Hemangioblastoma of the posterior fossa: the role of multimodality treatment

Georg, Alvaro E.; Lunsford, L. Dade; Kondziolka, Douglas; Flickinger, John C.; Maitz, Ann

doi:10.1590/S0004-282X1997000200016

Abstracts

The authors made a review of a series of patients with hemangioblastomas of the posterior fossa treated between 1973 and 1993. A total of 32 patients were analyzed with 24 patients receiving resection, 8 patients receiving radiosurgery and 2 patients receiving conventional radiotherapy. The mortality in the patients with a resection was considered acceptable with 2 deaths (8%) and with a morbidity of 3 patients (12.5%). A review of the literature suggests that conventional radiotherapy with high doses (45-60 Gy) may have a role in the post-operative control of hemangioblastomas and in some cases could be employed even before the resection in order to facilitate the surgery. The radiosurgical treatment is regarded like adjuvant. Poor results were obtained with radiosurgery in large tumors where low doses (less than 20 Gy) were used. Because of the rarity and complexity of these tumors, mainly when associated with von Hippel-Lindau disease, a multicenter study could be useful with the assessment of the optimal utilization and combination of these treatment modalities.

hemangioblastoma; treatment; radiosurgery; radiotherapy

Os autores fazem revisão de uma série de pacientes com hemangioblastomas da fossa posterior tratados entre 1973 e 1993: 32 pacientes foram analisados com 24 deles recebendo ressecção, 8 recebendo radiocirurgia e 2 recebendo radioterapia convencional. A mortalidade dos pacientes submetidos a ressecção foi considerada aceitável com 2 mortes (8%) c com morbidade de outros 3 pacientes (12,5%). A revisão de literatura sugere que a radioterapia convencional com altas doses (45-60 Gy) pode ter um papel no controle pós-operatório dos hemangioblastomas e em alguns casos pode ser empregada mesmo antes da ressecção com o objetivo de facilitar a cirurgia. O tratamento radiocirúrgico é considerado coadjuvante. Resultados ruins foram obtidos com a radiocirurgia em tumores grandes em que doses baixas (menos que 20 Gy) foram utilizadas. Devido a raridade e complexidade destes tumores, principalmente quando associados com a doença de von Hippel-Lindau, um estudo multicêntrico pode ser útil na avaliação da combinação e otimização dessas modalidades de tratamento.

hemangioblastoma; tratamento; radiocirurgia; radioterapia

Hemangioblastoma of the posterior fossa: the role of multimodality treatment

Hemangioblastoma da fossa posterior: papel do tratamento multimodal

Alvaro E. Georg^I; L. Dade Lunsford^II; Douglas Kondziolka^III; John C. Flickinger^IV; Ann Maitz^V

^IM.D., Neurosurgeon, Serviço de Neurologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia (UFBA), Salvador BA, Brasil

^IIM.D., Professor of Neurosurgery, Radiology and Radiation Oncology University of Pittsburgh Medical Center. Pittsburgh-PA, USA (UPMC)

^IIIM.D., M.Sc, F.R.C.S. (C) Associate Professor of Neurological Surgery and Radiation Oncology UPMC

^IVM.D., Associate Professor of Neurological Surgery and Radiation Oncology UPMC

^VM.S., Physicist, Department of Radiation Oncology UPMC

ABSTRACT

The authors made a review of a series of patients with hemangioblastomas of the posterior fossa treated between 1973 and 1993. A total of 32 patients were analyzed with 24 patients receiving resection, 8 patients receiving radiosurgery and 2 patients receiving conventional radiotherapy. The mortality in the patients with a resection was considered acceptable with 2 deaths (8%) and with a morbidity of 3 patients (12.5%). A review of the literature suggests that conventional radiotherapy with high doses (45-60 Gy) may have a role in the post-operative control of hemangioblastomas and in some cases could be employed even before the resection in order to facilitate the surgery. The radiosurgical treatment is regarded like adjuvant. Poor results were obtained with radiosurgery in large tumors where low doses (less than 20 Gy) were used. Because of the rarity and complexity of these tumors, mainly when associated with von Hippel-Lindau disease, a multicenter study could be useful with the assessment of the optimal utilization and combination of these treatment modalities.

Key words: hemangioblastoma, treatment, radiosurgery, radiotherapy.

