The Pancreatobiliary Pathology Society (PBPS) wants to thank Alain C. Borczuk, MD, and the Archives of Pathology & Laboratory Medicine for highlighting our society by publishing 3 review articles based on presentations given at the PBPS Companion Meeting during the 2022 United States and Canadian Academy of Pathology (USCAP) meeting.
The PBPS, officially formed in 2016, is actively collaborating with many international pathology associations/societies, including the College of American Pathologists, USCAP, the International Association of Pathologists, and the European Society of Pathology, and fosters excellence and collaboration in education, research, and the clinical practice of pancreatobiliary pathology around the world. Our website (https://pbpath.org) provides rich resources and educational materials on pancreatobiliary pathology.
The 2022 PBPS Companion Meeting, titled “Clonal Evolution of Pancreatobiliary Neoplasms,” consisted of 3 outstanding presentations: (1) neoplastic progression in neuroendocrine neoplasms of the pancreas, by David Klimstra, MD, on behalf of Aldo Scarpa, MD, PhD; (2) neoplastic progression in macroscopic precursor lesions of the pancreas, by Elizabeth Thompson, MD, PhD; and (3) neoplastic progression in macroscopic precursor lesions of the biliary tract by Yoh Zen, MD, PhD, FRCPath. Our special section includes 3 articles based on these presentations.
In the first article, Luchini and Scarpa review and discuss the histologic, molecular, and genomic alterations and the mechanisms associated with the neoplastic evolution and progression of pancreatic neuroendocrine neoplasms (PanNENs). The authors highlight 2 different pathways for the progression of PanNENs. The grade 1 or grade 2 well-differentiated pancreatic neuroendocrine tumor may progress to grade 3 tumor driven mainly by the DAXX/ATRX mutations and alternative lengthening of telomeres. In contrast, the histopathologic, molecular, and clinical features of poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs) are more closely related to pancreatic ductal adenocarcinoma, including KRAS mutations and alterations in tumor suppressors TP53 and Rb. The available data suggests that PanNEC may develop from a nonneuroendocrine glandular-epithelium origin. Therefore, accurate pathologic classification, grading, and molecular markers are important for the management of patients with PanNEN.
In the second article, Thompson systematically reviews the clinical and pathologic classifications of the macroscopic cystic precursor lesions of pancreatic ductal adenocarcinoma, including intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms, intraductal oncocytic papillary neoplasms (IOPNs), and intraductal tubulopapillary neoplasms. Thompson also provides an update on the molecular/genetic alterations that are associated with the development and progression of different types of cystic precursor lesions to invasive pancreatic ductal adenocarcinoma. The molecular signature, such as mutations in KRAS, GNAS, and RNF43 genes in IPMNs, PRKACA/PRKACB in IOPNs, and MAPK-associated genes, is increasingly used in the diagnosis and classification of pancreatic cystic lesions. Recent identification of molecular heterogeneity and polyclonality in IPMNs provides new insight into the tumorigenesis of cystic precursor lesions of the pancreas and their progression to invasive pancreatic ductal adenocarcinoma and has challenged traditional monoclonal models for the development of pancreatic neoplasia. More importantly, Thompson provides a timely update on the utility and clinical implications of the molecular marker testing by next-generation sequencing on cystic fluid or materials from fine-needle aspiration in the diagnosis, classification, clinical management, and prognosis of pancreatic cystic precursor lesions.
In the third article, Zen and Akita review the histopathologic, molecular, radiologic, and clinical features of intraductal papillary neoplasm of the bile duct (IPNB). Zen and Akita compared the clinical, histopathologic, and molecular features between type 1 IPNB and IPMN and between type 1 and type 2 IPNB. They demonstrate that type 1 IPNB is a unique, slow-growing precursor lesion of the bile duct with slow progression. Type 1 IPNB has distinct genetic features from de novo cholangiocarcinoma and shares clinical, histopathologic, and molecular features with IPMN of the pancreas, including mutations in APC, CTNNB1, STK11, and GNAS, although the frequencies of genetic mutations differ between these 2 entities. In contrast, type 2 IPNB often has invasive carcinoma at the initial presentation and has similar clinical, pathologic, and molecular features with cholangiocarcinoma. Based on the data that recurrent type 1 IPNB may develop in the biliary tree years after complete resection and typically has the same genetic abnormalities as the original neoplasm, the authors suggest that intrabiliary implantation rather than multifocal lesions is the possible mechanism of recurrence for type I IPNB. This paper provides new understanding for these rare entities, which may stimulate future collaborative studies on the molecular and genetic mechanisms underlying the malignant transformation of type 1 and type 2 IPNB.
