Skip to main content
SpringerLink
Log in

Biological Behavior and Tumorigenesis of Subependymal Giant Cell Astrocytomas

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

In spite of the benign nature of subependymal giant cell astrocytomas (SEGAs), some show massive hemorrhage, rapid growth, and tumor recurrence. This led us to investigate the biological behavior, cell dynamics, and nobreak tumorigenesis of SEGAs.

All patients (4 men and 3 women; age range, 6–27 years; mean, 13.6 years) had features of tuberous sclerosis complex and obstructive hydrocephalus. One patient had intratumoral bleeding. In two patients, sequential neuroimaging showed a subependymal nodule growing to become a SEGA. All underwent surgical resection without radiation therapy. One tumor recurred and was treated surgically. There were no postoperative deaths. The presence of cytologic atypia, mitoses and vascular proliferation had no implication in terms of the clinical course. MIB-1 labeling indices were low (mean, 0.9), indicating low proliferative potential. Unexpectedly, bcl-2 staining was sparse and bax staining predominated in majority of cases. However, the mean value of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling index was low. Immunohistochemically, tumors were positive for both glial and neuronal markers. In the majority of our cases, the expression of p53 was low. Only one tumor was focally positive for tuberin.

SEGAs have low proliferative potential and apoptotic activity, and exhibit features of mixed glial–neuronal differentiation. In contrast to p53, tuberin is suggested to be the tumor suppressor in this tumor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Haslem RH: Tuberous sclerosis. In: Behrman RE, Kliegman RM, Jenson HB (eds) Nelson's textbook of Pediatrics. Sixteenth edition. WB Saunders, Philadelphia, pp 1837

  2. Shepherd CW, Scheithauer BW, Gomez MR, Altermatt HJ, Katzmann JA: Subependymal giant cell astrocytoma: a clinical, pathological, and flow cytometric study. Neurosurgery 28: 864–868, 1991

    Google Scholar 

  3. Braffman BH, Bilaniuk LT, Naidich TP, Altman NR, Post MJ, Quencer RM, Zimmerman RA, Brody BA: MR imaging of tuberous sclerosis: pathogenesis of this phakomatosis, use of gadopentetate dimeglumine, and literature review. Radiology 183: 227–238, 1992

    Google Scholar 

  4. Kingsley DP, Kendall BE, Fitz CR: Tuberous sclerosis: a clinicoradiological evaluation of 110 cases with particular reference to atypical presentation. Neuroradiology 28: 38–46, 1986

    Google Scholar 

  5. Menor F, Marti-Bonmati L, Mulas F, Poyatos C, Cortina H: Neuroimaging in tuberous sclerosis: a clinicoradiological evaluation in pediatric patients. Pediatr Radiol 22: 485–489, 1992

    Google Scholar 

  6. Shepherd CW, Gomez MR, Lie JT, Crowson CS: Causes of death in patients with tuberous sclerosis. Mayo Clin Proc 66: 792–796, 1991

    Google Scholar 

  7. Altman NR, Purser RK, Post MJ: Tuberous sclerosis: characteristics at CT and MR imaging. Radiology 167: 527–532, 1988

    Google Scholar 

  8. Dotan SA, Trobe JD, Gebarski SS: Visual loss in tuberous sclerosis. Neurology 41: 1915–1917, 1991

    Google Scholar 

  9. Brown JM: Tuberose sclerosis with malignant astrocytoma. Med J Aust 1: 811–814, 1975

    Google Scholar 

  10. Waga S, Yamamoto Y, Kojima T, Sakakura M: Massive hemorrhage in tumor of tuberous sclerosis. Surg Neurol 8: 99–101, 1977

    Google Scholar 

  11. Stefansson K: Tuberous sclerosis. Mayo Clin Proc 66: 868–872, 1991

    Google Scholar 

  12. Chow CW, Klug GL, Lewis EA: Subependymal giant-cell astrocytoma in children. An unusual discrepancy between histological and clinical features. J Neurosurg 68: 880–883, 1988

    Google Scholar 

  13. Gyure KA, Prayson RA: Subependymal giant cell astrocytoma: a clinicopathologic study with HMB45 and MIB-1 immunohistochemical analysis. Mod Pathol 10: 313–317, 1997

    Google Scholar 

  14. Sinson G, Sutton LN, Yachnis AT, Duhaime AC, Schut L: Subependymal giant cell astrocytomas in children. Pediatr Neurosurg 20: 233–239, 1994

    Google Scholar 

  15. Bonnin JM, Rubinstein LJ, Papasozomenos SC, Marangos PJ: Subependymal giant cell astrocytoma. Significance and possible cytogenetic implications of an immunohistochemical study. Acta Neuropathol (Berl) 62: 185–193, 1984

    Google Scholar 

  16. Chou TM, Chou SM: Tuberous sclerosis in the premature infant: a report of a case with immunohistochemistry on the CNS. Clin Neuropathol 8: 45–52, 1989

