Oncocytic Tumors: Oncocytoma, Warthin Tumor, and Acinic Cell Carcinoma

Perhaps more than any other tissues in the body, the salivary glands exhibit a wide range of benign and neoplastic lesions that can have oncocytic or oncocyte-like features. True oncocytes have abundant densely granular eosinophilic cytoplasm due to the presence of numerous mitochrondria. In addition, they have central enlarged round nuclei with a distinct nucleolus. Sometimes the oncocytic features are a primary characteristic of the lesion such as in oncocytoma, and sometimes they are secondary to a process such as oncocytosis, a metaplastic change in the salivary glands of older adults. In the diffuse form of oncocytosis a majority of the salivary gland parenchyma, including ductal and acinar cells, is replaced by oncocytes. This process can even affect the neoplastic cells of many different salivary gland tumors. Radiologically, oncocytes concentrate technetium (99mTc), and therefore, tumors comprised of oncocytes are “hot” by radionuclide scanning. In this chapter, we will discuss the differential diagnosis of salivary gland lesions with true oncocytic features, as well as those that have eosinophilic features that can mimic those of an oncocyte.

One of the most common diagnostic challenges among salivary gland tumors with an oncocytic microscopic appearance is differentiating the benign tumor, oncocytoma, from the low-grade carcinoma, acinic cell carcinoma. In addition, other tumors or subtypes of tumors with oncocytic features include Warthin tumor, the oncocytic variant of mucoepidermoid carcinoma, pleomorphic adenoma with oncocytic features, oncocytic carcinoma, and metastatic tumors, especially renal cell carcinoma. With the exception of pleomorphic adenoma, the most common salivary gland tumors with oncocytic features lack myoepithelial differentiation.

Salivary gland proliferations of oncocytes include nodular or diffuse hyperplasia (oncocytosis), oncocytoma, and oncocytic carcinoma. Oncocytomas are rare benign salivary gland tumors, representing less than 1% of all salivary gland neoplasms. The majority occur in the parotid gland in older adults with a mean age in the sixth to seventh decade and an equal gender predilection. A small subset of oncocytomas occurs in the submandibular and minor salivary glands. Most present as a slowly enlarging, 3–4 cm, painless mass. Approximately 5% can be multifocal, and even by histologic evaluation, it may very difficult to reliably distinguish a true oncocytoma from a hyperplastic oncocytic nodule in the setting of oncocytosis. On gross examination, oncocytomas are well circumscribed with a characteristic brown-red coloration; microscopically they are encapsulated, while the hyperplastic nodules in oncocytosis are not. Oncocytic carcinomas are clinically expansile, invasive tumors.