RESUMO

Os autores fazem revisão de uma série de pacientes com hemangioblastomas da fossa posterior tratados entre 1973 e 1993: 32 pacientes foram analisados com 24 deles recebendo ressecção, 8 recebendo radiocirurgia e 2 recebendo radioterapia convencional. A mortalidade dos pacientes submetidos a ressecção foi considerada aceitável com 2 mortes (8%) c com morbidade de outros 3 pacientes (12,5%). A revisão de literatura sugere que a radioterapia convencional com altas doses (45-60 Gy) pode ter um papel no controle pós-operatório dos hemangioblastomas e em alguns casos pode ser empregada mesmo antes da ressecção com o objetivo de facilitar a cirurgia. O tratamento radiocirúrgico é considerado coadjuvante. Resultados ruins foram obtidos com a radiocirurgia em tumores grandes em que doses baixas (menos que 20 Gy) foram utilizadas. Devido a raridade e complexidade destes tumores, principalmente quando associados com a doença de von Hippel-Lindau, um estudo multicêntrico pode ser útil na avaliação da combinação e otimização dessas modalidades de tratamento.

Palavras-chave: hemangioblastoma, tratamento, radiocirurgia, radioterapia.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

ACKNOWLEDGEMENT

The authors would like to thank Dr. Ailton Melo for his review of this article.

Aceite: 19-dezembro-1997.

Dr. Alvaro E. Georg - Departamento de Neuropsiquiatria, Faculdade de Medicina UFBA - Av. Reitor Miguel Calmon s/n - 40.110-100 Salvador BA - Brasil. FAX: 071 245 8562.

