Acta Neuropathologica

, 116:289 | Cite as

Radiation-induced meningiomas: clinical, cytogenetic, and microarray features

  • Kevin O. Lillehei
  • Andrew M. Donson
  • B. K. Kleinschmidt-DeMasters
Original Paper


Limited information exists about the clinical and biological features of radiation-induced meningiomas (RIMs), particularly those that follow high-dose therapeutic radiation. We report our experience with 20 patients with RIMs (16 following high-dose radiotherapy) treated at our institution from 1993–2006. Patients (14 female, 6 male) had intervals from first radiotherapy to RIM diagnosis of 11–63 years; 12 had at least one RIM occur at an interval of 30 years or more after initial radiotherapy. Multiple RIMs were seen in six patients, with one patient developing his six RIMs sequentially over a 22-year interval. Most RIMs could be managed surgically, either with a single extensive resection or additional resection(s). Adjuvant stereotactic radiosurgery, external beam radiation, or chemotherapy were required in a minority (n = 6). Most were WHO grade I meningiomas. Complex karyotypes were found in three of four cases and abnormalities of chromosome 1p and/or LOH 1p36 were identified in five of 11 informative cases. Gene-expression microarray analysis of RIMs (n = 5) compared to non-RIMs (MEN, n = 6) and a panel of other tumors (n = 62) showed that RIM gene-expression was similar to that seen in MEN, and by clustering analysis did not separate from them. However, microarray comparative gene-expression analysis did demonstrate a few genes with significant differences in the expression level in RIM versus MEN. Of note, NF2 was under-expressed in four of five RIMs (P = 0.0065), at a similar level as measured in MEN.


Radiation-induced meningioma FISH Gene-expression microarray Affymetrix Cytogenetic LOH 1p 


