Oligodendroglioma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [16]Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[17]Sujit Routray, M.D. [18]

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], ATRX, NJDS, IDH1, IDH2, TERT promoter, H3 K27M (H3F3A, HIST1H3B/C), CIC, FUBP1, p53, Leu-7, TCF-12, TP53,MGMT, TP73, BRAF, EGFR, and PTEN. Common intracranial sites involved by oligodendroglioma include cerebral hemispheres, posterior fossa, and intramedullary spinal cord. On gross pathology, oligodendroglioma is characterized by a well-circumscribed, gelatinous, calcified, cystic, gray mass with focal hemorrhage which may expand a gyrus and remodel the skull. On microscopic histopathological analysis, oligodendroglioma is characterized by diffuse growthpattern of highly cellular lesion of monomorphic cells having rounded nucleus with atypia, speckled "salt-and-pepper" chromatin pattern and perinuclear haloresembling fried eggs, distinct cell borders, clear cytoplasm, abundant calcification and "chicken-wire" like vascularity pattern. Oligodendroglioma is demonstrated by positivity to tumor markers such as IDH1-R132H, MAP2, GFAP, S-100, SOX10, EMA, ATRX, Ki-67, NSE, synaptophysin, OLIG1, and OLIG2.

Pathophysiology

Pathogenesis

Genetics

Gross Pathology

Oligodendroglioma involving frontal lobe [1]
Mixed astrocytoma and oligodendroglioma [2]
Oligodendroglioma gross appearance [3]

Microscopic Pathology

On microscopic histopathological analysis, oligodendroglioma is characterized by:[20][60][61][62][63]

Oligodendroglioma HE stain [4]
Low power magnification of a Oligodendroglioma biopsy specimen showing discrete infiltration of the surrounding brain [5]
Oligodendroglioma HE stain [6]
Oligodendroglioma HE stain [7]
Oligodendroglioma HE stain [8]
GFAP immunohistochemistry in a histopathology specimen of oligodendroglioma grade II WHO [9]
High magnification micrograph of an oligodendroglioma showing the characteristic branching, small, chicken wire-like blood vessels and fried egg-like cells, with clear cytoplasm and well-defined cell borders. H&E stain. [10]
Low magnification micrograph of an oligodendroglioma showing the characteristic, small, branching, chicken wire-like blood vessels. H&E stain. [11]

Microscopic histopathological findings in anaplastic oligodendroglioma

On microscopic histopathological analysis, anaplastic oligodendroglioma, IDH mutant and 1p/19q codeleted, is characterized by:[60]

Brisk mitotic rate in anaplastic oligodendroglioma [12]
Vascularproliferation Source: Roger E McLendon, MD et al.
Histopathology of anaplastic oligodendroglioma (MAP2 staining) showing perinuclear immunoreactivity of tumor cells[13]
"Fried egg" appearance Source: John DeWitt, M.D., Ph.D.
Chicken wire vessels Source: John DeWitt, M.D., Ph.D.
"Fried egg" appearance Source: John DeWitt, M.D., Ph.D.
Infiltrating cortex Source: John DeWitt, M.D., Ph.D.
Histopathology of anaplastic oligodendroglioma (HE stain) showing minigemistocytes and mitoses among tumor cells with perinuclear halo.[14]
Histopathology of anaplastic oligodendroglioma (IDH1 R132H staining) showing immunoreactivity of tumor cells idicating presence of the isocitrate dehydrogenase 1 R132H mutation [15]

Immunohistochemistry

Oligodendroglioma is demonstrated by positivity to tumor markers such as:[68][69][20][7]

Oligodendroglioma stains negative for:

References

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  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. ↑ 7.0 7.1 Tanboon J, Williams EA, Louis DN (2016). "The Diagnostic Use of Immunohistochemical Surrogates for Signature Molecular Genetic Alterations in Gliomas". J Neuropathol Exp Neurol. 75 (1): 4–18. doi:10.1093/jnen/nlv009. PMID 26671986.
  8. ↑ Jiao Y, Killela PJ, Reitman ZJ, Rasheed AB, Heaphy CM, de Wilde RF; et al. (2012). "Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas". Oncotarget. 3 (7): 709–22. doi:10.18632/oncotarget.588. PMC 3443254. PMID 22869205.
  9. ↑ Sahm F, Koelsche C, Meyer J, Pusch S, Lindenberg K, Mueller W; et al. (2012). "CIC and FUBP1 mutations in oligodendrogliomas, oligoastrocytomas and astrocytomas". Acta Neuropathol. 123 (6): 853–60. doi:10.1007/s00401-012-0993-5. PMID 22588899.
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  11. ↑ Frenel JS, Leux C, Loussouarn D, Le Loupp AG, Leclair F, Aumont M; et al. (2013). "Combining two biomarkers, IDH1/2 mutations and 1p/19q codeletion, to stratify anaplastic oligodendroglioma in three groups: a single-center experience". J Neurooncol. 114 (1): 85–91. doi:10.1007/s11060-013-1152-0. PMID 23681562.
  12. ↑ Hacisalihoglu P, Kucukodaci Z, Gundogdu G, Bilgic B (2017). "The Correlation Between 1p/19q Codeletion, IDH1 Mutation, p53 Overexpression and Their Prognostic Roles in 41 Turkish Anaplastic Oligodendroglioma Patients". Turk Neurosurg. 27 (5): 682–689. doi:10.5137/1019-5149.JTN.16832-15.1. PMID 27651340.
  13. ↑ Molecular genetics of oligodendroglioma. https://en.wikipedia.org/wiki/Oligodendroglioma
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  15. ↑ Prognosis and treatment of oligodendroglioma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligodendroglioma
  16. ↑ 16.0 16.1 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
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  57. ↑ 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.
  58. ↑ 58.0 58.1 Gross appearance of oligodendroglioma. Dr Henry Knipe and Dr Frank Gaillard et al. http://radiopaedia.org/articles/oligodendroglioma
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  60. ↑ 60.0 60.1 Microscopic features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma
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  64. ↑ Images of microscopic appearance of oligodendroglioma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligodendroglioma
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  67. ↑ 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.
  68. ↑ IHC of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma
  69. ↑ 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.
  70. ↑ 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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