as a control. We reviewed histologic features of each MCLP and evaluated endoscopic and clinical findings for MCLP cases and controls.
Results: We identified 31 patients with MCLPs, with histologic features of collagenous colitis in 9 patients (29%) and lymphocytic colitis in 22 patients (71%). The MCLPs were unifocal in 13 patients (41.9%) and multifocal in 18 patients (58.1%). There was no difference in chronic diarrhea at time of procedure or on follow-up; at time of procedure 1 patient with MCLPs (5.6%) had chronic diarrhea compared with no patients in the control group (P = .44), and on follow-up 6 patients with MCLPs (28.6%) developed chronic diarrhea compared with 3 (10.3%) in the control group (P = .14). Of patients with follow-up biopsies, 1 patient with MCLPs (12.5%) and no control patients developed MC (P = .1).
Conclusions: MCLPs may be identified in asymptomatic patients and most patients do not develop chronic diarrhea, but there may be a trend for patients with MCLPs to develop diarrhea (29% versus 10% in controls). Thus, pathologists may suggest follow-up regarding chronic diarrhea in patients with MCLPs.
Correlation of Pre-operative Cytology With Malignant Histopathology of Pancreaticoduodenectomy Specimens
(Poster No. 36)
Areeba H. Rizvi, MD1 (email@example.com); Aisha Kousar, MD1; Anas Mohamed, MD1; Ann Sutton, MD1; Kim R. Geisinger, MD.2 1Department of Pathology and Laboratory Medicine, East Carolina University/Vidant Medical Center, Greenville, North Carolina; 2Department of Pathology and Laboratory Medicine, The Joint Pathology Center, Silver Spring, Maryland.
Context: Pancreaticoduodenectomy (PD) is the standard of care for resectable pancreatic and peri-ampullary cancers. Abnormal imaging and fine-needle aspiration (FNA) lack 100% specificity in identifying malignancies. PD is a high-risk surgery with significant morbidity and mortality. We assess the cyto-histo correlation of PDs and explore parameters that increase the yield for a final malignant diagnosis.
Design: We studied 250 PDs performed at our institute during the last decade. A representative sample of the data is presented. We calculated mean with standard error for continuous data, whereas categorical data were expressed as percentages. Differences between groups were assessed using the χ2 test. Data were analyzed using Stata v12.0.
Results: A total of 40 PDs were reviewed. Mean age was 65.7 ± 2.3 years. The predominant histopathologic diagnosis in resected specimens was malignancy (31 cases, 77.5%) followed by preneoplastic (12.5%) and benign (10%). Of the malignant cases, 87% strongly correlated with cytology (P < .001), 71% with gross findings (P = .03), 65% with imaging, and 55% with abnormal tumor markers (Figure 1.36). Among the 5 preneoplastic cases, 4 were either atypical or malignant on FNA, 4 had abnormal imaging results, and all 5 had abnormal gross findings. Of the 4 benign cases, 3 FNA results were atypical/malignant, 3 were detected as “mass” on imaging, and 3 had ill-defined gross findings.
Conclusions: Our study demonstrates a strong positive correlation between the malignant histologic diagnosis with cytology and gross findings. It remains to be determined whether molecular genetics will add significantly to the predictive power of preoperative evaluation of PDs.
Novel Lifting Agent ORISE Granuloma: Report of 2 Cases
(Poster No. 37)
Julieta A. D'Ardis, MD (firstname.lastname@example.org). Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas.
The use of lifting agents in the performance of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) of gastrointestinal neoplasms is an integral part of these new procedures. After injection for EMR or ESD procedures, these agents may remain in tissue for some time and may be found in subsequent surgical resections, where they can mimic other conditions. We report 2 cases where ORISE (Boston Scientific), a viscous gel lifting agent, was used in the setting of an incomplete (1 case) or aborted (second case) endoscopic submucosal dissection. Hematoxylin and eosin–stained sections demonstrated submucosal deposits of amorphous eosinophilic homogeneous material, mimicking amyloid (Figure 1.37, A through C). The material was neither refractile nor polarizable and was accompanied by a foreign body giant cell reaction. Because of the diagnostic consideration of amyloid, Congo red stains were performed on both cases, with negative results (Figure 1.37, D). It is important to be aware of the morphology of this new lifting agent for accurate diagnosis and to avoid the diagnostic pitfall of misinterpreting it as amyloid or other disease processes, with potential adverse clinical impact. This material can be definitively distinguished from amyloid by its nonreactivity on Congo red stain, familiarity with its histologic features, and recognition of its use in selected endoscopic resections.
Synchronous 2 Distinct Pancreatobiliary Tumors—Common Bile Duct Cholangiocarcinoma and Primary Pancreatic Ductal Adenocarcinoma
(Poster No. 38)
Huihua Li, MD, PhD (email@example.com); Yong-Jun Liu, MD, PhD. Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison.
Synchronous primary tumors of the pancreaticobiliary system are extremely rare. We present a case of a 65-year-old man with a history of ulcerative colitis status post total proctocolectomy and metabolic syndrome who presented with jaundice and elevated liver enzymes. Computed tomography (CT) scan revealed biliary tract dilatation and an enhancing masslike lesion at the junction of the common hepatic duct and cystic duct with adjacent adenopathy. Endoscopic retrograde cholangiopancreatography demonstrated common bile duct (CBD) stricture, and bile duct brushing confirmed adenocarcinoma. In addition, CT scan revealed a separate 1.7-cm mass in the pancreatic body that was diagnosed as pancreatic adenocarcinoma by tissue biopsy. The patient underwent 6 months of chemotherapy followed by surgical resection. The resection specimen of CBD demonstrated moderately differentiated invasive adenocarcinoma (ypT1N0), with extensive low-grade and high-grade biliary intraepithelial neoplasia (BilIN), periductal concentric fibrosis, and diffuse chronic inflammation (Figure 1.38, A and B). The histologic findings, in conjunction with patient's known history of ulcerative colitis, support the diagnosis of cholangiocarcinoma arising in primary sclerosing cholangitis with BilIN. The resected pancreas showed moderately differentiated adenocarcinoma (ypT1N0) in a background of low-grade pancreatic intraepithelial neoplasia (PanIN) and chronic pancreatitis (Figure 1.38, C and D). Subsequent molecular genetic analyses were performed to further delineate the nature of these 2 distinct neoplasms. The pancreatic adenocarcinoma showed KRAS p.G12V mutation while molecular signature of CBD adenocarcinoma is pending. This case provides a unique synchronous presentation of 2 distinct neoplasms within the pancreaticobiliary system. Although this presentation is rare, it should be considered when assessing multiple pancreaticobiliary lesions.
Metastatic Spindle Cell Hepatocellular Carcinoma: A Diagnostic Dilemma
(Poster No. 39)
Anindita Ghosh, MD, PhD (Anindita.Ghosh@uth.tmc.edu); Jamie Buryanek, MD; Songlin Zhang, MD, PhD. Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston.
Spindle cell hepatocellular carcinoma (HCC) is very rare and has only been reported sporadically. Spindle cell HCC presenting with bone metastasis can cause a significant diagnostic challenge. We report a 67-year-old woman with a history of hepatitis C and well-differentiated HCC (Figure 1.39, A) in 2012. She was on regular monitoring until March 2020 with no recurrence. In November 2020, she had a sclerotic lesion in the left iliac bone. The lesion was biopsied and revealed cellular bland spindle cell lesion (Figure 1.39, B). Tumor cells were positive for CAM 5.2, but negative for hepar-1, glypican-3, arginase, and AFP. The multiple bone lesions and positive CAM5.2 were suggestive of metastatic spindle cell HCC. A follow-up liver biopsy showed a spindle cell HCC (Figure 1.39, C) with a similar morphology as the metastatic spindle cell carcinoma. Albumin RNA in situ hybridization (ISH) was performed on the bone lesion and the spindle cells were diffusely positive for albumin RNA ISH (Figure 1.39, D), supporting the diagnosis of metastatic spindle cell HCC. The liver spindle cell HCC might be a new primary because the location and morphology are different from the 2012 well differentiated HCC, but a recurrent HCC with spindle cell morphology cannot be excluded. In conclusion, spindle cell HCC may present as a metastatic spindle cell lesion in bone and stain negative for glypican-3, hepar-1, arginase, and AFP may lead to misdiagnosis. Albumin RNA ISH is a more sensitive and specific marker and can be used for diagnosis of HCC in poorly differentiated or rare variants of HCC such as spindle cell HCC.
Soft Tissue Metastasis From Gastric Carcinoma Mimicking Epithelioid Sarcoma
(Poster No. 40)
Yihe Yang, MD; Ilan Reder, MD (IReder@northwell.edu); Morris Edelman, MD; Qing Chang, MD, PhD. Department of Pathology, Northwell Health, Greenvale, New York.
Soft tissue metastasis of gastric carcinoma is extremely rare. We report a 22-year-old man with abdominal fullness and nausea found to have an 11.8-cm right iliac bone and soft tissue mass, with osseous destruction. Extensive retroperitoneal lymphadenopathy was also identified. Differential diagnosis included primary sarcoma, lymphoma, and metastatic carcinoma. Fine-needle aspiration and core biopsy of the soft tissue mass was cellular with neoplastic cells arranged in clusters and singly, showing nuclear pleomorphism, irregular chromatin, prominent nucleoli, high nuclear to cytoplasmic ratio, and cytoplasmic vacuoles. Scattered intracytoplasmic pink globules were also present (Figure 1.40, A and B). Immunohistochemical stains showed the tumor to express cytokeratin AE1/3 and Cam5.2 (Figure 1.40, C), and to be negative for SOX10, S-100, ERG, myogenin, MyoD1, smooth muscle actin, desmin, CD99, GFAP, CD34, CD31, CD3, CD20, and CD30. The possibility of epithelioid sarcoma was raised, but the tumor cells showed retained INI1 expression (Figure 1.40, D). The patient quickly developed pleural effusion and a repeat biopsy of the iliac mass showed the tumor to express cytokeratin 7, cytokeratin 20, BerEP4, MOC31, and CDX2. The tumor was diagnosed as a poorly differentiated carcinoma of possible gastrointestinal origin. Next-generation sequencing showed mutations of ERBB2 V777L and CDH-1 S337fs*3, splice site 1009-1G>A. Unfortunately, the patient died soon thereafter. Per literature review, this is one of the youngest patients identified with CDH1-mutated gastric carcinoma presenting with distant metastasis as the initial manifestation.
Solitary Peutz-Jeghers–Type Polyp of Jejunum With Gastric Fundic and Antral Gland Lining Mucosa
(Poster No. 41)
Lingjia Liu, MD1 (firstname.lastname@example.org); Huifang Zhou, MD, PhD1; Martina Risech, DO1; Alex Ky, MD, FACS, FASCRS2; Jane Houldsworth, PhD1; Stephen Ward, MD, PhD.1 Departments of 1Pathology and 2Surgery, Mount Sinai Hospital, New York, New York.
Solitary Peutz-Jeghers–type polyp (PJP) is a rare lesion characterized by a hamartomatous polyp of the gastrointestinal tract in a patient without mucocutaneous pigmentation, family history of Peutz-Jeghers syndrome, or STK11/LKB1 mutations. These polyps can arise anywhere along the gastrointestinal tract and are characterized by arborizing smooth muscles lined by nondysplastic mucosa. Although the lining mucosa is generally the same as the organ in which it arises, gastric pyloric and foveolar metaplasia have been reported in PJP arising in the small intestine. We present a case of a small intestinal PJP with gastric antral and fundic gland lining mucosa. A 43-year-old man was admitted for small bowel obstruction. Diagnostic laparoscopy and enterotomy revealed intussusception of jejunum, with an associated polyp measuring 7.2 cm (Figure 1.41, A). Histologic examination showed a hamartomatous polyp with arborizing smooth muscles extending from the muscular mucosae (Figure 1.41, B). The polyp was lined by nondysplastic gastric antral and fundic gland mucosa (Figure 1.41, C), and was sharply demarcated from the adjacent nonpolypoid intestinal mucosa (Figure 1.41, D). Colonoscopy, esophagogastroduodenoscopy, and small bowel enteroscopy revealed no additional polyps or masses. Thorough investigation of the patient's family history was negative for PJP or mucocutaneous pigmentation. Molecular characterization of the lesion is underway. A diagnosis of solitary PJP of the small bowel with gastric antral and fundic gland mucosal lining was rendered. Although pyloric and foveolar metaplasia in PJP has been described, we believe this to be the first report of small intestinal PJP with gastric fundic gland lining mucosa.
Extramucosal Anal Adenocarcinoma Arising From a Fistula Tract in a Patient With Longstanding Crohn Disease
(Poster No. 42)
Saman S. Karimi, MD, MS1 (email@example.com); Vivek Chaudhry, MD2; Vikas Mehta, MD1; Elizabeth Wiley, MD.1 Departments of 1Pathology and 2Surgery, University of Illinois at Chicago.
Anal cancer accounts for 1% of all gastrointestinal malignancies in the United States. Although primary anal squamous cell carcinoma is well characterized, limited documentation of primary anal adenocarcinoma exists and its pathogenesis is not well understood, though it is hypothesized to arise in the setting of chronic inflammation and fistula tracts in the perianal region. We present a case of a 70-year-old man with a 24-year history of Crohn disease complicated by recurrent anal fistula formation, fistulotomy, and seton placement presenting with recurrent anal fistula, abscess formation, and rectal pain. No mucosal high-grade dysplasia or malignancy was identified on recent colonos-copy. Patient was found to have an atypical external opening on rectal examination under anesthesia, and a biopsy was sent for histopathologic evaluation. Microscopic examination revealed a poorly differentiated adenocarcinoma with mucinous features involving the perianal skin. Neoadjuvant chemoradiation therapy was initiated and abdominoperineal resection was performed post completion of neoadjuvant therapy. Resection specimen was sent to pathology for histopathologic evaluation, treatment response, and tumor staging. Gross examination revealed a large lobulated posterior perianal mass localized to the posterior anal canal, disrupting the internal/external anal sphincters and involving a right cutaneous anal fistula (Figure 1.42, A through D). Microscopic examination showed extramucosal, poorly differentiated adenocarcinoma with mucinous features arising from a preexisting fistula. Primary extramucosal anal adenocarcinoma is a rare entity with unusual presentation and no established therapeutic evidence-based algorithm. We report this case to highlight its occurrence in patients with long-standing Crohn disease and lack of mucosal malignancy on surveillance colonoscopy.
Colonic Hemangioma Masquerading as Colonic Adenocarcinoma
(Poster No. 43)
Saman S. Karimi, MD, MS (firstname.lastname@example.org); Maria F. Gonzalez, MD. Department of Pathology, University of Illinois at Chicago.
Gastrointestinal tract hemangiomas can occur singly or multiply from the esophagus to the rectum. Colonic hemangioma is an uncommon benign neoplastic proliferation of endothelial cells and often presents as an incidental finding with spontaneous bleeding. We report a case of a 79-year-old man with a history of “known colorectal cancer,” unclear history of human immunodeficiency, and coronariopathy presenting with chronic fatigue. During hospitalization, the patient had several episodes of melena and hematochezia and was found to have severe iron-deficiency anemia. Upper endoscopy did not reveal a source of bleeding. On computed tomography scan and colonoscopy, the patient was found to have a partially obstructing, malignant-appearing, ulcerated mass localized to the splenic flexure of the transverse colon. The patient subsequently had an ileocolectomy. Gross examination revealed a 6.5-cm polypoid, partially circumferential mass. Microscopically, the lesion consisted of an ulcerative vascular lesion composed of thin-walled vessels involving the mucosa, submucosa, and pericolic tissue, mimicking a colorectal adenocarcinoma on imaging. The differential diagnosis included adenocarcinoma (clinically) and various vascular lesions (arteriovenous malformation, epithelioid hemangioendothelioma, Kaposi sarcoma, and angiosarcoma). The tumor was positive for CD31/CD34 (Figure 1.43, A through D), whereas it was negative for CAMTA1, FOSB1, had HHV8 and had a low proliferative index, supporting the diagnosis of hemangioma. Colonic hemangiomas have rarely been described in the literature. They can present with occult or acute bleeding and bowel obstruction mimicking a colorectal carcinoma. Colonic hemangiomas are often an incidental finding. There have been limited cases in the literature reporting overt gastrointestinal bleeding secondary to colonic hemangioma.
Patients With Definite Distal Esophageal Adenocarcinoma Have Significantly Better Outcomes Than Patients With Carcinomas in Other Gastroesophageal Junction Regions: A Retrospective Study of 303 Consecutive Patients Treated in Boston
(Poster No. 44)
Qin Huang, MD, PhD1 (email@example.com); Yuqing Cheng, MD, MSc3; Edward Lew, MD2; Jiong Shi, MD, PhD.4 Departments of 1Pathology and Laboratory Medicine and 2Gastroenterology, VA Boston Healthcare System/Harvard Medical School, West Roxbury, Massachusetts; 3Department of Pathology, Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China; 4Department of Pathology, Nanjing Drum Tower Hospital affiliated with Nanjing University, Nanjing, China.
Context: Distal esophageal adenocarcinoma (EAC) is part of carcinomas in the gastroesophageal junction (GEJ) region with dismal prognosis and unknown mechanisms. Recently, the Cancer Genome Atlas (TCGA) published genomic profiles of those carcinomas in 5 groups but the prognostic significance of categorizing patients into these groups remains unclear.
Design: We followed the TCGA grouping criteria and retrospectively studied and statistically compared clinicopathologic and prognostic features of GEJ carcinomas in 5 groups of 303 consecutive patients treated at VA Boston during a 20-year period. The patients were grouped as G1, definite EAC (20.5%); G2, probable EAC (30.7%); G3, carcinoma straddling GEJ (13.9%); G4, probable proximal gastric carcinoma (27.7%); and G5, definite proximal gastric carcinoma (7.3%).
Results: More than 99% of patients were white men, with a mean age of 69.1 years and an average body mass index of 28.0. No significant difference was found in age, gender, ethnicity, body mass index, presence of cardiovascular diseases, diabetes, and history of tobacco/alcohol abuse among groups. Compared with patients in other groups, G1 patients showed significantly more frequent severe reflux disease, long-segment Barrett esophagus, common adenocarcinoma type, smaller tumor size, well-moderate differentiation, more stage I but fewer stage III cases, scarcer lymphovascular invasion, fewer nodal and distant metastases, and significantly better overall disease-free and relapse-free survival. The 5-year overall survival rate was 41.3% in the G1 group, significantly higher than in other groups (17.2%; P < .001) (Figure 1.44, A through D).
Conclusions: With the TCGA grouping criteria, patients with definite EAC showed significantly better prognosis than those with carcinomas in other GEJ regions, suggesting different pathogenesis mechanisms.
Clinicopathologic Features of Esophageal and Esophagogastric Junction Gastrointestinal Stromal Tumors in the Targeted Therapy Era: An Institutional Review During an 18-Year Period
(Poster No. 45)
Alan A. George, DO1 (firstname.lastname@example.org); Natalia Yanchenko, MD1; Melissa Duarte, MD1; Emily Mejia, BS2; Elizabeth A. Montgomery, MD.3 1Department of Pathology, Jackson Memorial Hospital/University of Miami, Florida; 2Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida; 3Department of Pathology, University of Miami, Florida.
Context: Gastrointestinal stromal tumors (GISTs), usually gastric (60%–70%), arise throughout the gastrointestinal tract and comprise approximately 80% of mesenchymal GIST neoplasms. Esophageal GISTs are rare (0.7% of all GISTs); esophageal and esophagogastric junction (EGJ) GISTs have a reported incidence of 0.1–0.3/million patients. Given their rarity, we investigated their clinicopathologic features and frequency at our institution.
Design: Our pathology database was queried for GIST specimens from January 2003 through December 2020. The pathology reports and pertinent clinical notes were reviewed. Incidental microscopic lesions, so-called seedling GISTs, were excluded.
Results: A total of 1082 patients with 1458 GIST specimens (biopsies and resections) were histologically evaluated. Of these, 12 patients (1.1%; median age, 68.5 years [45–90 years]) with esophageal (n = 6, 50%) and EGJ (n = 6, 50%) GISTs were identified, with 16 specimens total, including 4 metastases (bone n = 1, liver n = 2, subcutaneous tissue n = 1) among 3 patients, and 1 recurrence (stomach). Two metastases were from the esophagus (1 liver, 1 bone) and 2 (1 liver, 1 subcutaneous tissue from same patient) from the EGJ. Primary tumors accounted for 0.8% of all specimens. There were 8 males (67%; median age, 67.5 years [49–73 years]) and 4 females (33%; median age, 74.5 years [62–90 years]). Primary site distribution between genders was as follows: esophageal, 4 males, 2 females; EGJ, 4 males, 2 females. Follow-up was available in 8 of 12 patients, none of whom died from their disease.
Conclusions: This further demonstrates the rarity of esophageal and EGJ GISTs, and the clinicopathologic features show low risk of aggressive or fatal disease. Whereas this subtype was often lethal in the past, it has a low risk for fatal disease in the targeted therapy era, even when metastatic.
Atypical Presentation of Aggressive Systemic Mastocytosis in a Pediatric Patient
(Poster No. 46)
Tao Zhang, MD (email@example.com); Catherine Turner; Richard D. Hammer, MD; Katsiaryna Laziuk, MD; Deepthi Rao, MD. Department of Pathology and Anatomical Sciences, University of Missouri, Columbia.
Systemic mastocytosis (SM) in children is extremely rare and has a bimodal distribution. We report a case of aggressive SM with an atypical presentation in a 12-year-old girl. The patient had no significant past medical history and presented with 1-year duration of daily cramping abdominal pain, aggravated by eating. The condition was not relieved by proton-pump inhibitors. The patient underwent colonoscopy. The mucosa was edematous and friable with loss of vascular markings. Biopsies of all portions of colon were obtained. On microscopy, the biopsy fragments showed clusters and dense lamina propria infiltration consisting of mast cells with round-shaped nuclei and moderate amount of pale to clear cytoplasm. The background also showed numerous eosinophils. Immunohistochemical staining for CD117, mast cell tryptase (MCT), CD2, and CD25 highlighted increased numbers of neoplastic mast cells. KIT mutation testing was performed, and no pathogenic genetic alterations were detected. A subsequent bone marrow biopsy was performed that demonstrated mast cells in clusters adjacent to bony trabeculae, with spindled, round, and atypical morphology. Increased clusters of eosinophils were present around the atypical mast cells. Immunostaining for MCT and CD117 showed positive expression. By flow cytometry, atypical mast cells with aberrant expression of CD25 and CD2 and hematogone hyperplasia were identified. SM is a rare and heterogeneous disease characterized by the accumulation of abnormal mast cells in various tissues. Although cutaneous mastocytosis is the classical presentation in children, our case emphasizes the importance of considering SM in the differential diagnosis and further performing appropriate systemic screening in patients with atypical presentation.
Hammer is a consultant for Roche, Caris, and Foundation Medicine, and shareholder/owner for PathEdEx.
Biliary Atresia: A Biliary Cyst Distinct From Choledochal Cyst
(Poster No. 47)
Katherine A. Lehman, BS1 (firstname.lastname@example.org); Suzanna Logan, MD2; Miriam Conces, MD3; Bonita Fung, MD3; Archana Shenoy, MD.3 1Department of Pathology, The Ohio State University College of Medicine, Columbus; 2Department of Pathology, Nationwide Children's Hospital, Columbus, Ohio; 3Department of Pathology, Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus.
Cystic biliary atresia (CBA) is a variant of biliary atresia characterized by cystic dilation of atretic bile ducts. It comprises approximately 10% of biliary atresia cases and can mimic a choledochal cyst (CC) on imaging. Both disorders present in infancy with direct hyperbilirubinemia and a cystic structure near the hepatic hilum. A female neonate born at 36 weeks 2 days' gestation was noted to have elevated direct bilirubin at birth. Ultrasound demonstrated a 3.1-cm cystic abnormality at the hepatic hilum, suspicious for CC. The patient was discharged but developed worsening jaundice and hepatomegaly. Repeat ultrasound at 4 weeks of age demonstrated enlargement of the cystic structure. Diagnostic cholangiogram found absence of bile duct communication and abnormal intrahepatic bile ducts concerning for CBA. Needle biopsy demonstrated obstructive pattern of cholestasis (Figure 1.47, A) and periportal fibrosis with focal bridging fibrosis. The patient underwent a hepatoportoenterostomy (Kasai procedure) at 6 weeks of age. The biliary remnants were examined in pathology. The gallbladder was atretic (Figure 1.47, B). The wall of the excised cystic lesion was thickened and demonstrated a luminal band of sclerosis (Figure 1.47, C). The portal plate showed numerous diminutive bile duct remnants associated with dense fibrosis (Figure 1.47, D). In summary, CBA may be challenging to differentiate from CC. CC demonstrates cholangiographic evidence of a patent biliary tree. Histopathologic features such as a luminal band of fibrosis/scarring and absence of epithelium are commonly seen in CBA when compared with CC. The distinction between CBA and CC is critical for appropriate and timely surgical management.
Prostatic Adenocarcinoma Presenting as a Rectal Mass
(Poster No. 48)
Alwalid Ammoun, MD (email@example.com); Min Cui, MD. Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, Ohio.
Rectal infiltration by prostatic carcinoma is an extremely rare presentation of advanced disease in the prostate. We report a case of an 80-year-old man with no history of malignancy presenting with change in bowel habits and weight loss. His serum carcinoembryonic antigen (CEA) level was elevated at 6.8 μg/L. Colonoscopy revealed a circumferential villous and fungating mass with near-complete obstruction in the rectum. Biopsies were taken for histologic evaluation. Representative sections were selected, paraffin embedded, and hematoxylin-eosin stained. Immunohistochemical studies (cytokeratin AE1/AE3, CK7, CK20, CDX-2, SATB2, NKX3.1, INSM-1, chromogranin, and synaptophysin) were also performed. Histologic examination showed glands/acini involving smooth muscle and infiltrating lamina propria of the rectum without overlying surface epithelial dysplasia (Figure 1.48, A). The tumor cells were positive for pancytokeratin AE1/AE3 (Figure 1.48, B) and negative for CK7, CK20, and neuroendocrine markers (INSM-1, chromogranin, synaptophysin). Both SATB2 (Figure 1.48, C) and CDX-2 showed weak and focal staining. The tumor cells were diffusely positive for NKX3.1 (Figure 1.48, D). The overall morphology and immunohistochemical profile were consistent with rectal involvement by prostatic adenocarcinoma. Review of literature shows infiltration of the rectosigmoid occurs in 4% of patients with prostatic adenocarcinoma, with only 40% of patients with a preceding diagnosis before the gastrointestinal presentation. In the literature, some patients underwent rectal resection because the preoperative diagnosis was primary rectal adenocarcinoma. Since prostate carcinoma may show weak nonspecific staining for markers of colorectal carcinoma (SATB2 and CDX-2), a high index of suspicion is required for correct diagnosis of the biopsy material to avoid inappropriate resection.
Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Pancreas: A Rare Case in a Young Male
(Poster No. 49)
Tao Zhang, MD (firstname.lastname@example.org); Katsiaryna Laziuk, MD; Deepthi Rao, MD. Department of Pathology and Anatomical Sciences, University of Missouri, Columbia.
