Hemangioblastoma in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome: a phenotypic overlap between VHL and HLRCC Syndromes

Abstract

Hemangioblastomas are rare vascularized central nervous system tumors, which can occur sporadically or be associated with von Hippel Lindau Syndrome. The pathogenesis of hemangioblastomas in von Hippel Lindau Syndrome is proposed to involve a pseudohypoxic intracellular state induced by dysregulation of hypoxia inducible factor alpha due to the absence of von Hippel Lindau protein complex mediated destruction. Dysregulation of fumarate hydratase, a tricarboxylic acid cycle enzyme, occurs in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome due to germline fumarate hydratase gene mutations, and also results in oncogenesis via hypoxia inducible factor alpha dysregulation. We present a c..