Hybrid oncocytic/chromophobe renal cell tumours do not display genomic features of chromophobe renal cell carcinomas

Abstract

Hybrid oncocytic/chromophobe tumours (HOCT) are renal tumours recently described displaying histological features of both renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC), raising the question of their precise signification in the RO/ChRCC group. This study aimed to describe clinicopathological features of so called HOCT and to characterise their genomic profile. Five hundred and eighty-three tumours belonging to the ChRCC/RO group were retrospectively reviewed. Twelve tumours that could not be classified as RO or CHRC were considered as HOCT. Hale staining and cytokeratin 7 (CK7) immunostaining were performed. Genomic profile was established by array comparative genomic hybridisation (array-CGH) on frozen samples. Mean age at diagnosis was 70 years (range 46-83). No recurrence was observed (median follow-up: 18 months; range 9-72). Tumour size ranged from 1 to 11 cm. HOCT showed an admixture of RO- and ChRCC-like areas and/or "hybrid" cells with overlapping cytonuclear and/or histochemical features. Hale staining was apical in 50 to 100 % of cells, and CK7 was expressed in 10 to 100 % of cells. Genomic profile was balanced in seven cases or showed a limited number of random imbalances in five cases, as observed in RO. In no instances were observed the characteristic chromosome losses of ChRCC. These results suggest that so called HOCT are not true hybrid tumours and rather could represent a morphological variant of RO. From a diagnostic perspective, an array-CGH analysis could be performed in ambiguous ChRCC/RO cases to formally exclude the diagnosis of ChRCC.

Metabolic reprogramming and elevation of glutathione in chromophobe renal cell carcinomas

“…A histopathological differentiation of benign renal oncocytomas from malignant chRCC is still difficult, even using multiple immunohistochemistry markers (Ng et al, 2016). There are also case reports on rare hybrid tumors (Noguchi et al, 1995), including oncocytic content (Pote et al, 2013) and the rare genetic disorder Brit-Hogg-Dube (BHD) syndrome (Vera-Badillo et al, 2012), where the coexistence of renal oncocytomas and chRCC was shown. The defective mitochondriogenesis was named as a possible source of microvesicles in chromophobe renal cell carcinomas.…”

Identification and Validation of Radiographic Enhancement for Reliable Differentiation of CD117(+) Benign Renal Oncocytoma and Chromophobe Renal Cell Carcinoma

“…However, to our knowledge, HOCT metastatic behavior has never been confirmed, raising the assertion by some investigators that these hybrid tumors might be benign (30). Consistent with this possibility, Pote and colleagues recently concluded that HOCT is genetically more similar to renal oncocytoma than ChRCC and may therefore be a renal oncocytoma variant (31). Regardless, given its indolent clinical behavior and lack of known metastatic potential, the rare possibility of HOCT should not justify routine resection of tumors with renal oncocytoma diagnosis favored on biopsy, because HOCT too is appropriate for surveillance (49).…”

“…A prospectively maintained nephrectomy database was queried to identify all patients who underwent partial or radical nephrectomy for pathologically confirmed renal oncocytoma or ChRCC between August 2003 and December 2012. One patient with four hybrid renal oncocytoma-ChRCC tumors was excluded from analyses due to indeterminate malignant versus benign pathology (30,31). CD117 and CK7 immunostain results were obtained from pathology reports, and classified as positive for moderate-to-strong/diffuse membranous stain, or as negative for absent or weak/focal (<10%) stain (25).…”

The normal and pathologic renal medulla: A comprehensive overview

“…Hybrid renal tumors are uncommon types of cancer containing areas of renal oncocytoma and areas of chromophobe cell kidney carcinoma, and are the focus of several studies [35].…”