Pathology of Salivary Gland Disease

Salivary gland lesions are rare and can be pathologically challenging due to their wide morphologic spectra. Non-neoplastic diseases Acute and chronic non-autoimmune sialadenitis each have fairly characteristic pathologic features though they may have a variety of etiologic factors and pathogenetic mechanisms. Autoimmune sialadenitis is largely comprised of the myoepithelial sialadenitis seen in Sjogren’s syndrome, though several autoimmune diseases may manifest in the salivary gland. A complication may be B-cell lymphoproliferative disorders. A subset of chronic sclerosing sialadenitis belongs to this group of diseases. Necrotizing sialometaplasia is a benign selflimited process that may histologically mimic squamous cell carcinoma or mucoepidermoid carcinoma. Subacute necrotizing sialadenitis is a relatively newly described related entity. Sialadenosis is a manifestation of generalized metabolic disturbances while adenomatoid hyperplasia is often an incidental finding. Salivary lymphoepithelial cysts of the salivary gland include salivary type, first branchial cleft cysts, and lymphoepithelial cystic disease of HIV. Dysgenetic polycystic disease is an extremely rare entity. Benign tumors Pleomorphic adenomas are the most common benign tumors and have a broad histologic spectrum. These tumors can recur if incompletely excised and may rarely metastasize without having histologic features of malignancy. Basal cell adenomas are benign tumors with specific histologic patterns. The membranous type is associated with cylindromatosis gene (CYLD1) mutations, cutaneous syndromes, and can be multifocal and is more likely to undergo malignant transformation. Canalicular adenomas are minor salivary tumors that are clinicopathologically distinct from basal cell adenomas. Myoepitheliomas also have varied patterns and should show at most a few ducts. Warthin’s tumor is linked to smoking and older age and is thus demographically distinct from other cystadenomas. Morphologically it has a characteristic lymphoid stroma resembling a lymph node. Oncocytoma and oncocytosis are benign tumors and tumor-like lesions comprised of solid nests of large polygonal cells with abundant granular eosinophilic cytoplasm that may occasionally mimic metastatic renal cell carcinoma. Sclerosing polycystic adenosis is a rare clonal proliferation that resembles fibrocystic disease of the breast, and though benign, may show changes resembling salivary duct carcinoma. Malignant tumors Adenoid cystic carcinoma is a slow growing but relentless malignancy for which stage, histologic grade based on solid component, and p53 expression are important prognosticators. These characteristically overexpress c-kit. Mucoepidermoid carcinoma is the most common salivary malignancy with three cell types (mucous, intermediate, and epidermoid). Most grading systems are three tiered and generally correlate with prognosis; mucoepidermoid carcinomas of the submandibular gland appear more aggressive than those of the parotid gland. Malignant mixed tumors can be subcategorized into carcinoma ex-pleomorphic adenoma, true malignant mixed tumor (carcinosarcoma), and metastasizing mixed tumor. Acinic cell carcinoma is a low-grade tumor that can rarely dedifferentiate into an aggressive high grade tumor. Epithelial-myoepithelial carcinoma is a rare biphasic low-grade neoplasm characterized by clear myoepithelial cells and small ducts and may mimic other clear cell lesions of the head and neck. Basal cell adenocarcinoma resembles its benign counterpart, basal cell adenoma, and is distinguished mainly by the presence of invasion, though ancillary studies such as immunoperoxidase stains for Ki 67, p53, bc1-2, and epidermal growth factor receptor may help in diagnosis. Myoepithelial carcinoma also resembles its benign counterpart and is separated mainly by the presence of invasion, mitoses, and necrosis. Nuclear pleomorphism may be a poor prognostic sign. Salivary duct carcinoma is a high grade carcinoma that expresses androgen receptor and her-2-neu. It can be confused with low-grade cribriform cystadenocarcinoma, a recently characterized entity that resembles a lowgrade mammary type ductal carcinoma. Rare malignant tumors include cystadenocarcinomas, large cell carcinoma, small cell carcinoma, and primary squamous cell carcinomas; all but cystadenocarcinomas behave in an aggressive fashion.