Extraosseous Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) is a rare, aggressive malignant tumor that has been reported in various sites such as lungs, biliary tract, and kidney. ES involving pancreas is considered exceptionally rare. We report a case of primary pancreatic ES in a 33-year-old man. The patient had no significant past medical history and presented with severe abdominal pain, distention, and scrotum swelling. A subsequent computed tomography scan showed ascites, diffuse lymphadenopathy, and a 20 × 19 × 13-cm abdominal mass involving pancreas and multiple smaller tumors along the peritoneum. Both CEA and CA19-9 were within normal limits. Patient underwent exploratory laparoscopy and a biopsy was obtained. On microscopy, the tumor showed nests of small, round blue cells. Immunohistochemical staining was performed. Tumor cells were positive for CD99, FLI-1, CD200, and CD56 and negative for CK7, CK20, CK17, AE1/AE3, Cam 5.2, CDX2, S100, LCA, inhibin, CD117, DOG-1, β-catenin, progesterone, and CD10. Focal expression was noted with synaptophysin and chromogranin. Ki-67 showed proliferation index of 20.3%. Fluorescence in situ hybridization studies showed rearrangement of EWSR1 gene at 22q12 with FLI1 at 11q24 (t[11;22]). The diagnosis of extraosseous ES/PNET was rendered. Extraosseous ES involving pancreas is extremely rare, and similar morphology with small, round blue cells can be noted in a broad spectrum of tumors. But early recognition of ES/PNET can be critical to produce the best chance of survival with current treatment modalities. Therefore, our case emphasizes the importance of considering extraosseous ES/PNET in the differential diagnosis of pancreatic masses.
Neuroendocrine Carcinoma Originating From a Villous Adenoma With Squamous Morules
(Poster No. 50)
Marcela Mejia-Arango, MD (email@example.com); Rocio Lopez-Panqueva, MD. Department of Pathology and Laboratories, Fundación Santa Fe de Bogotá–Universidad de los Andes, Bogotá, Colombia.
Colorectal adenomas with squamous morules are a rare phenomenon described in the literature, with up to 0.4% incidence. Neuroendocrine carcinomas associated with adenomas have also been described, although they are extremely rare. Colonic adenoma with squamous morules can exhibit some degree of neuroendocrine differentiation, which has been defined as adenoma microcarcinoid. However, the presence of high-grade neuroendocrine carcinoma has not been reported before. We present a 64-year-old woman with a 3-cm polypoid lesion in the right colon not amenable to endoscopic resection. A right hemicolectomy was performed, and a 3.5-cm sessile polypoid lesion was found in the right colon. Hematoxylin-eosin slides showed a villous adenoma with high-grade dysplasia. In the base of the lesion, a high-grade, small cell neuroendocrine carcinoma, 0.9 cm in greatest dimension and limited to the submucosa, was also found (Figure 1.50, A). As an unusual feature the adenoma showed frequent squamous morules (Figure 1.50, B). Immunohistochemistry studies showed positive staining for synaptophysin (Figure 1.50, C) and chromogranin in the neuroendocrine carcinoma and negative in the squamous morules and the adenoma. Cytokeratin 20 and CDX2 (Figure 1.50, D) were negative in the neuroendocrine carcinoma and in squamous morules, and positive in the adenoma. With β-catenin there was positive nuclear staining in the neuroendocrine carcinoma and in the squamous morules, but not in the adenoma. Coexistence of positive nuclear expression for β-catenin in the neuroendocrine carcinoma and in the squamous morules may suggest a similar origin; however, molecular studies must be performed to confirm this hypothesis.
Benign Liver Cysts–Echinococcal Cysts: A Case Report and a Concise Review
(Poster No. 51)
Aljunaid Alhussain, MD (firstname.lastname@example.org); Charles Middleton, MD; Rachel Mullins, MD; Zerelda Esquer Garrigos, MD; Ithiel James Frame, MD; Neha Varshney, MD. Department of Pathology, University of Mississippi Medical Center, Jackson.
Various benign liver cysts are encountered in daily pathology practice, namely simple biliary cysts and congenital cysts. One of these that is rarely diagnosed in the United States is echinococcal cysts (ECs). ECs are usually found in immigrants from the Middle East, North Africa, or South America. They are often subclinical, but some patients develop hepatomegaly, abdominal enlargement, and ascites. Secondary infection may also develop. Ultimately, some patients experience liver failure, involvement of adjacent organs, and death. We describe a case of a 25-year-old man who presented with abdominal pain and nausea that worsened during several weeks. He grew up in Yemen and immigrated to the United States many years prior. Imaging studies showed left hepatic lobe with cystic lesions, which were partially exophytic and deformed the liver capsule (Figure 1.51, A). The left hepatic lobe was excised and sent for pathology. Grossing showed 2 cysts (6.5 and 3.5 cm) within the liver parenchyma; each was filled with several smaller “daughter cysts” (Figure 1.51, B). Histologic sections of the cysts revealed the inner layer of the cysts consisted of a thin lining of epithelial cells that gave rise to the “brood” capsules from which scolices, or immature heads of adult worms, develop. The outer cyst layers were composed of hyalinized material surrounded by fibrosis (Figure 1.51, C and D). The differential diagnosis includes amebic abscess, pyogenic abscess, and noninfectious processes. Recognition of these rare entities is crucial for optimal patient care and because of the high risk of death associated with cyst rupture.
FXYD2 Is a Novel and Specific Marker for Intrahepatic Cholangiocarcinoma
(Poster No. 52)
Mrinal Sarwate, MD1 (email@example.com); Daniela S. Allende, MD1; Haiyan Lu, MD, PhD1; Zhen Wang, MD, PhD1; Rondell P. Graham, MBBS2; Daniel E. Roberts, MD.1 1Department of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio; 2Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Context: Adenocarcinoma of uncertain origin often presents as a liver mass and represents a frequent diagnostic challenge. In particular, adenocarcinomas originating in the upper gastrointestinal tract (GI), liver, extrahepatic biliary system, and pancreas demonstrate an overlapping morphology and immunophenotype that is difficult to distinguish in clinical practice.
Design: Sections from 69 tumors were evaluated with a panel of markers, including albumin in situ hybridization (ISH), FXYD2, DPC4, S100P, BAP1, CAV2, MUC5AC, IMP3, and K17. This cohort consisted of 19 intrahepatic cholangiocarcinomas (ICCs), 20 pancreatic ductal adenocarcinomas (PDACs), 15 upper GI adenocarcinomas (stomach, small intestine, and gastroesophageal junction), and 15 extrahepatic cholangiocarcinomas (ECCs), including both hilar and distal bile duct cholangiocarcinoma. DPC4 and BAP1 expression was scored as either retained or fully lost. The remaining markers were interpreted as positive if moderate to strong staining was present in at least 10% of tumor cells.
Results: FXYD2 expression was seen exclusively in ICC (63%), whereas albumin ISH labeling was significantly more common in, but not exclusive to, ICC (58%). Loss of DPC4 was only seen in ECC (40%) and PDAC (45%). S100P is expressed in all other tumors, but frequently lost in ICC. Results for BAP1, CAV2, MUC5AC, IMP3, and K17 were less discriminatory and are summarized in the Table.
Conclusions: FXYD2 shows higher sensitivity and specificity for identifying intrahepatic cholangiocarcinoma compared with albumin ISH in a limited cohort. The combination of DPC4 and FXYD2 may represent a diagnostically useful panel in differentiating adenocarcinomas of upper GI and pancreatobiliary origin.
A Case of Mixed Neuroendocrine-Nonneuroendocrine Neoplasm of the Gastroesophageal Junction Utilizing Endoscopic Submucosal Dissection: An Exceedingly Rare Site
(Poster No. 53)
Anu Abraham, MD1 (firstname.lastname@example.org); Hardik Sonani, MD1; Jacob Moremen, MD2; William Daley, MD1; Neha Varshney, MD.1 Departments of 1Pathology and 2Surgery, University of Mississippi Medical Center, Jackson.
Neuroendocrine tumors of the esophagus are rare, comprising only 0.2% of cases. The most recent World Health Organization classification of 2019 defines mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) as neoplasms in which both neuroendocrine and nonneuroendocrine components exceed 30%. Only 4 cases of MiNEN of the gastroesophageal (GE) junction are reported in the literature, and this is the second case report of the utilization of the endoscopic submucosal dissection technique. A 61-year-old man presented with dyspepsia and epigastric pain. Endoscopy revealed a medium-sized nonobstructing, fungating mass at the GE junction (Figure 1.53, A), which was initially biopsied and diagnosed as invasive adenocarcinoma. Subsequently, the mass was resected with endoscopic submucosal dissection with negative margins. On histopathologic examination, the tumor showed a mixed tumor composed of adenocarcinoma (50%) and neuroendocrine carcinoma (50%) (Figure 1.53, B). The neuroendocrine component was strikingly positive for synaptophysin (Figure 1.53, C), chromogranin, CD56, and Ki-67 (80%). MOC-31 was positive in both components (Figure 1.53, D). Our case was consistent with the aforementioned diagnostic criteria and was diagnosed as MiNEN. The patient was treated with adjuvant chemotherapy, including cisplatin and etoposide. This very rare case adds to the scant literature on this topic. The preoperative diagnosis of MiNEN is challenging until the final analysis of the resection specimen. Because of its uncommon presentation, little is known about the optimal management strategy, and more studies are needed to recommend new therapeutic approaches. Prognosis depends on the stage and tumor type, with a better prognosis for those tumors without distant metastatic involvement.
PD-L1 Expression in 2 Cases of Malignant Gastrointestinal Neuroectodermal Tumor in Young Adults
(Poster No. 54)
Blerta Dimo, MD, PhD1 (Blerta.Dimo@Pennmedicine.upenn.edu); Ioannis Ioannidis, MD, PhD2; Fengwei Wang, MD, PhD2; Michael Husson, MD1; Franz Fogt, MD, PhD, MBA1; Paul Zhang, MD.3 1Department of Pathology, Pennsylvania Hospital, Philadelphia; 2Department of Pathology, Virtua Health System, Camden, New Jersey; 3Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia.
Malignant gastrointestinal neuroectodermal tumor (GNET), also known as clear cell sarcoma of the gastrointestinal tract, is an extremely rare entity. We report 2 cases in small bowel of young adults. Our first case involves a 24-year-old man who presented with painless lower gastrointestinal bleeding. Imaging confirmed small bowel bleeding and Meckel scan was positive in the right lower quadrant. Our second case involves a 27-year-old man who presented with severe anemia, jejunal mass, and multiple pelvic masses. Both patients underwent segmental small bowel resection with frozen section revealing malignant neoplasm, “possibly stromal tumor.” Grossly the specimens demonstrated intramural masses, 4.5 and 4.7 cm, respectively, with fleshy cut surface, focally involving the mucosa and covered by serosa. Microscopically the tumors were located predominantly in the submucosa and muscularis propria; they displayed spindle cells in sheets, fascicles, and pseudorosettes, with weakly eosinophilic cytoplasm (case 1; Figure 1.54, A) and polygonal, epithelioid cells with clear cytoplasm, prominent nucleoli, and osteoclast-type giant cells (case 2; Figure 1.54, B). Immunohistochemical stains revealed tumor cells positive for S100, SOX10, and synaptophysin, and negative for HMB45, Melan-A, AE1/3, SMA, DOG-1, CD34, and CD117. Fluorescence in situ hybridization for EWSR1 translocation was positive, confirming the diagnosis of GNET (Figure 1.54, C). The tumor from case 2 expressed PD-L1 (22C3) with 15% tumor proportion score (Figure 1.54, D), whereas case 1 was negative. Our cases highlight the importance of including GNET in the differential diagnosis of gastrointestinal tumors in young patients. Immunohistochemistry and fluorescence in situ hybridization are crucial for differentiating GNET from other intramural tumors of the GI tract. PD-L1 expression in subset of GNET might provide a target for immunotherapy for aggressive cases.
Regression of Alcoholic Cirrhosis: Histological Evaluation of 2 Cases
(Poster No. 55)
Devin Allison, BS (email@example.com); Tao Zhang, MD; Deepthi Rao, MD. Department of Pathology and Anatomical Sciences, University of Missouri, Columbia.
Cirrhosis is known to be a dynamic process in which regression is possible with appropriate therapy. Wanless et al described the histology of cirrhosis regression as the “hepatic repair complex” in 2000. Since that time, few reports have provided supportive evidence regarding alcoholic liver disease. The aim of this report is to describe 2 cases of diagnosed cirrhosis related to chronic alcohol use in which histologic evaluation after abstinence revealed regression of disease. A 33-year-old man with chronic alcohol consumption, F4 fibrosis on FibroTest, and an esophagogastroduodenoscopy that showed small esophageal varices and mild gastritis underwent liver biopsy 5 months after alcohol cessation. Microscopy showed areas of nodular regeneration juxtaposing areas of normal hepatic parenchyma with no evidence of bridging fibrosis or cirrhosis. A 41-year-old man with chronic alcohol consumption and F4 fibrosis on Fibroscan liver elastography underwent liver biopsy 3 months after alcohol cessation. Microscopy showed preserved hepatic architecture with foci of hepatocellular regeneration and no bridging fibrosis or cirrhosis. Histology remains the gold standard for the diagnosis and understanding of the progression/regression of cirrhosis, yet it is rarely performed, especially in a setting of alcoholic liver disease. We provide 2 cases in which the histology supports regression of clinically diagnosed cirrhosis due to chronic alcohol use.
Acute Liver Failure Triggered by Therapeutic Dose of Acetaminophen in a Patient With Cystic Fibrosis
(Poster No. 56)
Andrew Biesemier, BA1; Charles E. Middleton, MD2 (firstname.lastname@example.org); Elvia Rivera-Figueroa, MD3; Hansini Laharwani, MD2; Hardik Sonani, MD2; Jan Petrasek, MD4; Jennifer Hong, MD3; Neha Varshney, MD.2 1School of Medicine, University of Mississippi, Jackson; Departments of 2Pathology, 3Pediatrics, and 4Internal Medicine, University of Mississippi Medical Center, Jackson.
Acetaminophen (APAP) toxicity is the most common cause of acute liver failure (ALF) in the United States. Even therapeutic doses can be hepatotoxic in susceptible individuals. Patients with cystic fibrosis (CF) often have glutathione deficiency and increased susceptibility to liver injury. Our case involves ALF in a 22-year-old man with CF (ΔF508/c.2657+5G>A) treated with elexacaftor/tezacaftor/ivacaftor. Following an episode of binge drinking and unintentional ingestion of 2.5 g of APAP, the patient developed nausea and vomiting, with aminotransferases >7000, synthetic liver dysfunction, renal failure, and lactic acidosis. He was outside the therapeutic window for N-acetylcysteine and developed ALF. He underwent liver transplantation 6 days after the onset of symptoms. Microscopic evaluation of the explant liver showed extensive perivenular hepatocytic damage and inflammation (Figure 1.56, A) with a moderate amount (40%) of macrovesicular and microvesicular steatosis (Figure 1.56, B). Ballooning degeneration and apoptotic hepatocytes (Figure 1.56, C) were present along with cholestasis (Figure 1.56, D). No fibrosis was identified on trichrome stain. These findings were consistent with drug/toxin injury in this patient with a history of CF and recent APAP use. This case suggests the possibility that CF patients are at increased risk for APAP-related hepatotoxicity compared with the general population. It is unknown whether this is due to glutathione depletion, underlying steatosis, concomitant medications, or other factors. The ubiquitous use of APAP in conjunction with the potential for morbidity in CF patients warrants further investigation with the goal of preventing further harm to this already vulnerable population.
NK-Cell Enteropathy: An Indolent Lymphoproliferative Disorder as a Diagnostic Pitfall for NK/T-Cell Lymphoma
(Poster No. 57)
Anup Jnawali, MD (email@example.com); Jacob Bledsoe, MD. Department of Pathology, University of Massachusetts Memorial Medical Center, Worcester.
A 43-year-old woman presented with a chief complaint of intermittent abdominal pain for several years. Colonoscopy revealed suspected patch of diverticular-related mucosal changes at 20 cm from anal verge, which was biopsied. Microscopic examination showed eroded colonic mucosa with dense infiltrate of mononuclear cells with damage of adjacent colonic crypts (Figure 1.57, A). The atypical cells had ovoid to folded nuclei and moderate to abundant pale cytoplasm with variable azurophilic cytoplasmic granules (Figure 1.57, B). By immunohistochemistry, the atypical cells were positive for CD3, CD7, CD56, TIA-1, and perforin and negative for CD5, CD8, CD25, CD30, and CD34 (Figure 1.57, C and D). In situ hybridization for EBV-encoded RNA was negative. Polymerase chain reaction for TCR gene rearrangement failed because of insufficient DNA. The findings were most consistent with NK-cell enteropathy (NKCE). NKCE is a rare indolent lymphoproliferative disorder characterized by atypical proliferation of NK cells within the mucosa of the gastrointestinal tract in adults presenting with nonspecific abdominal symptoms. NKCE shows significant immunophenotypic overlap with extranodal NK/T-cell lymphoma, which may result in misdiagnosis and unnecessary investigation and treatment. In contrast to NK/T-cell lymphoma, NKCE is not associated with EBV and does not demonstrate clonal T cell gene rearrangements. Lymphomatoid gastropathy, an entity restricted to the stomach of Japanese patients, shares overall histologic, immunophenotypic, and clinical features with NKCE.
Clinically Occult Mixed Neuroendocrine-Nonneuroendocrine Neoplasm Masquerading as Perianal Extramammary Paget Disease: A Small Series
(Poster No. 58)
Daniela Pereira, MD1 (firstname.lastname@example.org); Kun Jiang, MD, PhD.2 1Department of Pathology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal; 2Department of Pathology, Moffitt Cancer Center, Tampa, Florida.
Context: Extramammary Paget disease (EMPD) is a rare group of insidious yet challenging entities characterized by intraepithelial infiltration by mucin-rich signet ring–like neoplastic cells. It can be primary (skin intraepidermal) or secondary to skin adnexal adenocarcinomas or visceral malignancies. EMPD remains notorious for its underdiagnoses and recurrence following resections. EMPD associated with mixed neuroendocrine-nonneuroendocrine neoplasm (MINEN) has remained elusive and poorly understood clinically and pathologically.
Design: Review of the gastrointestinal archive identified 3 perianal EMPD cases that were originally diagnosed as skin adnexal primary, but progressed despite clinical interventions. Subsequently rebiopsies were performed, and systemic ancillary testing was conducted.
Results: All cases (79-year-old woman and 77- and 38-year-old men) showed intraepidermal spreading of Paget cells; additionally, the first 2 showed poorly differentiated mucinous carcinoma containing signet ring–like and polygonal cells with pink granular cytoplasm arranged in clusters, glands, and single files, whereas the third patient showed portion of tubulovillous adenoma with intramucosal carcinoma and EMPD involving adjacent anal mucosa. Immunostains revealed strongly positive synaptophysin, chromogranin A, INSM1, CDX2, and CK20, negative GATA3, and weak CK7 in both carcinomas and intradermal Paget cells of all cases, with amphicrine features. Combined, these findings uncovered an originally unsuspected MINEN-EMPD association. Two patients underwent FOLFOX chemotherapy followed by resection; no recurrence was detected more than 60 months later. The third patient is currently undergoing prechemo radiology/imaging studies.
Conclusions: This study illustrates an underrecognized MINENEMPD association, highlighting the pivotal roles of systemic histomorphologic and immunohistochemical evaluation. Awareness of this differential diagnosis is essential for ensuring pathologic diagnosis and proper patient management.
Supplemental Studies Including Aberrant CD43 Expression as a Helpful Marker in Evaluation of Post-treatment Gastric MALT Lymphoma
(Poster No. 59)
Anup Jnawali, MD (email@example.com); Karen Dresser, BS; Jacob Bledsoe, MD. Department of Pathology, University of Massachusetts Memorial Medical Center, Worcester.
Context: Evaluation of posttreatment biopsies for gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is challenging given the morphologic and immunophenotypic overlap with gastritis and reactive lymphoid hyperplasia. The GELA histologic scoring system is commonly used. We hypothesized that immunohistochemical (IHC) and molecular methods may supplement hematoxylin-eosin evaluation of such cases.
Design: We reviewed 24 cases of gastric MALT lymphoma and follow-up biopsies diagnosed at our institution between 2005 and 2020. MALT lymphoma was diagnosed based on the World Health Organization classification. Potential useful markers for MALT lymphoma in pretreatment and posttreatment biopsies were evaluated including aberrant CD43 expression, presence of clonal plasma cells by IHC or in situ hybridization (ISH), presence of clonal B cells, or presence of MALT1 translocation.
Results: CD43 IHC was performed in 19 of 24 cases and showed aberrant expression in lymphoma cells in 14 cases (74%). Clonal plasma cells were identified by IHC/ISH in 5 of 20 cases (25%). Molecular B cell clonality was positive in 11 of 14 cases (79%). FISH for MALT1 rearrangement was positive in 3 of 9 cases (33%). Overall, 5 of 19 cases (26%) did not demonstrate CD43 aberrancy or evidence of clonality or MALT1 rearrangement.
Conclusions: Identification of aberrant CD43 expression, clonal plasma cells, B cell clonality, and MALT1 translocation are useful markers that may be used in posttreatment biopsies for gastric MALT lymphoma. We show that aberrant CD43 expression is frequent in gastric MALT lymphoma. Prior studies have shown low rates of CD43 positivity in MALT lymphomas of various sites, but its frequency in gastric MALT lymphoma is not well studied.
A Case of Mucinous Adenocarcinoma Arising From Retrorectal Cystic Hamartoma
(Poster No. 60)
Alexander Smith, MD (firstname.lastname@example.org); Sahar Nozad, MD. Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington.
Retrorectal cystic hamartoma or tailgut cyst is a rare congenital malformation that presents in the presacral space. Tailgut cysts arise from tailgut embryonic remnants and are more common in females. Malignant transformation of tailgut cysts is very rare. We report a case of an 83-year-old woman who presented with progressive pelvic pressure and elevated serum carcinoembryonic antigen levels. Imaging studies revealed a cystic mass with irregular wall thickening and enhancing solid component centered in the retrorectal/presacral space. The mass was resected, and the initial extensive samplings of specimen showed a multiloculated cystic structure with mucinous glandular epithelium as well as squamous linings. A focus of dysplastic columnar epithelium (Figure 1.60, A) was identified and therefore the entire specimen was submitted for histologic examination. The additional sections revealed few floating malignant epithelial cells within pools of extracellular mucin (Figure 1.60, B) as well as foci of invasive adenocarcinoma (Figure 1.60, C). Immunohistochemical stain for CK20 highlighted the neoplastic glands (Figure 1.60, D). The diagnosis of mucinous adenocarcinoma arising from a tailgut cyst was rendered. The carcinoma focally extended to the surgical resection margin and there was also acellular mucin present at the margin. Periodic positron emission tomography–computed tomography scans and serum carcinoembryonic antigen levels for assessing the treatment response and early detection of possible future recurrence were recommended. Although malignancy arising in tailgut cyst is very uncommon, this case demonstrates the importance of adequate samplings in these lesions to avoid missing an important diagnosis with significant impact on patient prognosis and follow-up.
Small Bowel Diverticulosis and Malrotation
(Poster No. 61)
Randa Dafalla, MD (email@example.com). Department of Pathology, Rutgers Robert Wood Johnson, New Brunswick, New Jersey.
Diverticulosis of the small bowel is a rare entity; it is seen in approximately 1% of the population. It is commonly multiple and can vary from a few millimeters to several centimeters in size. Small bowel diverticulosis generally lacks a true muscular wall. The clinical picture may be an incidental finding without symptom, an acute complication, or chronic symptoms. A 65-year-old woman with past medical history of GERD presented with severe abdominal pain and was found to have small bowel diverticulosis complicated by diverticulitis and perforation. Computed tomography of abdomen with contrast also showed an unusual anatomic variant consisting of the ascending colon, terminal ileum, and cecum extending across the midline into the left upper quadrant. She underwent small bowel resection. Specimen received in pathology consisted of a segment of small bowel (44 cm) with more than 20 diverticula, the largest measuring 3.2 cm with focal exudate formation. Histology revealed diverticulosis, severe diverticulitis with abscess formation, and focal perforation. This case reports a jejunal diverticulosis associated with congenital dislocation of the terminal ileum, cecum, and ascending colon. The most common types of small bowel diverticula are congenital in origin and include Meckel diverticulum and duodenal diverticulosis. Less commonly, acquired cases of small bowel diverticulosis are encountered secondary to neuromuscular abnormalities. In this case, it is unclear if the diverticulosis is due to a congenital cause or acquired (Figure 1.61).
Primary Gastrointestinal Stromal Tumor of the Liver Presenting as a Cystic Mass
(Poster No. 62)
Anna S. Bouck, BS (Anna.firstname.lastname@example.org); Blaire A. Anderson, BS; Bing Ren, MD, PhD. Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal-origin tumors of the gastrointestinal tract. They commonly arise in interstitial cells of Cajal that have acquired receptor tyrosine kinase gene mutations, most commonly KIT or PDGFRA mutations. GISTs are most frequently located in the luminal gastrointestinal tract. Primary GIST of the liver is exceedingly rare, though metastatic spread of GIST to the liver is fairly common. We present a case of primary GIST of the liver in a patient with a large cystic liver mass. A 70-year-old woman presented with a 6-month history of abdominal pain and distention. Computed tomography scan revealed a cystic hepatic mass measuring 23 × 20 × 14 cm with an irregular thickened wall and septations replacing nearly the entire right lobe of the liver (Figure 1.62, A). A fine-needle aspiration was nondiagnostic with a mixture of erythrocytes, macrophages, and leukocytes. Resection was performed. Intraoperatively, 1.5 L of bloodlike fluid was drained from the mass and the cystic wall was submitted for pathology. Histologic examination revealed the wall consisted of GIST cells, epithelioid type, with fibrosis and fibrin along the inner surface (Figure 1.62, B). The histologic grade was high with a mitotic rate of 18/5 mm2. CD117 and DOG1 were diffusely positive on immunostains (Figure 1.62, C and D). Immunohistochemistry revealed intact nuclear staining in tumor cells for MLH1, MSH2, MSH6, and PMS2. To our knowledge, this is the largest reported primary GIST of the liver with epithelioid features and a high mitotic rate. The patient remains without recurrence after 3 months of follow-up.
Steatohepatitic Variant of Hepatocellular Carcinoma in Pediatric Population Represents Distinct Clinicopathologic Entity
(Poster No. 63)
Natalia Yanchenko, MD, PhD (email@example.com); Ali G. Saad, MD. Department of Pathology, University of Miami Miller School of Medicine, Jackson Memorial Health System, Miami, Florida.
Context: Steatohepatitic variant of hepatocellular carcinoma (SH-HCC) is a variant recapitulating steatohepatitis and often associated with metabolic syndrome. The demographics, risk factors, clinicopathologic characteristics, and prognosis of SH-HCC in the pediatric population are not well characterized, which may lead to underdiagnosis and ineffective treatment approaches.
Design: The pathology databases (2004–2021) of the participating institutions were searched for hepatocellular carcinoma with steatosis in the pediatric population. Cases for which histologic materials and follow-up information were available were included in the study. Slides were reviewed to satisfy SH-HCC criteria. Targeted next-generation sequencing was used for genomic analysis.
Results: Eight cases fulfilled the study criteria. Genetic information was available for case 1. The results are summarized in the Table. Important findings included the following: SH-HCC occurred predominantly in white boys 9.0 ± 7.1 years old. It was not associated with infectious hepatitis or metabolic syndrome. It often arose with a background of cirrhosis (63%) or steatosis (63%). At diagnosis, SH-HCC was predominantly confined to the liver, and AFP was increased in 50%. SH-HCC was refractory to chemotherapy but had favorable prognosis with surgical treatment. Histologically SH-HCC tended to be multifocal (89%) mpT2 and well differentiated (G1) with bland features and very rare mitoses or lymphovascular invasion (13%). Genetic alterations in case number 1 included CTNNB1 in-frame exon 3 156-bp deletion and MAPK1 p.Glu322Lys missense variant.
