Oligodendroglioma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2]Sujit Routray, M.D. [3]

Overview

Oligodendroglioma arises from the tripotential glial precursor cells and not from the bipotential oligodendrocytes. Genes associated with the pathogenesis of oligodendroglioma include t[1;19][q10;p10], NJDS, IDH1, IDH2, CIC, FUBP1, p53, Leu-7, TCF-12, MGMT, TP73, EGFR, and PTEN. On gross pathology, oligodendroglioma is characterized by a well-circumscribed, gelatinous, calcified, gray mass which may expand a gyrus and remodel the skull. On microscopic histopathological analysis, oligodendroglioma is characterized by diffuse growth pattern of highly cellular lesion with rounded nucleus with atypia and perinuclear halo resembling fried eggs, distinct cell borders, clear cytoplasm, and abundant calcification. Oligodendroglioma is demonstrated by positivity to tumor markers such as MAP2, GFAP, S-100, EMA, IDH1-R132H, ATRX, Ki-67, NSE, Synaptophysin, OLIG1, and OLIG2.

Pathophysiology

Pathogenesis

Genetics

  • There is a strong association of oligodendroglioma with expression of receptor tyrosine kinases that activate PI3K/AKT, RAS/MAP, and PLC/PKC pathways[14]

Gross Pathology

  • On gross pathology, oligodendroglioma is characterized by a well-circumscribed, gelatinous, gray mass which may expand a gyrus and remodel the skull[46]
  • Other characteristic gross pathological features associated with oligodendroglioma include:[46][14]
  • Common intracranial sites associated with oligodendroglioma include:[47]

Microscopic Pathology

On microscopic histopathological analysis, oligodendroglioma is characterized by:[14][48][49][50][51]

  • Diffusely growing, infiltrative tumor
  • Moderate cellularity
  • Highly cellular lesion composed of typically monomorphic cells resembling fried eggs with:
    • Round nucleus - key feature
    • Distinct cell borders
    • Moderate-to-marked nuclear atypia with speckled "salt-and-pepper" chromatin pattern
    • Inconspicuous nucleoli
    • Clear cytoplasm (artifactual retraction of the cytoplasm on routinely processed formalin fixed, paraffin embedded material, leading to the characteristic "fried egg" appearance)
      • Some oligodendrogliomas have eosinophilic cytoplasm with focal perinuclear clearing
    • Dense network of acutely fine branched capillary sized vessels -classically referred to as a "chicken-wire" like appearance/pattern[52]
      • Abundant and delicate appearing; may vaguely resemble a paraganglioma at low power
  • Small punctate Calcifications, particularly along the blood vessels is a striking feature (but not a specific finding)
  • Perifocal edema - rare
  • Few tumors may exhibit eosinophilic granular bodies
  • Some tumors may show a spongioblastoma-like growth pattern
  • Tumor cells may form following secondary structures in the surrounding infiltrated brain parenchyma:
    • Perineuronal satellitosis
    • Subpial accumulation
    • Perivascular distribution (less common)
  • Microgemistocytic appearance of tumor cells with a rounded belly of eccentric GFAP+ eosinophilic cytoplasm (maybe present)[53]
  • A predominant fibrillar astrocytic phenotype is compatible with the diagnosis when following appropriate molecular findings are present:[15]
    • IDH mutation
    • 1p/19q codeletion

Microscopic histopathological findings in anaplastic oligodendroglioma

On microscopic histopathological analysis, anaplastic oligodendroglioma, IDH mutant and 1p/19q codeleted, is characterized by:[48]

Immunohistochemistry

Oligodendroglioma is demonstrated by positivity to tumor markers such as:[56][57][14]

Oligodendroglioma stains negative for:

  • p53 (rare weakly positive cells can be seen)
  • Keratins (although cocktails may show cross reactivity)

