UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2018 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

IDH-mutant, 1p/19q-codeleted oligodendrogliomas: Clinical features, pathology, and prognostic factors

Author
Martin van den Bent, MD, PhD
Section Editors
Patrick Y Wen, MD
Jay S Loeffler, MD
Deputy Editor
April F Eichler, MD, MPH

INTRODUCTION

There are significant differences between oligodendrogliomas and other glial tumors in pathology, molecular pathogenesis, and natural history. These differences have important prognostic implications, which can affect treatment.

As of the 2016 update of the World Health Organization (WHO) classification of central nervous system tumors, oligodendroglial tumors are now more narrowly defined by molecular diagnostics to include only those diffuse gliomas harboring both a mutation in isocitrate dehydrogenase type 1 (IDH1) or type 2 (IDH2) and codeletion of chromosomes 1p and 19q [1]. Mixed oligoastrocytoma no longer exists for fully characterized tumors, but the terminology is retained when referring to historically diagnosed tumors and for tumors with mixed oligoastrocytoma histology for which molecular testing is not available (ie, oligoastrocytoma not otherwise specified [NOS]). (See "Classification and pathologic diagnosis of gliomas".)

The clinical manifestations, classification, pathologic classification, and molecular prognostic factors associated with IDH-mutant, 1p/19q-codeleted oligodendroglioma and anaplastic oligodendroglioma will be reviewed here. The treatment of these tumors is discussed separately. (See "Management of low-grade glioma" and "Management of anaplastic oligodendroglial tumors".)

EPIDEMIOLOGY

Oligodendroglial tumors are rare tumors, constituting approximately 5 percent of all neuroepithelial tumors of the central nervous system [2]. Together, oligodendroglioma and anaplastic oligodendroglioma are one-tenth as common as glioblastoma, the most commonly occurring malignant primary brain tumor in adults. Approximately 1000 oligodendroglial tumors are diagnosed in the United States each year. (See "Incidence of primary brain tumors".)

CLINICAL FEATURES

Age of onset — Most oligodendrogliomas present in adults between 25 and 45 years of age. The median age at diagnosis is approximately 5 to 10 years older for World Health Organization (WHO) grade III (anaplastic) tumors compared with WHO grade II (low-grade) tumors. Oligodendrogliomas are occasionally diagnosed in teenagers and in adults over the age of 65 years.