Conclusions: Despite extreme infrequency, SH-HCC occurs in the pediatric population even in children without underlying liver disease. Strict diagnostic criteria and genetic profiling of this tumor is required to avoid unnecessary chemotherapy and develop effective targeted therapy of pediatric SH-HCC.
Granular Cell Tumor of the Intra-pancreatic Common Bile Duct: A Rare Entity
(Poster No. 64)
Mohammad M. Al-Attar, MD (firstname.lastname@example.org); Jacob R. Bledsoe, MD. Department of Pathology, University of Massachusetts Medical School, Worcester.
Granular cell tumor (GCT) is an uncommon, largely benign neoplasm with neuroectodermal differentiation usually found in peripheral soft tissue, trunk, head, and neck with predilection of the tongue and the gastrointestinal tract. GCT of the common bile duct (CBD) is uncommon, with a variable presentation depending on the degree and site of involvement, with most being located in the extrapancreatic CBD. GCTs of the intrapancreatic CBD are exceedingly rare. We report a case of a 41-year-old woman presenting with epigastric pain. Abdominal imaging revealed a CBD defect with upstream dilation, concerning for either a neoplasm or a stone. Subsequent endoscopic retrograde cholangiopancreatography revealed a partially occluding CBD mass. The duct was stented, and fine-needle aspiration of the mass was consistent with GCT. Persistence of the patient's symptoms prompted the decision to perform a Whipple procedure. Grossly, the specimen revealed an ovoid, tan-white, 1.3 × 0.6 × 0.5-cm mass (Figure 1.64, A) arising from the wall of the intrapancreatic CBD, 4.0 cm proximal to the ampulla of Vater, and causing duct obstruction. Microscopically (Figure 1.64, B, asterisk), the tumor consisted of sheets of cytologically bland cells with eosinophilic granular cytoplasm (Figure 1.64, C) and no features concerning for malignancy. The tumor cells were positive for S100 (Figure 1.64, D, asterisk) and CD68. Postprocedure, the patient's symptoms improved markedly. This case illustrates a rare location of GCT, posing a challenge in terms of diagnosis and management of an already uncommon entity.
Function of Enhancer of Zeste Homolog 2 (EZH2) Protein and Its Associated Intracellular Signaling Molecules P-ERK, MYC, and P-STAT3 in Pancreatic Cancer
(Poster No. 65)
Linlin Yang, MD, PhD1 (email@example.com); Shaomin Hu, MD, PhD2; Jiani Chai, MD, PhD3; Qiang Liu, MD3; Xuejun Tian, MD, PhD.3 1Department of Pathology, Case Western Reserve University–MetroHealth Medical Center, Cleveland, Ohio; 2Department of Pathology, Cleveland Clinic, Cleveland, Ohio; 3Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York.
Context: EZH2, an important histone methyltransferase, has been shown to play an important role in tumorigenesis of various carcinomas and hematopoietic neoplasms. Here we investigated the expressions of EZH2 and its associated potential regulators p-ERK, MYC, and p-STAT3 in pancreatic cancer.
Design: Immunohistochemical staining for EZH2, p-ERK, p-STAT3, and MYC was performed in 41 pancreatic adenocarcinoma and 6 intraductal papillary mucinous neoplasm (IPMN) cases. Positive staining of neoplastic cells was scored. Statistical analysis was performed using Fisher exact test by Graphpad Prism (San Diego, California).
Results: Thirty-five of 41 cases of pancreatic adenocarcinoma (85.3%) showed strong EZH2 expression, whereas the low-grade IPMN showed no or very low EZH2 expression. Among pancreatic adenocarcinoma cases, 65.8% (27 of 41) showed strong p-ERK expression; 43.3% (16 of 37) showed strong MYC expression; and 47.2% (17 of 36) showed strong p-STAT3 expression (Table). Interestingly, EZH2 and p-ERK1/2 expression showed no significant association with tumor grades and lymph nodal metastasis, whereas MYC and p-STAT3 expression significantly increased in moderate to poorly differentiated carcinoma (P < .01). Further study of EZH2-positive cases showed 66% (23 of 35) coexpressed pERK1/2, 41% (13 of 32) coexpressed MYC, and 56% (19 of 34) coexpressed pSTAT3. MYC and/or pSTAT3 coexpression with EZH2 were significantly increased in the higher-grade tumors with or without metastasis and strongly associated with survival/prognosis (P < .01).
Conclusions: EZH2 is strongly expressed in advanced stage of pancreatic adenocarcinoma, indicating its oncogenic role in pancreatic cancer. MYC and/or pSTAT3 in association with EZH2 expression appears to play a critical role in driving tumor progression. These molecules may service as prognostic biomarkers and therapeutic targets for advanced pancreatic cancer.
Morphological Correlates of Tumor Mutation Burden in Colorectal Adenocarcinoma: A Tertiary Cancer Center Experience
(Poster No. 66)
Swachi Jain, MBBS (firstname.lastname@example.org); Yonah Ziemba, MD; Taisia Vitkovski, DO; Rebecca Thomas, MD; Arvind Rishi, MD. Department of Pathology, Northwell Health–Long Island Jewish Medical Center, New Hyde Park, New York.
Context: Tumor mutation burden (TMB) is defined as the number of mutations per megabase region of tumor. Colorectal carcinoma (CRC) with low TMB is shown to have poor treatment response. Our study reports association of TMB with known morphologic prognostic factors of CRC.
Design: Retrospective review of 1374 primary CRCs was performed at a tertiary care center from 2016 to 2020. TMB analysis was done at Foundation Medicine, Cambridge, Massachusetts. The association of TMB with microsatellite (MS) status, nodal metastases, lymphovascular invasion (LVI), and tumor budding was studied and analyzed using χ2 test. Cases with fewer than 12 mutations were classified as low TMB as per The Cancer Genome Atlas for CRC.
Results: Molecular analysis including TMB was requested in 8.6% of primary CRCs (n = 119), of which 80.6% (n = 96) had low TMB. Presence of low TMB (Table) was associated with a lower incidence of MS instability (2.1% versus 82.6%; P < .05), higher incidence of nodal metastases (82.29% versus 43.48%; P < .05), LVI (80.90% versus 43.48%; P < .05), and high tumor budding (31.11% versus 28.57%; P = .41). Mutation profiling of low-TMB cancers showed high frequency of mutations in TP53 and APC, followed by PIK3CA, SMAD4, SOX9, CTNNB1, FBXW7, and ARID1A.
Conclusions: Low TMB showed significantly high association with poor prognostic factors including MS instability, LVI, and regional nodal metastases. Our study suggests that routine TMB analysis of primary CRC may be helpful in predicting prognosis and personalize management. Further studies in mutation profiling may identify novel therapeutic targets that could improve survival in this subset of CRCs.
Ki-67 Proliferation Index in Fine-Needle Aspiration to Predict the Tumor Biological Aggressiveness in Pancreatic Neuroendocrine Tumors
(Poster No. 67)
Bahram Dabiri, MD1 (email@example.com); Bebu Ram, MD1; Chaohui Lisa Zhao, MD2; Iman Hanna, MD2; Mala Gupta, MD2; Jianhong Zhou, MD.2 1Department of Pathology, NYU Winthrop Hospital, Mineola, New York; 2Department of Pathology, NYU Langone Long Island Hospital, Mineola, New York.
Context: Nonfunctioning (NF) pancreatic neuroendocrine tumors (PNETs) are small, asymptomatic, and vary in growth rate with malignant potential. It is unclear when surgery is necessary when the tumor size is between 1 and 2 cm. The proliferation rate in PNETs can help to predict the aggressiveness of the tumor.
Design: A retrospective observational study performed on patients undergoing surveillance for PNETs (January 2010 to May 2020). Data collection included age, sex, size of tumor in imaging, location, grade, Ki-67 index, and mitotic activity in fine-needle aspiration (FNA) and surgical specimen with diagnosis of PNETs confirmed by 2 gastrointestinal pathologists.
Results: A total of 40 surgical resection specimens were identified (18 F, 22 M), with an age of 61.9 ± 13.6 years (range, 29–84 years). The range of tumor size was 0.2 to 10 cm (3.38 ± 2.55 cm). In these 40 cases, 23 (57.5%) had prior EUS-FNA. The concordance rate of PNET grade between EUS-FNA and surgical specimens was 79% (P < .01). All grade 1 tumors were correctly graded on FNA except one case without tumor cells on FNA. However, in grade 2 and grade 3 tumors, the concordance rate was only 43%. Compared with the surgical specimens, the Ki-67 index in EUS-FNA tended to underestimate when the value was more than 2%.
Conclusions: Grade and Ki-67 index in EUS-FNA can be used to predict grade and Ki-67 in surgical specimens. However, Ki-67 index evaluated on EUS-FNA tends to undergrade PNETs when the value is more than 2%. Grade 2 and grade 3 PNETs could be underestimated in a significant number of cases in EUS-FNA.
A Rare Phenotype of α-1 Antitrypsin Mutation
(Poster No. 68)
Busha Hika, BS1 (firstname.lastname@example.org); Kelly Bowers, DO1; Neal Sharma, MD2; Deepthi Rao, MD.1 Departments of 1Pathology and Anatomical Sciences and 2Division of Gastroenterology and Hepatology, University of Missouri Health, Columbia.
A PiFZ heterozygote phenotype is a rare variant of α-1 antitrypsin (AAT) with normal plasma levels of AAT and the inability to inhibit serine proteases such as elastase. Liver cirrhosis in a PiFZ phenotype was first reported in 1974. Since then, only a few more cases of PiFZ phenotype have been reported. Most of these reports have suggested that PiFZ phenotype may predispose to lung and liver diseases. Here, we present the case of a 36-year-old woman with a PiFZ mutation. The patient had a history of diabetes mellitus, obesity, and hyperlipidemia, and initially presented with elevated liver enzymes and ultrasound findings of hepatomegaly with steatosis. During workup for hepatomegaly and steatosis, her AAT level was found to be 93 mg/dL (NL 100–300 mg/dL). Subsequent phenotyping showed a PiFZ variant of AAT with a level of 108 mg/dL. This phenotype is an uncommon variant of heterozygous mutation of AAT deficiency. Liver biopsy showed steatohepatitis with a NAFLD score of 3/8 (steatosis grade 1/3, lobular inflammation 1/3, and hepatocellular ballooning 1/2). In the periportal areas, minute eosinophilic intracytoplasmic globules of PAS and AAT positivity were noted, although the intracytoplasmic globules were less prominent compared with the conventional type of AAT deficiency with PiZZ mutation. Studies have reported the correlation between PiZZ mutation and NAFLD; however, the synergistic effect of PiFZ mutation and NAFLD in the development of liver fibrosis remains to be determined. Our case highlights the clinical significance of this uncommon variant of AAT mutation and the need for further studies.
Expression of Immunohistochemical Markers (CD117, mCEA, and CD56) in Giardia lamblia Trophozoites
(Poster No. 69)
Swachi Jain, MBBS (email@example.com); Yonah Ziemba, MD; Lili Lee, MD. Department of Pathology, Northwell Health–Long Island Jewish Medical Center, New Hyde Park, New York.
Context: Giardiasis is an infectious cause of diarrhea seen in 0.11% of duodenal biopsies. Duodenal biopsies demonstrate highest sensitivity (82.5%–100%) for diagnosis but can often be missed or misinterpreted on hematoxylin and eosin slides. Considering a low prevalence and simple treatment, we interpreted expression pattern of different immunohistochemical stains for the diagnosis of Giardia lamblia.
Design: Retrospective analysis of duodenal biopsies from January 2011 through January 2020 in our health system was performed. Seven cases of giardiasis were identified, and diagnosis was confirmed. Five cases had material remaining on the paraffin block, and the expression of CD117, monoclonal carcinoma embryonic antigen (mCEA), and CD56 was studied. Duodenal biopsies without giardiasis were paired as controls.
Results: CD117 stained the paired nuclei and apical cellular membrane of trophozoites in 4 of 5 cases (80%). Three of 5 cases (60%) were positive for mCEA and stained the paired nuclei. All cases were negative for CD56 stain. The lamina propria showed internal control staining of mast cells (CD117) and natural killer cells (CD56).
Conclusions: CD117 staining is currently the best immunohistochemical stain for diagnosis of giardiasis because of its consistent and typical staining pattern, followed by mCEA. Other stains need further studies to identify utility in daily practice. Frequent antigenic shifts can occur following interaction with the duodenal mucosa and treatment, which could explain the variable expression of markers. Routine staining of duodenal biopsies with CD117 in cases with high clinical suspicion and travel history should be encouraged to confirm the diagnosis and enhance patient care.
A Case of Checkpoint Inhibitor–Induced Colitis in the Pediatric Population
(Poster No. 70)
Roshan Mahabir, MD (firstname.lastname@example.org); Crystal Bockoven, MD; Murad Alturkustani, MD; Nick Shillingford, MD; Shengmei Zhou, MD; Mika Warren, MD; Larry Wang, MD, PhD; Larry Wang, MD, PhD; Bruce Pawel, MD. Department of Pathology, Children's Hospital Los Angeles, California.
Immune checkpoint inhibitors are immunotherapeutics with fewer side effects than chemotherapy. However, colitis is an important complication and has been described in adults; we present the first case in an adolescent male. An 18-year-old male with a history of Lynch syndrome and glioblastoma multiforme status post resection and radiation but without history of inflammatory bowel disease, transplant, or infection presented with weeks of abdominal pain and bloody stools (more than 10 episodes per day). He had started PD-1 inhibitor (pembrolizumab) therapy 10 days prior. Clinical workup for infectious etiologies and inflammatory bowel disease were all negative. Endoscopy and colonoscopy visualized evidence of esophagitis, gastritis, duodenitis, and severe left-sided colitis. Consistently, biopsies showed mild to moderate acute and chronic inflammation in the esophagus, stomach, and duodenum; severe active colitis with ulceration, neutrophilic microabscesses, epithelial cell apoptosis, and necroinflammatory exudates in the transverse and descending colon; severe chronic active colitis with reactive atypia in the sigmoid colon and rectum; and no significant histopathologic abnormalities in the ileum and ascending colon. No granulomas, dysplasia, or viral inclusions were identified. There was no basal plasmacytosis or lymphoplasmacytic expansion of the lamina propria. Given both the history and clinicopathologic findings, this case most likely represented a side effect of the patient's immunotherapy, though a remote possibility of early-stage Crohn disease cannot be completely ruled out. Because of these findings, the patient is undergoing reevaluation of his immunotherapy regimen. We present this case to raise awareness of this entity in pediatrics.
“Mesenteric Cyst”—Differential Diagnoses and Associated Uncommon Histologic Features
(Poster No. 71)
Sanica Bhele, MD1 (email@example.com); Rahul Jawale, MD1; Victoria Pepper, MD2; Ashraf Khan, MD.1 Departments of 1Pathology and 2Pediatric Surgery, UMass-Baystate, Springfield, Massachusetts.
Enteric duplication cysts are rare congenital abnormalities and are most often detected in the first few years of life. The most common involved site is ileum, but it can occur anywhere along the gastrointestinal tract. The presenting symptoms can be variable depending upon size and location of the cyst. We report an unusual presentation of a “mesenteric cyst,” the differential diagnoses, and associated uncommon histologic features. A 3-year-old girl presented to the emergency department with abdominal pain, vomiting, and low-grade fever. Imaging revealed a thick-walled cystic mass above the bladder with fluid-filled levels. On diagnostic laparoscopy, the cystic mass was noted within the mesentery of the terminal ileum. The resection specimen was a 4.2-cm unilocular cystic structure with predominantly smooth lining. The cyst wall exhibited mucosa, submucosa, a well-defined muscularis propria with nerves and ganglion cells, and serosa. The lining epithelium was variable, predominantly demonstrating ciliated pseudostratified columnar epithelium. The organized muscular layer excluded an enterogenous cyst and mesenteric cyst, and a diagnosis of enteric duplication cyst was rendered, highlighting that assessment of ganglion cells in the muscular wall in a “mesenteric cyst” is essential. Several case reports have reported respiratory epithelium in foregut duplication cysts; however, ciliated epithelium in a midgut enteric duplication is very rare, and only a few cases have been reported. Albeit rare, given the advent of advanced imaging and laparoscopic surgery, these cases have frequently involved a surgical specimen and warrant an increased awareness of diverse microscopic findings.
A Granular Cell Tumor of the Rectum: A Very Rare Entity
(Poster No. 72)
Rana Shadid, MD (firstname.lastname@example.org); Surendra Singh, MD. Department of Pathology, University of Toledo Medical Center, Toledo, Ohio.
Granular cell tumor, also known as Abrikossoff tumor, is a soft tissue neoplasm arising from Schwann cells. Although it is predominantly a benign tumor, 1% of the cases are reported to be malignant. About 10% of the tumors develop in the gastrointestinal tract, with esophagus being the most common site and rectum being the rarest. We report a case of granular cell tumor in a 52-year-old man who presented to the gastroenterology clinic for screening colonoscopy. The patient denied any gastrointestinal-related complaints with no family history of colon cancer. Colonoscopy revealed a submucosal, smooth, yellowish 10-mm semisessile polyp in the rectum at 10 cm proximal to the anus, which was removed with a hot snare without complication (Figure 1.72, A). Histologic examination on low power showed a polyp with intact mucosa overlying a submucosal, poorly circumscribed unencapsulated tumor (Figure 1.72, B). On higher magnification, the tumor was composed of plump polygonal cells with abundant granular eosinophilic cytoplasm and small to large nuclei with vesicular chromatin (Figure 1.72, C). Immunohistochemical stains showed the neoplastic cells were diffusely and strongly positive for S100 (Figure 1.72, D) and negative for desmin, smooth muscle actin, c-kit, and CD34. Thus, the resected tumor was diagnosed as a benign granular cell tumor with uninvolved margins. It is important for pathologists to be aware of varying benign and malignant entities that show granular cell changes. Differential diagnoses include leiomyoma and leiomyosarcoma, gastrointestinal stromal tumor, melanoma, and metastatic renal cell carcinoma. Careful evaluation of clinical, histologic, and immunohistochemical findings should facilitate an accurate diagnosis.
Pancreatic Heterotopia of the Gallbladder
(Poster No. 73)
Mohamed A. Yakoub, MD1 (email@example.com); Nicola H. Jing, MD1; Aisha Sethi, MD.2 1Department of Pathology, University of Cincinnati Medical Center, Cincinnati, Ohio; 2Department of Pathology, VA Cincinnati Medical Center, Cincinnati, Ohio.
Pancreatic heterotopia is aberrantly located pancreatic tissue having no vascular, neural, or anatomic connection to the normal pancreas. Commonly located in the stomach, it has also been reported in the small bowel, omentum, hepatobiliary system, spleen, and mediastinum. Involvement of the gallbladder is rare with reported incidence being 0.1%. Clinically it can present as acute and chronic cholecystitis and rarely an obstructing mass. We report a case of a 36-year-old man with a history of hyperlipidemia who presented with history of right upper quadrant abdominal pain and weight loss. Abdominal ultrasound demonstrated cholelithiasis and sludge within the gallbladder. Grossly, the gallbladder measured 8 × 3.5 × 3 cm and appeared distended with cholelithiasis. Microscopic examination revealed a focus of pancreatic heterotopia measuring 7 mm within the muscularis propria. It was composed of pancreatic acini, ducts, and islets and was classified as modified Heinrich type I. No dysplasia or malignancy was identified. The gallbladder was extensively sampled but no other foci of pancreatic heterotopia or other lesions were identified. Background gallbladder showed acute and chronic cholecystitis with focal intestinal metaplasia. Pancreatic heterotopia of the gallbladder is a very rare condition. It is important to recognize this entity to prevent overdiagnosis as a malignancy. Additionally, recognition is important to avoid potential complications and related pathologies.
Lifting Agent Granuloma—Gross Specimen, Frozen Section Analysis, Hematoxylin and Eosin Findings, and Immunohistochemical Phenotype
(Poster No. 74)
Jacky Z. Akhter, MD, MS (firstname.lastname@example.org); Ashwyna Sunassee, MD; Douglas Lynch, MD. Department of Pathology, Sanford School of Medicine, Sioux Falls, South Dakota.
We present the case of a 58-year-old woman with a lifting agent granuloma (LAG), a novel entity that occurs because of use of nonsaline lifting agents Eleview and ORISE gel during gastrointestinal (GI) procedures. The gels elevate the mucosa from the muscularis propria, aiding in the removal of lesions confined to the mucosa or submucosa. However, the gels linger within the submucosa of the GI tract for an extended amount of time, leading to clinical presentations that can be concerning for malignancy, as was the case with our patient. Our patient had a tubulovillous adenoma, which was partially removed with the use of ORISE gel. Approximately 4 months later, she underwent a robotic assisted partial cecectomy, during which a frozen section analysis was requested because of clinical concern for malignancy. The gross specimen revealed a firm, tan-yellow to tan-white, well-circumscribed nodule within the submucosa (Figure 1.74, A). Microscopic examination showed colonic mucosa with submucosal amorphous material, with giant cell reaction (Figure 1.74, B). The material was nonrefractile, nonpolarizable, Congo red negative, with a faint blush on Alcian blue and variable positivity on trichrome, and was negative for mucicarmine, PAS, and PAS-D, consistent with a LAG (Figure 1.74, C and D). This helped the patient avoid a colon resection, as the diagnosis was deemed benign. It is imperative to gain awareness of this entity, as this will not only result in accurate diagnosis but also avoid the diagnostic pitfall of amyloid or a malignant neoplasm, which will avoid unnecessary surgeries or morbidity for patients.
RNA-Seq Analysis of Hepatocellular Carcinoma Liver Samples Identified Oxidative Phosphorylation as the Major Pathogenetic Feature
(Poster No. 75)
Yongjun Liu, MD, PhD1; Geunyoung Jung, MD1 (GJung@uwhealth.org); Yao-Zhong Liu, MD, PhD.2 1Department of Pathology, University of Wisconsin–Madison; 2Department of Biostatistics and Data Science, Tulane University, New Orleans, Louisiana.
Context: Dysregulation of mRNAs and associated genes plays critical roles in the etiology and progression of hepatocellular carcinoma (HCC). Previous transcriptomic studies of HCC have been largely focused on Asian populations based on microarray platforms. Next-generation–based RNA sequencing has provided an unparalleled power to comprehensively characterize HCC at the whole transcriptome level.
Design: We identified 17 fresh frozen HCC samples of white patients with paired nonneoplastic liver from our Biobank inventory. RNA-seq analyses were performed to identify genes, pathways, and functional terms differentially regulated in HCC versus normal tissues.
Results: At an FDR level of 0.1, a total of 13% (n = 4335) of transcripts were upregulated and 19% (n = 6454) down-regulated in HCC versus normal tissues, suggesting major transcriptomic dysregulation in HCC. Eighty-five KEGG pathways were differentially regulated (FDR <0.10), with almost all pathways (n = 83) upregulated in HCC. Among the top upregulated pathways was oxidative phosphorylation (hsa00190) (FDR = 1.12 × 10−15), which was confirmed by DAVID enrichment analysis using upregulated genes (Bonferroni corrected, P < .05). Consistent with oxidative stress, several DNA damage–related signals, for example, the upregulated hsa03420 nucleotide excision repair (FDR = 1.14 × 10−4) and hsa03410 base excision repair (FDR = 2.71 × 10−4), were observed. Additionally, among down-regulated genes (Bonferroni corrected, P < .05), terms related to cellular structures, for example, cell membrane (FDR = 3.05 × 10−21) and cell junction (FDR = 2.41 × 10−7), were highly enriched, suggesting a breakdown of cellular structure in HCC.
Conclusions: Our findings support oxidative phosphorylation and the associated oxidative stress damage as the major driving factor and pathologic feature in HCC.
Congenital Pouch Colon With Aganglionosis: A Distinct Anorectal Malformation
(Poster No. 76)
Bryce Parkinson, DO, MBA1 (email@example.com); Amal Shukri, MBBS2; Richard Wood, MD3; Archana Shenoy, MD.4 1Department of Pathology, The Ohio State University Wexner Medical Center, Columbus; Departments of 2Pathology and 3Pediatric Colorectal and Pelvic Reconstructive Surgery, Nationwide Children's Hospital, Columbus, Ohio; 4Department of Pathology, Nationwide Children's Hospital and The Ohio State University Wexner Medical Center, Columbus.
Congenital pouch colon is a rare phenomenon characterized by a congenital dilatation of a segment of distal colon. It is often associated with an imperforate anus/anorectal malformation and sometimes with vesicular fistula. There are several subtypes, which represent a spectrum of disease differentiated by the amount of colon involved ranging from the entire colon to only a short distal segment. The majority of cases are reported in northern India with rare cases reported elsewhere. Here we report a 23-month-old female with a history of trisomy 21, congenital imperforate anus, and previous diverting colostomy where a congenital pouch colon was identified and resected during a planned exploratory laparotomy and anoplasty procedure (Figure 1.76, A and B). No vesicular anastomosis was identified. Gross examination revealed a blind-ending dilated segment of large bowel. Histologically, absence of ganglion cells as well as submucosal nerve hypertrophy (up to 90 μm in diameter) was noted in the distal 10 cm of the specimen with negative calretinin staining (Figure 1.76, C and D). Adjacent to the blind end, focal mucosal heterotopia was seen consisting of ciliated columnar epithelium. The proximal 6 cm of the specimen exhibited normal ganglion cells without submucosal nerve hypertrophy (up to 40 μm in diameter). In summary, this case represents a rare occurrence of congenital pouch colon outside the Indian subcontinent. As demonstrated, congenital pouch colon is a distinct anorectal malformation that may be associated with ganglionitis, as demonstrated here. Post resection and anoplasty, our patient is demonstrating clinical improvement with appropriate nutritional supplementation.
Utilization of a Systematic Histopathology Protocol Led to the Discovery of High Prevalence of Eosinophilic Gastritis and/or Eosinophilic Duodenitis in Patients With Moderate-Severe Gastrointestinal Symptoms: Results From 2 Prospective Studies
(Poster No. 77)
Robert M. Genta, MD1 (firstname.lastname@example.org); Kevin O. Turner, DO2; Margaret H. Collins, MD3; Marjorie M. Walker, BMBS4; Amol P. Kamboj, MD6; Henrik S. Rasmussen, MD, PhD6; Nicholas J. Talley, MD, PhD.5 1Department of Pathology, Inform Diagnostics, Irving, Texas; 2Department of Pathology, UT Southwestern, Dallas, Texas; 3Cincinnati Center for Eosinophilic Disorders, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Departments of 4Anatomical Pathology and 5Faculty of Health and Medicine, University of Newcastle, New South Wales, Australia; 6Department of Clinical Development and Medical Affairs, Allakos, Inc, Redwood City, California.
Context: Eosinophilic gastritis (EG) and/or duodenitis (EoD) are detected with increasing frequency. Although there are not yet consensus diagnostic criteria, recent prospective trials have used standardized diagnostic criteria for EG/EoD as agreed upon by the US Food and Drug Administration to evaluate novel therapies and study the prevalence of these diseases.
Design: We developed a pathology protocol to quantify eosinophilia in 8 gastric and 4 duodenal biopsies from subjects with moderate-severe gastrointestinal (GI) symptoms but no prior history of EG/EoD in 2 separate prospective studies (ENIGMA and AK002-019). Eosinophils were counted in 5 separate nonoverlapping high-power fields (hpf; 0.237 mm2) for each biopsy sample. Eosinophilia was defined as ≥30 eosinophils in ≥5 gastric hpf (EG), and/or ≥30 eosinophils in ≥3 duodenal hpf (EoD).
Results: Of 88 subjects biopsied in the ENIGMA study, 72 (82%) were found to have EG and/or EoD (Table). Furthermore, of 26 subjects biopsied in ENIGMA without a prior diagnosis of EG and/or EoD, 58% were found to have EG and/or EoD. Similarly, of 405 subjects in the AK002-019 study, most of whom (93%) were diagnosed as having functional GI disorders, 181 (45%) met histologic criteria for EG and/or EoD.
