Advertisement

Classification of Tumours of the Central Nervous System

  • Luca BerteroEmail author
  • Paola Cassoni
Chapter

Abstract

CNS tumours include both primary and secondary neoplasms. The diagnostic criteria of primary CNS tumours have been significantly updated by the latest WHO classification (Fourth Edition, Revised), published in 2016. Molecular parameters, which were previously considered as supplementary information, are now used to define CNS tumours by employing an integrated histological–molecular classification. This novel approach allowed to define specific entities which are more consistent in terms of phenotypical, genotypical and clinical characteristics, compared to the previous criteria which were based on histopathological findings alone. Diffuse gliomas are a paradigmatic example of this novel approach: the newly introduced classification, which is mainly based on two molecular alterations (IDH1/IDH2 mutation and 1p/19q codeletion), allows to recognize specific prognostically relevant entities, despite possible morphological ambiguities. These changes will hopefully help provide the best case possible to patients.

References

  1. 1.
    Ostrom QT, Gittleman H, Xu J, Kromer C, Wolinsky Y, Kruchko C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro-Oncology. 2016;18(Suppl_5):v1–v75.  https://doi.org/10.1093/neuonc/now207.CrossRefPubMedGoogle Scholar
  2. 2.
    Louis DN. International Agency for Research on Cancer. WHO classification of tumours of the central nervous system. Revised 4th ed. World Health Organization classification of tumours. Lyon: International Agency For Research On Cancer; 2016.Google Scholar
  3. 3.
    Reuss DE, Mamatjan Y, Schrimpf D, Capper D, Hovestadt V, Kratz A, et al. IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO. Acta Neuropathol. 2015;129(6):867–73.  https://doi.org/10.1007/s00401-015-1438-8.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Hubner JM, Kool M, Pfister SM, Pajtler KW. Epidemiology, molecular classification and WHO grading of ependymoma. J Neurosurg Sci. 2017;  https://doi.org/10.23736/S0390-5616.17.04152-2.
  5. 5.
    Waitkus MS, Diplas BH, Yan H. Isocitrate dehydrogenase mutations in gliomas. Neuro-Oncology. 2016;18(1):16–26.  https://doi.org/10.1093/neuonc/nov136.CrossRefPubMedGoogle Scholar
  6. 6.
    Walsh KM, Wiencke JK, Lachance DH, Wiemels JL, Molinaro AM, Eckel-Passow JE, et al. Telomere maintenance and the etiology of adult glioma. Neuro-Oncology. 2015;17(11):1445–52.  https://doi.org/10.1093/neuonc/nov082.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, et al. The somatic genomic landscape of glioblastoma. Cell. 2013;155(2):462–77.  https://doi.org/10.1016/j.cell.2013.09.034.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    LeBlanc VG, Marra MA. DNA methylation in adult diffuse gliomas. Brief Funct Genomics. 2016;  https://doi.org/10.1093/bfgp/elw019.
  9. 9.
    Reuss DE, Kratz A, Sahm F, Capper D, Schrimpf D, Koelsche C, et al. Adult IDH wild type astrocytomas biologically and clinically resolve into other tumor entities. Acta Neuropathol. 2015;130(3):407–17.  https://doi.org/10.1007/s00401-015-1454-8.CrossRefPubMedGoogle Scholar
  10. 10.
    van den Bent MJ, Brandes AA, Taphoorn MJ, Kros JM, Kouwenhoven MC, Delattre JY, et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2013;31(3):344–50.  https://doi.org/10.1200/JCO.2012.43.2229.CrossRefPubMedGoogle Scholar
  11. 11.
    Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J, et al. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2013;31(3):337–43.  https://doi.org/10.1200/JCO.2012.43.2674.CrossRefPubMedGoogle Scholar
  12. 12.
    Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459–66.  https://doi.org/10.1016/S1470-2045(09)70025-7.CrossRefPubMedGoogle Scholar
  13. 13.
    Hartmann C, Hentschel B, Simon M, Westphal M, Schackert G, Tonn JC, et al. Long-term survival in primary glioblastoma with versus without isocitrate dehydrogenase mutations. Clin Cancer Res. 2013;19(18):5146–57.  https://doi.org/10.1158/1078-0432.CCR-13-0017.CrossRefPubMedGoogle Scholar
  14. 14.
    Rodriguez FJ, Scheithauer BW, Burger PC, Jenkins S, Giannini C. Anaplasia in pilocytic astrocytoma predicts aggressive behavior. Am J Surg Pathol. 2010;34(2):147–60.  https://doi.org/10.1097/PAS.0b013e3181c75238.CrossRefPubMedGoogle Scholar
  15. 15.
    Fernandez C, Figarella-Branger D, Girard N, Bouvier-Labit C, Gouvernet J, Paz Paredes A, et al. Pilocytic astrocytomas in children: prognostic factors--a retrospective study of 80 cases. Neurosurgery. 2003;53(3):544–53. discussion 54–5CrossRefGoogle Scholar
  16. 16.
    Ida CM, Rodriguez FJ, Burger PC, Caron AA, Jenkins SM, Spears GM, et al. Pleomorphic Xanthoastrocytoma: natural history and long-term follow-up. Brain Pathol. 2015;25(5):575–86.  https://doi.org/10.1111/bpa.12217.CrossRefPubMedGoogle Scholar
  17. 17.
    de Ribaupierre S, Dorfmuller G, Bulteau C, Fohlen M, Pinard JM, Chiron C, et al. Subependymal giant-cell astrocytomas in pediatric tuberous sclerosis disease: when should we operate? Neurosurgery. 2007;60(1):83–9.; discussion 9–90.  https://doi.org/10.1227/01.NEU.0000249216.19591.5D.CrossRefPubMedGoogle Scholar
