Pleomorphic adenoma is the most common benign salivary gland neoplasm primarily affecting the parotid gland and minor salivary glands. They are usually solitary, slow-growing, firm and painless lesions. Surgical excision is curative. Malignant transformation is seen in up to 10% of cases and is associated with the longstanding untreated tumour, large tumour size (>2 cm), multiple recurrences, older patient age (>40), male gender, and deep lobe tumours.

Grossly, pleomorphic adenomas are irregular with variable thick fibrous capsule and homogenous pale-tan to white surface.

Microscopically, pleomorphic adenomas demonstrate epithelial, myoepithelial and mesenchymal differentiation. They can have solid, tubular, trabecular or cystic architecture lined by cuboidal-columnar epithelium with epithelial tissue of variable morphology (spindled, plasmacytoid, clear cell, or basaloid). Squamous metaplasia is commonly found. Mesenchymal tissue is composed of chondromyxoid, myxoid or hyaline stroma. Fatty changes, sebaceous metaplasia, crystalloids and necrosis can also be identified.

The findings in cytology specimens reflect the multicellular lineage of pleomorphic adenomas with epithelial and mesenchymal cells set in fibrillary background. Epithelial cells appear in cohesive clusters and may form branching trabeculae. Bipolar spindled myoepithelial cells have eccentric rounded nuclei and are usually embedded in chondromyxoid stroma. Atypical single cells may be identified. The stroma has feathered edges and may focally contain cells that line up along the edge of matrix that should not be confused with adenoid cystic carcinoma. The stroma appears pale green on Papanicolau stain and deep purple on air-dried Romanowsky stains.

By immunohistochemistry, pleomorphic adenomas are positive for cytokeratin, p63, GFAP, S100 and nuclear PLAG1 staining. SMA staining is variable.

Major cytogenetic abnormalities are rearrangements involving PLAG1 gene such as t(3;8) and t(5;8) and HMGA2 gene such as t(9;12).