Oncocytes are cells which can be seen in various tissues and a variety of conditions ranging from hyperplastic changes to malignant conditions. In 1894, the German pathologist Hurthle first described these granular cells in normal canine thyroid glands, while the term “Oncocyte” was coined by Hamperl in 1931.[
2] Three years later, Tandler
et al.[
3] revealed by electron microscopy that the oncocytes contained unusually large number of mitochondria. Oncocytic cells are thought of as metaplastic cells formed in response to adverse changes, with the normal cells losing their original specialization.[
2] Aging is also thought to cause a functional exhaustion of mitochondrial enzymes, and a compensatory hyperplasia of mitochondria can occur, which in turn is responsible for the oncocytic change. Indeed, solitary oncocytes appear most often as incidental findings in aging salivary tissue, with studies showing upto 80% presence in persons older than 70 years of age.[
1]
Areas of oncocytic metaplasia can be seen in a host of salivary gland tumors like basal cell adenoma, pleomorphic adenoma, myoepithelioma, cystadenoma, canalicular adenoma, polymorphous low grade adenocarcinoma, Warthin's tumor, acinic cell carcinoma[
2] and mucoepidermoid carcinoma. However, oncocytes also give rise to neoplasms like oncocytomas and its malignant counterpart, the oncocytic carcinoma.
FNAC has increasingly been used as a primary screening tool for salivary gland lesions with high levels of sensitivity and specificity. However, as salivary glands are notorious for having overlapping morphological features, diagnosis by cytology alone often becomes difficult.[
2] The situation may slightly improve by using multiple passes from the swelling.
Finding oncocytes predominantly in salivary gland aspirates can pose much difficulty. However, certain clues may prove helpful. In acinic cell carcinoma, the cells appear to be more granular and finely vacuolated than those of oncocytoma. More so, in MGG stain, the cytoplasm appears more slate-gray, and may be seen containing fine red granulation. The nuclei in acinic cell carcinoma appear larger with more pleomorphism and there are usually many stripped nuclei. Warthin's tumors usually have a mixed lymphoid cell population along with oncocytes in a fluidy background containing lymphocytes and debris. However, paucicellular Warthin's tumor is extremely difficult to differentiate from oncocytoma and oncocytosis.[
4] Mucoepidermid carcinomas usually have epidermoid, intermediate and glandular cells in a dirty, necrotic background. Differentiating oncocytoma from oncocytic carcinoma can be difficult on cytology as the former can appear cytologically malignant looking, while the later can look deceptively monomorphic for which the term “oncocytic neoplasm” is preferred on cytology smears. Differentiating oncocytosis from oncocytoma on cytology is difficult, and on some occasions, even impossible.[
4]
World health organization (WHO) classification of salivary gland neoplasms recognizes three oncocytic entities: Oncocytosis, oncocytoma and oncocytic carcinoma.[
2,
5] Oncocytosis is considered a hyperplastic change which may present with generalized enlargement of salivary gland. Oncocytosis has further been categorized as diffuse hyperplastic oncocytosis (DHO) and multifocal nodular oncocytic hyperplasia (MNOH).[
6] Oncocytomas are more common than oncocytic carcinomas.[
2] Diffuse hyperplastic oncocytosis can only be diagnosed on histopathology by finding an unencapsulated lesion with the entire gland replaced by oncocytic cells; while, in oncocytomas we usually get a well-circumscribed, encapsulated lesion, comprising of an apparent organoid pattern and thin capillary network, with features of compression to adjacent tissue.[
2] DHO is an extremely rare lesion with very few reported cases in world literature.[
7]
The other salivary gland tumors where oncocytes are found can usually be differentiated on basis of their more typical cytologic details. The present case posed one such difficult scenario where aspiration from a tumor-like firm mass revealed oncocytes only showing mild pleomorphism without any fluid, debris or lymphoid cells in the background. A diagnosis of an oncocytic neoplasm was clinically and cytologically suspected; however, subsequent histopathological examination showed diffuse hyperplastic oncocytosis. Thus, oncocytic lesions of salivary gland can pose considerable difficulty to the cytopathologist, and a histopathological examination often remains the cornerstone of diagnosis.
