Hemangioblastomas and Other Vascular Origating Tumors of Brain or Spinal Cord

Adv Exp Med Biol. 2023:1405:377-403. doi: 10.1007/978-3-031-23705-8_14.

Abstract

Hemangioblastomas (HBs) are highly vascularized, slow-growing, rare benign tumors (WHO grade I). They account for about 2% of intracranial neoplasms; however, they are the most common primary cerebellar tumors in adults. Another frequent seat is the spinal cord (2-10% of primary spinal cord tumors). HBs are constituted by stromal and capillary vascular cells; macroscopically, HBs appear as nodular tumors, with or without cystic components. Although most of the HBs are sporadic (57-75%), they represent a particular component of von Hippel-Lindau disease (VHL), an autosomal dominant syndrome with high penetrance, due to a germline pathogenic mutation in the VHL gene, which is a tumor suppressor with chromosomal location on the short arm of chromosome three. VHL disease determines a variety of malignant and benign tumors, most frequently HBs, renal cell carcinomas, pheochromocytomas/paragangliomas, pancreatic neuroendocrine tumors, and endolymphatic sac tumors. Up to 20% of cases are due to de novo pathogenic variants without a family history. Many epidemiologic details of these tumors, especially the sporadic forms, are not well known. The median age of patients with sporadic HBS is about 40 years. More than two-third of VHL patients develop one or more central nervous system HBs during their lifetime; in case of VHL, patients at first diagnosis are usually younger than the patients with sporadic tumors. The most common presenting signs and symptoms are related to increased intracranial pressure, cerebellar signs, or spinal cord alterations in case of spinal involvement. Magnetic resonance imaging is the gold standard for the diagnosis, assessment, and follow-up of HBs, both sporadic and syndrome-related; angiography is rarely performed because the diagnosis is easily obtained with magnetic resonance. However, the diagnosis of an asymptomatic lesion does not automatically result in therapeutic actions, as the risks of treatment and the onset of possible neurological deficit need to be balanced, considering that HBs may remain asymptomatic and have a static or slow-growing behavior. In such cases, regular follow-up can represent a valid therapeutic option until the patients remain asymptomatic. There are no actual pharmacological therapies that are demonstrated to be effective for HBs. Surgery represents the primary therapeutic approach for these tumors. Observation or radiotherapy also plays a role in the long-term management of patients harboring HBs, especially in VHL; in few selected cases, endovascular treatment has been suggested before surgical removal. This chapter presents a systematic overview of epidemiology, clinical appearance, histopathological and neuroradiological characteristics of central nervous system HBs. Moreover, the genetic and molecular biology of sporadic and VHL HBS deserves special attention. Furthermore, we will describe all the available therapeutic options, along with the follow-up management. Finally, we will briefly report other vascular originating tumors as hemangioendotheliomas, hemangiomas, or angiosarcomas.

Keywords: Angiosarcoma; Fluorescein; HIF; Hemangioblastoma; Hemangioendothelioma; ICG; Solitary fibrous tumor/hemangiopericytoma; VHL; von Hipple-Lindau disease.

Publication types

  • Review

MeSH terms

  • Adult
  • Brain / pathology
  • Central Nervous System Neoplasms* / complications
  • Central Nervous System Neoplasms* / genetics
  • Central Nervous System Neoplasms* / surgery
  • Hemangioblastoma* / genetics
  • Hemangioblastoma* / pathology
  • Hemangioblastoma* / surgery
  • Humans
  • Kidney Neoplasms*
  • Spinal Cord / pathology
  • Spinal Cord Neoplasms* / diagnostic imaging
  • Spinal Cord Neoplasms* / genetics
  • Syndrome
  • von Hippel-Lindau Disease* / genetics