Management Strategies and Outcomes for VHL-related Craniospinal Hemangioblastomas

Abstract

Hemangioblastomas are rare and benign tumors accounting for less than 2% of all central nervous system (CNS) tumors. The vast majority of hemangioblastomas occur sporadically, whereas a small number of cases, especially in younger patients, are associated with Von Hippel–Lindau (VHL) syndrome. It is thought that loss of tumor suppressor function of the VHL gene results in stabilization of hypoxia-inducible factor alpha with downstream activation of cellular proliferative and angiogenic genes that promote tumorigenesis. VHL-related hemangioblastomas predominantly occur in the cerebellum and spine. Lesions are often diagnosed on contrast-enhanced craniospinal MRIs, and the diagnosis of VHL occurs through assessment for germline VHL mutations. Surgical resection remains the primary treatment modality for symptomatic or worrisome lesions, with excellent local control rates and neurological outcomes. Stereotactic radiotherapy can be employed in patients who are deemed high risk for surgery, have multiple lesions, or have non-resectable lesions. Given the tendency for development of either new or multiple lesions, close radiographic surveillance is often recommended for asymptomatic lesions.

Incidence, Prognostic Factors and Survival for Hemangioblastoma of the Central Nervous System: Analysis Based on the Surveillance, Epidemiology, and End Results Database

“…To our knowledge, this study of the SEER database represents the largest published cohort of patients with CNS hemangioblastomas at present. This study analyzed the incidence, demographic and clinical characteristics, and prognosis of CNS hemangioblastomas, which may be more generalizable than previously published literature with relatively small case series ( 1 , 7 , 10 – 12 , 17 – 19 ). Our analysis of incidence indicates that CNS hemangioblastomas are relatively rare neoplasms, with an overall incidence of 0.141 per 100,000 person-years and highest incidence among Caucasian males between age 65–69.…”

“…To date, both surgery and radiotherapy have roles in the management of CNS hemangioblastomas. Early studies have suggested that surgical resection of hemangioblastomas, which contributes to the timely relief of regional pressure, remains the optimal option ( 10 – 12 , 19 ). Gross total resection is curative ( 9 ).…”

Sporadic and Hereditary Hemangioblastoma: The Role of Endothelial Cells

“…In contrast, under hypoxic conditions, the wild-type pVHL does not recognize and bind to HIF-1α, thus preventing its degradation. Similarly, it is postulated that mutated pVHL stabilizes HIF-α, resulting in downstream upregulation of cellular proliferative and angiogenic genes, such as vascular endothelial growth factor and platelet-derived growth factor, which promote tumorigenesis [24]. Moreover, in addition to VHL mutations, a variety of genes and microRNAs (miRNAs) have been implicated in the pathogenesis of HBs, all of them being functionally involved in cell proliferation and angiogenesis promoting pathways [25].…”

“…Although benign, HBs can be a significant source of neurological morbidity or even mortality following intratumoral hemorrhage or cystic expansion of the tumor. Surgical resection of symptomatic or progressing lesions is the preferred treatment modality and can be curative, although observation is reasonable for asymptomatic lesions with minimal growth [24]. Unfortunately, no biomarkers have yet been identified to predict the onset, recurrence, or progression of HB.…”

Long‐term outcome of a dog with surgically resected thoracic intramedullary haemangioblastoma and concurrent lumbosacral disease

“…They comprise less than 3% of the central nervous system tumours in humans 1 . These tumours are thought to be associated with the Von Hippel–Lindau (VHL) syndrome, 3 which is a hereditary disease caused by mutations in the VHL tumour suppressor gene, 4 leading to an increased risk of tumour formation 5 . These tumours frequently arise in the cerebellum, but occur in the spinal cord less commonly 6 .…”