Medulloblastoma

Epidemiology and Etiology:

•  Children predominantly
• Within the category of primitive neuroectodermal tumours (PNET)
• May arise from granular cell layer of cerebellum

Common sites:

•  cerebellum exclusively
• midline in children
• lateral more often in adults
• a similar tumour supratentorially may be called primitive neuroectodermal tumour (PNET) – (NOT the peripheral PNET with Ewing’s translocation)
• may see dissemination via CSF
• ex. Cauda equina (« drop metastases »)

Gross features:

•  well-circumscribed
• gray
• friable

Histologic features:

• cellular sheets of anaplastic cells
• little cytoplasm
• hyperchromatic nuclei
• frequently elongated (carrot or crescent-shaped)
• abundant mitoses
• Homer Wright rosettes (neuropil at the centre) often
• At edges with normal cerebellum:
• Linear chains of tumour cells
• Tendency to accumulate beneath the pia
• Penetration of pia with seeding into subarachnoid space
• Desmoplastic variant:
• Collagen and reticulin deposition in areas
• “pale islands”
• nodules of cells with more neuropil
• lack reticulin deposition

Immunophenotype:

Marker:	Sensitivity:	Specificity:
Synaptophysin (particularly in Homer-Wright rosettes)	Almost always
Chromogranin	+ / -
GFAP	+ / -
Microtubule-associated protein (neuropil)
Class-III beta tubulin
Neurofilament protein	+ / -
Neurotropin receptor p75NTR	Nodular / desmoplastic variant
MIB-1 (high)

Molecular features:

•  17p loss is most common alteration
• REN is involved in regulation of the hedgehog-signaling pathway, implicated in medullobalstoma development
• note p53 does not appear to be the relevant gene in this case
• i(17)(q10) is most common abnormality In medulloblastoma
• MYC amplification (associated with a worse outcome) (6-8%)
• MYC
• MYCN
• Sonic hedgehog/patched pathway dysregulation
• PTCH loss of function
• PTCH and other members of Shh pathway (ex. smoothened) play key roles
• GLI family members play key role
• Wnt / Beta-catenin pathway dysregulation in some
• Increased trkC have better clinical outcome
• Gene expression signatures may be able to stratify
• Also difference between classic and desmoplastic

Other features:

•  hydrocephalus may occur
• highly aggressive
• dismal prognosis if untreated
• exquisitely radiosensitive
• better survival with complete resection
• 75% 5-year survival with total excision and radiation

References:

• Robbins & Cotran Pathologic Basis of Disease (2005)
• Heim S, Mitelman F. Cancer Cytogenetics. 3rd ed. Wiley-Blackwell; 2009.