Open AccessPathology of the Nervous System in Von Hippel-Lindau Disease
Author(s) -
Alexander O. Vortmeyer,
Ahmed K. Alomari
Publication year - 2015
Publication title -
journal of kidney cancer and vhl
Language(s) - English
Resource type - Journals
ISSN - 2203-5826
DOI - 10.15586/jkcvhl.2015.35
Subject(s) - hemangioblastoma , carcinogenesis , von hippel–lindau disease , biology , pathology , disease , tumor suppressor gene , cancer research , germline mutation , germline , progenitor cell , central nervous system , cancer , medicine , neuroscience , mutation , stem cell , gene , genetics
Von Hippel-Lindau (VHL) disease is a tumor syndrome that frequently involves the central nervous system (CNS). It is caused by germline mutation of the VHL gene. Subsequent VHL inactivation in selected cells is followed by numerous well-characterized molecular consequences, in particular, activation and stabilization of hypoxia-inducible factors HIF1 and HIF2. The link between VHL gene inactivation and tumorigenesis remains poorly understood. Hemangioblastomas are the most common manifestation in the CNS; however, CNS invasion by VHL disease-associated endolymphatic sac tumors or metastatic renal cancer also occur, and their differentiation from primary hemangioblastoma may be challenging. Finally, in this review, we present recent morphologic insights on the developmental concept of VHL tumorigenesis which is best explained by pathologic persistence of temporary embryonic progenitor cells.