Abstract and case study poster sessions will be conducted during the 2017 College of American Pathologists Annual Meeting (CAP17), which is scheduled for October 8 to 11, 2017. The meeting will take place at the Gaylord National Hotel in National Harbor, Maryland. The poster sessions will occur in the CAP17 Exhibit Hall. Specific dates and times for each poster sessions are listed below; “poster focus” times are dedicated poster-viewing periods. Also shown before each poster session are the subject areas that will be presented during each session.
Hepatic Hemophagocytic Lymphohistiocytosis Presenting With a Cholestatic Injury Pattern: A Rare Presentation of a Potentially Fatal Disease (Poster No. 1)
Hemophagocytic lymphohistiocytosis (HLH) is an uncommon disease that often presents with nonspecific findings. A high index of suspicion is necessary to make a prompt diagnosis and prevent fatal disease. A 45-year-old man presented with fever, hypotension, abdominal pain, nausea, and vomiting. He also reported a 4- to 6-week history of weakness, fatigue, and weight loss. Because of a history of Crohn disease, systemic lupus erythematous, and rheumatoid arthritis, the patient was on immune suppressants, including infliximab. Laboratory tests revealed a cholestatic pattern of injury with elevated alkaline phosphatase and total bilirubin, pancytopenia, and increased ferritin, and imaging showed hepatosplenomegaly. A liver wedge biopsy revealed areas of sinusoidal dilatation with enlarged, activated macrophages containing erythrocytes and intracytoplasmic iron (Figure 1, A and B), consistent with hemophagocytosis due to HLH. The portal tracts showed mixed lymphoplasmacytic inflammation, a prominent bile ductular reaction, periportal fibrosis, and scattered large cells with occasional binucleation and prominent nucleoli (Figure 1, D). These cells stained positive for Epstein-Barr virus (EBER-ish; Figure 1, C), PAX5, CD15, and CD30, and hepatic involvement by classic Hodgkin lymphoma was diagnosed and determined to be the cause of the HLH. A bone marrow biopsy revealed similar histopathologic findings. Aggressive treatment failed and the patient succumbed to multi-organ failure. HLH is a rare, potentially fatal disease with nonspecific signs and symptoms and should be considered in any patient presenting with fever and pancytopenia.
TTF-1 Expression in Metastatic Colorectal Carcinoma: Report of a Case and Review of the Literature (Poster No. 2)
Thyroid transcription factor 1 (TTF-1) is a homeodomain transcription factor specifically expressed in the normal thyroid and lung. Its expression in adenocarcinoma of the lung is considered a highly sensitive and specific marker for lung primary. Therefore, in the context of adenocarcinoma, immunohistochemical stain for TTF-1 has been clinically used as a reliable tool in distinguishing lung primary from other origins. A few case reports, however, have confirmed occasional TTF-1 expression in adenocarcinomas from other sites. A case of metastatic colonic adenocarcinoma in a liver biopsy specimen that showed positive nuclear staining for TTF-1 is reported here. The patient was a 73-year-old man with a large colon mass and multiple liver lesions and pulmonary nodules. Biopsy of the colon mass showed an adenoma with high-grade dysplasia. A biopsy of a liver lesion revealed metastatic adenocarcinoma. Immunohistochemical stains demonstrated that the tumor cells were diffusely positive for CK20, CDX2, and TTF-1, and negative for CK7. The histologic features, positivity for CK20 and CDX2, and negativity for CK7 were consistent with colonic primary. Seven other cases/studies of TTF-1 expression in colon cancer were compiled from the literature and integrated with this report. Determination of primary origin in the setting of adenocarcinoma is critical for further molecular analysis and corresponding targeted therapies. Based on our finding and previous reports, we think TTF-1 expression in adenocarcinoma should be interpreted cautiously and correlated with additional immunohistochemical profile, histologic features, clinical history, and possible primary tumor.
A Case of Gastrointestinal Syphilis With Pauci-Inflammatory Response (Poster No. 3)
Syphilis cases are rising in the United States. Identifying syphilis in gastrointestinal biopsies involves depending on clinical history or nonspecific histologic features such as lymphoplasmacytic and histiocytic expansion of the lamina propria, mild to moderate active inflammation, or ulceration. These can serve as a clue to conduct further workup with stains such as a Warthin-Starry or immunohistochemistry (IHC). We present a case of a homosexual male with an ongoing diarrheal illness, vomiting, and fatigue. A workup revealed a positive RPR and secondary syphilis with neurosyphilis involvement via cerebrospinal fluid VDRL testing. On endoscopy, stomach inflammation and duodenal ulcers were noted and biopsied. The duodenal biopsy showed focal gastric-type mucosa admixed with intestinal mucosa and Brunner glands. There was a minimal inflammatory response (Figure 2, A and B). The stomach showed a mild, focally active chronic gastritis. A Treponema IHC (Biocare Medical, California) was performed on each and showed an extremely high Treponema pallidum burden, especially in the areas of gastric-type mucosa (Figure 2, C and D). The paucity of immune response in the case was originally attributed to HIV because of a positive screening test, but the patient's confirmatory testing was negative. This case is noteworthy for a lack of an immune response to secondary-stage syphilis in the duodenum despite overwhelming infection, and it highlights the importance of having a low threshold for IHC use in highly suspicious cases.
Low-Grade Mucinous Neoplasm Originated From Retroperitoneal Colonic Duplication Cyst (Poster No. 4)
Duplications of the digestive tract are uncommon congenital lesions that can undergo malignant change as an extremely rare complication. Only 6 cases of mucinous neoplasms arising from enteric duplication cysts had been reported. We describe the first case of a low-grade mucinous neoplasm that originated in a retroperitoneal colonic duplication cyst. A 26-year-old woman with history of polycystic ovarian syndrome and occasional abdominal cramps was found to have a retroperitoneal mass during follow-up transvaginal ultrasound. Computed tomography and magnetic resonance imaging showed a cystic mass adjacent to the sacrum, unrelated to adnexa. A retroperitoneal partially cystic and solid tumor without communication to the gastrointestinal tract was found and completely resected during laparoscopic surgery. Sections revealed a unilocular cyst filled with mucin and lined by colonic-type epithelium with muscularis propria and submucosal glands (Figure 3, A). The colonic mucosa showed only a focal area of bizarre architecture and hyperplastic changes reminiscent of a serrated polyp (Figure 3, B and C). The wall was hyalinized with intramural dystrophic calcification, ossification, and mucin extravasation (Figure 3, D). These findings were consistent with a low-grade mucinous neoplasm originating from a retroperitoneal colonic duplication cyst. Complete surgical resection and histologic examination of duplication cysts is recommended in order to exclude the presence of malignant component and avoid other complications.
Modified Sendai-Based Algorithm Is Extremely Sensitive in Identifying Neoplastic Pancreatic Cystic Lesions (Poster No. 5)
Context: In recent years, many attempts have been made for earlier and more accurate diagnosis of pancreatic cystic lesions (PCLs). These lesions are increasingly being recognized with the advent of ultrasensitive imaging modalities. Although only about 10% of PCLs are neoplastic, their proper diagnosis saves many lives by preventing progression to the extremely aggressive pancreatic adenocarcinoma.
Design: Based on the latest publication of Sendai guidelines, we created an algorithm with the aim to identify the pancreatic mucinous cystic neoplasm (PCN) by taking into account characteristics such as cytology diagnosis, carcinoembryonic antigen (CEA) levels, cyst size, mural nodule, cyst fluid viscosity, and clinical impression (Figure 4). The proposed algorithm was applied to 46 pancreatic cystic lesions with available surgical resection specimens and its accuracy is compared with final surgical diagnoses.
Results: From 46 cases with surgical resections (19 intraductal papillary mucinous neoplasms [IPMNs], 9 mucinous cystic neoplasms [MCNs], 8 pancreatic adenocarcinomas [PACs], 3 pancreatic neuroendocrine tumors [PNETs], 5 pseudocysts, 2 serous cystadenomas [SCAs]), the algorithm correctly classified 44 cases as neoplastic or nonneoplastic cystic lesions, achieving 95.6% concordance with final surgical diagnoses. Of 2 misclassified cases, 1 was a pseudocyst and 1 was a SCA; they were classified as neoplastic and nonneoplastic lesions, respectively, by the algorithm.
Conclusions: The proposed Sendai guideline–based algorithm was able to identify the pancreatic cystic neoplasms with a sensitivity of 97.4%. The specificity of the algorithm was 75% because of misclassification of a pseudocyst by the algorithm as neoplastic, which was mainly due to large size and grave clinical impression.
Primary Hepatic Epithelioid Angiomyolipoma: Novel Hormone Receptor Expression in a Rare Entity (Poster No. 6)
Hepatic epithelioid angiomyolipomas are rare neoplasms that belong to the perivascular epithelioid cell family of tumors and mimic hepatocellular carcinomas on imaging and histomorphology. A literature search revealed fewer than 90 reported cases from the years 2000 to 2016. We report a case of a 37-year-old woman with an isolated 5.6-cm left hepatic lesion incidentally identified by computed tomography imaging. MRI with contrast suggested hepatocellular carcinoma versus hepatic adenoma. Percutaneous biopsy of the lesion revealed neoplastic cells with round to oval vesicular nuclei, voluminous granular eosinophilic cytoplasm with subtle vacuolation, and indistinct cell borders. Vessels and vascular-type channels were identified, as well as rare adipocytes. The neoplastic cells were positive for HMB45/Melan-A (Figure 5, A), patchy/faint for smooth muscle antigen, and negative for S100, arginase, and pancytokeratins. A diagnosis of epithelioid angiomyolipoma was rendered. The patient did not have a history of tuberous sclerosis and renal lesions were not appreciated on imaging. The lesion was subsequently resected, revealing a well-circumscribed yellow-brown mass with histomorphology consistent with the biopsy specimen. Epithelioid cells comprised an estimated 60% of the lesion (Figure 5, B and C). Although there was infiltration into adjacent hepatic parenchyma, there was no overt evidence of high-grade morphology. Interestingly, the tumor cells demonstrated weak estrogen receptor and moderate progesterone receptor (Figure 5, D) antibody positivity. Hormone receptor positivity has been well documented in renal and gynecologic perivascular epithelioid tumors, but not in the liver. In conclusion, we describe a hepatic epithelioid angiomyolipoma with novel estrogen and progesterone receptor antibody positivity.
Gastrointestinal Stromal Tumor: First Presentation of a Patient With NF1 Mutation (Poster No. 7)
Gastrointestinal stromal tumor (GIST) is a mesenchymal neoplasm that most commonly occurs in the stomach and is derived from interstitial cells of Cajal. Approximately 10% of these tumors lack KIT and PDGFRA gene mutations. Patients with neurofibromatosis type 1 (NF1) have an increased risk for developing GIST, which usually occurs in the small intestine. The NF1 gene mutation results in the lack of neurofibromin 1, which leads to activation of RAS pathway and subsequent tumor formation. We present a 57-year-old man with no significant past medical history who presented with upper gastrointestinal bleed. He underwent endoscopic examination, which showed a duodenal ulcer and a duodenal subepithelial lesion. Fine-needle aspiration of the mass demonstrated neoplastic spindle cells that were strongly positive for DOG-1 and weakly positive for CD117, consistent with GIST. The patient underwent surgical excision of the 15 × 11-mm tumor and pathologic evaluation confirmed the diagnosis of GIST. Next-generation sequencing assays performed on the lesional tissue revealed an NF1 mutation (M991del variant). Subsequent single site mutation analysis on peripheral blood confirmed the presence of a germline NF1 mutation. Additional physical examination revealed 3 café-au-lait macules on the trunk and axillary freckling. No Lisch nodules or lesions suspicious for cutaneous neurofibromas were identified. This case illustrates an unusual initial presentation of NF1 mutation and highlights the need for NF1 mutation analysis in GISTs that lack the classic KIT mutation.
Gastric Metastatic Merkel Cell Carcinoma (Poster No. 8)
Merkel cell carcinoma (MCC) is a relatively rare but aggressive primary neuroendocrine carcinoma of the skin. MCC frequently occurs on sun-exposed areas in elderly white patients and has a propensity for local recurrence, regional lymph node invasion, and distant metastases. However, gastric metastasis of MCC has been reported in only a few cases. We report the case of a 75-year-old white man with a history of Merkel cell carcinoma 4 years prior who presented with a syncope, anemia, and melena, and underwent esophagogastroduodenoscopy. A single polypoid mass with ulcer was found in the lesser curvature of the stomach body (Figure 6, A). On microscopic examination, the neoplasm was composed with sheets of round to oval, small, blue cells with amphophilic sparse cytoplasm and vesicular nuclei, with a diffuse infiltrated pattern (Figure 6, B). Immunohistochemically, the neoplastic cells showed positive staining for cytokeratin (CK20), with a perinuclear dotlike pattern (Figure 6, C). In addition, they were also diffusely and strongly positive for synaptophysin (Figure 6, D), chromogranin, and CD56. The morphologic features and immunostaining profile were consistent with gastric metastasis of MCC. Although MCC metastasis to the stomach is very rare, it should be considered in the differential diagnosis of patients with medical histories of MCC who present with symptoms of recent weight loss and gastrointestinal bleeding.
A Rare Case of Mixed Adenoneuroendocrine Carcinoma (MANEC) Presenting as a Gastric Polyp in a Background of Adenoma, Intestinal Metaplasia, and Chronic Gastritis (Poster No. 9)
Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumor of the gastrointestinal tract that consists of 2 components: neuroendocrine carcinoma and adenocarcinoma. Either must form 30%–70% of the lesion. In 2016, there were fewer than 40 cases of MANEC reported in the stomach. The term MANEC was first used by the World Health Organization in 2010. Before that date these tumors were referred to as mixed or composite carcinomas. We report a case of gastric MANEC in a 70-year-old African American man with a history of heavy alcohol and tobacco abuse. The patient's medical history included dementia, chronic hepatitis C infection, and colonic adenoma removed 5 years previously. The patient presented with a 2-year history of intractable nausea and vomiting. An upper gastrointestinal endoscopy was performed and multiple biopsies from several sites were obtained demonstrating chronic gastritis and patchy intestinal metaplasia. At one of the biopsy sites designated “midstomach,” a single 15-mm pedunculated bleeding polyp was removed. Microscopic examination of this lesion revealed a combined poorly differentiated adenocarcinoma and high-grade large cell neuroendocrine carcinoma (MANEC), arising in a background of adenoma. An additional gastric adenoma with low-grade dysplasia was removed from the same area. Immunohistochemical studies using synaptophysin and Ki-67 confirmed the diagnosis of large cell neuroendocrine carcinoma in half the tumor with Ki-67 staining of 90% of the nuclei. Synaptophysin staining was negative in the poorly differentiated adenocarcinoma component and Ki-67 stained only 20% of nuclei.
Giant Duodenal Lipoma as a Rare Cause of Intussusception, Vomiting, Anorexia, and Unintentional Weight Loss Mimicking Malignancy (Poster No. 10)
Gastrointestinal lipomas are benign tumors, comprising only 5% to 6% of all gastrointestinal tumors. The majority (60%–75%) of gastrointestinal lipomas are in the colon, followed by the small intestine (20%–25%). Duodenal lipomas are usually asymptomatic but larger ones can, in rare cases, cause abdominal pain, intestinal obstruction, or hemorrhage. We report a 75-year-old man complaining of abdominal pain, nausea, vomiting, and anorexia with an unintentional weight loss of 20 pounds during 2 weeks. Abdominal MRI showed a large multilobulated fat-containing duodenal mass (11.9 × 5.6 × 5.6 cm), gastric distention, and gastric outlet obstruction. Endoscopy showed a large submucosal mass in the duodenal bulb and the second part of the duodenum. Multiple biopsies taken from the mass showed polypoid inflammatory-type duodenal mucosa with gastric surface foveolar metaplasia. No submucosal tissue or malignancy was identified in this biopsy. A partial duodenal resection was performed. A luminal bilobed mass lesion (6 × 3.5 × 2.5 cm and 7 × 6 × 2.1 cm, respectively) with continuation of an extraluminal fatty mass lesion (11.5 × 6 × 3.5 cm) was identified. Microscopically, the mass underneath the metaplastic gastric foveolar-type duodenal mucosa showed mature adipose tissue with areas of inflammatory reactive changes and focal fibrosis. A diagnosis of duodenal lipoma was made. Duodenal lipomas are rare nonepithelial benign tumors. Their accurate preoperative diagnosis is difficult and they can be mistaken for malignancy, especially when the lesion is large with clinical complications. A surgical approach remains the treatment of choice for large and complicated cases.
Retrospective Review of Colonic Hyperplastic Polyps Diagnosed at Danbury Hospital (Poster No. 11)
Context: Patients with sessile serrated adenomas require more extensive management than those with hyperplastic polyps. Some authors advocate for stricter criteria than the current criteria from the World Health Organization to diagnose hyperplastic polyps. The goal of this study is to apply stricter criteria to possibly identify sessile serrated adenomas in previously diagnosed cases of hyperplastic polyps at Danbury Hospital in 2015.
Design: The first 400 cases diagnosed with exclusively hyperplastic polyp(s) were selected and their surgical pathology reports and histologic slides were then retrieved and reviewed accordingly. To meet the diagnosis of sessile serrated adenoma, at least 1 of the 4 following criteria must be met: (1) any horizontal growth along the muscularis mucosa, (2) dilatation of the crypt base (basal third of the crypt) such that it is wider than the luminal opening, (3) serration extending into the crypt base, or (4) asymmetric proliferation.
Results: Sessile serrated adenoma(s) was identified in 9.8% (39 of 400) of cases previously diagnosed just as hyperplastic polyp(s). Seventy-four percent (29 of 39) met just 1 of the 4 criteria, and 25.6% (10 of 39) met 2 or more of the 4 criteria. Of those that met just 1 of the 4 criteria, 69.0% (20 of 29) met the “any horizontal growth along the muscularis mucosa” criterion, 27.6% (8 of 29) met the “serration extending into the crypt base” criterion, and 3.4% (1 of 29) met the “asymmetric proliferation” criterion.
Conclusions: Applying stricter criteria to hyperplastic polyp diagnosis would result in reclassification as sessile serrated adenomas in 9.8% of cases at our institution.
Malignant Gastrointestinal Neuroectodermal Tumor: Report of a Pediatric Case (Poster No. 12)
Malignant gastrointestinal neuroectodermal tumor (GNET), also known as clear cell sarcoma–like tumor of the gastrointestinal tract, is a rare neoplasm that arises in the tubular gut wall, predominantly in younger adults (average age 35 years), with predilection for the small bowel in children. It is characterized by the t(12;22) translocation, resulting in EWS-ATF1 or EWS-CREB1 gene fusion, similar to its soft tissue counterpart. However, unlike clear cell sarcoma of soft parts, which had been historically likened to melanoma because of its immunophenotype and morphology, malignant GNET lacks immuno-reactivity for Melan-A and HMB45, despite S-100 positivity. We present a case of this rare entity in one of the youngest reported patients. A 16-year-old adolescent boy with growth failure was found to have small bowel obstruction on imaging after presenting to the hospital with severe abdominal discomfort. Surgery revealed an obstructive mass, which was resected with wide margins. Grossly, the tumor was white and firm, arising in the bowel wall and focally ulcerating through the mucosa, with associated luminal narrowing. Histologic examination revealed an infiltrating mass composed of sheets of epithelioid cells with irregular nuclei, prominent nucleoli, and eosinophilic granular cytoplasm, with numerous interspersed osteoclast-like giant cells (Figure 7, A). The lymph nodes were negative for tumor. The tumor was positive for vimentin (Figure 7, B), Sox10, and S100 (Figure 7, C), and negative for HMB45, Melan-A, CD117, DOG1, CD163, CD45, synaptophysin, CD68, and CD1a. EWS gene rearrangement was detected by break-apart fluorescence in situ hybridization (Figure 7, D), confirming the diagnosis of malignant GNET.
A Case Report of Mantle Cell Lymphoma Causing Lymphomatoid Polyposis of the Gallbladder (Poster No. 13)
Mantle cell lymphoma is a B-cell non-Hodgkin lymphoma arising from naive pregerminal center B lymphocyte present in mantle zones of secondary follicles. Patients can present with lymphadenopathy, bone marrow involvement, splenomegaly, lymphomatoid polyposis of small bowel, and other extranodal involvement. We present a 61-year-old man who presented with abdominal pain and fever. He was diagnosed with ascending cholangitis and biliary sepsis. Computed tomography scan showed dilated gallbladder with thickening of the wall, dense opacity near the gallbladder neck, intrahepatic and extrahepatic dilation of biliary ducts, soft tissue thickening in the ampulla of Vater, focal thickening involving the lesser curvature of the stomach, extensive lymphadenopathy, and splenomegaly. He subsequently had laparoscopic cholecystectomy. Grossly, the gallbladder mucosa was diffusely nodular (Figure 8, A). Microscopic examination showed nodular lymphocytic proliferation infiltrating the gallbladder mucosa and wall. The infiltrates were composed of a monotonous population of small lymphocytes with clumped chromatin, irregular nuclear contours, and scant cytoplasm (Figure 8, B through D). Similar lymphoid cells were also noted in the lymph nodes. Immunohistochemistry showed the lymphoid cells to be positive for CD20, CD5 (partial), bcl1, bcl2, and SOX-1 but negative for CD3, CD10, bcl6, and LEF1. Fluorescence in situ hybridization study result was positive for t(11;14). Bone marrow biopsy showed involvement by the neoplastic process. A final diagnosis of mantle cell lymphoma was made. This case demonstrates that mantle cell lymphoma can involve the gallbladder and produce an appearance identical to lymphomatoid polyposis of the gastrointestinal tract.
