Departments of Pathology and Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Department of Biochemistry, Molecular Biology, and Biophysics, College of Biological Sciences.
Am J Surg Pathol. 2021 Oct 1;45(10):1337-1347. doi: 10.1097/PAS.0000000000001688.
Mucin-producing salivary adenocarcinomas were historically divided into separate colloid carcinoma, papillary cystadenocarcinoma, and signet ring cell carcinoma diagnoses based on histologic pattern, but have recently been grouped together in the adenocarcinoma not otherwise specified category. It is currently unclear if these tumors represent 1 or more distinct entities and how they are related to well-circumscribed papillary mucinous lesions with recurrent AKT1 E17K mutations that were recently described as salivary intraductal papillary mucinous neoplasm. Here, we sought to evaluate the clinicopathologic and molecular features of salivary mucinous adenocarcinomas to clarify their classification. We identified 17 invasive mucin-producing salivary adenocarcinomas, 10 with a single histologic pattern, and 7 with mixed patterns. While most tumors demonstrated papillary growth (n=15), it was frequently intermixed with colloid (n=6) and signet ring (n=3) architecture with obvious transitions between patterns. All were cytokeratin 7 positive (100%) and cytokeratin 20 negative (0%). Next-generation sequencing performed on a subset demonstrated recurrent AKT1 E17K mutations in 8 cases (100%) and TP53 alterations in 7 cases (88%). Of 12 cases with clinical follow-up (median: 17 mo), 4 developed cervical lymph node metastases, all of which had colloid or signet ring components. Overall, overlapping histologic and immunohistochemical features coupled with recurrent AKT1 E17K mutations across patterns suggests that mucin-producing salivary adenocarcinomas represent a histologically diverse single entity that is closely related to tumors described as salivary intraductal papillary mucinous neoplasm. We propose a unified mucinous adenocarcinoma category subdivided into papillary, colloid, signet ring, and mixed subtypes to facilitate better recognition and classification of these tumors.
黏液性产唾液腺癌在历史上根据组织学模式分为单独的胶样癌、乳头状囊腺癌和印戒细胞癌诊断，但最近已被归入非特指性腺癌类别。目前尚不清楚这些肿瘤是否代表 1 种或多种不同的实体，以及它们与最近被描述为唾液导管内乳头状黏液性肿瘤的界限清楚的乳头状黏液性病变有何关系，这些病变具有复发性 AKT1 E17K 突变。在这里，我们试图评估唾液黏液性腺癌细胞癌的临床病理和分子特征，以阐明其分类。我们鉴定了 17 例侵袭性黏液性产唾液腺癌，其中 10 例具有单一组织学模式，7 例具有混合模式。虽然大多数肿瘤表现出乳头状生长（n=15），但常与胶样（n=6）和印戒细胞（n=3）结构混合，模式之间有明显的过渡。所有肿瘤均 CK7 阳性（100%）和 CK20 阴性（0%）。对一部分进行下一代测序显示，8 例（100%）存在 AKT1 E17K 突变，7 例（88%）存在 TP53 改变。在有临床随访的 12 例病例中（中位数：17 个月），4 例发生颈部淋巴结转移，其中所有均具有胶样或印戒细胞成分。总的来说，重叠的组织学和免疫组织化学特征加上模式间复发性 AKT1 E17K 突变提示黏液性产唾液腺癌代表一种组织学上多样化的单一实体，与被描述为唾液导管内乳头状黏液性肿瘤的肿瘤密切相关。我们建议将一个统一的黏液性腺癌类别细分为乳头状、胶样、印戒细胞和混合亚型，以促进对这些肿瘤的更好识别和分类。
