Skip to main content
SpringerLink
Log in

Classification of Gliomas

  • Chapter
  • First Online:
Emerging Concepts in Neuro-Oncology

  • 1251 Accesses

Abstract

For almost a century, histopathological evaluation of gliomas has provided the gold standard for classification of these neoplasms. Indeed, the (neuro)pathologist is able to render an unequivocal diagnosis of glioma in most specimens and to indicate low- or high-grade malignant character of the lesion. It is increasingly clear, however, that the traditional histopathological diagnosis lacks the robustness and specificity that is needed for more tailored treatment of glioma patients. Even for the experienced neuropathologist, at least three factors may hamper reaching an unequivocal histopathological diagnosis on glioma tissue: (a) tissue quantity and quality, (b) lack of unequivocal histopathological criteria, and (c) incomplete representation of biology by morphology. Smart integration of information on the underlying molecular aberrations in the diagnosis of gliomas will undoubtedly result in a more sophisticated classification of these tumors. Modern neuropathology is thus rapidly moving toward a combined morphological and molecular approach, the challenge being to implement this approach in an affordable way that optimally serves the individual patients suffering from these neoplasms.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Fuller GN, Scheithauer BW. The 2007 revised World Health Organization (WHO) classification of tumours of the central nervous system: newly codified entities. Brain Pathol. 2007;17:304–7.

    Article  PubMed  Google Scholar 

  2. CBTRUS. Central Brain Tumor Registry of the United States, 2010. www.cbtrus.org.

  3. Kohler BA, Ward E, McCarthy BJ, Schymura MJ, Ries LA, Eheman C, Jemal A, Anderson RN, Ajani UA, Edwards BK. Annual report to the nation on the status of cancer, 1975–2007, featuring tumors of the brain and other nervous system. J Natl Cancer Inst. 2011;103:714–36.

    Article  PubMed  Google Scholar 

  4. Burnet NG, Jefferies SJ, Benson RJ, Hunt DP, Treasure FP. Years of life lost (YLL) from cancer is an important measure of population burden – and should be considered when allocating research funds. Br J Cancer. 2005;92:241–5.

    PubMed  CAS  Google Scholar 

  5. Wesseling P, Kros JM, Jeuken JWM. The pathological diagnosis of diffuse gliomas: towards a smart synthesis of microscopic and molecular information in a multidisciplinary context. Diagn Histopathol. 2011;17:486–94.

    Article  Google Scholar 

  6. Ohgaki H, Kleihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol. 2005;64:479–89.

    PubMed  CAS  Google Scholar 

  7. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. WHO classification of tumours of the central nervous system. 3rd ed. Lyon: IARC Press; 2007.

    Google Scholar 

  8. Burger PC, Scheithauer BW. Tumors of the central nervous system, vol. 4. 7th ed. Washington: AFIP Atlas of tumor pathology; 2007.

    Google Scholar 

  9. Perry A, Brat DJ. Practical surgical neuropathology. Philadelphia: Churchill Livingstone; 2010.

    Google Scholar 

  10. Bailey PC, Cushing H. A classification of the tumors of the glioma group on a histogenetic basis with a correlated study of prognosis. Philadelphia: J.B. Lippincott Co; 1926.

    Google Scholar 

  11. Stiles CD, Rowitch DH. Glioma stem cells: a midterm exam. Neuron. 2008;58:832–46.

    Article  PubMed  CAS  Google Scholar 

  12. Venere M, Fine HA, Dirks PB, Rich JN. Cancer stem cells in gliomas: identifying and understanding the apex cell in cancer’s hierarchy. Glia. 2011;59:1148–54.

    Article  PubMed  Google Scholar 

  13. Kernohan JW, Mabon RF, Svien HJ, Adson AW. A simplified classification of the gliomas. Proc Staff Meet Mayo Clin. 1949;24:71–5.

    PubMed  CAS  Google Scholar 

  14. Kros JM. Grading of gliomas: the road from eminence to evidence. J Neuropathol Exp Neurol. 2011;70:101–9.

    Article  PubMed  Google Scholar 

  15. Scheithauer BW. Development of the WHO classification of tumors of the central nervous system: a historical perspective. Brain Pathol. 2009;19:551–64.

