Hemangioblastoma

INTRODUCTION

Hemangioblastomas are uncommon, slow-growing tumors of the central nervous system, which most commonly occur in the cerebellum, brainstem, or spinal cord. They account for approximately 4 percent of all spinal cord tumors, and 7 to 10 percent of tumors arising in the posterior fossa in adults.

Hemangioblastomas occur both sporadically and as an important component of von Hippel-Lindau (VHL) disease. VHL disease is an inherited, autosomal-dominant syndrome manifested by a variety of benign and malignant tumors, including hemangioblastomas, retinal angiomas, endolymphatic sac tumors, renal cell carcinoma (RCC), pheochromocytomas, pancreatic cysts, and neuroendocrine tumors.

The clinical manifestations and management of patients with hemangioblastomas are reviewed here. The clinical manifestations and overall management of patients with VHL disease are discussed separately.

CLINICAL MANIFESTATIONS

Sporadic versus VHL-associated tumors — Hemangioblastomas may occur either sporadically or as a manifestation of von Hippel-Lindau (VHL) disease. Although approximately 75 percent of all hemangioblastomas appear to be sporadic, some of these may represent occult cases of VHL that can be detected if patients are appropriately screened for germline VHL pathogenic variants.

Symptoms — Hemangioblastomas can cause local symptoms by compression of neural structures, bleeding, or paraneoplastic complications. In patients with VHL disease, asymptomatic hemangioblastomas are diagnosed based upon imaging surveillance.

Neuroimaging — The majority of hemangioblastomas occur in the posterior fossa, with 80 percent in the cerebellar hemispheres and 15 percent in the cerebellar vermis. The characteristic appearance on MRI is either that of an intra-axial cystic mass with an enhancing mural nodule abutting the pia or a solid, intensely enhancing mass, often with flow-voids from dilated vessels next to or within the tumor. Smaller hemangioblastomas (<10 mm) may be isointense on T1-weighted images and hyperintense on T2-weighted images, with homogeneous contrast enhancement.

TREATMENT

Hemangioblastomas are highly vascular tumors that are often located in neurologically sensitive areas in the neuraxis. The anatomic location of the lesion plays an important role in determining the therapeutic approach. Patients are best managed in a multidisciplinary fashion with input from neurosurgeons, interventional neuroradiologists, radiation oncologists, and neurooncologists with expertise in central nervous system malignancies.

For patients with von Hippel-Lindau (VHL) disease, multiple tumors are common, and therapeutic efforts should focus on avoiding treatment-related morbidity by minimizing the frequency of surgical interventions.

Women with existing retinal, brain, and spinal cord lesions are at risk for tumor growth during pregnancy. A noncontrast magnetic resonance imaging (MRI) in the fourth month of pregnancy may be considered in these patients. Neuroimaging findings, along with clinical signs and symptoms, may be used to make decisions regarding the management of labor and delivery.

Both surgical resection and radiation therapy (RT) have a role in the management of appropriately selected patients with sporadic tumors. The hypoxia inducible factor-2alpha (HIF-2alpha) inhibitor, belzutifan, is an additional option in patients with VHL-associated hemangioblastomas.

Surgery — Surgical resection offers definitive therapy for sporadic, isolated hemangioblastomas, particularly those arising in the cerebellum. The role of surgery in patients with VHL disease is less well defined because of the frequent occurrence of additional synchronous and metachronous lesions.

Radiation therapy — Although there are no randomized clinical trials comparing RT with surgery in patients with hemangioblastomas, increasing data with relatively long follow-up support the role of RT, particularly for patients with multiple tumors and those with surgically inaccessible lesions. Most of the contemporary data come from series using stereotactic radiosurgery (SRS), although external beam RT (EBRT) or proton beam RT may be useful in selected cases.

Antiangiogenic therapy — Because of the role of vascular endothelial growth factor (VEGF) in the formation of hemangioblastomas, inhibitors of angiogenesis (eg, bevacizumab) may offer a potential therapeutic approach for lesions not amenable to surgery or RT. Preliminary experience with this approach has been derived from the treatment of patients with retinal angiomas.

When to refer for genetic testing — All patients with more than one hemangioblastoma, the presence of other manifestations of VHL disease, or a family history of VHL should undergo genetic screening for germline VHL pathogenic variants. The likelihood of having a pathogenic variant in VHL varies inversely with age. Patients should be referred for appropriate genetic advice in conjunction with genetic testing.