Conclusions: Systematic and intentional evaluation of gastric and duodenal eosinophilia in subjects with chronic, moderate-severe GI symptoms in 2 separate studies found 45% of patients without a previous diagnosis of EG/EoD met the histologic criteria for EG/EoD. Given the high diagnostic yield, a standardized biopsy and histopathology protocol is indicated to evaluate symptomatic patients for EG/EoD so that targeted therapies may be utilized.
Genta is a consultant with Allakos, Adare/Ellodi, and Red Hill Pharmaceuticals. Turner is a consultant with Allakos and Adare. Collins is a consultant with Allakos, Arena, BMS/Celgene/Receptos, Esocap, GlaxoSmithKline, Regeneron, and Takeda/Shire, and has received grant or research support from BMS/Celgene/Receptos, Regeneron, and Takeda/Shire. Kamboj is a shareholder in Allakos. Rasmussen is a shareholder in Allakos. Talley is a consultant with Allakos, Bayer, Danone, Planet Innovation, Takeda, Viscera Labs, twoXAR, and IFFGD, and has received an NHMRC Investigator grant.
Demographic, Clinical, and Pathologic Characteristics of Inflammatory Bowel Disease in a Reference Center in Bogotá, Colombia
(Poster No. 78)
Rocío López-Panqueva, MD1 (email@example.com); Marcela Mejía-Arango, MD1; Rafael García-Duperly, MD2; Mónica Ortiz-Pereira, MD4; Belen Mendoza de Molano, MD.3 Departments of 1Pathology and Laboratories, 2Surgery and 3Gastroenterology, Fundación Santa Fe de Bogotá/Universidad de los Andes, Bogota, Colombia; 4Department of Internal Medicine, Fundación Santa Fe de Bogotá, Bogota, Colombia.
Context: Inflammatory bowel disease (IBD) is a chronic immunemediated illness with an increasing incidence in Latin America.
Design: Descriptive retrospective study of the demographic, clinical, and pathologic characteristics of patients with IBD at Hospital Universitario Fundación Santa Fe de Bogotá between 1996 and 2019. Pathologic and clinical characteristics were reviewed and compared with other institutions from Colombia.
Results: A total of 379 patients were included, 277 with ulcerative colitis (UC) and 102 with Crohn disease (CD). Gender, age at diagnosis, hospitalization rate, mortality, and surgery rate are shown in the Table. UC involvement was rectal (35.7%), descending colon (21.7%), and pancolitis (42.6%). A total of 35.4% of patients had clinically severe disease. Surgical intervention rate was significant (OR 3.70, P < .01) and 13% of UC patients received biologic therapy. CD involvement was colonic (12.9%), ileocolonic (43.6%), and ileal (43.6%). Clinicopathologic pattern was inflammatory (51%), stenosing (32%), and fistulizing (17%). Forty-five percent of the patients received biologic therapy and 55.9% surgical intervention. Perianal complications were the first indication. Sclerosing primary cholangitis was found in 4% (n = 15); 2 of these patients developed colorectal carcinoma (OR 4.18; P = .008). Sixteen of the IBD patients developed colorectal carcinoma, 13 with UC, and 3 with CD. Dysplasia was found in 7 patients with UC.
Conclusions: The characteristics of the patients with IBD diagnosed and treated at Hospital Universitario de la Fundación Santa Fe de Bogotá are, overall, consistent with the findings and literature from other institutions in Colombia. Further histopathologic, imageology, and laboratory studies may increase our knowledge of the disease in our specific population.
Focal Nodular Hyperplasia Presenting in an Infant With Niemann Pick Disease
(Poster No. 79)
Crystal Bockoven, MD (firstname.lastname@example.org); Roshan Mahabir, MD, MPH, PhD; Murad Alturkustani, MD; Bruce Pawel, MD; Nick Shillingford, MD; Shengmei Zhou, MD; Ryan Schmidt, MD; Mika Warren, MD; Larry Wang, MD, PhD. Department of Pathology and Laboratory Medicine, Children's Hospital of Los Angeles, California.
A 20-month-old male with developmental delay and chronic vomiting presented with hepatosplenomegaly. He was also evaluated by medical genetics with concerns for lysosomal storage disease. He was referred to hepatology after laboratory workup showed elevated transaminases. A 4.5-cm liver mass was identified by ultrasound. Percutaneous liver biopsy showed nodular structures separated by fibrous septa containing reactive ductular structures. Normal portal triads were not appreciated. Immunohistochemical stain for glutamine synthetase showed a patchy, maplike staining pattern in the nodular areas, typical for focal nodular hyperplasia (FNH). Both the nodules and background liver contained foamy cells with a soap bubble–like cytoplasm, and small round nuclei with coarse chromatin in clusters and singly. Electron microscopy demonstrated diffusely enlarged hepatocytes and Kupffer cells with numerous intracytoplasmic vacuoles containing lamellar material. Targeted exome sequencing showed compound heterozygous disease-causing missense variants in the SMPD1 gene. These findings were consistent with Niemann-Pick disease (NPD). FNH comprises approximately 2% of all pediatric liver tumors and can present at any age. There are very few reports of FNH in infancy in the English literature and no reports of FNH in NPD (PubMed and Google search). We report a rare case of FNH in infancy in the setting of NPD. Although rare in infancy, FNH can occur in the setting of other diseases, and care should be taken not to miss background liver disease.
Eosinophilic Appendicitis: Report of a Series
(Poster No. 80)
Nuha Shaker, MD (email@example.com); Shadi Qasem, MD. Department of Pathology, University of Kentucky, Lexington.
Context: Eosinophilic appendicitis is not a well-defined entity. Rare reports can be found in the literature, but the exact etiology and significance are not clear. In this series we review our institutional experience with this entity.
Design: We searched the pathology laboratory information system (LIS) for the terms appendicitis and eosinophils or eosinophilic. We also interrogated the LIS system for the number of appendices resected during the same time period.
Results: We identified 9 cases during the course of 50 years (1971– 2021) where the diagnosis included the search terms. There were 13 766 appendectomies during the same period (0.02%). The patient ages ranged from 11 to 49 (average = 24.4 years); male to female ratio = 1.25. Only one case had Enterobius vermicularis identified in the appendix. All cases showed increased mural eosinophils. Three cases showed acute inflammation, 1 case showed granulomatous inflammation, and 2 cases showed fibrosis. Three of the cases were grossly inflamed, but none of the cases showed perforation (Figure 1.80).
Conclusions: Eosinophilic appendicitis is rare in its pure form; it is occasionally associated with helminths infestation of the appendix. The clinical significance of mild forms of the disease is not clear; however, more severe forms do present with an appendicitis-like clinical picture. More attention is suggested for this entity as it may be underreported.
An Unusual Presentation of Taxane Effect in Acute Cholecystitis After Exposure to Paclitaxel
(Poster No. 81)
Natali Ronen, MD (firstname.lastname@example.org); John Evans, MD. Department of Pathology, MCWAH, Wauwatosa, Wisconsin.
Taxanes (paclitaxel and docetaxel) are chemotherapeutic agents used to treat malignancies, including carcinomas of the esophagus, breast, and lung. These drugs target cells with high turnover and inhibit mitosis by interfering with microtubule breakdown during cell division. Documented side effects include myelosuppression, alopecia, arthralgia, myalgia, neuropathy, diarrhea, mucosal toxicity, and skin changes. We report a case of a 72-year-old woman who presented to the emergency department with abdominal pain, dizziness, nausea, and emesis during an 8-week chemotherapy regimen for invasive ductal carcinoma of the breast. Her last dose of paclitaxel was 4 days prior to presentation. Imaging revealed cholelithiasis with mild gallbladder wall hyperemia and thickening, compatible with acute calculus cholecystitis and she subsequently underwent cholecystectomy. Gross and microscopic examination of the gallbladder revealed hemorrhage and edema within the gallbladder wall with neutrophilic infiltration (Figure 1.81). The mucosal epithelium contained apoptosis and increased mitotic activity with numerous atypical ring mitoses. The gallbladder mucosa lacked significant cytoarchitectural complexity and nuclear hyperchromasia. The microscopic features of taxane effect are well described in the luminal gastrointestinal tract mucosa, but less commonly described in the biliary tree. This case represents an unusual finding of taxane effect in the gallbladder. The frequent atypical mitotic figures may lead to the misdiagnosis of high-grade biliary intraepithelial neoplasia (BilIN-3) or possible malignancy. Recognition of ring mitoses and correlation with the clinical history are imperative to arrive at the correct diagnosis. Additionally, this report supports acute cholecystitis as a rare side effect of paclitaxel therapy.
Histopathologic Diagnostic Criteria for Eosinophilic Gastritis and Eosinophilic Duodenitis
(Poster No. 82)
Kevin O. Turner, DO1 (email@example.com); Evan S. Dellon, MD, MPH2;MargaretH. Collins,MD3; Lauren T. Gehman, PhD4; Henrik S. Rasmussen, MD, PhD5; Robert M. Genta, MD.6 1Department of Pathology, UT Southwestern, Dallas, Texas; 2Department of Medicine, University of North Carolina, Chapel Hill; 3Cincinnati Center for Eosinophilic Disorders, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Departments of 4Planning and Analytics and 5Clinical Development and Medical Affairs, Allakos, Inc, Redwood City, California; 6Department of Pathology, Inform Diagnostics, Irving, Texas.
Context: Eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD) are diagnosed via endoscopy with biopsy and histopathologic detection of eosinophils in the stomach and duodenum. EG and/or EoD (EG/EoD) are more common than generally realized; however, lack of diagnostic guidelines, perceived rarity, and nonspecific clinical presentation contribute to their underdiagnosis. Standardized histopathologic criteria will improve detection of these diseases, thereby enabling patients to receive targeted treatment.
Design: Patients with moderate to severe gastrointestinal symptoms underwent endoscopy with systematic gastric and duodenal biopsy protocol (8 gastric + 4 duodenal) and histopathologic evaluation. At least 5 nonoverlapping high-power fields (hpfs) were evaluated per biopsy. Histopathologic criterion for EG was ≥30 eos/hpf in ≥5 gastric hpfs and for EoD was ≥30 eos/hpf in ≥3 duodenal hpfs. We analyzed diagnostic yields for EG/EoD and examined EG/EoD histopathologic diagnostic criteria using screening data from a randomized controlled trial of lirentelimab.
Results: Of the 88 patients evaluated, 72 met criteria for EG/EoD, including 15 of 26 (58%) with no prior diagnosis of EG/EoD. Morphologic abnormalities were present in 49% (22 of 45) of EG and 5% (3 of 62) of EoD patients. Eosinophilia was highly patchy; 41% of gastric biopsies (136 of 329) and 23% of duodenal biopsies (51 of 230) had 0 or 1 hpfs with ≥30 eos (Table). Evaluation of ≥5 nonoverlapping hpfs in ≥8 gastric and ≥4 duodenal biopsies was required to capture 100% of EG/EoD cases.
Conclusions: EG/EoD biopsies often showed patchy eosinophil distribution in otherwise normal- or almost normal-appearing gastric or duodenal mucosa, indicating that the careful high-power examination of 5 hpfs in all 12 biopsies is necessary to ensure detection.
Turner is a consultant with Allakos and Adare. Dellon is a consultant with Abbott, Adare/Ellodi, Aimmune, Allakos, Amgen, Arena, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, GSK, Gossamer Bio, Parexel, Regeneron, and Robarts/Alimentiv, and has received grant or research support from Adare/Ellodi, Allakos, AstraZeneca, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Shire/Takeda, Banner, and Holoclara. Collins is a consultant with Allakos, Arena, BMS/Celgene/Receptos, Esocap, GlaxoSmithKline, Regeneron, and Takeda/Shire, and has received grant or research support from BMS/Celgene/Receptos, Regeneron, and Takeda/Shire. Gehman is a shareholder in Allakos, Inc. Rasmussen is a shareholder in Allakos, Inc. Genta is a consultant with Allakos, Adare/Ellodi, and Red Hill Pharmaceuticals.
Autoimmune Hepatitis With Peliosis-like Changes
(Poster No. 83)
Catherine Turner, MS (firstname.lastname@example.org); Kelly Bowers, DO, MPH; Deepthi Rao, MD, MS. Department of Pathology and Anatomical Sciences, University of Missouri Health Care, Columbia.
Peliosis is a vascular proliferation composed of strikingly dilated sinusoids, which can affect any organ, but most commonly affects the liver. There are numerous etiologies for peliosis-like changes as well as peliosis mimics (lipopeliosis), which can be difficult to differentiate from one another. Peliosis-like changes frequently alter the normal architecture of the organ, which can also make secondary diagnoses more difficult. We report a case of a 29-year-old woman with Crohn disease who was taking chronic corticosteroid and monoclonal antibody therapies and presented with persistent elevated alkaline phosphatase and mildly elevated transaminases. Serologic workup was significant for a positive antinuclear antibody. Liver biopsy showed marked sinusoidal dilation distorting the normal liver architecture (Figure 1.83, A; hematoxylin-eosin [H&E], ×40). The extensive dilatation resembled peliosis hepatis; however, the sinusoidal endothelium was intact. This nonspecific finding can be caused by obstructive venous outflow conditions, inflammatory disorders, and medications; the latter was most likely caused by chronic corticosteroid use for her Crohn disease. Additionally, there was a mixed portal inflammation, lymphoplasmacytic interface hepatitis, and periportal fibrosis (Figure 1.83, B; H&E, ×400). This pattern of inflammation in combination with serologic studies supports autoimmune hepatitis. The corticosteroid treatment for her Crohn disease likely suppressed the inflammatory component of her autoimmune hepatitis, which was further masked by altered architecture caused by peliosis change. This case provides a reminder that thorough clinical history, including medications, is important for pathologic diagnosis, especially in medical liver, and emphasizes the importance of not allowing architecture-altering conditions, like peliosis, to distract from underlying secondary conditions.
Localized Amyloidosis of the Prostatic Urethra Mimicking Urothelial Carcinoma
(Poster No. 84)
Katrina Collins, MD1 (email@example.com); Khaleel Al-Obaidy, MD1; Laura Warmke, MD1; Clint Cary, MD, MPH2; John N. Eble, MD1; Shaoxiong Chen, MD.1 Departments of 1Pathology and 2Urology, Indiana University, Indianapolis.
Amyloidosis is a disease characterized by extracellular deposition of amyloid protein fibrils in tissues and rarely involves the urethra, with fewer than 50 cases previously reported, and may mimic urothelial carcinoma at presentation. We report a 69-year-old man who presented to the emergency department with shortness of breath. An abdominal computed tomography scan demonstrated a right hydronephrotic kidney and bladder largely occupied by a large, predominantly hyperdense lesion, presumed hematoma (Figure 1.84, A). Pancystoscopy revealed a 6-cm bladder mass involving the prostatic urethra displacing the right ureteral orifice, which was biopsied. Histologic examination showed large deposits of amorphous eosinophilic material associated with numerous osteoclast-type giant cells, with areas of calcifications and multifocal ossification (Figure 1.84, B through D). Amyloid deposits were confirmed by Congo red (Figure 1.84, D, inset) and sulfated Alcian blue stains. Light chromatography tandem mass spectrometry was performed and detected all types including serum amyloid P component, apolipoprotein A4, and apolipoprotein E; however, a specific amyloid type was indeterminate. The patient had no history of gonorrhea. Further investigations for systemic amyloidosis were all negative. Amyloidosis of the urethra is extremely rare and may be either localized and idiopathic or a manifestation of systemic amyloidosis. Pathologists should be aware of this rare entity as this lesion may be indistinguishable from carcinoma, further emphasizing the importance of tissue diagnosis before definitive surgery. Long-term follow-up in the absence of symptoms may not be required.
Somatic-Type Yolk Sac Tumor Arising as a Predominant Component of Bladder Urothelial Carcinoma
(Poster No. 85)
Ahmad M. Alkashash, MD1 (firstname.lastname@example.org); Katrina Collins, MD1; Michael Hwang, MD1; Hristos Z. Kaimakliotis, MD2; Liang Cheng, MD1; Muhammad Idrees, MD.1 Departments of 1Pathology and 2Urology, Indiana University, Indianapolis.
Yolk sac tumor is a malignant germ cell tumor (GCT) that occurs at both gonadal and extragonadal sites. Extragonadal GCTs are most commonly represented at mediastinum, retroperitoneal, and cranial sites. Occurrence in the urinary bladder is extremely rare. To our knowledge, this is the second report of urothelial carcinoma with a yolk sac tumor component. We report a 62-year-old man with a history of lung cancer (unknown type), a left adrenal gland mass, and a 5.6-cm left bladder wall mass; concurrent cystoscopy demonstrated a large papillary mass on the left anterior bladder wall. The tumor from the cystectomy specimen formed papillary structures with thin fibrovascular cores lined by neoplastic cells with clear cytoplasm (Figure 1.85, A, C, and D). Immunohistochemical stains were performed and were positive for pancytokeratin, CK20 (focal), CDX2, SALL4, glypican-3 (Figure 1.85, B), and AFP, and negative for CK7, epithelial membrane antigen, PAX-8, NKX3.1, TTF-1, PAX-8, GATA3, PAX-2, p63, prostate-specific antigen, NKX3.1, TTF-1, inhibin, and Oct4. On prior biopsy, there were focal tumor areas highlighted by GATA3 and p40 expression and similar positive expression for GATA3 and p63 with negative immunoreactivity for SALL4 and glypican-3. No chromosome 12p abnormalities were identified by fluorescent in situ hybridization study. A diagnosis of yolk sac tumor derived from urothelial carcinoma was made. Yolk sac tumor should be considered in the differential diagnosis of a high-grade urothelial carcinoma, particularly when glandular or other unusual architectural patterns are present. A somatic origin with underlying genomic instability similar to what has been described in uterus and ovaries is suggested (PMID: 32558949).
High Intensity Focused Ultrasound Ablation for Prostate Cancer: A Retrospective Review of the Histological Characteristics and Clinicopathologic Correlates After Treatment
(Poster No. 86)
Katrina Collins, MD1 (email@example.com); Eric Brocken, PA(ASCP), MHS, AAPA1; Clinton D. Bahler, MD2; Michael O. Koch, MD3; Liang Cheng, MD.1 Departments of 1Pathology, 2Urology and Radiology and Imaging Sciences, and 3Urology, Indiana University, Indianapolis.
Context: High-intensity focused ultrasound (HIFU) is a noninvasive treatment option used for localized prostate cancer or salvage surgery after failed radiation therapy. We report histologic findings in prostate needle biopsies following HIFU treatment.
Design: Between 2002 and 2020, 34 patients with localized prostate cancer underwent a single HIFU treatment. None had prior radiation therapy. Inclusion criteria were pathologically confirmed prostate cancer, Gleason score 7 (3 + 4, 4 + 3), cancer limited to a single side, and amenable to Sonablate HIFU treatment (<40-g prostate, no or minimal prostatic calcifications on treatment side). Biopsies were taken 6 months after HIFU treatment.
Results: Morphologic alterations included a spectrum of changes ranging from coagulative stromal necrosis to atrophic changes in benign prostatic tissue. All biopsies showed variable degree of fibrosis ranging from mild to moderate. Twenty-five cases (73.5%) showed necrosis usually associated with acute and/or chronic inflammation. Benign glands revealed glandular heterogeneity including atrophy and basal cell hyperplasia. Minimal morphologic changes in low-volume residual adenocarcinoma after HIFU treatments were identified in 18 patients (52.9%) beyond the ablation zone, including nuclear pyknosis, 5; nuclear enlargement, 15; cytoplasmic vacuolization, 10; otherwise no discernable effects of treatment. The pathologic changes in benign and malignant prostatic tissue are summarized in the Table.
Conclusions: We provide a review of common histologic findings in prostatic biopsies after HIFU treatment. Particular attention should be placed on recognizing changes observed in both benign and malignant prostatic tissue. We propose reporting Gleason scores of posttreatment prostate cancer to provide information that will optimize patient management.
Myelolipomatous Adrenal Adenomas: A Report of 15 Cases
(Poster No. 87)
Katrina Collins, MD1 (firstname.lastname@example.org); Diana M. Oramas, MD2; Jeffrey Guccione, MD5; Khaled M. Elsayes, MD3; Mouhammed A. Habra, MD4; Miao Zhang, MD, PhD2; Liang Cheng, MD.1 1Department of Pathology, Indiana University, Indianapolis; Departments of 2Pathology, 3Abdominal Imaging and 4Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston; 5Department of Diagnostic and Interventional Imaging, The University of Texas Health Sciences Center at Houston.
Context: The presence of a myelolipomatous component of adrenal incidentalomas is a rare, but well-known, occurrence in both hyperplastic and neoplastic lesions of the adrenal cortex and has been associated with adrenocortical dysfunction. Although improved imaging modalities have increased detection, given the rarity of this lesion and nonspecific symptoms, these lesions can cause diagnostic uncertainty and can make subsequent management difficult. This study presents clinicopathologic features of pathologically proven cases of myelolipomatous adrenal adenomas with radiologic correlation.
Design: Fifteen myelolipomatous adrenal adenomas were retrieved from the files of the authors (1985 to 2020). Clinicopathologic and radiologic data were recorded for all cases.
Results: Of the 15 patients, 5 were male and 10 were female, with ages ranging from 28 to 84 years (median, 52 years). Clinical presentation included adrenal incidentaloma (n = 10), preclinical Cushing syndrome (n = 4), and Carney complex (n = 1). The adrenal tumors ranged from 0.7 to 12.5 cm (median 4.5 cm) and the gland weight ranged from 5.8 to 300 g (median 60 g). The clinicopathologic and radiologic features are summarized in the Table.
Conclusions: Myelolipomatous adrenal adenomas are rare, benign tumors, typically unilateral and hormonally inactive. They may be indistinguishable from a myelolipoma or carcinoma with a myelolipomatous component using conventional imaging techniques, resulting in a false clinical impression. It is important to appreciate that these tumors have been linked with endocrine syndromes, such as Cushing syndrome, and may have an underlying genetic cause.
Plasmacytoid Urothelial Carcinoma: Histomorphologic and Clinical Analysis
(Poster No. 88)
Melad N. Dababneh, MBBS1 (email@example.com); Dylan Martini, MD3; Mehmet A. Bilen, MD2; Sara E. Wobker, MD, MPH4; Lara R. Harik, MD.1 Departments of 1Pathology and Laboratory Medicine and 2Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia; 3Department of School of Medicine, Emory University, Atlanta, Georgia; 4Department of Pathology, The University of North Carolina at Chapel Hill.
Context: Plasmacytoid urothelial carcinoma (PUC) is a rare aggressive variant of invasive urothelial carcinoma (UC). A recent histologic categorization by Perrino et al divided PUC into classical, pleomorphic, and desmoplastic. We present our clinicopathologic experience with attention to the newly described subcategories.
Design: A search of our database yielded 39 patients with PUC, with 47 specimens during the last 20 years. Glass slides were reviewed for histomorphologic characterization. The clinical information was reviewed through chart abstraction.
Results: PUC showed male predominance (>6:1 M:F) with mean age of 69 years (40–84 years). Clinical follow-up was available for 30 patients (median, 10 months; range, 1–36 months). Seventy-four percent (n = 29) of cases were stage ≥pT2, 44% (n = 17) had lymph node involvement, and 38.5% (n = 15) showed distant metastasis (see Table). Metastatic sites included small bowel, omentum, liver, lungs, bone, and peritoneum. The overall mortality rate was 18%. The most frequently seen histology was pleomorphic, often admixed with classical and/or desmoplastic subtypes. PUCs were commonly admixed with other UC variants (glandular and sarcomatoid) and associated with flat UC in situ (35%). PUC comprised ≥80% of tumor in 28% (n = 11), 50%–80% in 31% (n = 12), and <50% in 41% (n = 16) of cases.
Conclusions: PUC presents at advanced pathologic stage, with predisposition for nodal and/or distant metastasis. Awareness of the spectrum of histologic changes helps in recognizing this prognostically significant variant. The presence of abdominal visceral spread underlines PUC's ability to cross fascial planes; the characteristics of UC at these sites could be an interesting future direction.
NHERF1/EBP50 Expression and Ultrastructural Findings in Clear Cell Renal Cell Carcinoma
(Poster No. 89)
Aliaksandr Aksionau, MD1 (firstname.lastname@example.org); Brandon Hartman, BS1; Roberto A. Silva, MD2; Ashley Flowers, MD.1 1Department of Pathology and Translational Pathobiology, LSUniversity Health Shreveport, Louisiana; 2Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha.
Context: Na/H exchanger (NHE) maintains the alkaline pH of epithelial cells working at the cellular membrane and exchanging 1 intracellular H+ ion for 1 extracellular Na+ ion. In renal tubular cells, the reabsorption of NaCl is implemented by NHE3 isoform, which is regulated by NHE regulatory factor 1 (NHERF1). NHERF1 directly interacts with merlin, ezrin, radixin, and moesin proteins, which participate in cytoskeletal reorganization and signal transduction. In the normal proximal tubule, it is located in the apical zone, facilitating structural stability and ion exchange. Our aim was to characterize NHERF1 expression in renal cell carcinoma (RCC).
Design: Using immunohistochemistry, we analyzed the expression of NHERF1/EBP50 (ThermoFisher Scientific, Waltham, Massachusetts) on RCCs including papillary, chromophobe, and clear cell subtypes (21 [33%], 9 [14%], and 34 cases [53%], respectively). Twelve clear cell RCC (ccRCC) tumors were further analyzed by transmission electron microscopy.
Results: All neoplasia-transformed tubular cells, regardless of tumor grade and stage, had altered expression of NHERF1/EBP50. Changes ranged from complete absence to aberrant expression in the basolateral cell membrane or cytoplasmic locations. Among the subtypes, only ccRCC showed microlumen formation in singles or clusters as dot-shaped condensations of immunostaining at paranuclear, membranous, and submembranous sites. The latter 2 locations were common for Fuhrman grades 1 and 2. Ultrastructurally, the microlumens represented aggregates of microvilli surrounded by a monolayer membrane (Figure 1.89).
Conclusions: For ccRCC, the dysfunctional NHERF1 relocates inside the cell forming microlumens. It confirms significant changes in the intracellular environment, ionic imbalance, and may contribute to tumor progression, metastasis, and drug resistance requiring further analysis.
The Clinical Utility of a 17-Gene Molecular Classifier Score in Men With NCCN Intermediate-Risk Prostate Cancer
(Poster No. 90)
Chien-Kuang C. Ding, MD, PhD (Cornelia.Ding@ucsf.edu); Emily Chan, MD, PhD; Bradley A. Stohr, MD, PhD; Jeffry P. Simko, PhD, MD; Nancy Y. Greenland, MD, PhD. Department of Pathology, University of California, San Francisco.
Context: The Genomic Prostate Score (GPS, OncotypeDx, Genomic Health, Redwood City, California) is a 17-gene RT-PCR test on prostate biopsies that predicts risk of adverse pathology at prostatectomy and provides a posttest NCCN risk category. We have previously shown that cribriform pattern and higher percentages of Gleason pattern 4 are associated with higher GPS posttest NCCN risk category. In 2017, the test began subdividing the posttest intermediate NCCN risk category into intermediate favorable and intermediate unfavorable. We hypothesized that the intermediate unfavorable category would be associated with higher rates of cribriform pattern and higher average percentage Gleason pattern 4 than the intermediate favorable category.
Design: Prostate biopsies from our institution from October 2016 to December 2018 that had received a GPS and intermediate favorable or intermediate unfavorable posttest category were included. The slide from the block tested was rereviewed in a blinded manner for percentage Gleason pattern 4 and presence of cribriform pattern. GPS data were obtained from the medical record.
