University of California San Francisco Department of Pathology 35 th - PDF document

University of California San Francisco Department of Pathology 35 th Annual Current Issues in Anatomic Pathology May 23, 2019 12:15-1:15 pm Problematic Cases on the GI service grace.kim@ucsf.edu Topics Covered Focus on problematic areas in the gastrointestinal tract and pancreatobiliary tree on biopsy or resection that are encountered in daily practice, particularly to recognize relevant differential diagnoses and order appropriate stains. Objective Distinguish polyps and their malignant risks Develop differential diagnosis and strategies to resolve them Apply immunohistochemical stains to facilitate diagnosis Disclosures Shareholder / Adicet Bio and Five Prime Therapeutics Consultant / Celgene Outline I. Colonic serrated polyps II. Gallbladder polyps Page 1

I. Colonic serrated polyps Case A History: The patient is a 51-year-old woman undergoing colorectal carcinoma screening. Colonoscopy showed a 3 mm sessile polyp in the ascending colon. Case B History: The patient is a 58-year-old woman with history of colonic polyp undergoing surveillance colonoscopy. Colonoscopy showed a 12 mm sessile polyp in the transverse colon. Case C History: The patient is a 72-year-old woman with undergoing surveillance colonoscopy. Endoscopy revealed a 12 mm sessile polyp in the rectum. Brief review on colonic serrated polyps Histology/Immunohistochemistry Serrated lesions share a serrated/stellate architecture of the epithelium • Distinguishing features of sessile serrated adenoma (SSA) 1 , 2 - a low power assessment SSA Hyperplastic polyp (microvesicular) Crypts size and Marked variation; asymmetric Uniform evenly spaced, straight or shape funnel shaped crypts; orderly growth Serration Excess of deeper crypt Increases towards surface epithelium; location serrations; basal 1/3 limited to upper 2/3 Serration Variation in size of serration Architecture of Inverted growth, boot or No deep lateral crypt growth, narrow crypt base anchor shaped; horizontal growth Proliferation Away from crypt base; Basal portion uniformly zone variable from crypt to crypt Quantification 1 to 3 abnormal crypts without prolapse effect Bettington et al in their SSA study used the following features: (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. 3 • Problematic when not optimally oriented, then perform level sections to visualize base of crypt. If still not present, diagnosis as “serrated polyp, unclassified” with an explanation in the comment. In these cases, the ones in the right colon are likely managed as SSA and those from the left as hyperplastic polyp Page 2

SSA with dysplasia is not subclassified into low and high grade. Morphologic abrupt transition from non-dysplastic SSA to area with increased complex architecture and various forms of cytologic atypia including: 1) Resembles conventional adenoma with columnar cells with elongated pseudostratified nuclei mitotically active 2) Cytologically have high grade nuclear features in low columnar to cuboidal cells with eosinophilic cytoplasm and round stratified nuclei 3) Similar to #1 but cells are cuboidal and have round nuclei (more MSI) • Pitfall is “enteric metaplasia” 4 that is not dysplastic that look like normal small intestinal absorptive cells and are composed of tall cuboidal cells with eosinophilic cytoplasm, ovoid nuclei, but are not mitotically active. • It is not recommended to grade dysplasia in serrated polyps 2 Loss of MLH1 is found in SSA with dysplasia Reference 5 Reference 6 Polyp SSA with dysplasia 23% 73% Non-dysplastic crypts in polyps with SSA 18% 32% Distinguishing features of traditional serrated adenoma (TSA) 1 TSA TVA Gross Sessile Location Left colon Architecture Villous with bulbous tips Tall villous architecture (25%-75%) and (tennis racquet like) rest is tubular structures Cytology Tall columnar cells, Pseudostratified nuclei eosinophilic cytoplasm, bland oval elongated nuclei without mitotic activity Cytoplasm Eosinophilic (enteric metaplasia-like*) or have predominant goblet cells Glandular aspect Luminal: Undulating border Smooth luminal border Basal: Small abortive crypts (ectopic crypts) Mitosis Ectopic crypts or deep aspect Mitotic activity may be brisk near muscularis mucosae *Absorptive-like enterocytes line the crypts and are composed of tall columnar eosinophilic cytoplasm and elongated benign-appearing nuclei, luminal surface has prominent brush border • Problematic when TSA are flat and minimally polypoid, but key is enteric metaplastic epithelium and locating a few ectopic crypts; not prominently villous Page 3

• TSA can also develop conventional dysplasia like a villous adenoma or exhibit serrated cytologic dysplasia (similar to SSA 2) above) Reporting • AJCC 8 th edition pT stage for Colon and Rectum key change is that high grade dysplasia is only HGD and not considered pTis T Category T Criteria Tis Carcinoma in situ, intramucosal carcinoma • Surgical resection is recommended for carcinoma in a polyp if it contains high grade carcinoma, lymphatic/venous invasion, or invasive carcinoma at or <1mm from resection. Colonoscopy surveillance recommendation based on first colonoscopy findings 7 *Proximal is to sigmoid colon and Distal is defined as rectosigmoid References 1. Snover DC. Diagnostic and reporting issues of preneoplastic polyps of the large intestine with early carcinoma. Ann Diagn Pathol. 2019 Apr;39:1-14. 2. Pai RK, et al. An update on the morphology and molecular pathology of serrated colorectal polyps and associated carcinomas. Mod Pathol. 2019 Apr 25. doi: 10.1038/s41379-019-0280-2. [Epub ahead of print] 3. Yokoo H, et al. Colorectal polyps with extensive absorptive enterocyte differentiation: histologically distinct variant of hyperplastic polyps. Arch Pathol Lab Med. 1999 May;123(5):404-10. 4. Bettington M, et al. Critical appraisal of the diagnosis of the sessile serrated adenoma. Am J Surg Pathol. 2014;38(2):158–166. 5. Yozu M, et al. Loss of expression of MLH1 in non-dysplastic crypts is a harbinger of neoplastic progression in sessile serrated adenomas/polyps. Histopathology. 2019 Apr 11. doi: 10.1111/his.13874. [Epub ahead of print] Page 4

6. Liu C, et al. Sessile serrated adenomas with dysplasia: morphological patterns and correlations with MLH1 immunohistochemistry. Mod Pathol. 2017 Dec;30(12):1728-1738. 7. Lindholm CR, et al. The dark side of the colon: current issues surrounding the significance, prevalence, detection, diagnosis and management of serrated polyps. Curr Opin Gastroenterol. 2019 Jan;35(1):34-41. II. Gallbladder polyp Case E History: 52 y/o woman with history of gallstone pancreatitis. Gross description: A 1 cm transmural nodule in the fundus. Case F History: 42 y/o woman with acute abdominal pain. CT scan revealed probable small gallstones and questionable gallbladder wall thickening. Gross description: Free-floating within the specimen container are two golden yellow, polypoid and friable soft tissue fragments (up to 0.5 cm in greatest dimension). No choleliths are identified within the lumen or the specimen container. Case G History: 62 y/o woman with right upper quadrant pain. A 1.1 cm gallbladder polyp was seen on ultrasound. Gross description: A green polypoid soft tissue (0.8 x 0.6 x 0.2 cm) is received separately within the container. Per surgeon, this is the gallbladder polyp that came loose from the gallbladder wall in the operating room. Case H History: 59 y/o woman with a 1.9 cm fundal gallbladder mass on abdominal ultrasound/1.3 cm on CT scan. Gross description: Free-floating in the container is a fragment of yellow-brown tissue (1.4 x 0.9 x 0.6 cm), consistent with a polyp. Case I History: 47 y/o woman with epigastric pain and ultrasound showing gallstones. Gross description: Three firm stones and a 0.4 cm polyp. Case J History: 35 y/o man with 2 cm gallbladder mass. Gross description: One, soft, irregular, red-tan mass of tissue (1.8 x 1 x 0.6 cm) is free floating within the gallbladder. No cholelith. Case K History: 45 y/o woman with 2.5 cm mass. Page 5