    Google Scholar 

  17. Frerebeau P, Benezech J, Segnarbieux F, Harbi H, Desy A, Marty-Double C: Intraventricular tumors in tuberous sclerosis. Child's Nerv Syst 1: 45–48, 1985

    Google Scholar 

  18. Hirose T, Scheithauer BW, Lopes MB, Gerber HA, Altermatt HJ, Hukee MJ, VandenBerg SR, Charlesworth JC: Tuber and subependymal giant cell astrocytoma associated with tuberous sclerosis: an immunohistochemical, ultrastructural, and immunoelectron and microscopic study. Acta Neuropathol (Berl) 90: 387–399, 1995

    Google Scholar 

  19. Iwasaki Y, Yoshikawa H, Sasaki M, Sugai K, Suzuki H, Hirayama Y, Sakuragawa N, Arima M, Takashima S, Aoki N: Clinical and immunohistochemical studies of subependymal giant cell astrocytomas associated with tuberous sclerosis. Brain Dev 12: 478–481, 1990

    Google Scholar 

  20. Lopes MB, Altermatt HJ, Scheithauer BW, Shepherd CW, VandenBerg SR: Immunohistochemical characterization of subependymal giant cell astrocytomas. Acta Neuropathol (Berl) 91: 368–375, 1996

    Google Scholar 

  21. Nakamura Y, Becker LE: Subependymal gaint-cell tumor: astrocytic or neuronal? Acta Neuropathol (Berl) 60: 271–277, 1983

    Google Scholar 

  22. Stefansson K, Wollmann R: Distribution of glial fibrillary acidic protein in central nervous system lesions of tuberous sclerosis. Acta Neuropathol (Berl) 52: 135–140, 1980

    Google Scholar 

  23. Stefansson K, Wollmann R: Distribution of the neuronal specific protein, 14–3–2, in central nervous system lesions of tuberous sclerosis. Acta Neuropathol (Berl) 53: 113–117, 1981

    Google Scholar 

  24. Fujiwara S, Takaki T, Hikita T, Nishio S: Subependymal giant-cell astrocytoma associated with tuberous sclerosis. Do subependymal nodules grow? Child's Nerv Syst 5: 43–44, 1989

    Google Scholar 

  25. Morimoto K, Mogami H: Sequential CT study of subependymal giant-cell astrocytoma associated with tuberous sclerosis. Case report. J Neurosurg 65: 874–877, 1986

    Google Scholar 

  26. Kalina P, Drehobl KE, Greenberg RW, Black KS, Hyman RA: Hemorrhagic subependymal giant cell astrocytoma. Pediatr Radio 25: 66–67, 1995

    Google Scholar 

  27. Turgut M, Akalan N, Ozgen T, Ruacan S, Erbengi A: Subependymal giant cell astrocytoma associated with tuberous sclerosis: diagnostic and surgical characteristics of five cases with unusual features. Clin Neurol Neurosurg 98: 217–221, 1996

    Google Scholar 

  28. Cooper JR: Brain tumors in hereditary multiple system hamartomatosis (tuberous sclerosis). J Neurosurg 34: 194–202, 1971

    Google Scholar 

  29. Faillace WJ, Canady AI: Cerebrospinal fluid shunt malfunction signaled by newor recurrent seizures. Child's Nerv Syst 6: 37–40, 1990

    Google Scholar 

  30. Koshino K, Nakano M, Miki M, Matsumura H: Stereotaxic operation for the control of infantile epilepsy and associated behavorial disorder. Confin Neurol 37: 223–231, 1975

    Google Scholar 

  31. Oltvai ZN, Milliman CL, Korsmeyer SJ: Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74: 609–619, 1993

    Google Scholar 

  32. Hara A, Hirose Y, Yoshimi N, Tanaka T, Mori H: Expression of Bax and bcl-2 proteins, regulators of programmed cell death, in human brain tumors. Neurol Res 19: 623–628, 1997

    Google Scholar 

  33. Nakasu S, Nakasu Y, Nioka H, Nakajima M, Handa J: bcl-2 protein expression in tumors of the central nervous system. Acta Neuropathol (Berl) 88: 520–526, 1994

    Google Scholar 

  34. Krajewski S, Krajewska M, Ehrmann J, Sikorska M, Lach B, Chatten J, Reed JC: Immunohistochemical analysis of Bcl-2, Bcl-X, Mcl-l, and Bax in tumors of central and peripheral nervous system origin. Am J Pathol 150: 805–814, 1997

    Google Scholar 

  35. Scheithauer BW: The neuropathology of tuberous sclerosis. J Dermatol 19: 897–903, 1992

    Google Scholar 

  36. Huttenlocher PR, Wollmann RL: Cellular neuropathology of tuberous sclerosis. AnnNYAcad Sci 615: 140–148, 1991

    Google Scholar 

  37. McMurdo SK Jr, Moore SG, Brant-Zawadzki M, Berg BO, Koch T, Newton TH, Edwards MS: MR imaging of intracranial tuberous sclerosis. AJR Am J Roentgenol 148: 791–796, 1987