1. Anson JA, Glick RP, Crowell RM. Use of gadolinium-enhanced magnetic resonance imaging in the diagnosis and mangement of posterior fossa hemangioblastomas. Surg Neurol 1991 ;35:300-304.
2. Bilge T, Bilge S, Barut S, Cokneseli B. Familial hemangioblastoma and von Hippel-Lindau's disease: case report. Acta Neurol Belg 1991;91:223-229.
3. Bouchard J. Radiation therapy of brain tumors and diseases ofthe nervous system. Philadelphia: Lea & Fabiger, 1966:147-149.
4. Braffman BH, Bilaniuk LT, Zimmerman n RA. MR of the central nervous system neoplasia of phakomatoses. Semin in Roentgen 1990;25:198-217.
5. Cobb CA, Youmans JR. Sarcomas and neoplasms of blood vessels. In Youmans JR (ed). Neurological surgery. Ed 2. Philadelphia: WB Saunders, 1992:2845-2862.
6. Decker H-JH, Neumann HPH, Walter TA, Sandberg AA. 3p involvement in arenal cell carcinoma in von Hippel-Lindau syndrome: region of tumor breakpoint clustering on 3p? Cancer Genet Cytogenet 1988;33:59-65.
7. Diehl PR, Symon L. Supratentorial intraventricular hemangioblastoma: case report and review of literature. Surg Neurol 1980;15:435-443.
8. Duma CM, Lunsford LD, Kondziolka D, Harsh GR, Flickinger JC. Stereotactic radiosurgery of cavernous sinus meningiomas as an addition or alternative to microsurgery. Neurosurgery 1993;32:699-705.
9. Elster AD, Arthur DW. Intracranial hemangioblastomas: CT and MR findings. J Comput Assist Tomogr 1988; 12:736-739.
10. Filling-Katz MR, Choyke PL, Oldfield E, Charnas L, Patronas NJ, Glenn GM, Gorin MB, Morgan JK, Linehan WM, Seizinger MD, Zbar B. Central nervous system involvement in von Hippel-Lindau disease. Neurology 1991;41:41-46.
11. Filling-Katz MR, Choyke PL, Patronas NJ, Goring MB, Barba D, Chang R, Doppman JL, Seizinger B Oldfield EH. Radiologic screening for von Hippel-Lindau disease: the role of Gd-DTPA enhanced MR imaging of the CNS. J Comput Assist Tomogr 1989;13:743-755.
12. Glenn GM, Daniel LN, Choyke P, Linehan WM, Oldfield E, Gorin MB, Hosoe S, Latif F, Weiss G, Walther M, Lerman MI, Zbar B. von Hippel-Lindau (VHL) disease: distinct phenotypes suggest more than one mutant allele at the VHL locus. Hum Genet 1991;87:207-210.
13. Glenn GM, Linehan WM, Hosoe S, Latif F, Yao M, Choyke P, Goring MB, Chew E, Oldfield E, Manolatos C, Orcutt ML, Walther MM, Weiss GH, Tory K, Jensson O, Lerman M, Zbar B. Screening for von Hippel-Lindau disease by DNA polymorphism analysis. JAMA 1992;267:1226-1231.
14. Go RCP, Lamiell JM, Hsia YE, Yuen JW-M, Paik Y. Segregation and linkage analyses of von Hippel-Lindau disease among 220 descendants from one kindred. Am J Hum Genet 1984;36:131 -142.
15. Green JS, Bowmer MI, Johnson GJ. von Hippel-Lindau disease in a Newfoundland kindred. Can Med Assoc J 1986; 134:133-146.
16. Hardjasudarma M, Fowler M. Craniospinal magnetic resonance imaging enhanced with Gd-DTPA in von Hippel-Lindau disease. Can Assoc Radiol J 1991,42:283-286.
17. Hardwig P, Robertson DM. von Hippel-Lindau disease: a familial, often lethal, multisystem phakomatosis. Ophthalmology 1984;91:263-270.
18. Helle TL, Conley FK, Britt RH. Effect of radiation therapy on hemangioblastoma: a case report and review of the literature. Neurosurgery 1980;6:82-86.
19. Horton WA, Wong V, Eldridge R. von Hippel-Lindau disease: clinical and pathological manifestations in nine families with 50 affected members. Arch Intern Med 1976;136:769-777.
20. Hosoe S, Brauch H, Latif F, Glenn G, Daniel L, Bale S, Choyke P, Gorin M, Oldfield E, Berman A, Goodman J, Orcutt ML, Hampsch K, Delisio J, Modi W, McBride W, Anglard P, Weiss G, Walther MM, Linehan WM, Lerman MI, Zbar B. Localization ofthe von Hippel-Lindau disease gene to a small region of chromosome 3. Genomics 1990;8:634-640.
21. Huson SM, Harper PS, Hourihan MD, Cole G, Weeks RD, Compston DAS. Cerebellar hemangioblastoma and von Hippel-Lindau disease. Brain 1986;109:1297:1310.
22. Jennings AM, Smith C, Cole DR, Jennings C, Shortland JR, Williams JL, Brown CB. von Hippel-Lindau disease in a large British family: clinicopathological features and recommendations for screening and follow-up. Q J Med 1988,66:233-249.
23. Jordan DK, Divelbiss JE, Waziri MH, Burns TL, Patil SR. Fragile site expression in families with von Hippel-Lindau disease. Cancer Genet Cytogenet 1989;39:157-166.
24. Kondiziolka D, Lunsford LD, Coffey RJ, Bissonette DJ, Flickinger JC. Stereotactic radiosurgery of angiographically occult vascular malformations: indications and preliminary experience. Neurosurgery 1990,27:892-899.
25. Lamiell JM, Salazar FG. Hsia YE. von Hippel-Lindau disease affectings 43 members of a single kindred. Medicine 1989;68:1 -29.