References

  1. ↑ General features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma#cite_note-1
  2. ↑ Suzuki H, Aoki K, Chiba K, Sato Y, Shiozawa Y, Shiraishi Y; et al. (2015). "Mutational landscape and clonal architecture in grade II and III gliomas". Nat Genet. 47 (5): 458–68. doi:10.1038/ng.3273. PMID 25848751.
  3. ↑ Leeper HE, Caron AA, Decker PA, Jenkins RB, Lachance DH, Giannini C (2015). "IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas". Oncotarget. 6 (30): 30295–305. doi:10.18632/oncotarget.4497. PMC 4745799. PMID 26210286.
  4. ↑ Sabha N, Knobbe CB, Maganti M, Al Omar S, Bernstein M, Cairns R; et al. (2014). "Analysis of IDH mutation, 1p/19q deletion, and PTEN loss delineates prognosis in clinical low-grade diffuse gliomas". Neuro Oncol. 16 (7): 914–23. doi:10.1093/neuonc/not299. PMC 4057130. PMID 24470545.
  5. ↑ Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B; et al. (2013). "Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas". Nat Genet. 45 (6): 602–12. doi:10.1038/ng.2611. PMC 3727232. PMID 23583981.
  6. ↑ Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y; et al. (2014). "The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma". Nat Genet. 46 (5): 444–450. doi:10.1038/ng.2938. PMC 4056452. PMID 24705251.
  7. ↑ Molecular genetics of oligodendroglioma. https://en.wikipedia.org/wiki/Oligodendroglioma
  8. ↑ Bettegowda C, Agrawal N, Jiao Y, Sausen M, Wood LD, Hruban RH; et al. (2011). "Mutations in CIC and FUBP1 contribute to human oligodendroglioma". Science. 333 (6048): 1453–5. doi:10.1126/science.1210557. PMC 3170506. PMID 21817013.
  9. ↑ Prognosis and treatment of oligodendroglioma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligodendroglioma
  10. ↑ Yip S, Butterfield YS, Morozova O, Chittaranjan S, Blough MD, An J; et al. (2012). "Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers". J Pathol. 226 (1): 7–16. doi:10.1002/path.2995. PMC 3246739. PMID 22072542.
  11. ↑ Labreche K, Simeonova I, Kamoun A, Gleize V, Chubb D, Letouzé E; et al. (2015). "TCF12 is mutated in anaplastic oligodendroglioma". Nat Commun. 6: 7207. doi:10.1038/ncomms8207. PMC 4490400. PMID 26068201.
  12. ↑ Suri V, Jha P, Agarwal S, Pathak P, Sharma MC, Sharma V; et al. (2011). "Molecular profile of oligodendrogliomas in young patients". Neuro Oncol. 13 (10): 1099–106. doi:10.1093/neuonc/nor146. PMC 3177666. PMID 21937591.
  13. ↑ Hagel C, Laking G, Laas R, Scheil S, Jung R, Milde-Langosch K; et al. (1996). "Demonstration of p53 protein and TP53 gene mutations in oligodendrogliomas". Eur J Cancer. 32A (13): 2242–8. PMID 9038605.
  14. ↑ 14.0 14.1 14.2 14.3 14.4 von Deimling, A; Hartmann, C (2005). "Oligodendrogliomas: Impact of molecular genetics on treatment". Neurology India. 53 (2): 140. doi:10.4103/0028-3886.16394. ISSN 0028-3886.
  15. ↑ 15.0 15.1 Cancer Genome Atlas Research Network. Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR; et al. (2015). "Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas". N Engl J Med. 372 (26): 2481–98. doi:10.1056/NEJMoa1402121. PMC 4530011. PMID 26061751.
  16. ↑ 16.0 16.1 Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H; et al. (2015). "Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors". N Engl J Med. 372 (26): 2499–508. doi:10.1056/NEJMoa1407279. PMC 4489704. PMID 26061753.
