medulloblastoma

Epidemiology

• 3% of intracranial neoplasms
• primarily children & young adults
• majority of medulloblastomas occur sporadically; however, some manifest within familial cancer syndromes such as Turcot syndrome & basal cell nevus syndrome (Gorlin syndrome)

Pathology

• rapidly growing tumor arising from posterior fossa, usually cerebellum
• arise from neural precursor cells
• tumor may spread to the cerebellar peduncle, floor of the 4th ventricle, above the tentorium or via the CSF intracranially &/or to the spinal cord

prognosis:

• age < 3 years, metastases at presentation & incomplete surgical resection associated with poor prognosis
• high apoptotic index associated with better outcome
• MYC amplification associated with resistance to therapy
• shorter survival times with large cell histologic variant
• corresponds histologically to grade IV.

Microscopic pathology

• tumor comprised of undifferentiated cells resembling cells of the primitive medullary tube
• generally located in the vermis of the cerebellum
• may occur on the sufaces of the cerebellum, brain stem, spinal cord
• malignant cells are compactly arranged, rounded or ovoid, with hyperchromatice nuclei, scant cytoplasm
• neoplastic cells lie in small & poorly defined goups, occasionally in pseudorosettes
• densely packed round/oval/carrot shaped hyperchromatic nuclei
• scant cytoplasm
• Homer-Wright (neuroblastic) rosettes ~40% circular configuration of cells around cytoplasmic processes
• mitoses usually numerous
• apoptosis frequent
• vascular proliferation, calcification, hemorrhage in minority of cases
• variants:
  • desmoplastic medulloblastoma
    • 20-30% of medulloblastomas
    • more nodular architecture than other medulloblastomas
    • prognosis may be better than other medulloblastomas
  • large cell variant medulloblastoma: appear to be biologically more aggressive
  • medulloblastoma with extensive nodularity and advanced neuronal differentiation: associated with favorable outcome
  • medullomyoblastoma: rare variant with rhabdomyoblastic differentiation
  • melanotic medulloblastoma

Immunophenotype

• synaptophysin +
• nestin +
• vimentin +
• GFAP occasional stellate cells +
• retinal S antigen, rhodopsin focally +
• PAX5 (in situ hybridization)/PAX6 +/-

Genetics

• isochromosome 17q ~50% of cases
• variable chromosome 1 abnormalities
• amplification of MYC or MYCN higher incidence of MYC amplification in large cell variant
• chromosome 17p deletion,
  • 17p11.2-pter, sometimes restricted to 17p13.2-13.3 (50%)
• PTCH2 gene inactivating mutations ~8% sporadic
• axin1 mutations noted
• allelic loss of DMBT1 gene in 59%
• allelic loss of KCTD11 gene
• associated with defects in SUFU
  • role in desmoplastic medulloblastoma
• other implicated genes SLITRK6, CDCA7L, APC, CTNNB1

Laboratory

• autoantibodies: PHF20

Management

• surgical resection
• optimal chemotherapy under study
  • more effective in higher grade tumors
• optimal radiation under study
• prognosis:
  • depends on staging following surgical resection
  • tendency to spread along spinal axis
  • 70% 5 year survival
  • fewer than 50% of children survive into adulthood

More general terms

• embryonal neoplasm

Patient information

medulloblastoma patient information

Database

• OMIM: https://mirror.omim.org/entry/155255