Sarcomatoid Carcinoma in Small Intestine Showing Complex Karyotype and Abnormal Translocations and Deletions (Poster No. 14)
Sarcomatoid carcinoma (SCA) is a rare type of small bowel cancer with an aggressive biological behavior. The clinical presentation of SCA of the small intestine is nonspecific and includes abdominal pain, anemia, obstruction, and gastrointestinal bleeding. There are about 30 case reports to date in the literature, with a focus on the diagnostic morphologic features. However, the underlying molecular mechanisms for SCA remain unknown. For the first time, we report here a case of SCA of small intestine with complex karyotype and abnormal translocation and deletion using cytogenetic studies. Grossly, the tumor had an endophytic growth pattern with central ulceration. On microscopic examination, the tumor had a solid sheet growth pattern with a mixture of epithelioid cells and spindle cells (Figure 9, A and B). A focal anaplastic component, consisting of bizarre giant tumor cells, was present. Immunohistochemically, both epithelioid and spindle cells were diffusely and strongly positive for cytokeratin and vimentin (Figure 9, C and D). These tumor cells were negative for CD117, DOG-1, and CDX2, pan-melanoma markers. The cytogenetic data revealed the complex karyotype, a translocation of t(9;22)(q34;q11.2), and multiple deletions including del(17)(p11.2) and insertions. The t(9;22) and deletion of 17p have been seen in various tumor types and the complex karyotype is generally associated with an unfavorable clinical course. This study presents the first case study of SCA of the small intestine with cytogenetic analysis. More molecular characterization is needed to elucidate the pathogenesis and provide more prognosis-relevant information for this rare aggressive tumor.
Neonatal Giant Cell Hepatitis in 2 Infants With Septo-Optic Dysplasia (Poster No. 15)
Congenital hypopituitarism is an underrecognized cause of neonatal giant cell hepatitis (NGCH). Two patients who presented with cholestasis and hypoglycemia prompted a multidisciplinary team approach including pediatric gastroenterology, endocrinology, ophthalmology, neurology, radiology, and pathology. Clinical investigation found both patients to have septo-optic dysplasia consisting of optic nerve hypoplasia and midline structural abnormalities of the brain, including absence of septum pellucidum and ectopic posterior pituitary and hypoplastic pituitary stalk with clinical panhypopituitarism. The liver biopsies showed classic features of NGCH. Initiation of hormone replacement therapy resulted in resolution of the cholestasis and hypoglycemia in both infants. Hypopituitarism is an important and treatable cause of NGCH. Untreated hypopituitarism can result in acute life-threatening events. Recognition of the clinical presentation of hypopituitarism in a patient with NGCH by the pathologist can prompt a more rapid and focused team approach and prompt initiation of therapy.
Unexpected PDGFRA D842V Mutation in a Spindle Cell–Type Gastrointestinal Stromal Tumor: Cost-Benefit Implications of Mutational Analysis in a Developing Country (Poster No. 16)
Gastrointestinal stromal tumors (GISTs) have activating mutations in C-kit exons 9, 11, 13, 17 and PDGFRA exons 12, 14, and 18. Specific mutations are associated with specific histology and prognosis. PDGFRA mutation in exon 18, in particular, is associated with an epithelioid histology and resistance to treatment with Imatinib. We report a case of a 75-year-old man who presented with epigastric pain, early satiety, and vomiting. Abdominal computed tomography scan showed a 3 × 2.4 × 2-cm soft tissue mass with intraoperative gastroscopy. Pathologic diagnosis was GIST, spindle cell type, with a mitotic count of <1/50 high-power fields and focal necrosis. The tumor cells were CD117 positive. In spite of the spindle cell–type histology, next-generation sequencing with the TruSight Tumor panel showed a PDGFRA D842V mutation, which is resistant to imatinib. In the Philippines, CKIT and PDGFRA mutation testing of GISTs has not yet been implemented, despite its clinical relevance as a predictive and prognostic marker. Patients with GIST qualifying for treatment with tyrosine kinase inhibitors (TKIs) (imatinib, sunitinib) have been based solely on the demonstration of CD117 positivity. This case highlights the critical role of genetic testing of GIST to identify primary resistance mutations that could avoid unnecessary treatment. Because TKI drug reimbursement is not available in the Philippines, the relatively low cost for CKIT/PDGFRA mutation testing will introduce a huge potential financial savings when tailored use of TKI is implemented based on genotyping.
Tubulovillous Adenomas With Serrated Features Are Biologically Advanced Polyps Commonly Associated With Aberrant β-Catenin (Poster No. 17)
Context: Tubulovillous adenoma (TVA) and traditional serrated adenoma (TSA) represent precursor lesions for 2 discrete pathways of colorectal carcinogenesis. Occasionally, TVA shows focal features resembling TSA. The biological significance and molecular features of this histologic variant of TVA are unknown. The goal of this study was to evaluate a group of TVAs with serrated features (TVASFs), correlate with clinicopathologic variables, and evaluate for markers commonly mutated in colorectal neoplasia.
Design: A total of 225 consecutive TVAs were retrospectively reviewed for TSA-like features. A tissue microarray was constructed with 29 TVASFs, 14 pure TVAs, and 11 pure TSAs. Immunohistochemical stains for selected markers were performed and graded according to previously reported criteria. Clinicopathologic information was collected through chart review.
Results: Thirty-seven TVAs (16.4%) from 36 patients showed serrated features (mean age 70; M:F 1:1.1). Patients with TVASF were significantly older than patients with TVA (P = .007). Fifteen TVASFs had low-grade dysplasia, 7 had high-grade dysplasia, 4 had intramucosal adenocarcinoma, and 11 had invasive carcinoma. TVASFs were significantly more likely to have advanced neoplasia compared with TVAs (HGD or greater, 59.5% versus 16.5%, P < .001). TSA-like areas within TVASFs showed significantly higher rates of nuclear β-catenin compared with pure TSAs (38.9% versus 0%, P < .01). TVASFs also showed significantly higher rates of nuclear β-catenin compared with pure TVAs (49% versus 29%, P = .046). Within TVASF, TSA-like areas had significantly lower Ki-67 expression compared with conventional adenomatous areas (P < .01).
Conclusions: TVASFs are commonly associated with advanced neoplasia and frequently have abnormal β-catenin expression. TSA-like areas in TVASF may be a result of decreased cellular proliferation.
Association of Reactive Gastropathy With Autoimmune Gastritis and Gastric Atrophy (Poster No. 18)
Context: Autoimmune gastritis (AIG) is characterized by body-predominant gastritis and atrophy due to autoantibodies, mostly to parietal cells and/or intrinsic factor. Histology features include chronic gastritis and atrophy of oxyntic mucosa with metaplasia and endocrine cell hyperplasia. Antrum may show reactive gastropathy (RG). This study aimed to evaluate the pathology of AIG in detail.
Design: The pathology database was searched for possible AIG cases between 2015 and 2016. Findings of corpus-predominant Helicobacter-negative chronic gastritis with atrophy were considered suggestive of AIG. Those with positive autoantibodies against parietal cell and/or intrinsic factor were considered definite AIG. Those without serology results were considered possible AIG. Cases with Helicobacter infection, negative autoantibodies, or history of nonsteroidal anti-inflammatory drug use were excluded. The pathology of gastric biopsies was evaluated.
Results: A total of 38 patients (10 definite, 28 possible AIG) were identified. RG in the antrum was seen in 76.3% of all and 90% of definite AIG cases. Other associated findings in the antrum included G-cell hyperplasia and minimal chronic gastritis. Oxyntic mucosa pathology included atrophy (43.4% mild, 6.7% moderate, 26.3% severe), intestinal metaplasia (73.7%), pyloric gland metaplasia (26.3%), endocrine cell hyperplasia (50%), neuroendocrine tumor (26.3%), and gastric adenocarcinoma (10.5%). Statistical analysis showed association of RG with pyloric gland metaplasia and degree of gastritis in the oxyntic mucosa.
Conclusions: Patients with AIG and gastric atrophy frequently show RG in the antrum. The underlying mechanism is unclear; however, we speculate duodenal bile reflux as etiologic. Bile is considered toxic to gastric mucosa and possibly carcinogenic; the role of bile reflux in gastric mucosal injury under hypochlorhydria needs further study.
Hilar Cholangiocarcinoma With Signet Ring Cell Features (Poster No. 19)
Hilar cholangiocarcinoma is an uncommon disease with a poor prognosis, with most tumors being unresectable at presentation. Even rarer are those hilar cholangiocarcinomas with mucin accumulation, as most biliary tract cancers with mucin tend to be from the distal bile duct. In the English literature there is only one case report that describes a signet ring cell hilar cholangiocarcinoma. We report a case of hilar cholangiocarcinoma with a signet ring cell component, in addition to a moderately differentiated glandular component, in a patient with a history of recurrent cholangitis and secondary biliary cirrhosis due to a remote complicated cholecystectomy, first diagnosed on the explant liver when the patient received a liver transplant. The patient had a postoperative course complicated by hepatic artery and portal vein thrombosis, leading to diffuse liver necrosis and death. Autopsy histology showed poorly formed glands with signet ring cells infiltrating from the serosal surface of multiple digestive tract organs, with similar morphology to the native liver explant pathology. Cytokeratin staining was consistent with a cholangiocarcinoma of extrahepatic origin. We present this case to enhance knowledge of the clinical and histologic spectrum of this entity, and provide molecular genetic findings with the purpose of further elucidating its pathogenesis.
Very Well-Differentiated Gastric Adenocarcinoma of Intestinal Type: A Challenging Case to Diagnose on Biopsy (Poster No. 20)
We report the case of a 55-year-old obese woman with a history of persistent anemia. She underwent multiple endoscopies for workup of anemia, which showed a polypoid lesion, and biopsies from the lesion showed features suggestive of chronic gastritis with intestinal metaplasia and cytologically benign-appearing glands with glandular architectural distortion. An endoscopic ultrasound revealed an intramural mass underlying the polypoid lesion. No definitive evidence of malignancy was rendered on endoscopic ultrasound-guided fine-needle aspiration. Because of the intramural mass lesion, our patient subsequently underwent subtotal gastrectomy. On the resection specimen, the mucosa showed findings similar to those of biopsy, including chronic gastritis with intestinal metaplasia (Figure 10, A). The deeper basal glands were breaching the muscularis mucosa (Figure 10, B) and extending to the circumferential surface. Overall it was a highly infiltrative adenocarcinoma composed of dilated, branching glands (Figure 10, C) with large areas of intraluminal eosinophilic debris (Figure 10, D) and a very well-differentiated lining. Immunostains were performed to further characterize the lesion. The tumor cells were positive for pankeratin (AE1/AE3), CK7, CK20, CDX2, CD10, and monoclonal CEA. Overall, the findings were most consistent with the so-called very well-differentiated, intestinal-type form of gastric adenocarcinoma. Very well-differentiated gastric adenocarcinoma of intestinal type is a rare tumor entity characterized by highly differentiated glands with low-grade nuclear atypia. These features are potential pitfalls in diagnosing this entity on the biopsy specimens. Important diagnostic clues to this entity include the presence of intraglandular necrotic debris within the architecturally distorted glands.
Epstein-Barr Virus–Associated Acute Liver Failure in a 74-Year-Old Immunocompetent Man (Poster No. 21)
Acute liver failure is rare but can be fatal. We present a rare case of primary Epstein-Barr virus (EBV) infection–related acute liver failure in an immunocompetent adult. A 74-year-old previously healthy man presented with 10 days of fever. At admission, he had encephalopathy with INR of 1.6. AST, ALT, alkaline phosphatase, and total bilirubin were all elevated at 289 U/L, 291 U/L, 557 U/L, and 8.9 mg/dL. Results of serologies for viral and autoimmune hepatitis were negative. Liver needle biopsy showed moderately active hepatitis. The portal areas showed a moderate polymorphous lymphoid infiltrate with few admixed plasma cells and eosinophils. Some of the lymphoid cells were larger with irregular nuclear contours and clumped chromatin. The hepatic lobule showed focal sinusoidal lymphocytosis. EBV RNA in situ hybridization was positive within the intermediate to large CD20-positive B lymphocytes. CD2, CD3, CD5, and TCR β F1 stained admixed small T lymphocytes, which were a combination of mixed CD4- and CD8-positive cells. κ and λ immunostains showed polytypic plasma cells. Subsequent blood EBV polymerase chain reaction was positive with 31 900 copies/mL. However, the serum EBV EBNA Ab, EBV VCA IgG Ab, and EBV VCA IgM Ab were all negative, suggesting primary EBV infection rather than reactivation of past EBV infection. He was treated with high-dose steroids and a single dose of rituximab. The patient improved significantly and his liver enzymes normalized in 6 weeks. This case highlights the importance of early recognition and diagnosis of EBV-associated acute liver failure by detection of EBV from a liver biopsy, even in immunocompetent adults.
Patterns of PD-L1 Expression and CD8+ T-Cell Infiltration in the Progression of Pancreatic Ductal Neoplasms (Poster No. 22)
Context: Programmed cell death ligand-1 (PD-L1) is crucial for immune regulation and self-tolerance and has been associated with tumor immune evasion. Although PD-L1 expression has been reported in pancreatic ductal adenocarcinoma (PDAC), it remains unknown if PD-L1 is acquired during progression from precursor lesion to invasive or metastatic disease. Additionally, the relationship between tumor PDL1 and CD8+ T cells has not been established.
Design: Fifty-three cases from 36 patients were evaluated in a tissue microarray containing 6 LG–pancreatic intraepithelial neoplasia (Pan-IN), 6 HG-PanIN, and 14 PDAC cases with 10 nodal metastases, 7 distant metastases, and 8 nonneoplastic pancreas samples. Immunohistochemical studies for PD-L1 and CD8 were performed.
Results: PD-L1 expression was absent in benign samples, whereas both tumor epithelium and stroma PD-L1 expression tended to increase with neoplastic progression (see Table). Median intraepithelial CD8+ count was 2/high-power field (HPF) in benign ducts, peaked in LG-PanIN, and decreased with neoplastic progression. The median CD8+ count in benign stroma was 31/HPF, whereas PanIN showed a median of 47/HPF and metastatic lesions a median of 15/HPF. All 5 PDL1+ neoplasms showed above median stromal CD8+ counts whereas 3 of 3 PD-L1+ metastases showed below median stromal CD8+ counts. One matched case of HG PanIN and PDAC showed tumor PD-L1 expression in both lesions, whereas another matched case demonstrated a gain of PD-L1 in the invasive lesion. Six matched cases showed PD-L1 consistently across progressive samples.
Conclusions: Differential PD-L1 expression and CD8+ T-cell counts among precursor lesions, invasive disease, and metastatic disease suggests dynamic immune regulation across stages of tumor development.
Systemic Amyloidosis (AL) Identified by Upper Gastrointestinal Biopsy: Evidence for Expanding the Differential Diagnoses of Malabsorption (Poster No. 23)
Amyloidosis is a heterogeneous group of diseases that is characterized by the misfolding of extracellular precursor proteins causing the deposition of aggregates of insoluble fibrillary proteins. A major form of amyloidosis is AL, a plasma cell dyscrasia in which monoclonal Ig light chains are produced in the bone marrow, resulting in systemic disease. We herein report 2 cases of patients presenting with years of nonspecific gastrointestinal symptoms resulting in malabsorption that were ultimately proven to be systemic amyloidosis. Both cases included middle-aged adults with complaints of abdominal pain, unintentional weight loss, progressive weakness, and fatigue. The patients had extensive workups and interventions without symptomatic relief. They subsequently underwent upper gastrointestinal endoscopic biopsies, which showed lesions consistent with amyloid deposition with characteristic Congo red apple green birefringent. Amyloidosis was confirmed with liquid chromatography–tandem mass spectrometry revealing AL (λ)–type amyloid. Although this is a rare disease, with an incidence of 6–10 per 1 million and a median survival for untreated patients of 13 months, early recognition is crucial for the proper management of patients, underscoring the importance of including amyloidosis as a differential diagnosis of malabsorption.
Noninvasive Serum Biomarkers to Predict Significant Fibrosis on Liver Biopsy in Patients With Morbid Obesity (Poster No. 24)
Context: Approximately 90% of patients with morbid obesity (MO) have fatty liver and approximately 25%–30% have significant liver fibrosis-cirrhosis. Noninvasive serum biomarkers have shown variable ability to predict significant fibrosis (SF; bridges of fibrosis) versus no SF (NSF) on liver biopsy in obesity. The aim of this study was to determine the ability of these tests to predict SF on liver biopsy, specifically in patients with MO.
Design: Liver biopsies of MO patients (BMI ≥40 kg/m2 or ≥35 with diabetes or hypertension) undergoing gastric bypass surgery were studied in retrospective sequence (2016–2014) and fibrosis scored as SF (bridges of fibrosis in 9%) or NSF; additional biopsies with SF (all from 2013–2004) were added to increase representation of SF. Inclusion criteria included most recent presurgical data (<6 months) to calculate serum biomarker results, excluding other potential causes of liver pathology. Serum biomarker test results were determined using online calculators (http://gihep.com/calculators/hepatology/) for NAFLD fibrosis, BARD, APRI (0.7 and 1.0 cutoffs), and FIB-4 scores for SF.
Results: The study set included 155 patients, 31 with SF (20%), average 45 ± 11 years of age, BMI 46.7 ± 8.6 kg/m2, and 83% female. The only significant difference between SF and NSF patients was association of diabetes with SF (83% versus 54%, P < .001). Serum biomarker test results are shown in the Table.
Conclusions: No single serum biomarker showed sufficient sensitivity and specificity to recommend it; however, results suggest that a sequential combination of these noninvasive test results might improve their predictive value.
Chemical Proctitis Due to Hydrogen Peroxide Enema (Poster No. 25)
Chemical colitis is an underrecognized and underreported entity that can result from accidental or intentional administration of caustic chemicals. We present the unusual case of a 25-year-old woman admitted for rectal bleeding and abdominal pain for 3 days. The patient noted a history of intermittent episodes of rectal bleeding for at least 3 years with an anal fistula and associated Staphylococcus infection that was successfully treated with antibiotics. The patient's most recent sexual encounter (anal intercourse) was 5 months prior and she had been treated for gonorrhea and syphilis in the past. The patient indicated that she tried to “treat the bleeding” by self-administering hydrogen peroxide by rectal enemas. Colonoscopy showed a patchy erythema in the distal colon coalescing into a circumferential, confluent, and indurated pattern of erythema in the rectum. A rectal biopsy showed ischemic mucosal changes with ulceration, areas of crypt injury with associated reactive and regenerative changes, and pseudomembrane formation with adherent necrotic debris admixed with mucus and neutrophils on the luminal mucosal surface. This histologic pattern has been rarely described in hydrogen peroxide enema use. This form of chemical colitis results in colonic damage similar to that of ulcerative colitis and pseudomembranous colitis and demonstrates the importance of correlating with a thorough patient history (Figure 11).
Potential Diagnostic Pitfalls of CDX2 Expression in Carcinomas of Unknown Origin (Poster No. 26)
CDX2 is a homeobox transcription factor and a marker often used for establishing colorectal lineage in carcinomas of unknown origin. However, studies have identified its expression in several carcinomas outside the gastrointestinal tract, including ovarian carcinoma and bladder adenocarcinoma. Data on CDX2 immunoreactivity in tumors outside the intestine are limited. We report 2 cases of nonintestinal malignancies where CDX2 positivity posed a potential diagnostic pitfall in determining tumor origin. A 32-year-old woman with a history of Crohn disease and a diagnosis of liver metastases with unknown primary presented with ascites, sepsis, and elevated serum AFP and hCG. Clinically, a gastrointestinal primary was suspected. Liver biopsy revealed a poorly differentiated neoplasm positive for CDX2, villin, pancytokeratin, SALL4, and AFP, and negative for hepatocellular, neuroendocrine, and breast/gynecologic markers (Figure 12). The diagnosis was malignant germ cell tumor with features of yolk sac tumor. A 72-year-old man with a history of prostate cancer presented to another institution with abdominal pain. Imaging demonstrated a pelvic mass with extension into the bladder and perirectal tissues. He underwent anal biopsy and was diagnosed with rectal carcinoma. Review of the anal biopsies at our institution showed poorly differentiated carcinoma positive for CDX2 and AE1/AE3 and negative for CK7, CK20, P63, CK5, and S100 (Figure 12). PSA and PSAP were added and were positive, favoring carcinoma of prostatic origin. These cases highlight the potential diagnostic pitfall of CDX2 positivity in carcinomas of unknown origin. Histopathology, immunohistochemistry, and clinical information must be taken together in rendering diagnoses.