    Article  PubMed  Google Scholar 

  16. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109.

    Article  PubMed  Google Scholar 

  17. Scherer HJ. Structural development in gliomas. Am J Cancer. 1938;34:333–51.

    Google Scholar 

  18. Claes A, Idema AJ, Wesseling P. Diffuse glioma growth: a guerilla war. Acta Neuropathol. 2007;114:443–58.

    Article  PubMed  Google Scholar 

  19. Dunbar E, Yachnis AT. Glioma diagnosis: immunohistochemistry and beyond. Adv Anat Pathol. 2010;17:187–201.

    Article  PubMed  Google Scholar 

  20. Ducray F, Mokhtari K, Crinière E, Idbaih A, Marie Y, Dehais C, Paris S, Carpentier C, Dieme MJ, Adam C, Hoang-Xuan K, Duyckaerts C, Delattre JY, Sanson M. Diagnostic and prognostic value of alpha internexin expression in a series of 409 gliomas. Eur J Cancer. 2011;47:802–8.

    Article  PubMed  CAS  Google Scholar 

  21. Durand K, Guillaudeau A, Pommepuy I, Mesturoux L, Chaunavel A, Gadeaud E, Porcheron M, Moreau JJ, Labrousse F. Alpha-internexin expression in gliomas: relationship with histological type and 1p, 19q, 10p and 10q status. J Clin Pathol. 2011;64:793–801.

    Article  PubMed  CAS  Google Scholar 

  22. Ohgaki H, Kleihues P. Genetic pathways to primary and secondary glioblastoma. Am J Pathol. 2007;170:1445–53.

    Article  PubMed  CAS  Google Scholar 

  23. Scheithauer BW, Fuller GN, VandenBerg SR. The 2007 WHO classification of tumors of the nervous system: controversies in surgical neuropathology. Brain Pathol. 2008;18:307–16.

    Article  PubMed  Google Scholar 

  24. Rodriguez FJ, Scheithauer BW, Burger PC, Jenkins S, Giannini C. Anaplasia in pilocytic astrocytoma predicts aggressive behavior. Am J Surg Pathol. 2010;34:147–60.

    Article  PubMed  Google Scholar 

  25. Burger PC, Heinz ER, Shibata T, Kleihues P. Topographic anatomy and CT correlations in the untreated glioblastoma multiforme. J Neurosurg. 1988;68:698–704.

    Article  PubMed  CAS  Google Scholar 

  26. Burger PC, Kleihues P. Cytologic composition of the untreated glioblastoma with implications for evaluation of needle biopsies. Cancer. 1989;63:2014–23.

    Article  PubMed  CAS  Google Scholar 

  27. Groenen PJ, Blokx WA, Diepenbroek C, Burgers L, Visinoni F, Wesseling P, van Krieken JH. Preparing pathology for personalized medicine: possibilities for improvement of the pre-analytical phase. Histopathology. 2011;59:1–7.

    Article  PubMed  Google Scholar 

  28. Perry A, Scheithauer BW, Macaulay RJ, Raffel C, Roth KA, Kros JM. Oligodendrogliomas with neurocytic differentiation. A report of 4 cases with diagnostic and histogenetic implications. J Neuropathol Exp Neurol. 2002;61:947–55.

    PubMed  Google Scholar 

  29. Wesseling P, Schlingemann RO, Rietveld FJ, Link M, Burger PC, Ruiter DJ. Early and extensive contribution of pericytes/vascular smooth muscle cells to microvascular proliferation in glioblastoma multiforme: an immuno-light and immuno-electron microscopic study. J Neuropathol Exp Neurol. 1995;54:304–10.

    Article  PubMed  CAS  Google Scholar 

  30. Coons SW, Johnson PC, Scheithauer BW, Yates AJ, Pearl DK. Improving diagnostic accuracy and interobserver concordance in the classification and grading of primary gliomas. Cancer. 1997;79:1381–93.

