Diagnostic Pearls and Pitfalls in the Interpretation of Small Biopsies and Frozen Sections of the Pancreatobiliary Tract

The Pancreatobiliary Pathology Society (PBPS) wants to thank Alain C. Borczuk, MD, and the Archives of Pathology & Laboratory Medicine for showcasing our society through the publication of 4 review articles derived from presentations at the PBPS Companion Meeting during the 2023 United States and Canadian Academy of Pathology (USCAP) meeting.The PBPS, established in 2016, is dedicated to fostering excellence and collaboration in education, research, and clinical practice within the realm of pancreatobiliary pathology worldwide. We actively engage in partnerships with many international pathology associations and societies, including the College of American Pathologists, USCAP, the International Association of Pathologists, and the European Society of Pathology. Through our commitment to advancing knowledge and understanding of pancreatobiliary pathology, the PBPS aims to provide valuable resources and educational materials. Our website (https://pbpath.org) serves as a hub for accessing a wealth of information, empowering pathologists worldwide with essential resources to enhance their practice and contribute to the ongoing advancements in pancreatobiliary pathology.The 2023 PBPS Companion Meeting at the 2023 USCAP meeting, themed “Diagnostic Pearls and Pitfalls in the Interpretation of Small Biopsies and Frozen Sections of the Pancreatobiliary Tract,” featured 4 exceptional presentations: (1) “WHO (World Health Organization) International Classification System for the Reporting of Pancreatobiliary Cytology Specimens,” by Martha B. Pitman, MD; (2) “Diagnostic Pearls and Pitfalls in the Evaluation of Small Biopsies and Cytologic Samples From the Bile Duct and Ampulla,” by Alyssa M. Krasinskas, MD; (3) “Diagnostic Pearls and Pitfalls in the Evaluation of Small Biopsies of the Pancreas,” by Claudio Luchini, MD, PhD; and (4) “Intraoperative Evaluation of Pancreatobiliary Specimens,” by Wendy L. Frankel, MD, followed by a roundtable and question-and-answer section hosted by Vikram Deshpande, MD, and Grace Kim, MD. Our special section features 4 articles based on these presentations.In the first article, Martha B. Pitman, MD, systematically reviews the new WHO Reporting System for Pancreaticobiliary Cytopathology (the WHO System), which was developed jointly by the WHO, the International Academy of Cytology, and the International Agency for Research on Cancer. The new WHO System has 7 diagnostic categories, including (1) insufficient/inadequate/nondiagnostic; (2) benign (negative for malignancy); (3) atypical; (4) pancreaticobiliary neoplasm, low risk/low-grade; (5) pancreatic neoplasm, high risk/high-grade; (6) suspicious for malignancy; and (7) malignant. The criteria, differential diagnoses, and clinical implications for each diagnostic category are described and illustrated. Close correlation with imaging studies and integration of results from ancillary testing, such as biochemical (carcinoembryonic antigen [CEA] and amylase) and molecular testing of cyst fluid and bile duct brushings into the final diagnosis, are recommended by the WHO System to enhance diagnostic accuracy. This comprehensive approach ensures a thorough evaluation and facilitates a more precise final diagnosis. It also helps to improve the communication between clinicians and cytopathologists regarding pancreatobiliary cytology/biopsy results.In the second article, Alyssa M. Krasinskas, MD, compares the sensitivity of various techniques used to evaluate bile duct lesions, including percutaneous transhepatic approach with core biopsy, endoscopic ultrasound with fine-needle aspiration, endoscopic retrograde cholangiopancreatography with brushings or forceps biopsies, and peroral cholangioscopy with intraductal endoscopy and targeted biopsies. She emphasizes the importance of appropriate handling and special cutting protocols for tiny bile duct biopsies, which can enhance the yield of diagnostic materials. Histopathologic features of invasive and intraductal biliary neoplasms and challenges, diagnostic pearls, and pitfalls associated with these biopsies, as well as ancillary testing such as immunohistochemical markers (insulin-like growth factor-II mRNA binding protein-3 [IMP3], S100 calcium binding protein P [S100P], CEA, p53, Ki-67, maspin, etc), fluorescence in situ hybridization (FISH) using either the UroVysion FISH probe set or pancreatobiliary FISH probe set, and molecular markers, are also discussed. These tests not only aid in establishing diagnoses but also assist in guiding appropriate management decisions.In the third article, Claudio Luchini, MD, PhD, discusses the challenges and pitfalls associated with interpreting small pancreatic biopsies. He first describes the histopathologic features, immunohistochemical markers (such as p53, SMAD family member 4 [SMAD4], and AT-rich interaction domain 1A [ARID1A]), and molecular alterations that are useful in distinguishing pancreatic ductal adenocarcinoma from chronic pancreatitis and autoimmune pancreatitis. Dr Luchini then reviews the histopathologic features and immunohistochemical markers for solid cellular neoplasms of the pancreas, including pancreatic neuroendocrine neoplasms, acinar cell carcinoma, pancreatoblastoma, and solid pseudopapillary neoplasms. He discusses the grading of neuroendocrine neoplasms based on the Ki67 labeling index and mitotic activity, along with the histopathologic features and immunohistochemical markers (such as DAXX/ATRX, p53, RB1, and p16) useful in differentiating well-differentiated pancreatic neuroendocrine tumors from poorly differentiated pancreatic neuroendocrine carcinomas. Diagnostic pitfalls, immunohistochemical markers, and molecular markers for cystic fluid in diagnosing and differentiating intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, serous cystic neoplasms, and other benign pancreatic cysts are also presented.In the final article, authors Jennifer Vazzano, DO, MS, Wei Chen, MD, PhD, and Wendy L. Frankel, MD, review the diagnostic features essential for distinguishing pancreatic ductal carcinoma from chronic pancreatitis and metastatic pancreatic ductal carcinoma from benign liver lesions, including bile duct adenoma (peribiliary hamartoma) and von Meyenburg complex on frozen section analysis. This differentiation is pivotal for guiding intraoperative surgical decisions in pancreatic cancer patients, although it poses a significant challenge for many practicing pathologists. Notably, they emphasize that the pancreatic margin should be considered positive if it contains high-grade dysplasia (pancreatic intraepithelial neoplasia or intraductal papillary mucinous neoplasm) or invasive carcinoma. In such cases, surgeons may opt for additional resection to achieve a negative pancreatic margin. Their article underscores the critical importance of clear intraoperative communication between pathologists and surgeons to ensure appropriate surgical management for patients.We take immense pride in our society and its members, who dedicate themselves to enhancing the diagnosis, classification, and comprehension of neoplasms in the pancreatobiliary tree. We are delighted to present these review articles, which offer expert insights into the pearls and pitfalls in the interpretation of small biopsies and frozen sections of the pancreatobiliary tract. We hope readers find them both informative and enriching, contributing to a deeper understanding of this complex field.

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