Department of Pathology, Technical University Munich, Trogerstr. 18, 81675, Munich, Germany.
Member of the German Cancer Consortium (DKTK), Munich, Germany.
Virchows Arch. 2022 Feb;480(2):359-368. doi: 10.1007/s00428-021-03202-6. Epub 2021 Sep 9.
Limited data exist on high-grade neuroendocrine tumors (NETs G3) which represent a new category among neuroendocrine neoplasms (NEN). We analyzed NETs G3 in a consultation series regarding prevalence, origin, metastasis, and diagnostic problems. Based on the WHO classification of digestive system tumors, 130 NETs G3 (9%) were identified in 1513 NENs. NET G3 samples were more often obtained from metastatic sites (69%) than NET G1/G2 samples (24%). NET G3 metastases presented most frequently in the liver (74%) and originated from the pancreas (38/90, 42%), followed by the lung (9%), ileum (7%), stomach (3%), rectum (1%), and rare sites (2%) such as the prostate and breast. The primaries remained unknown in 15%. NETs G3 had a median Ki67 of 30% that distinguished them from NECs (60%), though with great overlap. The expression of site-specific markers, p53, Rb1, and SST2 was similar in NETs G3 and NETs G1/G2, except for p53 and Rb1 which were abnormally expressed in 8% and 7% of liver metastases from NET G3 but not from NET G1/G2. NETs G3 were frequently referred as NECs (39%) but could be well distinguished from NECs by normal p53 (92% versus 21%) and Rb1 expression (93% versus 41%) expression. In conclusion, NETs G3 are frequently discovered as liver metastases from pancreatic or pulmonary primaries and are often misinterpreted as NEC. p53 and Rb1 are powerful markers in the distinction of NET G3 from NEC. Rarely, carcinomas from non-digestive, non-pulmonary organs with neuroendocrine features may present as NET G3.
关于高级神经内分泌肿瘤 (NET G3) 的数据有限，其是神经内分泌肿瘤 (NEN) 中的一个新类别。我们分析了一系列咨询中 NET G3 的患病率、起源、转移和诊断问题。根据世界卫生组织消化系统肿瘤分类，在 1513 例 NEN 中发现了 130 例 NET G3（9%）。NET G3 样本更常来自转移部位（69%），而 NET G1/G2 样本则来自转移部位（24%）。NET G3 转移最常发生在肝脏（74%），起源于胰腺（38/90，42%），其次是肺（9%）、回肠（7%）、胃（3%）、直肠（1%）和罕见部位（2%），如前列腺和乳房。15%的原发灶仍未知。NET G3 的 Ki67 中位数为 30%，与 NEC（60%）有所区别，尽管有很大的重叠。NET G3 和 NET G1/G2 的特异性标志物 p53、Rb1 和 SST2 的表达相似，除了 p53 和 Rb1 在 NET G3 的肝转移中异常表达（8%和 7%），而在 NET G1/G2 中则无异常表达。NET G3 常被误诊为 NEC（39%），但通过正常的 p53（92%对 21%）和 Rb1 表达（93%对 41%）可以很好地区分 NET G3 和 NEC。总之，NET G3 常作为胰腺或肺原发灶的肝转移被发现，常被误诊为 NEC。p53 和 Rb1 是区分 NET G3 和 NEC 的有力标志物。罕见情况下，具有神经内分泌特征的非消化、非肺器官的癌可能表现为 NET G3。
