Nervous system: Medulloblastoma

2000-07-01   Anne Marie Capodano 

1.Laboratoire de Cytogénétique Oncologique, Hpital de la Timone, 264 rue Saint Pierre, 13005 Marseille, France

Clinics and Pathology

Epidemiology

It represents 10 at 20 % of brain tumours and 30 % of tumours localized in posterior fossa; annual incidence is 0,5 per 100 000 children; peak of occurrence at 7 years.
Atlas Image
Histological features of a typical medulloblastoma: Homer-Wright rosettes - Anne Marie Capodano.

Pathology

Belongs to the primitive neurectodermal tumours (PNET): highly malignant embryonal tumours of the CNS with predominant neuronal differentiation.
Several variants medulloblastoma are recognized in the OMS classification :
  • Classic medulloblastoma composed of densely jacked round-cells with round to oval hyperchromatic nuclei.
  • Desmoplastic medulloblastoma represents a variant with abundant reticulin and collagen.
  • Large cell medulloblastoma is a rare variant composed of cells with large round nuclei.
    Immuno histo chemistry : Classic medulloblastoma is strongly immuno-reactive for Vimentin. Some tumours are immunoreactive for NSE, Synaptophysine and GSAP.

    • Treatment

    The treatment associates total surgical resection and radiotherapy or, according to the age, chemotherapy.

    Prognosis

    Survival without recurrence is 50 at 70 %; depends on the quality of surgical resection and on the presence of metastases at the time of diagnosis.

    Cytogenetics

    Atlas Image
    i(17q) - R-banding.

    Cytogenetics morphological

  • The most common specific abnormality in medulloblastomas, which is present in approximately 50 % of cases, is isochromosome 17q [i(17q)]. The breakpoint is in the proximal portion of p-arm at 17p11.2, so that the resultant structure is dicentric. In a few cases, partial or complete loss of 17p occurs through interstitial deletion, unbalanced translocation or monosomy 17.
  • Chromosome 1 is also involved in medulloblastomas. The most frequent abnormalities are unbalanced translocations, deletions and duplications. Rearrangements of chromosome 1 often result in trisomy 1q without loss of the p-arm.
  • Others less common chromosomal changes are: deletions of 6q, 9q, 10q, 11q, 11p and 16q, monosomy 22 and in rare cases double minutes.

    • Cytogenetics molecular

  • Isochromosome 17 q has been observed in interphase nuclei using fluorescence in situ hybridization. This technique is used in particular when only a few metaphases are obtained or when only normal diploid cells are obtained in culture.

    • Genes Involved and Proteins

    Note

  • Studies on loss of heterozygosity (LOH) have confirmed loss of portions of 17p in 30-45 % of cases. Some studies showed a correlation between LOH for 17p and a poor response to therapy and shortened survival. Mutations of p53 gene located on 17p13 have been found in only 5-10 % of these tumors.
  • Expression of PAX5 and PAX6 mRNA was shown in 70 % of medulloblastomas. The precise mechanism by which these genes are involved remains unknown.
  • Inactivation of PTCH tumor suppressor gene occurs in a subset of medulloblastomas.

    • Bibliography

    Pubmed IDLast YearTitleAuthors

    Citation

    Anne Marie Capodano

    Nervous system: Medulloblastoma

    Atlas Genet Cytogenet Oncol Haematol. 2000-07-01

    Online version: http://atlasgeneticsoncology.org/solid-tumor/5065/haematological-explorer/