HEMANGIOBLASTOMA OF THE CENTRAL NERVOUS SYSTEM: DIAGNOSTIC CHALLENGES AND NEW THERAPEUTIC FRONTIERS
Keywords:
Hemangioblastoma, Von Hippel-Lindau Syndrome, Neurosurgery, Targeted Therapy, HIF-2α Inhibitors, Imaging Diagnosis, RadiosurgeryAbstract
This chapter provides a comprehensive and updated review of central nervous system (CNS) hemangioblastomas, rare but clinically significant benign neoplasms. It addresses epidemiology, molecular pathophysiology with emphasis on the VHL-HIF pathway, which is central to both sporadic forms and those associated with Von Hippel-Lindau (VHL) syndrome, and the multifaceted challenges in differential diagnosis. The analysis details neuroimaging findings, from conventional magnetic resonance imaging to advanced techniques such as arterial spin labeling perfusion, and explores immunohistochemical pitfalls that can mimic other neoplasms, such as metastatic renal cell carcinoma. Standard therapeutic modalities, including microsurgical resection as the gold standard for symptomatic lesions and stereotactic radiosurgery for selected cases, are discussed in depth, based on long-term outcome evidence. The main focus is on new therapeutic frontiers, notably targeted therapy with hypoxia-inducible factor 2-alpha (HIF-2α) inhibitors, such as belzutifan. This agent represents a paradigm shift in management, especially for patients with VHL, by offering a systemic approach that targets the molecular basis of the disease, with the potential to alter its natural history.