26. Latif F, Tory K, Gnarra J, Yao M, Duh F-M, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L, Schimidt L, Zhou F, Li H, Wei MH, Chen F, Glenn G, Choyke P, Walther MM, Weng Y, Duan D-SR, Dean M, Glavac D, Richards FM, Crossey PA, Ferguson-Smith MA, Le Paslier D, Chumaknow I, Cohen D, Chinault AC, MaherER, Linehan WM, Zbar B, Lerman MI. Identification of the von Hippel-Lindau disease tumor supressor gene. Science 1993;260:1317-1320.
27. Lee SR, Sanches J, Mark AS, Dillon WP, Norman D, Newton TH: Posterior fossa hemangioblastomas: MR imaging. Radiology 1989;171:463-468.
28. Lunsford LD, Kondziolka D, Flickinger JC: Radiosurgery as an alternative to microsugery of acoustic tumors. Clin Neurosurg 1992;38:619-634.
29. Lunsford LD, Kondziolka D, Flickinger JC, Bissonette DJ, Jungreis CA, Maitz NA, Horton JA, Coffey RJ. Stereotactic radiosurgery for arteriovenous malformations of the brain. J Neurosurg 1991,75:512-524.
30. Maher ER, Bentley E, Yates JRW, Barton D, Jennings A, Fellows IW, Ponder MA, Ponder BAJ, Benjamin C, Harris R, Ferguson-Smith MA. Mapping of von Hippel-Lindau disease to chromosome 3p confirmed by genetic linkage analysis. J Neurol Sci 1990;100:27-30.
31. Maher ER, Bentley E, Yates JRW, Latif F, Lerman M, Zbar B, AffaraNA, Ferguson Smith MA. Mapping of the von Hippel-Lindau disease locus to a small region of chromosome 3p by genetic linkage analysis. Genomics 1991; 10:957-960.
32. Maher ER, Yates JRW, Harries R, Benjamin C, Harris R, Moore AT, Ferguson-Smith MA. Clinical features and natural history of von Hippel-Lindau disease. Q J Med 1990;77:1151-1163.
33. Melmon KL, Rosen SW: Lindau's disease: review of the literature and study of a large kindred. Am J of Med 1964,36:595-617.
34. Moore AT, Maher ER, Rosen P, GregorZ, Bird AC. Ophthalmological screening for von Hippel-Lindau disease. Eye 1991 ;5:723-728.
35. Neumann HPH, Wiestler OD. Clustering of features of von Hippel-Lindau Syndrome: evidence for a complex genetic locus. Lancet 1991;337:1052-1054.
36. Neumann HPH, Eggert HR, Weigel K, Friedburg H, Wiestler OD, SchollmeyerP. Hemangioblastomas of the central nervous system: A 10 year study with special reference to von Hippel-Lindau syndrome, J Neurosurg 1989;70:24-30.
37. Rengachary SS: Hemangioblastomas. In Wilkias RH & Rengachary SS (eds). Neurosurgery. New York: McGraw-Hill, 1985:772-782.
38. Rengachary SS,SuskindDL. Hemangioblastomas. In Apuzzo MJL (ed). Brain surgery, complications: avoidance and management New York: Churchill Livingstone, 1993:1825-1833.
39. Rho YM. von Hippel-Lindau disease: a report of five cases. Can Med Ass J 1969,101:135-142.
40. Russel DS, Rubinstein LJ. Pathology of tumors of the nervous system. Ed 5. Baltimore: Williams & Wilkins, 1989:639-662.
41. Salazar FG, Lamiell JM. Early identification of retinal angiomas in a large kindred with von Hippel-Lindau disease. Am J Ophthtalmol 1980;89:540-545.
42. Sato Y, Waiziri M, Smith W, Frey E, Yuh WTC, Hanson J, Franken EA. Hippel-Lindau disease: MR imaging. Radiology 1988;166:241-246.
43. Seizinger BR, Rouleau GA, Ozelius LI, Lane AH, Farmer GE, Lamiell JM, Haines J, Yuen JWM, Collins D, Majoor-Krakauer D, Bonner T, Mathew C, Rubenstein A, Halperin J, McConke-Rosell A, Green JS, Trofatter JA, Ponder BA, Eierman L, Bowmer MI, Schimke R, Oostra B, Aronin N, Smith DI, Drabkin H, Waziri MH, Hobbs WJ, Martuza RL, Conneally PM. Hsia YE, Gusclla JF. von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature 1988;332:268-269.
44. Seizinger BR, Smith Dl, Filling-Katz MR, Neumann H, Green JS, Choyke PL, Anderson KM, Freiman RN, Klauk SM, Whaley J, Decker H-J H, Hsia YE, Collins D, Halperin J, Lamiell JM, Oostra B, Waziri MH, Gorin MB, Scherer G, Drabkin HA. Aronin N, Schinzel A, Martuza RL, Gusella JF, Haines JL. Genetic flanking markers refine diagnostic criteria and provide insights in to the genetics of von Hippel-Lindau disease. Proc Natl Acad Sci 1991;88:2864-2868.
45. Smalley SR, Schomberg PJ, Earle JD, Laws ER, Scheithauer BW, O'Fallon JR. Radiotherapeutic considerations in the treatment of hemangioblastomas of the central nervous system. Int J Radiation Oncol Biol Phys 1990; 18:1165:1171.
46. Sung DI, Chag CH, Harisiadis L. Cerebellar hemangioblastomas. Cancer 1982;49:553-555.
47. Symon L, Murota T, Pell M, Bordi L. Surgical management of hemangioblastoma of the posterior fossa. Acta Neurochir (Wien) 1993;120:103-110.
48. Tory K, Brauch H. Linehan M, Barba D, Oldfield E, Filling-Kartz M, Seizinger B, Nakamura Y, White R, Marshall FF. Lerman MI, Zbar B. Specific genetic change in tumors associated with von Hippel-Lindau disease. J. Nat Cancer Inst 1989;81:1097-1101.
49. Vance JM, Smal KW, Jones MA, Jeffrey M, Stajich JM, Yamoaka LH, Roses AD, Hung W-Y, Pericak-Vance MA. Confirmation of linkage in von Hippel-Lindau disease. Genomics 1990;6:565-567.
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Publication Dates

