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

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