Renal oncocytoma is a benign renal epithelial neoplasm, that comprises approximately 5-7% of renal tubular epithelial tumors. ¹

Renal oncocytomas can present in familial or sporadic forms; that latter which is much more common and has an unknown etiology. Rare cases that show multiple oncocytic tumors can be referred to as oncocytosis .  Oncocytosis, as well as hybrid oncocytic tumors may occur sporadically or in association with Birt-Hogg-Dubé syndrome. OMIM:135150, resulting from FLCN (folliculin) gene mutations with variable penetrance.

Renal oncocytomas occur across a broad age range, peaking in the seventh decade. There is a male predominance (2:1) and tumors are frequently small and found incidentally

Macroscopically , oncocytomas are well-circumscribed, slightly lobulated solid tumors with generally mahogany brown or dark red cut surface. The tumors are typically solitary, but can be multifocal or bilateral. A central scar is frequently observed. Some cases show involvement of the perinephric fat or rarely the renal vein with no change in prognosis

Microscopically, the tumor is composed of nests and tubular structures made up from oncocytic cells, and is frequently associated with fibrous or edematous stroma (Fig 1 A). The tumor cells are large round eosinophilic cells with granular cytoplasm that is packed with mitochondria. Nuclei are round and monomorphic and contain small nucleoli. A proliferation of non-neoplastic renal tubules may be present in the area of scar.  Occasionally oncocytomas extend into perinephric adipose tissue.  (Fig1B)  Bizarre cells with pleomorphic nuclei may be present in some tumors and have no affect on outcome (Fig. 1C). Mitoses and necrosis are not seen.

Fig. 1A. Oncocytomas contain small oncocytic cells with round, regular nuclei that sometimes contain a small nucleolus. Architecturally the tumors are solid, nested or tubular, and are frequently associated with edematous stroma

Fig. 1B: Occasionally oncocytomas extend into perinephric adipose tissue; this findings has no affect on clinical outcome (i.e., the tumor is still benign).

Fig. 1C: A small subset of oncocytomas demonstrate nuclear atypia and/or multinucleation. Some think this is due to degenerative change. Regardless, these nuclear features do not affect clinical outcome (i.e., the tumor is still benign).

Tumor cells are typically immunoreactive for KIT (DC117), S100A (multifocal), and HNF1beta, and are negative for CD10, AMACR and vimentin. CK7 is usually negative or patchy positive with immunoreactivity in single scattered cells; this is in contrast to chromophobe renal cell  carcinoma (ChRCC)carcinoma and low grade oncocytic tumor (LOT) which show diffuse CK7 positivity. ²  Proteomic expression profiling has highlighted the accumulation of mitochondrial proteins in renal oncocytoma. Some of these proteins correspond to traditional immunohistochemical markers used to distinguish renal oncocytoma from ChRCC. ^3,4

The WHO now recognizes other specific renal oncocytic neoplasm that share some morphologic and immunophenotypic findings with oncoctyoma.^5-7   Low grade oncocytic tumor (LOT) and eosinophilic vaculoated tumor (EVT) are also benign renal tumors in the differential diagnosis with oncocytoma. LOT diffusely expresses CK7 and is negative for KIT whereas EVT has a similar immunoprofile to oncocytoma but also expresses CathepsinK.  Both LOT and EVT are associated with MTOR pathway mutations. ^8,9  Eosinophilic solid and cystic renal cell caricinoma (ESC-RCC) occurs mostly in females and is typically negative for CK7 and KIT and is positive for CK20.  Lastly, tumors associated with familial syndromes (e.g., succinate dehydrogenase deficient RCC and fumarate hydratase deficient RCC) can rarely have overlapping morphologic features with oncocytoma, and if so, should be excluded.

Oncocytomas behave in a benign facsion and can be monitored or surgically removed if causing symptoms.  Enucleation, wedge resection or ablation may also be considered for treatment options but are less common. Atypical pathologic features, such as nuclear pleomorphism, perinephric fat involvement and extension into a renal vein branch does not influence prognosis. Pathologists now classify certain tumors with some of the above atypical features as oncocytic renal cell carcinoma, not otherwise specified, if they cannot be classified as a definitive eosinophilic renal neoplasm

Oncocytomas frequently exhibit losses of chromosome 1/1p-, chromosome 14 or 21 and/or a sex chromosome (Fig.2), arguing for more genetic overlap with chromophobe renal cell carcinoma in this subgroup of oncocytoma ^10-12
Structural rearrangement of 11q13 have been reported, with t(9;11) (p23;q13)and  t(5;11) (q35;q13) representing the most common translocations, ^12,13 (Fig.3) with  increased expression of cyclinD1, demonstrate by immunohistochemistry; however, it should be noted that the latter is not used diagnostically.^11,14  A t(6;9)(p21;p23)has been reported in 3 cases.¹⁵ A subset of oncocytomas exhibit non-recurrent numerical or structural abnormalities, but normal karyotype can be also frequently observed. ¹³

Fig.2 . Microarray profile of a renal oncocytoma showing loss of one sex – chromosome (X) and one chromosome 1.  

Fig 3 . Partial GTG-banding karyotype showing the 2 most frequent translocation involving 11q13 band : a) t(9;11)(p23;q12) and b) t(5;11)(q35;q13)

NGS  for hotspot mutations or gene copy number changes analysis revealed multiple abnormalities,  with RB1 and ERBB4 the two most common deletions in ChRCC but not in renal oncocytoma.¹⁶