Updates in histopathological classification and tissue biomarkers of digestive neuroendocrine neoplasms: What the clinician should know

Histopathological classifications of neuroendocrine neoplasms (NEN) change regularly and the latest WHO classification published in 2022, which concerns all NEN in the body, attempts to standardize classi-fications in the different locations. Differentiation and proliferation mainly assessed by Ki-67 index are still the cornerstone of those classifications. However, many markers are now used for diagnostic (to check neuroendocrine differentiation, to identify the site of origin of a metastasis, to help separating high-grade neuroendocrine tu-mors/NET and neuroendocrine carcinoma/NEC), prognostic or ther-anostic purposes. NENs are often heterogeneous and this can lead to difficulties in classifications, biomarker and prognostic assessment. These different points are discussed successively in this review, in-sisting especially on the frequent digestive, gastro-entero-pancreatic (GEP) localizations.(c) 2023 Published by Elsevier Ltd.