High-Grade Salivary Carcinomas: A Current Insight on Diagnostic Pathology and the Key to Clinical Decision Making

High-grade carcinomas of the salivary glands are a group of several tumor entities with highly malignant histologic appearances, and have an aggressive biological behavior accompanied by poor prognosis. In general, they require more intensive treatment than low- or intermediate-grade carcinomas. High-grade salivary carcinomas are rare occurrence and often have overlap of microscopic features between different tumor types, making an appropriate diagnosis challenging in daily practice settings. However, with recent rapid advances in molecular pathology and molecular-targeted therapy in this fields, there is a growing need to properly classify tumors, rather than just diagnosing the cases as "high-grade carcinomas" as this leads to specific treatment strategies. In this article, we review representative high-grade salivary gland carcinomas, including salivary duct carcinoma and its histologic subtypes, high-grade mucoepidermoid carcinoma, solid-type adenoid cystic carcinoma, and high-grade transformation of low- or intermediate-grade carcinomas, and discuss on their differential diagnosis and clinical implication. Other rare entities, such as neuroendocrine carcinoma, NUT carcinoma, and metastatic carcinoma, should also be kept in mind before diagnosing as high-grade carcinoma, NOS. Of these tumors, salivary duct carcinoma has received the most attention because of its strong association with androgen deprivation therapy and anti-HER2 therapy. Other tumor-type specific treatment includes anti-TRK therapy against high-grade transformation of secretory carcinoma, but further therapeutic options are expected to be developed in the future. It should be emphasized that detailed histological evaluation with adequate sampling in addition to the effective use of molecular ancillary tests, is of utmost importance for a suitable diagnosis.