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Nervous system: Meningioma

Written2000-07Anne Marie Capodano
Laboratoire de Cytogénétique Oncologique, Hpital de la Timone, 264 rue Saint Pierre, 13005 Marseille, France

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ICD-Morpho 9530/0 Meningioma, NOS / Microcystic meningiom / Secretory meningioma / Lymphoplasmacyte-rich meningioma / Metaplastic meningioma
Atlas_Id 5014
Phylum Central Nervous system::Meningioma
WHO/OMS Classification Central Nervous system


Note Macroscopic aspect of a parassagital meningioma - Anne Marie Capodano.

Clinics and Pathology

Disease Meningiomas are tumors arising from cells of the meningeal covering of the brain and spinal cord. These tumors are generally slow growing masses. Neurological signs and symptoms appear by compression of adjacent structures.
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.
  • 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.
    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.
  • 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

    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.
  • 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.

    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 NameNF2 (neurofibromatosis type 2)
    Location 22q12.2
    Dna / Rna Tumor suppressor gene
    Protein Called merlin or schwannomin
    Germinal mutation In neurofibromatosis type 2 patients
    Somatic mutation
  • 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

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    Cancer research. 1990 ; 50 (18) : 5863-5867.
    PMID 2393856
    Kleihues P, Cavenee WK
    Pathology and Genetics. 1997.
    Cloning and characterization of MN1, a gene from chromosome 22q11, which is disrupted by a balanced translocation in a meningioma.
    Lekanne Deprez RH, Riegman PH, Groen NA, Warringa UL, van Biezen NA, Molijn AC, Bootsma D, de Jong PJ, Menon AG, Kley NA
    Oncogene. 1995 ; 10 (8) : 1521-1528.
    PMID 7731706
    Chromosomal deletions in anaplastic meningiomas suggest multiple regions outside chromosome 22 as important in tumor progression.
    Lindblom A, Ruttledge M, Collins VP, Nordenskjö M, Dumanski JP
    International journal of cancer. Journal international du cancer. 1994 ; 56 (3) : 354-357.
    PMID 8314321
    Neuropathology and molecular genetics of neurofibromatosis 2 and related tumors.
    Louis DN, Ramesh V, Gusella JF
    Brain pathology (Zurich, Switzerland). 1995 ; 5 (2) : 163-172.
    PMID 7670657
    Classic, atypical, and anaplastic meningioma: three histopathological subtypes of clinical relevance.
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    Journal of neurosurgery. 1992 ; 77 (4) : 616-623.
    PMID 1527622
    Identification by fluorescence of the G chromosome lost in human meningomas.
    Mark J, Levan G, Mitelman F
    Hereditas. 1972 ; 71 (1) : 163-168.
    PMID 4142025
    Homozygous deletions of the CDKN2/p16 gene in dural hemangiopericytomas.
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    Acta neuropathologica. 1996 ; 91 (3) : 221-225.
    PMID 8834533
    Somatic mutations in the neurofibromatosis type 2 gene in sporadic meningiomas.
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    Human genetics. 1995 ; 95 (3) : 347-351.
    PMID 7868131
    Abnormalities of chromosome 22 in human brain tumors determined by combined cytogenetic and molecular genetic approaches.
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    Cancer genetics and cytogenetics. 1993 ; 66 (1) : 1-10.
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    Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22.
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    Nature. 1987 ; 329 (6136) : 246-248.
    PMID 2888021
    Russell DS, Rubinstein LJ
    Pathology of Tumors of the Nervous System,. 1989.
    Molecular genetic approach to human meningioma: loss of genes on chromosome 22.
    Seizinger BR, de la Monte S, Atkins L, Gusella JF, Martuza RL
    Proceedings of the National Academy of Sciences of the United States of America. 1987 ; 84 (15) : 5419-5423.
    PMID 3037550
    On the pathology of meningiomas. A study of 412 cases.
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    Acta neuropathologica. Supplementum. 1981 ; 7 : 119-121.
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    Telomeric association of chromosomes in human meningiomas.
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    PMID 1524412
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    Correlation between clinical and cytogenetical data in 180 meningiomas.
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    Contribution of cytogenetics and FISH in the diagnosis of meningiomas. A study of 189 tumors.
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    This paper should be referenced as such :
    Capodano, AM
    Nervous system tumors: Meningioma
    Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):149-152.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    Other genes implicated (Data extracted from papers in the Atlas) [ 28 ]


    External links

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