We are extremely proud of our society and its members, who strive to improve the diagnosis and classification of and to advance our understanding of the neoplasms of the pancreatobiliary tree. We hope that you will enjoy these review articles highlighting the experts’ perspectives on the clonal evolution of pancreatobiliary neoplasms.
Huamin Wang, MD, PhD, is one of the founding members of the PBPS. Currently, he serves as the chair of the education committee and the chair of the Neoadjuvant Working Group of the PBPS. Wang is an internationally well-known gastrointestinal and pancreatic pathologist and a National Institutes of Health–funded physician scientist in the field of translational research on pancreatic cancers. Wang received his MD from Tongji Medical University (Wuhan, China) in 1987 and earned his PhD from the University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences (Houston) in 1999. His postgraduate training journey includes pathology residency training at the University of Texas McGovern Medical School (1999–2003) and a fellowship in selective surgical pathology at the University of Texas MD Anderson Cancer Center (2003–2004). Wang joined the Department of Pathology at MD Anderson Cancer Center in 2004. He is currently a professor with tenure and serves as the chief of gastrointestinal, liver, and pancreatic pathology. In addition, he holds joint appointments as a professor in the Department of Translational Molecular Pathology and in the MD Anderson UTHealth Graduate School of Biomedical Sciences. Wang has served as the principal investigator (PI), pathology core PI/leader, co-PI/coinvestigator for more than 50 ongoing or completed research grants, including SPOREs, P01s, U01s, many other National Institutes of Health/National Cancer Institute grants, and funding from various foundations. His laboratory research focuses on many aspects of pancreatic cancer, including protein kinase and phosphatase alterations, novel pathophysiologic mechanisms, and the development of new biomarkers. He has served as the chair or member for Department of Defense study sections. Wang has published more than 290 peer-reviewed publications, 21 invited review articles/letters to the editor, and 15 book chapters. He is the editor/section editor for 18 prestigious scientific journals, including serving as a section editor in gastrointestinal pathology for the Archives of Pathology & Laboratory Medicine and an ad-hoc reviewer for more than 40 journals. Wang served as the president of the Chinese American Pathologists Association from 2016 to 2017 and as a member of the USCAP publication committee and USCAP Young Investigator Award committee from 2017 to 2020. He is currently a member of the College of American Pathologists publication committee. His multifaceted role as a researcher, educator, and leader underscores his profound impact on the advancement of pancreatobiliary pathology and cancer research.
Olca Basturk, MD, is a world-renowned pathologist in the field of pancreas and biliary tract pathology. She currently serves as an attending pathologist at Memorial Sloan Kettering Cancer Center in New York, New York, as well as chair of the tissue utilization committee at the David M. Rubenstein Center for Pancreatic Cancer Research in New York, New York. Basturk earned her MD from the Ege University School of Medicine in Izmir, Turkey. She then successfully completed 2 pathology residencies (one in anatomic pathology at Celal Bayar University, Manisa, Turkey, and another in anatomic and clinical pathology at New York University, New York). Basturk also completed 2 clinical fellowships (oncologic surgical pathology at Memorial Sloan Kettering Cancer Center and gastrointestinal pathology at Memorial Sloan Kettering Cancer Center and Cornell University, New York, New York). Basturk joined the faculty of Memorial Sloan Kettering Cancer Center and Weill Medical College, Cornell University, in 2012. Since then, she has conducted numerous scientific studies on pancreas, gallbladder, and biliary cancers and published more than 160 PubMed-indexed articles as well as more than 45 book chapters, including chapters in the 2019 WHO Classification of Tumours of the Digestive System and 2022 WHO Classification of Tumours: Endocrine and Neuroendocrine Tumours. She is on the editorial boards of leading pathology journals, including the Archives of Pathology & Laboratory Medicine as a section editor for gastrointestinal pathology. Each year she gives multiple presentations at national and international congresses, courses, and meetings. Basturk is also a founding member of the PBPS and has served as the chair of the PBPS education committee. She is currently the president of the PBPS.