Nervous system: Meningioma

2000-07-01   Anne Marie Capodano 

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

Classification

Atlas Image
Macroscopic aspect of a parassagital meningioma - Anne Marie Capodano.

Clinics and Pathology

Etiology

Meningiomas are known to be induced by radiation with an average time interval to tumor appearence of 20-35 years. The majority of patients with radio-induced meningiomas have received irradiation for tinea capitis or for primary brain tumor.

Epidemiology

  • Meningiomas account for 15-25% of primary intracranial and intraspinal neoplasms, with an annual incidence of approximatively 6 per 100.000 individuals.
  • Meningiomas are often multiple in patients with neurofibromatosis type 2 (NF2). Sporadic meningiomas may also be multiple.
  • Meningiomas are most common during the sixth and seventh decade of life, but can occur in both childrens and in the elderly. There is a marked high frequency in females.

    • Clinics

    The vast majority of meningiomas arise within the intracranial, orbital, and intravertebral cavities.
    Atlas Image
    Histological features of a fibroblastic meningioma - Anne Marie Capodano.

    Pathology

    According to the World Health Classification (WHO 1993), the tumors are defined as Meningiothelial meningioma, Fibroblastic meningioma, Transitional meningioma, Psamommatous meningioma, Angiomatous meningioma, Chordoïd meningioma., and are classified according to increased degrees of anaplasia in grades I, II and III.
  • 90% of meningiomas are slowly growing benign tumors that histologically correspond to grade I according WHO classification.
  • 6-8% of meningiomas are designated as atypical meningiomas : WHO grade II. These tumors show a tendancy for local recurrence even after complete resection.
  • 2-3% of meningiomas exibit histological signs of malignancy : these tumors are classified as anaplastic malignant meningiomas of WHO grade III. They have a high risk for local recurrence and metastasis.

    • Treatment

    The treatment consists of total surgical resection of tumor.

    Prognosis

  • The major evolution is recurrence. The tumor grade provides the most useful predictor of recurrence.
  • Benign meningiomas have a recurrence rate of about 7-20%. Atypical meningiomas recur in 29-38% of cases, and anaplastic meningiomas in 50-78% of cases.
  • So, proliferation indices have been used to predict recurrence and survival.

    • Cytogenetics

    Atlas Image
    Top: del(22q) (G-banding) - Courtesy G. Reza Hafez, Eric B. Johnson, Sara Morrison-Delap Cytogenetics at the Waisman Center; bottom: partial karyotype of a fibroblatic meningioma cell; there was hypoploidy (39,XX), a monosommy 22 (arrow), and tas (arrowheads) - Courtesy Anne Marie Capodano.

    Cytogenetics morphological

    Meningiomas were among the first solid tumors recognized as having cytogenetic alterations.
  • The most consistent change reported in benign meningiomas is partial (del(22)(q12)) or total deletion of chromosome 22. Loss of chromosome 22 more often occurs in meningiomas grade I.
  • Other karyotypic abnormalities, associated or not with monosomy 22, are seen in grade II (atypical meningiomas), and grade III (anaplastic meningiomas); The most frequent abnormalities changes are deletion of the short arm of chromosome 1, partial or complete loss of chromosome 10, and loss of chromosome 14. Unstable chromosome alterations including rings, dicentrics and telomeric associations, have been observed.
  • A statistical correlation between fibroblastic type and some chromosome abnormalities (monosomy 22 and telomeric associations), was reported. Studies support a postulated role of chromosome 22 as the primary event in the developpement of the majority of the meningiomas.

    • Genes Involved and Proteins

    Note

    Allelic losses: Molecular genetic findings using polymorphic DNA markers, confirmed that half of meningiomas have allelic loss of band q12 on chromosome 22. Atypical and anaplastic meningiomas often show allelic losses of chromosomal arms 1p, 9q, 10q, 14q, and 17p. LOH of chromosome 14 was the most frequent abnormality in atypical meningiomas : for this reason it is considered to be a step of malignant progression.

    Gene name

    NF2 (neurofibromatosis type 2)

    Location

    22q12.2

    Dna rna description

    Tumor suppressor gene

    Protein description

    Called merlin or schwannomin

    Germinal mutations

    In neurofibromatosis type 2 patients

    Somatic mutations

  • Mutations in the NF2 gene are detected in aproximatively in 60% of sporadic meningiomas. The majority of mutations are small insertions, deletions or non-sens mutations that affect splice sites. The common effect of such mutations is a truncated merlin protein. The frequency of NF2 gene mutations varies according to the meningiomas types. Few mutations of NF2 gene were observed in meningothelial meningiomas : only 25% of cases. 70-80% of fibroblastic and transitional meningiomas carry NF2 gene mutations.
  • Mutations and allelic loss events are also found in other tumors (schwannomas) and in neurofibromatosis type 2 tumours.

    • Note

  • LOH studies on chromosome 22 have also detected losses of genetic material outside the NF2 region. NF2 is likely to be the major tumor suppressor gene of meningiomas, but other genes localized in other loci on chromosome 22 are probably involved.
  • Another candidate gene on chromosome 22 is MN1 wich has been implicated in a case of translocation in a meningioma.
  • PTEN mutations, a gene localized in 10q23, were described in anaplastic meningiomas.
  • Rare mutations were reported on the CDKN2A gene.

    • Bibliography

    Pubmed IDLast YearTitleAuthors
    23938561990Molecular genetic analysis of chromosome 22 in 81 cases of meningioma.Dumanski JP et al
    77317061995Cloning and characterization of MN1, a gene from chromosome 22q11, which is disrupted by a balanced translocation in a meningioma.Lekanne Deprez RH et al
    83143211994Chromosomal deletions in anaplastic meningiomas suggest multiple regions outside chromosome 22 as important in tumor progression.Lindblom A et al
    76706571995Neuropathology and molecular genetics of neurofibromatosis 2 and related tumors.Louis DN et al
    15276221992Classic, atypical, and anaplastic meningioma: three histopathological subtypes of clinical relevance.Maier H et al
    41420251972Identification by fluorescence of the G chromosome lost in human meningomas.Mark J et al
    88345331996Homozygous deletions of the CDKN2/p16 gene in dural hemangiopericytomas.Ono Y et al
    78681311995Somatic mutations in the neurofibromatosis type 2 gene in sporadic meningiomas.Papi L et al
    84674681993Abnormalities of chromosome 22 in human brain tumors determined by combined cytogenetic and molecular genetic approaches.Rey JA et al
    28880211987Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22.Rouleau GA et al
    30375501987Molecular genetic approach to human meningioma: loss of genes on chromosome 22.Seizinger BR et al
    69392161981On the pathology of meningiomas. A study of 412 cases.Tedeschi F et al
    15244121992Telomeric association of chromosomes in human meningiomas.Vagner-Capodano AM et al
    94056791997Analysis of genomic alterations in benign, atypical, and anaplastic meningiomas: toward a genetic model of meningioma progression.Weber RG et al
    77174501995Analysis of the neurofibromatosis 2 gene reveals molecular variants of meningioma.Wellenreuther R et al
    98330721998Contribution of cytogenetics and FISH in the diagnosis of meningiomas. A study of 189 tumors.Zattara-Cannoni H et al

    Citation

    Anne Marie Capodano

    Nervous system: Meningioma

    Atlas Genet Cytogenet Oncol Haematol. 2000-07-01

    Online version: http://atlasgeneticsoncology.org/solid-tumor/5014/meningiomaid5014