    Article  PubMed  CAS  Google Scholar 

  31. Giannini C, Scheithauer BW, Weaver AL, Burger PC, Kros JM, Mork S, Graeber MB, Bauserman S, Buckner JC, Burton J, Riepe R, Tazelaar HD, Nascimento AG, Crotty T, Keeney GL, Pernicone P, Altermatt H. Oligodendrogliomas: reproducibility and prognostic value of histologic diagnosis and grading. J Neuropathol Exp Neurol. 2001;60:248–62.

    PubMed  CAS  Google Scholar 

  32. Kros JM, Gorlia T, Kouwenhoven MC, Zheng PP, Collins VP, Figarella-Branger D, Giangaspero F, Giannini C, Mokhtari K, Mørk SJ, Paetau A, Reifenberger G, van den Bent MJ. Panel review of anaplastic oligodendroglioma from European Organization For Research and Treatment of Cancer Trial 26951: assessment of consensus in diagnosis, influence of 1p/19q loss, and correlations with outcome. J Neuropathol Exp Neurol. 2007;66:545–51.

    Article  PubMed  CAS  Google Scholar 

  33. van den Bent MJ. Interobserver variation of the histopathological diagnosis in clinical trials on glioma: a clinician’s perspective. Acta Neuropathol. 2010;120:297–304.

    Article  PubMed  Google Scholar 

  34. Tabatabai G, Stupp R, van den Bent MJ, Hegi ME, Tonn JC, Wick W, Weller M. Molecular diagnostics of gliomas: the clinical perspective. Acta Neuropathol. 2010;120:585–92.

    Article  PubMed  CAS  Google Scholar 

  35. Mellinghoff IK, Lassman AB, Wen PY. Signal transduction inhibitors and antiangiogenic therapies for malignant glioma. Glia. 2011;59:1205–12.

    Article  PubMed  Google Scholar 

  36. Yip S, Iafrate AJ, Louis DN. Molecular diagnostic testing in malignant gliomas: a practical update on predictive markers. J Neuropathol Exp Neurol. 2008;67:1–15.

    Article  PubMed  CAS  Google Scholar 

  37. Riemenschneider MJ, Jeuken JW, Wesseling P, Reifenberger G. Molecular diagnostics of gliomas: state of the art. Acta Neuropathol. 2010;120:567–84.

    Article  PubMed  CAS  Google Scholar 

  38. von Deimling A, Korshunov A, Hartmann C. The next generation of glioma biomarkers: MGMT methylation, BRAF fusions and IDH1 mutations. Brain Pathol. 2011;21:74–87.

    Article  Google Scholar 

  39. Reifenberger J, Reifenberger G, Liu L, James CD, Wechsler W, Collins VP. Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. Am J Pathol. 1994;145:1175–90.

    PubMed  CAS  Google Scholar 

  40. Aldape K, Burger PC, Perry A. Clinicopathologic aspects of 1p/19q loss and the diagnosis of oligodendroglioma. Arch Pathol Lab Med. 2007;131:242–251.

    PubMed  CAS  Google Scholar 

  41. Idbaih A, Marie Y, Pierron G, Brennetot C, Hoang-Xuan K, Kujas M, Mokhtari K, Sanson M, Lejeune J, Aurias A, Delattre O, Delattre JY. Two types of chromosome 1p losses with opposite significance in gliomas. Ann Neurol. 2005;58:483–7.

    Article  PubMed  CAS  Google Scholar 

  42. Jeuken JW, Sijben A, Bleeker FE, Boots-Sprenger SH, Rijntjes J, Gijtenbeek JM, Mueller W, Wesseling P. The nature and timing of specific copy number changes in the course of molecular progression in diffuse gliomas: further elucidation of their genetic “life story”. Brain Pathol. 2011;21:308–20.

    Article  PubMed  Google Scholar 

  43. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz Jr LA, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu E, Kinzler KW. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321:1807–12.

    Article  PubMed  CAS  Google Scholar 

  44. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360:765–73.

