Oncocytic salivary gland carcinomas

Abstract

Oncocytic carcinomas of the salivary glands represent a rare and diverse group of malignancies characterised by granular eosinophilic cytoplasm due to abundant mitochondria. This review provides a comprehensive overview of oncocytic salivary gland carcinomas, categorised by their morphological patterns: monophasic, biphasic, and complex. Monophasic entities include oncocytic intraductal carcinoma (OIDC), oncocytic salivary duct carcinoma (OSDC), acinic cell carcinoma (ACC), and secretory carcinoma (SC). These tumours vary significantly in histological architecture, immunohistochemical profiles, and genetic alterations, ranging from TRIM33::RET fusions and BRAF V600E mutations in OIDC to NR4A3 rearrangements in ACC and ETV6::NTRK3 fusions in SC. Biphasic tumours, such as oncocytic epithelial-myoepithelial carcinoma (OEMC) and oncocytic adenocarcinoma not otherwise specified (OANOS), further complicate diagnosis due to dual cellular composition and overlapping features with other neoplasms. Complex-pattern tumours, particularly oncocytic mucoepidermoid carcinoma (OMEC), highlight diagnostic challenges and underscore the need for advanced molecular diagnostics. This article emphasises the critical role of integrated histopathological examination, immunohistochemical staining, and molecular profiling in the accurate classification of these neoplasms. Despite diagnostic advancements, some entities, like OANOS, remain provisional, pending widespread access to transcriptomic tools. Recognising the molecular heterogeneity and clinicopathologic nuances of oncocytic carcinomas is essential for improving diagnostic precision, prognostication, and guiding targeted therapy.