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.

• Oligodendroglioma does not arise from the bipotential oligodendrocytes, although the tumor cells look very similiar.^[1]
• Oligodendroglioma arises from the tripotential glial precursor cells.

• Development of oligodendroglioma is the result of multiple genetic mutations.^{[2][3][4][5][6][7][8][9][10][11][12]}
• Genes associated with the pathogenesis of oligodendroglioma include:^{[13][14][15][16][17][18][19][20][21][22][23][24][25]}

• t(1;19)(q10;p10) (co-deletion of chromosomal arms 1p36 and 19q13; most common)^[26][10][27]
• ATRX^[28]
• IDH1^{[29][30][31][32][33][34][35][36][37]}
• IDH2^{[38][39][40][41][42][43]}
• TERT promoter^{[22][44][45][46][47][48]}
• H3 K27M mutations in either H3F3A (one of two genes encoding the histone H3.3 variant) or HIST1H3B/C (encoding the histone H3.1 variant).^{[49][50][51][52][53][54]}
• NJDS (A 2009 Oxford Neurosymposium study illustrated that there’s a 69% correlation between NJDS gene mutation and tumor initiation).
• CIC^[55][16]
• FUBP1
• TP53
• p53^[56]
• BRAF alterations:^[57]
  • KIAA1549–BRAF fusion
  • BRAF V600E mutation
• Leu-7
• TCF-12
• MGMT
• TP73
• EGFR
• PTEN

• There is a strong association of oligodendroglioma with expression of receptor tyrosine kinases that activate PI3K/AKT, RAS/MAP, and PLC/PKC pathways.^[20]

• On gross pathology, oligodendroglioma is characterized by a well-circumscribed, gelatinous, gray mass which may expand a gyrus and remodel the skul.l^[58]
• Other characteristic gross pathological features associated with oligodendroglioma include:^[58][20]
  • Calcification (70-90%; one of the most frequently calcifying tumors)
  • Focal hemorrhage
  • Cystic (20%)
• Common intracranial sites associated with oligodendroglioma include:^[59]
  • Cerebral hemispheres (cortex and white matter) – distribution between frontal (most common, > 50% of cases), parietal, temporal, and occipital lobe approximates 3:2:2:1.
  • Posterior fossa (rare)
  • Intramedullary spinal cord (very rare, only 1.5% of oligodendrogliomas).

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

• 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.^[64]
    • 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).^[65]
• A predominant fibrillar astrocytic phenotype is compatible with the diagnosis when following appropriate molecular findings are present:^[21]
  • IDH mutation
  • 1p/19q codeletion

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

• Focal or diffusely increased cell density
• Atypical to frankly pleomorphic cells or multinucleated giant cells
• Tumor cells may be plasmacytoid (i.e. have a plasma cell-like appearance)
  • Also called as minigemistocytes
• Significant/brisk infrequent mitotic activity (≥ 6 mitoses per 10 HPF)^[66][67]
• Rare foci of:
  • Necrosis
  • Apoptotic cells
  • Microvacular proliferation either in the form of:
    • Glomeruloid‘ vessels or
    • Endothelial hyperplasia

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

• IDH1-R132H (majority of cases)^[70]
• MAP2
• GFAP (positive in intermingled reactive astrocytes and minigemistocytes)
• SOX10
• S-100
• EMA
• ATRX
• Ki-67
• NSE
• Synaptophysin
• OLIG1
• OLIG2

Oligodendroglioma stains negative for:

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

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