- Eric T Wong, MD
Eric T Wong, MD
- Associate Professor of Neurology
- Harvard Medical School
- Jeffrey Joseph, MD, PhD
Jeffrey Joseph, MD, PhD
- Professor of Pathology
- University of Calgary School of Medicine
- Julian K Wu, MD
Julian K Wu, MD
- Professor of Neurosurgery
- Tufts University School of Medicine
- Section Editors
- Jay S Loeffler, MD
Jay S Loeffler, MD
- Section Editor — Neurooncology
- Professor of Radiation Oncology
- Harvard Medical School
- Patrick Y Wen, MD
Patrick Y Wen, MD
- Section Editor — Neurooncology
- Professor of Neurology
- Harvard Medical School
Hemangioblastomas are uncommon, slow-growing tumors of the central nervous system, which most commonly occur in the cerebellum, brainstem, or spinal cord. They account for approximately 4 percent of all spinal cord tumors, and 7 to 10 percent of tumors arising in the posterior fossa in adults.
Hemangioblastomas occur both sporadically and as an important component of von Hippel-Lindau (VHL) disease, along with retinal angiomas, renal cell carcinoma, pheochromocytomas, pancreatic cysts and neuroendocrine tumors.
The clinical manifestations and management of patients with hemangioblastomas are reviewed here. The clinical manifestations and overall management of patients with VHL disease are discussed separately. (See "Clinical features, diagnosis, and management of von Hippel-Lindau disease".)
Sporadic versus VHL-associated tumors — Hemangioblastomas may occur either sporadically or as a manifestation of VHL disease. Although approximately 75 percent of all hemangioblastomas appear to be sporadic , some of these may represent occult cases of VHL that can be detected if patients are appropriately screened for germline VHL mutations. (See "Clinical features, diagnosis, and management of von Hippel-Lindau disease", section on 'Hemangioblastomas'.)
Sporadic and VHL-related hemangioblastomas differ significantly in their presentation:
- Neumann HP, Eggert HR, Weigel K, et al. Hemangioblastomas of the central nervous system. A 10-year study with special reference to von Hippel-Lindau syndrome. J Neurosurg 1989; 70:24.
- Aldape, KD, Plate, KH, Vortmeyer, AO, et al Haemangioblastoma. In Louis, DN, Ohgaki, H, Wiestler, OD, Cavenee,WK (editors). WHO Classification of Tumours of the Nervous System. IARC Press, Lyon 2007.
- Roonprapunt C, Silvera VM, Setton A, et al. Surgical management of isolated hemangioblastomas of the spinal cord. Neurosurgery 2001; 49:321.
- Wakai S, Inoh S, Ueda Y, Nagai M. Hemangioblastoma presenting with intraparenchymatous hemorrhage. J Neurosurg 1984; 61:956.
- Adegbite AB, Rozdilsky B, Varughese G. Supratentorial capillary hemangioblastoma presenting with fatal spontaneous intracerebral hemorrhage. Neurosurgery 1983; 12:327.
- Yu JS, Short MP, Schumacher J, et al. Intramedullary hemorrhage in spinal cord hemangioblastoma. Report of two cases. J Neurosurg 1994; 81:937.
- Cerejo A, Vaz R, Feyo PB, Cruz C. Spinal cord hemangioblastoma with subarachnoid hemorrhage. Neurosurgery 1990; 27:991.
- Kormos RL, Tucker WS, Bilbao JM, et al. Subarachnoid hemorrhage due to a spinal cord hemangioblastoma: case report. Neurosurgery 1980; 6:657.
- WALDMANN TA, LEVIN EH, BALDWIN M. The association of polycythemia with a cerebellar hemangioblastoma. The production of an erythropoiesis stimulating factor by the tumor. Am J Med 1961; 31:318.
- Zec N, Cera P, Towfighi J. Extramedullary hematopoiesis in cerebellar hemangioblastoma. Neurosurgery 1991; 29:34.
- Kühne M, Sidler D, Hofer S, et al. Challenging manifestations of malignancies. Case 1. Polycythemia and high serum erythropoietin level as a result of hemangioblastoma. J Clin Oncol 2004; 22:3639.
- Tachibana O, Yamashima T, Yamashita J. Immunohistochemical study of erythropoietin in cerebellar hemangioblastomas associated with secondary polycythemia. Neurosurgery 1991; 28:24.
- Chu BC, Terae S, Hida K, et al. MR findings in spinal hemangioblastoma: correlation with symptoms and with angiographic and surgical findings. AJNR Am J Neuroradiol 2001; 22:206.
- Bohling, T, Hatva, E, Plate, KH, et al. Von Hippel-Lindau disease and capillary haemangioblastoma. In: Tumor of the Nervous system Pathology and Genetics, Kleihues, P, Cavenee, WK (Eds) International Agency for Research on Cancer, Lyon, France 1997. p.179.
- Burger, PC, Scheithauer, BW. Tumors of the Central Nervous System. Armed Forces Institute of Pathology, Washington, DC 1994. p.239.
