Anaplastic ganglioglioma in children

  • Michael Karremann
  • Torsten Pietsch
  • Gisela Janssen
  • Christof M. Kramm
  • Johannes E. A. Wolff
Clinical study - patient study


Purpose Anaplastic gangliogliomas (AGG) are gangliogliomas with areas of pronounced hypercellularity, vascular proliferation, necrosis, and many mitotic figures. As very few pediatric patients have been studied, we analyzed the cases registered in the HIT-GBM database. Patients and Methods Patient data were obtained from the German HIT-GBM database. Inclusion criteria were diagnosis of AGG proven by a central neuropathological review and patient age 0 to 17 years. Eight patients (five male and three female) were identified. Results Patients’ median age was 10 years. The median history of disease was 9 months (range, 1.0–43.0 months). Initial symptoms included signs of raised intracranial pressure, seizures, and, in the case of spinal cord tumor, bladder dysfunction. In five cases, AGGs were localized supratentorially with three patients having multiple lobes involved. The tumors affected the frontal (n = 3 cases), parietal (n = 2), temporal (n = 2), and occipital lobes (n = 1), as well as the brainstem (n = 1) and the spinal cord (n = 2). Gross total tumor resection was achieved in six patients. The estimated 5-year overall survival rate ± standard error was 88 ± 12%, and the event-free survival rate was 63 ± 17%. While gender and tumor location did not affect survival rates, gross total tumor resection provided a better overall survival than non-total resection. Conclusion The prognosis of pediatric patients with AGG is good, especially for those who undergo gross total tumor resection.


Gliomas Pediatrics Central nervous system neoplasms Ganglioglioma Brain cancer 



The ongoing support of the Deutsche Kinderkrebsstiftung, Bonn, Germany, is greatly appreciated. We also thank our colleagues who contributed patient data to the HIT-GBM studies.