  17. ↑ Ueki K, Nishikawa R, Nakazato Y, Hirose T, Hirato J, Funada N; et al. (2002). "Correlation of histology and molecular genetic analysis of 1p, 19q, 10q, TP53, EGFR, CDK4, and CDKN2A in 91 astrocytic and oligodendroglial tumors". Clin Cancer Res. 8 (1): 196–201. PMID 11801559.
  18. ↑ Labussière M, Boisselier B, Mokhtari K, Di Stefano AL, Rahimian A, Rossetto M; et al. (2014). "Combined analysis of TERT, EGFR, and IDH status defines distinct prognostic glioblastoma classes". Neurology. 83 (13): 1200–6. doi:10.1212/WNL.0000000000000814. PMID 25150284.
  19. ↑ Nambirajan A, Suri V, Kedia S, Goyal K, Malgulwar PB, Khanna G; et al. (2018). "Paediatric diffuse leptomeningeal tumor with glial and neuronal differentiation harbouring chromosome 1p/19q co-deletion and H3.3 K27M mutation: unusual molecular profile and its therapeutic implications". Brain Tumor Pathol. 35 (3): 186–191. doi:10.1007/s10014-018-0325-0. PMID 30030640.
  20. ↑ McDonald JM, See SJ, Tremont IW, Colman H, Gilbert MR, Groves M; et al. (2005). "The prognostic impact of histology and 1p/19q status in anaplastic oligodendroglial tumors". Cancer. 104 (7): 1468–77. doi:10.1002/cncr.21338. PMID 16088966.
  21. ↑ Barbashina V, Salazar P, Holland EC, Rosenblum MK, Ladanyi M (2005). "Allelic losses at 1p36 and 19q13 in gliomas: correlation with histologic classification, definition of a 150-kb minimal deleted region on 1p36, and evaluation of CAMTA1 as a candidate tumor suppressor gene". Clin Cancer Res. 11 (3): 1119–28. PMID 15709179.
  22. ↑ Reifenberger J, Reifenberger G, Liu L, James CD, Wechsler W, Collins VP (1994). "Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p". Am J Pathol. 145 (5): 1175–90. PMC 1887413. PMID 7977648.
  23. ↑ Reuss DE, Sahm F, Schrimpf D, Wiestler B, Capper D, Koelsche C; et al. (2015). "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. 129 (1): 133–46. doi:10.1007/s00401-014-1370-3. PMID 25427834.
  24. ↑ Chen N, Yu T, Gong J, Nie L, Chen X, Zhang M; et al. (2016). "IDH1/2 gene hotspot mutations in central nervous system tumours: analysis of 922 Chinese patients". Pathology. 48 (7): 675–683. doi:10.1016/j.pathol.2016.07.010. PMID 27780605.
  25. ↑ Zhou YX, Wang JX, Feng M, Sun CM, Sun T, Chen GL; et al. (2012). "Analysis of isocitrate dehydrogenase 1 mutation in 97 patients with glioma". J Mol Neurosci. 47 (3): 442–7. doi:10.1007/s12031-011-9681-5. PMID 22113362.
  26. ↑ Capper D, Weissert S, Balss J, Habel A, Meyer J, Jäger D; et al. (2010). "Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors". Brain Pathol. 20 (1): 245–54. doi:10.1111/j.1750-3639.2009.00352.x. PMID 19903171.
  27. ↑ Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W; et al. (2009). "IDH1 and IDH2 mutations in gliomas". N Engl J Med. 360 (8): 765–73. doi:10.1056/NEJMoa0808710. PMC 2820383. PMID 19228619.
  28. ↑ Balss J, Meyer J, Mueller W, Korshunov A, Hartmann C, von Deimling A (2008). "Analysis of the IDH1 codon 132 mutation in brain tumors". Acta Neuropathol. 116 (6): 597–602. doi:10.1007/s00401-008-0455-2. PMID 18985363.
  29. ↑ Pan Y, Qi XL, Wang LM, Dong RF, Zhang M, Zheng DF; et al. (2013). "[Mutation of isocitrate dehydrogenase gene in Chinese patients with glioma]". Zhonghua Bing Li Xue Za Zhi. 42 (5): 292–8. doi:10.3760/cma.j.issn.0529-5807.2013.05.002. PMID 24004584.
