Renal cell carcinoma with fibromyomatous stroma and renal hemangioblastoma represent a continuum of one tumor spectrum: a comprehensive, critical review of the literature

Latest evidence suggests that renal hemangioblastoma (RHB) belongs in the morphologic and molecular spectrum of renal cell carcinoma with fibromyomatous stroma (RCC-FMS) that often exhibits hemangioblastoma-like areas (RCC-FMS-HB). This emerging concept suggests that HB-like areas in various proportions, including in pure form, represent a variant differentiation within a TSC/mTOR pathway–altered RCC-FMS family, distinct from the classical clear cell RCC and from the central nervous system HB. Several recent publications examined the relationship between RHB and RCC-FMS-HB, mostly in a sporadic setting, but also in a setting of Tuberous Sclerosis Complex (TSC), to elucidate and highlight the similarities in their pathology, immunohistochemistry, and molecular findings. The molecular insights have unequivocally confirmed their uniform association with alterations of the TSC/mTOR pathway, leading to the conclusion that these tumours belong within the spectrum of one tumor entity. In this review, we provide an in-depth comparison of the collected clinicopathological, immunohistochemical, and molecular evidence on RHB and RCC-FMS-HB. This critical review particularly focuses on the recent evidence that supports the paradigm of a continuous spectrum between RHB and RCC-FMS.