Unclassified Renal Cell Carcinoma with Reverse Polarity and Pathogenic von Hippel-Lindau Mutation in a Congenital Renal Malformation

Renal tumors that develop in congenitally malformed kidneys often fall outside standard histologic classifications. We present an unusual renal neoplasm in a 19-year-old boy with a hypoplastic right kidney. Computed tomography revealed a 70-mm sized unilocular cyst containing a 25-mm sized mural nodule, and laparoscopic nephroureterectomy was performed. Histologic examination showed low-grade papillary structures with reverse polarity. Immunohistochemistry demonstrated cytoplasmic (but not membranous) CA9 positivity, and RNA sequencing identified a pathogenic von Hippel-Lindau (VHL) splicing-site mutation (c.341-2A > G). Despite the VHL alteration, the tumor did not fulfill the morphologic and immunohistochemical criteria for clear cell renal cell carcinoma and was diagnosed as unclassified renal cell carcinoma. This report illustrates the diagnostic complexity of renal tumors arising in congenital renal anomalies and underscores the importance of integrating molecular, morphologic, and immunophenotypic data when standard criteria are inconclusive.