Results: There were 59 patients whose prostate biopsies underwent GPS testing and were assigned a posttest category of intermediate favorable (17 patients) or intermediate unfavorable (42 patients). Compared with patients in the intermediate favorable category, patients in the intermediate unfavorable category had higher GPS (29.5 versus 24.4, P = .02), higher average percentage of Gleason pattern 4 (20.8% versus 10%, P = .002), and higher rates of cribriform pattern (31% versus 6%, P = .04).
Conclusions: NCCN posttest intermediate subcategory provided by GPS can be partially explained by careful histologic examination of prostate biopsy.
Perinephric Myxoid Pseudotumor of Fat: A Rare and Emerging Entity
(Poster No. 91)
Jessica Muldoon, MD (email@example.com); Katrina Collins, MD; Laura Warmke, MD; Muhammad Idrees, MD. Department of Pathology, Indiana University, Indianapolis.
Perinephric myxoid pseudotumor of fat is a newly described entity that may mimic fat-containing soft tissue tumors, such as well-differentiated liposarcoma or fibrosclerosing lesions associated with IgG4-related disease. To our knowledge, a total of 12 cases were previously reported, of which 11 cases are from 1 case series (PMID 30826321). We presently report the 13th case. A 70-year-old woman with history of rheumatoid arthritis, diabetes mellitus type 2, and hypothyroidism presented with a long-standing abdominal mass and worsening abdominal distention and pain. Computed tomography imaging showed a large right retroperitoneal mass measuring 21 cm (Figure 1.91, A) as well as gallstones. Histologic sections showed a lipomatous lesion with focal myxoid change (Figure 1.91, B) and lymphoplasmacytic infiltrate (Figure 1.91, C and D). No atypical stromal cells characteristic of atypical lipomatous tumor/well-differentiated liposarcoma were identified. The presence of necrosis and lymphoplasmacytic infiltrate was concerning for IgG4-related fibrosclerosing disease; however, immunohistochemistry showed IgG plasma cells were polyclonal with no increase in IgG4+ cells. MDM2 immunohistochemical expression was negative. Fluorescence in situ hybridization study was performed and showed no evidence of MDM2 gene amplification. Perinephric myxoid pseudotumor of fat is an extremely rare, fat-containing perirenal mass. The exact etiology is unclear but thought to result from perinephric fat irritation secondary to underlying nonneoplastic renal disease. Although this mass has imaging findings that overlap with liposarcoma, this lesion is favored to represent a pseudotumor of fat. MDM2 amplification by fluorescence in situ hybridization can help to distinguish this benign lipomatous tumor from liposarcoma.
Leydig Cell Tumor of the Testes With Ectopic Leydig Cells Mimicking Metastasis: An Unusual Finding
(Poster No. 92)
Dokpe Emechebe, MD (Dokpe.Emechebe@downstate.edu); Shabnam Seydafkan, MD; Jianying Zeng, MD. Department of Pathology, SUNY Downstate Medical Center, Brooklyn, New York.
Leydig cell tumors represent 1%–3% of testicular neoplasms. The majority are benign; however, 5%–10% are malignant. Metastasis is the only criterion for malignancy. Benign perineural Leydig cells may be seen in extratesticular tissue. This finding may be challenging and lead to an incorrect diagnosis of malignant perineural invasion. We report a case of testicular Leydig cell tumor with benign perineural Leydig cells in the spermatic cord. We need to be aware of this phenomenon to avoid misdiagnosis. A 24-year-old man presented with a testicular mass. Imaging revealed a hypoechoic 1.6-cm mass of the left testicle (Figure 1.92, A). Imaging of the chest, abdomen, and pelvis showed no metastatic disease. Preoperative laboratory results were normal, including LDH 149 u/L, β-HCG <1.2 u/L, and AFP 1 ng/mL. Histology revealed the tumor had well-defined borders and was confined within the testicle (Figure 1.92, B). The neoplastic cells were bland looking with a single round nucleus and abundant eosinophilic cytoplasm (Figure 1.92, C). Present within the spermatic cord were small foci of cellular clusters within nerve that were morphologically similar to the tumor cells with bland cytology (Figure 1.92, D) Both tumor cells and cells within the nerve stained positive for inhibin, Melan-A, and calretinin. We conclude these were benign perineural Leydig cells mimicking malignant perineural invasion. The simultaneous occurrence of Leydig cell tumor and benign perineural Leydig cells in extratesticular tissue is uncommon but must be recognized. The tumor morphology and cytologic features were helpful in differentiating this benign perineural condition from the malignant Leydig cell tumor counterpart.
Malignancy Following Augmentation Cystoplasty: A Single Institution Experience
(Poster No. 93)
Aysha Mubeen, MD1 (firstname.lastname@example.org); Sofia Canete-Portillo, MD1; Soroush Rais-Bahrami, MD2; Pankaj Dangle, MD2; Cristina Magi-Galluzzi, MD.1 Departments of 1Pathology and 2Urology, University of Alabama, Birmingham.
Context: Augmentation cystoplasty (AC) is a procedure where the bladder is anastomosed with segments of ileum, colon, or stomach in conditions like spina bifida, history of bladder exstrophy, or other neurogenic bladder etiology limiting bladder capacity and compliance. Limited literature is available on malignancy developing in AC because of the low incidence and long latency.
Design: We describe the clinicopathologic features of 5 patients who underwent AC at our institution and subsequently developed cancer in the augmented bladder.
Results: All patients were female; age at diagnosis ranged from 44 to 57 years. The histologic diagnoses were intestinal-type adenocarcinoma (n = 1), invasive high-grade papillary urothelial carcinoma (HGPUC) (n = 1), urothelial carcinoma in situ (CIS), (n = 1) and squamous cell carcinoma (SCC) (n = 2). Median latency period between AC and carcinoma diagnosis was 28.6 years (range, 15–52 years). Follow-up range was 2 to 80 months (mean, 29.9 months). The clinicopathologic features are summarized in the Table.
Conclusions: Many theories have been proposed for carcinogenesis in AC, including infection, chronic inflammation, interaction between 2 different epithelia, and altered bladder microenvironment. Close follow-up is necessary for an early diagnosis. Endoscopic detection of these tumors, however, can be challenging owing to the inflammatory changes. It is controversial if AC is an independent risk factor for bladder cancer development. Malignancy in AC is reported to have a poor prognosis. We conclude that malignancy in AC can have different histologic subtypes and arise after a long latency period.
Utility of P53 and Ki-67 Immunostaining in Balanitis Xerotica Obliterans (Lichen Sclerosus Et Atrophicus)
(Poster No. 94)
Lubna Suaiti, MD; Tao Zuo, MD, PhD (email@example.com); Zhichun Lu, MD; Artem Shevtsov, MD; Eric Burks, MD. Department of Pathology & Laboratory Medicine, Boston Medical Center, Boston, Massachusetts.
Context: Balanitis xerotica obliterans (BXO)/lichen sclerosus et atrophicus (LSA) has an increased risk to develop differentiated penile intraepithelial neoplasia (d-PeIN) and squamous cell carcinoma (SCC). The aim of our study is to evaluate the utility of p53 and Ki-67 immunostains for BXO/LSA.
Design: From September 2018 to October 2020, all foreskin excisions from our institution were included. Immunostains for p53 and Ki-67 were reviewed and performed in selected cases.
Results: Among 180 patients (26 to 81 years of age with a median age at 46 years), 15 (8.3%) were diagnosed with BXO/LSA; 2 (13.3%) had dysplasia, including 1 (6.7%) with SCC; 13 (86.7%) had no dysplasia. p53 and Ki-67 immunostains were performed on 7 cases. Five cases showed mild atypia at basal layer, however, there was no significantly increased Ki-67 labeling, and p53 expression showed wild-type (normal) pattern in 4 cases. The hyperplastic changes of squamous epithelium were noted, exhibiting increased Ki-67 index, and only 1 had increased p53 expression at basal layer without cytologic dysplasia. Severe dysplasia was seen in BXO/LSA lesion (Figure 1.94, A) in a 48-year-old patient with SCC. Increased Ki-67 index (Figure 1.94, B) and complete loss of p53 (Figure 1.94, C) were seen. The sensitivity and specificity of immunostains of p53 and Ki-67 for d-PeIN was 67% and 100%, respectively.
Conclusions: Our data demonstrate the importance of the utility of p53 and Ki-67 in BXO/LSA patients for detecting d-PeIN lesions.
A Rare Case of Primary Small Cell Carcinoma of the Urinary Bladder With Sarcomatoid Differentiation
(Poster No. 95)
Ahned F. Lazim, MD (firstname.lastname@example.org); Salvatore Luceno, MD; Anu Peter, MD; Eli Balshan, MD. Department of Pathology, Temple University Hospital, Philadelphia, Pennsylvania.
Small cell carcinoma of the bladder (SCCB) is considered an aggressive, poorly differentiated extrapulmonary neuroendocrine tumor that comprises <1% of bladder tumors. The tumor is associated with a poor prognosis, high metastatic potential, a male preponderance, and a mean age of 78 years. Histologically, small cell carcinoma of the bladder is difficult to distinguish from small cell lung carcinoma (SCLC). However, unlike SCLC, it shares similar molecular alterations with urothelial carcinoma. Our case involves an 87-year-old man with a known medical history of hypertension, diabetes mellitus (II), intestinal diverticulitis, and renal caliculi. He presented with hematuria and a 7.5 × 4.8-cm lobulated left urinary bladder mass with perivesical soft tissue involvement (computed tomography abdomen/pelvis). A transurethral resection of the bladder tumor was performed. The tumor grossly measured 9.5 × 8.5 × 2.5 cm in aggregate (weighed 42 g) and had a redtan appearance. The specimen was processed routinely and a diagnosis of primary small cell carcinoma with focal areas of sarcomatoid differentiation was given. Infiltration of the muscularis propria was identified. The diagnosis was confirmed with the use of properly controlled immunohistochemical stains, which demonstrated diffuse positivity in tumor cells for CD56 and synaptophysin, and focal reactivity for both AE1/AE3 and GATA3. The tumor cells were negative for chromogranin, TTF1, CD45, and CD20. The association of sarcomatoid features in SCCB is extremely rare, with few cases recorded in literature. The sarcomatoid components described in literature are nonspecific malignant spindle cells, chondrosarcoma, myxoid sarcomatous, osteosarcoma, and rhabdomyosarcoma (Figure 1.95).
Comparison of Partial Versus Radical Nephrectomies During a 10-Year Period: An Institutional Review
(Poster No. 96)
Georges Tabet, MD (email@example.com); Aileen Grace Arriola, MD. Department of Pathology, Temple University Hospital, Philadelphia, Pennsylvania.
Context: Kidney sparing surgery (partial nephrectomy [PN]) has become the standard of care for all early-stage (pT1) kidney tumors; however, radical/total nephrectomy (RN) is still unavoidable in some cases. The objectives of this study are to examine the tumor size and type, tumor extent, and patient follow-up across PN and RN cases at our institution.
Design: We identified nephrectomy cases between 2010 and 2020. Data from electronic medical records were used to determine procedure type, tumor size, tumor type, pathologic staging, and follow-up data. Fisher exact test and/or χ2 test was used to test for associations.
Results: Tumor size ranged from 0.6 to 15.5 cm for PN and 0.6 to 24 cm for RN, with PN being performed for smaller tumors (<7cm) as compared with RN (P < .001). Only 6.8% (n = 31) of PNs demonstrated recurrence/metastasis; however, most of these cases were staged as confined to the kidney (n = 29, 94%). Among the 59 cases of RN with recurrence or metastasis, only 18 (31%) were staged as confined to the kidney (Table).
Conclusions: At our institution, PN is being performed more often on small tumors as compared with RN. The majority of PN tumors are being staged as confined to the kidney and these cases accounted for the majority of recurrences and/or metastasis seen in the PN group. This result warrants attention and review as to whether pathologists are underrecognizing pertinent staging features for PN cases.
PUNLMP Diagnosis in a General Surgical Pathology Sign-Out Setting: Institutional Experience Spanning 10 Years
(Poster No. 97)
Georges Tabet, MD (firstname.lastname@example.org); Aileen Grace Arriola, MD. Department of Pathology, Temple University Hospital, Philadelphia, Pennsylvania.
Context: Papillary urothelial neoplasm of low malignant potential (PUNLMP) is a diagnosis associated with significant diagnostic confusion. PUNLMP has been shown to have varied recurrence rates, poor interobserver agreement, and overlapping features with low-grade papillary urothelial carcinoma (LGPUC). Cases diagnosed as PUNLMP were examined.
Design: We identified all cases of PUNLMP between 2010 and 2020 from our institution. Data from electronic medical records were used to determine age, prevalence, history of bladder lesions, cystoscopy findings, recurrence, and progression. Fisher exact test was used to test for associations.
Results: PUNLMP cases were uncommon (only 25 diagnoses made during 10 years). The mean age was 65 (15 males, 10 females). Of the 25 cases, 11 (44%) had a history of bladder cancer whereas 14 (56%) did not. Most cases (n = 21; 84%) were viewed as papillary lesions on cystoscopy and the rest presented as erythematous mucosa. Overall, a total of 10 cases (40%) demonstrated either recurrence or progression on follow-up. In those who had a history of bladder cancer, no recurrence was documented, and nearly half progressed to LGPUC (n = 5; 45%). A history of bladder cancer had no statistically significant association with recurrence or progression rates of PUNLMP, although the sample size is small (Table).
Conclusions: Our findings suggest that PUNLMP cases at our institution might be overdiagnosed. History of bladder cancer can be a criterion used to refine diagnostic criteria for PUNLMP, as progression rate was higher in cases with a prior history of bladder cancer. Cases with no history of bladder cancer were most likely nonrecurrent and nonprogressive.
Indoleamine 2,3-Dioxygenase Expression in Upper Tract Urothelial Carcinoma
(Poster No. 98)
Georges Tabet, MD (email@example.com); Aileen Grace Arriola, MD; Salvatore Luceno, MD. Department of Pathology, Temple University Hospital, Philadelphia, Pennsylvania.
Context: Indoleamine 2,3-dioxygenase (IDO) is an immunomodulatory enzyme known to suppress T-cell function. There is evidence suggesting IDO assists in the capability of tumor cells to evade a host immune system, and clinical trials are investigating the use of IDO inhibitors for various solid tumors. The aim of this study was to determine the clinicopathologic significance of IDO expression in upper-tract urothelial carcinoma (UTUC).
Design: We studied 49 UTUC cases from our archives (2006–2019). Clinicopathologic data were collected (quality of tumor-infiltrating lymphocytes [TILs] and type of desmoplastic response at invasive front). All cases were stained for IDO and staining 1% in tumor cells was considered positive. Fisher exact and/or χ2 test was used to assess for associations.
Results: Different patterns of staining were identified, with 15 showing stronger staining at the invasive component/interface with stroma, and 5 showing more superficial staining. Five tumors with variant morphologies (squamous and sarcomatoid) displayed stronger staining in the variant histology compared with the urothelial component. Metastasis and recurrence were found in 26% (n = 9) and 29% (n = 4) for IDO+ and IDO− cases, respectively. There was no evidence of disease in 45% (n = 16) of IDO+ and 29% (n = 4) of IDO− cases (Table). These differences were not statistically significant.
Conclusions: UTUC frequently expresses IDO and expression is not associated with the clinicopathologic features studied including TILs or maturity of the stromal reaction. There is no difference in outcomes with respect to IDO expression. Additional larger studies are warranted, especially in relation to the expression of other immunotherapy biomarkers such as PD-L1.
Indeterminate Urothelial Diagnoses in a General Surgical Pathology Sign-Out Setting: Institutional Experience Spanning 10 Years
(Poster No. 99)
Georges Tabet, MD (firstname.lastname@example.org); Aileen Grace Arriola, MD; Danial Mir, MD. Department of Pathology, Temple University Hospital, Philadelphia, Pennsylvania.
Context: Interpreting bladder biopsies can be challenging because of the nature of management and frequency of surveillance performed for patients with bladder cancer. Several confounding factors, such as biopsy artifact, histology artifact, prior therapies, and infection, can lead diagnostic pitfalls for malignancy. We reviewed indeterminate urothelial cases at our institution.
Design: We identified indeterminate urothelial diagnoses made at our institution (2010–2020). Cases with a descriptive diagnosis that included papillomas, hyperplastic, atypical, and dysplastic were included. PUNLMP cases were excluded. Data from electronic medical records were used to determine age, history of bladder lesions, cystoscopy findings, recurrence, and progression. Cases were stratified by history of bladder cancer. Fisher exact test was used.
Results: Overall, 49 cases were identified. The mean age was 67.58 (27 males, 21 females, 1 unknown). Twenty-two patients (44.9%) had a history of bladder cancer and 27 (55.1%) did not have any prior history of bladder cancer. A total of 5 cases (10.2%) demonstrated either recurrence or progression, with 1 recurrence and 4 progressions. All 5 cases with progression or recurrence had a history of bladder cancer. However, there was no significant difference in recurrence and progression when analyzing each diagnostic category separately (Table).
Conclusions: Our findings show that cases with a de novo indeterminate urothelial diagnosis had different outcomes as compared with those cases with a history of bladder cancer. However, this difference was not found to be statistically significant when analyzing each diagnostic category separately, likely because of the small sample size. Hence, larger studies are warranted.
Donor-Derived Neuroendocrine Carcinoma Transmission to 2 Kidney Transplant Recipients Demonstrated by Short Tandem Repeat Analysis
(Poster No. 100)
Kotaro Takeda, MD1 (email@example.com); Rhonda Mittenzwei, MD2; Kim Geisinger, MD1; Michael Datto, MD, PhD2; Lorita M. Rebellato, PhD.1 1Department of Pathology and Laboratory Medicine, East Carolina University and Vidant Medical Center, Greenville, North Carolina; 2Department of Pathology, Duke University Medical Center, Durham, North Carolina.
Kidney transplantation has improved the quality of life in patients with end-stage renal disease. However, transplantation is associated with an increased risk of malignancy, partially because of the need of chronic immunosuppression. One of the devastating scenarios is transmission of donor-derived cancers, which is frequently fatal. We report a case of lung cancer transmission from a deceased donor to 2 adult kidney recipients. Approximately 1 year after uneventful kidney transplantation, both recipients developed acute kidney failure. Computerized tomography for both recipients showed masses in the transplanted kidneys and innumerable masses in the livers. Pathologic examinations for both cases demonstrated high-grade neuroendocrine carcinoma with “mirror-image” histology in the transplant kidneys and liver metastases. Short tandem repeat (STR) analyses were performed to determine the origin of the tumors. STR analyses of both tumors were nearly identical to that of the donor, proving that both tumors were from the same donor. Immunohistochemical analyses showed that both tumors were positive for thyroid transcription factor 1, supporting a lung primary. One recipient died as a direct sequela to metastatic tumor, and the other required transplant nephrectomy and chemo-therapy. STR analysis plays a crucial role for rapid and unequivocal determination of donor tumor transmission and significantly alters patient management, including reduction of immunosuppression and/or organ explant. Furthermore, it may spur investigation among other recipients of organs from the same donor. Awareness of this largely nonpreventable complication and prompt implementation of molecular testing if cancer transmission is suspected are critical for proper management of these patients.
Persistent Müllerian Duct Syndrome
(Poster No. 101)
Andriy Kostyuk, MD1 (firstname.lastname@example.org); Maria Isabel Almira Suarez, MD2; Ali Azeer, MD.1 1Department of Pathology, Medstar Georgetown University Hospital, Washington, DC; 2Department of Pathology, Children's National Medical Center, Washington, DC.
A 1-year-old boy underwent a bilateral orchiectomy for bilateral gonadal dysgenesis. The patient had an uncomplicated prenatal history. Postpartum evaluation revealed micropenis without ambiguity and undescended testis. Ultrasound identified atrophic gonads in the inguinal canals (Figure 1.101, A). The karyotyping confirmed the presence of XY chromosomes, and the SRY gene was detected by fluorescence in situ hybridization. Laboratory testing showed increased follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and undetectable testosterone, inhibin, and anti-Müllerian hormone (AMH) blood concentrations. The resection specimens contained benign atrophic testicular and para-testicular tissue (Figure 1.101, B) along with fallopian tube tissue (Figure 1.101, C). Undescended testes with Müllerian duct derivatives (Figure 1.101, D) have been associated with genetic abnormalities such as persistent Müllerian duct syndrome (PMDS). It is a rare autosomal recessive entity most commonly caused by mutations in the AMH gene (PMDS type 1) or the AMHR2 gene (PMDS type 2), responsible for AMH and AMH receptor 2 production, respectively. These 2 proteins induce regression of the Müllerian duct (the precursor to female reproductive organs), which develops as default in both fetus genders. Mutations in the AMH and AMH receptor 2 genes lead to Müllerian duct failure regression in males. As a result, the Müllerian duct persists to form a uterus and fallopian tubes. Pathologists should be aware of PMDS presentation and be able to correlate histologic findings with clinical, imaging, and genetic studies. It is essential to document every case of rare syndromes like this to continue to provide data that can be collected for further characterization and recognition.
Post-pubertal Pure Yolk Sac Tumor of Testis: An Extremely Rare Entity
(Poster No. 102)
Simmi Patel, MD1 (email@example.com); Swati Satturwar, MD1; Dayne P. Ashman, MD2; Gabriela Quiroga-Garza, MD.1 1Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; 2Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, Ohio.
Context: Postpubertal pure yolk sac tumors (YSTs) are an extremely rare type of malignant germ cell tumor (GCT) that accounts for <1% of testicular GCTs. Their clinical behavior is aggressive compared with the more common prepubertal counterpart. The aim of this study was to analyze clinical presentation, histomorphologic spectrum, ancillary tests, and clinical outcomes in a case series of this entity.
Design: A retrospective review of 3 cases of postpubertal pure YST of testis was performed. Data collected for each patient included demographics, clinical presentation, serum markers, radiology and pathologic findings, treatment, and clinical outcomes.
Results: The Table summarizes the results of this study. One patient presented with metastatic disease at the time of diagnosis. All patients presented with testicular mass with or without associated pain and elevated serum α-fetoprotein level. Median age at presentation was 25 years (range, 25–27 years). Histologic patterns and features were germ cell neoplasia in situ (n = 3), reticular/microcystic (n = 3), solid (n = 2), glandular, papillary, cystic (n = 1) and angio-lymphatic invasion (n = 3). Fluorescence in situ hybridization test performed on case 2 showed presence of isochromosome 12p. Case 1 showed metastatic disease on follow-up.
Conclusions: Diagnosis of postpubertal pure YST remains challenging because of the variety of morphologic patterns seen in YSTs. Extensive sampling along with use of ancillary tests is the key to the correct diagnosis. In our case series, 2 of the 3 patients had metastatic disease at or after the diagnosis, confirming the aggressive nature of this rare entity.
Mucinous Tubular and Spindle Cell Carcinoma With Unusual Features
(Poster No. 103)
Aysha Mubeen, MD1 (firstname.lastname@example.org); Shuko Harada, MD1; Charles Peyton, MD2; Eddy Yang, MD, PhD3; Haider Mejbel, MD1; Cristina Magi-Galluzzi, MD.1 Departments of 1Pathology, 2Urology, and 3Radiation Oncology, University of Alabama at Birmingham.
Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma. Typically, it affects young adults with female predominance, and demonstrates indolent behavior. We report a case of locally advanced MTSCC with necrosis. A 61-year-old woman presented with a large renal tumor with mass effect on inferior vena cava. A 20.6-cm yellow-tan mass with hemorrhage and necrosis replaced most of the nephrectomy specimen. Microscopic examination revealed a mixture of tubular and spindle components in mucinous stroma. The tubules were lined by cuboidal cells with low-grade nuclei and scant cytoplasm; spindle cells had similar cytologic features (Figure 1.103, A). Tumor necrosis represented 15% of the lesion (Figure 1.103, B); sarcomatoid features were not present. Tumor extended into hilar fat (pT3a). Differential diagnoses were excluded by ancillary studies. Neoplastic cells were positive for PAX8 (Figure 1.103, C), CK7 (Figure 1.103, D), AMACR, and CD10 (focal), and negative for cathepsin K and ALK-1. Fumarate hydratase, INI-1, and mismatch repair (MMR) protein expression was retained. A custom-designed Archer FusionPlex panel run on Illumina NextSeq 550 failed to detect fusion transcript including TFE3, TFEB, ETV6, EWSR1, NTRK1, NTRK2, NTRK3, ALK, and ROS1. Since CDKN2A/B alterations have been reported in locally advanced/metastatic MTSCC, we assessed cyclin D1 protein expression as a surrogate marker and found no overexpression. Presence of unusual features in MTSCC (necrosis, solid or sarcomatoid growth, mitotic activity, vascular invasion, advanced stage) can pose diagnostic challenges. Our case showed necrosis and hilar fat invasion, features frequently associated with aggressive behavior. Additional molecular analysis is ongoing. Close follow-up is recommended.
Mixed Epithelial-Stromal Tumor With Diffuse Müllerian Differentiation: A Case Report of an Incidental Renal Mass
(Poster No. 104)
Mohammad A. Khan, MBBS1 (email@example.com); Elizabeth Arze, MD2.1Department of Pathology, East Tennessee State University, Mountain Home; 2Department of Pathology, Johnson City Medical Center, Johnson City, Tennessee.
Mixed epithelial-stromal tumor (MEST) is a term applied to biphasic epithelial and stromal tumor characterized by distinctive histologic appearance ranging from predominantly cystic tumors (adult cystic nephroma) to variably solid. MEST occurs in middle-aged and older women and is thought to be related to hormonal imbalance or other hormonal factors. Most common gross appearance is solid and cystic (47%). The stromal component of MEST is composed of spindle cell proliferation that resembles ovarian stroma, with characteristic estrogen and progesterone immunoreactivity. The epithelial component is usually flat to hobnailed cells typical of collecting duct epithelium but can be more heterogeneous and exhibit focal features suggestive of Müllerian-type differentiation, including epithelium of endometrioid, tubal, clear cell, or squamous cell type. We report a case of a 44-year-old woman with incidental finding of right renal mass. Grossly, the 4.8-cm tumor was well circumscribed, unencapsulated, and with a cystic cut surface. Histologic sections demonstrated diffuse Müllerian-type epithelium composed predominantly of endometrioid-like glands with bland columnar epithelium containing pseudostratified nuclei. Occasional broad phyllodes-like architecture was noted. The stromal component intervened among glands and was condensed ovarian-like stroma. Immunostains showed stromal PR and ER (focal) reactivity. MSA was positive in intervening smooth muscle bands surrounding lobular units. Cytokeratin AE1/AE3 highlighted the interspersed epithelial component. CD10 was positive in the stromal and epithelial components. HMB45 showed focal positivity in luminal epithelium. Immunostaining pattern was consistent with MEST. Our case is the first reported instance where epithelial component of MEST demonstrates diffuse Müllerian-type differentiation.
Primary Alveolar Soft Part Sarcoma of the Prostate: Report of a Deceptive Case
(Poster No. 105)
Parnaz Daneshpajounejad, MD (firstname.lastname@example.org); Casey Morrison, MD; Kumarasen Cooper, MD, PhD; Lauren Schwartz, MD; Xiaofeng Zhao, MD; Paul Zhang, MD; Priti Lal, MD. Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia.
