Answer: Nodular oncocytic hyperplasia with clear cell change

Histology: The parotid parenchyma harbors multiple discrete nodules that vary in size from 1 to 20 mm. The nodules are sharply circumscribed, and are non-encapsulated or partially surrounded by a thin capsule. The cells are growing in an organoid pattern. Occasional lumens are noted in the center of the cellular nests. The nests are surrounded by a delicate fibrovascular network. The tumor cells have vesicular nuclei with a prominent central nucleolus. The cytoplasm varies from finely granular to clear. Mitotic activity and significant pleomorphism is not appreciated.

Discussion: The differential diagnosis of clear cell tumors involving the parotid gland is lengthy and includes (but is not limited to) acinic cell carcinoma, mucoepidermoid carcinoma, clear cell adenocarcinoma, epithelial myoepithelial carcinoma, and metastatic renal cell carcinoma. Although oncocytic salivary gland tumors are usually recognized by their abundant pink granular cytoplasm, the pathologist must be aware that oncocytic tumors often undergo prominent clear cell change such that they too should be included in the differential diagnosis of clear cell tumors. It is helpful that even in those oncocytic neoplasms where clear cells predominate, conventional eosinophilic oncocytes can usually be found within or adjacent to the clear cell nodules. Conversely, oncocytic lesions lack the epidermoid component and the mucinous cells of mucoepidermoid carcinoma, the ductal component of epithelial-myoepithelial carcinoma, and do not show the serous acinar differentiation of acinic cell carcinomas. Perhaps most difficult of all is discerning a clear cell predominant oncocytic tumor from metastatic renal cell carcinoma. Immunohistochemical markers (e.g. RCC, CD10) may be of some help; and some still use the PTAH stain to confirm the presence of oncocytes. A PTAH stain imparts a bluish granularity to the cytoplasm as a result of mitochondrial staining. If any doubt persists, the patient should be evaluated for a renal mass.

Not uncommonly a dominant oncocytic nodule will occur in the setting of multiple smaller oncocytic nodules. The longstanding argument over whether this process is hyperplastic or neoplastic in nature is not of much clinical relevance. The important point is that the presence of multiple nodules is not to be interpreted as invasive tumor growth and, in turn, invasive oncocytic carcinoma. Oncocytic carcinomas are generally high grade carcinomas that exhibit overtly malignant cytologic atypia and truly invasive tumor growth (e.g. vascular and perineural invasion). As demonstrated in the present case, nodular oncocytic hyperplasia is especially prone to demonstrate a dominant clear cell component (nodular oncocytic hyperplasia with clear cell change).