Classification and Prognostic Stratification of Bronchopulmonary Neuroendocrine Neoplasms

Naomi Oka, Atsuko Kasajima, Björn Konukiewitz, Akira Sakurada, Yoshinori Okada, Toru Kameya, Wilko Weichert, Yuichi Ishikawa, Hiroyoshi Suzuki, Hironobu Sasano, Günter Klöppel

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)393-403
Number of pages11
Issue number5
Publication statusPublished - 2020 Apr 1


  • Lung
  • Neuroendocrine neoplasm
  • World Health Organization classification


Dive into the research topics of 'Classification and Prognostic Stratification of Bronchopulmonary Neuroendocrine Neoplasms'. Together they form a unique fingerprint.

Cite this