PREVALENCE OF MICROSCOPIC LESIONS IN GROSSLY NORMAL DISEASE, SPORADIC RENAL CELL CARCINOMA AND NO RENAL DISEASE: CLINICAL IMPLICATIONS RENAL PARENCHYMA FROM PATIENTS WITH VON HIPPEL-LINDAU

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 fiom 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 HippelLindau gene in a kidney results in the cytological cell type of clear cell renal cancer as the initial product of cellular transformation. von Hippel-Lindau disease is an autosomal dominant disorder characterized by the presence of retinal angiomas, central nervous system hemangioblastomas, pancreatic cysts and tumors, pheochromocytomas and renal carcinomas.1 Inheritance of the syndrome has been linked to chromosome 3pZ-4 and, recently, the von Hippel-Lindau gene has been identified.4 Patients with renal manifestations of von HippelLindau disease have a spectrum of disease ranging from benign to malignant renal lesions. Because von Hippel-Lindau disease patients have inherited a gene that is linked to the formation of renal tumors, they frequently have multiple tumors and are at risk for new tumors throughout their lives.5. Several cytological cell types and architectural types have been described in the renal tumors removed from patients with von Hippel-Lindau disease.7.S To our knowledge the microscopic forms of these lesions have not been described previously. We examined grossly normal renal tissue from patients with von Hippel-Lindau disease for the presence of microscopic lesions that may represent potential precursors of renal cystic lesions and carcinomas. We compared these findings to the lesions present in grossly normal renal parenchyma from patients with advanced sporadic renal cell carcinoma and from those who died with no known renal carcinoma or other renal disease. In addition, based on these findings we projected the prevalence of microscopic renal lesions present in this subgroup of patients with renal manifestations of von Hippel-Lindau disease.