INNV-43. Sporadic hemangioblastomatosis: a case of remarkable response to belzutifan in the absence of von Hippel-Lindau syndrome

Abstract Hemangioblastomatosis of the central nervous system is predominantly associated with von Hippel-Lindau (VHL) syndrome but can rarely occur sporadically. In sporadic cases of hemangioblastoma, lesions are typically solitary, and patients tend to present at an older age (median 40–50 years) compared to those with VHL-associated disease. Sporadic hemangioblastomas are more likely to be symptomatic at presentation, often due to mass effect or cyst formation. Outside of surgical resection or radiation, there are currently no approved treatment options for sporadic cases. A 75-year-old woman with a remote history of localized breast cancer treated definitively presented with ataxia, neck pain, and bladder incontinence. Imaging revealed a 2.4 cm intradural extramedullary cervical spinal cord lesion and diffuse leptomeningeal enhancement of the brain and spinal cord. Despite corticosteroids, her condition rapidly declined. She underwent partial resection of the cervical lesion, which was diagnosed as a WHO grade 1 hemangioblastoma. Postoperatively, she experienced worsening headaches and progressive lethargy. She was diagnosed with pulmonary emboli and started on anticoagulation. Due to her extensive leptomeningeal disease and declining functional status—including loss of independent ambulation—hospice enrollment was considered. Given the tumor pathology, expedited genetic testing for von Hippel-Lindau (VHL) disease was pursued. Meanwhile, palliative treatment with belzutifan at a reduced dose (80 mg daily) was initiated. Within four weeks, she showed marked clinical improvement, including the ability to walk unassisted. Genetic testing ultimately revealed no evidence of a hereditary syndrome, including VHL. Eight weeks after starting belzutifan, neuroimaging showed significant improvement. Due to fatigue, her dose was reduced to 40 mg daily at eight months, which she tolerated well. After 22 months of therapy, she continues to demonstrate sustained clinical and radiographic improvement with excellent quality-of-life. This represents a new potential systemic therapy option for individuals with unresectable sporadic hemangioblastoma.