  1. 1.
    Addo-Yobo SO, Straessle J, Anwar A, Donson AM, Kleinschmidt-DeMasters BK, Foreman NK (2006) Paired overexpression of ErbB3 and Sox 10 in pilocytic astrocytoma. J Neuropathol Exp Neurol 65:769–775. doi:10.1097/01.jnen.0000229989.25171.aa PubMedCrossRefGoogle Scholar
  2. 2.
    Al-Mefty O, Topsakal C, Pravdenkova S, Sawyer JR, Harrison MJ (2004) Radiation-induced meningiomas: clinical, pathological, cytokinetic, and cytogenetic characteristics. J Neurosurg 100:1002–1013PubMedGoogle Scholar
  3. 3.
    Andreassen CN, Alsner J, Overgaard M, Overgaard J (2003) Prediction of normal tissue radiosensitivity from polymorphisms in candidate genes. Radiother Oncol 69:127–135. doi:10.1016/j.radonc.2003.09.010 PubMedCrossRefGoogle Scholar
  4. 4.
    Begnami MD, Rushing EJ, Santi M, Quezado M (2007) Evaluation of NF2 gene deletion in pediatric meningiomas using chromogenic in situ hybridization. Int J Surg Pathol 15:110–115. doi:10.1177/1066896906299128 PubMedCrossRefGoogle Scholar
  5. 5.
    Choudhary A, Pradhan S, Huda MF, Mohanty S, Kumar M (2005) Radiation induced meningioma with a short latent period following high dose cranial irradiation—case report and literature review. J Neurooncol 10:11060–11065Google Scholar
  6. 6.
    Donson AM, Erwin NS, Kleinschmidt-DeMasters BK, Madden JR, Addo-Yobo SO, Foreman NK (2007) Unique molecular characteristics of radiation-induced glioblastoma. J Neuropathol Exp Neurol 66:740–749. doi:10.1097/nen.0b013e3181257190 PubMedCrossRefGoogle Scholar
  7. 7.
    Green S, Nair N, Ojemann JG, Avellino AM (2008) Meningiomas in children. Pediatr Neurosurg 44:9–13. doi:10.1159/000110656 CrossRefGoogle Scholar
  8. 8.
    Joachim T, Ram Z, Rappaport ZH, Simon M, Schramm J, Wiestler OD et al (2001) Comparative analysis of the NF2, TP53, PTEN, KRAS, NRAS and HRAS genes in sporadic and radiation-induced human meningiomas. Int J Cancer 94:218–221. doi:10.1002/ijc.1467 PubMedCrossRefGoogle Scholar
  9. 9.
    Kleinschmidt-DeMasters BK, Kang JS, Lillehei KO (2006) The burden of radiation-induced central nervous system tumors: a single institution’s experience. J Neuropathol Exp Neurol 65:204–216PubMedGoogle Scholar
  10. 10.
    Kleinschmidt-DeMasters BK, Lillehei KO (1995) Radiation induced meningioma with 63 year latency period. J Neurosurg 82:487–488PubMedCrossRefGoogle Scholar
  11. 11.
    Kleinschmidt-DeMasters BK, Meltesen L, McGavran L, Lillehei KO (2006) Characterization of glioblastomas in young adult patients. Brain Pathol 16:273–286. doi:10.1111/j.1750-3639.2006.00029.x PubMedCrossRefGoogle Scholar
  12. 12.
    Lomas J, Bello MJ, Arjona D, Alonso ME, Martinez-Glez V, Lopez-Marin I et al (2005) Genetic and epigenetic alteration of the NF2 gene in sporadic meningiomas. Genes Chromosomes Cancer 42:314–319. doi:10.1002/gcc.20141 PubMedCrossRefGoogle Scholar
  13. 13.
    Murakami M, Hashimoto N, Takahashi Y, Hosokawa Y, Inazawa J, Mineura K (2003) A consistent region of deletion on 1p36 in meningiomas: identification and relation to malignant progression. Cancer Genet Cytogenet 140:99–106. doi:10.1016/S0165-4608(02)00653-2 PubMedCrossRefGoogle Scholar
  14. 14.
    Musa BS, Pople IK, Cummins BH (1995) Intracranial meningiomas following irradiation—a growing problem? Br J Neurosurg 9:629–637. doi:10.1080/02688699550040918 PubMedCrossRefGoogle Scholar
  15. 15.
    Pagni CA, Canavero S, Fiocchi F, Ponzio G (1993) Chromosome 22 monosomy in a radiation-induced meningioma. Ital J Neurol Sci 14:377–379PubMedGoogle Scholar
  16. 16.
    Perry A, Louis DN, Budka Scheithauer BW, von Deimling A (2007) Meningiomas. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumours of the central nervous system. IARC Press, Lyon, pp 164–172Google Scholar
  17. 17.
    Pfisterer WK, Hank NC, Preul MC, Hendricks WP, Pueschel J, Coons SW et al (2004) Diagnostic and prognostic significance of genetic regional heterogeneity in meningiomas. J Neurooncol 6:290–299Google Scholar
  18. 18.
    Pistolesi S, Boldrini L, Gisfredi S, De Ieso K, Camacci T, Caniglia M et al (2004) Immunohistochemical and molecular study of radiation-induced multiple meningiomas with pleural and pulmonary metastasis. Tumori 90:328–332PubMedGoogle Scholar
  19. 19.
    Pollak L, Walach N, Gur R, Schiffer J (1998) Meningiomas after radiotherapy for tinea capitis—still no history. Tumori 84:65–68PubMedGoogle Scholar
  20. 20.
    Ron E, Modan B, Boice JD Jr, Alfandary E, Stovall M, Chetrit A et al (1988) Tumors of the brain and nervous system after radiotherapy in childhood. N Engl J Med 319:1033–1039PubMedGoogle Scholar
  21. 21.
    Rubinstein AB, Shalit MN, Cohen ML, Zandbank U, Reichenthal E (1984) Radiation-induced cerebral meningioma: a recognizable entity. J Neurosurg 61:966–971PubMedGoogle Scholar
  22. 22.
    Sadetzki S, Flint-Richter P, Ben-Tal T, Nass D (2002) Radiation-induced meningioma: a descriptive study of 253 cases. J Neurosurg 97:1078–1082PubMedCrossRefGoogle Scholar
  23. 23.
    Sadetzki S, Flint-Richter P, Starinsky S, Novikov I, Lerman Y, Goldman B et al (2005) Genotyping of patients with sporadic and radiation-associated meningiomas. Cancer Epidemiol Biomarkers Prev 14:969–976. doi:10.1158/1055-9965.EPI-04-0366 PubMedCrossRefGoogle Scholar
  24. 24.
    Sadetzki S, Modan B, Chetrit A, Freedman L (2000) An iatrogenic epidemic of benign meningioma. Am J Epidemiol 151:266–272PubMedGoogle Scholar
  25. 25.
    Shoshan Y, Chernova O, Jeun S, Somerville RP, Israel Z, Barnett GH et al (2000) Radiation-induced meningioma: a distinct molecular genetic pattern? J Neuropathol Exp Neurol 59:614–620PubMedGoogle Scholar
  26. 26.
    Yilmaz Z, Sahin FI, Atalay B, Ozen O, Caner H, Bavbek M et al (2005) Chromosome 1p36 and 22qter deletions in paraffin block sections of intracranial meningiomas. Pathol Oncol Res 11:224–228PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Kevin O. Lillehei
    • 1
  • Andrew M. Donson
    • 4
  • B. K. Kleinschmidt-DeMasters
    • 1
    • 2
    • 3
    • 5
  1. 1.Department of NeurosurgeryUniversity of Colorado at Denver Health Sciences CenterAuroraUSA
  2. 2.Department of PathologyUniversity of Colorado at Denver Health Sciences CenterAuroraUSA
  3. 3.Department of NeurologyUniversity of Colorado at Denver Health Sciences CenterAuroraUSA
  4. 4.Department of PediatricsUniversity of Colorado at Denver Health Sciences CenterAuroraUSA
  5. 5.Department of Surgical PathologyUCDHSCAuroraUSA

Personalised recommendations