Introduction
In 1928, Cushing and Bailey introduced the term hemangioblastoma.1 It refers to a benign vascular neoplasm that arises almost exclusively in the central nervous system. According to the World Health Organization classification of tumors of the nervous system, hemangioblastomas are classified as meningeal tumors of uncertain origin.2,3
Supratentorial hemangioblastoma proved by histologic analysis. Carotid arteriogram demonstrates a vascular, dense, tumor filled from the anterior cerebral vessels and not involving the sagittal sinus.
History of the Procedure
Since its original description, hemangioblastomas have been found in multiple regions of the central nervous system. Predominant involvement of the cerebellum and the spinal cord was noted, but true incidence of this tumor was not discovered until the recent increased availability of noninvasive diagnostic imaging modalities, particularly magnetic resonance imaging. This, in addition to significant improvement in surgical approaches and microsurgical technique, have made hemangioblastoma, although dangerous, a potentially treatable and curable disease.
Frequency
Incidence and location
Hemangioblastomas are rare, and according to various series, they account for 1-2.5% of all intracranial neoplasms.4,5 Most hemangioblastomas are located in the posterior cranial fossa; in that region, hemangioblastomas comprise 8-12% of neoplasms. Hemangioblastoma is the most common primary adult intraaxial posterior fossa tumor.6 Cerebellar hemangioblastomas are frequently referred to as Lindau tumors because Swedish pathologist Arvid Vilhelm Lindau first described them in 1926.7
The second most common location of hemangioblastomas is the spinal cord,8,9,10,11 where the frequency ranges from 2-3% of primary spinal cord neoplasms to 7-11% of spinal cord tumors. This tumor's occurrence in other locations, such as the supratentorial compartment,12,13,14 the optic nerve,15 the peripheral nerves,16 or the soft tissues of extremities17 is extremely rare.
Sex and age distribution
Hemangioblastomas are more common in men than in women. In most clinical series, the male-to-female ratio is approximately 2:1. Although hemangioblastomas may develop at any age, they rarely affect children; the usual age at diagnosis is between the third and fifth decades.
von Hippel-Lindau disease
Most hemangioblastomas arise sporadically. However, in approximately one quarter of all cases, they are associated with von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary syndrome that includes retinal angiomatosis, central nervous system hemangioblastomas, and various visceral tumors most commonly involving the kidneys and adrenal glands.18 This syndrome is classified as a phakomatosis, although it does not include any cutaneous manifestations. The syndrome has variable penetrance, but its dominant mode of transmission compels performing at least a screening of family members of patients diagnosed with VHL disease. In some patients with VHL disease, hemangioblastomas may produce erythropoietinlike substances, resulting in polycythemia at the time of diagnosis.
Etiology
Etiology of the hemangioblastoma is obscure, but its presence in various clinical syndromes may suggest an underlying genetic abnormality. The genetic hallmark of hemangioblastomas is the loss of function of the von Hippel-Lindau (VHL) tumor suppressor protein.19
Pathophysiology
Upon gross examination, hemangioblastomas are usually cherry red in color. They may include a cyst that contains a clear fluid, but solid tumors are as common as cystic ones. The tumor usually grows inside the parenchyma of the cerebellum, brain stem, or spinal cord; it is attached to the pia mater and gets its rich vascular supply from the pial vessels. However, extramedullary and extradural hemangioblastomas also have been described.20
Presentation
The clinical presentation of hemangioblastomas usually depends on the anatomical location and growth patterns. Cerebellar lesions may present with signs of cerebellar dysfunction, such as ataxia and discoordination, or with symptoms of increased intracranial pressure due to associated hydrocephalus.
In general, intracranial hemangioblastomas present with a long history of minor neurological symptoms that, in most cases, are followed by a sudden exacerbation, which may necessitate immediate neurosurgical intervention.
Patients with spinal cord lesions most frequently present with pain, followed by signs of segmental and long-track dysfunction due to progressive compression of the spinal cord.
Patients with VHL disease may present with ocular or systemic symptoms due to involvement of other organs and systems.
The polycythemia that may develop in some patients with hemangioblastomas usually is clinically asymptomatic.
Spontaneous hemorrhage is possible in both intraspinal and intracranial hemangioblastomas,21 but this risk is low and tumors smaller than 1.5 cm carry virtually no risk of spontaneous hemorrhage.
Indications
In many cases, symptoms caused by the growth of the neoplasm itself may be an indication for surgical intervention. In others, symptomatic obstruction of the cerebrospinal fluid (CSF) pathways may necessitate the operation. Asymptomatic lesions that sometimes are encountered in patients with multiple hemangioblastomas may be safely observed with frequent MRI scans to rule out tumor enlargement.
Relevant Anatomy
Presence of a hemangioblastoma rarely, if ever, alters normal anatomy. In choosing the appropriate surgical approach to the tumor, one must take into consideration the position of the mass, presence (or absence) of a large cystic component, associated hydrocephalus and surrounding edema, and the eloquence of neighboring neural and vascular structures. In most cases, cerebellar lesions may be removed through a suboccipital craniectomy, whereas spinal lesions are best addressed from a posterior direction through a laminectomy approach.