Publication in this collection
10 Nov 2010
Date of issue
June 1997

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Anson JA, Glick RP, Crowell RM. Use of gadolinium-enhanced magnetic resonance imaging in the diagnosis and mangement of posterior fossa hemangioblastomas. Surg Neurol 1991 ;35:300-304.

[2] 2. Bilge T, Bilge S, Barut S, Cokneseli B. Familial hemangioblastoma and von Hippel-Lindau's disease: case report. Acta Neurol Belg 1991;91:223-229.

[3] 3. Bouchard J. Radiation therapy of brain tumors and diseases ofthe nervous system. Philadelphia: Lea & Fabiger, 1966:147-149.

[4] 4. Braffman BH, Bilaniuk LT, Zimmerman n RA. MR of the central nervous system neoplasia of phakomatoses. Semin in Roentgen 1990;25:198-217.

[5] 5. Cobb CA, Youmans JR. Sarcomas and neoplasms of blood vessels. In Youmans JR (ed). Neurological surgery. Ed 2. Philadelphia: WB Saunders, 1992:2845-2862.

[6] 6. Decker H-JH, Neumann HPH, Walter TA, Sandberg AA. 3p involvement in arenal cell carcinoma in von Hippel-Lindau syndrome: region of tumor breakpoint clustering on 3p? Cancer Genet Cytogenet 1988;33:59-65.

[7] 7. Diehl PR, Symon L. Supratentorial intraventricular hemangioblastoma: case report and review of literature. Surg Neurol 1980;15:435-443.

[8] 8. Duma CM, Lunsford LD, Kondziolka D, Harsh GR, Flickinger JC. Stereotactic radiosurgery of cavernous sinus meningiomas as an addition or alternative to microsurgery. Neurosurgery 1993;32:699-705.

[9] 9. Elster AD, Arthur DW. Intracranial hemangioblastomas: CT and MR findings. J Comput Assist Tomogr 1988; 12:736-739.

[10] 10. Filling-Katz MR, Choyke PL, Oldfield E, Charnas L, Patronas NJ, Glenn GM, Gorin MB, Morgan JK, Linehan WM, Seizinger MD, Zbar B. Central nervous system involvement in von Hippel-Lindau disease. Neurology 1991;41:41-46.

[11] 11. Filling-Katz MR, Choyke PL, Patronas NJ, Goring MB, Barba D, Chang R, Doppman JL, Seizinger B Oldfield EH. Radiologic screening for von Hippel-Lindau disease: the role of Gd-DTPA enhanced MR imaging of the CNS. J Comput Assist Tomogr 1989;13:743-755.

[12] 12. Glenn GM, Daniel LN, Choyke P, Linehan WM, Oldfield E, Gorin MB, Hosoe S, Latif F, Weiss G, Walther M, Lerman MI, Zbar B. von Hippel-Lindau (VHL) disease: distinct phenotypes suggest more than one mutant allele at the VHL locus. Hum Genet 1991;87:207-210.

[13] 13. Glenn GM, Linehan WM, Hosoe S, Latif F, Yao M, Choyke P, Goring MB, Chew E, Oldfield E, Manolatos C, Orcutt ML, Walther MM, Weiss GH, Tory K, Jensson O, Lerman M, Zbar B. Screening for von Hippel-Lindau disease by DNA polymorphism analysis. JAMA 1992;267:1226-1231.

[14] 14. Go RCP, Lamiell JM, Hsia YE, Yuen JW-M, Paik Y. Segregation and linkage analyses of von Hippel-Lindau disease among 220 descendants from one kindred. Am J Hum Genet 1984;36:131 -142.

[15] 15. Green JS, Bowmer MI, Johnson GJ. von Hippel-Lindau disease in a Newfoundland kindred. Can Med Assoc J 1986; 134:133-146.