                     
To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Dec 2017. | This topic last updated: Jan 10, 2018.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2018 UpToDate, Inc.
References
Top
  1. WHO Classification of Tumours of the Central Nervous System, 4th ed, Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (Eds), IARC, Lyon 2016.
  2. Ostrom QT, Gittleman H, Liao P, et al. CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2010-2014. Neuro Oncol 2017; 19:v1.
  3. Lassman AB, Iwamoto FM, Cloughesy TF, et al. International retrospective study of over 1000 adults with anaplastic oligodendroglial tumors. Neuro Oncol 2011; 13:649.
  4. Strickland BA, Cachia D, Jalali A, et al. Spinal Anaplastic Oligodendroglioma With Oligodendrogliomatosis: Molecular Markers and Management: Case Report. Neurosurgery 2016; 78:E466.
  5. Lee YY, Van Tassel P. Intracranial oligodendrogliomas: imaging findings in 35 untreated cases. AJR Am J Roentgenol 1989; 152:361.
  6. Jenkinson MD, du Plessis DG, Smith TS, et al. Histological growth patterns and genotype in oligodendroglial tumours: correlation with MRI features. Brain 2006; 129:1884.
  7. Megyesi JF, Kachur E, Lee DH, et al. Imaging correlates of molecular signatures in oligodendrogliomas. Clin Cancer Res 2004; 10:4303.
  8. Reifenberger G, Kros JM, Louis DN, Collins VN. Oligodendroglioma. In: World Health Organization Classification of Tumours, Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (Eds), IARC Press, Lyon 2007. p.53.
  9. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016; 131:803.
  10. Sahm F, Reuss D, Koelsche C, et al. Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma. Acta Neuropathol 2014; 128:551.
  11. Watanabe T, Nobusawa S, Kleihues P, Ohgaki H. IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 2009; 174:1149.
  12. Griffin CA, Burger P, Morsberger L, et al. Identification of der(1;19)(q10;p10) in five oligodendrogliomas suggests mechanism of concurrent 1p and 19q loss. J Neuropathol Exp Neurol 2006; 65:988.
  13. Jenkins RB, Blair H, Ballman KV, et al. A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res 2006; 66:9852.
  14. Fallon KB, Palmer CA, Roth KA, et al. Prognostic value of 1p, 19q, 9p, 10q, and EGFR-FISH analyses in recurrent oligodendrogliomas. J Neuropathol Exp Neurol 2004; 63:314.
  15. Bigner SH, Matthews MR, Rasheed BK, et al. Molecular genetic aspects of oligodendrogliomas including analysis by comparative genomic hybridization. Am J Pathol 1999; 155:375.
  16. Dubbink HJ, Atmodimedjo PN, Kros JM, et al. Molecular classification of anaplastic oligodendroglioma using next-generation sequencing: a report of the prospective randomized EORTC Brain Tumor Group 26951 phase III trial. Neuro Oncol 2016; 18:388.
  17. Reuss DE, Sahm F, Schrimpf D, et al. ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an "integrated" diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. Acta Neuropathol 2015; 129:133.
  18. 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.
  19. Buckner JC, Shaw EG, Pugh SL, et al. Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma. N Engl J Med 2016; 374:1344.
  20. van den Bent MJ, Brandes AA, Taphoorn MJ, 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; 31:344.
  21. Cairncross G, Wang M, Shaw E, et al. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol 2013; 31:337.
  22. Gorlia T, Delattre JY, Brandes AA, et al. New clinical, pathological and molecular prognostic models and calculators in patients with locally diagnosed anaplastic oligodendroglioma or oligoastrocytoma. A prognostic factor analysis of European Organisation for Research and Treatment of Cancer Brain Tumour Group Study 26951. Eur J Cancer 2013; 49:3477.
  23. Panageas KS, Reiner AS, Iwamoto FM, et al. Recursive partitioning analysis of prognostic variables in newly diagnosed anaplastic oligodendroglial tumors. Neuro Oncol 2014; 16:1541.
  24. Olar A, Wani KM, Alfaro-Munoz KD, et al. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. Acta Neuropathol 2015; 129:585.
  25. Suzuki H, Aoki K, Chiba K, et al. Mutational landscape and clonal architecture in grade II and III gliomas. Nat Genet 2015; 47:458.
  26. Figarella-Branger D, Mokhtari K, Dehais C, et al. Mitotic index, microvascular proliferation, and necrosis define 3 pathological subgroups of prognostic relevance among 1p/19q co-deleted anaplastic oligodendrogliomas. Neuro Oncol 2016; 18:888.
  27. Intergroup Radiation Therapy Oncology Group Trial 9402, Cairncross G, Berkey B, et al. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol 2006; 24:2707.
  28. van den Bent MJ, Carpentier AF, Brandes AA, et al. Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol 2006; 24:2715.
  29. van den Bent MJ. Long-term follow-up results of EORTC 26951: A randomized phase III study on adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors (AOD) (abstract #2). J Clin Oncol 2012; 30.
  30. Cairncross JG, Wang M, Shaw EG, et al. Chemotherapy plus radiotherapy versus RT alone for patients with anaplastic oligodendroglioma: Long-term results of the RTOG 9402 phase III study (abstract #2008b). J Clin Oncol 2012; 30:2008b.
  31. Pekmezci M, Rice T, Molinaro AM, et al. Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT. Acta Neuropathol 2017; 133:1001.
  32. Snuderl M, Eichler AF, Ligon KL, et al. Polysomy for chromosomes 1 and 19 predicts earlier recurrence in anaplastic oligodendrogliomas with concurrent 1p/19q loss. Clin Cancer Res 2009; 15:6430.
  33. Jiang H, Ren X, Zhang Z, et al. Polysomy of chromosomes 1 and 19: an underestimated prognostic factor in oligodendroglial tumors. J Neurooncol 2014; 120:131.
  34. Gleize V, Alentorn A, Connen de Kérillis L, et al. CIC inactivating mutations identify aggressive subset of 1p19q codeleted gliomas. Ann Neurol 2015; 78:355.
  35. van den Bent MJ, Dubbink HJ, Marie Y, et al. IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clin Cancer Res 2010; 16:1597.
  36. Cairncross JG, Wang M, Jenkins RB, et al. Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH. J Clin Oncol 2014; 32:783.
  37. Clark O, Yen K, Mellinghoff IK. Molecular Pathways: Isocitrate Dehydrogenase Mutations in Cancer. Clin Cancer Res 2016; 22:1837.
  38. van den Bent MJ, Erdem-Eraslan L, Idbaih A, et al. MGMT-STP27 methylation status as predictive marker for response to PCV in anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC study 26951. Clin Cancer Res 2013; 19:5513.
  39. Watanabe T, Nakamura M, Kros JM, et al. Phenotype versus genotype correlation in oligodendrogliomas and low-grade diffuse astrocytomas. Acta Neuropathol 2002; 103:267.