喉部神经内分泌肿瘤（NETs）

文献信息

中文摘要

目的： 综述关于喉部神经内分泌肿瘤（NETs）的当前知识状况，特别关注其流行病学、病因发病机制、临床病理特征、免疫组化表型及鉴别诊断。方法：叙述性综述。结果：喉部NETs的诊断标准最近在第5版WHO头颈部肿瘤分类中被定义，该分类新引入了NET、3级（G3 NET）这一实体。然而，其中一些标准仍被认为是暂定性的。喉部最常见的NET是G2 NET。这些肿瘤通常影响老年男性，声门上区是最常见的部位。为了明确诊断，必须使用细胞角蛋白和神经内分泌标志物（如嗜铬粒蛋白、INSM1、突触素）来证明这些肿瘤的上皮来源和神经内分泌分化。各NET类型之间的区分基于核分裂活性和/或Ki-67增殖指数，以及坏死的存在与否。喉部NETs通常表现为野生型p53表达以及保留的Rb1和生长抑素受体2表达。这可用于与神经内分泌癌（NECs）的鉴别诊断。鉴于喉部NETs常表达降钙素，必须与甲状腺髓样癌（MTC）相鉴别，尤其是在淋巴结转移中。最近已证实喉部NETs中HRAS基因突变频率高，这强调了它们与胃肠胰和胸肺对应肿瘤的独特性。结论：通过利用所提出的各类型喉部NETs诊断标准，预计将获得关于这些极其罕见肿瘤的临床病理特征的更精确知识，特别是关于其生物学行为和预后方面。

英文摘要

To review the current state of knowledge regarding neuroendocrine tumors (NETs) of the larynx, with a particular focus on their epidemiology, etiopathogenesis, clinico-pathological features, immunohistochemical profile, and differential diagnostics. Narrative review. Diagnostic criteria for laryngeal NETs were recently defined in the 5th edition of the WHO Classification of Head and Neck Tumors, which newly introduces the entity of NET, grade 3 (G3 NET). However, some of these criteria are still considered provisional. The most common NET of the larynx is the G2 NET. These tumors typically affect older men, with the supraglottic region being the most frequent localization. For a definitive diagnosis, it is essential to demonstrate the epithelial origin and neuroendocrine differentiation of these tumors using cytokeratins and neuroendocrine markers (e.g., chromogranin, INSM1, synaptophysin). The differentiation between individual NET types is based on mitotic activity and/or Ki-67 proliferation index, as well as the presence or absence of necrosis. Laryngeal NETs typically exhibit wild-type p53 expression and retained Rb1 and somatostatin receptor 2 expression. This can be utilized in the differential diagnosis from neuroendocrine carcinomas (NECs). Given that laryngeal NETs frequently express calcitonin, they must be differentiated from medullary thyroid carcinoma (MTC), particularly in lymph node metastases. A high frequency of HRAS gene mutations has been recently demonstrated in laryngeal NETs, underlining their distinctness from their gastroenteropancreatic and thoracopulmonary counterparts. By utilizing the proposed diagnostic criteria for individual types of laryngeal NETs, it is anticipated that more precise knowledge regarding the clinico-pathological characteristics of these exceedingly rare tumors will be obtained, particularly with respect to their biological behavior and prognosis.