What is a medulloblastoma?

Medulloblastoma: Definition and Clinical Characteristics

Medulloblastoma is a malignant embryonal tumor of the cerebellum with a propensity to invade and disseminate in the cerebrospinal fluid (CSF), representing one of the most common primary brain tumors in children. 1

Epidemiology and Prevalence

• Accounts for 10-20% of all pediatric brain tumors (incidence: 0.47 per 100,000 for children 0-14 years) 1
• Most common in children, though it can affect adults (relatively rare in this population) 1
• Predominantly located in the cerebellum 1

Molecular Classification

Medulloblastoma comprises four distinct molecular subtypes, each with different prognosis and treatment implications:

1. WNT-activated tumors (10% of cases):

   • Most common in children 7-14 years
   • Excellent prognosis (>90% long-term survival) 1

2. SHH-activated tumors (10-20% of cases):

   • Further classified as TP53-wild-type or TP53-mutant
   • TP53 mutations and/or MYCN amplification associated with poor prognosis 1

3. Group 3 tumors (25% of cases):

   • Less favorable prognosis (20-30% 5-year survival) 1

4. Group 4 tumors (35% of cases):

   • Better prognosis than Group 3 (75-90% overall survival) 1

Imaging Characteristics

• Typically appears as a large, heterogeneous posterior fossa mass occupying either the fourth ventricle or cerebellar hemisphere 1
• Usually hypointense or isointense on T1- and T2-weighted imaging 1
• Characteristically demonstrates:
  • Reduced diffusion due to high cellularity
  • Heterogeneous enhancement
  • Intratumoral cysts or necrotic foci may be present 1
  • Leptomeningeal dissemination may be present at diagnosis or develop during disease course 1

Prognostic Factors

Poor prognostic factors include:

• Age <3 years
• Metastatic disease at diagnosis
• Suboptimal surgical resection
• Certain molecular subtypes (particularly Group 3 and SHH with TP53 mutations) 1

Treatment Approach

Treatment is multimodal and includes:

1. Surgery:

   • Maximal safe resection is the goal
   • Reduces tumor-associated mass effect
   • Provides relief from hydrocephalus
   • Obtains tissue for histologic and molecular classification 1

2. Radiation therapy:

   • Craniospinal irradiation with boost to tumor bed
   • Reduced doses (23.4 Gy) with tumor bed boost (54 Gy) for average-risk disease 2
   • Young age at diagnosis (<7 years) is a significant risk factor for cognitive impairment 2

3. Chemotherapy:

   • Used in conjunction with radiation therapy
   • Specific regimens based on risk stratification 1

Long-term Outcomes and Complications

• With advances in multimodality therapies, approximately 75% of children with medulloblastoma achieve prolonged survival 1
• Long-term survivors face significant risks for:
  • Neurocognitive deficits (particularly in young children)
  • Endocrinologic complications
  • Psychological sequelae 2, 3
  • Risk of subsequent malignant neoplasms 2

Special Considerations

• Treatment for children <3 years requires special approaches to minimize radiation-related neurocognitive damage 1, 2
• Molecular classification should guide risk stratification and treatment planning 1
• Referral to specialized centers or "centers of excellence" is strongly recommended, especially for adult patients with this rare diagnosis 1

For optimal outcomes, comprehensive assessment using MRI (brain and spine), CSF cytology, and neurologic examination is essential for accurate diagnosis, staging, and treatment planning 1.