Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2022; 28(17): 1751-1767
Published online May 7, 2022. doi: 10.3748/wjg.v28.i17.1751
New insights in diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms
Feng Yin, Zi-Hao Wu, Jin-Ping Lai
Feng Yin, Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO 65212, United States
Zi-Hao Wu, Department of Surgery, University of Missouri, Columbia, MO 65212, United States
Jin-Ping Lai, Department of Pathology, Kaiser Permanente Sacramento Medical Center, Sacramento, CA 95825, United States
Author contributions: Yin F wrote and finalized the manuscript; Wu ZH critically reviewed the manuscript; Lai JP collected and analyzed the data, made the figures, and finalized the manuscript; all authors have approved the final manuscript.
Conflict-of-interest statement: The authors declare that they have no competing interests in this study.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jin-Ping Lai, MD, PhD, Associate Professor, Doctor, Department of Pathology, Kaiser Permanente Sacramento Medical Center, 2025 Morse Ave, Sacramento, CA 95825, United States. jinping.x.lai@kp.org
Received: October 21, 2021
Peer-review started: October 21, 2021
First decision: December 27, 2021
Revised: January 6, 2022
Accepted: April 4, 2022
Article in press: April 4, 2022
Published online: May 7, 2022
Processing time: 190 Days and 2.9 Hours
Abstract

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare epithelial neoplasms derived from pluripotent endocrine cells along the gastrointestinal tract and pancreas. GEP-NENs are classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas. Despite overlapping morphological features, GEP-NENs vary in molecular biology, epigenetic, clinical behavior, treatment response, and prognosis features and remain an unmet clinical challenge. In this review, we introduce recent updates on the histopathologic classification, including the tumor grading and staging system, molecular genetics, and systemic evaluation of the diagnosis and treatment of GEP-NENs at different anatomic sites, together with some insights into the diagnosis of challenging and unusual cases. We also discuss the application of novel therapeutic approaches for GEP-NENs, including peptide receptor radionuclide therapy, targeted therapy, and immunotherapy with immune checkpoint inhibitors. These findings will help improve patient care with precise diagnosis and individualized treatment of patients with GEP-NENs.

Keywords: Gastroenteropancreatic neuroendocrine neoplasms; Neuroendocrine tumours; Neuroendocrine carcinoma; World Health Organization classification; Diagnosis; Treatment

Core Tip: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors, but their incidence rates have been steadily increasing over the past 3 decades. GEP-NENs consist of a genetically heterogeneous group of tumors ranging from slow-growing well-differentiated neuroendocrine tumor to aggressive, poorly differentiated neuroendocrine carcinoma. Surgery is the cornerstone for the clinical management of localized tumors. However, GEP-NENs have frequently been diagnosed at a later stage and, therefore, remain an unmet clinical challenge. In this review, we discuss recent updates on the histopathologic classification, molecular genetics, and systemic evaluation of diagnosis and treatment of GEP-NENs at different anatomic sites.