Hybrid oncocytic/chromophobe renal cell tumor: An integrated genetic and epigenetic characterization of a case

Hybrid oncocytic/chromophobe tumor (HOCT) is a renal cell neoplasm displaying overlapping cellular and architectural features of both renal oncocytoma (RO) and chromophobe renal cell carcinoma (chRCC). It has been described in the context of oncocytosis, Birt-Hogg-Dubé syndrome, and also sporadically. Thus far, HOCT immunohischemical profile and cytogenetic alterations have been reported, but not epigenetic alterations. Herein, we characterize a HOCT case, including microRNA expression, comparing it to sporadic RO and chRCC.

An HOCT was entirely submitted. Representative paraffin blocks were selected for histochemical, immunohistochemical and FISH analyses. MicroRNAs were extracted from the two components separately and selected microRNA expression was performed.

This 4 cm HOCT, from a 69 year-old female, was composed mainly by oncocytic cells with an insular distribution (RO-like) and areas of larger clarified cells (chRCC-like). The two areas displayed different features: RO-like areas showed negative colloidal iron staining, multifocal CD15, negative CK7, focal multiple tetrasomies, and higher miR21 expression; chRCC-like areas showed colloidal iron diffuse staining with moderate intensity, focal CD15 and CK7, no numeric chromosomic alterations, and higher miR141 and miR200b expression.

microRNA expression in the two HOCT components is similar to its sporadic tumors counterparts. Morphologic, immunohistochemical, cytogenetic and epigenetic data on this case suggest either two independent pathogenic pathways or an early pathogenic divergence for RO-like and chRCC-like components of HOCT.