Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
National Hospital Organization, Sendai Medical Center, Sendai, Japan.
Neuroendocrinology. 2020;110(5):393-403. doi: 10.1159/000502776. Epub 2019 Aug 19.
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.
世界卫生组织（WHO）2015 年版支气管肺神经内分泌肿瘤（BP-NEN）分类的准确性和可重复性存在争议。本研究旨在使用 WHO 2019 年消化系统神经内分泌肿瘤（DiS-NEN-WHO 2019）分类对 BP-NEN 进行分类和分级，并分析其准确性和预后影响。对来自日本和德国的两个 BP-NEN 队列的 393 个肿瘤（88%为手术切除）进行了回顾性分析，并将切除肿瘤的临床病理数据（n=301）与患者无病生存（DFS）相关联。DiS-NEN-WHO 2019 将 350 个肿瘤分为 91 个（26%）神经内分泌肿瘤（NET）G1、52 个（15%）NET G2、15 个（4%）NET G3 和 192 个（55%）神经内分泌癌（NEC）。NECs，但不是 NETs，免疫组织化学特征为异常的 p53（100%）和视网膜母细胞瘤 1（83%）表达。Ki67 指数比有丝分裂计数平均高 4 倍（p<0.0001），比有丝分裂计数更能准确预测预后。NET G3 患者的预后比 NET G1（p<0.01）和 NET G2 患者（p=0.02）差。在 5 年 DFS 后，NET G3 和 NEC 患者之间未检测到预后差异。研究结论为，如果仅基于 Ki67 指数对 BP-NEN 患者进行分级，根据 DiS-NEN-WHO 2019 分类将患者分为 3 个预后明确的 NET 组。单独使用有丝分裂计数可能会低估 NET 的恶性潜能。
