Purpose: We sought to describe the earliest renal lesions in patients with von Hippel-Lindau disease to gain insight into the genesis of renal neoplasms in this condition.
Materials and methods: Grossly normal renal parenchyma from von Hippel-Lindau disease patients was examined microscopically and compared to findings in similar tissues obtained from patients with sporadic renal cancer and from autopsy subjects with no renal disease.
Results: Microscopic renal cystic and solid neoplasms containing only clear cell cytological features were found in patients with von Hippel-Lindau disease. Benign cysts with clear cell cytological features were found only in patients with von Hippel-Lindau disease. Benign cysts lined by cuboidal cells with eosinophilic cytoplasm, similar to renal tubular cells, were present only in patients with renal cancer. The extrapolated number of clear cell lesions in an average kidney with von Hippel-Lindau disease was estimated as 1,100 cysts (benign or atypical) with clear cell lining and 600 clear cell neoplasms.
Conclusions: These findings support the hypothesis that abnormalities in the von Hippel-Lindau gene in a kidney results in the cytological cell type of clear cell renal cancer as the initial product of cellular transformation.