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Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?
Endocrine Pathology ( IF 4.4 ) Pub Date : 2021-02-27 , DOI: 10.1007/s12022-021-09668-z
Marco Volante 1 , Ozgur Mete 2 , Giuseppe Pelosi 3 , Anja C Roden 4 , Ernst Jan M Speel 5 , Silvia Uccella 6
Affiliation  

Thoracic (pulmonary and thymic) neuroendocrine tumors are well-differentiated epithelial neuroendocrine neoplasms that are classified into typical and atypical carcinoid tumors based on mitotic index cut offs and presence or absence of necrosis. This classification scheme is of great prognostic value but designed for surgical specimens, only. Deep molecular characterization of thoracic neuroendocrine tumors highlighted their difference with neuroendocrine carcinomas. Neuroendocrine tumors of the lung are characterized by a low mutational burden, and a high prevalence of mutations in chromatin remodeling and histone modification-related genes, whereas mutations in genes frequently altered in neuroendocrine carcinomas are rare. Molecular profiling divided thymic neuroendocrine tumors into three clusters with distinct clinical outcomes and characterized by a different average of copy number instability. Moreover, integrated histopathological, molecular and clinical evidence supports the existence of a grey zone category between neuroendocrine tumors (carcinoid tumors) and neuroendocrine carcinomas. Indeed, cases with well differentiated morphology but mitotic/Ki-67 indexes close to neuroendocrine carcinomas have been increasingly recognized. These are characterized by specific molecular profiles and have an aggressive clinical behavior. Finally, thoracic neuroendocrine tumors may arise in the background of genetic susceptibility, being MEN1 syndrome the well-defined familial form. However, pathologists should be aware of rarer germline variants that are associated with the concurrence of neuroendocrine tumors of the lung or their precursors (such as DIPNECH) with other neoplasms, including but not limited to breast carcinomas. Therefore, genetic counseling for all young patients with thoracic neuroendocrine neoplasia and/or any patient with pathological evidence of neuroendocrine cell hyperplasia-to-neoplasia progression sequence or multifocal disease should be considered.



中文翻译:

分化良好的肺和胸腺神经内分泌肿瘤的分子病理学:病理学家需要了解什么?

胸部(肺和胸腺)神经内分泌肿瘤是分化良好的上皮神经内分泌肿瘤,根据有丝分裂指数截止和是否存在坏死分为典型和非典型类癌肿瘤。这种分类方案具有很大的预后价值,但仅针对手术标本设计。胸部神经内分泌肿瘤的深层分子特征突出了它们与神经内分泌癌的差异。肺部神经内分泌肿瘤的特点是突变负荷低,染色质重塑和组蛋白修饰相关基因突变发生率高,而神经内分泌癌中经常改变的基因突变很少见。分子分析将胸腺神经内分泌肿瘤分为三类,具有不同的临床结果,并以不同的平均拷贝数不稳定性为特征。此外,综合组织病理学、分子和临床证据支持神经内分泌肿瘤(类癌)和神经内分泌癌之间存在灰色地带类别。事实上,形态分化良好但有丝分裂/Ki-67 指数接近神经内分泌癌的病例已得到越来越多的认可。它们具有特定的分子特征并具有侵袭性的临床行为。最后,胸部神经内分泌肿瘤可能在遗传易感性的背景下出现,MEN1 综合征是明确的家族形式。然而,病理学家应该意识到与肺部神经内分泌肿瘤或其前体肿瘤(例如 DIPNECH)与其他肿瘤(包括但不限于乳腺癌)并发相关的罕见种系变异。因此,应考虑对所有患有胸部神经内分泌肿瘤的年轻患者和/或任何具有神经内分泌细胞增生到肿瘤进展顺序或多灶性疾病病理证据的患者进行遗传咨询。

更新日期:2021-02-28
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