Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2022; 28(10): 1009-1023
Published online Mar 14, 2022. doi: 10.3748/wjg.v28.i10.1009
An update on the diagnosis of gastroenteropancreatic neuroendocrine neoplasms
Jiayun M Fang, Jay Li, Jiaqi Shi
Jiayun M Fang, Jiaqi Shi, Department of Pathology & Clinical Labs, University of Michigan, Ann Arbor, MI 48109, United States
Jay Li, Medical Scientist Training Program, University of Michigan, Ann Arbor, MI 48109, United States
Author contributions: Fang JM drafted the manuscript and prepared the figures and tables; Li J drafted the manuscript and provided input in the writing; Shi J formulated the idea, designed the outline, and edited the manuscript.
Supported by the National Cancer Institute of the National Institutes of Health, No. K08CA234222 (JS).
Conflict-of-interest statement: Dr. Shi reports grants from NIH/NCI, during the conduct of the 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: Jiaqi Shi, MD, PhD, Associate Professor, Department of Pathology & Clinical Labs, University of Michigan, 2800 Plymouth Rd. NCRC Bldg 35, Ann Arbor, MI 48109, United States. jiaqis@umich.edu
Received: October 17, 2021
Peer-review started: October 17, 2021
First decision: November 17, 2021
Revised: November 26, 2021
Accepted: February 10, 2022
Article in press: February 10, 2022
Published online: March 14, 2022
Abstract

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) arise from neuroendocrine cells found throughout the gastrointestinal tract and islet cells of the pancreas. The incidence and prevalence of GEP-NENs have been increasing each year due to higher awareness, improved diagnostic modalities, and increased incidental detection on cross-sectional imaging and endoscopy for cancer screening and other conditions and symptoms. GEP-NENs are a heterogeneous group of tumors and have a wide range in clinical presentation, histopathologic features, and molecular biology. Clinical presentation most commonly depends on whether the GEP-NEN secretes an active hormone. The World Health Organization recently updated the classification of GEP-NENs to introduce a distinction between high-grade neuroendocrine tumors and neuroendocrine carcinomas, which can be identified using histology and molecular studies and are more aggressive with a worse prognosis compared to high-grade neuroendocrine tumors. As our understanding of the biology of GEP-NENs has grown, new and improved diagnostic modalities can be developed and optimized. Here, we discuss clinical features and updates in diagnosis, including histopathological analysis, biomarkers, molecular techniques, and radiology of GEP-NENs. We review established diagnostic tests and discuss promising novel diagnostic tests that are currently in development or require further investigation and validation prior to broad utilization in patient care.

Keywords: Neuroendocrine tumor, Neuroendocrine carcinoma, Gastrointestinal, Pancreas, Pathology, Diagnosis

Core Tip: Over the past decade, our understanding of the molecular biology underlying gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) has improved our available diagnostic tools. Although there have been many reviews on the diagnosis of GEP-NENs, the majority focus on one aspect of the diagnosis. This review provides a comprehensive discussion of the current and upcoming diagnostic tools available for GEP-NENs, including histopathology, new biomarkers, molecular techniques, and radiology.