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Oncocytes are epithelial cells with abundant, granular, eosinophilic cytoplasm due to presence of numerous large mitochondria of varied sizes. The presence of oncocytes in salivary glands can occur in a variety of conditions. Here, we present a rare case of a 68 year old male patient who presented with a 6 cm diameter swelling in the right parotid region. A fine needle aspiration cytology done from the lesion showed a cellular oncocytic lesion. A possibility of oncocytoma was entertained. Histopathology of the mass showed a rare entity called diffuse hyperplastic oncocytosis. Originally believed to be a metaplastic process, oncocytes can occur in various lesions ranging from hyperplastic conditions to malignant neoplasms. However, diagnosis on cytological smears can be very challenging for the cytopathologist.
Oncocytes are epithelial cells which appear as cells with abundant, granular, eosinophilic cytoplasm, a central pyknotic nucleus, and ultrastructurally are crammed with numerous mitochondria of various sizes. Oncocytes are seen in various organs like salivary glands, thyroid, parathyroid, pituitary, nasal cavities, sinuses, ocular caruncle, lacrimal glands, buccal mucosa, eustachian tube, larynx, esophagus and organs like liver, pancreas, and kidney.[1,2] In salivary glands, they may be present in a plethora of conditions ranging from hyperplasia to overtly malignant lesions. Diagnosis by fine-needle aspiration cytology (FNAC) may be very difficult due to focal sampling of the lesion, as oncocytic change can occur in a large variety of neoplastic as well as non-neoplastic conditions. Histopathology remains the gold standard to clinch the precise diagnosis. Here, we present a case of a cytologically diagnosed oncocytic lesion with a possibility of oncocytoma. However, on subsequent histopathology the lesion was diagnosed as diffuse hyperplastic oncocytosis.
A 68-year old male patient presented to the outpatient department with a 6 cm swelling in the right parotid region. He noticed it seven months back, and it increased gradually to the present size. On examination, the swelling was firm, slightly irregular, non-tender and not fixed to the skin or deeper structures. The patient had no other complaint. FNAC was done using a 26-gauge needle fitted to a 10 mL syringe. The aspirate was blood mixed and granular, and the smears were stained with May-Grünwald-Giemsa (MGG) stain and hematoxylin and eosin (H and E) stain. The cellular smears showed cohesive clusters of oncocytes - large cells with abundant, granular, eosinophilic cytoplasm with round centrally-placed or occasionally eccentric nucleus. The pleomorphism was of mild degree and prominent nucleoli were present in few cells. The background was more-or-less clear with absence of fluid, debris and lymphoid cells [Figure 1]. A cytopathological diagnosis of an oncocytic lesion with the possibility of an oncocytic neoplasm was given, which needed to be confirmed by subsequent histopathology. The patient underwent superficial parotidectomy and the specimen was sent for biopsy confirmation. The sections showed that the entire resected gland was replaced by oncocytic cells with granular eosinophilic cytoplasm, which were admixed at places with some clear cells as well [Figure 2]. The mass lacked a definite capsule. There was no associated tissue response in the form of fibrosis or inflammation. No original salivary tissue could be sampled from the specimen. The patient was diagnosed as case of diffuse hyperplastic oncocytosis. No further treatment was given and the patient was free of any complaints at 1 year follow-up.
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. Three years later, Tandler et al. 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. 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.
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 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. 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. 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.
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). Oncocytomas are more common than oncocytic carcinomas. 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. DHO is an extremely rare lesion with very few reported cases in world literature.
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.
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Conflict of Interest: None declared.