Pediatric Medulloblastoma

Updated: Oct 04, 2017
  • Author: Michael A Huang, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Practice Essentials

Medulloblastoma is the most common malignant brain tumor in children, accounting for up to 20% of primary CNS neoplasms and approximately 40% of all posterior fossa tumors.

It is a high-grade (WHO grade IV) embryonal neuroepithelial tumor that arises in the cerebellum and has a tendency to disseminate via the cerebrospinal fluid (CSF).

With aggressive surgery, craniospinal radiotherapy and chemotherapy, more than 50% of children with medulloblastoma can be expected to be free of disease 5 years later. Using current treatments, 80-90% of those without disseminated disease can be cured; however, treatment for this disease often results in significant long-term neurological, endocrinological and intellectual sequelae.



Medulloblastoma is a heterogeneous disease. Recent advances in understanding the molecular characteristics of medulloblastoma cells allowed for sub-typing based on abnormalities seen at the molecular level. These subgroups are defined by their unique clinical behavior and outcomes.

The WNT-subgroup, which accounts for 10% of medulloblastoma cases in children, is characterized by aberrant activation of the Wingless (WNT) signaling pathway. The most frequently mutated genes in WNT medulloblastoma are CTNNB1 and TP53.

The SHH-subgroup accounts for 30% of medulloblastoma cases in children and is characterized by aberrant activation of the Sonic hedgehog (SHH) signaling pathway. The most frequently mutated genes in SHH medulloblastoma are PTCH1, SMO, SUFU, GLI1 and TP53.

Groups 3 and 4 which accounts for 25 and 35% of medulloblastoma cases respectively, lack involvement of any clearly defined signaling pathway. Common genetic alterations involves MYC, OTX2 and SMARCA4 in group 3, and KDM6A and MYCN in group4.

The most recent WHO classification of medulloblastoma is as follows [1] :

  • Medulloblastoma, genetically defined.
    • Medulloblastoma, WNT-activated.
    • Medulloblastoma, SHH-activated and TP53-mutant.
    • Medulloblastoma, SHH-activated and TP53-wildtype.
    • Medulloblastoma, non-WNT/non-SHH.
      • Medulloblastoma, group 3.
      • Medulloblastoma, group 4.
  • Medulloblastoma, histologically defined.
    • Medulloblastoma, classic.
    • Medulloblastoma, desmoplastic/nodular.
    • Medulloblastoma with extensive nodularity.
    • Medulloblastoma, large cell/anaplastic.
  • Medulloblastoma, NOS.



United States

Approximately 250 new patients are diagnosed annually.


Exact figures are unknown. In general, brain tumors occur at a rate of 2.5-4 per 100,000 at-risk children per year. Of these, approximately 18% are medulloblastoma.


Clinical risk group stratification is continuing to evolve but is currently based on four principal features including age, extent of postoperative residual disease, and the metastasis stage.

Molecular subtype provides significant information regarding tumor behavior and response to treatment. Patients with WNT subtype for example have an excellent prognosis, while patients with MYC or MYCN amplification do poorly.  

Despite successful treatment, a significant number of patients have neurocognitive, neurologic and endocrinologic deficits. Many children subsequently develop learning difficulties that require individualized educational programs. Biochemical growth deficiency is observed in 70-80% of patients, and some degree of growth impairment is present in well over half of patients after treatment. Thyroid and gonadotropin hormonal deficiency may also occur. Craniospinal radiation, a mainstay of treatment, has been implicated as a major cause of these deficits.


No racial predisposition is noted. The latest data from the Surveillance, Epidemiology, and End Results (SEER) program showed that patients aged 0-14 years in the United States have an incidence rate per million population of 5.7 in whites and 5 in blacks. [2]


US incidence per 1 million population for patients aged 0-14 years is 6.1 for boys and 4.5 for girls.


Peak age of incidence is during the first decade of life. Approximately 80% of patients are diagnosed in the first 15 years of life.



Prognostic factors include the following:

  1. Age at diagnosis
  2. Metastatic stage (M stage) at time of presentation
  3. Extent of surgical resection
  4. Histology
  5. Molecular subtype

The specific risk groups based on clinical findings and morphology are defined below:

  • Average-risk disease: This risk group is defined as patients older than 3 years who have no evidence of dissemination and with less than 1.5 cm 2 of residual tumor postoperatively. The 5-year survival rate for this group is currently 85%.
  • High-risk disease: This risk group is defined as patients older than 3 years with evidence of metastatic disease, with more than 1.5 cm 2 of residual tumor postoperatively and/or large cell/anaplastic histology. Large cell/anaplastic histology is commonly associated with unfavorable molecular changes like MYC amplification and predicts poor outcome. The 5-year survival rate for this group is currently 30-60%.
  • Infants: This group is defined as patients younger than 3 years. The 5-year survival rate is 30-70% depending on clinical and molecular risk factors; patients with metastatic disease do considerably worse while those with WNT-activated or SHH-activated medulloblastoma are much more likely to survive.

The genetically defined subgroups have variable outcome:

  • Patients with WNT-activated medulloblastoma have excellent prognosis with more than 90% long term survival. 
  • Patients younger than 4 years with SHH-activated medulloblastoma do well with 5-year event free survival of 85% when treated with surgery and chemotherapy alone. Children older than 4 years with SHH-activated medulloblastoma without TP53 mutation do fairly well with 5-year event free survival of 60%. However, patients with SHH-subgroup with TP53 mutation do significantly worse.
  • Patients with Group 3 have the worst outcome with close to 50% long-term survival.
  • Patients with Group 4 have close to 75% long-term survival.