A 30-year-old never-smoker man presented with hematuria, dysuria, and constipation at an outside hospital and was diagnosed and treated for recurrent urinary tract infection. Because of continued symptoms, he underwent transurethral resection of bladder lesion (TURBT) and was diagnosed with urothelial carcinoma, AJCC stage pT2. Subsequently, he was transferred to the University of Pennsylvania. In-house radiology workup revealed a large vascular mass involving prostate pushing against bladder base. Prostate needle biopsies performed in house revealed an epithelioid neoplasm with nested growth pattern composed of cells with moderate amount of eosinophilic cytoplasm, mildly pleomorphic nuclei, and occasional prominent nucleoli (Figure 1.105, A). The differential diagnosis included carcinoma, sarcoma, and paraganglioma. Accordingly, a wide panel of keratins (Figure 1.105, B; negative AE1/3), along with S100, chromogranin, and synaptophysin, were negative. ERG and CD31 highlighted an extensive vascular network. Focal positivity for smooth muscle antigen prompted a TFE immunostain (Figure 1.105, C) and TFE3 break-apart fluorescence in situ hybridization assay, which were positive (Figure 1.105, D). Subsequently, using custom BAC probes, presence of an ASPSRC1 gene rearrangement was demonstrated. The outside hospital TURBT was reviewed and the diagnosis corrected to alveolar soft-part sarcoma (ASPS). Taking all the above findings together, the final diagnosis was ASPS with involvement of bladder. The patient was found to have bilateral lung metastases and was started on pazopanib and close follow-up for possible brain metastasis. ASPS is a rare soft tissue tumor that primarily involves the extremities, and to the best of our knowledge this is only the third case report of primary prostatic ASPS.
The Significance of Immunohistochemical Workup in the Diagnosis of Renal Oncocytic Neoplasms on Core Biopsies at a Single Institution
(Poster No. 106)
Liping Wang, MD, PhD (email@example.com); Ruth Asirvatham, MD; Adam Johnson, MD; Lina Liu, MD. Department of Pathology, Baylor Scott & White Health, Temple, Texas.
Context: Diagnosing renal oncocytic neoplasms on biopsy remains challenging because of morphologic overlap with other entities. We retrospectively reviewed cases of oncocytic neoplasms and compared histologic diagnosis, immunophenotype, and clinical follow-up.
Design: We conducted a 5-year retrospective review of our database's renal oncocytic neoplasms on core biopsies. All biopsies were stained with a minimum immunopanel of CK7, CD117, and vimentin. Additional stains, including AMACR, CAIX, and CK20, were performed if necessary. Clinical follow-up was assessed through EMR.
Results: Forty-eight renal oncocytic neoplasms were reviewed, including 46 core biopsies and 2 core biopsies with subsequent resection. At the time of original diagnosis, 32 cases (32 of 48; 67%) were diagnosed as low-grade oncocytic neoplasm. After the minimum immunopanel, 16 of 32 cases were classified as classic oncocytoma and 3 cases as RCC. With additional stains, 2 cases of RCC (2 of 32; 6.3%) were subtyped as papillary RCC, oncocytic variant, and the other RCC (1 of 32; 3%) remained unclassified. Four of 32 CK7+/CD117− cases (12.5%) were recognized as low-grade oncocytic tumor (LOT) of kidney. Nine of 32 cases with equivocal staining (CD117+ <5% or CK7+ 50%–80%) could not be further characterized. Clinical follow-up showed lung metastasis in 1 papillary RCC, oncocytic variant. No other cases showed recurrence/metastasis. Of note, in the remaining 16 of 48 cases, the original diagnosis remained unchanged following additional workup.
Conclusions: A select immunohistochemistry panel (CK7, CD117, vimentin) can identify malignancies and classic oncocytoma that would otherwise receive an uncertain diagnosis. In addition, our study helps to recognize an emerging entity, LOT of kidney.
Prostatic Basal Cell Carcinoma With ATMDeletion
(Poster No. 107)
Daniel Neelon, MD1 (firstname.lastname@example.org); Michael Goold, MD1; Sean Baraniak, MD1; Joel Moncur, MD, PhD.2 1Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland; Department of the Director, The Joint Pathology Center, Silver Spring, Maryland.
An 84-year-old man underwent transurethral resection of the prostate for prostate enlargement. Microscopically, 98% of the tissue was infiltrated by solid, anastomosing nests of basaloid cells with peripheral palisading in a desmoplastic stroma (Figure 1.107, A). The neoplastic cells were moderately pleomorphic with scant cytoplasm and prominent nucleoli. Perineural invasion and abundant mitotic figures were present. Necrosis was absent. Immunohistochemistry revealed strong nuclear p63 staining (Figure 1.107, B), diffuse cytoplasmic BCL-2 staining, and focal positivity with CK903 and NKX3.1. GATA3 expression was limited to benign urothelial cells lining the prostatic urethra and urethral ducts. The proliferative index was high (Ki-67 approximately 20%; Figure 1.107, C). The neoplastic cells were negative for prostate-specific antigen (Figure 1.107, D), PSAP, ERG, AMACR, CK20, and HER2, supporting the diagnosis of prostatic basal cell carcinoma (PBCC). Next-generation sequencing demonstrated deletion of ATM (ataxia-telangiectasia, mutated), which encodes a protein kinase that regulates DNA damage response. PBCC represents less than 0.01% of prostate carcinomas, and only 104 cases have been reported. Radical prostatectomy is often pursued because of lack of proven efficacy of chemoradiotherapy. There is no standard treatment. PBCC's molecular mutational landscape is ill defined. One other author has reported an ATM mutation, suggesting that the PARP inhibitor olaparib may be considered for targeted therapy. Furthermore, a recent report demonstrated a favorable response to olaparib in a patient with BRCA2-mutated PBCC. PARP inhibitors can effectively treat prostatic adenocarcinomas with mutations in genes involved in homologous recombination DNA repair. Further investigation may demonstrate that PARP inhibitors could also be indicated for PBCCs with mutations affecting homologous recombination.
Atypical Oncocytic Renal Neoplasm in the Setting of Sickle Cell Trait
(Poster No. 108)
Zachary S. Rubin, MD1 (email@example.com); Adina T. Paulk, MD2; Isabell A. Sesterhenn, MD.2 1Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland; 2Department of Pathology, The Joint Pathology Center, Silver Spring, Maryland.
Sickle cell trait is the heterozygous expression of hemoglobin S, which is typically clinically silent. Renal complications have nonetheless been described, such as unilateral hematuria, papillary necrosis, nephrotic syndrome, renal infarction, inability to concentrate urine, pyelonephritis, and renal medullary carcinoma. Recently, VCL-ALK renal cell carcinomas have also been described in these patients. We present an unusual atypical oncocytic tumor that does not fit into any well-described subtype of renal neoplasm, occurring in a patient with sickle cell trait. A 40-year-old woman from the Dominican Republic with a history of sickle cell trait was found to have a 2.0-cm left renal mass concerning for renal cell carcinoma after undergoing computed tomography scan for abdominal pain. The partial nephrectomy specimen exhibited a tan-brown, well-circumscribed mass consisting mainly of large cells with granular, eosinophilic cytoplasm in a nested and solid sheeted architecture with prominent vacuoles (Figure 1.108, A). Nuclear contours were round with even chromatin but showed prominent nucleoli. The neoplasm was positive for CD117 and negative for CK7, CAIX, ALK, and vimentin, an immunohistochemical phenotype frequently seen in renal oncocytomas. Interestingly, there were increased mitoses, with scattered atypical mitotic figures (Figure 1.108, B). Ki-67 was mildly increased at 5%–10% (Figure 1.108, C). Additionally, many of the capillaries in the tumor were filled with sickled red blood cells (Figure 1.108, D). This case illustrates an unusual atypical oncocytic tumor that has not been described in a patient with sickle cell trait.
Primary Signet Ring Cell Adenocarcinoma of the Urinary Bladder Following Nephrogenic Adenoma
(Poster No. 109)
Margarita Loxas, BS1 (firstname.lastname@example.org); Xing Zhao, MD2; Neil Alouch, MD2; Poonam Sharma, MBBS.2 1School of Medicine and 2Department of Pathology, Creighton University, Omaha, Nebraska.
Signet ring cell adenocarcinoma arising from the urinary bladder is uncommon, comprising less than 1% of primary bladder malignancies. In addition to their rarity, the reported cases exhibit varying immunohistochemical profiles, making them diagnostic dilemmas. We present a 34-year-old paraplegic man with a history of transurethral resection of a benign nephrogenic adenoma of the bladder who subsequently developed biopsy-proven poorly differentiated, infiltrating adenocarcinoma with signet ring features. An in situ adenocarcinoma component (Figure 1.109, A) was identified as well. The nephrogenic adenoma possibly underwent malignant transformation into this adenocarcinoma. Upon radical cystoprostatectomy, the bladder was diffusely involved (Figure 1.109, B) with areas of hemorrhage and necrosis. The tumor was staged at pT4a, invading directly into prostatic stroma and seminal vesicles, and at pN2 for lymph node metastasis. Colonoscopy, endoscopy, and evaluation of the urachus did not reveal malignancies, confirming the tumor as a primary adenocarcinoma of the bladder. The tumor stained positively for AE1/AE3, CK7, CDX2 (Figure 1.109, C), and GATA-3 (patchy), and negatively for PSA, CK20, and p40. β-catenin exhibited cytoplasmic staining (Figure 1.109, D). The majority of reported primary bladder adenocarcinomas demonstrate both CK20 and CK7 expression, with ours staining positively only for CK7. CDX2, which stained positive in our case, is also a marker of interest in this malignancy, but studies have provided inconsistent results in its positive predictive value. β-catenin has been looked at as a potential differentiator between colonic and bladder adenocarcinoma, showing cytoplasmic staining in primary bladder tumors versus nuclear staining in primary colonic adenocarcinomas. This aligns with our findings.
A Rare Case of a Sarcomatoid Tumor of the Prostate
(Poster No. 110)
Husam Jum'ah, MBBS (email@example.com); Devereaux Sellers, MD, MBA; Azzam Hammad, MD. Department of Pathology, Metrohealth Medical Center/Case Western Reserve University, Cleveland, Ohio.
Sarcomatoid carcinoma of the prostate is an extremely rare malignancy with a very poor prognosis and represents less than 1% of all prostate neoplasms. Histologically and/or immunohistochemically this entity demonstrates epithelial and mesenchymal differentiation. Most of the patients have a prior diagnosis of prostatic adenocarcinoma. We report a case of a 78-year-old man who was diagnosed with prostatic adenocarcinoma in 2003, underwent brachytherapy in 2005, and was diagnosed with recurrent prostatic ductal adenocarcinoma in 2019 that was treated with radiation and androgen deprivation therapy. One year later, he presented with hematuria, a normal PSA value of 0.2 ng/mL, and computed tomography (CT) scan showing a large complex prostatic mass invading the bladder and seminal vesicle. A transurethral resection of prostate and bladder was performed. Histopathologic examination of the entire tissue showed a malignant sarcomatoid tumor with predominant osteosarcoma and chondrosarcoma components. No prostatic adenocarcinoma or benign prostatic tissue was identified. Immunohistochemical stains did not show any evidence of prostatic epithelial differentiation. A repeat CT scan 3 months later showed the tumor almost doubled in size. The patient was transferred to hospice care and died a few months after diagnosis. In our case, since the patient did not undergo a radical prostatectomy, the entire tumor could not be examined so there was no way to differentiate between sarcomatoid carcinoma and secondary postradiation sarcoma. One important takeaway from this case is that sarcomatoid overgrowth in sarcomatoid carcinoma may be misdiagnosed as sarcoma of the prostate, since the sarcomatoid component may represent up to 99% of the tumor.
Three Cases of Malakoplakia of Prostate, One Associated With Increased IgG4-Positive Plasma Cells: Report of 3 Cases and Review of Literature
(Poster No. 111)
Renee Eng, MD1 (firstname.lastname@example.org); Ziad El-Zaatari, MD1; Jaehoon Shin, MD2; Yong Mee Cho, MD2; Dina Mody, MD1; Jae Ro, MD.1 1Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas; 2Department of Pathology, Asan Medical Center, Seoul, Republic of Korea.
Context: Prostate malakoplakia and immunoglobulin (Ig) G4-related sclerosing disease (IgG4-RSD) are 2 rare entities within the prostate that can present with clinical findings suspicious for malignancy. However, a possible association with malakoplakia and IgG4-RSD has not been previously reported.
Design: Three cases of histologically proven prostate malakoplakia were accrued from 2 institutions. Clinical parameters were documented including age, symptoms with duration, serum prostate-specific antigen level, image findings, and clinical diagnosis. Potential relationships between malakoplakia and IgG4-RSD were assessed through light microscopic evaluation with hematoxylin and eosin–stained sections. Special stains of periodic acid–Schiff with diastase and von Kossa were performed, as well as immunohistochemical stains with IgG and IgG4.
Results: All 3 cases showed elevated prostate-specific antigen with imaging findings suspicious for malignancy. On resection, histiocytic infiltration with Michaelis-Gutman bodies was identified (Figure 1.111, A and B). Positive staining for von Kossa (Figure 1.111, C) and periodic acid-Schiff–diastase special stains were seen, consistent with prostate malakoplakia. One of these cases demonstrated chronic sclerosing inflammation with >50 IgG4 plasma cells per 1 high-power field and IgG4:IgG ratio >40%, consistent with IgG4-RSD (Figure 1.111, D).
Conclusions: The findings of simultaneous prostate malakoplakia and IgG4-RSD may represent a concordance of 2 disease processes, or more likely a common biologic or immunologic mechanism of both disease processes. Malakoplakia is treated with antibiotics whereas IgG4-RSD is treated with steroids, and as such the concordance of both disease processes may present a clinical dilemma. The clinical significance of increased IgG4 plasma cells in association with malakoplakia is not well defined and awaits further study.
The Decline of Frozen Section Evaluation in the Genitourinary Tract: A 16-Year Institutional Experience
(Poster No. 112)
Anna-Lee Clarke-Brodber, MD (Clarkeannalee@gmail.com); Jerome Taxy, MD; Hussein Alnajar, MD. Department of Pathology, Northshore University Health Systems, Evanston, Illinois.
Context: Frozen section (FS) evaluation in the genitourinary (GU) tract is an effort between urologists and pathologists to guide intraoperative management; however, changes in surgical techniques and clinical outcome studies have altered the use of FS with downward utilization during urologic cancer procedures. This study examines an institutional experience of FS in urologic surgeries during the last 16 years.
Design: A retrospective search of the surgical pathology database between 2005 and 2020 was performed to identify cystectomies, prostatectomies, nephrectomies, and orchiectomies. The total number of each surgical procedure and FS was identified. The FS indications were also evaluated.
Results: A total of 270 cystectomies, 2649 prostatectomies, 1429 nephrectomies, and 389 orchiectomies were identified, with FS requested on 26.5%, 10.5%, 19%, and 6.8% of the total number of these surgical specimens, respectively. The overall decrease in FS requests per year from 53% to 13% of cystectomies, 23% to 0% of prostatectomies, and 29% to 0% of nephrectomies between 2005 and 2020 is highlighted in the figure (Figure 1.112). Indications for FS have also transitioned, particularly in the prostate, where lymph node examination accounted for 97% (25 of 27) in 2005, falling to 40% (2 of 5) in 2018, while margin evaluation requests have increased during the same time.
Conclusions: During a 16-year period, there has been a gradual decline in the use of FS in all GU cancer procedures, with a shift from routine use to limited use in certain unusual circumstances. Although the present study shows that FS in the GU tract has all but disappeared, potential changes in surgical techniques may dictate future utilization.
The Clinical Significance of Cribriform Pattern 4 in Prostate Biopsies: Our Institution Experiences
(Poster No. 113)
Oluwayomi S. Oyedeji, MD (email@example.com); Sameer C. Aryal, MD; Hovsep Ohan, MD; Shereen Zia, MD; Mohamed Alhamar, MD; Daniel Schultz, MD; Nilesh S. Gupta, MD; Oudai Hassan, MD. Department of Pathology and Laboratory Medicine, Henry Ford Hospital System, Detroit, Michigan.
Context: Prostatic carcinoma (PCa) with cribriform Gleason pattern 4 (CP4) on radical prostatectomy (RP) is generally considered more aggressive and associated with a higher stage on RP and biochemical recurrence. The significance of CP4 on needle biopsy (NBx) is not extensively correlated with subsequent RP findings.
Design: All NBx with the diagnosis of PCa grade group (GG) 2, 3, or 4 between 2007 and 2014 were initially included and were reviewed by a genitourinary pathologist. Any amount of CP4 was labeled as positive for CP4. Pathologic findings on the corresponding RP specimens, including Gleason score, pTN stage, and percentage of prostate tissue involved, were obtained from the pathology reports. The χ2 and Fisher exact test were used to analyze data.
Results: Of 144 patients evaluated, 46 had CP4 on their biopsies, whereas 98 had no evidence of CP4 on their biopsies. Patients with CP4 were significantly more likely to have higher-grade disease (odds ratio = 9; confidence interval, 3–26.8; P < .001). There was no significant difference between the 2 groups in terms of lymph node involvement, percentage of prostate tissue involved by tumor, or biochemical recurrence (Table).
Conclusions: Our study supports the general consensus that CP4 is associated with a more aggressive disease. This is important especially for patients with PCa GG2 with low percentage of Gleason pattern 4, as active surveillance is currently a management option for these patients at multiple institutions. The presence of any cribriform pattern 4 may be used as an exclusion criterion for active surveillance protocols.
Newly Emerging Renal Tumors: A Presentation of 2 Cases
(Poster No. 114)
Nibras Fakhri, MD (firstname.lastname@example.org); Christopher Girardo, DO; Wenjing Qiu, MD; Ritu Bhalla, MD. Department of Pathology, LSUHSC-NO, New Orleans, Louisiana.
Recently described rare renal tumors that have not yet been added to the World Health Organization (WHO) classification present diagnostic difficulties, and several of these tumors have a favorable prognosis. We present 2 such cases: 1 case each of eosinophilic solid and cystic renal tumor (ESCRT), and biphasic squamoid alveolar renal tumor (BSART); the latter may represent a subtype of papillary renal cell carcinoma. ESCRT has indolent behavior in most patients and is a member of the oncocytic renal neoplasms category, along with clear cell RCC, eosinophilic chromophobe RCC, oncocytoma, translocation-associated RCC, SDH-deficient RCC, and epithelioid angiomyolipoma. A 59-year-old woman presented with an incidental 5.1-cm exophytic, well-demarcated left renal mass. Microscopically, solid, alveolar, and focally cystic patterns were present with voluminous granular eosinophilic cytoplasm (Figure 1.114, A) with rare pink cytoplasmic granules (Figure 1.114, B), enlarged irregularly contoured nuclei, and occasionally prominent nucleoli. Immunohistochemistry was positive for PAX8, focal CK7, and CK20, and negative for pancytokeratin, CD117, cathepsin K, TFE3, and TFEB. A diagnosis of ESCRT was made. A 61-year-old woman presented with a 5-cm round, solid renal lesion. Microscopically, biphasic patterns with nests of large squamoid cells surrounded by alveolar-shaped cuboidal flattened cells and foci of emperipolesis (Figure 1.114, C, and D) were noted. The neoplasm expressed CK7 and AMACR diffusely with cyclin D1 and high-molecular-weight cytokeratin in the larger squamoid cells, consistent with BSART. The differential diagnosis for this entity includes mucinous tubular and spindle cell carcinoma, metanephric adenoma, clear cell RCC, and urothelial carcinoma. Awareness of these emerging entities, which may be included in the next WHO classification, is essential to prevent misdiagnosis.
A Case Series of Mixed-Grade Papillary Urothelial Carcinomas of the Renal Pelvis and Ureter
(Poster No. 115)
Meagan Chambers, MD, MS, MSc1 (MeaganMD@UW.edu); Jonathan Wright, MD2; Michael Haffner, MD, PhD3; Nicholas Reder, MD, PhD1; Maria Tretiakova, MD, PhD1; Funda Vakar-Lopez, MD1; Lawrence True, MD.1 Departments of 1Pathology, 2Urology, and 3Fred Hutchinson Cancer Center, University of Washington, Seattle.
Context: Though most papillary urothelial carcinomas are graded either low or high grade, a minority are mixed grade, being composed of predominantly low-grade cells with a minor high-grade component. Prior analyses of these mixed-grade lesions have focused on the bladder. We present a series of mixed-grade papillary carcinomas of the upper urinary tract with a focus on clinical course and outcomes.
Design: Pathology records between 2009 and 2021 from our hospital were searched for diagnoses of papillary carcinomas of the ureter. Predominantly low-grade cancers with <10% of a high-grade component and >2 months follow-up were included. Exclusion criteria included a prior or concurrent high-grade diagnosis including carcinoma in situ.
Results: Twenty-seven cancers met inclusion criteria: M:F, 4.4:1; average age, 68 years, with median follow-up 22.3 months (range, 2.4–87 months). At diagnosis, 8 cancers (30%) invaded the lamina propria/subepithelial connective tissue and 1 invaded the muscularis (3.7%). Nineteen patients (70%) underwent nephroureterectomy. Recurrences occurred in those without resection (n= 2) and 1 status post ureterectomy with negative margins. There were 3 cases of fatal metastases, 2 in patients with nephroureterectomies with negative margins.
Conclusions: In this series, mixed-grade non–muscle-invasive cancers arising in the ureter/renal pelvis had a range of outcomes including fatal metastatic disease despite nephroureterectomy. This stands in contrast to these lesions in the bladder, where they appear to have a more indolent course. This may reflect difficulty in sampling, diagnosis, and/or treatment.
Unusual Presentation of Renal Cell Carcinoma Unspecified With Medullary Phenotype
(Poster No. 116)
Jim C. Lee, MD, MPH (email@example.com); Jonathan Earle, MD; Ronald Araneta, MD. Department of Pathology, Hartford Hospital, Hartford, Connecticut.
Renal medullary carcinoma is a high-grade renal cell carcinoma with an aggressive clinical behavior. The diagnosis is often made in young adults, with a male to female ratio of 2:1. Most cases occur in African Americans with sickle cell trait or disease. According to the 2016 World Health Organization classification, tumors with the same morphology and immunoprofile but without sickle cell hemoglobinopathy are termed renal cell carcinoma unclassified with medullary phenotype. We report a 74-year-old white woman without sickle cell trait with this entity. The patient presented with incidental microhematuria. Imaging studies revealed a renal mass and an enlarged retrocaval lymph node. At nephrectomy, there was a 5.6-cm tumor. Histologically, the tumor cells exhibited extreme pleomorphism associated with extensive necrosis (Figure 1.116, A) and sarcomatoid differentiation (Figure 1.116, B), with retrocaval node. Immunohistochemistry studies were positive for PAX-8 and pan-cytokeratin AE1/AE3 and focally for CK7, supporting a renal cortical carcinoma. The tumor was negative for GATA-3, p63, 34βE12 (Figure 1.116, C) arguing against urothelial or collecting duct origin. Cathepsin-K, HMB-45, Mel-C, and TFE3 were all negative, ruling out translocation carcinoma. There was loss of INI-1 (SMARCB1) (Figure 1.116, D), favoring a diagnosis of a renal medullary carcinoma. Spinal metastasis was found 3 months postoperatively, for which she received palliative radiotherapy immunotherapy. However, she developed extensive deep vein thrombosis and pulmonary embolism and died 4 months after the diagnosis. Because of the extremely aggressive clinical course, careful histologic examination and a panel of immunohistochemistry are required to render the correct diagnosis.
DNA Sequencing Profile of Micropapillary Urothelial Carcinoma
(Poster No. 117)
Ziad M. El-Zaatari, MD (firstname.lastname@example.org); Jae Y. Ro, MD, PhD; Randall J. Olsen, MD, PhD; Heather L. Hendrickson, MBA; Steven Shen, MD, PhD; Alberto Ayala, MD; Mukul Divatia, MD. Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas.
Context: Micropapillary urothelial carcinoma (MPUC) is a distinct morphologic variant associated with aggressive behavior. Knowledge of the molecular profile of MPUC is limited, and to the best of our knowledge no DNA sequencing data have yet been published on MPUC.
Design: Nine cases of urothelial carcinoma with MPUC components were identified. Hematoxylin-eosin slides of the tumors were reviewed by a genitourinary pathologist and a genitourinary pathology fellow. Microdissection from 10 μm formalin-fixed, paraffin-embedded slides was performed to obtain both MPUC and non-MPUC DNA samples from each of the tumors. A next-generation hotspot sequencing assay on 50 genes was performed on paired MPUC and non-MPUC samples to detect somatic mutations.
Results: A summary of pathologic features and mutations detected in each case is presented in the Table. Identical mutations were detected in both MPUC and non-MPUC components in 4 of 9 cases and no mutations were detected in either component in 3 of 9 cases. One case showed no mutation in the MPUC component but KRAS c.183A>T mutation in the non-MPUC component. In 1 case with sarcomatoid urothelial carcinoma, different mutations were detected in the MPUC and sarcomatoid carcinoma components.
Conclusions: Most cases studied showed identical 50-gene molecular profiles in both MPUC and non-MPUC components within the same tumor. This suggests a common clonal histogenesis for both components in these tumors. Therefore, sequencing MPUC components can aid in the detection of mutations for targeted therapies, which may be particularly beneficial given the worse prognosis of this urothelial carcinoma variant.
Collision Tumors of Kidney: A 5-Year Single-Institutional Experience
(Poster No. 118)
Donghwa Baek, MD (email@example.com); Michelle Lin, MD; Lukas Cara, MD; Steven Shen, MD, PhD; Alberto G. Ayala, MD; Jae Y. Ro, MD, PhD. Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas.
Context: Collision tumor is an uncommon entity characterized by 2 histogenetically and histologically different tumors “colliding” within a single mass. Although previously considered rare, collision tumors have been increasingly recognized in the kidney; more than 20 cases have been reported in the English literature. Here, we describe 6 additional cases of renal collision tumors at our institution within the past 5 years.
Design: Kidney tumors composed of more than 2 histotypes were selected from our institutional archives from 2015 to 2020. Cases of metachronous or synchronous tumors without collision, tumor-to-tumor metastasis, and hybrid oncocytoma-chromophobe renal cell carcinoma (RCC) were excluded.
Results: Six cases were reviewed. The patient ages at presentation ranged from 55 to 78 years, and the tumor sizes ranged from 1.4 to 8 cm (mean, 3.8 cm). The major tumor components were oncocytoma (n = 3), urothelial carcinoma (n = 1), chromophobe RCC (n = 1), and acquired cystic disease–associated RCC (n = 1). The minor components were mucinous tubular and spindle cell carcinoma (n = 2), type 1 papillary RCC (n = 1), clear cell papillary RCC (n = 1), tubulocystic RCC (n = 1), and papillary adenomatosis (n = 1) (see Table).
Conclusions: Renal collision tumors are recognized more frequently than previously documented. To detect collision tumors, generous sampling, particularly from areas with distinctly different gross appearances, is highly recommended. In addition, for an unequivocal diagnosis of collision tumor, dedifferentiation, hybrid tumors, secondary degenerative changes, and tumor-to-tumor metastasis should be excluded. Molecular studies may be required to further elucidate the histogenetic origins of collision tumors.
Urothelial Carcinoma With Primary Angiomatous Differentiation: A Diagnostic Challenge With Ominous Clinical Outcome
(Poster No. 119)
Sara Abu Mehsen, MD (firstname.lastname@example.org); Maria Kamal, MD; Lewis A. Hassell, MD; Kar-Ming Fung, MD, PhD; Wenyi Luo, MD, PhD. Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City.
