Salivary gland neoplasms usually occur in adults and are a special group among head and neck tumors due to the comparatively rare occurrence, high variation in histologic subtypes, and often overlapping features. There are more than 20 malignant and 15 benign salivary gland neoplasms. These tumors can arise from the 3 major salivary glands (parotid, submandibular, and sublingual glands) or any of the thousands of minor glands that line the mouth and extend into the nose, pharynx, and esophagus.

The major and minor salivary glands are associated with a remarkable diversity of neoplasms, and many of them harbor tumor type-specific genetic rearrangements, which primarily serve as diagnostic tools, but some also have promises as prognostic or predictive biomarkers. ^1-3

Fine needle aspiration (FNA) of salivary gland tumors is an important diagnostic tool for preoperative risk stratification. Immunostains directed at commonly overexpressed proteins /fusion proteins have the potential to resolve diagnostic uncertainty, when molecular/FISH diagnostic tools are not routinely available. ^1,4-6

Benign salivary gland tumors are more frequent with pleomorphic adenoma and Warthin’s tumor being the most observed histological types, while the most reported malignant tumors are mucoepidermoid carcinoma, adenoid cystic carcinoma, polymorphous adenocarcinoma, acinic cell carcinoma, and salivary duct carcinoma.

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. Using various immunohistochemical stains and genetic techniques as ancillary tests will help the accuracy of a pathological diagnosis, for appropriate treatment choices for these heterogeneous tumors with poor prognoses. ⁷

Salivary gland tumors can display a spectrum of oncocytoid features, in various benign and malignant salivary tumors, SOX10 and/or S100 protein immunopositivity in conjunction with PLAG1 rearrangement may reclassify a subset of oncocytomas as oncocytic variants of pleomorphic adenomas (PA) and myoepitheliomas (ME) .⁸

Salivary gland involvement in Brooke-Spiegler syndrome OMIM:605041, also known as CYLD cutaneous syndrome, an autosomal dominantly inherited disease, is known though not frequent. This association emphasizes the necessity of thorough salivary gland examination in all patients with skin lesions. ⁹