胃神经内分泌肿瘤临床分型的共识和争议

Consensus and controversy on subtype classification of gastric neuroendocrine neoplasms

胃神经内分泌肿瘤（NEN）是一组高度异质性的少见肿瘤，多为惰性生长．也可能进展迅速，类似于胃腺癌的发展进程。欧洲神经内分泌肿瘤学会（ENETS）指南（2006版）将分化良好的胃神经内分泌瘤（NET）分为1型、2型和3型；北美神经内分泌肿瘤学会（NANETS）和美国国立综合癌症网（NCCN）指南也是如此。但是，自从ENETS指南（2012版）发布以来，胃NEN临床分型处于混乱状态．主要对第3型病理学描述上出现了较大改动，界定不清，令人迷惑不解。ENETS指南（2012版）中说到，3型NEN通常是单发，病理分级多数为WHO3级（NECG3），Ki-67指数较高，肿瘤直径较大，呈浸润性生长；而2006版对3型肿瘤指分化良好或中等分化，不是1型也不是2型，无背景疾病的其他胃NEN。而2016版ENETS共识指南更新中，关于临床和组织学特点的描述，文字改为“分化良好的胃NEN可分为3型”。但病理学依旧为G3NEC，照此分类方法．那些分化良好的不是1型也不是2型的胃NET患者似乎无法分型了。本文提出“中国胃肠胰神经内分泌肿瘤专家共识（2016版）”对胃NEN临床分型的建议（4型分类法），即分化良好的胃NET分3型，分化差的胃NEC9-3于第4型。这种4型分类法涵盖了所有的胃NEN患者，建议临床医师推广使用。

Gastric neuroendocrine neoplasms （g-NENs） are a heterogeneous group of tumors. Often silent, g-NENs may however be aggressive and sometimes mimic the course of gastric adenocarcinoma. Well-differentiated gastric neuroeudocrine tumors （NET） can be subclassified into 3 distinct groups （type1, type 2 and type 3） according to Neuroendocrine Neoplasm Society （ENETS） guideline version 2006 as well as North America Neuroendocrlne Tumor Society （NANETS） and National Comprehensive Cancer Network （NCCN） guidelines. However, since the publication of ENETS guideline version 2012, the subtype classification of g-NENs has been confusing due to the revised definition of type 3 g-NEN in versions 2012 and 2016. ENETS version 2012 indicated that type 3 g-NEN was usually solitary and its pathology was mostly WHO grade 3 （neuroendocrine carcinoma, NEC G3） with higher Ki-67 index, greater tumor diameter and infiltrative growth. While ENETS version 2006 showed that type 3 g-NEN was well-differentiated or moderate-differentiated, neither type 1 nor type 2, and other g-NENs without basic diseases. Besides, in renewal consensus guidance of ENETS version 2016, description about clinical and histological features altered as ＂well-differentiated g-NEN can be classified as type 3＂, but its pathology is still NEC G3. According to such classification, those gastric NET patients with well-differentiated, neither type 1 nor type 2 tumors, seem to be unable to classify. In this article, description about the subtype classification of g-NENs in several guidelines, including ENETS versions 2006, 2012 and 2016, NANETS version 2010 and NCCN version 2016, is introduced and the controversy focuses on type 3 g-NEN definition by ENETS versions 2012 and 2016. Hence, the four- type classification of g-NENs is recommended, which has been written in Chinese Consensus for the Diagnosis and Management of GEP-NEN （version 2016）. Well-differentiated gastric NET is classified as type 3, and poor-differentiated gastric NEC as type 4. This four-type classification of g-NENs covers all the patients with g-NENs. Advances on clinical research of g-NENs in China are reviewed and the existing problems are analyzed. We also put forward the research direction in the future.