Contraindications
As always, surgical resection should be offered to the patient unless the risk of operation outweighs its potential benefits. Acute anticoagulation, the presence of active systemic infection, and severe medical problems that would make general anesthesia too risky generally are considered contraindications for an elective neurosurgical operation. However, the decision should be made on an individual basis.
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References
Cushing H, Bailey P. Tumors Arising from Blood Vessels of the Brain: Angiomatous Malformations and Hemangioblastomas. Springfield, Ill: Charles C Thomas Publisher; 1928.
Rubinstein LJ. Atlas of Tumor Pathology: Tumors of the Central Nervous System. Washington, DC: US Government Printing Office; 1972:235.
Gonzales MF. Classification and pathogenesis of brain tumors. In: Kaye AH, Laws ER, eds. Brain Tumors. ed. New York, NY: Churchill Livingstone; 1995:31-45.
Zulch KJ. Brain Tumors: Their Biology and Pathology. New York, NY: Springer-Verlag; 1986.
Neumann HP, Eggert HR, Weigel K, Friedburg H, Wiestler OD, Schollmeyer P. Hemangioblastomas of the central nervous system. A 10-year study with special reference to von Hippel-Lindau syndrome. J Neurosurg. Jan 1989;70(1):24-30. [Medline].
Constans JP, Meder F, Maiuri F, Donzelli R, Spaziante R, de Divitiis E. Posterior fossa hemangioblastomas. Surg Neurol. Mar 1986;25(3):269-75. [Medline].
Lindau A. Studien uber Kleinhirncysten. Bau, Pathogenese und Beizeihunger zur Angiomatosis Retinae. Acta Pathol Microbiol Scand. 1926;1(Suppl):3-120.
Yasargil MG, Antic J, Laciga R, de Preux J, Fideler RW, Boone SC. The microsurgical removal of intramedullary spinal hemangioblastomas. Report of twelve cases and a review of the literature. Surg Neurol. Sep 1976;141-8. [Medline].
Murota T, Symon L. Surgical management of hemangioblastoma of the spinal cord: a report of 18 cases. Neurosurgery. Nov 1989;25(5):699-707; discussion 708. [Medline].
Fischer G, Brotchi J. Intramedullary Spinal Cord Tumors. ed. Stuttgart, Germany: Thieme Medical Publishers; 1996:72-7.
Roonprapunt C, Silvera VM, Setton A, Freed D, Epstein FJ, Jallo GI. Surgical management of isolated hemangioblastomas of the spinal cord. Neurosurgery. Aug 2001;49(2):321-7; discussion 327-8. [Medline].
Adegbite AB, Rozdilsky B, Varughese G. Supratentorial capillary hemangioblastoma presenting with fatal spontaneous intracerebral hemorrhage. Neurosurgery. Mar 1983;12(3):327-30. [Medline].
Goto T, Nishi T, Kunitoku N, et al. Suprasellar hemangioblastoma in a patient with von Hippel-Lindau disease confirmed by germline mutation study: case report and review of the literature. Surg Neurol. Jul 2001;56(1):22-6. [Medline].
Peker S, Kurtkaya-Yapicier O, Sun I, Sav A, Pamir MN. Suprasellar haemangioblastoma. Report of two cases and review of the literature. J Clin Neurosci. Jan 2005;12(1):85-9. [Medline].
Kerr DJ, Scheithauer BW, Miller GM, Ebersold MJ, McPhee TJ. Hemangioblastoma of the optic nerve: case report. Neurosurgery. Mar 1995;36(3):573-80; discussion 580-1. [Medline].
Giannini C, Scheithauer BW, Hellbusch LC, et al. Peripheral nerve hemangioblastoma. Mod Pathol. Oct 1998;11(10):999-1004. [Medline].
Patton KT, Satcher RL Jr, Laskin WB. Capillary hemangioblastoma of soft tissue: report of a case and review of the literature. Hum Pathol. Oct 2005;36(10):1135-9. [Medline].
Bradley S, Dumas N, Ludman M, Wood L. Hereditary renal cell carcinoma associated with von Hippel-Lindau disease: a description of a Nova Scotia cohort. Can Urol Assoc J. Feb 2009;3(1):32-6. [Medline].
Zagzag D, Krishnamachary B, Yee H, et al. Stromal cell-derived factor-1alpha and CXCR4 expression in hemangioblastoma and clear cell-renal cell carcinoma: von Hippel-Lindau loss-of-function induces expression of a ligand and its receptor. Cancer Res. Jul 15 2005;65(14):6178-88. [Medline].
Agostinelli C, Roncaroli F, Galassi E, Bernardi B, Acciarri N, Tani G. Leptomeningeal hemangioblastoma. Case illustration. J Neurosurg. Aug 2004;101(1 Suppl):122. [Medline].
Gläsker S, Van Velthoven V. Risk of hemorrhage in hemangioblastomas of the central nervous system. Neurosurgery. Jul 2005;57(1):71-6; discussion 71-6. [Medline].
