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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: 1) rapidly growing tumor arising from posterior fossa, usually cerebellum 2) arise from neural precursor cells 3) 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 Immunohistochemistry: - 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 [3] - 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: 1) surgical resection 2) optimal chemotherapy under study - more effective in higher grade tumors 3) optimal radiation under study 4) prognosis: a) depends on staging following surgical resection b) tendency to spread along spinal axis c) 70% 5 year survival d) fewer than 50% of children survive into adulthood

General

embryonal neoplasm

References

  1. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 2402
  2. WHO Classification Tumours of the Nervous System. Kleihues & Cavenee eds. IARC Press 2000
  3. Baeza N et al. AXIN1 mutations but not deletions in cerebellar medulloblastomas. Oncogene 22:632-6, 2003 PMID: 12555076
  4. Medical Knowledge Self Assessment Program (MKSAP) 16, 17. American College of Physicians, Philadelphia 2012, 2015
  5. Call JA, Naik M, Rodriguez FJ et al Long-term outcomes and role of chemotherapy in adults with newly diagnosed medulloblastoma. Am J Clin Oncol. 2014 Feb;37(1):1-7. PMID: 23111362

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