Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., Lisbon, Portugal.
Pathobiology. 2018;85(1-2):85-95. doi: 10.1159/000479070. Epub 2017 Sep 21.
Salivary gland tumor classification encompasses a vast list of benign and malignant neoplasms. Their morphological diversity is recognized not only between different entities but also within individual tumors. Tumor categories as described by the World Health Organization reflect, in part, a true genetic heterogeneity (e.g., translocations involving CRTC1 and CRTC3-MAML2 genes in mucoepidermoid carcinoma and MYB-NFIB fusion in adenoid cystic carcinoma). Carcinoma ex pleomorphic adenoma shows diversity in its histological appearance, but recurrent rearrangements on PLAG1 and HMGA2 are common to its benign precursor. More recently, new categories have been defined, like secretory carcinoma with the t(12;15) (p13;q25) ETV6-NTRK3 translocation and clear-cell carcinoma with EWSR1-ATF1 fusion. Recent studies on cribriform adenocarcinoma of minor salivary gland origin and epithelial-myoepithelial carcinoma point to a correlation with their morphological features. All of these advances show that the search of a histogenetic and genetic basis for salivary gland tumors is helping to clarify morphological categories and unraveling new ones. Nevertheless, currently morphology is still the hallmark of tumor classification and the gold standard. The therapeutic options for advanced tumors remain very limited but the discovery of translocation-generated gene fusions and increased knowledge of the genomic information of salivary gland tumors is creating opportunities for the development of specific targeted therapies.
唾液腺肿瘤的分类包括大量的良性和恶性肿瘤。它们的形态多样性不仅在不同实体之间存在,而且在单个肿瘤中也存在。世界卫生组织(WHO)所描述的肿瘤类别部分反映了真正的遗传异质性(例如,在黏液表皮样癌中涉及 CRTC1 和 CRTC3-MAML2 基因的易位,以及在腺样囊性癌中 MYB-NFIB 融合)。癌在多形性腺瘤中的表现出多样性,但其良性前体中常见的是 PLAG1 和 HMGA2 的反复重排。最近,已经定义了新的类别,如具有 t(12;15)(p13;q25)ETV6-NTRK3 易位的分泌癌和具有 EWSR1-ATF1 融合的透明细胞癌。最近对来源于小唾液腺的筛状腺癌和上皮-肌上皮癌的研究表明,它们与形态特征相关。所有这些进展表明,对唾液腺肿瘤的组织发生和遗传基础的研究有助于阐明形态类别并揭示新的类别。然而,目前形态仍然是肿瘤分类的标志和金标准。晚期肿瘤的治疗选择仍然非常有限,但易位产生的基因融合的发现以及对唾液腺肿瘤基因组信息的深入了解,为开发特异性靶向治疗创造了机会。