i) Medulloblastoma

Epidemiology

Incidence

Medulloblastoma is the most common posterior fossa malignancy of childhood, making up 15-20% of all diagnoses and 4% of all paediatric malignancies. The incidence is about 5 per 1,000,000 children under 15 per year.

Age

The median age of diagnosis is 7. Although uncommon, medulloblastoma can occur in older children and adults.

Geography/Ethnicity

There is a relative lower number of medulloblastomas in Japan (10% of paediatric malignancies); in other parts of the world incidence is relatively stable at around 20%. Whites are more commonly affected than blacks (ratio 1.6:1).

Gender

Boys are more commonly affected (1.6:1).

Summary: Medulloblastoma is a relatively common CNS malignancy, with a median age of diagnosis of 7-8. It is most common in Caucasian boys.


Aetiology and Pathogenesis

The aetiology of medulloblastoma is not fully understood. Some clue towards the required genetic mutations comes from its association with Basal Cell Naevus Syndrome (Gorlin) syndrome (PTCH1 deficiency). BCNS is associated with mutations of PTCH1, a member of the sonic hedgehog signal transduction pathway. PTCH1, when active, prevents activity of SMO (smoothened), which promotes cellular proliferation and survival through its downstream effects. BCNS patients have an elevated risk of medulloblastoma (about 5%); mutations in PTCH1 and other members of the sonic hedgehog pathway are present in 10-15% of sporadic medulloblastomas. Other identified genes include Wingless, Notch2, and the ERBB2 signal transduction pathway.


Natural History

Medulloblastoma almost always arises in the cerebellum, bordering the 4th ventricle. The disease is especially notable for spread throughout the cerebrospinal fluid and extensive involvement of the leptomeninges. In some cases it can spread to sites outside the CNS.


Clinical Presentation

Symptoms

Symptoms relate to the age of diagnosis, and are mostly due to obstructive hydrocephalus. In young children, this causes irritability, drowsiness and vomiting. Older children typically complain of headache. Cerebellar signs may be present. Advanced disease may present with spinal cord compression, hemiparesis, or symptoms related to sites outside the CNS.

Signs

Papilloedema related to hydrocephalus is common. Cerebellar signs may also be present. Signs of advanced disease should also be sought (eg. spinal cord compression).

Bloods

Blood tests are typically unhelpful except in suggesting organ failure due to metastatic disease. Lumbar puncture looking for CSF involvement should be performed when overt leptomeningeal disease is not visible on imaging (below).

Imaging

On CT, medulloblastoma appears as a uniformly enhancing posterior fossa mass. MRI shows a T1 hypointense and T2 hyperintense lesion with heterogenous uptake of gadolinium.
Spread to leptomeningies is usually visible on MRI with contrast enhancement. Not all cases of CSF involvement are visible on MRI, requiring lumbar puncture to exclude involvement.


Tumour Features

Macroscopic

The tumour is usually well circumscribed and grey in colour.

Microscopic

Medulloblastoma is a small round blue cell tumour. Cells can form Homer-Wright pseudorosettes (cells clustered around a central area of neuropil, substance lying between cells). There are five architectural types:

  • Classical medulloblastoma, with the features described above.
  • Desmoplastic medulloblastoma, with contains a stromal reaction of collagen that may surrounds groups of cells
  • Medulloblastoma with extensive nodularity, where the malignant cells are arranged in nodules surrounded by a stromal reaction.
  • Anaplastic medulloblastoma, containing larger cells with increased cytoplasm
  • Large cell medulloblastoma, notable for high mitotic rate and apoptosis

Immunohistochemistry

Most patients present

Staging / Classification

Chang staging is used for medulloblastoma. The T stage is not commonly used as it has no impact on prognosis; the M stage has significant impact on prognosis and is used to classify patients into standard and high risk groups.


Links


Bibliography

1. Dhall, G. Medulloblastoma. Journal of Child Neurology 24, 1418–1430 (2009).