Classification and Prognostic Stratification of Bronchopulmonary Neuroendocrine Neoplasms

Neuroendocrinology. 2020;110(5):393-403. doi: 10.1159/000502776. Epub 2019 Aug 19.

Abstract

The accuracy and reproducibility of the World Health Organization (WHO) 2015 classification of bronchopulmonary neuroendocrine neoplasms (BP-NENs) is disputed. The aim of this study is to classify and grade BP-NENs using the WHO 2019 classification of digestive system NENs (DiS-NEN-WHO 2019), and to analyze its accuracy and prognostic impact. Two BP-NEN cohorts from Japan and Germany, 393 tumors (88% surgically resected), were reviewed and the clinicopathological data of the resected tumors (n = 301) correlated to patients' disease-free survival (DFS). The DiS-NEN-WHO 2019 stratified the 350 tumors into 91 (26%) neuroendocrine tumors (NET) G1, 52 (15%) NET G2, 15 (4%) NET G3, and 192 (55%) neuroendocrine carcinomas (NEC). NECs, but not NETs, were immunohistochemically characterized by abnormal p53 (100%) and retinoblastoma 1 (83%) expression. The Ki67 index, which was on average 4 times higher than mitotic count (p < 0.0001), was prognostically more accurate than the mitotic count. NET G3 patients had a worse outcome than NET G1 (p < 0.01) and NET G2 patients (p = 0.02), respectively. No prognostic difference was detected between NET G3 and NEC patients after 5 year DFS. It is concluded that stratifying BP-NEN patients according to the DiS-NEN-WHO 2019 classification results in 3 prognostically well-defined NET groups, if grading is solely based on Ki67 index. Mitotic count alone may underestimate malignant potential of NETs.

Keywords: Lung; Neuroendocrine neoplasm; World Health Organization classification.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor*
  • Cohort Studies
  • Female
  • Humans
  • Ki-67 Antigen
  • Lung Neoplasms* / classification
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Neoplasm Grading / standards*
  • Neuroendocrine Tumors* / classification
  • Neuroendocrine Tumors* / diagnosis
  • Neuroendocrine Tumors* / metabolism
  • Neuroendocrine Tumors* / pathology
  • Prognosis
  • World Health Organization

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • MKI67 protein, human