Clear cell papillary renal cell carcinoma in patients with von Hippel-Lindau syndrome--clinicopathological features and comparative genomic analysis of 3 cases.

Clear cell papillary renal cell carcinoma (CCPRCC) is a renal neoplasm that has recently received widespread recognition in the literature. There have been several reports of this tumor arising in a sporadic setting and in patients with end-stage renal disease; however, there is limited information available about the clinical, pathologic, and genetic characteristics of this tumor in the setting of von Hippel-Lindau (VHL) disease. We herein report a series of 3 patients who developed CCPRCC in this unique clinical setting. The histology and immunohistochemical profile for all 3 cases was similar to that which has been previously reported for CCPRCC. All tumors were diffusely and strongly positive for cytokeratin 7, negative for α-methyl-CoA-racemase, and showed at least focal staining for CD10. Comparative genomic analysis was performed on tumors from all 3 patients. One tumor demonstrated monosomy 3, and the other 2 tumors showed normal chromosomal content. All 3 patients were alive without evidence of disease progression 5, 3, and 3 years after surgery. CCPRCC represents a distinct tumor type that may occur in the setting of VHL disease and should be considered in the differential diagnosis of extensively cystic renal tumors arising in this clinical setting. Molecular analysis in our series of cases suggests that CCPRCC does indeed represent a unique histologic subtype and must be distinguished from clear cell renal cell carcinoma due to different biological potentials. Ancillary studies for accurate classification are recommended due to significant morphologic overlap with clear cell renal cell carcinoma.