Hemangioblastoma

Hemangioblastoma is a benign (grade 1), highly vascular tumor of the central nervous system. It makes up 1 to 2% of CNS tumors and 7 to 12% of adult posterior fossa tumors. About 60 to 75% are sporadic, usually solitary, with onset at 40 to 50 years. The remaining 25 to 40% occur in von Hippel-Lindau disease (VHL gene on chromosome 3p25, autosomal dominant), where tumors are often multiple and appear at a mean age of about 30 years.

Sites are the cerebellum (about 80%), brainstem (obex and area postrema), and spinal cord (mainly dorsal, cervical and thoracic). About 60% have a cyst with a small enhancing mural nodule, and the nodule is the tumor. Growth is saltatory, with long quiescent periods. Erythropoietin secretion causes polycythemia in 10 to 20%.

Complications

• Hydrocephalus
• Intratumoral or subarachnoid hemorrhage
• Syringomyelia and cord compression
• Cranial neuropathy
• Recurrence at residual or new sites, nearly universal over time in VHL

• Headache, vomiting, truncal and limb ataxia, dysmetria and gait instability
• Spinal lesions: dysesthesia, progressive sensory loss, myelopathy, pain
• Plethora and raised hematocrit
• In VHL: retinal angiomas (visual loss), renal cell carcinoma, pheochromocytoma, pancreatic cysts and neuroendocrine tumors, endolymphatic sac tumors (hearing loss, tinnitus, vertigo), epididymal cystadenomas
• Red flags: sudden deterioration (hemorrhage), falling consciousness (hydrocephalus), acute cord syndrome

1. MRI brain and whole spine with gadolinium: a cyst with an intensely enhancing nodule on the pial surface, or a solid enhancing mass with flow voids. Spinal lesions show cord edema or syrinx.
2. Hemoglobin and hematocrit (polycythemia).
3. Angiography only for planning embolization of large solid tumors.
4. Germline VHL sequencing and deletion analysis in every patient under 50, with multiple lesions, or with a family history, since up to 20% of apparently sporadic cases under 30 carry a mutation.
5. VHL screening when positive: dilated retinal examination, MRI abdomen, plasma free metanephrines, MRI of the internal auditory canals and audiology.

Differentials: metastasis (renal cell carcinoma), pilocytic astrocytoma, meningioma, cavernous malformation, arteriovenous malformation, ependymoma.

• Surgery: complete microsurgical excision of the nodule, with early control of the feeding vessels and no need to remove the cyst wall. Embolization before surgery for large solid tumors. Dexamethasone 4 mg orally or IV every 6 hours for edema, with omeprazole 20 mg orally daily. Cefazolin 2 g IV before incision (3 g if over 120 kg).
• Hydrocephalus: external ventricular drain or endoscopic third ventriculostomy after tumor control.
• Stereotactic radiosurgery for small tumors (under 3 cm), multiple lesions and residual disease: marginal dose 12 to 15 Gy in a single fraction. Cystic tumors respond less well.
• Belzutifan for VHL-associated tumors that do not need immediate surgery: 120 mg orally once daily until progression or toxicity. Monitor hemoglobin (anemia is common), oxygen saturation (hypoxia), and exclude pregnancy first, as it is teratogenic and reduces the effect of hormonal contraceptives, so use a barrier method.
• Polycythemia: venesection of 250 to 500 mL to keep hematocrit under 45%.
• Retinal angiomas: laser photocoagulation or cryotherapy.

Surveillance in VHL: MRI brain and spine every 1 to 2 years, retinal examination yearly, and renal and adrenal assessment. Sporadic disease needs MRI at 3 months, then yearly for 5 years. Offer genetic counseling and testing to relatives.