[16] 16. Hardjasudarma M, Fowler M. Craniospinal magnetic resonance imaging enhanced with Gd-DTPA in von Hippel-Lindau disease. Can Assoc Radiol J 1991,42:283-286.

[17] 17. Hardwig P, Robertson DM. von Hippel-Lindau disease: a familial, often lethal, multisystem phakomatosis. Ophthalmology 1984;91:263-270.

[18] 18. Helle TL, Conley FK, Britt RH. Effect of radiation therapy on hemangioblastoma: a case report and review of the literature. Neurosurgery 1980;6:82-86.

[19] 19. Horton WA, Wong V, Eldridge R. von Hippel-Lindau disease: clinical and pathological manifestations in nine families with 50 affected members. Arch Intern Med 1976;136:769-777.

[20] 20. Hosoe S, Brauch H, Latif F, Glenn G, Daniel L, Bale S, Choyke P, Gorin M, Oldfield E, Berman A, Goodman J, Orcutt ML, Hampsch K, Delisio J, Modi W, McBride W, Anglard P, Weiss G, Walther MM, Linehan WM, Lerman MI, Zbar B. Localization ofthe von Hippel-Lindau disease gene to a small region of chromosome 3. Genomics 1990;8:634-640.

[21] 21. Huson SM, Harper PS, Hourihan MD, Cole G, Weeks RD, Compston DAS. Cerebellar hemangioblastoma and von Hippel-Lindau disease. Brain 1986;109:1297:1310.

[22] 22. Jennings AM, Smith C, Cole DR, Jennings C, Shortland JR, Williams JL, Brown CB. von Hippel-Lindau disease in a large British family: clinicopathological features and recommendations for screening and follow-up. Q J Med 1988,66:233-249.

[23] 23. Jordan DK, Divelbiss JE, Waziri MH, Burns TL, Patil SR. Fragile site expression in families with von Hippel-Lindau disease. Cancer Genet Cytogenet 1989;39:157-166.

[24] 24. Kondiziolka D, Lunsford LD, Coffey RJ, Bissonette DJ, Flickinger JC. Stereotactic radiosurgery of angiographically occult vascular malformations: indications and preliminary experience. Neurosurgery 1990,27:892-899.

[25] 25. Lamiell JM, Salazar FG. Hsia YE. von Hippel-Lindau disease affectings 43 members of a single kindred. Medicine 1989;68:1 -29.

[26] 26. Latif F, Tory K, Gnarra J, Yao M, Duh F-M, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L, Schimidt L, Zhou F, Li H, Wei MH, Chen F, Glenn G, Choyke P, Walther MM, Weng Y, Duan D-SR, Dean M, Glavac D, Richards FM, Crossey PA, Ferguson-Smith MA, Le Paslier D, Chumaknow I, Cohen D, Chinault AC, MaherER, Linehan WM, Zbar B, Lerman MI. Identification of the von Hippel-Lindau disease tumor supressor gene. Science 1993;260:1317-1320.

[27] 27. Lee SR, Sanches J, Mark AS, Dillon WP, Norman D, Newton TH: Posterior fossa hemangioblastomas: MR imaging. Radiology 1989;171:463-468.

[28] 28. Lunsford LD, Kondziolka D, Flickinger JC: Radiosurgery as an alternative to microsugery of acoustic tumors. Clin Neurosurg 1992;38:619-634.

[29] 29. Lunsford LD, Kondziolka D, Flickinger JC, Bissonette DJ, Jungreis CA, Maitz NA, Horton JA, Coffey RJ. Stereotactic radiosurgery for arteriovenous malformations of the brain. J Neurosurg 1991,75:512-524.

[30] 30. Maher ER, Bentley E, Yates JRW, Barton D, Jennings A, Fellows IW, Ponder MA, Ponder BAJ, Benjamin C, Harris R, Ferguson-Smith MA. Mapping of von Hippel-Lindau disease to chromosome 3p confirmed by genetic linkage analysis. J Neurol Sci 1990;100:27-30.

[31] 31. Maher ER, Bentley E, Yates JRW, Latif F, Lerman M, Zbar B, AffaraNA, Ferguson Smith MA. Mapping of the von Hippel-Lindau disease locus to a small region of chromosome 3p by genetic linkage analysis. Genomics 1991; 10:957-960.

