Pathologic Considerations in Gastroenteropancreatic Neuroendocrine Tumors

Surg Oncol Clin N Am. 2020 Apr;29(2):185-208. doi: 10.1016/j.soc.2019.11.003.


This review serves as a primer on contemporary neuroendocrine neoplasm classification, with an emphasis on gastroenteropancreatic well-differentiated neuroendocrine tumors. Topics discussed include general features of neuroendocrine neoplasms, general neuroendocrine marker immunohistochemistry, the distinction of well-differentiated neuroendocrine tumor from pheochromocytoma/paraganglioma and other diagnostic mimics and poorly differentiated neuroendocrine carcinoma from diagnostic mimics, the concepts of differentiation and grade and the application of Ki-67 immunohistochemistry to determine the latter, the various WHO classifications of neuroendocrine neoplasms including the 2019 WHO classification of gastroenteropancreatic tumors, organ-specific considerations for gastroenteropancreatic well-differentiated neuroendocrine tumors, immunohistochemistry to determine site of origin in metastatic well-differentiated neuroendocrine tumor of occult origin, immunohistochemistry in the distinction of well-differentiated neuroendocrine tumor G3 from large cell neuroendocrine carcinoma, and, finally, required and recommended reporting elements for biopsies and resections of gastroenteropancreatic neuroendocrine epithelial neoplasms.

Keywords: Differentiation; Grade; Immunohistochemistry; Ki-67; Neuroendocrine; Site of origin; WHO classification.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / analysis*
  • Cell Differentiation
  • Humans
  • Immunohistochemistry
  • Intestinal Neoplasms / metabolism
  • Intestinal Neoplasms / pathology*
  • Neoplasm Grading
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / pathology*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*


  • Biomarkers, Tumor

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor