ABSTRACT
Purpose: To report a series of three patients with von Hippel-Lindau (VHL) disease who demonstrated regression of their retinal hemangioblastomas (RH) using belzutifan in conjunction with photocoagulation therapy. Observations: Patient 1, a 23-year-old female, presented with multiple RHs in her right eye (OD) that were lasered. Her left eye (OS) revealed a large inferotemporal RH that measured approximately 2.1 mm2. Systemic belzutifan was administered. Four months after initiation of treatment, the lesion regressed to 1.4 mm2, but belzutifan was not well-tolerated and was discontinued due to side effects. At the date of belzutifan discontinuation, the lesion measured about 1.1 mm2. Focal laser photocoagulation was applied. The lesion regressed to around 0.6 mm2. Two additional laser treatments were applied one month later. On the most recent follow-up, the lesion was completely fibrosed.Patient 2, a 32-year-old male, presented with one RH OD and two RHs OS. Belzutifan was administered for one month before the patient began experiencing side effects of the medication. Consequently, the dose of belzutifan was decreased. After one month with the lowered dose, laser coagulation was applied to OS. In the most recent follow-up, five months after the initial presentation, the lesions remain less vascularized and reduced in size.Patient 3, is a 44-year-old male with a large RH OD. Following seven months of belzutifan daily, there was a significant reduction in the RH size. Conclusions: Belzutifan, a hypoxia-inducible factor inhibitor, is an FDA-approved medication for VHL disease associated with renal cell carcinoma, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors that do not require immediate surgical resection. Because of the high incidence of VHL-associated RHs, adjuvant laser photocoagulation therapy when belzutifan is suspended or withheld can allow for the regression of large lesions. In this case series, we also propose a reproducible and technically simple method to measure RH lesions size, using Optos fundus imaging.
ABSTRACT
Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare neoplasm of the central nervous system (CNS) that primarily affects the leptomeninges. However, it can also involve the brain parenchyma and spinal cord. We report the first case of metastasis of this primary CNS tumor to the lung and bone marrow. An 18-year-old male was diagnosed with DLGNT through meningeal biopsy after multiple events of transient neurologic signs and symptoms that included recurrent episodes of encephalopathy, seizures, cerebral vasospasms, cranial nerve palsy, and urinary dysfunction. Five months after diagnosis, the patient presented with pancytopenia and pulmonary effusion. At that time, he was being treated with temozolomide, after radiation treatment to the brain and spinal cord. Bone marrow biopsy and pleural cytology revealed systemic metastases from the primary CNS tumor. He was then treated with chemotherapy with carboplatin and vincristine which improved his condition for two and a half months. Unfortunately, the patient died of a high systemic metastatic burden. Primary CNS tumors rarely produce systemic metastases, and this is the first report of DLGNT with bone marrow and pulmonary metastases. Chemotherapy with carboplatin and vincristine should be considered as a treatment for patients with DLGNT, as the patient presented a systemic response with clinical and radiological improvement.