- Jung SM, Kuo TT. Immunoreactivity of CD10 and inhibin alpha in differentiating hemangioblastoma of central nervous system from metastatic clear cell renal cell carcinoma. Mod Pathol 2005; 18:788.
- Kanno H, Kondo K, Ito S, et al. Somatic mutations of the von Hippel-Lindau tumor suppressor gene in sporadic central nervous system hemangioblastomas. Cancer Res 1994; 54:4845.
- Lee JY, Dong SM, Park WS, et al. Loss of heterozygosity and somatic mutations of the VHL tumor suppressor gene in sporadic cerebellar hemangioblastomas. Cancer Res 1998; 58:504.
- Gläsker S, Bender BU, Apel TW, et al. Reconsideration of biallelic inactivation of the VHL tumour suppressor gene in hemangioblastomas of the central nervous system. J Neurol Neurosurg Psychiatry 2001; 70:644.
- Gijtenbeek JM, Jacobs B, Sprenger SH, et al. Analysis of von hippel-lindau mutations with comparative genomic hybridization in sporadic and hereditary hemangioblastomas: possible genetic heterogeneity. J Neurosurg 2002; 97:977.
- Vortmeyer AO, Gnarra JR, Emmert-Buck MR, et al. von Hippel-Lindau gene deletion detected in the stromal cell component of a cerebellar hemangioblastoma associated with von Hippel-Lindau disease. Hum Pathol 1997; 28:540.
- Krieg M, Marti HH, Plate KH. Coexpression of erythropoietin and vascular endothelial growth factor in nervous system tumors associated with von Hippel-Lindau tumor suppressor gene loss of function. Blood 1998; 92:3388.
- Conway JE, Chou D, Clatterbuck RE, et al. Hemangioblastomas of the central nervous system in von Hippel-Lindau syndrome and sporadic disease. Neurosurgery 2001; 48:55.
- Wanebo JE, Lonser RR, Glenn GM, Oldfield EH. The natural history of hemangioblastomas of the central nervous system in patients with von Hippel-Lindau disease. J Neurosurg 2003; 98:82.
- Lonser RR, Weil RJ, Wanebo JE, et al. Surgical management of spinal cord hemangioblastomas in patients with von Hippel-Lindau disease. J Neurosurg 2003; 98:106.
- Weil RJ, Lonser RR, DeVroom HL, et al. Surgical management of brainstem hemangioblastomas in patients with von Hippel-Lindau disease. J Neurosurg 2003; 98:95.
- Frantzen C, Kruizinga RC, van Asselt SJ, et al. Pregnancy-related hemangioblastoma progression and complications in von Hippel-Lindau disease. Neurology 2012; 79:793.
- Eskridge JM, McAuliffe W, Harris B, et al. Preoperative endovascular embolization of craniospinal hemangioblastomas. AJNR Am J Neuroradiol 1996; 17:525.
- Tampieri D, Leblanc R, TerBrugge K. Preoperative embolization of brain and spinal hemangioblastomas. Neurosurgery 1993; 33:502.
- Lonser RR, Heiss JD, Oldfield EH. Tumor devascularization by intratumoral ethanol injection during surgery. Technical note. J Neurosurg 1998; 88:923.
- Vázquez-Añón V, Botella C, Beltrán A, et al. Preoperative embolization of solid cervicomedullary junction hemangioblastomas: report of two cases. Neuroradiology 1997; 39:86.
- Jagannathan J, Lonser RR, Smith R, et al. Surgical management of cerebellar hemangioblastomas in patients with von Hippel-Lindau disease. J Neurosurg 2008; 108:210.
- Kanno H, Yamamoto I, Nishikawa R, et al. Spinal cord hemangioblastomas in von Hippel-Lindau disease. Spinal Cord 2009; 47:447.
- Parker F, Aghakhani N, Ducati LG, et al. Results of microsurgical treatment of medulla oblongata and spinal cord hemangioblastomas: a comparison of two distinct clinical patient groups. J Neurooncol 2009; 93:133.
- Fukuda M, Takao T, Hiraishi T, et al. Clinical Factors Predicting Outcomes After Surgical Resection for Sporadic Cerebellar Hemangioblastomas. World Neurosurg 2014; 82:815.
- Moss JM, Choi CY, Adler JR Jr, et al. Stereotactic radiosurgical treatment of cranial and spinal hemangioblastomas. Neurosurgery 2009; 65:79.
- Kano H, Niranjan A, Mongia S, et al. The role of stereotactic radiosurgery for intracranial hemangioblastomas. Neurosurgery 2008; 63:443.
- Koh ES, Nichol A, Millar BA, et al. Role of fractionated external beam radiotherapy in hemangioblastoma of the central nervous system. Int J Radiat Oncol Biol Phys 2007; 69:1521.
- Hanakita S, Koga T, Shin M, et al. The long-term outcomes of radiosurgery for intracranial hemangioblastomas. Neuro Oncol 2014; 16:429.