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.