Hemangioblastoma and von Hippel-Lindau disease: genetic background, spectrum of disease, and neurosurgical treatment

Abstract

Introduction Hemangioblastomas are rare, histologically benign, highly vascularized tumors of the brain, the spinal cord, and the retina, occurring sporadically or associated with the autosomal dominant inherited von Hippel-Lindau (VHL) disease. Children or adults with VHL disease have one of > 300 known germline mutations of the VHL gene located on chromosome 3. They are prone to develop hemangioblastomas, extremely rarely starting at age 6, rarely at age 12–18, and, typically and almost all, as adults. There is a plethora of VHL-associated tumors and cysts, mainly in the kidney, pancreas, adrenals, reproductive organs, and central nervous system. Due to a lack of causal treatment, alleviation of symptoms and prevention of permanent neurological deficits as well as malignant transformation are the main task. Paucity of data and the nonlinear course of tumor progression make management of pediatric VHL patients with hemangioblastomas challenging. Methods The Freiburg surveillance protocol was developed by combining data from the literature and our experience of examinations of > 300 VHL patients per year at our university VHL center. Results Key recommendations are to start screening of patients at risk by funduscopy with dilated pupils for retinal tumors with admission to school and with MRI of the brain and spinal cord at age 14, then continue biannually until age 18, with emergency MRI in case of neurological symptoms. Indication for surgery remains personalized and should be approved by an experienced VHL board, but we regard neurological symptoms, rapid tumor growth, or critically large tumor/cyst sizes as the key indications to remove hemangioblastomas. Since repeated surgery on hemangioblastomas in VHL patients is not rare, modern neurosurgical techniques should encompass microsurgery, neuronavigation, intraoperative neuromonitoring, fluorescein dye-based intraoperative angiography, intraoperative ultrasound, and minimally invasive approaches, preceded in selected cases by endovascular embolization. Highly specialized neurosurgeons are able to achieve a very low risk of permanent morbidity for the removal of hemangioblastomas from the cerebellum and spinal cord. Small retinal tumors of the peripheral retina can be treated by laser coagulation, larger tumors by cryocoagulation or brachytherapy. Conclusion We consider management at experienced VHL centers mandatory and careful surveillance and monitoring of asymptomatic lesions are required to prevent unnecessary operations and minimize morbidity.

Central Nervous System Hemangioblastoma in a Pediatric Patient Associated With Von Hippel-Lindau Disease: A Case Report and Literature Review

“…Although the optimal surgical timing for resection of VHL-associated CNS HGBs and the effect of radiotherapy and chemotherapy remain unclear, tumor resection is currently the mainstay of therapy for VHL-associated CNS HGBs. The standard surgical approach for CNS HGBs is craniotomy and microsurgical treatment, which has the advantages of versatility and applicability for repeated surgeries using the same strategy and the disadvantage of invasiveness ( 6 , 10 , 32 ). Endoscopic transcranial surgery, a novel and emerging operation, is minimally invasive, but it is not clear whether it can achieve the same level of efficacy as conventional craniotomy ( 33 ).…”

“…Recently, stereotactic radiosurgery (SRS) has been investigated as an alternative treatment modality for CNS HGBs, and it is more suitable for patients with multiple or recurrent tumors and nonsurgical candidates ( 37 , 38 ). When it comes to pediatric patients, the potential risk of late sequelae should not be ignored ( 32 , 39 ). In addition, novel drugs have been developed based on the key pathways involved in HGB development, and their safety and effectiveness are being evaluated by several clinical studies ( 1 , 6 , 40 , 41 ).…”

Anesthetic Management for Resection of a Cerebellar Hemangioblastoma Leading to Brainstem Compression in a Patient With Von Hippel-Lindau Disease

“…It can be affected by the depth of anesthesia and a closed-loop communication between anesthesiologist and neurophysiology is crucial to avoid this undesirable intraoperative event. The correct identification of neural structures, such as cranial nerves and ascending and descending tracts, related to sensibility and motor function is directly related to decreased morbidity [ 29 ].…”

Efficacy and safety of current treatment options for peripheral retinal haemangioblastomas: a systematic review

“…2018; Klingler et al. 2020). Peripheral RHs are identified in approximately 85% and juxtapapillary lesions in 15% of patients (Wong et al.…”