(Poster No. 27)
Malignant Peritoneal Mesothelioma With Ventriculoperitoneal Shunt: A Previously Unreported Presentation (Poster No. 28)
We report a case of malignant peritoneal mesothelioma associated with ventriculoperitoneal shunt (VPS) diagnosed in a 31-year-old white man with a history of cerebral palsy, hydrocephalus with VPS placement since infancy, spina bifida, and seizure disorder. The patient presented with abdominal pain and distention. Computed tomography scan revealed a rim-enhancing fluid collection with a thickened wall, in contact with the tip of the VPS catheter, interpreted as pseudocyst in association with VPS. The patient was treated with paracentesis followed by VPS revision surgery. Intraoperatively, unresectable nodular tissue with adhesions was identified, completely fused with the peritoneum. The received surgical specimen consisted of multiple smoothly lined membranous fragments displaying nodules of varying size with firm grey-white cut surface. Microscopic examination demonstrated a tumefactive neoplastic proliferation of large atypical epithelioid cells forming sheets and trabeculae, and focally invading the underlying peritoneal fat. Immunohistochemically, the tumor cells showed strong reactivity for keratins AE1/AE3, CK7, CK5, and Cam5.2, positivity for epithelial membrane antigen, nuclear expression of Wilms tumor 1, and patchy staining for calretinin and D2-40. The findings were consistent with the diagnosis of malignant mesothelioma, epithelioid type. Peritoneal mesothelioma is rare. Unlike its pleural counterpart, peritoneal mesothelioma is not necessarily associated with asbestos exposure. The association of peritoneal mesothelioma with longstanding VPS has not been previously reported. In addition to the rarity of the disease, this case is particularly unique because of the young age at presentation and its hitherto unseen association with VPS.
Rate of Coexistence of Eosinophilic Esophagitis and Eosinophilic Gastritis/Enterocolitis on Combined Upper and Lower Endoscopic Biopsies (Poster No. 29)
Context: Eosinophilic gastrointestinal disorders (EGIDs), including eosinophilic esophagitis (EoE), gastritis (EG), enteritis (EE), and colitis (EC), refer to a spectrum of clinicopathologic atopic diseases with predominant eosinophilic infiltrate. The atopic triggers, clinical presentations, and organ localizations of eosinophilic inflammatory infiltrate vary widely among patients. The aim of our study was to identify if EoE is isolated within the gastrointestinal tract and how often the other gastrointestinal sites are simultaneously affected when EoE is present.
Design: Our surgical pathology files were reviewed from 2000 to 2016 to identify and select cases of EGIDs that had biopsy samples from the esophagus, stomach, duodenum, and colon at the same time. Pertinent clinical and pathologic diagnostic data were reviewed.
Results: A total of 79 cases with EGIDs were identified. There were 50 males and 29 females, with an age range from 0–69 years (mean, 24 years). Cases with isolated EoE were 62 (78.5%), cases of EoE with other gastrointestinal sites affected by eosinophilic disease were 8 (10.1%), and the remaining 9 cases (11.4%) had EGID not involving the esophagus. There were 2 cases with EoE with EG, 4 cases of EoE with EE, and 7 cases of EoE with EC.
Conclusions: EoE is the most common and isolated site, affecting 78.5% of all EGID cases. This is likely indicative of the majority of atopic triggers targeting the esophagus solely. In only 10% of EoE cases, other GI sites (EG, EE, EC) were also concomitantly involved. Additionally, 11% of cases with fewer atopic triggers spared the esophagus while affecting the other gastrointestinal sites.
Gastric Adenocarcinoma With Loss of MLH-1 and PMS-2: Report of 2 Cases With Correlation of Histologic Patterns (Poster No. 30)
Key histomorphologic features are often associated with particular molecular abnormalities in some neoplasms. About 9% to 15% of gastric adenocarcinomas are mismatch repair (MMR) deficient. We report 2 cases of gastric adenocarcinomas with MMR protein deficiency that demonstrate distinctive morphologies. The first case involves a 50-year-old woman with a gastric resection of a 4.5 × 4.0-cm mass. Microscopically, it was a poorly differentiated carcinoma with medullary features. The second case involves a 62-year-old man with a gastric resection of a 6.9 × 5.5 × 2.2-cm mass. Microscopically, it had a mixed pattern of poorly differentiated carcinoma with medullary and mucinous features. Both of the cases occurred at the greater curvature. They both had brisk intratumoral lymphocytes, regional lymph node metastasis, and Helicobacter pylori–associated gastritis in nonneoplastic mucosa. Immunohistochemistry (IHC) for both cases showed loss of MLH-1 and PMS-2, and intact MSH-2 and MSH-6. Epstein-Barr virus in situ hybridization performed on the first case was negative. Our observations suggest performing an MMR IHC panel for MLH-1, PMS-2, MSH-6, and MSH-2 in gastric adenocarcinomas with distinctive features such as (1) mucinous differentiation with pushing borders (Figure 13, A and B), (2) increased intratumoral lymphocytes (Figure 13, C), (3) poorly differentiated/medullary features (Figure 13, D), and (4) heterogeneous pattern including any of the above. These observed morphologic patterns on hematoxylin and eosin stain may initiate IHC testing for MMR protein loss even on the diagnostic biopsy, given that immunotherapy may be a tool in tumors with MMR loss.
Gastric Carcinosarcoma With Chondrosarcoma Component: A Rare Case Report (Poster No. 31)
Carcinosarcoma is a malignant tumor consisting of epithelial and mesenchymal elements that rarely occurs in the stomach. Gastric carcinosarcoma with a chondrosarcoma component is extremely rare. We report on the case of a 71-year-old man who presented with a large mass (5 × 4 cm) located at the lesser curvature of the gastric cardia. Computerized abdominal tomography revealed wall thickness of gastric cardia and enlarged solitary lymph nodes disseminated along the lesser curvature (Figure 14, A). A biopsy of the neoplasm revealed an adenocarcinoma. The mass was resected and grossly showed solid and brown-white cut surface. The mass infiltrated through the muscularis propria and extended to the distal esophagus and peripheral soft tissue. Microscopically, the tumor consisted of adenocarcinoma (90%, Figure 14, B) and chondrosarcoma components (10%, Figure 14, C). The former was composed of cells forming a nest and labyrinthine structure. The cells had scanty amphophilic cytoplasm, hyperchromatic or fine nuclei, occasional nucleoli, and frequent mitosis. Cartilage matrix was observed in multifocal areas. The adenocarcinoma cells gradually transformed their appearance to atypical chondrocytes (Figure 14, D), either in primary tumor or metastatic lymph nodes. The adenocarcinoma and chondrosarcoma cells were positive for CK8/18 and S100, respectively. Both of the 2 components were positive for p53 and Aspm (stem cell marker). The results suggest a monoclonal origin; the chondrosarcoma is derived from the carcinoma or from a stem cell that undergoes divergent differentiation. Diagnosis of this rare entity can be made difficult by insufficient sampling. Immunostains are useful in elucidating or confirming the diagnosis.
Squamous Cell Carcinoma Arising in a Retrorectal Cyst With Local Rectal Invasion: Case Report and Literature Review (Poster No. 32)
Squamous cell carcinoma (SCC) in the rectum presents a diagnostic challenge regarding specific site of tumor origin; the differential diagnosis includes a rectal primary, secondary invasion from adjacent sites, or metastatic disease. We report the case of a 64-year-old woman who presented with abdominal pain and a 9-cm pelvic cystic mass on imaging, presumed to be ovarian in nature. Surgical exploration revealed a cystic mass adherent to the rectum with no involvement of the gynecologic tract. Grossly, the bulk of the mass was cystic and involved the retrorectal space with rectal wall extension causing mucosal ulceration. Histology showed diffuse involvement of the cyst lining and wall with invasive poorly differentiated SCC (p63 and CK5 strongly positive; nonspecific focal ER staining; chromogranin, synaptophysin, CK20, CK7, CDX2, CEA, and PAX8 negative). The presence of rare foci of nonneoplastic stratified squamous epithelium lining the cyst and absence of nonsquamous epithelium or adnexal structures was consistent with an epidermoid cyst. In summary, the findings support secondary involvement of the rectum with poorly differentiated SCC arising in a retrorectal epidermoid cyst. Literature review identified only one case report of a SCC arising in a dermoid cyst with secondary rectal involvement and no previous cases regarding an epidermoid cyst. No cases of primary rectal SCC arising within a retrorectal lesion were identified at our institution during the past 15 years. This case highlights the retrorectal space as a rare but important site of origin differential that must be considered when encountering SCC in the rectum.
Portal Hypertensive Lesions of the Small Bowel and Colon: Histopathologic Features of an Easily Overlooked Diagnosis (Poster No. 33)
Context: Portal hypertensive gastropathy (PHG) can cause gastrointestinal (GI) bleeding. Histologic changes of PHG include reactive epithelium, lamina propria (LP) capillary proliferation, and sometimes polypoid architecture. Although PHG is the most studied, similar histologic findings can be seen in small bowel and colon, which are also a source of GI bleeding. The aim is to characterize nongastric portal hypertensive (PH) GI lesions to aid in recognition by pathologists.
Design: We searched our pathology database for PHG between 2011 and 2015; 35 cases were identified. Four additional biopsy sets (1 duodenal, 2 gastric, 1 colonic) from a cirrhotic patient and a colonic biopsy from another cirrhotic patient were included, and all cases reviewed for PH-related changes.
Results: All patients had PH, mainly from cirrhosis. Eleven of 37 patients (29.7%) with PHG had concomitant duodenal or colonic biopsies. Two of 9 (22.2%) duodenal biopsies were diagnosed as having PH-related changes; 7 of 9 as mild nonspecific duodenitis, ulcerated polypoid gastric foveolar metaplasia, erosive peptic duodenitis, benign mucosa with vascular congestion, or normal. On review, all 9 biopsies had PH-related changes. Of these, 3 had ulcer/erosion, whereas 3 were polypoid endoscopically, corresponding to frondlike edematous villi histologically. Of 2 colon biopsies, 1 was originally diagnosed as having PH-related changes and the other inflammatory-type polyp. On review, both had polypoid PH-related changes.
Conclusions: Nearly three-fourths of cases with nongastric PH-related changes were unrecognized, highlighting that this diagnosis is easily overlooked. Correlation of PH histologic features with clinical history and endoscopic findings can aid in recognition of nongastric PH-related lesions, which can be sources of occult GI bleeding.
Immunohistochemical and Ultrastructural Features of Hepatocellular Cytoplasmic Globules in Venous Outflow Impairment: Distinction From α1-Antitrypsin Deficiency (Poster No. 34)
Context: Hepatocellular cytoplasmic globules in patients with venous outflow impairment (VOI) have been described but their composition is not well understood.
Design: We screened for hepatocellular cytoplasmic globules in 63 liver biopsies diagnosed with VOI (1994–2016). We excluded patients with α1-antitrypsin (AAT) deficiency. Special stains for periodic acid–Schiff with diastase digestion (PAS-D), phosphotungstic acid hematoxylin (PTAH), and immunohistochemical (IHC) stains for complement protein 4d (C4d) and AAT were performed. Electron microscopy (EM) was performed in available cases.
Results: Hepatocellular cytoplasmic globules were identified in 8% (5 of 63) of cases. Three consultative referral cases were added (total of 8 cases). Causes of VOI included congestive heart failure (n = 5), Budd-Chiari syndrome (n = 1), and unknown (n = 2). The mean age was 46 years (range, 33–80 years). Half of the patients were women. The hepatocellular cytoplasmic globules showed size variability and a random lobular distribution. Special and IHC stains were successfully obtained on all but 1 case. The globules were positive for PAS-D in 8 cases (100%), for PTAH and AAT in 7 cases (100%), and for C4d in 4 cases (57%). EM (2 cases) demonstrated lysosome-bound inclusions containing microfibrillar material and small amounts of fibrinogen.
Conclusions: PAS-positive diastase-resistant hepatocellular cytoplasmic globules occur in 8% of patients with VOI. These globules are positive for AAT but can be distinguished from AAT globules by their appearance, lack of zone 1 localization, positivity for PTAH, and ultrastructural composition. IHC and EM features suggest that these globules represent plasma protein–laden (including fibrinogen) lysosomes.
Solitary Fibrous Tumor—A Rare Cause of Chronic Gastrointestinal Bleeding (Poster No. 35)
Solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm of fibroblastic or myofibroblastic origin that commonly occurs in pleura, pericardium, or peritoneum. Visceral origin of SFT is rare, but well described, with very few cases of stomach involvement. We report an 81-year-old woman with a history of chronic anemia and weight loss for several months. On esophagogastroduodenoscopy a 5-cm pedunculated mass with an erythematous, friable surface and oozing blood was found in the gastric body. Multiple endoclips were placed on the bleeding sites. Results of a biopsy were unremarkable. Based on the location and ongoing bleeding, the differential diagnosis was glomus tumor among others. A partial gastrectomy was performed. Grossly, a 7.5-cm pedunculated exophytic polyp with surface ulceration was found. Cut sections showed a well demarcated, nodular, 3.5-cm submucosal tumor with variegated tan, white appearance. Microscopic examination revealed a tumor composed of spindle to ovoid cells, in alternating hypocellular and hypercellular patternless pattern, along with keloid-type collagen, myxoid change, and branching, thin-walled vessels. In the cellular areas, slight nuclear hyperchromasia was noted, and the mitotic count was up to 3/10 high-power fields. By immunostains the tumor was positive for CD34, BCL2, and vimentin, and negative for CD117, DOG1, desmin, SMA, calponin, S100, ERG1, and CAM5.2. The tumor showed diffuse nuclear staining for STAT6, confirming the diagnosis of SFT. Our patient presented with chronic anemia due to bleeding from an unusual stomach polyp. A rare diagnosis of submucosal SFT was confirmed by immunocytochemical staining (Figure 15).
Histomorphologic Prediction Parameters of Survival and Lymph Node Metastasis in Gallbladder Cancer (Poster No. 36)
Context: Conventional prognostic parameters of gallbladder carcinoma in histomorphology include broad parameters like tumor size, lymph node metastasis, level of invasion, AJCC stage, resection margins, histologic type, and grade. We have additionally investigated inclusion of nuclear grade, mitoses, tumor buds, tumor-associated lymphocytic infiltration, necrosis, lymphovascular invasion, perineural invasion, depth of invasion, and percentage of wall infiltration.
Design: The study group comprised 82 subjects undergoing radical cholecystectomy. Mean age was 50.13, and subjects were followed up for up to 54 months (mean ± SD: 14.69 ± 10.65). Prognostic factors were analyzed by univariate and multivariate Cox regression model and by Kaplan-Meier method (log-rank test).
Results: The Table depicts the role of various clinicopathologic parameters in the prediction of overall survival. Strong, significant correlation was observed for tumor site, surgical resection margins, and histologic type, with mucinous, signet ring cell, gastric-type adenocarcinoma, and undifferentiated carcinoma carrying poorer survival. Interestingly, nuclear grade, mitoses, and tumor budding strongly correlated with poor survival apart from lymphovascular emboli, perineural invasion, level of invasion, and depth of invasion (mm). Cisplatin-based chemotherapy does not appear to make a significant difference in survival when given in post–radical cholecystectomy cases. Lymph node metastasis is significantly associated with tumor growth pattern, histologic types, nuclear grade, mitosis, tumor buds, and level and depth of invasion.
Conclusions: Our study corroborates the need for inclusion of nuclear grade and mitoses in grading and independent reporting of tumor budding apart from conventional parameters. Predictive indices for survival and lymph node metastasis will be presented.
Novel Heterozygous ACTG2 Mutation in Chronic Intestinal Pseudo-Obstruction With Visceral Myopathy and Actin-Positive Inclusions (Poster No. 37)
A 17-year-old adolescent male presented with chronic intestinal pseudo-obstruction. He had a history of corrected intestinal malrotation, multiple episodes of ileus, delayed gastric emptying, and multiple interventions for obstructive symptoms. Recent imaging showed dilated loops of bowel, a choledochal cyst, and dilated biliary ducts. He underwent surgical resection of the choledochal cyst, cholecystectomy, and biopsy of the duodenum. Microscopic examination of the duodenal biopsy showed a somewhat disorganized muscularis propria. Ovoid, eosinophilic, cytoplasmic inclusions were seen in the smooth muscle cells of duodenal muscularis propria (Figure 16, A) and the walls of gallbladder and choledochal cyst. The inclusions were highlighted by smooth muscle actin (Figure 16, B) and muscle specific actin. Ultrastructurally, the inclusions were composed of irregular whorled aggregates of filaments that measured 9.09–11.4 nm in diameter (Figure 16, C). The coding exons of the ACTG2 gene were Sanger sequenced, and a novel missense mutation (c.439G>T;p.Gly147Cys) was identified (Figure 16, D). This mutation is predicted to be deleterious by standard computational algorithms. Primary chronic intestinal pseudo-obstruction is a rare, potentially debilitating and life-threatening disease. The underlying etiology may be myopathic (visceral myopathy) or neuropathic (visceral neuropathy) and, depending upon the genetic defect, the disease may involve other organ systems such as genitourinary tract and blood vessels. Gastrointestinal specimens from patients with chronic intestinal pseudo-obstruction should be carefully examined for histologic changes. Although the case presented here showed actin-positive inclusions, many cases do not have specific histologic findings, and electron microscopy and DNA sequencing may help with definitive diagnosis.
Fine-Needle Aspiration Findings of a Rare Hematopoietic Neoplasm Presenting as Obstructive Jaundice (Poster No. 38)
A 51-year-old woman who presented with obstructive jaundice was found to have masses in the pancreatic head and tail as well as suspicious liver and periaortic masses on imaging. Aspiration cytology of the pancreatic tail mass showed abundant large single cells with vacuolated eosinophilic cytoplasm, marked nuclear pleomorphism, large bizarre irregular nuclei, binucleation, and prominent nucleoli (Figure 17, A and B). Numerous cells also showed intracytoplasmic black to brown pigmentation. A cell block was obtained and extensive immunohistochemical staining was performed. S-100, HMB-45, Sox10, pancytokeratin, CK7, RCC antigen, synaptophysin, Hepar 1, inhibin, CD45, CD21, and CD123 were negative, making melanoma, epithelial malignancies, lymphoma, follicular dendritic, and plasmacytoid dendritic cell neoplasms less likely. CD4 and CD56 showed partial positivity, and CD68, CD163, and CD14 were positive, supporting the diagnosis of histiocytic sarcoma (Figure 17, C and D). Surgical specimens and immunohistochemistry confirmed the cytologic findings. Histiocytic sarcoma is a rare aggressive malignancy of histiocytic origin with most cases presenting in adults in extranodal sites, most commonly the intestinal tract. Few cases are reported in the literature, presenting diagnostic challenges for cytopathologists when seen on fine-needle aspiration. We present a case of histiocytic sarcoma presenting as a pancreatic mass, diagnosed by endoscopic ultra-sound-guided fine-needle aspiration (EUS-FNA). This entity is rarely described on cytology and arose in a location in which EUS-FNA is the diagnostic modality of choice. This case study highlights that cytopathologists should be aware of histiocytic sarcoma occurring in extranodal locations accessible by EUS-FNA and be familiar with its cytomorphologic appearance.
Immature Gastric Teratoma With Rhabdomyosarcomatous and Primitive Neuroectodermal Tumor Components in an Adult Patient (Poster No. 39)
Gastric teratomas are extremely rare with just more than 100 cases reported; the majority are mature teratomas with fewer than 2 dozen immature cases reported. Most are reported in the pediatric population, with fewer than 10 reported in adults (age range, 20–83 years). Here we report a 55-year-old Hispanic man who presented with anemia (hemoglobin of 7.6 g/dL and hematocrit of 26% at presentation), epigastric abdominal pain, and melena. His past medical history included hyperlipidemia and type 2 diabetes mellitus. On physical examination, he had a soft, tender abdomen with normal bowel sounds. On computed tomography, an increased soft tissue density was identified in the proximal portion of the stomach. Upper GI endoscopy revealed a polypoid mass. A partial gastrectomy was performed. On gross examination, a fungating, partially fragmented, friable mass (8 × 6.5 × 2.6 cm) was located along the greater curvature and had a grayish tan and hemorrhagic cut surface. Histologic examination showed immature teratoma with sarcomatous components, which included rhabdomyosarcomatous areas confirmed by desmin and MyoD1 and primitive neuroectodermal tumor component confirmed by neurofilament, synaptophysin, and SALL-4. Most reported cases of gastric teratomas are benign, but malignant transformation (invasive adenocarcinoma) arising from an immature gastric teratoma has been reported in an 83-year-old man. Sarcomatous transformation with rhabdomyosarcomatous and primitive neuroectodermal tumor, as seen in this case, has not been reported. Complete surgical resection with tumor-free margins and long-term follow-up is standard management. Because of its rarity and various histologic patterns, gastric teratomas in adults may be misdiagnosed.