  30. ↑ Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A; et al. (2009). "Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas". Acta Neuropathol. 118 (4): 469–74. doi:10.1007/s00401-009-0561-9. PMID 19554337.
  31. ↑ Sonoda Y, Kumabe T, Nakamura T, Saito R, Kanamori M, Yamashita Y; et al. (2009). "Analysis of IDH1 and IDH2 mutations in Japanese glioma patients". Cancer Sci. 100 (10): 1996–8. doi:10.1111/j.1349-7006.2009.01270.x. PMID 19765000.
  32. ↑ Arita H, Narita Y, Yoshida A, Hashimoto N, Yoshimine T, Ichimura K (2015). "IDH1/2 mutation detection in gliomas". Brain Tumor Pathol. 32 (2): 79–89. doi:10.1007/s10014-014-0197-x. PMID 25008158.
  33. ↑ Diplas BH, Liu H, Yang R, Hansen LJ, Zachem AL, Zhao F; et al. (2019). "Sensitive and rapid detection of TERT promoter and IDH mutations in diffuse gliomas". Neuro Oncol. 21 (4): 440–450. doi:10.1093/neuonc/noy167. PMC 6422442. PMID 30346624.
  34. ↑ Sun ZL, Chan AK, Chen LC, Tang C, Zhang ZY, Ding XJ; et al. (2015). "TERT promoter mutated WHO grades II and III gliomas are located preferentially in the frontal lobe and avoid the midline". Int J Clin Exp Pathol. 8 (9): 11485–94. PMC 4637696. PMID 26617880.
  35. ↑ Yang P, Cai J, Yan W, Zhang W, Wang Y, Chen B; et al. (2016). "Classification based on mutations of TERT promoter and IDH characterizes subtypes in grade II/III gliomas". Neuro Oncol. 18 (8): 1099–108. doi:10.1093/neuonc/now021. PMC 4933482. PMID 26957363.
  36. ↑ Labussière M, Di Stefano AL, Gleize V, Boisselier B, Giry M, Mangesius S; et al. (2014). "TERT promoter mutations in gliomas, genetic associations and clinico-pathological correlations". Br J Cancer. 111 (10): 2024–32. doi:10.1038/bjc.2014.538. PMC 4229642. PMID 25314060.
  37. ↑ Nencha U, Rahimian A, Giry M, Sechi A, Mokhtari K, Polivka M; et al. (2016). "TERT promoter mutations and rs2853669 polymorphism: prognostic impact and interactions with common alterations in glioblastomas". J Neurooncol. 126 (3): 441–6. doi:10.1007/s11060-015-1999-3. PMID 26608520.
  38. ↑ Khuong-Quang DA, Buczkowicz P, Rakopoulos P, Liu XY, Fontebasso AM, Bouffet E; et al. (2012). "K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas". Acta Neuropathol. 124 (3): 439–47. doi:10.1007/s00401-012-0998-0. PMC 3422615. PMID 22661320.
  39. ↑ Harutyunyan AS, Krug B, Chen H, Papillon-Cavanagh S, Zeinieh M, De Jay N; et al. (2019). "H3K27M induces defective chromatin spread of PRC2-mediated repressive H3K27me2/me3 and is essential for glioma tumorigenesis". Nat Commun. 10 (1): 1262. doi:10.1038/s41467-019-09140-x. PMC 6425035. PMID 30890717.
  40. ↑ Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J; et al. (2012). "Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas". Nat Genet. 44 (3): 251–3. doi:10.1038/ng.1102. PMC 3288377. PMID 22286216.
  41. ↑ Castel D, Philippe C, Calmon R, Le Dret L, Truffaux N, Boddaert N; et al. (2015). "Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes". Acta Neuropathol. 130 (6): 815–27. doi:10.1007/s00401-015-1478-0. PMC 4654747. PMID 26399631.
  42. ↑ Castel D, Grill J, Debily MA (2016). "Histone H3 genotyping refines clinico-radiological diagnostic and prognostic criteria in DIPG". Acta Neuropathol. 131 (5): 795–6. doi:10.1007/s00401-016-1568-7. PMC 4835508. PMID 27038188.