    Article  PubMed  CAS  Google Scholar 

  45. Hartmann C, Hentschel B, Wick W, Capper D, Felsberg J, Simon M, Westphal M, Schackert G, Meyermann R, Pietsch T, Reifenberger G, Weller M, Loeffler M, von Deimling A. Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. Acta Neuropathol. 2010;120:707–18.

    Article  PubMed  Google Scholar 

  46. Capper D, Weissert S, Balss J, Habel A, Meyer J, Jäger D, Ackermann U, Tessmer C, Korshunov A, Zentgraf H, Hartmann C, von Deimling A. Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol. 2010;20:245–54.

    Article  PubMed  CAS  Google Scholar 

  47. Capper D, Reuss D, Schittenhelm J, Hartmann C, Bremer J, Sahm F, Harter PN, Jeibmann A, von Deimling A. Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology. Acta Neuropathol. 2011;121:241–52.

    Article  PubMed  Google Scholar 

  48. Camelo-Piragua S, Jansen M, Ganguly A, Kim JC, Cosper AK, Dias-Santagata D, Nutt CL, Iafrate AJ, Louis DN. A sensitive and specific diagnostic panel to distinguish diffuse astrocytoma from astrocytosis: chromosome 7 gain with mutant isocitrate dehydrogenase 1 and p53. J Neuropathol Exp Neurol. 2011;70:110–5.

    Article  PubMed  CAS  Google Scholar 

  49. Jones DT, Mulholland SA, Pearson DM, Malley DS, Openshaw SW, Lambert SR, Liu L, Bäcklund LM, Ichimura K, Collins VP. Adult grade II diffuse astrocytomas are genetically distinct from and more aggressive than their paediatric counterparts. Acta Neuropathol. 2011;121:753–61.

    Article  PubMed  Google Scholar 

  50. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352:997–1003.

    Article  PubMed  CAS  Google Scholar 

  51. Weller M, Stupp R, Reifenberger G, Brandes AA, van den Bent MJ, Wick W, Hegi ME. MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nat Rev Neurol. 2010;6:39–51.

    Article  PubMed  CAS  Google Scholar 

  52. Olson RA, Brastianos PK, Palma DA. Prognostic and predictive value of epigenetic silencing of MGMT in patients with high grade gliomas: a systematic review and meta-analysis. J Neurooncol. 2011;105:325–335.

    Article  PubMed  Google Scholar 

  53. Jeuken J, Sijben A, Alenda C, Rijntjes J, Dekkers M, Boots-Sprenger S, McLendon R, Wesseling P. Robust detection of EGFR copy number changes and EGFR variant III: technical aspects and relevance for glioma diagnostics. Brain Pathol. 2009;19:661–71.

    Article  PubMed  Google Scholar 

  54. Choi BD, Archer GE, Mitchell DA, Heimberger AB, McLendon RE, Bigner DD, Sampson JH. EGFRvIII-targeted vaccination therapy of malignant glioma. Brain Pathol. 2009;19:713–23.

    Article  PubMed  CAS  Google Scholar 

  55. Cin H, Meyer C, Herr R, Janzarik WG, Lambert S, Jones DT, Jacob K, Benner A, Witt H, Remke M, Bender S, Falkenstein F, Van Anh TN, Olbrich H, von Deimling A, Pekrun A, Kulozik AE, Gnekow A, Scheurlen W, Witt O, Omran H, Jabado N, Collins VP, Brummer T, Marschalek R, Lichter P, Korshunov A, Pfister SM. Oncogenic FAM131B-BRAF fusion resulting from 7q34 deletion comprises an alternative mechanism of MAPK pathway activation in pilocytic astrocytoma. Acta Neuropathol. 2011;121:763–74.

    Article  PubMed  CAS  Google Scholar 

  56. Korshunov A, Meyer J, Capper D, Christians A, Remke M, Witt H, Pfister S, von Deimling A, Hartmann C. Combined molecular analysis of BRAF and IDH1 distinguishes pilocytic astrocytoma from diffuse astrocytoma. Acta Neuropathol. 2009;118:401–5.