Incidental Synchronous Mucosa-Associated Lymphoid Tissue Lymphoma, Plasmacytoma, and Extensive Amyloidosis of the Lower Gastrointestinal Tract (Poster No. 40)
Mucosa-associated lymphoid tissue (MALT) lymphoma frequently affects the stomach and rarely involves the lower gastrointestinal (GI) tract. Colonic plasmacytomas are likewise uncommon. We present a case of synchronous MALT lymphoma and plasmacytoma in a right hemicolectomy specimen resected for unsuspected amyloidosis. A 60-year-old asymptomatic woman had a 2.5-cm colonic tubular adenoma with high-grade dysplasia biopsied during routine colonoscopy. Because of persistent clinical suspicion of underlying malignancy, surgery was performed. An enlarged appendix at surgery prompted a right hemicolectomy. Grossly, the terminal ileum, appendix, and colon demonstrated extensive wall thickening accompanied by enlarged lymph nodes. No discrete mucosal masses were identified. Histologically, marked and diffuse submucosal amyloid deposition was accompanied by λ-restricted B lymphocytes coexpressing BCL2 and CD43 and scattered atypical, megakaryocyte-like clonal CD138+ plasma cells (Figure 18). Subsequent bone marrow biopsy confirmed multiple myeloma featuring similar bizarre plasma cells. To the best of our knowledge, this is the first case of synchronous MALT lymphoma, plasmacytoma, and extensive amyloidosis within the lower GI tract. Though prior cases of amyloid masquerading as a malignancy have been reported, such cases typically present as discrete masses. Localized amyloid deposition associated with MALT lymphoma has been rarely reported; however, only 1 of these 20 cases involved the lower GI tract. Each disease alone is uncommon in this location; thus, the synchronous presentation of all 3 entities is rare and remarkable.
Shift in Gastric Mucosal Type in Anal Gastric Heterotopia Associated With Focal Melanosis Coli (Poster No. 41)
Gastric heterotopia is the presence of gastric mucosa in a foreign anatomic location. It can occur anywhere in the gastrointestinal tract and has been well documented in the esophagus, duodenum, and Meckel diverticula. Gastric heterotopia of the anorectum is a rare occurrence. We present a case of an asymptomatic 58-year-old man with a past medical history of iron deficiency anemia, hypertension, peripheral arterial disease, coronary artery disease, and remote history of tobacco use and alcohol abuse who presented for routine colonoscopy. The colonoscopy revealed a 9-mm nodule at the anal-rectal verge (Figure 19, A). Microscopic examination of the entire lesion revealed oxyntic gastric mucosa with chronic active gastritis and melanosis coli (Figure 19, B and C). The foci of melanosis coli were positive for periodic acid–Schiff diastase (PAS-D) and Fontana Masson. During a subsequent colonoscopy 6 years later, a pigmented skin tag in the anus was biopsied. Microscopic examination revealed antral gastric mucosa with chronic active gastritis (Figure 19, D). Immunohistochemistry stains for Helicobacter pylori with adequate controls were negative in both biopsies. A literature review showed that there have been 72 reported cases of gastric heterotopia of the anorectum. Four cases occurred in the anus; 68 occurred in the rectum. To our knowledge, this is the first report of a shift in gastric mucosal type in anal gastric heterotopia associated with focal melanosis coli on repeat biopsy.
Age-Related Prevalence of Inorganic Microparticles in Terminal Ileum Biopsies (Poster No. 42)
Context: Human terminal ileum biopsies occasionally harbor “pigment cells,” which contain intracellular microparticles (MPs) composed predominantly of exogenous inorganic compounds. Our study investigates the association between age and presence of MPs observed in hematoxylin and eosin (H&E)–stained biopsies of terminal ileum.
Design: We evaluated 200 consecutive H&E-stained terminal ileum biopsy specimens taken routinely from 2015 to 2016 for the presence of pigment cells containing MPs. Specimens were categorized by age group as follows: less than 20, 21–40, 41–60, and older than 60 (see Table). Corresponding findings of active ileitis and colonic inflamma-tory bowel disease (IBD) were also noted. Data were evaluated using Z test and Fisher exact test.
Results: Our cases included 75 males and 125 females ranging in age from 4 to 88 years (mean = 40.2 years). MPs were present in 107 biopsies. Statistically significant differences in prevalence of MPs existed between nearly all age groups (P < .05, 95% CI), with the outright exception of between 41 and 60 and older than 60. Comparison of groups less than 20 and 21–40 resulted in Z test P value of .03 and Fisher exact test P value of .05 (we suspect this value will become definitively significant with larger n). No significant differences were observed between patients with and without active ileitis or colonic IBD.
Conclusions: Our data suggest an inverse relationship between the presence of MPs in terminal ileum biopsies and age. Of note, no significant associations between the presence of MPs and prevalence of active ileitis or colonic IBD were identified.
Incidence and Significance of GATA-3 Positivity in Pancreatic Ductal Adenocarcinoma and Cholangiocarcinoma (Poster No. 43)
Context: GATA-3 is a reliable immunohistochemical marker for mammary and urothelial carcinoma. It is reportedly positive in 10%–37% of pancreatic ductal adenocarcinomas (PDACs) and 3%–9% of cholangiocarcinomas (CCs). GATA-3 positivity in these tumors has not been analyzed relative to clinical or histologic findings. We aimed to determine whether GATA-3 positivity in PDACs and CCs is associated with pertinent clinicopathologic features.
Design: Slides from tissue microarrays containing 99 PDACs and 60 CCs were stained using a monoclonal antibody against GATA-3. Percentage and staining intensity of GATA-3–positive tumor nuclei were recorded. Clinicopathologic parameters evaluated included patient age, sex, race, and overall survival; (neo)adjuvant therapy; lymphovascular and/or perineural invasion; and tumor site, size, grade, histologic subtype, and pathologic stage. Margin status was also analyzed for PDAC.
Results: Positive staining for GATA-3 was seen in 10 of 99 PDACs (10%) and 3 of 60 CCs (5%). PDAC staining intensity varied but was weak in all 3 GATA-3–positive CCs. No significant clinicopathologic differences were noted between GATA-3–positive and GATA-3–negative PDACs or CCs, including overall survival. All 3 GATA3-positive CCs were poorly differentiated (P = .07).
Conclusions: GATA-3 staining is uncommon in PDACs and CCs, consistent with previous reports. GATA-3 immunoreactivity in PDAC and CC is typically weak, though PDAC may rarely show strong staining. GATA-3 expression in PDAC and CC showed no significant association with clinicopathologic features or overall survival. However, the fact that these tumors can occasionally express GATA-3 should be considered when interpreting immunohistochemical results from a metastatic lesion of unknown primary, in order to avoid misdiagnosis.
Presence of Intestinal Metaplasia Immediately Distal to the Endoscopic Gastroesophageal Junction Is Associated With Visible Columnar-Lined Esophagus (Poster No. 44)
Context: The proximal limit of gastric rugal folds currently defines the gastroesophageal junction (GEJ) endoscopically. Controversy exists as to whether cardiac epithelium immediately distal to this is proximal stomach or esophageal. This study evaluates the association between intestinal metaplasia (IM) immediately distal to the endoscopic GEJ and visible columnar lined epithelium (CLE).
Design: Patients undergoing endoscopy at the University of Southern California from 2008 to 2011 had biopsies routinely taken immediately distal to the endoscopic GEJ and in visible CLE, if this was present. The association of IM in the 2 locations was evaluated.
Results: Visible CLE was present in 91 of 1024 patients (8.9%; Table). Twenty-three of 165 patients (13.9%) with IM distal to the endoscopic GEJ had visible CLE, significantly higher than the 68 of 791 (7.9%) without (P = .02). There was no significant difference between IM distal to the endoscopic GEJ and length of visible CLE (P = .18) or presence of IM in it (P = .72).
Conclusions: Presence of IM immediately distal to the endoscopic GEJ is associated with a significantly increased incidence of visible CLE, irrespective of its length or the presence of IM. This finding suggests that IM in cardiac epithelium distal to the endoscopic GEJ is associated with reflux-induced pathology in the tubular esophagus, supporting the notion that cardiac epithelium is esophageal and not gastric in origin. IM in cardiac epithelium distal to the endoscopic GEJ is likely a precursor lesion for visible CLE and can be a marker for increased risk of future Barrett esophagus.
Sarcina ventriculi: A Cytologic and Histologic Study of 5 Cases (Poster No. 45)
Context: Sarcina ventriculi is a gram-positive anaerobic bacterium with distinctive morphology of tightly packeted cocci in tetrads and octets that can survive in very low pH. Although it is a known pathogen in livestock, only a few infectious cases in humans have been documented. Presence of Sarcina in the gastrointestinal tract has been associated with dyspepsia, nausea, ulcers, and even life-threatening complications including emphysematous gastritis and gastric perforation.
Design: Cytology and histology specimens and clinical outcomes of 5 patients with Sarcina from our institute were reviewed.
Results: Sarcina was identified in 5 gastrointestinal biopsies and 5 cytology specimens (2 pyloric fine-needle aspirations [FNAs], 2 pancreatic FNAs, and 1 bronchial washing) from 5 patients within a 6-month period. All 5 patients had symptoms of delayed gastric emptying. Patients' previous history included cystic fibrosis, advanced pancreatic carcinoma, diabetic gastroparesis, esophageal strictures, and pyloric stenosis. All cases showed chronic/active inflammation in association with Sarcina. Two patients were treated with metronidazole and ciprofloxacin, with subsequent clinicopathologic improvement in gastrointestinal symptoms.
Conclusions: Sarcina ventriculi is known to cause life-threatening infections in livestock, but its pathogenicity in humans is still controversial; however, presence of inflammation and gastrointestinal symptoms that improved with antibiotics might suggest some degree of pathogenicity and a role for treatment. Awareness of Sarcina and reporting its presence is important, because it is associated with delayed gastric emptying and could prompt additional workup for underlying causes of gastric outlet obstruction, including malignancy (Figure 20).
Myxoid Variant of Epithelioid Mesothelioma: A Rare Cause of Peritoneal Carcinomatosis (Poster No. 46)
Myxoid variant of epithelioid mesothelioma involving the peritoneum is an extremely rare tumor. To date, only 4 cases have been reported in the literature. It has many histologic mimics like mucinous carcinoma or pseudomyxoma peritonei from which it has to be carefully distinguished. Accurate identification of this tumor is essential for proper management of the patient. We present a case of a 59-year-old man who presented with abdominal bloating and vague abdominal pain. Computed tomography and PET scan showed ascites and findings suggestive of peritoneal carcinomatosis; however; no primary could be identified. Peritoneal fluid cytology showed mucinous cells with nuclear atypia. A diagnostic laparoscopy with omental biopsies was performed, and 2 weeks later a debulking procedure was done. The patient died after 6 months. Histologically, the tumor consisted of discohesive medium-sized to large epithelioid cells with a moderate amount of eosinophilic cytoplasm dispersed in a myxoid background (Figure 21, A and B). The nuclei showed coarse chromatin with prominent nucleoli, and mitotic figures were inconspicuous. Immunohistochemically, the tumor cells showed diffuse positivity for calretinin, D2-40, EMA, CK 5/6, and vimentin (Figure 21, C). MOC 31 and BER Ep4 were negative in tumor cells (Figure 21, D), supporting mesothelial differentiation. Although it is rare, myxoid variant of mesothelioma can be a cause of carcinomatosis peritonei and needs to be accurately distinguished from its histologic mimics.
Why Axial Slicing Technique for Pancreas Specimens? (Poster No. 47)
Context: Several techniques are described for the dissection of pancreatic specimens: bivalving along the ducts (the traditional technique), bread loafing, and axial slicing (AS) (novel technique).
Design: We used the AS technique in 20 pancreas resections, 14 proximal and 6 distal, including solid and cystic lesions: 12 pancreatic ductal adenocarcinomas (2 post treatment), 1 common bile duct adenocarcinoma, 4 intraductal papillary mucinous neoplasms, 4 neuroendocrine tumors, and 2 solid-pseudopapillary neoplasms. First the stomach/enteric, common bile duct, and pancreatic duct resection margins were shaved and submitted. Then the uncinate/retroperito-neal margin, SMV groove, anterior, and posterior surfaces were inked. After 6–12 hours of formalin fixation, the pancreas was serially sectioned in 3-mm-thick slices perpendicular to the long axis of the duodenum. Gross photographs of intact and axially sectioned specimens were taken.
Results: The AS technique allowed better preservation of the specimen, optimized the macroscopic examination of lesions/tumors in relation to margins, surfaces, and adjacent organs/structures, and enhanced the quality of the sections submitted for microscopic evaluation (Figure 22). The lymph nodes were retrieved in place along with the tumor. AS is easier to teach to residents and physician assistants and makes it less challenging for them to submit proper sections. A better correlation with preoperative imaging studies, like CT and MRI, was appreciated.
Conclusions: AS is easy to use and gives better macroscopic and microscopic assessment and documentation for the staging of pancreatic tumors.
Clinical Relevance of PD-L1 and HER2 Expression in Gallbladder Cancer: Potential Targets for Therapy (Poster No. 48)
Context: Gallbladder cancers (GBCs) have limited therapeutic options and poor outcome with conventional therapy. PD-L1 has been sparingly studied in GBCs. We investigated expression of PD-L1 and HER2 in relation to clinicopathologic characteristics and survival.
Design: Study group comprised a large GBC cohort of 336 cases. HER2 immunohistochemistry (IHC) was performed in 318 cases where positive status was called when IHC score was 3+ in 10 tumor cells. Tissue microarrays were analyzed for PD-L1 (SP263 clone) in 174 cases; IHC was analyzed at different cutoffs and positivity taken as >1% positive tumor cells.
Results: The Table depicts the demographics, histopathology, and stage of GBC in the study group. Mean age was 49.4 years with female preponderance (77.7%). Frequency of HER2 and PD-L1 expression was 24.8% and 24.1%, respectively. There was no significant association between HER2 status and clinicopathologic variables, except histologic grade (P = .02). HER2 positivity decreased with increasing grade. HER2 was negative in all 7 cases of neuroendocrine carcinoma and 3 cases of squamous cell carcinoma. There was no significant association between PD-L1 status and clinicopathologic variables except age (P = .004). No significant difference in marker expression was evident at primary versus metastatic sites. Overall survival showed no significant association with HER2 and PD-L1 expression (P = .43 and P = .59). At cutoff of 10%, 13.8% of cases expressed PD-L1, and at 50% the number of cases was 7.5%.
Conclusions: Conventional chemotherapy outcomes did not vary with HER2- or PD-L1–positive versus negative status. HER2 and PD-L1 may be useful potential targets for therapy in GBC cases.
The Correlation Between Pancreatic Cystic Mucinous Neoplasm Epithelial Subtypes and Cyst Fluid Carcinoembryonic Antigen Levels (Poster No. 49)
Context: Pancreatic cystic mucinous neoplasms (PanCMNs), including intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN), are considered premalignant. IPMNs are characterized by different epithelial subtypes (ESs) with distinct clinicopathologic characteristics. Because of sparse data in the literature, we sought to investigate the correlation between cyst fluid (CF)–carcinoembryonic antigen (CEA) level and PanCMN ES.
Design: A retrospective search was performed to identify IPMN and MCN resections with corresponding preoperative CF-CEA levels. The ES percentage (ES%) and histologic grade of both IPMNs and MCNs were evaluated. Flat epithelium without defining ES characteristics was included. Other features including cyst size and duct involvement were taken from ultrasound and grossing records. Statistical analysis comparing CF-CEA levels with these various features was performed.
Results: Thirty-seven IPMNs and 7 MCNs were included. Among 37 IPMNs (Table), gastric ES was dominant. There was no correlation between CF-CEA level and gastric ES% (Spearman correlation [SC] = .04; P > .99). There was a weak positive correlation with intestinal ES% (SC = 0.36; P = .09) and a weak negative correlation with pancreatobiliary ES% (SC = −0.37; P = .09). Analysis of combined IPMNs and MCNs (44 PanCMNs) showed similar trends. No strong associations were found between CF-CEA levels and largest cystic dimension (P = .84), duct involvement (P = .17), or histologic grade (P = .48).
Conclusions: In our series, no strong correlation between PanCMN gastric ES and CF-CEA level was identified. However, a possible positive trend between intestinal ES and CF-CEA level and a possible negative trend between pancreatobiliary ES and CF-CEA level were identified. Further studies with larger patient cohorts may help determine if intestinal and pancreatobiliary ES correlate with CF-CEA levels.
Hypercalcemia as the Initial Presentation for Primary Cholangiocarcinoma (Poster No. 50)
Hypercalcemia of malignancy is a fairly common finding in patients with cancer and can be found in 20%–30% of cancer patients. The most common malignancies associated with hypercalcemia are lung cancer, breast cancer, multiple myeloma, and some cancers of the head and neck. Although it is a common finding in many malignancies, hypercalcemia of malignancy is a rare manifestation in patients with primary cholangiocarcinoma, and often represents a poor prognosis. Cholangiocarcinoma is an adenocarcinoma that arises from intrahepatic bile duct epithelial cells, and represents about 10% of liver malignancies. We report an unusual case of hypercalcemia as the presenting symptom in a patient with undiagnosed primary cholangiocarcinoma. A 67-year-old woman presented to the emergency room with symptoms of confusion and altered mental status, and was found to be hypercalcemic with a calcium level of 14.1 mg/dL, consistent with non–parathyroid-related hypercalcemia. The patient's elevated calcium level was successfully treated with normal saline, calcitonin, and zoledronic acid. Subsequent MRI and CT scans revealed multiple lesions in the liver, consistent with malignancy. Histologic examination of the liver mass showed a malignancy that was immunohistochemically consistent with a primary cholangiocarcinoma (Figure 23, A through D). We present this unusual case to bring awareness to the fact that, although rare, cholangiocarcinoma may initially present with hypercalcemia, and medical treatment of hypercalcemia may significantly improve a patient's quality of life in the setting of an otherwise dismal prognosis.
IgG4-Associated Cholangitis With Markedly Elevated Serum CA 19-9 Level: A Mimic of Hilar Cholangiocarcinoma (Poster No. 51)
IgG4-associated cholangitis (IAC) is a manifestation of IgG4-associated sclerosing disease and may present as a biliary mass. The diagnosis depends on a combination of clinical and histopathologic findings but is challenging in cases with atypical presentations. CA19-9 is used as a tumor marker for pancreatic and biliary tract cancers, but levels can also be increased in several inflammatory conditions. Herein we report a rare case of IAC with a markedly elevated CA 19-9 level. A 70-year-old woman presented with abdominal pain 3 months after cholecystectomy and stent placement in the common bile duct for a retained cholelith. Results of liver function tests showed slightly elevated serum alkaline phosphatase and CA 19-9 level of 1009 U/mL, with a 1.7-cm mass and biliary obstruction on imaging. Two biopsies showed liver parenchyma with fibroinflammatory nodules, sclerosing fibrosis, and an inflammatory infiltrate of lymphocytes, plasma cells, and eosinophils. Obliterative phlebitis and bile duct epithelial injury were present. Immunohistochemistry for IgG and IgG4 demonstrated increased IgG4-positive plasma cells and an IgG4:IgG plasma cell ratio of 25%. The patient had marked improvement of her symptoms, regression of the biliary lesion, and normalization of CA19-9 levels following steroid treatment. Correct diagnosis of IAC with steroid therapy can significantly improve outcomes. obviating unnecessary surgical intervention and significantly reducing the high relapse rates in the absence of steroid treatment. This case highlights potential diagnostic pitfalls associated with considering elevated levels of serum tumor markers in isolation in the evaluation of possible malignancy.
A Possible Role of Mast Cells in the Pathogenesis of Pediatric Nonspecific Abdominal Pain (Poster No. 52)
Context: Mast cells (MCs) and a low-grade mucosal inflammatory process are known to be increased in the colonic mucosa of adult patients with irritable bowel syndrome. The number of MCs in the colonic mucosa of children presenting with nonspecific abdominal pain has not been previously investigated.
Design: Pediatric patients who presented with nonspecific abdominal pain, normal colonoscopy findings, and apparently histologically normal colon biopsies between May 2015 and February 2017 were studied. The control group consisted of 12 autopsy cases of patients who died of isolated central nervous system diseases. Colonic biopsies from patient and control groups were reviewed and stained with CD117. In each region of the colon, the area with the highest number of MCs (hot spot) was selected and the number of MCs was counted per high-power field (×400).
Results: The patients group consisted of 36 patients (age range, 1.7–17 years). The control group consisted of 12 autopsies (age range, 0.4–16.3 years). Clinical presentations of the patients group included abdominal pain (in all patients), abnormal bowel movement, blood in stools, and joint pain. Histologic examination of both groups showed no pathologies beside increased number of MCs in the patients group. Details of the numbers of MCs in various parts of the colon are presented in the Table.
Conclusions: Our results show an increased number of MCs in all parts of the colon in the patients group compared with the controls group. It is tempting to hypothesize that these patients may benefit from antihistamines or other MC stabilizers.
A Case of Solid Pseudopapillary Tumor of Pancreas in a 12-Year-Old Boy (Poster No. 53)
Solid pseudopapillary tumor (SPPT) is a rare and enigmatic pancreatic neoplasm. Although it is a neoplasm of low-grade malignant potential, it has a favorable prognosis with aggressive local resection. It occurs predominantly in females, with a ratio of 20:1, and at a median age of 20–35 years. It presents most commonly as a palpable abdominal mass, and some of the cases are found incidentally with typical radiographic features of well-circumscribed cystic and solid mass with heterogeneous enhancement. We present a case of SPPT of the pancreas in a 12-year-old boy who initially presented with abdominal pain. Contrast-enhanced computed tomography demonstrated a 11-cm mass midway between the liver and the pancreas. The mass had been increasing in size progressively and was associated with abdominal pain. Biopsy was performed, which showed microscopically necrosis and areas with increased cellularity having pseudopapillae covered by several layers of epithelial cells. The nuclei were ovoid and coffee bean shaped. Immunohistochemical stains for cyclin D1, α1-antitrypsin, and β-catenin were positive on the tumor cells. The patient underwent pylorus-preserving Whipple procedure. The mass had necrosis, grossly measured 15 cm, and invaded small bowel mesentery directly. There is no evidence of recurrence or metastases with 6 years' follow-up. Although SPPT is found mostly in females, one should not forget the diagnosis of SPPT in male patients and in the pediatric population because of its favorable prognosis with complete resection alone.
Biopsy Diagnosis of Pancreatic Cysts by Histology and MUC Immunohistochemistry (Poster No. 54)
Context: Incidental pancreatic cysts have been increasing because of advanced imaging technology. Pancreatic cystoscopy enables us to directly biopsy the cyst wall with higher diagnostic yield compared with fine-needle aspiration. However, diagnostic scheme and interpretation for such biopsies, especially in pancreatic mucinous cysts, have not been established.
Design: Thirty-four pancreatic cyst biopsies from March 2016 to February 2017 were examined by microscopy and MUC immunohistochemistry. Six cases had no epithelium, and 3 nonmucinous cysts were serous cystadenoma, squamoid cyst, and cystic neuroendocrine tumor. Mucinous cysts were classified into 3 categories: 14 gastric-type mucinous epithelium with papillae (2 with rare intestinal metaplasia), 8 gastric-type mucinous epithelium without papillae, and 3 with indeterminate mucinous epithelium. Only low-grade dysplasia was present in the mucinous cysts.
Results: (1) Mucinous epithelium with papillae favors branch duct IPMN; without papillae it may represent IPMN, MCN, or simple mucinous cyst. (2) Intestinal metaplasia may arise from the gastric-type mucinous epithelium. (3) Gastric-type mucinous epithelium shows diffuse cytoplasmic, but not apical cell surface, staining of MUC1 and MUC6. (4) Flat mucinous epithelium may show apical MUC1 staining, but that is regarded as indeterminate in predicting cyst nature. (5) Although no intestinal or pancreatobiliary branch ductal IPMN is identified in the study, it cannot be entirely excluded based upon the small biopsies.
Conclusions: Diagnosis of pancreatic cysts by biopsy is challenging but important. There is an urgent need to establish a standardized diagnostic scheme in this rapidly expanding area.
Sevelamer Crystals Associated With Colonic Perforation: A Case Report of a Newly Described Complication (Poster No. 55)
Sevelamer is a noncalcium phosphate binder used in chronic renal failure to treat hyperphosphatemia and commonly used in patients on dialysis. Sevelamer does not get metabolized in the liver and is associated with gastrointestinal tract injury resulting in chronic mucosal damage, ulceration, ischemia, and necrosis. Colonic perforation, however, has yet to be described in association with sevelamer. We report a case of a 60-year-old man with end-stage renal disease on hemodialysis who presented to the emergency department with abdominal pain and diarrhea. Computed tomography of the abdomen showed pneumoperitoneum, and the patient underwent an emergent exploratory laparotomy with left colectomy. Pertinent findings during surgery included diffuse fibrinous adhesions, purulent and feculent fluid throughout the abdomen, and a perforation in the mid descending colon. On gross examination, a transmural defect consistent with a perforation and multiple diverticula were found. Histopathologically, transmural acute inflammation and necrosis associated with a foreign crystalline material (Figure 24, A and B) with a fish-scale–like appearance was identified (Figure 24, C and D). The crystals were orange-yellow on H&E stain, were violet on PAS-D stain, and had curvilinear lines of intersection, consistent with sevelamer. The remainder of the colon showed sevelamer crystals in the lumen and impacted within diverticula. We report the first case of colonic perforation associated with sevelamer, and would like to emphasize close surveillance in patients who may be at risk of developing serious complications, such as those on long-term sevelamer use and with underlying anatomic or inflammatory disorders such as diverticulosis.
Esophageal Mucosal Calcinosis: A Rare Site of Gastrointestinal Mucosal Calcification (Poster No. 56)
Gastrointestinal tract mucosal calcinosis (MC) tends to affect the gastric mucosa, whereas esophageal involvement is rare. Gastric MC may be seen with solid organ transplantation, use of aluminum-containing antacids or sucralfate, malignancy, and chronic renal failure. Although the incidence of gastric MC in renal transplant patients undergoing gastric biopsy is common (between 15% and 29%), to our knowledge, esophageal MC has been previously reported only once. A 68-year-old man with dialysis-dependent end-stage renal disease due to type 2 diabetes mellitus recently status post deceased donor kidney transplant underwent an esophagogastroduodenoscopy (EGD) for dysphagia and diffuse esophageal wall thickening seen on imaging studies. EGD demonstrated diffuse, circumferential, thick, white esophageal plaques (Figure 25, A) and mucosal friability. Esophageal biopsies demonstrated erosive esophagitis with basophilic calcium deposits within the fibrinopurulent exudate and squamous mucosa (Figure 25, B). Stains for fungal organisms and viruses were negative. Review of medications revealed use of sucralfate, and he was noted to have an elevated calcium-phosphorus product. MC may appear endoscopically as adherent white or white-yellow plaques or flecks. Esophageal MC may be secondary to multiple factors including renal transplantation, sucral-fate therapy, an elevated calcium-phosphorus product, and/or dystrophic calcification in inflamed/eroded mucosa. Although a high calcium-phosphorus product along with hypercalcemia and hyper-phosphatemia and underlying inflammation are likely key factors in its development, the pathogenesis and clinical significance of esophageal MC is not fully understood and is likely due to multiple collective etiologies, as illustrated in this case.
Gastric Glandular Siderosis: A Rare Yet Important to Recognize Entity (Poster No. 57)
Context: Gastric glandular siderosis is relatively uncommon but important to recognize as it may alert clinicians to evaluate patients for iatrogenic iron overload or hemochromatosis. It is characterized by uniform and subtle fine golden deposits in deep antral and oxyntic glands.
Design: We searched the Johns Hopkins Pathology Data System for gastric glandular siderosis from 1984 to 2016 and identified 10 cases. Clinical information and slides were reviewed.
Results: Gastric glandular siderosis occurred in equal numbers of men and women with a mean age of 48.2 years (range, 20–84 years). Most cases involved oxyntic mucosa (n = 7, 70%). The most common finding in the background mucosa was reactive chemical gastropathy (n = 5, 50%), with 1 case showing marked reactive epithelial changes mimicking dysplasia. Three cases showed no background abnormality (n = 3, 30%) and 2 cases had mild inactive chronic gastritis (n = 2, 20%). No Helicobacter pylori organisms were identified in any of the cases. Six patients received multiple transfusions for hematologic malignancies or sickle cell disease (n = 6, 60%). Three patients had cirrhosis with abundant hepatocellular stainable iron (n = 3, 30%) but only 1 was tested for C282Y and H63D mutation in the HFE gene with negative results. In 1 patient, no history of transfusion or liver disease was noted.
Conclusions: Gastric glandular siderosis can be associated with systemic iron overload due to multiple blood transfusions or hemochromatosis; thus, it is important to recognize this pattern of iron deposition and differentiate it from iron pill gastritis, where iron deposits are typically superficial.
Fatal Imatinib-Induced Acute Liver Failure: Case Report and Review of the Literature (Poster No. 58)
Drug-induced liver injury (DILI) is a rare but important cause of liver failure with potentially life-threatening complications. DILI and its relationship with autoimmune hepatitis are complex and often difficult to diagnosis. It is a well-known mimic of other acute liver diseases; determination of the cause of injury is crucial and often only possible on histologic analysis. Histologic features suggesting DILI include portal neutrophils and cholestasis. DILI usually manifests within 6 months of therapy, with the most common culprits being antibiotics; however, hundreds of agents have been implicated. Imatinib mesylate is a tyrosine kinase inhibitor (TKI) approved for the treatment of chronic myelogenous leukemia (CML) and gastrointestinal stromal tumor. Although imatinib is generally well tolerated, we report just the fifth case of fatal imatinib-induced acute liver failure. A 71-year-old woman with a history of CML on imatinib therapy for 6 months presented with severe acute hepatitis. After a thorough workup excluded more common causes, a biopsy was performed. Microscopic analysis revealed both acute hepatitis and acute cholangitis with significant portal inflammation, bile duct obliteration, cholestasis, neutrophilic infiltration, and coagulative necrosis (Figure 26, A through D). Imatinib was stopped and corticosteroids were begun. Although the patient experienced early improvement in her liver studies, this improvement was short lived, as renal failure and persistent hepatitis led to her death 2 weeks later. This case is important because as the incidence of patients on TKIs increases, it is increasingly relevant to acknowledge their potential for hepatotoxicity. Our goal is to increase awareness of this entity and review the literature.
An Unusual Case of CD34-Negative and PDGFR-A Mutation–Positive Inflammatory Fibroid Polyp (Poster No. 59)
Inflammatory fibroid polyps (IFPs) are rare benign mesenchymal neoplasms of the gastrointestinal tract. They commonly occur in the gastric antrum but can rarely occur in the jejunum. We describe an unusual case of a jejunal IFP that was negative for CD34 but showed PDGFR-A gene mutation. A 51-year-old African American man presented with abdominal pain and episodes of bilious, nonbloody vomiting. Imaging studies revealed an intussusception of the small bowel. Surgical resection of distal jejunum was performed. Gross examination showed an intraluminal 5 × 2.5 × 1.5-cm large ulcerated pedunculated polyp with tan-pink and hemorrhagic glistening cut surface. Microscopic examination showed an ulcerated, submucosal polypoid lesion with stellate fibroblastic cells, edema, and prominent inflammatory cell infiltration, with abundant eosinophils and granulation tissue–like vessels. No perivascular concentric fibroblastic proliferation (onion skinning) was identified. The stromal cells were positive for vimentin and negative for CD34, S100, EMA, DOG1, and CD117. The proliferation index as assessed by Ki-67 was <5%. PDGFR-A gene mutation was identified by polymerase chain reaction. IFPs, typically, are submucosal proliferations of stellate mesenchymal cells with a distinct perivascular concentric (onion skin) pattern and an inflammatory infiltrate rich in eosinophils. The mesenchymal cells are positive for CD34. The tumors show PDGFR-A gene mutation. Our case is unusual because, although it showed mesenchymal proliferation with an eosinophil-rich inflammatory infiltrate, it lacked the characteristic perivascular pattern, was negative for CD34, and showed PDGFR-A mutation. This appears to be a rare histologic variant of PDGFR-A–driven mesenchymal tumors.
Diffuse Intestinal Lipomatosis: A Rare Pathologic Diagnosis (Poster No. 60)
Lipomas in the gastrointestinal tract are usually small, solitary, asymptomatic masses that are detected incidentally during a colonoscopy or laparoscopy. Diffuse intestinal lipomatosis is a very rare condition, characterized by submucosal accumulation of lobules of mature adipose tissue diffusely involving the entire colon. It affects people of all ages and has a variety of clinical presentations. The exact etiology of diffuse intestinal lipomatosis is not known. We present a case of a 79-year-old man admitted for multiple fractures due to seizures. The patient was conservatively treated for his fractures, but developed acute abdominal pain. The physical examination was significant for abdominal distension, but a colonoscopy failed to establish a reason for the distention and pain. Our patient underwent exploratory laparotomy and subtotal colectomy. On gross examination of the intestine, the viable large bowel was massively distended from the cecum to the descending colon. The mucosa was pale with focal hyperemia. No distinct masses or lesions were identified except multiple diverticula. Microscopic sections taken every 10 cm revealed numerous diverticula as well as lobules of adipose tissue throughout the colon. The adipocytes were present transmurally; however, they were predominantly in the submucosa. Oil red O stain highlighted the transmural adipocytes present within the bowel wall. Although the prognosis for diffuse intestinal lipomatosis is good, perforation and hemorrhage are 2 of the most serious complications associated with this disease and have dire consequences if it is not properly diagnosed. Diffuse intestinal lipomatosis should not be overlooked in the differential diagnosis of acute abdominal pain.
A Report of a Unique Case of Recurrent Schwann Cell Hamartoma (Poster No. 61)
Mucosal Schwann cell hamartoma is a rare benign mesenchymal proliferation that can arise anywhere in the colorectum. It is not inherited syndrome related, with limited follow-up data; there have been no previous cases of patients with recurrent Schwann cell hamartoma reported. We report a unique case of a recurrent mucosal Schwann cell hamartoma in a male patient who first presented in 2003 with a discrete polyp in the descending colon that was referred to as schwannoma. We compared the histologic findings as well as ancillary studies from the earlier biopsy with those in the latest biopsy from the same part of the colon in 2016. We believe this is the same lesion, a recurrent mucosal Schwann cell hamartoma of the colon. To the best of our knowledge, this is the first report of a case of recurrent mucosal Schwann cell hamartoma. As this is a new entity, there is not enough literature covering it and its clinical behavior; it has always been thought to be nonrecurrent. However, this is a unique case that shows that this rare lesion can be recurrent.
A Unique Case of Appendiceal Mixed Adenoneuroendocrine Carcinoma (Poster No. 62)
Appendiceal mixed adenoneuroendocrine neoplasms are rare neoplasms, with the largest case series describing 63 cases. Appropriate pathologic classification is crucial for accurate prediction of outcomes. We present a case of a 43-year-old woman with a 2-month history of abdominal pain with bilateral ovarian masses, omental caking, and ascites. Ascites fluid cytology showed high-grade adenocarcinoma with signet ring cell and mucinous differentiation of uncertain origin. Hysterectomy and tumor debulking was performed 5 months after presentation, status post 4 rounds of chemotherapy. Bilateral 7-cm solid ovarian masses and a 4-cm, firm, gray appendiceal mass were identified. On histology, the appendix showed an infiltrative pattern of single tumor cells with goblet and signet ring cells and small foci of cribriform glands within a desmoplastic stroma with destruction of the wall. Immunohistochemistry showed positive staining for neuroendocrine markers and SATB2. Molecular studies revealed an NRAS mutation with preserved DNA mismatch repair proteins. Histology of the ovarian and omental masses was similar to that of the appendiceal primary. The tumor is thought to arise from pluripotent intestinal epithelial stem cells with dual neuroendocrine and mucinous differentiation. The most common clinical presentations are abdominal pain with a palpable mass (50%) or symptoms of acute appendicitis (44%). Fifty percent of female patients have ovarian metastases at presentation. The majority of patients present at an advanced clinical stage, with a 5-year survival of 38%, versus 100% survival for classic goblet cell carcinoid tumors. Treatment regimens are similar to those of adenocarcinoma of the colon.
Solitary Fibrous Tumor Presenting as a Submucosal Colonic Polyp: A New Addition to the Family of Mesenchymal Polyps of the Gastrointestinal Tract (Poster No. 63)
Solitary fibrous tumor (SFT) is a rare fibroblastic neoplasm most often arising from the pleura and rarely in extrapleural locations, including the gastrointestinal tract. To the best of our knowledge, SFT has never been previously reported in the colon. We describe the first case of a SFT presenting as a submucosal polyp in the cecum and review the literature on SFTs in the rest of the tubular gastrointestinal tract. The literature was reviewed, and no prior case of SFT presenting as a solitary colonic polyp was identified. A 54-year-old asymptomatic man presented for elective screening colonoscopy where a 10-mm pedunculated polyp was identified in the cecum (Figure 27, A) and completely excised by snare polypectomy. Histologically, the colonic mucosa overlying the polyp was unremarkable, and a well-circumscribed spindle cell neoplasm arranged in short fascicles, blending with abundant collagenous stroma, was identified in the submucosa (Figure 27, B and C). On immunohistochemistry, the cells were positive for CD34, STAT6 (Figure 27, D), and CD99, supporting the diagnosis of SFT. Pertinent negative immunohistochemical stains included S100, EMA, SMA, MSA, CD31, factor XIIIa, CD117, and DOG1. The MIB-1 labeling index was low, with focal activity of ~1%. The patient is alive and well 1 year after polypectomy. This report shows for the first time that SFT can also occur in the large intestine as a submucosal mesenchymal polyp and that complete endoscopic resection can successfully remove the polyp with promising short-term prognosis. SFT should be included in the differential diagnosis of submucosal mesenchymal polyps of the gastrointestinal tract.
Abdominal Actinomycosis Mimicking Colon Cancer (Poster No. 64)
Actinomycosis is a chronic infection caused by Actinomyces israelii involving the cervicofacial, thoracic, and abdominopelvic regions. Diagnosis becomes crucial, as the management of mimickers such as colonic neoplasms, Crohn disease, and tuberculosis is very different. We report a case of a 52-year-old immunocompetent man who presented to the emergency room with right lower quadrant pain for 2 days. Computed tomography imaging revealed an enhancing cecal mass compatible with colorectal carcinoma and thickening of the appendix consistent with acute appendicitis. Colonoscopy showed a mass concerning for malignancy and biopsies demonstrated mild active colitis. A right hemicolectomy was performed and a mass measuring 3.5 × 2.7 cm was identified in cecum located 2.1 cm from the appendiceal orifice. Microscopic examination of the mass revealed marked ulceration, cryptitis, crypt abscesses, necrotizing granulomatous inflammation (Figure 28, A through C), and no evidence of dysplasia or carcinoma. AFB and GMS stains were negative. Microscopic examination of the entire appendix exhibited similar findings along with the presence of filamentous bacteria consistent with Actinomyces sp (Figure 28, D). The patient's infection resolved after receiving weeks of intravenous penicillin followed by oral amoxicillin. This case emphasizes the importance of submitting the entire appendix for evaluation in the presence of necrotizing granulomatous inflammation and negative stains for microorganisms. Accurate diagnosis of Actinomyces sp in this setting is essential for proper patient management.
A Case of Entamoeba histolytica in an Asymptomatic Patient From a Nonendemic Area (Poster No. 65)
Entamoeba histolytica is a parasite that causes amoebic colitis, amoebic dysentery, and amoebic liver abscess. Ten percent of the global population and up to 60% of children in endemic area show serologic evidence of infection. Amebiasis is usually uncommon in the United States, except in returning travelers, immigrants, men who have sex with men, and institutionalized persons. The usual presentation is amoebic colitis followed by amoebic dysentery. Amoebic liver abscess, the most common extraintestinal presentation, can rupture and lead to empyema and acute abdomen. We present a case of a 57-year-old man who presented for a routine screening colonoscopy that revealed a 3-mm sessile polyp with inflamed and ulcerated cecum. Microscopic examination showed 15–28-μm, loosely aggregating, round to ovoid-shaped structures with vacuolated cytoplasm and relatively small, round nuclei with prominent cell borders and erythrocytosis, which highly suggested the diagnosis of E histolytica (Figure 29). Additional stool testing and EIA with serologic IgG testing were recommended for confirmation. Stool examination of ova and parasite was negative, but serology test result was positive. In conclusion, although E histolytica is uncommon in the United States, we present a case of asymptomatic amoebic colitis in a patient with no remarkable travel history to emphasize the importance of identifying micrometer-sized organisms in asymptomatic patients who are not from endemic areas.
Esophageal Pyogenic Granuloma: A Case Report and Review of the Literature (Poster No. 66)
Pyogenic granuloma (PG) is a lobular capillary hemangioma mainly found in the skin and oral mucosa, but rarely described in the esophagus. We report the case of a 66-year-old man who presented with retrosternal pain. Endoscopic studies showed a 28-mm hyperechoic polypoid mass located at the distal esophageal mucosa (Figure 30, A). The patient underwent endoscopic resection, and polypectomy revealed a neoplastic proliferation of capillaries with a lobular architecture (Figure 30, B), edematous stroma, and variable amount of inflammatory infiltrate (Figure 30, C). Special stains for fungus showed rare yeasts and several nonseptate pseudohyphae morphologically compatible with Candida spp on PAS and Gomori stains (Figure 30, D)) that involved the epithelial surface and submucosa. Findings were consistent with those of esophageal PG associated with Candida spp. To the best of our knowledge, only 13 cases of esophageal PG have been reported in the English literature. The median age of the patients was 57 years (15–78 years) with a male predominance (6:1). Half of the patients had symptoms at presentation, with the most common being dysphagia (28.6%), followed by retrosternal pain (21.4%); the other half were asymptomatic. The median size was 10 mm (4–28 mm). Four patients had associated severe esophagitis, Barrett esophagus, squamous cell carcinoma, and Helicobacter pylori infection. It is important to remember that PG can be found in the esophagus, can be associated with other benign processes such as Candida infection, and is one of the differential diagnoses of small vascular neoplastic proliferations that can mimic malignancy.
Heterogeneity of Chymotrypsin Immunoreactivity in Acinar Cell Carcinomas of Pancreas (Poster No. 67)
Context: Pancreatic acinar cell carcinoma (ACC) has variable pattern and extent of immunoreactivity with chymotrypsin (CHY), presenting a diagnostic challenge. This study evaluates the spectrum of CHY immunoreactivity in ACC, mixed acinar-neuroendocrine tumors (ACCNETs), and pancreatoblastoma (PB).
Design: Retrospective review of 9 cases (ACC, n = 5; ACCNET, n = 2; PB, n = 2) was performed between 2000 and 2016. A tissue microarray was made from tumor/normal tissue with a minimum of 3 cores from different regions of the lesion and stained with antibodies to CHY, synaptophysin (SYN), chromogranin (CHR), and Ki67. Positive CHY immunoreactivity was further stratified according to intensity, percentage of positive tumor cells, and staining pattern. SYN and CHR immuno-reactivity were assessed as negative or positive, including the positivity percentage. The proliferative index was calculated with Ki67 stain.
Results: All cases of ACC and ACCNET stained for CHY. The staining pattern varied from membranous (n = 4) to membranocytoplasmic (n = 3). In 5 ACCs, all tumor cores were CHY positive, with significant variation in staining of different cores of the same lesion in 3 ACCs ranging from weak to strong with 5%–100% of tumor cells staining. ACCNET showed strong diffuse SYN and CHR staining with Ki-67 indexes of 10% and 90%. Both ACCNET cases had weak focal membranous CHY staining in 2 of 5 cores and 4 of 5 cores, with 1%–20% of tumor cells staining in positive cores. All cases of PB were negative for CHY.
Conclusions: There is a considerable intratumoral and intertumoral heterogeneity in pattern, intensity, and extent of CHY stain in pancreatic ACC and ACCNET, representing a diagnostic challenge, particularly with limited tumor sampling.
Distinctive Histopathology in a Patient With Hepatic LECT2 Amyloidosis: A Case Report and Review of the Literature (Poster No. 68)
Amyloidosis is a protein-deposition disorder caused by pathologic accumulation of fibrils, leading to organ dysfunction. The newest protein is leukocyte cell–derived chemotaxin 2 amyloid (ALECT2), which shows ethnic predilection for Hispanics, individuals from the Middle East, and other minority groups. We report a case of a 71-year-old Persian man with history of hepatitis B and resected hepatocellular carcinoma who presented with acute onset jaundice and abnormal liver function test results. Liver biopsy performed for diagnostic workup revealed hepatic ALECT2 with distinct signet ring–shaped proteinaceous deposits infiltrating hepatic parenchyma, mimicking epithelioid/histiocytic neoplasm. The infiltrative spherular material was positive for Congo red and negative for pankeratin stains. Amyloid protein analysis by liquid chromatography tandem mass spectrometry identified a peptide profile indicative of ALECT2. This is the first documentation of such distinct morphology for hepatic ALECT2 compared with the previously described deposition of amorphous material around periportal parenchyma and central venules. Although ALECT2 accounts for the second most common cause of hepatic amyloidosis, only limited cases are reported in the literature and little is known about etiology, patient management, and role of transplant as curative option. Unlike light chain amyloidosis, bone marrow biopsy does not appear warranted. Liver transplant has never been performed, precluding determination of its curative potential, and recurrence is a theoretical concern because LECT2 is a wild-type protein that accumulates secondary to LECT2 gene upregulation. In summary, ALECT2 is an emerging disorder with relatively high prevalence that deserves increased awareness and accurate recognition to better understand its pathogenesis, clinical significance, and therapeutic strategies (Figure 31, A and B).
Hepatic Kaposi Sarcoma Presenting With Peliosis-like Lesion (Poster No. 69)
Kaposi sarcoma (KS), a low-grade vascular neoplasm, is caused by human herpesvirus 8 (HHV-8)/KS-associated herpesvirus. The most common presentation is multicentric skin involvement; however, KS can present with mucosal and visceral lesions, often in HIV-positive patients with low CD4 counts (<50/μL). We report a case of a 34-year-old HIV-positive man not currently on HAART therapy, with CD4 count of 17/μL, who presented with dyspnea and multiple violaceous skin lesions on the scalp, anterior chest, and left cheek, which were confirmed to be KS when biopsied. Upper endoscopy showed candidal esophagitis and multiple red esophageal, gastric, and duodenal polyps. Colonoscopy also revealed polyps in the ascending, transverse, descending, and sigmoid colon and rectum; biopsies revealed KS characterized by atypical HHV-8–positive spindle cell proliferation, forming slitlike spaces. Computed tomography core-needle biopsy of a hypodense area in the right lobe of the liver revealed cystically dilated spaces displaying a peliosis-like appearance, lined by cells positive for HHV-8 and CD31. HHV-8 and CD31 were also diffusely and strongly expressed by an atypical spindle cell proliferation expanding the portal tracts. It is important to consider disseminated KS in HIV-positive patients, especially those with very low CD4 counts. This case study highlights the importance of recognizing a peliosis-like pattern of hepatic KS confirmed by positive HHV-8 and CD31 immunostains.
(Poster No. 70)
Polypoid Gastric Heterotopia and Brunner Gland Hyperplasia Causing Duodenal Obstruction (Poster No. 71)
Gastric heterotopia is the presence of mature gastric tissue outside the stomach, with Meckel diverticulum being the most common site. It is a rare finding in the first or second part of the duodenum and can be either congenital or acquired. Although often incidental, it may cause obstruction, bleeding, ulceration, intussusception, and even intestinal perforation. Our patient, a 53-year-old woman, presented with nausea and vomiting. An esophagogastroduodenoscopy revealed a 4.0-cm tan, cauliflower-like mass in the second portion of the duodenum, obstructing 70% of the lumen. The patient underwent biopsy of the mass followed by Whipple procedure. Histologic examination of the mass in the first part of the duodenum showed polypoid gastric heterotopia, composed of fundic-type mucosa with parietal and chief cells, associated with changes of reactive gastropathy. Florid polypoid Brunner gland hyperplasia was also present in the second part of the duodenum. The resected proximal pancreas showed extensive pancreatic intraepithelial neoplasia grades 1B and 2 involving pancreatic margin of resection. It is important to differentiate gastric heterotopia from gastric metaplasia; the latter is defined by the presence of superficial foveolar epithelium in the duodenum and is usually secondary to acid peptic disease caused by H. pylori infection. Gastric heterotopia may either be composed of predominantly foveolar epithelium with full mucosal thickness (congenital or acquired) or foveolar epithelium with oxyntic glands (congenital only). This case study highlights that congenital gastric heterotopia may present later in life as an obstructive duodenal mass suspicious for malignancy and may require Whipple procedure.
Heterotopic Respiratory Mucosa in the Rectum: An Unusual Type and Site of Heterotopia in the Gastrointestinal Tract (Poster No. 72)
Heterotopia is the presence of histologically normal ectopic tissue outside of the original anatomic location. Although pancreatic and gastric heterotopias are common findings in the gastrointestinal tract, heterotopic respiratory mucosa (HRM) in the rectum is extremely rare and has only been reported twice previously. We are presenting, to our knowledge, the third case of HRM in the rectum. A 56-year-old man with a history of chronic diarrhea presented for routine colonoscopy where he was found to have multiple hyperplastic polyps and tubular adenomas in the ascending, descending, and sigmoid colon, as well as a rectal submucosal nodule for which he underwent flexible sigmoidos-copy with endoscopic ultrasound and endoscopic mucosal resection. Endoscopically, the nodule was hypoechoic, 2–3 mm in size, located in the submucosa, and did not appear to invade the muscularis propria. Microscopically, the nodule showed a multicystic complex lesion located in the submucosa, lined by ciliated pseudostratified columnar epithelium and surrounded by thin to moderately thick smooth muscle bundles and multiple lobules of seromucinous glands (Figure 32, A and B). There was associated acute and chronic inflammation. The rectum overlying the submucosal lesion was lined by congested and edematous colonic mucosa and demonstrated no connection with the underlying cystic lesion. HRM is a benign nonneoplastic lesion with unclear etiology. Pathologists and gastroenterologists should be aware of this entity and consider it in their differential diagnosis for a submucosal nodule in the rectum, keeping in mind that neoplastic processes can also develop in this location.
The Incidence of the Steatohepatitic Variant of Hepatocellular Carcinoma in Patients With End-Stage Alcoholic Liver Disease (Poster No. 73)
Context: The steatohepatitic variant of hepatocellular carcinoma (SH-HCC) was recently described, and the histologic features include steatosis, hepatocyte ballooning degeneration, Mallory-Denk bodies, inflammation, and pericellular fibrosis. Previous studies have suggested an association between SH-HCC and underlying steatohepatitis. We investigated the incidence of SH-HCC in patients with liver failure secondary to alcoholic liver disease.
Design: The transplant database at a tertiary academic transplant center was queried for patients requiring liver transplant because of alcoholic liver disease between June 1999 and November 2015. All explants were reviewed by a single hepatic pathologist and assessed for activity of steatosis in background liver, presence of HCC, and histologic features of SH-HCC.
Results: A total of 206 of 926 patients (22%) were transplanted for alcoholic liver disease. Seven cases did not have slides available for review. Forty-eight of 206 alcoholic liver disease patients (23%) had HCC. Thirteen had multiple HCCs, and a total of 72 HCCs were available for review. Twelve showed 100% necrosis from treatment and were excluded. Nineteen of 60 (32%) had histologic features of SHHCC, including inflammation (n = 12), Mallory-Denk bodies (n = 14), pericellular fibrosis (n = 17), and ballooning (n = 18). Most cases of SHHCC showed all 4 features. Only 3 of 48 patients (6%) showed an active steatohepatitis; 10 of 48 (21%) had some component of steatosis in the background liver.
Conclusions: In comparison with other studies, we found a lower incidence of SH-HCC in patients transplanted for alcoholic liver disease. The lack of SH-HCC features may be related to abstinence from alcohol, as evidenced by the low incidence of active steatohepatitis.
Adenocarcinomas of the Lower Gastrointestinal Tract Fistulas Can Resemble Mismatch Repair–Deficient Mucinous Tumors (Poster No. 74)
Context: In adenocarcinomas of fistula tracts, origin and route of tumorigenesis is debatable. Upon encountering a cancer of perianal fistula with unexpected immunophenotype, we reviewed the morphology, immunoperoxidase, and mismatch repair status of adenocarcinomas involving fistula tracts of the lower gastrointestinal (GI) tract.
Design: Search of our institutional archives from the last 20 years resulted in 55 cases of lower GI adenocarcinomas with a fistula. Those without direct involvement of the fistula or when a fistula extended into genitourinary or upper GI tract were removed. The remaining 19 cases were adenocarcinomas involving fistulas of colorectal (CR) or perianal region. In cases with available material, immunostainings for CK7, CK20, and CDX2 and mismatch repair proteins (MMRs) were performed and reviewed, respectively.
Results: Patient age ranged from 33 to 90 years. Five had prior colectomy due to inflammatory bowel disease, carcinoma, or diverticulitis. Sixteen of the 19 cases were mucin rich, containing epithelial clusters with signet ring cells, resembling microsatellite (MS) instability high-mucinous tumors. Twelve cases were stained and strongly positive for CDX2 and CK20, but negative for CK 7; all 7 cases with available MMRs had retained expression, keeping with the expected profile for microsatellite stable CR cancer.
Conclusions: Tumors arising in fistulas of lower GI tract/perianal region have a tendency to be mucin rich and can resemble mucin-rich MSI-high tumors. But their expression of keratins and MMRs is in keeping with classic MS-stable tumors. Whether this interesting morphology can be attributed to the inflammatory milieu or adenomatous metaplasia of fistula tract may need further investigation.
Mucinous Gastric Carcinoma With a Micropapillary Component: A New Entity in the Stomach Not Previously Described (Poster No. 75)
Micropapillary carcinoma (MPC) is a rare variant of carcinoma that has been described in the stomach and other organs. It is characterized by a distinct histologic pattern consisting of small tumor cell nests with inverse nuclear polarization that are present within lacunar spaces. In most cases, this type of carcinoma has been associated with a poor prognosis. MPC has been reported in tubular or papillary subtypes of gastric tumors, but not, to the best of our knowledge, in mucinous gastric tumors. Herein, we describe a case of a gastric mucinous carcinoma with an MPC component, the first of its kind reported in the stomach or any organ outside the breast. Our patient, a 69-year-old man, presented with anemia and on endoscopy was found to have a 1.7-cm gastric ulcer. The patient underwent a partial gastrectomy. The mucinous tumor was moderately differentiated, with an MPC component consisting of small nests floating within mucin pools. Metastatic carcinoma with micropapillary features was present in 1 of 18 lymph nodes. The tumor was positive for epithelial membrane antigen in both the micropapillary and conventional areas and negative for CK7, CK20, CA-125, synaptophysin, and chromogranin. Although the mucinous subtype of our case in association with a micropapillary component is unique, our patient's tumor shares similar features to other reported cases of micropapillary gastric carcinoma in its presentation with lymph node metastasis, focality of the micropapillary component, and immunohistochemical profile.
Epstein-Barr Virus–Associated Lymphoepithelioma-like Intrahepatic Cholangiocarcinoma in the Background of IgG4-Related Pattern of Sclerosing Cholangitis (Poster No. 76)
Epstein-Barr virus (EBV)–associated lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-IC) is a rare disease. We present the second domestic case of EBV-associated LEL-IC, furthermore distinctly complicated by a background of IgG4-related pattern of sclerosing cholangitis (IgG4-SC). A 34-year-old man with a history of ulcerative colitis was discovered to have 2 liver lesions on MRI, involving segments 8 (2.6 × 2.3 cm) and 1 (1.6 × 1.5 cm). Serum IgG4 levels were elevated (212.0 mg/dL). Liver biopsy demonstrated atypical bile ducts in the background of lymphoplasmacytic and neutrophilic inflammation with dense stromal fibrosis (Figure 33, A). IgG4/IgG immunohistochemical stains showed increased IgG4-positive plasma cells (Figure 33, B). An initial diagnosis of IgG4-SC was made. After immunosuppressive therapy, serum IgG4 levels normalized to 75.0 mg/dL. However, the 2 liver lesions became confluent on repeat MRI, measuring 4.2 × 6.3 × 3.5 cm. EBV-encoded RNA in situ hybridization (EBER-ISH) was subsequently performed. Significantly, the atypical biliary glandular component showed strong nuclear staining with EBER-ISH, whereas the background inflamma-tory cells were negative (Figure 33, C). Right hepatectomy revealed a 7.0 × 6.5 × 5.0-cm solitary mass. A final diagnosis was rendered as infiltrating moderate to poorly differentiated LEL-IC, associated with EBV infection in a background of IgG4-SC (Figure 33, D). Our case is unique as EVB-associated LEL-IC has never been reported concomitantly with IgG4-SC. A pattern of dense inflammatory infiltrate in a liver biopsy of a mass lesion in association with elevated serum IgG4 should raise suspicion for this interesting and rare entity of EVB-associated LEL-IC in a background of IgG4-SC.
Is β-Catenin Useful in the Diagnosis of Colon Polyps? (Poster No. 77)
Context: Colon cancer is one of the leading causes of cancer-related deaths in the United States. Regular screening colonoscopies every 10 years after the age of 50 are crucial in identifying precancerous lesions. Screening intervals are dependent on the types of polyps found on biopsies. Although hyperplastic polyps are not associated with malignancy, tubular adenomas and sessile serrated adenomas can develop into cancer. Many studies have documented interobserver variability in diagnosing sessile serrated adenomas and hyperplastic polyps, as they are both serrated. This is an important distinction because a small hyperplastic polyp will not change the screening interval, but the diagnosis of a small sessile serrated adenoma without dysplasia will require a colonoscopy in 5 years. Previous studies have shown that β-catenin stains the nucleus of sessile serrated adenomas, whereas hyperplastic polyps do not demonstrate nuclear staining of β-catenin.
Design: Five hyperplastic polyps, 5 tubular adenomas, and 10 sessile serrated adenomas were selected. The diagnoses were confirmed by a consensus consisting of 3 pathologists. All cases were stained with β-catenin.
Results: Both the sessile serrated adenomas and the tubular adenomas had foci of β-catenin nuclear staining. The nuclear staining patterns of the sessile serrated adenomas were more intense compared with the nuclear staining of the tubular adenomas. Hyperplastic polyps exhibited only membranous staining.
Conclusions: β-Catenin is useful in distinguishing sessile serrated adenomas from hyperplastic polyps, especially in right-sided lesions. However, it is not as advantageous in differentiating sessile serrated adenomas from tubular adenomas because the nuclear staining pattern is similar.
Histopathologic Changes in the Gastroduodenal Mucosa of Children With Functional Dyspepsia (Poster No. 78)
Context: Functional dyspepsia (FD) is a gastrointestinal disorder that affects numerous children with abdominal pain. Many of these children undergo endoscopic mucosal biopsies. We retrospectively studied the biopsies of these children to elucidate the histopathologic changes of gastroduodenal mucosa with special emphasis on mast cell (MC) and eosinophil numbers.
Design: We had 42 patients in the study from whom gastric antral and duodenal biopsies were available as formalin-fixed, paraffin-embedded tissue. We reviewed the H&E-stained slides and performed immunohistochemistry for tryptase to determine eosinophil and MC densities, respectively. The eosinophils were counted in the lamina propria of 5 high-power fields (hpf), using ×40 objective. The same strategy was used for tryptase-immunostained slides for counting the MCs.
Results: We found that the duodenum showed no evidence of chronic inflammation in 81% of patients, a median peak eosinophil count of 19/hpf, and a median peak MC count of 22/hpf. Notably, 81% of the patients had duodenal peak density of MC >15/hpf. The histopathologic features of the gastric antral mucosa comprised no evidence of inflammation in 52.4% of patients, mild chronic inflammation in one-third of subjects, a median peak eosinophil count of 9.5/hpf, and a median peak MC count of 18/hpf. Interestingly, 62% of the patients had antral peak density of MC >15/hpf. Further, one-third of FD patients demonstrated a peak eosinophil count >11/hpf in antrum and >20/hpf in duodenum.
Conclusions: A majority of children with FD lack active or chronic inflammation, but MC density is increased in >50% and eosinophil density is increased in more than one-third of patients.
Unexpected Finding of Globular Hepatic Amyloidosis Patient for Nonalcoholic Steatohepatitis Evaluation: Extensive Workup Warranted? (Poster No. 79)
Globular hepatic amyloidosis (GHA) is a rare pattern of amyloid deposition recognized within the literature; however, the etiology and clinical significance remain relatively unclear. We present a case of GHA in a Hispanic 66-year-old obese woman with multiple comorbidities who presented for evaluation of steatohepatitis due to persistent mild elevations of ALT and AST and elevated GGT. Antinuclear and anti–smooth muscle antibodies were negative. HCV antibodies were positive with an undetectable HCV viral load. Iron storage studies, ceruloplasmin, α1-antitrypsin, hepatitis viral panel, and HIV studies were within normal limits. The liver ultrasound showed diffuse steatosis and early cirrhosis. The patient denied herbal supplementation or alcohol use with no recent changes in medication. Given these findings, an ultrasound-guided random needle biopsy of the liver was performed. The core biopsy revealed perivenular and periportal hepatocytes with extrahepatocellular and intrahepatocellular globules of pale, eosinophilic, amorphous material compressing hepatocyte nuclei. The globules were pale blue on trichrome, resistant to diastase digestion appearing pale pink on PAS-D, and exhibited apple-green birefringence on Congo red stain with polarized light microscopy. They demonstrated positivity for amyloid A, focal positivity for ubiquitin, and staining of λ without κ positivity on in situ hybridization. The background liver showed stage 2 steatohepatitis with preserved bile ducts. A diagnosis of GHA was rendered. Literature suggests GHA associated with early systemic amyloidosis, and awareness of this entity is importation for recommendation of further studies. Long-term follow-up of these patients may be warranted for confirmation (Figure 34).
Undifferentiated Carcinoma of the Pancreas With Osteoclast-like Giant Cells Reported in an Asymptomatic Patient: A Rare Case (Poster No. 80)
Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UC-OGC) is a rare malignancy constituting less than 1% of pancreatic nonendocrine neoplasia. It comprises mononuclear, pleomorphic, and undifferentiated cells as well as osteoclast-like giant cells. We describe a case of UC-OGC with likely epithelial origin. A 69-year-old man with a history of abdominal aortic aneurysm was discovered on CT angiogram to have a lesion in the body of the pancreas (Figure 35, A). Upon resection, a 3.5-cm heterologous mass was identified that was predominated by pleomorphic spindle cells, hemorrhage, and abundant hemosiderin pigment. Osteoclast-like giant cells were present individually and in clusters and were admixed within a background of numerous foamy histiocytes (Figure 35, B). With immunohistochemical staining, occasional pleomorphic spindle cells and glandular structures were immunoreactive with CK AE1/AE3 and CK Cam5.2. A spindle cell sarcomatous component was diffusely immunoreactive with vimentin. Six months post resection, the patient is in good health with no signs of recurrence. This is the first case of UC-OGC discovered incidentally on CT angiogram. Undifferentiated pancreatic carcinomas have significant histologic overlap with UC-OGC. Although undifferentiated pancreatic carcinomas have a poor prognosis, with average survival being less than 1 year, UC-OGC has a far better prognosis, with some cases being curative with complete resection of the tumor. It is important, therefore, to differentiate UC-OGC from other undifferentiated pancreatic malignancies because of the relative improvement in survival. Further study may help establish treatment modalities and possible molecular biomarkers.
Ghrelin Expression and Microsphere Distribution in a Porcine Model Post Bariatric Radioembolization (Poster No. 81)
Context: Infusion of yttrium-90 microspheres into arteries supplying the gastric fundus (bariatric radioembolization [BAE]) has shown promise in previous preclinical investigations as a possible minimally invasive alternative to bariatric surgery. The goal of BAE is to reduce hunger by decreasing the number of ghrelin-producing cells (GPCs). In this study, we documented pathologic findings in a porcine model after BAE and analyzed the microsphere distribution and ghrelin expression in different gastric regions.
