Medulloblastomas

Chapter 11 - Classification and Treatment of Paediatric Brain Tumours

Medulloblastoma (MB) is an embryonal tumour of the cerebellum and the most common malignant brain tumour in children (15%–20% of primary central nervous system [CNS] neoplasms). 

Peak age of incidence for MB is between 3 and 5 years, with 80% of cases diagnosed in the first 15 years of life. In 30% of patients the disease is metastatic at diagnosis.

This kind of tumour is biologically more aggressive in children, with a higher surgical risk and a poorer long-term survival than in adults.

The diagnostic work-up<\strong> includes: brain and spine magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) examination for tumour cells before surgery, molecular analysis (important for molecular subgroups) and risk stratification of patients with MB.<\p>

In the 2016 World Health Organization (WHO) classification of CNS tumours, MBs are separated into the classic tumour and four variants: desmoplastic/nodular (D/N), medulloblastoma with extensive nodularity (MBEN), anaplastic MB and large cell MB.

Infants with MBENs and D/N MBs have a better outcome than those with classic tumours, while large cell and anaplastic MBs behave aggressively.

Four molecular subgroups have been identified:

  1. WNT: Activation of WNT/beta-catenin signalling, overexpression of genes of the WNT pathway, with frequent mutations of the CNNTB1 Gene, loss of chromosome 6 and accumulation of nuclear beta- catenin (favourable marker).
  2. Activation of the Sonic Hedgehog (SHH) pathway: For most desmoplastic MBs, which arise in a context of inactivating mutations in PTCH1 and SUFU genes, loss of 9q.
  3. Group 3 tumours: High incidence of large cell/anaplastic histology, very frequently metastatic, frequent MYC Amplification.
  4. Tumours of Group 4: Identified by isochromosome 17q as a frequent chromosomal alteration, mostly histologically of the classic variant.

Treatment (according to molecular classification): multimodal treatment including surgical resection, radiotherapy (RT) and chemotherapy (ChT) has led to an improvement in long-term survival (66%), but also to a major related toxicity.

In conclusion: standard-risk MB is a curable disease, unlike high-risk MB, thanks to better therapy and a reduction of side effects.

Revision Questions

  1. In MBs, what should be part of the diagnostic work-up?
  2. Which of the MB molecular subgroups has the better prognosis?
  3. Is MB a rare malignant brain tumour in children?

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Last update: 18 September 2017