  1. 1.
    Selch MT, Goy BW, Lee SP, El-Sadin S, Kincaid P, Park SH, Withers HR (1998) Gangliogliomas: experience with 34 patients and review of the literature. Am J Clin Oncol 21:557–564. doi: 10.1097/00000421-199812000-00006 PubMedCrossRefGoogle Scholar
  2. 2.
    Nair V, Suri VS, Tatke M, Saran RK, Malhotra V, Singh D (2004) Gangliogliomas: a report of five cases. Indian J Cancer 41:41–46PubMedGoogle Scholar
  3. 3.
    Liauw SL, Byer JE, Yachnis AT, Amdur RJ, Mendenhall WM (2007) Radiotherapy after subtotally resected or recurrent ganglioglioma. Int J Radiat Oncol Biol Phys 67:244–247. doi: 10.1016/j.ijrobp.2006.08.029 PubMedGoogle Scholar
  4. 4.
    Johnson MD, Jennings MT, Toms ST (2001) Oligodendroglial ganglioglioma with anaplastic features arising from the thalamus. Pediatr Neurosurg 34:301–305. doi: 10.1159/000056042 PubMedCrossRefGoogle Scholar
  5. 5.
    Luyken C, Blumcke I, Fimmers R, Urbach H, Wiestler OD, Schramm J (2004) Supratentorial gangliogliomas: histopathologic grading and tumor recurrence in 184 patients with a median follow-up of 8 years. Cancer 101:146–155. doi: 10.1002/cncr.20332 PubMedCrossRefGoogle Scholar
  6. 6.
    Becker AJ, Lobach M, Klein H, Normann S, Nothen MM, von Deimling A, Mizuguchi M, Elger CE, Schramm J, Wiestler OD, Blumcke I (2001) Mutational analysis of TSC1 and TSC2 genes in gangliogliomas. Neuropathol Appl Neurobiol 27:105–114. doi: 10.1046/j.0305-1846.2001.00302.x PubMedCrossRefGoogle Scholar
  7. 7.
    Zhu JJ, Leon SP, Folkerth RD, Guo SZ, Wu JK, Black PM (1997) Evidence for clonal origin of neoplastic neuronal and glial cells in gangliogliomas. Am J Pathol 151:565–571PubMedGoogle Scholar
  8. 8.
    Becker AJ, Wiestler O, Figarella-Branger D, Blümcke I (2007) Ganglioglioma and gangliocytoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumors of the central nervous system. IARC Press, Lyon, pp 103–105Google Scholar
  9. 9.
    Mekni A, Chelly I, Haouet S, Zitouna M, Kchir N (2006) Malignant cerebellar ganglioglioma. A case report and review of the literature. Neurochirurgie 52:119–122. doi: 10.1016/S0028-3770(06)71206-1 Google Scholar
  10. 10.
    Karabekir HS, Balci C, Tokyol C (2006) Primary spinal anaplastic ganglioglioma. Pediatr Neurosurg 42:374–378. doi: 10.1159/000095568 PubMedCrossRefGoogle Scholar
  11. 11.
    Nakajima M, Kidooka M, Nakasu S (1998) Anaplastic ganglioglioma with dissemination to the spinal cord: a case report. Surg Neurol 49:445–448. doi: 10.1016/S0090-3019(97)00293-0 PubMedCrossRefGoogle Scholar
  12. 12.
    Chintagumpala MM, Armstrong D, Miki S, Nelson T, Cheek W, Laurent J, Woo SY, Mahoney DH Jr (1996) Mixed neuronal-glial tumors (gangliogliomas) in children. Pediatr Neurosurg 24:306–313. doi: 10.1159/000121060 PubMedCrossRefGoogle Scholar
  13. 13.
    Wolff JE, Classen CF, Wagner S, Kortmann RD, Palla SL, Pietsch T, Kuhl J, Gnekow A, Kramm CM (2008) Subpopulations of malignant gliomas in pediatric patients: analysis of the HIT-GBM database. J Neurooncol 87:155–164. doi: 10.1007/s11060-007-9495-z PubMedCrossRefGoogle Scholar
  14. 14.
    Wolff JE, Gnekow AK, Kortmann RD, Pietsch T, Urban C, Graf N, Kuhl J (2002) Preradiation chemotherapy for pediatric patients with high-grade glioma. Cancer 94:264–271. doi: 10.1002/cncr.10114 PubMedCrossRefGoogle Scholar
  15. 15.
    Wolff JE, Molenkamp G, Westphal S, Pietsch T, Gnekow A, Kortmann RD, Kuehl J (2000) Oral trofosfamide and etoposide in pediatric patients with glioblastoma multiforme. Cancer 89:2131–2137. doi:10.1002/1097-0142(20001115)89:10<2131::AID-CNCR14>3.0.CO;2-JPubMedCrossRefGoogle Scholar
  16. 16.
    Wolff JE, Wagner S, Reinert C, Gnekow A, Kortmann RD, Kuhl J, Van Gool SW (2006) Maintenance treatment with interferon-gamma and low-dose cyclophosphamide for pediatric high-grade glioma. J Neurooncol 79:315–321. doi: 10.1007/s11060-006-9147-8 PubMedCrossRefGoogle Scholar
  17. 17.
    Wolff JE, Wagner S, Sindichakis M, Pietsch T, Gnekow A, Kortmann RD, Strater R, Kuehl J (2002) Simultaneous radiochemotherapy in pediatric patients with high-grade glioma: a phase I study. Anticancer Res 22:3569–3572PubMedGoogle Scholar
  18. 18.
    Wagner S, Leuthold U, Schmid H-J, Wolff JE (2003) Pilotstudie mit hochdosiertem Methotrexat und nachfolgender simultaner Radiochemotherapie bei neun Kindern mit hochgradig-malignen Gliomen. Monatsschr Kinderheilkd 151:467–476. doi: 10.1007/s00112-003-0693-2 abstractCrossRefGoogle Scholar
  19. 19.
    Wagner S, Reinert C, Schmid HJ, Liebeskind AK, Jorch N, Langler A, Graf N, Warmuth-Metz M, Pietsch T, Peters O, Wolff JE (2005) High-dose methotrexate prior to simultaneous radiochemotherapy in children with malignant high-grade gliomas. Anticancer Res 25:2583–2587PubMedGoogle Scholar
  20. 20.
    Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JE, Kortmann RD, Kuehl J (2005) Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352:978–986. doi: 10.1056/NEJMoa042176 PubMedCrossRefGoogle Scholar