    Google Scholar 

  38. Margo CE, Barletta JP, Staman JA: Giant cell astrocytoma of the retina in tuberous sclerosis. Retina 13: 155–159, 1993

    Google Scholar 

  39. Levine AJ, Perry ME, Chang A, Silver A, Dittmer D, Wu M, Welsh D: The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesis. Br J Cancer 69: 409–416, 1994

    Google Scholar 

  40. van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S, Lindhout D, van den Ouweland A, Halley D, Young J, Burley M, Jeremiah S, Woodward K, Nahmias J, Fox M, Ekong R, Osborne J, Wolfe J, Povey S, Snell RG, Cheadle JP, Jones AC, Tachataki M, Ravine D, Sampson JR, Reeve MP, Richardson P, Wilmer F, Munro C, Hawkins TL, Sepp T, Ali JBM, Ward S, Green AJ, Yates JRW, Kwiatkowska J, Henske EP, Short MP, Haines JH, Jozwiak S, Kwiatkowski DJ: Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 277: 805–808, 1997

    Google Scholar 

  41. Identification and characterization of the tuberous sclerosis gene on chromosome 16. The European Chromosome 16 Tuberous Sclerosis Consortium. Cell 75: 1305–1315, 1993

  42. Carbonara, C, Longa L, Grosso E, Borrone C, Garre MG, Brisigotti M, Migone N: 9q34 loss of heterozygosity in a tuberous sclerosis astrocytoma suggests a growth suppressor-like activity also for the TSCl gene. Hum Mol Genet 3: 1829–1832, 1994

    Google Scholar 

  43. Jin F, Wienecke R, Xiao GH, Maize JC Jr, DeClue JE, Yeung RS: Suppression of tumorigenicity by the wild-type tuberous sclerosis 2 (Tsc2) gene and its C-terminal region. Proc Natl Acad Sci USA 93: 9154–9159, 1996

    Google Scholar 

  44. Henske EP, Wessner LL, Golden J, Scheithauer BW, Vortmeyer AO, Zhuang Z, Klein-Szanto AJ, Kwiatkowski DJ, Yeung RS: Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors. Am J Pathol 151: 1639–1647, 1997

    Google Scholar 

  45. Vinters HV, Kerfoot C, Catania M, Emelin JK, Roper SN, DeClue JE: Tuberous sclerosis-related gene expression in normal and dysplastic brain. Epilepsy Res 32: 12–23, 1998

    Google Scholar 

  46. Wienecke R, Maize JC Jr, Reed JA, de Gunzburg J, Yeung RS, DeClue JE: Expression of the TSC2 product tuberin and its target Rap1 in normal human tissues. Am J Pathol 150: 43–50, 1997

    Google Scholar 

  47. Park SH, Pepkowitz SH, Kerfoot C, De Rosa MJ, Poukens V, Wienecke R, DeClue JE, Vinters HV: Tuberous sclerosis in a 20-week gestation fetus: immunohistochemical study. Acta Neuropathol (Berl) 94: 180–186, 1997

    Google Scholar 

  48. Kerfoot C, Wienecke R, Menchine M, Emelin J, Maize JC Jr, Welsh CT, Norman MG, DeClune JE, Vinters HV: Localization of tuberous sclerosis 2 mRNAand its protein product tuberin in normal human brain and in cerebral lesions of patients with tuberous sclerosis. Brain Pathol 6: 367–375, 1996

    Google Scholar 

  49. Mizuguchi M, Kato M, Yamanouchi H, Ikeda K, Takashima S: Loss of tuberin from cerebral tissues with tuberous sclerosis and astrocytoma. Ann Neurol 40: 941–944, 1996

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery and Laboratory for Fetal Medicine Research in Clinical Research Institute, Seoul National University Hospital, Seoul, Korea

    Seung-Ki Kim, Kyu-Chang Wang, Byung-Kyu Cho, Hee-Won Jung, Yun Jin Lee, Young Seob Chung & Ji-Young Lee

  2. Department of Neurosurgery, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea

    Se-Hyuck Park

  3. Department of Pathology, Seoul National University Hospital, Seoul, Korea

    Yoen-Mee Kim, Gheeyoung Choe & Je G. Chi

Authors
  1. Seung-Ki Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyu-Chang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Byung-Kyu Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hee-Won Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yun Jin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Young Seob Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ji-Young Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Se-Hyuck Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yoen-Mee Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gheeyoung Choe
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Je G. Chi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, SK., Wang, KC., Cho, BK. et al. Biological Behavior and Tumorigenesis of Subependymal Giant Cell Astrocytomas. J Neurooncol 52, 217–225 (2001). https://doi.org/10.1023/A:1010664311717

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1010664311717

Search

Navigation