Neuroendocrine tumor G3 of bronchopulmonary origin and its classification

Pathol Int. 2022 Oct;72(10):488-495. doi: 10.1111/pin.13266. Epub 2022 Aug 19.


Neuroendocrine tumors (NET) with high proliferative activity (Ki-67 index >20% and/or mitotic counts >2 mm2 ) are defined as NET G3 in the 2019 World Health Organization (WHO) classification of digestive system neuroendocrine neoplasms (NENs). NETs G3 occur mostly in the pancreas, colon, rectum, and stomach and only rarely in the small intestine and the appendix. In the bronchopulmonary system, similar tumors have also been recognized and were mostly classified as atypical carcinoid (AC) or large cell neuroendocrine carcinoma. Bronchopulmonary NENs that were classified as NETs G3 are characterized by histological and immunohistochemical similarities with carcinoids/NETs, and a clinical course that is more aggressive than with ACs and similar to that of neuroendocrine carcinomas. The morphomolecular and clinical features of bronchopulmonary neoplasms with a high proliferative activity were reviewed and a future classification system that is applicable for both digestive and bronchopulmonary NETs is proposed.

Keywords: Ki-67; NET G3; classification; lung neuroendocrine neoplasms.

Publication types

  • Review

MeSH terms

  • Bronchi
  • Carcinoid Tumor*
  • Carcinoma, Neuroendocrine*
  • Humans
  • Ki-67 Antigen
  • Neuroendocrine Tumors*
  • Pancreatic Neoplasms*
  • Receptor Protein-Tyrosine Kinases


  • Ki-67 Antigen
  • Receptor Protein-Tyrosine Kinases

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