WHAT’S NEW IN PATHOLOGY? Issue 12 || February 2020 on “other tumors” covering mucosal • High grade appendiceal mucinous melanoma, germ cell tumors and neoplasm (HAMN) is added as a THE LATEST metastases. diagnostic entity similar to LAMN but showing high grade dysplasia. NEWS IN GI • Goblet cell carcinoid is renamed By Raul S. Gonzalez, M.D. Esophagus goblet cell adenocarcinoma, with • Gastroesophageal junction a new grading system. High grade examples represent what was he 5th Edition of the WHO Clas- carcinomas have been incorporated into the esophagus chapter. previously termed “adenocarcinoma Tsification of Tumours: Digestive ex goblet cell carcinoid” (Figure 1). System Tumours “blue book” was • Undifferentiated carcinoma is released in mid-2019. Key updates separated into its own entity rather are below. than a squamous cell carcinoma subtype. Lymphoepithelioma-like carcinoma is considered a subtype of General updates this entity. • The classification of digestive neuro- endocrine neoplasms is revised. They are categorized as neuroendocrine Stomach tumors (NETs, formerly “carcinoids”) • Undifferentiated carcinoma is now or neuroendocrine carcinomas its own separate entity with many (NECs) based primarily on histology. subtypes (large cell carcinoma with • NETs can be grade 1, 2 or 3, with rhabdoid phenotype, pleomorphic Figure 1: Goblet cell carcinoid of a Ki67 of less than 3% qualifying as the appendix is renamed goblet cell carcinoma, sarcomatoid carcinoma adenocarcinoma. grade 1 (formerly 0 - 2%). Mitotic and carcinoma with osteoclast-like rate is counted per 2 mm2, not per 10 giant cells). • Tubular carcinoid and L-cell high power fields. • Micropapillary adenocarcinoma carcinoid are renamed tubular NET • NECs are always high grade and is added as an aggressive subtype of and L-cell NET, respectively. therefore do not require numerical adenocarcinoma. grading. Mixed adenoneuroendo- • Gastroblastoma is added as an crine carcinoma (MANEC) has been entity. Colorectum replaced with the more inclusive conceptual term of mixed neuroendo- • Sessile serrated adenoma / polyp crine-nonneuroendocrine neoplasm is renamed to sessile serrated lesion, (MiNEN); the actual diagnosis should Small bowel / with the reasoning that they are not indicate the lesion’s components. Ampulla always polypoid on colonoscopy. Only • Carcinoma grading is generally now one unequivocally distorted crypt is • Ampullary carcinomas have now needed to make this diagnosis. two tier (low grade and high grade). been incorporated into the small • Poorly cohesive carcinoma is a bowel chapter, though the chapter • Adenoma-like adenocarcinoma diagnostic term incorporated into distinguishes between ampullary and is added as a subtype of colorectal most organ system chapters, with nonampullary carcinomas. carcinoma (CRC) with a good prognosis. Adenosquamous signet ring cell carcinoma considered Intra-ampullary papillary-tubular a subtype. • carcinoma is also now considered a neoplasm has been added as a CRC subtype. • Hematolymphoid lesions, mesen- subtype of ampullary adenoma. chymal lesions and syndromes have • Cribriform-comedo type been separated into their own respec- adenocarcinoma is removed as a CRC tive chapters. Appendix subtype. • There is now a separate chapter • Spindle cell carcinoma is renamed • Low grade appendiceal mucinous to carcinoma with sarcomatoid Sponsored by an unrestricted grant neoplasm (LAMN) is formalized as a components. from Mayo Clinic Laboratories separate entity rather than a form of • Rather than grading CRC based appendiceal adenocarcinoma. on the predominant component, the WHO now recommends grading based on the least differentiated Genetics component, regardless of amount. • Several new polyposis syndromes are added, including gastric adenocarcinoma and proximal Liver / Intrahepatic polyposis syndrome (GAPPS), bile ducts NTHL1 associated polyposis, polymerase proofreading associated • Several subtypes of hepatocellular polyposis (caused by POLD1 or carcinoma (HCC) have been POLE mutation), AXIN2 associated added: steatohepatitic, clear cell Figure 2: IOPN of pancreas is polyposis and immune deficiency (formerly a “cytological variant”), associated polyposis. macrotrabecular-massive, officially distinct from IPMN. • Familial pancreatic cancer chromophobe and neutrophil-rich. The neuroendocrine section is The lymphoepithelioma-like subtype • (caused by many potential germline markedly expanded, including mutations) is added. is renamed to lymphocyte-rich. discussion of each hormone Molecular features of HCC subtypes • Criteria for serrated polyposis have • producing subtype and emphasis on been modified: either (1) ≥ 5 serrated are emphasized, particularly the new molecular data. DNAJB1-PRKACA translocation of lesions ≥ 5 mm in size proximal to the fibrolamellar HCC. rectum, with at least 2 ≥ 10 mm, or (2) > 20 serrated lesions throughout • Emphasis is placed on categorizing Lymphoma the colorectum, with ≥ 5 proximal to intrahepatic cholangiocarcinoma into the rectum. large and small duct types. • Duodenal-type follicular lymphoma, intestinal T cell • Hepatoblastoma subtypes have lymphoma NOS, indolent T cell been reorganized, and calcifying proliferative disorder of the nested stromal-epithelial tumor is gastrointestinal tract and EBV Meet the separated out as a distinct entity positive inflammatory follicular Author rather than a variant / related dendritic cell sarcoma are added as neoplasm. distinct entities. aul S. Gonzalez, • The subtypes of combined HCC- • Monomorphic CD56+ intestinal cholangiocarcinoma are less strictly RM.D. is an T cell lymphoma is renamed to Assistant Professor of defined. Cholangiolocarcinoma is monomorphic epitheliotrophic moved from this classification scheme intestinal T cell lymphoma. Pathology at Harvard and is now considered a type of small Medical School and the duct cholangiocarcinoma instead. Associate Director of • Primary neuroendocrine neoplasms Mesenchymal Gastrointestinal Pathology at Beth of the liver have been formally added. • Malignant gastrointestinal Israel Deaconess Medical Center. neuroectodermal tumor is added as He is a Deputy Editor-in-Chief and Gallbladder / a distinct entity. It may represent the gastrointestinal pathology editor for same entity as clear cell sarcoma-like Pathology Outlines, Reviews Editor Extrahepatic bile tumor of the gastrointestinal tract or for Histopathology, Membership ducts a subtype. Chair for the Rodger C. Haggitt • Grading of biliary intraepithelial • Molecular information on neoplasia (BilIN) is now two tier (low gastrointestinal stromal tumors Gastrointestinal Pathology Society and high grade) rather than three (GISTs) is added, in particular the and Vice Chair for the College of tier. succinate dehydrogenase (SDH) American Pathologists Surgical deficient subtype. Pathology Committee. He has • Epithelioid inflammatory Pancreas authored a liver pathology textbook myofibroblastic sarcoma is added and has published more than 60 Acinar cystadenoma is as an aggressive subtype of • peer reviewed journal articles. He officially renamed acinar cystic inflammatory myofibroblastic tumor transformation. with RANBP2 rearrangement. has been invited to speak at multiple • Pancreatic intraepithelial neoplasia • New hemangioma subtypes national conferences and maintains (PanIN) is now two tier. Numerical are specified: anastomosing active social media pages dedicated grading (PanIN-1A, etc.) is no longer hemangioma, diffuse hepatic to gastrointestinal pathology. You used. hemangiomatosis and hepatic small can follow Dr. Gonzalez on Twitter Intraductal oncocytic papillary vessel neoplasm. • @RaulSGonzalezMD, and join his neoplasm (IOPN) is established • Molecular data is added to as a distinct entity separate from epithelioid hemangioendothelioma, Facebook group for gastrointestinal intraductal papillary mucinous namely the characteristic WWTR1- pathology at https://www.facebook. neoplasm (IPMN), due to a different CAMTA1 and YAP1-TFE3 com/groups/GIpathology. mutational profile (Figure 2). translocations..