Hemangioblastoma of the Kidney—A Comprehensive Clinical, Pathological, and Genetic Analysis of Four Cases

Hemangioblastoma (HB) is a benign central nervous system (CNS) tumor associated with mutations in the von Hippel-Lindau (VHL) gene. Although rare outside the CNS, the pathological and genetic features remain poorly understood. We analyzed four renal hemangioblastomas (RHB). Demographics, clinical presentation, and follow-up data were collected. After assessing hematoxylin and eosin-stained slides, immunophenotyping was conducted using CA9, α-inhibin, AE1/AE3, CD10, CD56, PAX8, S100, MelanA, HMB45, CD117, FH, SDHB, and brachyury antibodies, alongside mismatch repair (MMR) deficiency examination. Additionally, whole-exome sequencing (WES) was performed in 3 tumors. Our cohort comprised 3 male and 1 female patients, with a median age of 49 years. No data on VHL disease were available. Well-circumscribed tumors (median size: 25.5 mm) displayed clear vacuolated cytoplasm with a vascular component. Immunostaining revealed expression of PAX8, α-inhibin, AE1/AE3, S100, and cytoplasmic brachyury. WES analysis detected no pathogenic mutations. No cancer-related deaths or progressions were observed. Histologically, RHB resembles low-grade ccRCC and shares expression of PAX8, pancytokeratin, and CA9. However, RHB is uniquely positive for α-inhibin, S100, and lacks VHL alterations. Its favorable prognosis underscores the importance of distinguishing it from ccRCC to prevent unnecessary treatments. Further research is warranted to elucidate the underlying genetic mechanisms.