Design: One swine treated using BAE was euthanized; the stomach was harvested, examined, fixed, mapped, and entirely submitted for microscopic examination. H&E sections were scanned using a Leica whole slide scanner and microspheres were counted on each histologic section. Ghrelin stain was performed on all sections and the density of GPCs was evaluated by counting in 10 different fields at 20× magnification; an average value for each section was recorded. Pearson correlation was used as a measure of association between ghrelin and microsphere density.
Results: Excised stomach showed 2 small healed superficial gastric erosions, mucosal atrophy, and submucosal fibrosis in the right side of the gastric fundus. Mapping the untreated portions of the stomach identified that the highest ghrelin expression was located in the fundic area, with less expression in other gastric regions. Analyses revealed that microsphere density correlated negatively with ghrelin expression in the treated portion of the stomach fundus (r = −0.95, P = .001).
Conclusions: Increased microsphere density correlates with decreased ghrelin expression in treated areas of the porcine stomach. These data histologically confirm a dose-response relationship for BAE, supporting previous preclinical investigations demonstrating weight loss.
Robust Nuclear Expression of Hes1 Is a Sensitive Immunohistochemistry Marker for Neuroendocrine Neoplasm From Gastrointestinal Tract and Pancreas (Poster No. 82)
Context: Neuroendocrine tumors (NETs) are uncommon tumors. Immunohistochemistry is often used to help to establish the diagnosis, with chromogranin considered to be a relatively specific marker, although its suboptimal sensitivity could cause diagnostic challenges. Both chromogranin and synaptophysin (considered more sensitive although less specific) have cytoplasmic staining pattern, which could be challenging to interpret in some less than optimal specimens. In this study we identified Hes1 to be a very sensitive marker in neuroendocrine neoplasms from gastrointestinal tract and pancreas with a unique nuclear staining pattern.
Design: Hes1 immunohistochemistry was performed in a total of 21 cases of NETs, including 13 cases from the gastrointestinal tract and 8 cases of pancreatic NETs. Intensity (scored from − to +++) and distribution of the staining of Hes1 were evaluated.
Results: Representative H&E and strong Hes1 nuclear staining of NETs from small intestine (Figure 36, A and B) and pancreas (Figure 36, C and D) are shown. Hes1 demonstrated uniform robust (+++) nuclear staining pattern in the tumor cells of all NETs (21 of 21). In the gastrointestinal tract, inflammatory cells in lamina propria and basal crypt cells were positive for Hes1 (++). In pancreas, acinar showed a mixed expression pattern (+/−), and islet cells showed robust positive staining (+++) as well.
Conclusions: We identified Hes1 as a neuroendocrine lineage marker with robust nuclear expression pattern in NETs from gastrointestinal tract and pancreas. Hes1 has the potential to be a new and very sensitive immunohistochemistry marker for NETs in diagnostically challenging cases.
Recurrence of Lysosomal Acid Lipase Deficiency in a Liver Allograft (Poster No. 83)
We present an interesting case of recurrent lysosomal acid lipase deficiency (LAL-D) in the liver allograft. LAL-D is an ultrarare disease, characterized by LAL gene (LIPA) mutation, causing accumulation of cholesteryl esters especially in the liver, leading to liver failure, atherosclerosis, and premature death. LIPA activity levels determine whether the patient presents early in life or later in adolescence/adulthood with the above-mentioned symptoms. A 22-year-old woman who underwent liver transplantation (LT) 5 years previously for LAL-D cirrhosis was admitted to our hospital with decompensated cirrhosis and septicemia. She was diagnosed with chronic rejection at an outside hospital and was being considered for another LT. However, her medical condition continued to deteriorate, complicated by acute kidney injury and pneumonia. At autopsy, the liver allograft showed micronodular cirrhosis with microvesicular steatosis and cholestasis; enlarged kidneys with vacuolated tubular epithelium; calcified adrenals, a pathognomonic feature of LAL-D; and bilateral pneumonia. The unique finding of microvesicular steatosis (Figure 37, A; PAS reaction) and cirrhosis raised suspicion of recurrent LAL-D in the allograft. This was confirmed by positive immunostaining of LAMP1 and LAMP2 (lysosome-associated membrane protein; Figure 37, B; LAMP2) as well as blood lysosomal acid lipase level of 7.5 nmol/h/mg (normal 79.0–695.6). To our knowledge, this is the first described case of LAL-D recurrence in an allograft. It is possible that cirrhosis secondary to LAL-D recurrence overshadowed rejection changes. In patients transplanted for LAL-D who develop allograft dysfunction, recurrence of the disease should be considered, especially as treatment is now available.
Jejunal Anisakiasis With Pseudotumor and Volvulus: A Case Study and Clinicopathologic Characterization (Poster No. 84)
Gastrointestinal anisakiasis, caused by nematodes of the Anisakis genus present in seafood, is a rare cause of acute abdomen in North America. However, its incidence is rising because of globalization and spread of international cuisine. We present a case of a previously healthy 29-year-old man who presented with 1 day of severe abdominal pain. Imaging was suggestive of a jejunal volvulus around a mass and there was no evidence of intestinal obstruction. The patient reported no recent consumption of seafood; however, he had 2 prior episodes of crampy abdominal pain, the first upon travel to Europe. Histologic examination revealed an eosinophilrich fibroinflammatory lesion surrounding a degenerating parasite. A review of the literature reveals 2 distinct presentations of gastrointestinal anisakiasis: an acute presentation upon hours of seafood consumption, where nematodes can often be extracted from the stomach by endoscopy, and a more prolonged course of abdominal pain resulting in a mass-forming lesion, usually located in the distal small bowel wall, that can clinically be mistaken for a tumor. This pseudotumor is composed of eosinophilic microabscesses surrounding a nematode with bilateral Y-shaped lateral cords in the cross section of its body. This is the first reported case of intestinal anisakiasis presenting with volvulus and no evidence of obstruction. Intestinal anisakiasis should be considered in the differential diagnosis of volvulus and mass-forming intestinal lesions.
Rare Presentation of a Pancreatic Lymphoepithelial Cyst Mimicking a Gastric Neoplasm (Poster No. 85)
Pancreatic lymphoepithelial cyst, a benign cyst commonly found incidentally in middle-aged men, accounts for approximately 0.5% of all pancreatic cysts. It is lined by squamous epithelium, surrounded by lymphoid tissue with prominent follicles, and filled with keratin debris. These histologic components are seen on cytologic examination. A sharp distinct cyst from the pancreas is diagnostic on radiologic studies. However, distinction from other tumors of the pancreas and other closely associated organs can be challenging by radiologic and cytologic studies. This case involves a 55-year-old Hispanic woman with right upper quadrant abdominal pain who had an upper endoscopy and ultrasound showing a 2.6-cm subepithelial mass originating from the stomach, abutting the distal pancreas, and suspicious for gastrointestinal stromal tumor on gastric biopsy. A fine-needle aspiration of the lesion showed numerous anucleated squamous cells with a background of histiocytes, lymphoid tissue, benign-appearing glandular epithelium, and no evidence of malignancy. Thus, a differential diagnosis of benign cysts including lymphoepithelial cyst was given. A distal pancreatectomy with a gastric wedge and splenectomy revealed a pancreatic tail 3.5-cm cystic mass adherent to the gastric serosa with extension into the gastric mucosa. Histology was consistent with a pancreatic lymphoepithelial cyst with evidence of rupture (Figure 38). The granulomatous reaction extending into the gastric wall with extensive fibroblastic proliferation likely mimicked a gastric gastrointestinal stromal tumor (Figure 38). Although pancreatic lymphoepithelial cyst is a relatively poorly recognized lesion and rarely reported in women, cytologic studies can establish the diagnoses and avoid extensive surgical intervention.
Gastrointestinal Stromal Tumor Presenting as Enlarging Complex Pelvic Mass (Poster No. 86)
Gastrointestinal tract mesenchymal tumors can be asymptomatic and discovered incidentally. They are often associated with nonspecific gastrointestinal tract symptoms unless they ulcerate or grow to cause pain, obstruction, or even intussusception. Uncommonly, intestinal perforation can also occur. We present a case of a 44-year-old woman with endometriosis who presented with the complaint of abdominal pain. Imaging revealed an air-containing complex pelvic mass adjacent to the lower uterine segment that did not appear to communicate with the colon or the small intestine. Based on the clinical history of endometriosis and the radiologic findings there was suspicion of a gynecologic tumor. Subsequent MRI of pelvis showed the ovarian mass was enlarging and lobulated solid and centrally cystic with internal locules of air. Radiologically the origin of the tumor could not be ascertained as gastrointestinal or gynecologic. The patient underwent total abdominal hysterectomy with en bloc removal of a portion of jejunum. Grossly, the hysterectomy specimen had an intestinal segment adherent to the posterior wall of the uterus; the intestinal wall was perforated. On low power, spindle cell neoplasm was seen involving the muscularis propria of small bowel, fallopian tube, and myometrium with high mitotic figures and focal necrosis. Spindle cells were also present in the ovarian cystic content. On high power, the cells had pleomorphic nuclei and a moderate amount of eosinophilic cytoplasm. Immunohistochemistry was positive for CD117, vimentin, DOG1, and CD34. In summary, this case shows gastrointestinal tumor can clinically present as gynecologic malignancy, which may be difficult to determine radiologically (Figure 39).
Colonic Cryptococcal Infection as the Initial Manifestation of Disseminated Cryptococcosis in an AIDS Patient (Poster No. 87)
Cryptococcus neoformans is a major opportunistic fungal pathogen in patients with acquired immunodeficiency syndrome (AIDS). Disseminated cryptococcosis usually manifests as pneumonia or meningoencephalitis, which is fatal if left untreated. Gastrointestinal cryptococcosis is only rarely reported and mainly identified post mortem. Herein we report a case of colonic cryptococcal infection as the initial manifestation of disseminated cryptococcosis in an AIDS patient who presented for routine colorectal cancer colonoscopy screening. Colonoscopy revealed a single 3-mm transverse-colon polyp, which was removed. H&E staining of the polyp revealed polypoid mucosa with focal granulomatous and mild acute inflammation and round to ovoid fungal organisms (Figure 40, A). Grocott methenamine silver stain highlighted many fungal organisms with occasional narrow-based budding (Figure 40, B). A mucicarmine stain highlighted mucopolysaccharide capsule (Figure 40, C). The overall findings were consistent with colonic C neoformans infection. Eleven days later, the patient presented with altered mental status. Cerebral spinal fluid India ink stain revealed encapsulated yeasts. Cerebral spinal fluid cryptococcal antigen screen, Gram stain, and culture were positive for C neoformans. Cryptococcal meningitis was diagnosed and the patient received systemic antifungal treatment. In summary, we report a rare case of colonic cryptococcosis diagnosed in a small colon polyp biopsy, which presented as the first manifestation of disseminated cryptococcosis in an AIDS patient.
Hepatolienal Fusion: A Rare Case Report (Poster No. 88)
Fusion of organs is rare. There have been such reports as splenogonadal fusion between spleen and left testicle or left ovary. We present a very rare case of fusion of liver with spleen. The patient is a 30-year-old African American man who presented to the emergency room because of a knife stab wound at left upper flank. A CT scan showed a grade II splenic laceration with extravasation. He was emergently taken to the operating room for an exploratory laparotomy and splenectomy. During the surgery, it was noticed that the patient's spleen was fused to the left lobe of his liver, forming a contiguous organ. The resected spleen and partial liver measured 10.3 × 5.4 × 1.7 cm and weighed 65 g. The capsule of the spleen was focally lacerated. Serial sectioning revealed a dark red splenic parenchyma with a portion of brown-tan surface discoloration measuring 3.5 × 1.5 × 1.2 cm. Histologically, the brown-tan tissue represented hepatic parenchyma, which was separated from spleen parenchyma by a thin fibrous capsule (Figure 41). No histologic abnormality was identified in either liver or spleen tissue except for splenic hemorrhage. To our knowledge, this is the second report of a hepatolienal fusion in the English literature. The first report was back in 1978. It was hypothesized that hepatolienal fusion is caused by developmental abnormality. The anatomic proximity of hepatic and splenic anlagen at about the 14th week of intrauterine development may be the basis leading to fusion between the developing left hepatic lobe and spleen.
An Unusual Case of Budd-Chiari Syndrome Caused by Idiopathic Hepatic Granulomatous Venulitis (Poster No. 89)
Budd-Chiari syndrome (BCS) is a rare condition caused by obstruction of the venous outflow of the liver. BCS caused by idiopathic hepatic granulomatous venulitis is exceedingly rare, with only one reported case in the literature. Here we report the second such case in the explant liver of a 26-year-old man. The patient presented with cryptogenic cirrhosis. Initial laboratory testing results were negative for hereditary, viral, or autoimmune liver diseases. Prior liver biopsy demonstrated chronic venous outflow obstruction. Subsequent hepatic venography showed alternating stenosis and dilation of intrahepatic hepatic veins with nonfilling of middle and left hepatic veins on computed tomography scan consistent with BCS. Workup for systemic inflammatory process, hypercoagulable, or myeloproliferative disorder was negative. The patient developed progressive complications related to portal hypertension, ultimately necessitating living-donor liver transplant. Grossly, the explant liver showed cirrhosis with perivascular fibrosis. Microscopically, the most striking finding was numerous granulomas involving small- and large-caliber central/hepatic veins. These granulomatous lesions displayed a spectrum of activity and chronicity, ranging from noncircumferential lymphohistiocytic infiltrate in the vessel wall to fibrosis, obliteration, and recanalization of the vessels. Occasional giant cells and necrotizing granulomas were also present. Evaluation for infection (bacterial, fungal, TB, virus), systemic vasculitis, sarcoidosis, drug-related diseases, and neoplasm-associated conditions was negative. Although there is no treatment guideline for BCS caused by idiopathic hepatic venulitis, the patient in the only other reported case responded well to steroids. Therefore, awareness of this rare cause of BCS may lead to earlier diagnosis and treatment, ultimately preventing disease progression (Figure 42).
Esophageal Tuberculosis in an HIV-Positive Patient: Mimicking a Spindle Cell Tumor (Poster No. 90)
Tuberculosis of the esophagus is an extremely rare entity even in immunocompromised patients. It represents about 0.3% of gastrointestinal tuberculosis cases and frequently affects the middle third of the esophagus. Most cases may present with dysphagia, weight loss, anorexia, or retrosternal pain, or with severe complications such as fistulae, ulcerations, and perforation. On endoscopic evaluation, it usually presents as an ulcerative lesion. We report the case of a 24-year-old man with history of HIV (CD4 count 86 cells/mm3) and pulmonary tuberculosis who presented with a 2-cm submucosal mass of the proximal esophagus. The mass protruded into the lumen and the mucosa was intact. Biopsy was referred from an outside institution as a spindle cell neoplasm; rule out a gastrointestinal stromal tumor (GIST). Sections revealed a submucosal lesion formed by spindle and epithelioid cells (Figure 43, A), admixed with chronic inflammation and focal areas of neutrophil aggregates (Figure 43, B). The spindle cells were positive for CD68 and S100 (Figure 43, C), but negative for smooth muscle actin, desmin, cytokeratin, ALK, and CD117. Ziehl-Neelsen stain was positive for numerous intracellular acid-fast bacilli (Figure 43, D), confirming the diagnosis of esophageal tuberculosis. This case report is a reminder that, although rare, esophageal tuberculosis may manifest as a submucosal lesion, and that a histiocytic/granulomatous reaction may mimic grossly and histologically a spindle cell neoplasm such as leiomyoma and GIST.
A Case of Perianal Extramammary Paget Disease Associated With Anorectal Villous Adenoma: Primary or Secondary Disease? (Poster No. 91)
Perianal extramammary Paget disease is an uncommon intraepidermal adenocarcinoma characterized by the presence of atypical Paget cells. It is divided into primary and secondary types. For primary type, malignant cells originate from apocrine glands that are GCDFP15+/CK20−/CDX2−. Secondary type is usually associated with underlying colorectal adenocarcinoma and has an immunoprofile of GCDFP15/CK20+/CDX2+. It is essential to distinguish primary from secondary type because their treatment approach and prognosis are different. Here we report an extremely rare case of perianal extramammary Paget disease associated with a premalignant lesion—anorectal villous adenoma. The patient was a 72-year-old man with a past medical history of hemorrhoids with no history of colorectal cancer who presented with perianal pruritus and skin rash. Physical examination showed multifocal erythematous change along bilateral perianal skin. Skin biopsy revealed diffuse intraepidermal Paget cells with signet ring cell differentiation. The atypical cells were CK7+/CK20+/CDX2+, consistent with the secondary perianal Paget disease. To evaluate the possibility of underlying malignancy, a colonoscopy was performed to reveal a hyperplastic polyp in the descending colon. An anoscopy showed a small polyp along the posterior anorectal wall. Multiple biopsies revealed strips of epithelium with long fronds of villous projections, suggestive of a villous adenoma. No evidence of invasive malignancy was found, but undersampled adenocarcinoma was suspected. The patient is being closely followed up for 1 year and the repeated anoscopy was negative for invasive malignancy. Taken together, this case represents secondary perianal Paget disease associated with anorectal villous adenoma.
Sirolimus-Associated Venous Occlusive Disease After Allogeneic Stem Cell Transplant (Poster No. 92)
Venous occlusive disease (VOD), also known as sinusoidal obstruction syndrome, is a potentially life-threatening complication that can develop after hematopoietic stem cell transplantation (HSCT). Sirolimus is an effective agent for prophylaxis of graft-versus-host disease (GVHD) after HSCT, but use of sirolimus (especially in combination with tacrolimus and methotrexate) is also known to pose a risk for developing VOD. Recently, diagnosis criteria for VOD that increases sensitivity and specificity for VOD was developed by the European Society for Blood and Marrow Transplantation. The criteria for diagnosis of classical VOD (in the first 21 days after HSCT) are bilirubin ≥2 mg/dL and 2 of the following: painful hepatomegaly, weight gain >5%, or ascites. Our patient was a 33-year-old man who had HSCT for Philadelphia chromosome–positive, precursor B-cell acute lymphoblastic leukemia/lymphoma after treatment with hyper-CVAD with a high dose of methotrexate followed by tacrolimus/sirolimus for GVHD prophylaxis. Thirteen days after HSCT he was found to have elevated transaminases, and he subsequently developed abdominal tenderness, weight gain (13.5%), hepatosplenomegaly, and ascites, but his bilirubin level was not diagnostic (initial: 0.3 mg/dL, before biopsy: 1.5 mg/dL). Transjugular liver biopsy performed on the 17th day showed pericentral hemorrhage and necrosis (Figure 44, A) and trichrome stain highlighted marked intimal thickening by edema and numerous extravasated erythrocytes in the terminal hepatic venule (Figure 44, B). The patient's liver function began to recover after sirolimus cessation and had returned to baseline 1 month later. For this case without diagnostic bilirubin level the biopsy was very helpful in making a diagnosis of VOD.
Autologous Graft-Versus-Host Disease Involving the Gastrointestinal Tract Following Hematopoietic Stem Cell Transplantation (Poster No. 93)
Graft-versus-host disease (GVHD) involving the gastrointestinal (GI) tract is most commonly a complication of allogeneic hematopoietic stem cell transplantation (HSCT). Rarely GVHD of the GI tract has also been reported following autologous HSCT. We present the case of a 68-year-old woman (past medical history of multiple myeloma, hypertension, type II diabetes mellitus, and chronic kidney disease) who underwent autologous HSCT. On day 19 after HSCT, she developed watery diarrhea, nausea, and vomiting. Endoscopy showed duodenal erosions, terminal ileum mucosal sloughing, and colonic diffuse loss of vascularity. Biopsies had shown findings consistent with GVHD, grade 3 of 4. The patient was treated with high-dose steroids, and her signs and symptoms improved. Because of the considerable clinicopathologic overlap, distinguishing medication effect (eg, mycophenolate-induced injury) from GVHD can be challenging. However, accurate and prompt diagnosis is critical because management differs based on the diagnosis. Histopathologic features favoring GVHD include apoptotic microabscesses, endocrine cell aggregates, hypereosinophilic degenerating crypts, architectural distortion, and a lack of eosinophilia. On the basis of the clinical presentation, histopathologic features, and clinical improvement with steroids, this patient was diagnosed with autologous GVHD. Patients treated with autologous HSCT, particularly those with multiple myeloma, may develop a potentially life-threatening syndrome pathologically identical to allogeneic GVHD. Pathologists should be aware of this rare condition because prompt recognition and early immunosuppressive therapy are associated with improved outcomes.
An Unexpected IgG4-Related Enteropathy Masquerading as a Stricturing Malignancy (Poster No. 94)
IgG4-related enteropathy is a rare entity that may mimic malignancy on clinical presentation. Early diagnosis is challenging, as it presents with a myriad of vague, nonspecific symptoms based on the location and subsequent organ dysfunction from fibrosis. The characteristic histologic picture includes a dense lymphoplasmacytic infiltrate with elevated IgG4 plasma cells, prominent fibrosis in a storiform pattern, and obliterative phlebitis. This report describes a 68-year-old woman who developed abdominal pain, nausea, and vomiting refractory to medical management. A computed tomography scan showed a 6-cm segment of thickened and strictured right colon without obstruction. Biopsies of the mucosa showed ulceration, granulation tissue, and diffuse mucosal regeneration. Because of clinical concern for malignancy, a right hemicolectomy was performed, with the final pathology showing characteristic histologic findings for IgG4-related disease, including fibrosis and multifocal lymphoplasmacytic infiltrates (Figure 45, A and B), with IgG- (Figure 45, C) and IgG4-positive (Figure 45, D) plasma cells enriched in markedly thickened fibrotic submucosa. Although there are many reports of IgG4-related sclerosing mesenteritis, there have been no reports of a solitary colonic IgG4-related lesion. This case demonstrates a unique presentation of IgG4-related disease solely involving the ascending colon causing circumferential wall thickening without significant mesenteric involvement. Very few cases of IgG4 enteropathy have been diagnosed on biopsy specimens. Therefore, this unique and challenging presentation of IgG4 enteropathy highlights the need for including it in the differential diagnosis and improving early detection to prevent unnecessary surgical morbidity, as this disease process is highly responsive to steroids.