  18. 18.
    Pajtler KW, Witt H, Sill M, Jones DT, Hovestadt V, Kratochwil F, et al. Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell. 2015;27(5):728–43.  https://doi.org/10.1016/j.ccell.2015.04.002.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, et al. C11orf95-RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature. 2014;506(7489):451–5.  https://doi.org/10.1038/nature13109.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ellison DW, Kocak M, Figarella-Branger D, Felice G, Catherine G, Pietsch T, et al. Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. J Negat Results Biomed. 2011;10:7.  https://doi.org/10.1186/1477-5751-10-7.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Chappe C, Padovani L, Scavarda D, Forest F, Nanni-Metellus I, Loundou A, et al. Dysembryoplastic neuroepithelial tumors share with pleomorphic xanthoastrocytomas and gangliogliomas BRAF(V600E) mutation and expression. Brain Pathol. 2013;23(5):574–83.  https://doi.org/10.1111/bpa.12048.CrossRefPubMedGoogle Scholar
  22. 22.
    Dougherty MJ, Santi M, Brose MS, Ma C, Resnick AC, Sievert AJ, et al. Activating mutations in BRAF characterize a spectrum of pediatric low-grade gliomas. Neuro-Oncology. 2010;12(7):621–30.  https://doi.org/10.1093/neuonc/noq007.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Schindler G, Capper D, Meyer J, Janzarik W, Omran H, Herold-Mende C, et al. Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol. 2011;121(3):397–405.  https://doi.org/10.1007/s00401-011-0802-6.CrossRefPubMedGoogle Scholar
  24. 24.
    Luyken C, Blumcke I, Fimmers R, Urbach H, Wiestler OD, Schramm J. Supratentorial gangliogliomas: histopathologic grading and tumor recurrence in 184 patients with a median follow-up of 8 years. Cancer. 2004;101(1):146–55.  https://doi.org/10.1002/cncr.20332.CrossRefPubMedGoogle Scholar
  25. 25.
    Majores M, von Lehe M, Fassunke J, Schramm J, Becker AJ, Simon M. Tumor recurrence and malignant progression of gangliogliomas. Cancer. 2008;113(12):3355–63.  https://doi.org/10.1002/cncr.23965.CrossRefPubMedGoogle Scholar
  26. 26.
    Karremann M, Pietsch T, Janssen G, Kramm CM, Wolff JE. Anaplastic ganglioglioma in children. J Neuro-Oncol. 2009;92(2):157–63.  https://doi.org/10.1007/s11060-008-9747-6.CrossRefGoogle Scholar
  27. 27.
    Kool M, Korshunov A, Remke M, Jones DT, Schlanstein M, Northcott PA, et al. Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, group 3, and group 4 medulloblastomas. Acta Neuropathol. 2012;123(4):473–84.  https://doi.org/10.1007/s00401-012-0958-8.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Zhukova N, Ramaswamy V, Remke M, Pfaff E, Shih DJ, Martin DC, et al. Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma. J Clin Oncol. 2013;31(23):2927–35.  https://doi.org/10.1200/JCO.2012.48.5052.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Ellison DW, Dalton J, Kocak M, Nicholson SL, Fraga C, Neale G, et al. Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroups. Acta Neuropathol. 2011;121(3):381–96.  https://doi.org/10.1007/s00401-011-0800-8.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Korshunov A, Remke M, Gessi M, Ryzhova M, Hielscher T, Witt H, et al. Focal genomic amplification at 19q13.42 comprises a powerful diagnostic marker for embryonal tumors with ependymoblastic rosettes. Acta Neuropathol. 2010;120(2):253–60.  https://doi.org/10.1007/s00401-010-0688-8.CrossRefPubMedGoogle Scholar
  31. 31.
    Nobusawa S, Yokoo H, Hirato J, Kakita A, Takahashi H, Sugino T, et al. Analysis of chromosome 19q13.42 amplification in embryonal brain tumors with ependymoblastic multilayered rosettes. Brain Pathol. 2012;22(5):689–97.  https://doi.org/10.1111/j.1750-3639.2012.00574.x.CrossRefPubMedGoogle Scholar
  32. 32.
    Torchia J, Picard D, Lafay-Cousin L, Hawkins CE, Kim SK, Letourneau L, et al. Molecular subgroups of atypical teratoid rhabdoid tumours in children: an integrated genomic and clinicopathological analysis. Lancet Oncol. 2015;16(5):569–82.  https://doi.org/10.1016/S1470-2045(15)70114-2.CrossRefPubMedGoogle Scholar
  33. 33.
    Johann PD, Erkek S, Zapatka M, Kerl K, Buchhalter I, Hovestadt V, et al. Atypical teratoid/rhabdoid tumors are comprised of three epigenetic subgroups with distinct enhancer landscapes. Cancer Cell. 2016;29(3):379–93.  https://doi.org/10.1016/j.ccell.2016.02.001.CrossRefPubMedGoogle Scholar
  34. 34.
    Louis DN, Aldape K, Brat DJ, Capper D, Ellison DW, Hawkins C, et al. Announcing cIMPACT-NOW: the consortium to inform molecular and practical approaches to CNS tumor taxonomy. Acta Neuropathol. 2017;133(1):1–3.  https://doi.org/10.1007/s00401-016-1646-x.CrossRefPubMedGoogle Scholar
  35. 35.
    Louis DN, Aldape K, Brat DJ, Capper D, Ellison DW, Hawkins C, et al. cIMPACT-NOW (the consortium to inform molecular and practical approaches to CNS tumor taxonomy): a new initiative in advancing nervous system tumor classification. Brain Pathol. 2017;27(6):851–2.  https://doi.org/10.1111/bpa.12457.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Pathology, Department of Medical SciencesUniversity of TurinTurinItaly

Personalised recommendations