Although angiosarcoma can rarely arise from the urinary tract, morphologically uniform urothelial carcinoma with partial vascular phenotype has not been reported. A urinary bladder tumor was discovered in a 64-year-old man without prior radiation history after presenting with hematuria. A muscle-invasive urothelial carcinoma was diagnosed at an outside hospital. The patient underwent radical cystectomy following preoperative adjuvant chemotherapy. A 3-mm tumor of small blue cell morphology with no cytokeratin and GATA3 expression was identified in the resected specimen. No residual conventional urothelial carcinoma was identified. The patient subsequently developed diffuse peritoneal tumor spread. The peritoneal tumor demonstrated classical angiosarcoma morphology with atypical vascular spaces (Figure 1.119, A) and expression of all vascular markers. When the tumor in the preoperative transurethral resection was retrospectively studied, a second tumor cell population was revealed. In contrast to the associated conventional urothelial carcinoma (Figure 1.119, B), which expressed GATA3 (Figure 1.119, C) and was negative for all vascular markers, the second tumor cell population (10% of the tumor), although morphologically similar to intermixed conventional urothelial carcinoma (with no atypical vascular spaces) (Figure 1.119, B), expressed vascular markers including ERG (Figure 1.119, D) but was negative for GATA3. We believe the tumor is best classified as urothelial carcinoma with primary angiomatous differentiation based on the intimate association between conventional and vascular components and indistinguishable morphology between them. Our case demonstrated a challenge in diagnosis and ominous clinical outcome because of its resistance to urothelial carcinoma chemotherapy. Further molecular studies are warranted to understand the pathogenesis of the entity and identify druggable targets for management.
Correlation of Preoperative Studies With Extraprostatic Extension of Prostatic Carcinoma in Radical Prostatectomies: A Retrospective Study
(Poster No. 120)
Nibras Fakhri, MD (email@example.com); Zaid Khreefa, MD; Maryam Shahmirzadi, MD; Wenjing Qiu, MD; Edward Peters, DMD, ScD; Madhav KC, MPH; Tracy Dewenter, MD; Raman Danrad, MD; Ritu Bhalla, MD. Department of Pathology, LSUHSC-NO, New Orleans, Louisiana.
Context: Prostate carcinoma (PCa) is the second leading cause of cancer and of cancer death in US men. Primarily, its diagnosis is made on needle biopsies, which dictates the treatment choices. Radical prostatectomy (RPC) is followed by a significant decline in mortality in confined diseases; however, overall prognosis is reduced with locally advanced disease. Extraprostatic extension (EPE) in RPC is a strong prognostic factor. No single parameter can accurately predict EPE in RPC. The purpose of our study is to correlate preoperative studies with adverse histologic finding of EPE in RPC, and their value in guiding treatment.
Design: Following IRB approval, retrospective review of electronic medical records was performed to identify patients who underwent RPC for PCa. Our study group included PCa patients with and without EPE. Correlation studies were conducted on preoperative parameters including serum prostate-specific antigen (PSA) levels, PIRADS score, and biopsy findings including Gleason score (GS), quantitative tumor volume (TV), perineural invasion (PNI), and tumor in fibroadipose tissue (TFAT), with resection findings.
Results: One hundred three patients (65 EPE, 38 without EPE; average age 59 years [range, 42–73 years]; PSA 16.8 ng/mL [range, 0.6–89.7 ng/mL) were identified. Ninety-eight corresponding biopsies were obtained. Correlation studies between preoperative parameters and resection findings are shown in the Table. Significantly increased incidence of EPE (P < .05) was noted with: PIRADS score >4; biopsy findings of TV >50%, GS, PNI, and TFAT. P value for >4 ng/mL PSA was .05.
Conclusions: This study suggests that a multi-parametric approach is essential for staging of PCA in patients with apparently localized cancer, which also helps direct the treatment strategy.
Myoid Gonadal Stromal Tumor
(Poster No. 121)
Saman S. Karimi, MD, MS (firstname.lastname@example.org); Vikas Mehta, MD. Department of Pathology, University of Illinois at Chicago.
Myoid gonadal stromal tumor (MGST) is a rare pure stromal neoplasm of the testis, classified as a newly emerging entity in the 2016 World Health Organization (WHO) classification. MGST is hypothesized to arise from peritubular myoid cells, although its histogenesis remains unknown. We present a case of a healthy 33-year-old man who presented for evaluation of azoospermia. Scrotal ultrasound demonstrated an incidental, 1.1-cm hypoechoic mass in the superior pole of the right testis with prominent vascularity, suspicious for a neoplasm. Right testicular nodulectomy was performed and gross examination demonstrated a well-circumscribed, homogenous, tan lesion. Microscopically, the lesion was composed of bland spindle cells with elongated nuclei and inconspicuous nucleoli, ectatic vasculature, and variable amount of collagen deposition, and lacked necrosis, abnormal mitoses, and lymphovascular invasion. Our differential diagnoses included leiomyoma, testicular fibrothecoma, granulosa cell tumor, unclassified sex-cord stromal tumor, and MGST. The lesional cells demonstrated strong, diffuse S100 staining, coexpression of SMA, strong SF-1 nuclear staining (Figure 1.121), and lack of h-caldesmon and inhibin immunoreactivity. The morphology and immunophenotype of the lesion were consistent with diagnosis of MGST. There have been <16 cases of MGST reported in the literature. The unifying diagnostic criteria consist of pure spindle cell lesion without atypia/sex-cord differentiation, and coexpression of S100, SMA, and SF-1 immunostaining. Treatment involves nodulectomy or partial orchiectomy. No cases of metastasis or recurrence have been reported in the literature. In summary, MGST is a newly emerging indolent spindle cell neoplasm of the testis and correct diagnosis is essential for appropriate patient care.
Enteric-Type Adenocarcinoma Presenting as a Very Late Relapse of Testicular Cancer at Site of Metastasis: Report of 2 Cases
(Poster No. 122)
Hardik Sonani, MD (email@example.com); Vijay Kumar, MD; Varsha Manucha, MD. Department of Pathology, University of Mississippi Medical Center, Jackson.
Somatic transformation of germ cell tumor (STGCT) occurs in 3%–6% of primary testicular nonseminomatous GCTs, in 8% of postchemotherapy retroperitoneal lymph node dissection (RPLND), and in 20% of late relapse cases. Very late relapse (>5 years after diagnosis) is very rare. We present 2 cases of STGCT that presented as recurrent retroperitoneal abscess and solid cystic abdominal mass 18 and 15 years postorchiectomy, RPLND, and chemotherapy for testicular cancer diagnosed at 30 and 34 years of age, respectively (Table). For the first case, the initial biopsy revealed abscess and repeat biopsy revealed dysplastic enteric-type glands. Extensive workup for the origin of the tumor was negative. Subsequent resection revealed an enteric-type adenocarcinoma, negative for SALL4, but positive for i12p by fluorescent in situ hybridization (FISH). In our second case biopsy showed an adenocarcinoma, confirmed on surgical resection with subsequent i12p positivity. Only case 1 received chemotherapy; the patient developed metastatic disease to neck lymph nodes and abdominal recurrence within 6 months, which was treated with surgical resection, and is disease free 1 year later. The second patient is doing well at 1-year follow-up. Besides remote history, a completely different histology and atypical presentationat an older age increase the chances of late diagnosis or misdiagnosis of a late relapse and STGCT. This case report signifies the importance of keeping STGCT in the top differential diagnosis and including i12p analysis up front in a patient with history of testicular tumor, however remote it is and even if histology of primary tumor is unknown.
Vasitis Nodosa With Extensive Perineural Invasion and CA19-9 Positivity
(Poster No. 123)
Mary E. Doan, MD1 (firstname.lastname@example.org); Shajia Rahman Ansari, MD1; Linda K. Green, MD.2 1Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas; 2Department of Pathology and Laboratory Medicine Section, Michael E. Debakey Veterans Affairs Medical Center, Houston, Texas.
Vasitis nodosa is a benign proliferation of the vas deferens epithelium, usually secondary to trauma or obstruction. This is commonly seen in the setting of prior vasectomy, occurring in approximately 50%–60% of patients presenting for vasovasostomy. Vasitis nodosa can have a variety of histologic characteristics that may be concerning for metastatic carcinoma, including infiltrative growth with perineural and vascular invasion and cytologic atypia with prominent nucleoli. We present a case of a 37-year-old man with prior vasectomy who underwent vasovasostomy. Histologic examination of the discarded vas segments revealed a proliferation of infiltrative ductules with and without sperm. The cells had enlarged nuclei and prominent nucleoli (Figure 1.123, A). Extensive perineural invasion was noted (Figure 1.123, B). The ductules demonstrated PAX-8 and AMACR positivity with loss of basilar p63. Ductules were negative for PSA and CDX-2. Interestingly, the tubules showed cytoplasmic and membranous staining for CA19-9 (Figure 1.123, C), which has not previously been described. CA19-9 was negative in the normal vas epithelium (Figure 1.123, D). CA19-9 is typically used as a marker for pancreatobiliary and gastrointestinal cancers. Levels may also be elevated in the urine of patients with urothelial carcinoma, benign ureteropelvic junction obstruction, or autosomal-dominant polycystic kidney disease. We hypothesize that CA19-9 levels may be elevated in some patients postvasectomy, which may explain the positive staining within the vasitis nodosa. CA19-9 staining of vasitis nodosa is a potential pitfall in rare cases of pancreatobiliary and gastrointestinal metastases to the male genitourinary tract.
A Rare Case of Clear Cell Renal Cell Carcinoma With Necrotizing Granulomatous Inflammation
(Poster No. 124)
Hala Abdelwahab, MD (email@example.com); Mahmut Akgul, MD. Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, New York.
A granulomatous reaction is a form of chronic inflammation composed of T lymphocytes and macrophages with or without necrosis. Clear cell renal cell carcinoma (RCC) associated with granulomatous reaction is a rare pathologic finding with only a few cases published in the literature. Among these few cases, the majority showed nonnecrotizing granulomatous reaction and only few showed granulomatous reaction with small foci of coagulative necrosis. We present a case of clear cell RCC with multiple intratumoral necrotizing granulomas. A 43-year-old man with no known history of tuberculosis or sarcoidosis was noted to have suprapubic pain and nocturnal incontinence. The patient had a computed tomography scan of the abdomen and pelvis with intravenous contrast that showed a 4-cm hypervascular, enhancing, intraparenchymal renal mass. The patient underwent a biopsy of the right renal mass, which was consistent with clear cell RCC. A right partial nephrectomy was performed. Microscopic examination showed classic clear cell RCC with multiple necrotizing granulomas (Figure 1.124). AFB and GMS stains were negative. The patient has been followed up in our hospital for the last 5 years with no evidence of metastasis or recurrence. Studies suggest that granulomatous reaction is caused by a T-cell–mediated reaction against tumor antigens that may be secondary to antigen shedding or an immune reaction against the tumor. Necrotizing granulomas in clear cell RCC are a rare finding that pathologists should be aware of after excluding bacterial or fungal infections.
Renal Mucormycosis—A Rare, Life-Threatening Infection in a Renal Transplant Patient With Concurrent Marijuana Use
(Poster No. 125)
Kayla Hoerschgen, MD (firstname.lastname@example.org); Ashwyna Sunassee, MD. Department of Pathology, University of South Dakota Sanford School of Medicine, Sioux Falls.
Mucormycosis is a serious fungal infection that typically affects immunocompromised patients. We present a case of disseminated mucormycosis infection in a 34-year-old man with a history of marijuana use and focal segmental glomerulosclerosis who underwent living unrelated kidney transplant. After his transplant, he developed recurrent focal segmental glomerulosclerosis. Two months later, he developed pleuritic chest pain, and imaging revealed a ground glass opacity with a surrounding dense consolidation within the right upper lobe, concerning for an angioinvasive fungal infection. During the hospitalization, his creatinine increased, and a biopsy of the allograft kidney demonstrated acute tubulointerstitial nephritis, acute vasculitis, and glomerular intracapillary fibrin thrombi with angioinvasive Mucorales fungal infection. The patient subsequently underwent transplant nephrectomy. Grossly, the allograft was pale white to dusky tan-red with poorly delineated cortical medullary junctions. Microscopic examination revealed necrotic tubules with a dense neutrophilic infiltrate, multinucleated giant cells (Figure 1.125, A and B), and ribbonlike, aseptate hyphae (Figure 1.125, C). Gomori methenamine silver stain highlighted the fungal elements (Figure 1.125, D), which are morphologically consistent with Mucorales. Review of the literature revealed that the infectious rate posttransplant is approximately 2%–14%, with disseminated disease having a mortality rate of 76%. However, the literature does not show a consistency in presenting symptoms and few case reports have been published demonstrating marijuana use as a cause of pulmonary mucormycosis or even disseminated disease. The purpose of our case report is to add knowledge to the presenting symptoms and investigate the association of marijuana use with pulmonary and disseminated mucormycosis.
Primary Adenocarcinoma of the Urinary Bladder: A Rare Malignancy and Diagnostic Dilemma
(Poster No. 126)
Fareed Rajack, MD1 (email@example.com); Ali Afsari, MD1; Lekidelu Taddesse-Heath, MD1; Adam R. Metwalli, MD2; Tammey J. Naab, MD.1 Departments of 1Pathology and 2Surgery, Howard University Hospital, Washington, DC.
Adenocarcinoma of the urinary bladder is a rare neoplasm, representing <2% of urinary bladder malignancies. A 59-year-old African American hypertensive male presented with painless hematuria and symptomatic anemia. A computed tomography scan revealed a markedly enlarged prostate gland, associated with a bladder mass, causing significant bilateral hydroureteronephrosis. Transurethral re-section of the bladder tumor revealed invasive adenocarcinoma with signet ring cells. Transurethral resection of the prostate showed prostatic adenocarcinoma with direct invasion of the prostatic stroma by invasive adenocarcinoma arising in the bladder. Immunostain performed on the bladder revealed positive CK20 (cytoplasmic), CDX2 (nuclear), villin (cytoplasmic), and β-catenin (cytoplasmic) and negative CK7, GATA3, PSA, PSAP, and NKX3.1. No histologic features of conventional high-grade urothelial carcinoma and lack of expression of GATA3 and CK7 rule against high-grade urothelial carcinoma with divergent differentiation. These aggregate findings support the diagnosis of primary adenocarcinoma of the urinary bladder. Lack of PSA, PSAP, and NKX3.1 expression rules against prostatic origin. Cytoplasmic β-catenin does not favor colorectal origin. Radical cystoprostatectomy revealed an ulcerated mass measuring 7.0 × 5.5 × 2.5 cm in the base of the bladder directly extending into the base of the prostate and diffusely infiltrating the prostatic stroma. There was diffuse thickening of the bladder wall with sparing of the dome. Histologic findings in the radical prostatectomy were similar to the features as described above. This rare tumor can be a diagnostic dilemma with adenocarcinomas in adjacent organs; therefore, clinical information, imaging, histology, and immunohistochemical correlation is essential to render a correct diagnosis.
Squamous Cell Histology of Tumors of Upper Urinary Tract: A Clinicopathologic Study of Pure Squamous Cell Carcinoma and Extensive Squamous Differentiation of Urothelial Carcinoma
(Poster No. 127)
Swati Bhardwaj, MBBS, MD1 (firstname.lastname@example.org); Deepthi Hoskoppal, MD2; Fang-Ming Deng, MD2; George K. Haines III, MD1; Quisheng Si, MD.1 1Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai Hospital, New York, New York; 2Department of Pathology, NYUniversity Langone, New York, New York.
Context: Squamous cell histology in tumors of the upper urinary tract is rare. Pure squamous cell carcinomas of the upper urinary tract are even rarer, and most of the knowledge about these tumors is derived from isolated case reports.
Design: We searched pathology databases in 2 institutions for pure squamous cell carcinomas and extensive (>50%) squamous differentiation in urothelial carcinomas and found 6 cases of pure squamous cell carcinoma and 4 cases of extensive squamous differentiation in urothelial carcinomas. The clinicopathologic details of these cases were studied.
Results: The patients' mean age at diagnosis was 67 years (range, 33–93 years); 5 were women, and 5 were men. Patients usually presented with renal mass (n = 5) and hydronephrosis (n = 3). The mean tumor size was 4.9 cm (range, 1.5–10.0 cm). Of the 6 pure squamous cell carcinomas, 5 occurred in the renal pelvis and 1 in the ureter. Of the 4 cases of extensive squamous differentiation, 2 were in the renal pelvis, 1 in the upper pole, and 1 in the midureter. Lymph node metastases was not found in any of the cases with submitted lymph nodes. One patient had a tumor recurrence after a few months and died. One patient developed a high-grade urothelial carcinoma of the bladder 1 year later.
Conclusions: Tumors with squamous cell histology usually present at higher stage and older ages with an equal incidence in both sexes. In our limited study, most patients responded well to treatment and, barring 1 patient, survived.
A Case of AL Amyloidosis Confirmed by Liquid Chromatography Tandem Mass Spectrometry With Negative Immunofluorescence Finding
(Poster No. 128)
Yuan Huang, MD, PhD (email@example.com); Diping Wang, MD, PhD. Department of Pathology, University of Cincinnati Medical Center, Cincinnati, Ohio.
Immunofluorescence microscopy of kidney biopsy specimens is one of the primary tools in the diagnosis of AL amyloidosis. However, cases of AL amyloidosis with negative immunofluorescence staining for κ and λ light chains are not uncommon. We present a case of amyloidosis with negative immunofluorescence finding from a 69-year-old white man. He presented with stage 3 chronic kidney disease with nephrotic range proteinuria, previously diagnosed with monoclonal gammopathy of undetermined significance. Both serum and urine protein electrophoresis showed IgG λ monoclonal gammopathy. His bone marrow biopsy showed approximately 8% λ-restricted plasma cells. Kidney biopsy revealed mesangial expansion by amorphous acidophilic material that stained weakly for PAS, negative for Jones silver, and positive for Congo red. In addition, the amyloid deposits involved the renal interstitium, many arterioles, and small interlobular arteries. Immunofluorescence staining by the standard method in our laboratory showed negative results for IgG, IgM, C3, and C1q, with IgA, κ, and λ highlighting tubular casts without light-chain restriction (Figure 1.128, A and B). Electron microscopy showed characteristic nonbranching, randomly oriented fibrils measuring 9–11 nm in thickness. The result of liquid chromatography tandem mass spectrometry performed at Mayo Clinic on microdissected areas of the paraffin-embedded tissue was consistent with AL-type amyloid deposition. AL amyloidosis is usually associated with systemic disease due to an underlying clonal plasma cell proliferation/B-cell lymphoma. It is crucial to differentiate AL amyloidosis from other types because of its distinct management. Liquid chromatography tandem mass spectrometry is proven to be helpful in this differentiation, especially in immunofluorescence-negative AL amyloidosis cases.
Distinguishing Benign and Malignant Oncocytic Tumors Using Deep Learning Algorithm
(Poster No. 129)
Andrei Kapustin, BS1; Karen Fang, MD2; Maria Tretiakova, MD, PhD2 (firstname.lastname@example.org). 1Graduate School of Arts and Science, New York University, New York, New York; 2Department of Laboratory Medicine and Pathology, University of Washington, Seattle.
Context: Convolutional neuronal networks are a powerful deep learning (DL) tool increasingly utilized in tumor subtyping. Differentiating oncocytoma (ONC) and malignant counterpart chromophobe renal cell carcinoma (ChRCC) remains one of the most challenging areas in uropathology because of overlapping morphology. We aimed to create a DL classifier for accurate differentiation of benign ONC from ChRCC.
Design: Eighty ONC and 175 CHRCC tumors (60% classic and 40% eosinophilic) including historic cases with immunohistochemical and molecular confirmation of diagnoses, diagnostic cases from 2010 to 2020, and ChRCC cases from the Genome Atlas Data Portal were used. Cases were randomly assigned to either training (69%), validation (15%), or test set (16%). A total of 9263 digital images captioned at ×20 magnification or selected from ×20 whole scanned images were split into 4 equal parts, resized to 320 × 180, and used for training several DL models. The best results were achieved with a custom ResNet-like model and further optimized.
Results: The best DL model achieved accuracy of 0.96, precision of 0.96, recall of 0.98, and AUC of 0.99 at a probability threshold of 0.6 (Figure 1.129). We then evaluated the model on a final held-out testing cohort with 90.4% accuracy for predicting benign ONC and 92% malignant ChRCC. Additionally, we tested the model on previously unseen cohort of hybrid tumors from Birt-Hogg-Dube patients or sporadic cases (n = 38, 477 images). Hybrid tumors were classified as benign in 92.7% of cases.
Conclusions: Our DL algorithm allowed accurate distinction between ONC and ChRCC, warranting further analysis of differentiating histopathologic features for diagnostic purposes. Novel finding of hybrid tumors classified as overwhelmingly benign by DL model supports their indolent behavior.
An International Validation Study of Automated Cancer Detection in Prostate Biopsies
(Poster No. 130)
Yuri Tolkach, MD1 (email@example.com); Vlado Ovtcharov2; Alexey Pryalukhin, MD3; Wolfgang Hulla, MD3; Marie-Lisa Eich, MD1; Peter Caie, PhD2; Eric Runde, MSME2; Reinhard Büttner, MD.1 1Department of Pathology, University Hospital Cologne, Germany; 2Indica Labs, Albuquerque, New Mexico; 3Department of Pathology, Landesklinikum Wiener Neustadt, Austria.
Context: Digital pathology provides an opportunity for computational analysis of histologic slides and the standardized automation of some pathologic tasks. The reporting of prostate cases is time-consuming because of the large number of slides per case. In this retrospective study, we validate a deep learning–based tool for prostate cancer detection from patient biopsy samples.
Design: A prostate cancer deep learning–based detection tool was previously developed and implemented in HALO AI and HALO AP software (Indica Labs, Albuquerque, New Mexico). Two external validation cohorts of patients with multifocal prostate biopsy were analyzed from 2 high-volume pathologic institutes: cohort 1/dataset 1 (Cologne, n full cases = 65) digitized by Hamamatsu S360 scanner; cohort 2 (Wiener Neustadt, n full cases = 57) digitized by Hamamatsu S360 scanner (dataset 2) and Leica GT450 scanner (dataset 3).
Results: Similar high-accuracy metrics were received for all 3 datasets, implying good generalization among cases from different institutes and digitized by different scanner systems (Table, without any forms of normalization). Several cores were detected where tumor was missed by pathologists (cohort 1: n = 7; cohort 2: n = 5). The average analysis time was 1 min/core in cohort 1, and 2 min/core for cohort 2.
Conclusions: The prostate cancer detection tool reported high accuracy for prostate cancer detection in biopsy cases during external validation independent of the institute or scanner used. It is fully integrated into Indica Labs' digital pathology platform and can assist pathologists in the form of prescreening or quality control during analysis of prostate biopsy cases.
De Novo Collecting Duct Carcinoma in a Transplant Kidney With Distant Metastasis
(Poster No. 131)
Mohamed A. Yakoub, MD (firstname.lastname@example.org); Diping Wang, MD, PhD. Department of Pathology, University of Cincinnati Medical Center, Cincinnati, Ohio.
Collecting duct carcinoma (CDC) is a rare type of renal cell carcinoma with aggressive behavior. De novo renal cell carcinomas in transplanted kidneys have been reported sporadically with incidence of about 0.5%, but reports of CDC in renal allograft are extremely rare. Cases presetting with distant metastasis have not been described before. We report a case of a 37-year-old woman with history of end-stage renal disease status post kidney-pancreas transplant and longtime BKV nephropathy. She presented 5 years later with an anterior abdominal mass. Biopsy showed metastatic undifferentiated high-grade carcinoma composed of highly pleomorphic cells, frequent mitoses (Figure 1.131, A), and positivity for CK7, P53, and PAX8. Suspicion for renal origin was raised. Subsequent imaging revealed a mass in the kidney transplant and retroperitoneal, pelvic, and mesenteric lymphadenopathy. The kidney mass biopsy confirmed the diagnosis of poorly differentiated CDC, showing tubular architecture, brisk mitoses, apoptosis, prominent nuclear atypia, and mixed inflammatory infiltrate (Figure 1.131, B and C). Comparative review with the prior abdominal biopsy showed identical features, confirming metastatic CDC. Tumor cells showed focal GATA-3 and CK7 positivity. SV40, a marker frequently used for BKV infection, showed positive nuclear staining (Figure 1.131, D), however, BKV RNA in situ hybridization was negative. Expression of BKV antigen was identified in tumor cells with no evidence of BKV RNA, raising a possible connection between CDC tumorigenesis and history of longtime BKV infection.
Heavy Metals in Prostate Tissue and Time to Biochemical Recurrence After Radical Prostatectomy
(Poster No. 132)
Virgilia Macias, MD1 (email@example.com); Andrey G. Sarafanov, PhD2; Todor I. Todorov, PhD3; José A. Centeno, MD2; Marion A. Gray, PhD4; Ujalla Sheikh, MD, MSc1; Batool H. Huzaifa, MD1; André Kajdacsy-Balla, MD, PhD.1 1Department of Pathology, University of Illinois at Chicago; 2Division of Biophysical Toxicology, Environmental and Infectious Disease Sciences, Armed Forces Institute of Pathology, Washington, DC; 3Office of Regulatory Science, Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, Maryland; 4Department of Occupational Therapy, School of Health and Sport Sciences, University of Sunshine Coast, Queensland, Australia.
Context: Our previous publication showed that low concentrations of iron and zinc in normal prostate tissue adjacent to tumor were associated with biochemical recurrence after prostatectomy.
Design: We are now presenting information on time to recurrence comparing patients in the lowest and the highest quartiles of iron and zinc concentrations using the same prostatectomy samples. The metal levels were obtained by inductively coupled plasma mass spectrometry from formalin-fixed, paraffin-embedded normal-appearing areas of prostate tissue adjacent to prostate cancer. Measurements were analyzed by log-rank test of time to recurrence, and Kaplan-Meier curves of the 20 cases of lowest quartile of metal ion concentration with those in the highest quartile.
Results: There was a trend but no statistical significance for faster time to recurrence in subjects with lower iron or zinc levels.
Conclusions: In contrast to prognosis for recurrence, time to recurrence is not influenced by low iron or zinc levels. The small number of subjects in our present study may not be sufficient for a definitive conclusion.
Malignant Solitary Fibrous Tumor in a Kidney of a 67-Year-Old Woman
(Poster No. 133)
Kaia M. Erickson, MD (firstname.lastname@example.org); Ashwyna Sunassee, MD; Ryan Askeland, MD. Department of Pathology, Sanford USD Medical Center, Sioux Falls, South Dakota.
Solitary fibrous tumor (SFT) is a mesenchymal fibroblastic neoplasm with prominent staghorn branching vessels, a “patternless” pattern, and characteristic immunostaining pattern of CD34, BCL-2, and STAT-6 positivity. It is typically benign unless there is necrosis, size greater than 10 cm, and increased mitoses. We present a case of malignant solitary fibrous tumor in a 67-year-old woman who initially presented with a 20-pound weight loss during several months, night sweats, and abdominal pain. Computed tomography (CT) of the abdomen showed a large heterogeneously enhancing right renal mass. She underwent a nephrectomy, revealing a 25.0 × 17.3 × 13.3-cm kidney entirely effaced by a tan-pink homogeneous mass with focal areas of necrosis. Microscopic examination revealed a spindle cell tumor with staghorn vasculature (Figure 1.133, A), necrosis (Figure 1.133, B), and up to 4 mitotic figures per 10 high-power fields. Immunohisto-chemical stains performed revealed the neoplastic cells were positive for STAT6 (Figure 1.133, C) and CD34 (Figure 1.133, D) and focally positive for BCL-2. The presence of necrosis, increased mitoses, and large tumor size are features described in solitary fibrous tumors that exhibit malignant behavior. This is an unusual case because solitary fibrous tumors make up only about 2% of soft tissue tumors. Among those, there have only been fewer than 100 cases reported in the kidney, with even fewer demonstrating histologic features suggestive of malignant behavior.