  43. ↑ Cordero FJ, Huang Z, Grenier C, He X, Hu G, McLendon RE; et al. (2017). "Histone H3.3K27M Represses p16 to Accelerate Gliomagenesis in a Murine Model of DIPG". Mol Cancer Res. 15 (9): 1243–1254. doi:10.1158/1541-7786.MCR-16-0389. PMC 5581686. PMID 28522693.
  44. ↑ Gillet E, Alentorn A, Doukouré B, Mundwiller E, van Thuijl HF, van Thuij H; et al. (2014). "TP53 and p53 statuses and their clinical impact in diffuse low grade gliomas". J Neurooncol. 118 (1): 131–9. doi:10.1007/s11060-014-1407-4. PMID 24590827.
  45. ↑ Rodriguez FJ, Schniederjan MJ, Nicolaides T, Tihan T, Burger PC, Perry A (2015). "High rate of concurrent BRAF-KIAA1549 gene fusion and 1p deletion in disseminated oligodendroglioma-like leptomeningeal neoplasms (DOLN)". Acta Neuropathol. 129 (4): 609–610. doi:10.1007/s00401-015-1400-9. PMC 4696044. PMID 25720745.
  46. ↑ 46.0 46.1 Gross appearance of oligodendroglioma. Dr Henry Knipe and Dr Frank Gaillard et al. http://radiopaedia.org/articles/oligodendroglioma
  47. ↑ Gross/radiologic findings of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma
  48. ↑ 48.0 48.1 Microscopic features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma
  49. ↑ Ersen, Ayca (2008), Pathology of malignant gliomas: Challenges of everyday practice and the WHO 2007, Turkish Journal of Pathology, retrieved 9 October, 2015 Check date values in: |accessdate= (help)
  50. ↑ Eskandar EN, Loeffler JS, O'Neill AM, Hunter GJ, Louis DN (2004). "Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 33-2004. A 34-year-old man with a seizure and a frontal-lobe brain lesion". N Engl J Med. 351 (18): 1875–82. doi:10.1056/NEJMcpc049025. PMID 15509821.
  51. ↑ Rodriguez FJ, Perry A, Rosenblum MK, Krawitz S, Cohen KJ, Lin D; et al. (2012). "Disseminated oligodendroglial-like leptomeningeal tumor of childhood: a distinctive clinicopathologic entity". Acta Neuropathol. 124 (5): 627–41. doi:10.1007/s00401-012-1037-x. PMID 22941225.
  52. ↑ Images of microscopic appearance of oligodendroglioma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligodendroglioma
  53. ↑ Kros JM, Van Eden CG, Stefanko SZ, Waayer-Van Batenburg M, van der Kwast TH (1990). "Prognostic implications of glial fibrillary acidic protein containing cell types in oligodendrogliomas". Cancer. 66 (6): 1204–12. PMID 2205356.
  54. ↑ Images of oligodendroglioma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Oligodendroglioma
  55. ↑ Smith SF, Simpson JM, Brewer JA, Sekhon LH, Biggs MT, Cook RJ; et al. (2006). "The presence of necrosis and/or microvascular proliferation does not influence survival of patients with anaplastic oligodendroglial tumours: review of 98 patients". J Neurooncol. 80 (1): 75–82. doi:10.1007/s11060-006-9158-5. PMID 16794749.
  56. ↑ IHC of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma
  57. ↑ Hilbig A, Barbosa-Coutinho LM, Netto GC, Bleil CB, Toscani NV (2006). "[Immunohistochemistry in oligodendrogliomas]". Arq Neuropsiquiatr. 64 (1): 67–71. doi:/S0004-282X2006000100014 Check |doi= value (help). PMID 16622556.
  58. ↑ Kato Y (2015). "Specific monoclonal antibodies against IDH1/2 mutations as diagnostic tools for gliomas". Brain Tumor Pathol. 32 (1): 3–11. doi:10.1007/s10014-014-0202-4. PMID 25324168.


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