[32] 32. Maher ER, Yates JRW, Harries R, Benjamin C, Harris R, Moore AT, Ferguson-Smith MA. Clinical features and natural history of von Hippel-Lindau disease. Q J Med 1990;77:1151-1163.

[33] 33. Melmon KL, Rosen SW: Lindau's disease: review of the literature and study of a large kindred. Am J of Med 1964,36:595-617.

[34] 34. Moore AT, Maher ER, Rosen P, GregorZ, Bird AC. Ophthalmological screening for von Hippel-Lindau disease. Eye 1991 ;5:723-728.

[35] 35. Neumann HPH, Wiestler OD. Clustering of features of von Hippel-Lindau Syndrome: evidence for a complex genetic locus. Lancet 1991;337:1052-1054.

[36] 36. Neumann HPH, Eggert HR, Weigel K, Friedburg H, Wiestler OD, SchollmeyerP. Hemangioblastomas of the central nervous system: A 10 year study with special reference to von Hippel-Lindau syndrome, J Neurosurg 1989;70:24-30.

[37] 37. Rengachary SS: Hemangioblastomas. In Wilkias RH & Rengachary SS (eds). Neurosurgery. New York: McGraw-Hill, 1985:772-782.

[38] 38. Rengachary SS,SuskindDL. Hemangioblastomas. In Apuzzo MJL (ed). Brain surgery, complications: avoidance and management New York: Churchill Livingstone, 1993:1825-1833.

[39] 39. Rho YM. von Hippel-Lindau disease: a report of five cases. Can Med Ass J 1969,101:135-142.

[40] 40. Russel DS, Rubinstein LJ. Pathology of tumors of the nervous system. Ed 5. Baltimore: Williams & Wilkins, 1989:639-662.

[41] 41. Salazar FG, Lamiell JM. Early identification of retinal angiomas in a large kindred with von Hippel-Lindau disease. Am J Ophthtalmol 1980;89:540-545.

[42] 42. Sato Y, Waiziri M, Smith W, Frey E, Yuh WTC, Hanson J, Franken EA. Hippel-Lindau disease: MR imaging. Radiology 1988;166:241-246.

[43] 43. Seizinger BR, Rouleau GA, Ozelius LI, Lane AH, Farmer GE, Lamiell JM, Haines J, Yuen JWM, Collins D, Majoor-Krakauer D, Bonner T, Mathew C, Rubenstein A, Halperin J, McConke-Rosell A, Green JS, Trofatter JA, Ponder BA, Eierman L, Bowmer MI, Schimke R, Oostra B, Aronin N, Smith DI, Drabkin H, Waziri MH, Hobbs WJ, Martuza RL, Conneally PM. Hsia YE, Gusclla JF. von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature 1988;332:268-269.

[44] 44. Seizinger BR, Smith Dl, Filling-Katz MR, Neumann H, Green JS, Choyke PL, Anderson KM, Freiman RN, Klauk SM, Whaley J, Decker H-J H, Hsia YE, Collins D, Halperin J, Lamiell JM, Oostra B, Waziri MH, Gorin MB, Scherer G, Drabkin HA. Aronin N, Schinzel A, Martuza RL, Gusella JF, Haines JL. Genetic flanking markers refine diagnostic criteria and provide insights in to the genetics of von Hippel-Lindau disease. Proc Natl Acad Sci 1991;88:2864-2868.

[45] 45. Smalley SR, Schomberg PJ, Earle JD, Laws ER, Scheithauer BW, O'Fallon JR. Radiotherapeutic considerations in the treatment of hemangioblastomas of the central nervous system. Int J Radiation Oncol Biol Phys 1990; 18:1165:1171.

[46] 46. Sung DI, Chag CH, Harisiadis L. Cerebellar hemangioblastomas. Cancer 1982;49:553-555.

[47] 47. Symon L, Murota T, Pell M, Bordi L. Surgical management of hemangioblastoma of the posterior fossa. Acta Neurochir (Wien) 1993;120:103-110.

[48] 48. Tory K, Brauch H. Linehan M, Barba D, Oldfield E, Filling-Kartz M, Seizinger B, Nakamura Y, White R, Marshall FF. Lerman MI, Zbar B. Specific genetic change in tumors associated with von Hippel-Lindau disease. J. Nat Cancer Inst 1989;81:1097-1101.

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