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Childhood Medulloblastoma Treatment (PDQ®)     
Last Modified: 04/07/2008
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Medulloblastoma



Medulloblastoma

This tumor usually originates in the cerebellum. It may spread contiguously to the cerebellar peduncle, floor of the fourth ventricle, into the cervical spine, or above the tentorium. In addition, it may spread via the cerebrospinal fluid intracranially and/or to the spinal cord. Every patient with medulloblastoma should be evaluated with diagnostic imaging of the entire neuraxis, and when possible, lumbar cerebrospinal fluid analysis for free-floating tumor cells.[1] The most sensitive method available for evaluating spinal cord subarachnoid metastasis is spinal magnetic resonance imaging performed with gadolinium. Because medulloblastoma occasionally metastasizes outside the central nervous system, especially to bone, a bone scan with plain film correlation as well as a bone marrow aspiration and biopsy may be useful in symptomatic patients or in those with abnormal blood cell counts at diagnosis. Cerebrospinal fluid shunts at the time of surgery have not been shown to increase the risk of leptomeningeal relapse. The most commonly used staging system has been proposed in a system that rates the tumor by an intraoperative evaluation of both size and extent as well as by the presence of metastatic disease. Alternative postoperative staging systems are now being used that are based on surgical impression and postoperative imaging studies. Patients with disseminated disease at diagnosis are clearly at highest risk for disease relapse.[2] Other factors that may portend an unfavorable outcome include younger age at diagnosis, brain stem involvement, subtotal resection, and anaplastic histologic features.[2-5] These prognostic variables must be evaluated in the context of the treatment received.

Biologic tumor characteristics have been associated with prognosis, though not all reports have consistently identified prognostic significance for the same markers. Nuclear expression of p53 and disruption of the p53/ARF tumor suppressor pathway, HER2/ErbB2 expression, and survivin expression have been associated with poor prognosis.[6-9] Amplification and overexpression of MYCC/MYCN have been associated with poor prognosis in some studies,[10-14] but not others.[8] Conversely, TrkC mRNA or protein expression has been linked to favorable outcome,[6,15] though not universally.[8] Gene expression profiling can also provide prognostic information that is independent of clinical variables.[16] There is no consensus for how these biological features should be applied to direct therapeutic decisions, though ongoing studies are seeking to provide data that will allow a valid risk classification scheme to be developed based on biological characteristics.[8,17]

Two major risk group categories defined by clinical criteria are now being used:

  • Average risk: Children older than 3 years with posterior fossa tumors; tumor is totally or near-totally (<1.5 cc’s of residual disease) resected; no dissemination.[3]


  • High risk: Children 3 years old or younger or those with metastatic disease and/or subtotal resection (>1.5 cc’s of residual disease) and/or nonposterior fossa location.[13]


References

  1. Fouladi M, Gajjar A, Boyett JM, et al.: Comparison of CSF cytology and spinal magnetic resonance imaging in the detection of leptomeningeal disease in pediatric medulloblastoma or primitive neuroectodermal tumor. J Clin Oncol 17 (10): 3234-7, 1999.  [PUBMED Abstract]

  2. Albright AL, Wisoff JH, Zeltzer PM, et al.: Effects of medulloblastoma resections on outcome in children: a report from the Children's Cancer Group. Neurosurgery 38 (2): 265-71, 1996.  [PUBMED Abstract]

  3. Yao MS, Mehta MP, Boyett JM, et al.: The effect of M-stage on patterns of failure in posterior fossa primitive neuroectodermal tumors treated on CCG-921: a phase III study in a high-risk patient population. Int J Radiat Oncol Biol Phys 38 (3): 469-76, 1997.  [PUBMED Abstract]

  4. Packer RJ, Siegel KR, Sutton LN, et al.: Efficacy of adjuvant chemotherapy for patients with poor-risk medulloblastoma: a preliminary report. Ann Neurol 24 (4): 503-8, 1988.  [PUBMED Abstract]

  5. Giangaspero F, Wellek S, Masuoka J, et al.: Stratification of medulloblastoma on the basis of histopathological grading. Acta Neuropathol 112 (1): 5-12, 2006.  [PUBMED Abstract]

  6. Ray A, Ho M, Ma J, et al.: A clinicobiological model predicting survival in medulloblastoma. Clin Cancer Res 10 (22): 7613-20, 2004.  [PUBMED Abstract]

  7. Frank AJ, Hernan R, Hollander A, et al.: The TP53-ARF tumor suppressor pathway is frequently disrupted in large/cell anaplastic medulloblastoma. Brain Res Mol Brain Res 121 (1-2): 137-40, 2004.  [PUBMED Abstract]

  8. Gajjar A, Hernan R, Kocak M, et al.: Clinical, histopathologic, and molecular markers of prognosis: toward a new disease risk stratification system for medulloblastoma. J Clin Oncol 22 (6): 984-93, 2004.  [PUBMED Abstract]

  9. Haberler C, Slavc I, Czech T, et al.: Histopathological prognostic factors in medulloblastoma: high expression of survivin is related to unfavourable outcome. Eur J Cancer 42 (17): 2996-3003, 2006.  [PUBMED Abstract]

  10. Grotzer MA, Hogarty MD, Janss AJ, et al.: MYC messenger RNA expression predicts survival outcome in childhood primitive neuroectodermal tumor/medulloblastoma. Clin Cancer Res 7 (8): 2425-33, 2001.  [PUBMED Abstract]

  11. Aldosari N, Bigner SH, Burger PC, et al.: MYCC and MYCN oncogene amplification in medulloblastoma. A fluorescence in situ hybridization study on paraffin sections from the Children's Oncology Group. Arch Pathol Lab Med 126 (5): 540-4, 2002.  [PUBMED Abstract]

  12. Herms J, Neidt I, Lüscher B, et al.: C-MYC expression in medulloblastoma and its prognostic value. Int J Cancer 89 (5): 395-402, 2000.  [PUBMED Abstract]

  13. Lamont JM, McManamy CS, Pearson AD, et al.: Combined histopathological and molecular cytogenetic stratification of medulloblastoma patients. Clin Cancer Res 10 (16): 5482-93, 2004.  [PUBMED Abstract]

  14. Eberhart CG, Kratz J, Wang Y, et al.: Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia. J Neuropathol Exp Neurol 63 (5): 441-9, 2004.  [PUBMED Abstract]

  15. Grotzer MA, Janss AJ, Fung K, et al.: TrkC expression predicts good clinical outcome in primitive neuroectodermal brain tumors. J Clin Oncol 18 (5): 1027-35, 2000.  [PUBMED Abstract]

  16. Fernandez-Teijeiro A, Betensky RA, Sturla LM, et al.: Combining gene expression profiles and clinical parameters for risk stratification in medulloblastomas. J Clin Oncol 22 (6): 994-8, 2004.  [PUBMED Abstract]

  17. Fisher PG, Burger PC, Eberhart CG: Biologic risk stratification of medulloblastoma: the real time is now. J Clin Oncol 22 (6): 971-4, 2004.  [PUBMED Abstract]