Pseudo–Ground-Glass Change in a 12-Year-Old Boy With Pre–B-Cell Acute Lymphoblastic Leukemia (Poster No. 95)
Ground-glass hepatocytes in chronic hepatitis B result from proliferation of hepatitis B surface antigen in smooth endoplasmic reticulum. This cytoplasmic change is also seen in patients not infected with hepatitis B, where it has been called pseudo–ground-glass change (GGC). We report pseudo-GGC in a 12-year-old boy with pre–B-cell acute lymphoblastic leukemia on maintenance mercaptopurine, 75 mg PO q day, and methotrexate, 22.5 mg PO q week. He complained of decreased energy and had scleral icterus. Laboratory showed total bilirubin at 11.0 mg/dL (reference range, 0.3–1.2 mg/dL), and direct bilirubin 10.8 mg/dL (reference range, <0.2 mg/dL). Transaminases were also elevated. Serologic test results for hepatitis A, B, and C were negative. Liver biopsy showed prominent cholestasis, increased iron, and scattered hepatocytes with finely granular glassy cytoplasm. These stained positively by GMS, PAS with and without diastase, and colloidal iron stains. Immunoperoxidase stains for hepatitis B surface antigen and hepatitis B core antigen (Neogenomics, Fort Myers, Florida) were negative. Transmission electron microscopy showed electron-dense granules suggestive of abnormal glycogen. With negative serology and negative immunoperoxidase stains for hepatitis B, a diagnosis of pseudo-GGC was made. Pseudo-GGC has been described in Lafora disease, cyanamide and disulfiram therapy, liver transplant, fibrinogen deposition, and type IV glycogenosis. This is the first case describing GGC in a patient with leukemia undergoing maintenance therapy.
The Role of CD90 in the Progression to Human Hepatocellular Carcinoma (Poster No. 96)
Context: Hepatocellular carcinoma is the third ranking cause of cancer-related deaths in the United States. Chronic and repetitive cycles of damage and repair, mediated by inflammatory markers, have a known contribution to liver disease that can potentially culminate in hepatocellular carcinoma. CD90, which is a cancer stem cell marker, has been previously described to play a role in hepatocellular carcinogenesis. It is involved with cell-to-cell signaling as well as cell-to-matrix interactions. Previously published studies have demonstrated a positive correlation with CD90 expression and hepatocarcinogenesis; however, CD90 stromal expression patterns in cirrhosis, dysplasia, and carcinoma have not yet been described.
Design: Tissue microarrays (TMAs) were constructed from explanted livers from 44 patients with end-stage liver disease and hepatocellular carcinoma. TMAs were established using samples demonstrating cirrhosis, dysplasia, and hepatocellular carcinoma. CD90 immunostaining patterns in the intralesional and periportal regions were analyzed independently by 2 observers (A.S., G.G.). Statistical analysis using χ2 test was performed (Y.Z.).
Results: Using χ2 analysis, our data demonstrated a significant correlation between CD90 staining intensity and tumor progression in the interlesional stroma (P < .001). Periportal staining of CD 90 did not show any significant trend (P > .1).
Conclusions: Our results support a significant correlation between CD90 intralesional stromal staining and the progression of liver disease from cirrhosis to dysplasia to carcinoma. This gradual increase in expression of CD90 in the intralesional stromal compartment raises the possibility of mesenchymal contribution to hepatocellular carcinogenesis, thus necessitating further studies for confirmation.
Florid Vascular Proliferation of the Colon and Small Bowel: A Potential Sarcomatous Impersonator (Poster No. 97)
Vascular abnormalities and lesions of the small bowel and colon are rare. A florid vascular proliferation (FVP) associated with colonic obstruction and intussusception has been described and can mimic a vascular tumor including angiosarcoma. We report a case of colonic FVP associated with colonic obstruction and a case of small bowel FVP associated with Meckel diverticulum. Case 1 involved a 62-year-old woman with multiple medical problems and biopsy-proven ischemic colitis. She was initially managed conservatively and developed large bowel obstruction with pan-ischemic colitis requiring total colectomy. The resection specimen demonstrated colonic transmural FVP with ulceration (Figure 46, A) highlighted by CD31 immunohistochemical stain (Figure 46, B). Case 2 involved an 80-year-old man with multiple medical problems who presented with 4 months of abdominal pain. Computed tomography scan demonstrated mesenteric haziness suggestive of a mesenteric mass. Intraoperatively, jejunal diverticulosis and Meckel diverticulum were observed. The resection specimen similarly demonstrated small bowel transmural FVP, as in case 1, with mild endothelial cell atypia and scattered mitoses (Figure 46, C and D). Although the pathogenesis of FVP is not entirely clear, it is thought to represent a benign reactive process. Colonic FVP has been associated with colonic obstruction and intussusception. To our knowledge, FVP has not been reported in the small bowel or in association with Meckel diverticulum. Given the ability to mimic a sarcoma, pathologists should be aware of FVP to avoid this diagnostic pitfall.
Liver Metastases in a 5-mm pT1 pN0 Low-Grade Colonic Carcinoma Associated With High-Grade Tumor Buds (Poster No. 98)
Tumor buds are defined as fewer than 5 clustered tumor cells, usually present at the invasive border. They represent an epithelial-tomesenchymal transformation, a prerequisite for invasion and local/distant spread of tumor. High-grade budding reveals more than 10 buds in a 20× high-power field. Our patient, a 64-year-old woman, presented with tachycardia, tachypnea, and weight loss. Computed tomography of the abdomen and pelvis revealed a right colon mass and many heterogeneous densities throughout the liver suspicious for metastases. A biopsy revealed a tubulovillous adenoma (TVA) with high-grade dysplasia. A right hemicolectomy revealed 3 sessile masses in the cecum ranging from 1.2 to 6.2 cm in greatest dimension. Grossly and microscopically, muscularis propria invasion was not seen. Histology of the largest completely submitted TVA showed invasive low-grade adenocarcinoma arising in the largest TVA, involving the submucosa (pT1) and measuring 5 mm in greatest dimension. Pancytokeratin immunostain showed high-grade tumor buds at the invading edge with vascular wall invasion and intraluminal malignant glands. Thirty-two lymph nodes were negative for malignancy (pN0). The other 2 polyps were also TVAs, 1 containing HGD. Liver biopsies showed metastatic CK7−, CK20+ well-differentiated adenocarcinoma (pM1a). This case study highlights the importance of tumor buds as a significant risk factor for distant metastasis irrespective of regional lymph node metastasis in low-grade, early-stage colonic carcinomas.
Rhabdoid Colorectal Carcinoma With Electron Microscopy Correlation in a 69-Year-Old Man (Poster No. 99)
Colorectal adenocarcinoma with rhabdoid features is a very rare tumor that is characterized by the presence of cells with a large, eccentrically placed nucleus and eosinophilic cytoplasm. A 69-year-old man presented with lightheadedness, right lower quadrant pain, and microcytic anemia. Computed tomography scan showed circumferential wall thickening of cecum and proximal ascending colon. A right hemicolectomy was performed. Specimen examination revealed external adhesions, ragged serosal surface, and a large circumferential ulcerated mass. Pathology demonstrated a pleomorphic adenocarcinoma with predominant rhabdoid features (90%), glandular pattern (5%), and mucinous pattern (5%). Adenocarcinoma involved the serosal surface and a vessel at the circumferential margin. Four of 10 mesenteric lymph nodes contained metastatic adenocarcinoma. A low-grade appendiceal mucinous neoplasm involved the appendix. The differential diagnosis of the rhabdoid cells included a lymphoma, melanoma, germ cell malignancy, rhabdomyosarcoma, and pleomorphic adenocarcinoma. The following immunohistochemical studies were negative: CD20, CD45, CD79a, HMB45, MART1 SOX10, α-fetoprotein, CD30, glypican-3, CDX2, CD20, CEA, smooth muscle actin, desmin, and synaptophysin. Positive markers included broad-spectrum cytokeratin AE1/3, CAM5.2, CD10, and EMA (focal). Electron microscopy revealed the presence of numerous cytoplasmic intermediate-type filaments. A total of 11 colonic rhabdoid adenocarcinomas have been reported. Only one previous case of colonic rhabdoid adenocarcinoma with low-grade appendiceal mucinous neoplasm has been reported. In a separate case report, electron microscopy findings have been described. This case demonstrates the broad differential diagnosis that is inherent in this rare variant of colonic adenocarcinoma.
Well-Differentiated Neuroendocrine Tumor of the Duodenum in a Patient With Peutz-Jeghers Syndrome (Poster No. 100)
A 29-year-old man with a history of Peutz-Jeghers syndrome underwent small bowel resection 15 years ago. Pathology of small bowel resection revealed multiple hamartomatous polyps in the jejunum and intussusception. Follow-up gastric and colonic biopsies revealed multiple hamartomatous polyps composed of treelike, elongated, branching crypts lined by normal epithelial cells with a core of characteristic interlaced smooth muscle bands, causing a distorted architecture (Figure 47, A). Recent workup on endoscopy revealed multiple polyps in the gastric fundus, body, and antrum and in the second part of the duodenum. Histology showed an incidental finding of well-differentiated neuroendocrine tumor on the duodenal polyp biopsy (Figure 47, B). Morphologically the tumor was composed of solid nests of monotonous small round cells with peripheral palisading, moderate finely granular cytoplasm, small nucleoli, and salt and pepper–type chromatin (Figure 47, C). The tumor cells were immunohistochemically positive for synaptophysin (Figure 47, D) and chromogranin (focal) with a proliferation index (Ki-67) of less than 2%. Based on the morphology and immunohistochemical staining pattern, the diagnosis of well-differentiated neuroendocrine carcinoma was rendered. To our knowledge, there are only 2 case reports showing a well-differentiated neuroendocrine tumor of the rectum and appendix in patients with Peutz-Jeghers syndrome and none showing duodenal or other carcinoids. The predisposition for well-differentiated neuroendocrine tumors in these patients is unclear. Hence, regular endoscopic biopsy procedures are needed for early detection and prevention of polyp-associated complications.
Bizarre Stromal Cells in Esophagitis: A Potential Diagnostic Pitfall Mimicking Malignancy (Poster No. 101)
Bizarre stromal cells in inflammatory conditions represent an important diagnostic pitfall, because they closely simulate malignancy or viral cytopathic effect. We present a case in a 43-year-old man with esophagitis who was 4 months post heart transplant and developed acute pancreatitis with pseudocyst formation status post cystogastrostomy. Endoscopy revealed severe ulceration and erythema at the distal esophagus. Histologic sections showed predominantly necroinflammatory debris. There was a subpopulation of cells that were discohesive and exhibited severe cytologic atypia with markedly enlarged nuclei, irregular nuclear contours, and pleomorphism. Cytoplasm was variable with relatively preserved nucleus to cytoplasm ratio. They were intermingled with many granulocytes and plump vessels in a background of granulation tissue. The morphologic findings raised the possibility of viral cytopathic effect. Immunohistochemical stains for CMV, HSV, adenovirus, SV-40 (polyoma virus), and p16 were all negative. The degree of cytologic atypia also raised the possibility of an esophageal malignancy. Further attempts to characterize the cells showed they were positive only for vimentin and were negative for pancytokeratin, p63, EMA, ERG, SOX-10, desmin, CK20, CD45, CD68, and CD30. This immunophenotype indicated the cells were likely mesenchymal in origin and represented severely reactive stromal cells. Bizarre stromal cells have been described in the literature in distal esophagus and are usually associated with inflamed polyps, although our patient did not have an esophageal polyp. Awareness of bizarre stromal cells can help to prevent misdiagnoses.
Acute Hepatic Injury Due to Kratom Toxicity in the Setting of Chronic Hepatitis C (Poster No. 102)
Kratom is an herbal product that has been gaining popularity because of its lack of regulation and similarities to opioids, with its primary alkaloid, mitragynine, acting on the μ and δ receptors. We report a case of a 42-year-old woman who presented with nystagmus, nausea, right upper quadrant pain, fatigue, scleral icterus, jaundice, and dark urine. Significant laboratory values included: AST, 387 U/L (reference 16–43); ALT, 658 U/L (reference 9–52); alkaline phosphatase, 368 U/L (reference 38–126); total bilirubin, 6.1 U/L (reference 0.2–1.3); direct bilirubin, 2.6 U/L (reference 0.0–1.1); and indirect bilirubin 3.5 U/L (reference 0.0–0.3). The patient also tested positive for hepatitis C antibodies, which was confirmed with a hepatitis RNA polymerase chain reaction level of 7.23 log IU/mL (reference <1.18). The patient reported drinking 1–2 cups of kratom tea daily for the last year for self-management of chronic pain and anxiety. She recalled that her last shipment of tea tasted different than normal, which correlated with the onset of symptoms. A liver biopsy showed a prominence of portal plasma cells, interface activity, and lobular inflammatory activity, findings unusual in the setting of chronic hepatitis C alone. Given the absence of autoimmune disease and quick recovery after cessation of the tea, kratom drug toxicity is a likely contributing factor. Only 2 other cases of hepatic toxicity related to kratom use have been reported. We present this case to encourage the consideration of kratom toxicity in the setting of unexplained hepatic injury with the histologic findings discussed above (Figure 48).
Improving Accuracy of Serrated Colon Polyp Designation (Poster No. 103)
Context: Serrated polyps are the most common polyps of the large bowel. In the past decade, the focus on sessile serrated polyp (SSP) has been increased as it has been proved that untreated SSP is associated with substantial increased risk of developing colon cancer. The microscopic diagnosis can be challenging because of overlapping features with hyperplastic polyps, which can cause misdiagnosis and inappropriate follow-up of patients.
Design: The purpose of this study is to assess the effect of educational sessions on appropriate designation of SSPs. We reevaluated hyperplastic polyps for 2 years and repeated the reevaluation after educational sessions.
Results: During the first phase, we evaluated 365 hyperplastic polyps and reclassified 60 (16%) of them as SSP. We also found 11 tubular adenomas, 2 traditional sessile serrated adenomas, and 8 mucosal tags. After the education sessions, phase 2, we reviewed another 191 hyperplastic polyps and reclassified 16 (8%) of them as SSP. We found 3 tubular adenomas but no other polyps. In total, 56% of the SSPs were in the distal colon (descending and sigmoid colon, and rectum). Twenty-five were smaller than 0.4 cm in diameter, and 51 polyps (67%) were 0.5 cm in diameter or larger.
Conclusions: Our study shows that the educational intervention was successful in significantly increasing the accurate designation of SSP.
Extra-Ampullary Epithelial Duodenal Polyps: Reappraisal Based on Current Morphologic and Immunohistochemical Features Provides a More Accurate and Clinically Significant Classification (Poster No. 104)
Context: The nomenclature of extra-ampullary epithelial duodenal polyps (EAEDPs) is not well established. Benign Brunner gland proliferative lesions (BGPLs) like Brunner gland hyperplastic nodule (BGHN) and Brunner gland hamartoma (BGH) have often been used interchangeably with the term BG adenoma (BGA), which is a preneoplastic lesion. Recently, it has been proposed that the term BGA be replaced by the term extragastric pyloric gland adenoma (ExG-PGA), a preneoplastic lesion with a morphologic and immunohistochemical (IHC) profile indistinguishable from BGA. Additionally, there are no definitive diagnostic criteria to differentiate hyperplastic polyps (HPs) from traditional serrated adenoma (TSA)–like polyps of duodenum and its clinical significance. The aim of our study is to develop a standardized classification of EAEDPs based on the most current morphologic and IHC features.
Design: We reviewed all the duodenal polyps diagnosed at our institution between January 2010 and April 2016 by applying the most current morphologic and IHC features (Table).
Results: The original diagnoses included 88 tubular adenomas (TAs), 79 BGHNs, 5 BGHs, 4 ExG-PGAs, 8 HPs, and 77 gastric metaplastic nodules. Based on our review, 3.4% of the remaining 261 polyps were reclassified, including 4 of 88 TAs, 1 of 5 BGHs, 2 of 4 ExG-PGAs, and 2 of 8 HPs.
Conclusions: Use of the outlined morphologic criteria and IHC profiles provides a more accurate and clinically significant classification of EAEDPs, useful in differentiating benign BGPLs from preneoplastic entities like ExG-PGA and benign serrated lesions like HPs from preneoplastic lesions like the TSA-like polyps.
Synchronous Occurrence of Gastrointestinal Stromal Tumor and Gastric Adenocarcinoma (Poster No. 105)
Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumors in the gastrointestinal tract (GI), although they comprise <1% of all GI tumors. Most GISTs are asymptomatic and diagnosed incidentally during the surgical exploration of other GI cancers. GISTs reportedly can occur synchronously with other GI neoplasms, and, according to a case series reported in the literature, the incidence of synchrony between GISTs and gastric adenocarcinoma is 0.53%. We report a case of a 53-year-old woman who presented with 2 months of progressive dysphagia, epigastric pain, fatigue, and weight loss. Computed tomography (CT) showed a circumferential irregular masslike thickening of the gastric body and fundus with a polypoid mass along the lesser curvature. Total gastrectomy revealed a 4.5-cm very low-risk GIST infiltrated by a 10.0-cm poorly differentiated gastric adenocarcinoma, diffuse type. The patient denied postoperative chemotherapy. Four-month follow-up showed progression of disease involving lymph nodes on CT. The synchronous occurrence of gastric adenocarcinoma and GIST raises the question whether this is a random event or whether the 2 lesions are connected by a causal relationship. As most of the synchronous GISTs are accidentally discovered during the surgical exploration of other GI cancers, careful sampling must be performed by pathologists while handling these specimens. Also, testing for c-kit/PDGFR can be performed in both tumors to see if there is an actionable target therapy. In our case, GIST was positive for c-kit whereas the adenocarcinoma was negative.
(Poster No. 106)
Pancreatic Acinar Differentiation in High-Grade Neuroendocrine Carcinomas of the Upper Gastrointestinal Tract (Poster No. 107)
Context: Pancreatic acinar differentiation has been reported in some pancreatic neuroendocrine tumors, but not in poorly differentiated neuroendocrine carcinomas of pancreas, and remains poorly characterized in neuroendocrine tumors and neuroendocrine carcinomas of the upper gastrointestinal tract.
Design: Thirty-five upper gastrointestinal tract neuroendocrine tumors, including 4 cases of poorly differentiated high-grade neuroendocrine carcinoma (PD-HG-NEC), were identified by retrospective search of archived formalin-fixed, paraffin-embedded tissues. Immunohistochemistry for synaptophysin, chromogranin, chymotrypsin, and Ki-67 was performed.
Results: Of the 35 cases, the primary sites included stomach (25), gastroesophageal junction (5), and small intestine (5). Twelve cases involved women and 23 cases involves men, with an average age of 61 years (range, 38–80 years). Fifteen were low grade (G1, Ki-67 <3%), 9 were intermediate grade (G2, Ki-67 3%–20%), 7 were high grade (G3, Ki-67 >20%), and 4 were PD-HG-NEC. Two PD-HG-NECs, arising in the stomach, showed positivity for both chymotrypsin and neuroendocrine markers, consistent with mixed pancreatic-type acinar and neuroendocrine carcinoma of the stomach. The tumors showed high mitotic activity (greater than 50 per 10 high-power fields) and Ki-67 proliferation indices of 40% and 50%. Synaptophysin and chymotrypsin were positive in at least a 25% area in both tumors and showed heterogeneous staining. Abdominal imaging showed no evidence of a pancreatic lesion.
Conclusions: Pancreatic acinar differentiation in upper gastrointestinal neuroendocrine tumors is rare but may occur in poorly differentiated high-grade mixed acinar-neuroendocrine carcinomas, whereas it has not been reported in pancreatic PD-HG-NEC. The finding of pancreatic acinar differentiation in PD-HG-NEC may be useful for distinguishing gastrointestinal metastasis of pancreatic PD-HG-NEC from primary gastric PD-HG-NEC.
Endometrial Cancer Risk After Diagnoses of World Health Organization Categories of Endometrial Hyperplasia: Report on a 6-Year Experience at a Large Academic Women's Hospital (Poster No. 108)
Context: Although hysterectomy is the favored treatment for atypical endometrial hyperplasia, no formal consensus guidelines exist for optimal management of the different categories of endometrial hyperplasia (EH).
Design: This retrospective study included patients with EH diagnosed by biopsy or curettage from 2010 to 2015. Reference diagnoses were as follows: simple hyperplasia (SH), simple atypical hyperplasia (SAH), complex hyperplasia (CH), complex atypical hyperplasia (CAH), endometrial polyps with hyperplasia without atypia (Polyp-H), polyps with hyperplasia and atypia (Polyp-AH), and focal cancer in a background of CAH.