Neuroendocrine Neoplasms of the GI Tract: Diagnosis, Reporting, and Clinical Correlates

Although neuroendocrine neoplasms (NEN) are encountered at virtually every anatomic site, the GI tract is the most common site of involvement. These tumors are common enough to be routinely encountered, but uncommon enough for most general pathologists to feel they haven’t achieved diagnostic mastery. This lack of comfort is further attributable to frequently shifting classification schemes and an ever-expanding list of applicable immunohistochemical markers. This lecture will focus on the most frequent diagnostic errors, challenges, and questions that are encountered in a neuroendocrine-heavy practice. Updates from the 2022 WHO Endocrine/Neuroendocrine Tumor Blue Book and the contemporary WHO classification of gastroenteropancreatic (GEP) NENs (contrasting it with the lung classification) will be presented. A brief discussion of the application of Ki-67 to NEN grading and GEP-neuroendocrine tumor (NET) site-specific diagnostic and reporting considerations will follow. Diagnostic algorithms for NET site of origin, neuroendocrine carcinoma (NEC) site of origin, and the distinction of NET G3 from NEC will be shared. A presentation of the essential elements of a NEN pathology report concludes the video.

Originally published on January 2, 2026

Lecture Presenter

Andrew M. Bellizzi, MD Clinical Professor, Director of Immunohistochemistry, Director of GI Pathology Fellowship Track, Department of Pathology University of Iowa Hospitals and Clinics Director of GI Pathology Holden Comprehensive Cancer Center

Dr. Andrew M. Bellizzi is a clinical professor in the Department of Pathology at the University of Iowa. Dr. Bellizzi completed undergraduate work in Anthropology and Science Preprofessional Studies at the University of Notre Dame and received his medical degree from Northwestern University. Following combined training in anatomic and clinical pathology at the University of Virginia, he completed a fellowship in gastrointestinal and liver pathology at The Ohio State University. Dr. Bellizzi served as a junior faculty member at Brigham and Women’s Hospital for two years before moving to Iowa.

Dr. Bellizzi is director of Immunohistochemistry and GI Pathology and codirector of the GI Pathology Fellowship at the University of Iowa. He is an active member of the United States and Canadian Academy of Pathology (USCAP), the American Society for Clinical Pathology (ASCP), the College of American Pathologists (CAP), and the North American Neuroendocrine Tumor Society (NANETS), including serving as the immediate past chair of the USCAP Stowell-Orbison Award and the CAP Immunohistochemistry committees. He is secretary-treasurer of the International Society for Immunohistochemistry and Molecular Morphology. Dr. Bellizzi serves as an associate editor (reviews) for Applied Immunohistochemistry and Molecular Morphology, a section editor (immunohistochemistry) for Archives of Pathology and Laboratory Medicine, and an assistant editor (GI pathology) for the American Journal of Clinical Pathology. He is on the Neuroendocrine Tumor Expert Panel for the ninth edition of the AJCC Cancer Staging Manual.

Dr. Bellizzi’s research interests include the diagnosis, classification, and etiopathogenesis of human disease, with an emphasis on gastrointestinal, pancreatic, neuroendocrine, and hereditary tumors. His research program focuses on applications of diagnostic immunohistochemistry.

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Objectives

After this presentation, participants will be able to:

• Apply the WHO 2019 GI “Blue Book” neuroendocrine classification to GEP-NENs
• Compare and contrast the GEP-NEN and WHO 2021 lung NEN classifications
• Cite GEP-NEN-relevant updates in the WHO 2022 Endocrine and Neuroendocrine Tumor “Blue Book”
• Describe clinically meaningful updates in the etiologic classification of gastric NETs, especially the emerging recognition of PPI-associated tumors
• Analyze NET site-specific frequent clinical/diagnostic conundrums
• Apply a panel of immunostains to determine NET and NEC site of origin
• Apply a panel of immunostains to adjudicate the differential diagnosis of NET G3 vs. NEC
• Apply an outcomes-centric approach Ki-67 IHC-based grading

Sponsored by:

University of Utah School of Medicine, Department of Pathology, and ARUP Laboratories