Lee SR, Sanches J, Mark AS, Dillon WP, Norman D, Newton TH. Posterior fossa hemangioblastomas: MR imaging. Radiology. May 1989;171(2):463-8. [Medline].
Lach B, Gregor A, Rippstein P, Omulecka A. Angiogenic histogenesis of stromal cells in hemangioblastoma: ultrastructural and immunohistochemical study. Ultrastruct Pathol. Sep-Oct 1999;23(5):299-310. [Medline].
Hasselblatt M, Jeibmann A, Gerss J, et al. Cellular and reticular variants of haemangioblastoma revisited: a clinicopathologic study of 88 cases. Neuropathol Appl Neurobiol. Dec 2005;31(6):618-22. [Medline].
Symon L, Murota T, Pell M, Bordi L. Surgical management of haemangioblastoma of the posterior fossa. Acta Neurochir (Wien). 1993;120(3-4):103-10. [Medline].
Zhou LF, Du G, Mao Y, Zhang R. Diagnosis and surgical treatment of brainstem hemangioblastomas. Surg Neurol. Apr 2005;63(4):307-15; discussion 315-6. [Medline].
Eskridge JM, McAuliffe W, Harris B, Kim DK, Scott J, Winn HR. Preoperative endovascular embolization of craniospinal hemangioblastomas. AJNR Am J Neuroradiol. Mar 1996;17(3):525-31. [Medline].
Takeuchi S, Tanaka R, Fujii Y, Abe H, Ito Y. Surgical treatment of hemangioblastomas with presurgical endovascular embolization. Neurol Med Chir (Tokyo). May 2001;41(5):246-51; discussion 251-2. [Medline].
Chang SD, Meisel JA, Hancock SL, Martin DP, McManus M, Adler JR Jr. Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery. Neurosurgery. Jul 1998;43(1):28-34; discussion 34-5. [Medline].
Niemela M, Lim YJ, Soderman M, Jaaskelainen J, Lindquist C. Gamma knife radiosurgery in 11 hemangioblastomas. J Neurosurg. Oct 1996;85(4):591-6. [Medline].
Patrice SJ, Sneed PK, Flickinger JC, et al. Radiosurgery for hemangioblastoma: results of a multiinstitutional experience. Int J Radiat Oncol Biol Phys. Jun 1 1996;35(3):493-9. [Medline].
Pan L, Wang EM, Wang BJ, et al. Gamma knife radiosurgery for hemangioblastomas. Stereotact Funct Neurosurg. Oct 1998;70 Suppl 1:179-86. [Medline].
Schuch G, de Wit M, Holtje J, et al. Case 2. Hemangioblastomas: diagnosis of von Hippel-Lindau disease and antiangiogenic treatment with SU5416. J Clin Oncol. May 20 2005;23(15):3624-6. [Medline].
Hande AM, Nagpal RD. Cerebellar haemangioblastoma with extensive dissemination. Br J Neurosurg. Oct 1996;10(5):507-11. [Medline].
Akil H, Statham PF, Gotz M, Bramley P, Whittle IR. Adult cerebellar mutism and cognitive-affective syndrome caused by cystic hemangioblastoma. Acta Neurochir (Wien). May 2006;148(5):597-8. [Medline].
Chung Y, Horoupian DS. Pathology of benign brain tumors. In: Morantz RA, Walsh JW, eds. Brain Tumors. New York, NY: Marcel Dekker; 1994:19-44.
Conway JE, Chou D, Clatterbuck RE, Brem H, Long DM, Rigamonti D. Hemangioblastomas of the central nervous system in von Hippel-Lindau syndrome and sporadic disease. Neurosurgery. Jan 2001;48(1):55-62; discussion 62-3. [Medline].
de la Monte SM, Horowitz SA. Hemangioblastomas: clinical and histopathological factors correlated with recurrence. Neurosurgery. Nov 1989;25(5):695-8. [Medline].
Ercan M, Kahraman S, Basgül E, Aypar U. Anaesthetic management of a patient with von Hippel-Lindau disease: a combination of bilateral phaeochromocytoma and spinal cord haemangioblastoma. Eur J Anaesthesiol. Jan 1996;13(1):81-3. [Medline].
Johnson J, Junewick J, Cottingham S. Phrenic nerve hemangioblastoma in a von Hippel-Lindau patient. AJR Am J Roentgenol. Mar 2005;184(3 Suppl):S10-1. [Medline].
Miyagami M, Katayama Y. Long-term prognosis of hemangioblastomas of the central nervous system: clinical and immunohistochemical study in relation to recurrence. Brain Tumor Pathol. 2004;21(2):75-82. [Medline].
Further Reading
Keywords
hemangioblastoma, Lindau tumor, Lindau's tumor, capillary hemangioblastoma, vascular neoplasm, tumor, tumors, brain tumors, brain tumor, head tumors, neoplasm, meningeal tumor, intracranial neoplasm, intracranial tumor, vascular tumor, von Hippel-Lindau disease, VHL disease, Gamma Knife