    Article  PubMed  CAS  Google Scholar 

  57. Roerig P, Nessling M, Radlwimmer B, Joos S, Wrobel G, Schwaenen C, Reifenberger G, Lichter P. Molecular classification of human gliomas using matrix-based comparative genomic hybridization. Int J Cancer. 2005;117:95–103.

    Article  PubMed  CAS  Google Scholar 

  58. Nutt CL, Mani DR, Betensky RA, Tamayo P, Cairncross JG, Ladd C, Pohl U, Hartmann C, McLaughlin ME, Batchelor TT, Black PM, von Deimling A, Pomeroy SL, Golub TR, Louis DN. Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res. 2003;63:1602–7.

    PubMed  CAS  Google Scholar 

  59. Gravendeel LA, Kouwenhoven MC, Gevaert O, de Rooi JJ, Stubbs AP, Duijm JE, Daemen A, Bleeker FE, Bralten LB, Kloosterhof NK, De Moor B, Eilers PH, van der Spek PJ, Kros JM, Sillevis Smitt PA, van den Bent MJ, French PJ. Intrinsic gene expression profiles of gliomas are a better predictor of survival than histology. Cancer Res. 2009;69:9065–72.

    Article  PubMed  CAS  Google Scholar 

  60. Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, Misra A, Nigro JM, Colman H, Soroceanu L, Williams PM, Modrusan Z, Feuerstein BG, Aldape K. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell. 2006;9:157–73.

    Article  PubMed  CAS  Google Scholar 

  61. Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O’Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17:98–110.

    Article  PubMed  CAS  Google Scholar 

  62. Huse JT, Phillips HS, Brennan CW. Molecular subclassification of diffuse gliomas: seeing order in the chaos. Glia. 2011;59:1190–9.

    Article  PubMed  Google Scholar 

  63. TCGA, The Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455:1061–8.

    Article  Google Scholar 

  64. Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP, Verhaak RG, Hoadley KA, Hayes DN, Perou CM, Schmidt HK, Ding L, Wilson RK, Van Den Berg D, Shen H, Bengtsson H, Neuvial P, Cope LM, Buckley J, Herman JG, Baylin SB, Laird PW, Aldape K. Identification of a CpG Island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010;17:510–22.

    Article  PubMed  CAS  Google Scholar 

  65. Faehndrich J, Weidauer S, Pilatus U, Oszvald A, Zanella FE, Hattingen E. Neuroradiological viewpoint on the diagnostics of space-occupying brain lesions. Clin Neuroradiol. 2011;21:123–39.

    Article  PubMed  CAS  Google Scholar 

  66. Chen W, Silverman DH. Advances in evaluation of primary brain tumors. Semin Nucl Med. 2008;38:240–50.

    Article  PubMed  Google Scholar 

  67. Colman H, Zhang L, Sulman EP, McDonald JM, Shooshtari NL, Rivera A, Popoff S, Nutt CL, Louis DN, Cairncross JG, Gilbert MR, Phillips HS, Mehta MP, Chakravarti A, Pelloski CE, Bhat K, Feuerstein BG, Jenkins RB. Aldape K A multigene predictor of outcome in glioblastoma. Neuro Oncol. 2010;12:49–57.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    Pieter Wesseling M.D., Ph.D.

  2. Department of Pathology, Canisius Wilhelmina Hospital Nijmegen, Nijmegen, The Netherlands

    Pieter Wesseling M.D., Ph.D.

  3. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands

    Pieter Wesseling M.D., Ph.D.

Authors
  1. Pieter Wesseling M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pieter Wesseling M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. , Department of Clinical Neurosciences, University of Cambridge, Hills Road, Cambridge, CB2 0QQ, United Kingdom

    Colin Watts

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag London

About this chapter

Cite this chapter

Wesseling, P. (2013). Classification of Gliomas. In: Watts, C. (eds) Emerging Concepts in Neuro-Oncology. Springer, London. https://doi.org/10.1007/978-0-85729-458-6_1

Download citation

  • DOI: https://doi.org/10.1007/978-0-85729-458-6_1

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-0-85729-457-9

  • Online ISBN: 978-0-85729-458-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation