Departments of Pathology.
Department of Pathology and Genetics, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
Am J Surg Pathol. 2018 Feb;42(2):e11-e27. doi: 10.1097/PAS.0000000000000980.
Salivary gland neoplasms are a morphologically heterogenous group of lesions that are often diagnostically challenging. In recent years, considerable progress in salivary gland taxonomy has been reached by the discovery of tumor type-specific fusion oncogenes generated by chromosome translocations. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive genomic characteristics. Mammary analog secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion. Hyalinizing clear cell carcinoma is a low-grade tumor with infrequent nodal and distant metastasis, recently shown to harbor an EWSR1-ATF1 gene fusion. The CRTC1-MAML2 fusion gene resulting from a t(11;19)(q21;p13) translocation, is now known to be a feature of both low-grade and high-grade mucoepidermoid carcinomas associated with improved survival. A t(6;9)(q22-23;p23-34) translocation resulting in a MYB-NFIB gene fusion has been identified in the majority of adenoid cystic carcinomas. Polymorphous (low-grade) adenocarcinoma and cribriform adenocarcinoma of (minor) salivary gland origin are related entities with partly differing clinicopathologic and genomic profiles; they are the subject of an ongoing taxonomic debate. Polymorphous (low-grade) adenocarcinomas are characterized by hot spot point E710D mutations in the PRKD1 gene, whereas cribriform adenocarcinoma of (minor) salivary glands origin are characterized by translocations involving the PRKD1-3 genes. Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with morphologic and molecular features akin to invasive ductal carcinoma of the breast, including HER2 gene amplification, mutations of TP53, PIK3CA, and HRAS and loss or mutation of PTEN. Notably, a recurrent NCOA4-RET fusion has also been found in SDC. A subset of SDC with apocrine morphology is associated with overexpression of androgen receptors. As these genetic aberrations are recurrent they serve as powerful diagnostic tools in salivary gland tumor diagnosis, and therefore also in refinement of salivary gland cancer classification. Moreover, they are promising as prognostic biomarkers and targets of therapy.
唾液腺肿瘤是一组形态学上异质性的病变，常常具有诊断挑战性。近年来，通过发现染色体易位产生的肿瘤类型特异性融合癌基因，在唾液腺分类学方面取得了相当大的进展。本综述描述了一组精选的唾液腺癌的临床病理特征，重点是其独特的基因组特征。乳腺样分泌癌是一种最近描述的实体，其特征是 t(12;15)(p13;q25)易位导致 ETV6-NTRK3 融合。透明细胞癌是一种低级别肿瘤，淋巴结和远处转移不常见，最近显示存在 EWSR1-ATF1 基因融合。CRTC1-MAML2 融合基因源于 t(11;19)(q21;p13)易位，现在已知是与改善生存相关的低级别和高级别黏液表皮样癌的特征。t(6;9)(q22-23;p23-34)易位导致 MYB-NFIB 基因融合已在大多数腺样囊性癌中被识别。多形性（低级别）腺癌和来源于小唾液腺的筛状腺癌是具有部分不同的临床病理和基因组特征的相关实体；它们是正在进行的分类学争论的主题。多形性（低级别）腺癌的特征是 PRKD1 基因中的热点 E710D 突变，而来源于小唾液腺的筛状腺癌的特征是涉及 PRKD1-3 基因的易位。唾液腺癌（SDC）是一种高级别腺癌，具有类似于乳腺浸润性导管癌的形态学和分子特征，包括 HER2 基因扩增、TP53、PIK3CA 和 HRAS 突变以及 PTEN 缺失或突变。值得注意的是，SDC 中也发现了复发性 NCOA4-RET 融合。具有大汗腺形态的 SDC 亚组与雄激素受体的过度表达相关。由于这些遗传异常是复发性的，因此它们可作为唾液腺肿瘤诊断的有力诊断工具，从而也可用于细化唾液腺癌的分类。此外，它们有希望成为预后生物标志物和治疗靶点。