POSTER SESSION 2: SUNDAY, SEPTEMBER 26, 2021
Gynecologic and Placental Pathology; Hematopathology; Practice Management
Correlation Between Sonographically Measured Endometrial Thickness and Histopathological Findings in Premenopausal and Postmenopausal Women With Abnormal Uterine Bleeding
(Poster No. 1)
Jwan A. Alallaf, MD1 (Jwan.email@example.com); Ethar Al-Husseinawi, MD2; Kamani M. Lankachandra, MD1; Evanthia Omoscharka, MD.1 1Department of Pathology, University of Missouri, Kansas City; 2Department of Pathology, University of Kansas, Kansas City.
Context: Abnormal uterine bleeding (AUB) can be due to a wide spectrum of gynecologic and nongynecologic causes. The differential diagnosis includes benign and malignant causes. This study aims to analyze correlation of endometrial biopsy (EMB) and Papanicolaou cervical cytology (Pap smear) results with ultrasound-measured endometrial thickness (ET) in women with AUB.
Design: A retrospective chart review was conducted on patients who presented to our institution from July 1, 2019, to July 1, 2020, for EMB. Patients with history of AUB and ET on ultrasonography were included. Two groups were identified: premenopausal and postmenopausal. Age, parity, body mass index (BMI), and use of hormonal therapy were recorded. The result of EMB was divided into normal (secretory, proliferative phase, and atrophic endometrium), abnormal (endometrial polyps, endometrial hyperplasia, endometrial cancer, and endometritis), and others (insufficient for diagnosis).
Results: A total of 59 patients were included: premenopausal women (47%) and postmenopausal women (52%). Normal EMB was found in 42%, and 47% of the patients had abnormal EMB. Endometrial polyp represented most abnormal findings (35.9%) especially in premenopausal patients, and atrophy represented most normal findings (27.7%), specifically in postmenopausal patients. Endometrial hyperplasia without atypia (5.1%), and endometrial cancer (3.1%) only presented in the postmenopausal group. BMI was high in all patients with endometrial cancer. Pap smear was normal in 73% of patients, and benign endometrial glands were identified in 8.4% of patients (Table).
Conclusions: Increased ET associated with AUB is mostly due to benign lesions of the uterus. EMB is the gold standard method for diagnosis of endometrial pathology. Radiologic and pathologic correlation is recommended for better patient outcome.
Evaluation of Immunotherapeutic Vulnerability Indicators Indoleamine-2,3-Dioxygenase, Programmed Death-Ligand 1, and Mismatch Repair Protein Expression in Uterine Carcinosarcomas
(Poster No. 2)
Joseph D. Coppock, MD, PhD (firstname.lastname@example.org); Taylor M. Jenkins, MD; Anne M. Mills, MD. Department of Pathology, University of Virginia, Charlottesville.
Context: Uterine carcinosarcomas are biphasic epithelial and mesenchymal malignancies. Therapy includes surgery +/− chemotherapy and/or radiation. High rates of recurrence and metastasis necessitate improved nonsurgical approaches. Indoleamine-2,3-dioxygenase (IDO) catalyzes the rate-limiting step in tryptophan metabolism. IDO can be upregulated by cancer cells, depleting microenvironment tryptophan, inhibiting regulatory T-lymphocyte activation/expansion, and impairing cytotoxic T-cell response. Inhibitors are under investigation for various cancers; however, expression is not well studied in carcinosarcoma, particularly with attention to PD-L1 and mismatch repair (MMR) status.
Design: Whole sections of formalin-fixed, paraffin-embedded tissue from 42 uterine carcinosarcomas with available MMR protein, PD-L1, and p53 expression status were evaluated. Hematoxylin-eosin diagnosis was confirmed. IDO expression was determined by immunohistochemistry (1:2000; HPA-023072, Sigma Prestige). At least 1% IDO tumoral staining was considered positive.
Results: Two cases were reclassified as dedifferentiated carcinoma, based on lack of mesenchymal differentiation. Seventy-five percent (30/40) of confirmed carcinosarcomas (Figure 2.2, A) demonstrated ≥1% IDO expression (Figure 2.2, B), including a single MMR-deficient carcinosarcoma. Only 4 cases showed >30% expression. Expression was most prominent within well-differentiated epithelial components. Seventy percent (21/30) of IDO-positive cases also expressed PD-L1 (CPS >1) (Figure 2.2, C), while 87% (26/30) demonstrated abnormal p53 expression. Both tumors reclassified as dedifferentiated carcinoma were IDO-positive (3% and 30%), PD-L1–positive, and MMR-deficient.
Conclusions: Most uterine carcinosarcomas express IDO, suggesting immunotherapy targeting IDO may have promise in this difficult-to-treat tumor type, potentially in combination with PD-1/PD-L1 axis inhibitors. Of note, dedifferentiated carcinomas may be misclassified as carcinosarcoma and appear particularly enriched for IDO expression, but also for other indicators of immunotherapeutic vulnerability including PD-L1 expression and MMR deficiency.
Limited Application of Silva System in Biopsies to Predict Clinical Behavior for Usual Type Endocervical Adenocarcinoma
(Poster No. 3)
Yun Wang, MD1; Yafei Qi, MD2; Rui Bi, MD, PhD3; Ming Li, MD, PhD3; Jinhang Li, MD1; Ruby Chang, MD4 (email@example.com); Wenxin Zheng, MD.4 1Department of Pathology, The First Medical Center of Chinese PLA General Hospital, Beijing, China;2 Department of Pathology, Sheng Jing Hospital of China Medical University, Shenyang, China; 3Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China; 4Department of Pathology, UT Southwestern Medical Center, Dallas, Texas.
Context: Silva pattern–based system (PBS) for usual-type endocervical adenocarcinoma (uEAC) relies on pattern of invasion (POI) and lymphovascular invasion and offers valuable information as to risk of nodal metastasis and therapeutic options after surgery. Ideally, the most valuable time in applying PBS should be in the preresection specimen—the cervical biopsy, which can be used to guide surgeons in selecting optimal surgical procedures. We investigated the role of PBS in cervical biopsies by focusing on biopsy tumor size in relation to POI assessment in a multi-institutional study.
Design: A total of 397 paired biopsy resections of uEACs were included. POI as well as tumor size was evaluated. Standard statistical analyses were performed.
Results: POI was inevaluable in 253 (64%) and assessable in 144 (36%) biopsy specimens. Tumor size on biopsy ranged from 0.1 to 2 cm (average, 0.6 cm). Most biopsy tumor sizes were 0.8 cm or less (83%). POI assessment was directly related to the biopsy tumor size; identifiability of POI increases significantly with the biopsy tumor size (trend test, P < .001; Table). Among 144 cases having POI identified in both biopsies and resections, 76%, 70%, and 94% of biopsies showed congruent pattern A, B, and C invasion on resection, respectively.
Conclusions: Although Silva PBS offers valuable prognostic information with regard to risk of nodal metastasis, its applicableness for triaging patients into low nodal metastasis group, before surgical resection and on cervical biopsies, is limited. This is likely secondary to small sample size limiting accurate POI assessment.
Ectopic Pregnancy Occurring in a Cesarean Section Scar
(Poster No. 4)
Saman S. Karimi, MD, MS (firstname.lastname@example.org); Grace Guzman, MD. Department of Pathology, University of Illinois at Chicago.
In the United States, ectopic pregnancy (EP) accounts for 2% of all pregnancies and 5%–6% of pregnancy-related mortality. EP can occur in the ampulla of the fallopian tube (most commonly), myometrium, cervix, ovaries, and abdomen, among others. We present a case of a 32-year-old woman (gravida 7, para 2, 1-3-3) at 7 weeks and 3 days' gestational age with history of 3 cesarean-section deliveries. Ultrasound imaging demonstrated an anteverted uterus with a gestational sac in the anterior portion of the uterine isthmus and a thin layer of myometrium between the gestational sac and the urinary bladder. After an unsuccessful attempt of methotrexate injection of the gestational sac to induce abortion, the patient elected to have a gravid hysterectomy, and the specimen was sent to pathology for histopathologic evaluation. Gross examination revealed a 131.0-g uterus with multiple adhesions along the scar tissue on the anterior serosa of the uterus involving the isthmus and lower third of the serosal surface of the fundus. Bivalved uterus revealed an endometrial cavity with gravid endometrium. Microscopy demonstrated immature chorionic villi consistent with products of conception and gestational trophoblasts and implantation site within a thin 2-mm layer of the anterior endomyometrium corresponding to primary cesarean section scar (PCSS) with serosal fibrinohemorrhagic adhesions (Figure 2.4, A through C). EP occurring in a PCSS is a rare condition but has been an increasing complication of the rising rate of CS delivery. Heightened awareness of EP occurring in a PCSS is an important clinical consideration in pregnant females with previous cesarean-section delivery that could potentially prevent life-threatening sequelae.
A Subset of Vulvovaginal Fibroepithelial Polyps With Stromal Atypia Shows Deficiency of Retinoblastoma by Immunohistochemistry
(Poster No. 5)
Salam Ashour, MBBS (email@example.com); Daniel Roberts, MD; Jesse McKenney, MD; Amy Joehlin-Price, MD. Department of Pathology, Cleveland Clinic Foundation, Cleveland, Ohio.
Context: Vulvovaginal fibroepithelial polyps (FEPs) occasionally demonstrate stromal atypia resembling that seen in pleomorphic lipomas (PLs) and cellular angiofibromas (CAFs) with atypia. PLs and CAFs are often diagnosed by retinoblastoma (Rb) immunohistochemistry, reported as fairly sensitive and specific. Because of the morphologic overlap, we investigated whether FEPs with stromal atypia could be Rb-deficient.
Design: Departmental FEPs were reviewed for stromal atypia. Monoclonal anti-Rb immunohistochemistry (IHC) (clone G3-245, BD Biosciences) was performed. Nuclear Rb expression was scored by 3 pathologists according to a prior publication. Cases were considered deficient if 2 of 3 pathologists scored the FEP as deficient. For the remaining cases, median or consensus scores were recorded.
Results: Twenty-eight patients with a median age of 51 years (range, 25–72) had FEPs with stromal atypia in the vagina (n = 13, 46%), vulva (n = 12, 43%), perineum (n = 2, 7%), and cervix (n = 1, 4%). Rb IHC identified 5 cases (18%) with consensus Rb deficiency. The remaining 23 cases showed consensus or median scores of 1 + (n = 9, 32%), 2+ (n = 3, 11%), 3 + (n = 5, 18%), or 4+ (n = 6, 21%) (Table).
Conclusions: FEPs with stromal atypia may show Rb deficiency, suggesting that Rb loss needs to be interpreted in the context of clinicopathologic findings and is not entirely specific to the PL/CAF family of tumors.
Endocrine Cell Micronests in an Ovarian Mucinous Borderline Tumor: A Potential Diagnostic Pitfall for Microinvasion
(Poster No. 6)
Katrina Collins, MD (firstname.lastname@example.org); Sheila Segura, MD; Michael Hwang, MD. Department of Pathology, Indiana University, Indianapolis.
The occurrence of endocrine cell micronests in ovarian tumors is rare. To our knowledge, there are only 3 prior cases reported to date, 2 occurring in an ovarian mucinous cystadenoma and 1 in an ovarian mucinous borderline tumor. This is a case of a 27-year-old woman who presented with a 1-month history of abdominal pain and fullness. Imaging studies revealed a large multiloculated cystic and solid mass measuring 23.9 cm, occupying most of the pelvis and abdomen, concerning for a primary ovarian malignancy. The patient underwent a right salpingo-oophorectomy with appendectomy. Histologic sections from the ovary showed a multiloculated, cystic, and focally solid mass lined by gastrointestinal-type mucinous epithelium with variable degrees of proliferation (Figure 2.6, A), accounting for greater than 10% of the epithelial volume. In addition to the mucinous epithelial component, there were several foci of bland, monotonous epithelioid cells arranged in solid nests with focal rosette formation within the fibrous septa and mucinous epithelium (Figure 2.6, B). Immunohistochemical studies show that these cells are positive for cytokeratin (Figure 2.6, C), EMA, synaptophysin (Figure 2.6, D), while negative for inhibin. The Ki-67 proliferation index is low (<1%). The presence of endocrine cell nests associated with an ovarian mucinous neoplasm is a rare phenomenon. Whether this represents preservation of endocrine cells in the context of epithelial degeneration or a true neoplasm is unclear. Progression related to this neuroendocrine cell proliferation is unlikely and the recognition of this phenomenon holds more diagnostic value than prognostic significance, as it could be confused with microinvasion.
Histologically Pleomorphic Variant of High Grade Endometrial Stromal Sarcoma With Novel YWHAE Gene Amplification May Portend Poor Prognosis
(Poster No. 7)
Asad Ullah, MD (email@example.com); Diana Kozman, MBBCH; Samantha Mattox, DO; Pramila Moideen, MD; Tiffany Javadi, MD; Saleh G. Heneidi, MD; Natasha M. Savage, MD; Joseph White, DO. Department of Pathology, Medical College of Georgia – Augusta University, Augusta.
High-grade endometrial stroma sarcomas (HG-ESS) can be subclassified on the basis of YWHAE or BCOR molecular findings, each with characteristic histologic features. In general, fusion-associated malignancies have a more uniform and less pleomorphic appearance. We report a case of HG-ESS without characteristic YWHAE or BCOR fusions, but instead with a novel YWHAE gene amplification. We conducted a thorough literature review looking for YWHAE amplifications or pleomorphic variants of HG-ESS. Additionally, The Cancer Gene Atlas (TCGA) and cBioPortal data were explored for YWHAE gene–associated uterine tumors in 259 patients. The HG-ESS with YWHAE gene–amplified tumor at our institution showed tonguelike destructive myometrial invasion with extreme nuclear pleomorphism and innumerable atypical mitoses. One of 259 cases from TCGA data was found to also have a YWHAE gene amplification, showing similar morphology, with extreme pleomorphism and was signed out as carcinosarcoma with heterologous elements. Review of the literature found a single case with a pleomorphic HG-ESS with negative fluorescence in situ hybridization but positive RT-PCR results, potentially making a third case of HG-ESS with YWHAE amplification. Additionally, traditional YWHAE fusion cases were also classified as lower-stage cancers, while the 3 YWHAE-amplified cases were classified as high-stage disease, all dying within 6 months. We describe a potential new subclass of HG-ESS, a pleomorphic variant with YWHAE gene amplification. YWHAE-amplified ESS appears to behave aggressively, most likely indicating a poorer prognosis. Given these findings, YWHAE gene–amplified tumor with pleomorphic morphology needs further exploration.
Epithelioid Trophoblastic Tumor: An Exceedingly Rare Entity and Diagnostic Challenge
(Poster No. 8)
Fahd Hussain, MD (firstname.lastname@example.org); Ayush C. Srivastava, MD; William P. Daley, MD; Veena Shenoy, MD. Department of Pathology, University of Mississippi Medical Center, Jackson.
Epithelioid trophoblastic tumor (ETT) is a rare pathologic entity with very few cases reported in the English literature. We present a case of a 47-year-old woman diagnosed with ETT who presented with dyspnea and chest pain. On imaging, multiple lesions in the lungs, liver, and a large necrotic pelvic mass were identified. The patient underwent endometrium, lung, and liver biopsies followed by hysterectomy. The hysterectomy specimen revealed an ill-defined, fungating, necrotic hemorrhagic mass in the uterus (Figure 2.8, A). Microscopic examination revealed nests of uniform chorionic-type intermediate trophoblasts often surrounding a small blood vessel. Tumor cells showed round nuclei and focal cytoplasmic clearing in a background of extensive necrosis and eosinophilic hyaline material (Figure 2.8, B). Lung and liver biopsies showed histologic findings consistent with metastasis from endometrial primary. The tumor cells were positive for broad spectrum cytokeratin (Figure 2.8, C), inhibin (Figure 2.8, D), p63, CD10, and PLAP with a Ki-67 proliferative index of 30%–40%. ETT is a rare gestational trophoblastic tumor arising from chorionic-type intermediate trophoblasts. Patients usually are of reproductive age and present with vaginal bleeding. The most common primary site is the uterus, followed by the cervix. Poor prognostic factors include tumor extension beyond the uterus, age >40 years, interval from prior pregnancy of >2 years, and mitotic counts of >5/10 high-power fields. The differential diagnosis includes choriocarcinoma, placental site trophoblastic tumor, placental site nodule, and cervical squamous cell carcinoma. The patient received adjuvant chemotherapy; however, her disease progressed, and she died 24 months after her diagnosis.
Carcinosarcoma Arising in the Uterine Cervix
(Poster No. 9)
Jordan Steinberg, MD1 (email@example.com); Sarah Werner, MD2; Hossein Hosseini, MD1; Doaa Morrar, MD1; Ryan DesJean, MD.1 Departments of 1Pathology and Laboratory Medicine and 2Obstetrics and Gynecology, Lenox Hill Hospital, New York, New York.
Carcinosarcoma, or malignant mixed Müllerian tumor (MMMT), is an uncommon diagnosis comprising 3%–4% of uterine malignancies. They contain both epithelial and stromal components. Typically, carcinosarcoma of the cervix results from local extension of a uterine primary rather than primary cervical tumor. There are fewer than 50 reported cases of cervical primaries. In one series of primary cervical tumors, carcinosarcomas represented 5/1583 tumors or 0.003%. When the tumor is confined to the cervix, establishing the site of origin is academic. However, when the uterus is involved, immunohistochemistry should be used. Estrogen receptors and progesterone receptors stain strongly with endometrial primaries and are weakly positive in those from the cervix. Staining with monoclonal CEA favors a cervical origin. p16 is strong and diffuse with cervical tumors but patchy and weak in endometrial ones. We present a case of a 65-year-old woman who underwent a hysterectomy for a cervical mass. It measured 1.5 × 1.3 × 0.6 cm and was confined to the cervix. Histologically the epithelial component showed complex, disordered glands with cribriforming (Figure 2.9, A). The cells were pleomorphic, with hyperchromatic vesiculated nuclei, chromatin margination, and prominent nucleoli (Figure 2.9, B). The stromal component showed dark, spindled cells with areas of myxoid change. The epithelial component stained with pancytokeratin and vimentin (Figure 2.9, C). ER and PR were weakly positive, and monoclonal CEA was negative (Figure 2.9, D). These findings are consistent with a cervical primary. Our case represents 1 of only 50 cases of this entity. We submit this case study to expand on the limited data available for this entity.
Papillary Thyroid Carcinoma Arising in Familial Struma Ovarii
(Poster No. 10)
Dhuha Al-Sajee, MD, PhD1 (firstname.lastname@example.org); Ipshita Kak, FRCPC1; JEM Young, FRCPC.2 Departments of 1Pathology and Molecular Medicine and 2Head and Neck Service, St Joseph's Health Care, McMaster University, Hamilton, Ontario, Canada.
The occurrence of familial ovarian teratomas in twins, triplets, and successive generations in female patients raises a possibility of genetic correlation. When a mature teratoma is composed entirely or more than 50% of thyroid tissue, it is classified as struma ovarii. None of the reported familial ovarian teratomas to date showed a struma ovarii component. We present a case of an asymptomatic 68-year-old woman who was followed up with imaging for renal stones. CT showed an enlarged and complex left ovarian lesion. Pathologic examination revealed a mature cystic teratoma with a major component of thyroid tissue with a 0.4-cm follicular variant of papillary thyroid carcinoma. No further treatment was initiated. During follow-up, our patient volunteered that her sister, at 65 years old, also had thyroid tissue within an ovarian tumor. Review of the sister's specimen revealed benign thyroid tissue in a left ovarian teratoma (struma ovarii). We are unaware of any known genetic links for struma ovarii and our patient had no offspring. Similar to many reports of teratoma and familial teratomas, no genetic studies offered for our cases. Although the follow-up period of 6 months in both cases was insignificant, familial teratomas occurring in children and younger women have a higher chance of recurrence, bilaterality, and secondary malignancies. We therefore recommended ovarian screening of the sister's only daughter who is now 50 years old. We also recommend additional gross sampling of mature cystic teratoma, especially in familial cases, to exclude associated malignancies.
Clear Cell Carcinoma and Borderline Mucinous Tumor of the Ovary: A Case Report of a Rare Mixed Epithelial Ovarian Tumor and Review of the Literature
(Poster No. 11)
Roselyne Choiniere, MD (email@example.com); Philippe Echelard, MD; Perrine Granger, MD. Department of Pathology, University of Sherbrooke, Québec, Canada.
Mixed epithelial ovarian tumors (MEOTs) are characterized by the coexistence of at least 2 distinct histologic subtypes in a single lesion. We present a case of MEOT and a review of the literature of all published cases of MEOT with mucinous and clear cell components. A 58-year-old, gravida 0, menopausal South American woman presented with lower abdominal pain and an ovarian mass with thick septations. Gross section showed a 1.5-cm yellow nodule protruding from one of the septations. It consisted of solid nests of clear cells with significant nuclear atypia and necrosis and no evident mucin production. This nodule was diagnosed as clear cell carcinoma (CCC) arising next to a borderline mucinous tumor with intestinal-type mucinous lining. The distinct immunohistochemistry profiles of the 2 components are presented in the Table. The patient was staged as FIGO stage 1A after negative surgical debulking. Platinum-based chemotherapy was administered, and she remained free of disease 10 months after surgery. MEOTs of CCC with mucinous tumor (benign, borderline, or malignant) are rare, with only 8 cases previously reported in the literature (Table). In our case, as in 2 others, the presence of ovarian endometriosis was noted, suggesting that the CCC most likely originated from an endometriotic implant. Our case also illustrates that it is necessary to maintain a high degree of suspicion when grossing any cystic ovarian mass. Generous sampling may be necessary to confirm the presence of a higher-grade component, which can directly impact surgical conduct and treatment.
Primary Adenoid Cystic Carcinoma of Bartholin Gland: A Rare Malignant Tumor
(Poster No. 12)
Samreen Fathima, MBBS (firstname.lastname@example.org); Metin Punar, MD. Department of Pathology, Baylor University Medical Center, Dallas, Texas.
Primary carcinoma of Bartholin gland is a rare malignant tumor arising from the posterior half of the vulvar region. Adenoid cystic carcinoma (ACC) of Bartholin gland is a distinctive entity of vulvar malignancy, accounting for 10%–15% of Bartholin gland carcinomas. We report a case of a 46-year-old woman, with pain in the right vulvar region. Ultrasound imaging revealed a 1.4 × 0.6 × 0.6-cm, fluid-filled cyst. The patient was taken for marsupialization of the Bartholin gland cyst. Intraoperatively, a 3.0-cm firm, irregular mass in the area of right Bartholin gland was discovered and portions of it were biopsied. Microscopic examination showed multiple fragments of tissue with an epithelial proliferation with lobular architecture and infiltrative with a cribriform pattern with lymphocytic host response (Figure 2.12, A). Immunostaining showed cytokeratin 7 positivity in lobular areas, while its expression was lost in some of the nested areas (Figure 2.12, D). The smooth muscle actin (Figure 2.12, C), P63, and S100 were positive in the cribriform areas. Polyclonal CEA was positive in the tumor. Ki-67 showed varying staining pattern (1%–2%) in well-preserved lobular areas and up to 20% focally in solid/cribriform areas with lymphocytic response. CD117 was positive (Figure 2.12, B). A diagnosis of adenoid cystic carcinoma was made, and the tumor was excised. ACC of Bartholin gland is a rare, vulvar malignancy with an aggressive and unpredictable biologic behavior. Owing to the small number of reported cases, there is no consensus regarding treatment.
Correlation Between Silva Pattern of Stromal Invasion and Endocervical Adenocarcinoma With Extra-Nodal Metastasis and Recurrence
(Poster No. 13)
Hanna Siatecka, MD1 (email@example.com); Anthony B. Costales, MD2; Ramya P. Masand, MD.1 Departments of 1Pathology & Immunology and 2Division of Gynecologic Oncology, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.
Context: Silva invasion pattern–based classification system of stromal invasion stratifies endocervical adenocarcinomas into 3 categories: pattern A (nondestructive invasion) not associated with lymph node metastasis (LNM), pattern B (limited destructive invasion) usually without LNM, and pattern C (diffuse destructive invasion) associated with LNM in 25% of cases. This system was developed to avoid unnecessary lymphadenectomy in low-risk patients, regardless of stage. In this study, we evaluated Silva pattern of invasion in endocervical adenocarcinomas with extranodal/distant metastasis.
Design: Patients with endocervical adenocarcinoma from 2010–2018 were retrospectively identified. Patients with extranodal/distant metastasis were included in the study. Data were collected from the electronic medical records and slides were reviewed.
Results: Forty-seven patients with a mean age of 49 years (range, 34–67 years) with endocervical adenocarcinoma were identified. Of the 15 patients with extranodal metastasis/recurrences, 14 were HPV related and 1 was non–HPV related. Silva system included pattern A (1), pattern B (4), and pattern C (10). Lymphovascular invasions were noted in 1 pattern B and 3 pattern C cases. Nine patients presented with metastatic disease. Only 1/15 patients had pelvic LNM. Six patients had recurrences post treatment (Table).
Conclusions: Silva pattern C was associated with higher stage at presentation and increased recurrences; however, pattern A and pattern B tumors were not exempt from extranodal metastasis and recurrences. Silva system, although reliable in predicting risk of nodal disease, is not a good predictor of extranodal disease and development of recurrences. Interestingly, only 1 patient with distant metastasis had nodal metastasis, suggesting nonlymphatic modes of spread (vascular, trans-tubal) are involved in metastases in these cases.
Anastomosing Hemangioma of the Ovary With Stromal Luteinization and Hilus Cell Hyperplasia: A Clinicopathologic Study of 12 Cases
(Poster No. 14)
Austin McHenry, MD (firstname.lastname@example.org); Natalia Buza, MD. Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
Context: Anastomosing hemangioma (AH) is a recently described vascular neoplasm consisting of thin-walled, irregularly anastomosing vessels lined by endothelial cells with hobnail morphology and minimal atypia cuffed by pericytic supportive cells. While initially identified in the male genitourinary tract, AH has since been reported in multiple sites. Very few cases have been documented in the female genital tract. Of those reported, nearly all occur within the ovary, with the largest series to date including 6 patients.
Design: In this study, we identified 12 cases of AH of the ovary from our institutional archives between 2005 and 2020 (Table). All cases were unilateral, occurred at the ovarian hilum, and contained a vaguely lobulated architecture with sinusoidal-like vessels lined by hobnail epithelial cells with minimal to no cytologic atypia.
Results: A rim of luteinized cells with abundant, eosinophilic cytoplasm and round, centrally placed nuclei surrounding the hemangioma was present in 9/12 cases, of which the volume of luteinized cells relative to the hemangioma mass ranged from 2%–30%. Hilus cell hyperplasia with definitive Reinke crystals was observed in 3 of these 9 cases, and all tumors with luteinized cells contained numerous eosinophilic, globular intracytoplasmic inclusions. Interestingly, the 3 cases without luteinized cells were exclusively intravascular lesions.
Conclusions: Awareness of this rare benign entity in the ovary is essential, as its association with stromal luteinization or hilus cell hyperplasia (often exuberant) may be misinterpreted as a steroid cell tumor, Leydig-cell tumor, or as a mixed stromal-vascular tumor.
Chemoradiation-Induced Osseous Metaplasia in Endometrioid Adenocarcinoma
(Poster No. 15)
Rosemary Mattaino, DO, MS (email@example.com); Agnes Balla, MD, MHS; Martin C. Chang, MD, PhD. Department of Pathology and Laboratory Medicine, The University of Vermont Medical Center, Burlington.
Osseous metaplasia within the endometrium is rare, with most reported cases citing incidental intrauterine bone seen in the setting of infertility or postpartum endometritis. Proposed mechanisms include heterotopia, dystrophic/metastatic calcifications, ossification of postabortive endometritis, metaplasia in heal