Review ArticlesNeuroendocrine Neoplasms of the Pancreas: Diagnostic Challenges and Practical ApproachAlipour, Zahra MD*; Sweeney, Jacob R. MD†; Zhang, Qingzhao MD, PhD*; Yang, Zhaohai MD, PhD* Author Information *Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman, School of Medicine, Philadelphia, PA †Department of Pathology, Cleveland Clinic, Cleveland, OH The authors have no funding or conflicts of interest to disclose. Reprints: Zhaohai Yang, MD, PhD, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 3400 Spruce Street, 6 Founders, Philadelphia, PA 19104 (e-mail: [email protected]). All figures can be viewed online in color at www.anatomicpathology.com. Advances In Anatomic Pathology 30(1):p 58-68, January 2023. | DOI: 10.1097/PAP.0000000000000369 Buy Metrics Abstract Most pancreatic neuroendocrine neoplasms are slow-growing, and the patients may survive for many years, even after distant metastasis. The tumors usually display characteristic organoid growth patterns with typical neuroendocrine morphology. A smaller portion of the tumors follows a more precipitous clinical course. The classification has evolved from morphologic patterns to the current World Health Organization classification, with better-defined grading and prognostic criteria. Recent advances in molecular pathology have further improved our understanding of the pathogenesis of these tumors. Various issues and challenges remain, including the correct recognition of a neuroendocrine neoplasm, accurate classification and grading of the tumor, and differentiation from mimickers. This review focuses on the practical aspects during the workup of pancreatic neuroendocrine neoplasms and attempts to provide a general framework to help achieve an accurate diagnosis, classification, and grading. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.