Hemangioblastoma: an updated primer

Hemangioblastomas are benign, WHO grade 1 tumors of vascular origin that occur in one or more regions of the central nervous system (CNS), but can also develop in other regions of the body [1]. They are capillary-rich neoplasms of the CNS that contain variably lipidized neoplastic stromal cells of unknown histogenesis [2]. Common areas of occurrence in the CNS include the cerebellum, spinal cord, and retina. Other areas where they can occur outside the CNS include organ systems such as the kidneys, liver, and pancreas. Since hemangioblastomas are usually benign and often curable if removed, they are classified as WHO grade I tumors when they occur in the CNS. Hemangioblastomas arise either in the setting of von Hippel–Lindau (VHL) disease or, more commonly, as a solitary sporadic lesion without additional stigmata or a family history [3]. VHL disease is an autosomal dominant inherited disorder caused by a germ-line mutation of the VHL gene located on the short arm of chromosome 3 (3p25-26) [2]. The presence of this mutated gene is characterized by intracranial or intraspinal hemangioblastomas, retinal angiomas, cystic lesions of the pancreas and epididymis, benign and malignant renal tumors, adrenal pheochromocytoma, extra-adrenal paragangliomas, and papillary endolymphatic sac tumors of the inner ear [4]. The association of hemangioblastomas with VHL disease makes the diagnosis and treatment of hemangioblastomas an even more clinically relevant topic of research exploration. The current review will discuss recent developments related to discovery of new factors and molecular pathways of potential clinical importance that are responsible of hemangioblastoma pathogenesis.