Renal oncocytoma: A diagnostic dilemma on cytology.

Sir,

Renal oncocytoma is a rare, benign renal epithelial tumor composed of large cells with mitochondria-rich cytoplasm thought to arise from intercalated cells of the collecting duct. The cytological features of renal oncocytoma show overlapping with other renal entities. We report a case of renal oncocytoma along with its cytological features and its differentials.

A 78-year-old woman presented with dull aching pain in the left lumbar region since 2 years. On examination, a left renal mass was palpable. The computed tomography scan showed a well-defined heterogeneous mass measuring 4 × 4 cm with nonenhancing central scar in mid and lower left kidney [Figure 1A]. An ultrasound-guided fine needle aspiration (FNA) of the left renal mass was performed. The smears revealed cells arranged in loosely cohesive clusters. The cells were pleomorphic with low nucleo-cytoplasmic ratio, round nuclei, inconspicuous nucleoli, fine chromatin, and granular basophilic cytoplasm [Figure 1B]. A cytodiagnosis of renal cell carcinoma with possibility of renal oncocytoma, chromophobe renal cell carcinoma (ChRCC) and RCC - granular variant was suggested. A left radical nephrectomy was done and sent for histopathological examination. The nephrectomy specimen measured 9 × 6 × 3 cm with ureter measuring 5 cm in length. Cut surface showed a well-circumscribed subcapsular growth measuring 4 × 4 cm occupying the lower pole of the kidney. The cut surface of the growth was tan-brown to mahogany-brown in color [Figure 1C]. Microscopic examination of the growth revealed nests, alveoli, and balls of tumor cells, surrounded by myxoid and focally hyalinized stroma [Figure 1D]. At some places tumor cells were arranged in the organoid pattern surrounded by thin fibrovascular septae. The tumor cells had central round, mildly pleomorphic nuclei, small nucleoli, and abundant eosinophilic granular cytoplasm. Occasional cystically dilated glands lined by oncocytic cells and dilated congested vascular spaces were also seen. No necrosis, papillae formation, or mitotic activity was seen. The ureter and renal vessels were free from tumor invasion. The Hale's iron colloidal stain was negative in the tumor cells. A diagnosis of oncocytoma of the left kidney was given.

Figure 1

(a) The CT scan showing a 4 × 4 cm heterogeneous mass in mid and lower left kidney. (b) The cytosmears show loosely cohesive clusters of cells with low nucleocytoplasmic ratio, round nuclei, inconspicuous nucleoli, fine chromatin, and granular cytoplasm (Giemsa, ×400). (c) Left nephrectomy specimen showing a circumscribed growth in the lower pole with mahogany-brown cut surface. (d) Nest of tumor cells with central round, mildly pleomorphic nuclei, small nucleoli and abundant eosinophilic granular cytoplasm separated by thin fibrovascular septae (H and E, ×400)

Renal oncocytoma was first described by Zippel[1] and was largely ignored until the publication of 13 cases by Klein and Valensi.[2] Oncocytomas comprise 3% to 7% of all primary renal neoplasms.[3] Oncocytoma has a wide age distribution, with peak incidence in seventh decade of life, men are affected twice as commonly as females.[3] The tumor is asymptomatic in most of the cases and is discovered during work up for other causes.[4] Angiography reveals an avascular or hypovascular core, secondary to central stellate scar. The central scar is used to differentiate between renal cell carcinoma (RCC) from oncocytoma radiologically; however, accuracy is poor. The scar can also be seen in chromophobe RCC or conventional RCC.[5] Grossly, oncocytoma is subcapsular, encapsulated, cut surface is uniform, and mahogany-brown colored. They can be multicentric and bilateral. Invasion of renal vein or renal capsule can also be encountered.[6] A condition called oncocytosis is described in which there is the presence of innumerable oncocytic nodules in one or both the kidneys, usually associated with the presence of dominant nodule. Renal oncocytomas are composed of large cells with granular, abundant, eosinophilic cytoplasm devoid of vacuoles, supported by delicate fibrovascular septae. The nuclei are small, round, and uniform. The other renal tumors with similar morphology are ChRCC and RCC with predominant granular features. Out of all there tumors, oncocytomas have smallest nucleoli measuring 8-10 μm in diameter. Cytological features of renal oncocytoma were first described by Rodriguez[7] in 1980. The cytology consists of uniform population of large eosinophilic granular cells that are either isolated or form small, loose aggregates. The cell borders are well defined and nucleoli are quite small and round. The oncocytic cells in ChRCC and granular cell types of conventional RCC show significant nuclear abnormalities. The lipid and glycogen stains are negative in renal oncocytoma. The cells of ChRCC are positive for Hale's colloidal iron, which stains the cytoplasmic acid mucins. Conventional RCC show positivity for lipid and glycogen stains in some cells. Renal oncocytoma is reactive for immune stains EMA, low molecular keratin and negative for vimentin. It is differentiated immunogically from conventional RCC by vimentin positivity in the latter. Ultrastructurally, the cytoplasm of tumor cells is packed with mitochondria to the virtual exclusion of any organelles other than a few lysosomes. Thus, electron microscopy remains the gold standard for confirming this diagnosis.

The most common genetic abnormality is loss of chromosome 1 and Y, also seen in ChRCC. Both tumors are thought to arise from intercalated cells of the renal cortex, accounting for striking gross and microscopic similarities. A coexistence of ChRCC in the same or contralateral kidney of patients with oncocytoma has been reported in one series in as high as 32% cases.[8] In some cases, ChRCC is found buried within an oncocytoma.[9] Renal oncocytoma is a benign lesion; however, there have been reports that some tumors may invade the parenchyma of the kidney and may recur.[7] If strict diagnostic criteria are followed and the diagnosis of oncocytoma is limited to tumors composed exclusively of well-differentiated oncocytes with small nuclei, the prognosis is excellent and the tumor is considered to be benign. For tumors diagnosed as oncocytomas that produce metastasis, the possibility of misclassification should be considered.

We present this case to highlight the pitfalls in the diagnosis of renal oncocytoma on cytology and its differential diagnosis.