Nervous system: Ependymomas

2001-04-01   Anne Marie Capodano  

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

Summary

Note

Ependymomal neoplasms are tumors of children and young adults, originating from the cerebral ventricle or from the spinal canal. In the central nervous system (CNS), they account for 3 - 9 % of all neuro-epithelial tumors .

Classification

Atlas Image
Histological feature of ependymoma : perivascular rosettes - Anne Marie Capodano

Classification

Ependymomas are well-delineated moderately cellular gliomas. Histolological features are perivascular pseudo rosettes and ependymal rosettes WHO classification differentiate four major types :
  • 1. Ependymoma and variants (grade II) :
    - Cellular ependymoma : a variant of ependymoma with conspicuous cellularity but often less prominent pseudo-rosette or rosette formation.
    - Papillary ependymoma : a rare variant which looks like choroid plexus papilloma.
    - Clear cell ependymoma : a rare variant which may be confused with oligodendroglioma neurocytoma or metastatic renal cell carcinoma.

  • 2. Anaplastic (malignant) ependymoma (grade III) : An ependymoma with histological evidence of anaplasia.
  • 3. Myxopapillary ependymoma (grade I) : It occurs almost exclusively in the conus-cauda-filum terminale region, with a generally favourable prognosis.
  • 4. Subependymoma (grade I) : Benign tumor composed of nests of ependymomal cells in a dense glial fibrillary matrix

    • Clinics and Pathology

    Epidemiology

  • In children, 30 % of ependymomas appear before the age of 3 years and are more aggressive than in adults. Nearly 90 % of pediatric ependymomas are intra cranial : they occur in supratentorial or posterior fossa locations, and only 10 % are intraspinal. Ependymomas account for 6 to 12 % of brain tumors in children and represent the third most common central nervous system neoplasms in this age range, following astrocytoma and medulloblastoma.
  • In adults, 60 % of ependymomas are tumors of spinal cord and only 40 % are intracranial. Intramedullary spinal ependymomas can be seen in patients with neurofibromatosis type 2 (NF2), a hereditary disease. Clustering of ependymomas has been noted in some families suggesting inheritance of a genetic susceptibility to this type of tumor.

    • Clinics

    Clinical manifestations of these tumors are localization dependent.

    Pathology

    Immunochemistry: The great majority of ependymomas display GFAP immunoreactivity. It is usually observed in pseudo-rosettes, but GFAP is not specific of ependymomas. It is observed in all gliomas. Ependymomas typically express S 100 protein and Vimentin. In ependymomas WHO grade II, epithelial membrane antigen (EMA) immunoreactivity has been reported.

    Treatment

    The treatment of ependymomas is mainly exeresis of tumor and radiotherapy after exeresis

    Prognosis

    Ependymoma is a recurrent tumor. The identification of parameters with prognostic value in ependymomas is very important, but controverted. By order of importance the following factors are considered :
  • Age and extent of resection Prognosis in children is significantly worse than in adults. The children¼s cancer group reported a 5 year progression-free survival of 5 % in children with intracranial ependymomas. A retrospective analysis of 83 pediatric ependymomas revealed are below 3 years incomplete tumour resection as indication of a poor outcome.
    In adult patients survival at 10 years is 45 %.
    Complete or near complete resection emerged as an independent prognostic factor.
  • Localization Supratentorial ependymomas are associated with better survival rates compared to posterior fossa tumors.
    Spinal ependymomas are associated with better outcome than cerebral tumors. Cerebrospinal localization shows a poor prognosis.

    • Cytogenetics

    Atlas Image
    Partial karyotype of a cell of ependymoma : 46, XX, del(22)(q11) with R-banding - Anne Marie Capodano

    Cytogenetics morphological

  • No specific cytogenetic abnormality has been described. But ependymomas with 30 % incidence of aberrations involve chromosome 22 as the most frequent change. Monosomy 22 as well as deletions or translocations involving 22q can appear
  • Less frequent are structural abnormalities of chromosomes 1, 6, and 17 and numerical abnormalities of 7, 9, 12 and 20.
  • Monosomy 10 was reported in few cases of anaplastic ependymomas associated with LOH of 17p.
  • Monosomy 13 was observed in eight cases half of which occurred in paediatrics patients.
  • Rearrangements or deletions of chromosome 6 were reported in five tumors.

    • Genes Involved and Proteins

    Note

  • Genes involved in ependymomas remain to be uncovered. Mutations or deletions of the tumor suppressor genes CDKN2 A et CDKN2 B and amplification of CDK4 or CCND1 have been reported. Mutations of TP53 were occasionally observed in ependymomas.
  • Increased incidence of ependymomas in neurofibromatosis type 2 has suggest that NF2 represents an obvious candidate gene. Some authors have presented evidence for mutations of NF2 suppressor gene at 22 q12 . Whereas others have been unable to identify such mutations of the NF2.
  • Investigators show that the most frequently recurrent genomic loss in ependymomas does not involve the proximal 22 q11.2 chromosome region. They suggest that another not-yet identified tumor suppressor gene located distally to the HSNF5 / INT1 locus on the 22q and independent of NF2 locus may be involved in ependymomas.

    • Article Bibliography

    Pubmed IDLast YearTitleAuthors
    22247801990Cancer in the families of children with soft tissue sarcoma.Birch JM et al
    83314011993Adult intramedullary spinal cord ependymomas: the result of surgery in 38 patients.Epstein FJ et al
    89063661996Prognostic relevance of localization and grading in intracranial ependymomas of childhood.Ernestus RI et al
    91617311997The molecular biology of ependymomas.Hamilton RL et al
    103638531999A multi-institutional retrospective study of intracranial ependymoma in children: identification of risk factors.Horn B et al
    35121391986An immunocytochemical comparison of the glia-associated proteins glial fibrillary acidic protein (GFAP) and S-100 protein (S100P) in human brain tumors.Kimura T et al
    82931851993The new WHO classification of brain tumours.Kleihues P et al
    95258351998Molecular cytogenetic studies of pediatric ependymomas.Kramer DL et al
    85592931995Intracranial ependymomas of childhood: long-term outcome and prognostic factors.Pollack IF et al
    95257161998Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children: a report of the Children's Cancer Group.Robertson PL et al
    84025551993Chromosomes in the genesis and progression of ependymomas.Rogatto SR et al
    110638142000Fluorescence in situ hybridization determination of 22q12-q13 deletion in two intracerebral ependymomas.Rousseau-Merck M et al
    80622761994The putative glioma tumor suppressor gene on chromosome 19q maps between APOC2 and HRC.Rubio MP et al
    97055911998Prognostic factors in childhood intracranial ependymomas: the role of age and tumor location.Sala F et al
    86212481996Infrequent alterations of the p15, p16, CDK4 and cyclin D1 genes in non-astrocytic human brain tumors.Sato K et al
    27932291989Cytogenetic abnormalities in human ependymomas.Stratton MR et al
    89503381997Multiple ependymomas in a patient with Turcot's syndrome.Torres CF et al
    105981401999Cytogenetic study of 33 ependymomas.Vagner-Capodano AM et al

    Citation

    Anne Marie Capodano

    Nervous system: Ependymomas

    Atlas Genet Cytogenet Oncol Haematol. 2001-04-01

    Online version: http://atlasgeneticsoncology.org/solid-tumor/5016/nervous-system-ependymomas