Neuroendocrinology

Research Article

Classification and Prognostic Stratification of Bronchopulmonary Neuroendocrine Neoplasms

Oka N.a,b · Kasajima A.a,c,d · Konukiewitz B.c · Sakurada A.e · Okada Y.e · Kameya T.f · Weichert W.c,d · Ishikawa Y.g · Suzuki H.b · Sasano H.a · Klöppel G.c

Author affiliations

aDepartment of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
bNational Hospital Organization, Sendai Medical Center, Sendai, Japan
cDepartment of Pathology, Technical University Munich, Munich, Germany
dMember of the German Cancer Consortium (DKTK), Heidelberg, Germany
eDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University Graduate School of Medicine, Sendai, Japan
fDivision of Pathology, Shizuoka Cancer Centre Hospital and Research Institute, Shizuoka, Japan
gDivision of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan

Keywords: LungNeuroendocrine neoplasmWorld Health Organization classification

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Neuroendocrinology 2020;110:393–403
https://doi.org/10.1159/000502776

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Article / Publication Details

First-Page Preview
Abstract of Research Article

Received: March 19, 2019
Accepted: August 13, 2019
Published online: August 19, 2019
Issue release date: April 2020

Number of Print Pages: 11
Number of Figures: 3
Number of Tables: 3

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN

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.

© 2019 S. Karger AG, Basel



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Article / Publication Details

First-Page Preview
Abstract of Research Article

Received: March 19, 2019
Accepted: August 13, 2019
Published online: August 19, 2019
Issue release date: April 2020

Number of Print Pages: 11
Number of Figures: 3
Number of Tables: 3

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN

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2020, Vol.110, No. 5

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