  21. 21.
    Haddad SF, Moore SA, Menezes AH, VanGilder JC (1992) Ganglioglioma: 13 years of experience. Neurosurgery 31:171–178. doi: 10.1097/00006123-199208000-00001 PubMedCrossRefGoogle Scholar
  22. 22.
    Jay V, Squire J, Becker LE, Humphreys R (1994) Malignant transformation in a ganglioglioma with anaplastic neuronal and astrocytic components. Report of a case with flow cytometric and cytogenetic analysis. Cancer 73:2862–2868. doi:10.1002/1097-0142(19940601)73:11<2862::AID-CNCR2820731133>3.0.CO;2-5PubMedCrossRefGoogle Scholar
  23. 23.
    Demaerel P, Droessaert M, Lammens M, Menten J, Nuttin B, Verbeeck R, Wilms G, Baert AL (1996) Anaplastic (malignant) ganglioglioma arising from heterotopic grey matter nodules. J Neurooncol 30:237–242. doi: 10.1007/BF00177274 PubMedCrossRefGoogle Scholar
  24. 24.
    Kurian NI, Nair S, Radhakrishnan VV (1998) Anaplastic ganglioglioma: case report and review of the literature. Br J Neurosurg 12:277–280. doi: 10.1080/02688699845159 PubMedCrossRefGoogle Scholar
  25. 25.
    Samadani U, Judkins AR, Akpalu A, Aronica E, Crino PB (2007) Differential cellular gene expression in ganglioglioma. Epilepsia 48:646–653. doi: 10.1111/j.1528-1167.2007.00925.x PubMedCrossRefGoogle Scholar
  26. 26.
    Pandita A, Balasubramaniam A, Perrin R, Shannon P, Guha A (2007) Malignant and benign ganglioglioma: a pathological and molecular study. Neurooncology 9:124–134. doi: 10.1215/15228517-2006-029 Google Scholar
  27. 27.
    Tarnaris A, O’Brien C, Redfern RM (2006) Ganglioglioma with anaplastic recurrence of the neuronal element following radiotherapy. Clin Neurol Neurosurg 108:761–767. doi: 10.1016/j.clineuro.2005.09.005 PubMedCrossRefGoogle Scholar
  28. 28.
    Hall WA, Yunis EJ, Albright AL (1986) Anaplastic ganglioglioma in an infant: case report and review of the literature. Neurosurgery 19:1016–1020. doi: 10.1097/00006123-198612000-00019 PubMedCrossRefGoogle Scholar
  29. 29.
    Tamiya T, Takao S, Ichikawa T, Chayama K, Date I (2006) Successful chemotherapy for congenital malignant gliomas: a report of two cases. Pediatr Neurosurg 42:240–244. doi: 10.1159/000092362 PubMedCrossRefGoogle Scholar
  30. 30.
    Lang FF, Epstein FJ, Ransohoff J, Allen JC, Wisoff J, Abbott IR, Miller DC (1993) Central nervous system gangliogliomas. Part 2: clinical outcome. J Neurosurg 79:867–873PubMedCrossRefGoogle Scholar
  31. 31.
    Bucci MK, Maity A, Janss AJ, Belasco JB, Fisher MJ, Tochner ZA, Rorke L, Sutton LN, Phillips PC, Shu HK (2004) Near complete surgical resection predicts a favorable outcome in pediatric patients with nonbrainstem, malignant gliomas: results from a single center in the magnetic resonance imaging era. Cancer 101:817–824. doi: 10.1002/cncr.20422 PubMedCrossRefGoogle Scholar
  32. 32.
    Finlay JL, Wisoff JH (1999) The impact of extent of resection in the management of malignant gliomas of childhood. Childs Nerv Syst 15:786–788. doi: 10.1007/s003810050471 PubMedCrossRefGoogle Scholar
  33. 33.
    Kramm CM, Wagner S, Van Gool S, Schmid H, Strater R, Gnekow A, Rutkowski S, Wolff JE (2006) Improved survival after gross total resection of malignant gliomas in pediatric patients from the HIT-GBM studies. Anticancer Res 26:3773–3779PubMedGoogle Scholar
  34. 34.
    Heideman RL, Kuttesch J Jr, Gajjar AJ, Walter AW, Jenkins JJ, Li Y, Sanford RA, Kun LE (1997) Supratentorial malignant gliomas in childhood: a single institution perspective. Cancer 80:497–504. doi:10.1002/(SICI)1097-0142(19970801)80:3<497::AID-CNCR18>3.0.CO;2-SPubMedCrossRefGoogle Scholar
  35. 35.
    Campbell JW, Pollack IF, Martinez AJ, Shultz B (1996) High-grade astrocytomas in children: radiologically complete resection is associated with an excellent long-term prognosis. Neurosurgery 38:258–264. doi: 10.1097/00006123-199602000-00006 PubMedCrossRefGoogle Scholar
  36. 36.
    Artico M, Cervoni L, Celli P, Salvati M, Palma L (1993) Supratentorial glioblastoma in children: a series of 27 surgically treated cases. Childs Nerv Syst 9:7–9. doi: 10.1007/BF00301926 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Michael Karremann
    • 1
    • 2
  • Torsten Pietsch
    • 3
  • Gisela Janssen
    • 4
  • Christof M. Kramm
    • 1
  • Johannes E. A. Wolff
    • 5
    • 6
  1. 1.Department of Pediatrics and Adolescence MedicineMartin-Luther-University Halle-WittenbergHalleGermany
  2. 2.Department of PediatricsUniversity Hospital MannheimMannheimGermany
  3. 3.Department of NeuropathologyUniversity of BonnBonnGermany
  4. 4.Department of Pediatric Oncology, Hematology and ImmunologyHeinrich-Heine-UniversityDüsseldorfGermany
  5. 5.Department of Pediatric Neuro-Oncology, Unit 87The University of Texas M. D. Anderson Cancer CenterHoustonUSA
  6. 6.Department of BiostatisticsThe University of Texas M. D. Anderson Cancer CenterHoustonUSA

Personalised recommendations