Oligodendroglioma

Oligodendroglioma, IDH mutant and 1p/19q codeleted is CNS tumour that is typically in the cerebral hemispheres. Molecular analysis of IDH1/2 hotspots and LOH1p/19q testing is required for diagnosis.

Oligodendroglioma
Diagnosis in short
Oligodendroglioma. H&E stain.
LM	highly cellular lesion composed of cells resembling fried eggs (oligodendrocytes) with a round nucleus (important), distinct cell borders, +/-clear cytoplasm - useful feature (if present), acutely branched capillary sized vessels ("chicken-wire" like appearance), calcifications
LM DDx	neurocytoma, clear cell variant of ependymoma, seminoma / dysgerminoma / germinoma
Molecular	+/-loss of 1p and 19q (common)
Site	neuropathology tumours - cerebral hemispheres, posterior fossa (rare), spinal cord (very rare)
Radiology	intra-axial mass, +/-calcifications (best seen on CT), nonenhancing or enhancing
Prognosis	moderate - dependent on grade

General

• Do not arise from oligodendrocytes, although tumor cells look very similiar.
  • Arise from glial precursor cells.

Prognosis by flavours (average survival):

• WHO CNS grade 2: 10-15 years.
• WHO CNS grade 3: 3-5 years.

Oligodendrogliomas account for approx 5% of all gliomas.

• Numbers may be higher when stringent classifiation criteria are not applied.
• Peak incidence: 40-45 years.
• First description of the tumor in 1926.

The WHO 2016 classification recognizes four tumor subtypes:

• Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, WHO Grade II (ICD-O: 9450/3).
• Anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted, WHO Grade III (ICD-O: 9451/3).
• Oligodendroglioma, NOS, WHO Grade II (ICD-O: 9450/3).
• Anaplastic oligodendroglioma, NOS, WHO Grade III (ICD-O: 9451/3).

Gross/radiologic

Location:

• Cerebral hemispheres - most often (50-60%) frontal lobe, followed by parietal and temporal lobes.
• Posterior fossa (rare).
• Intramedullary spinal cord (very rare).

Radiologic features:

• Intra-axial mass.
• +/-Calcifications (best seen on CT).
• Nonenhancing or enhancing.
• Occasionally well-circumscribed.

Clinical symptoms:

• Seizures.
• Intracranial pressure.
• Focal neurologic decifits.
• Cognitive changes.

Microscopic

Features:

• Diffusely growing tumor.
• Highly cellular lesion composed of:
  • Cells resembling fried eggs (oligodendrocytes) with:
    • Round nucleus - key feature.
    • Distinct cell borders.
    • Moderate-to-marked nuclear atypia.
    • Clear cytoplasm - useful feature (if present).
      • Some oligodendrogliomas have eosinophilic cytoplasm with focal perinuclear clearing.
  • Acutely branched capillary sized vessels - "chicken-wire" like appearance.
    • Abundant, delicate appearing; may vaguely resemble a paraganglioma at low power.
• Calcifications - important feature.
• Perifocal edema uncommon.
• Few tumors may exhibit eosinophilic granular bodies.
• Some tumors may show a Spongioblastoma-like growth pattern.

Anaplastic (grade III) criteria:

• "Significant" or "brisk" mitotic activity.
  • That means for most neuropathologists >= 6 mitoses per 10 HPF.
• Microvacular proliferation.
• Necrosis.

Note:

• Tumour cells may be plasmacytoid, i.e. have a plasma cell-like appearance.
  • Also called minigemistocytes.
  • The are usually strong GFAP+ve.

DDx:

• Neurocytoma also have perinuclear clearing and well-defined cellular borders.
  • Pineocytomatous/neurocytic rosettes = (irregular) rosette with a large meshwork of fibers (neuropil) at the centre.
• Clear cell ependymoma.
• Dysembryoplastic neuroepithelial tumour.
• Oligodendroglial-like cells in Pilocytic astrocytoma.
• Clear cell meningioma.
• Demyelinisation.

Notes:

• Few neural tumours have round nuclei - DDx:
  • Oligodendroglioma.
  • Lymphoma.
  • Clear cell variant of ependymoma.
  • Germ cell tumour (germinoma/dysgerminoma/seminoma).

Images

• 

  Oligodendroglioma high mag. (WC)

• 

  Oligodendroglioma low mag. (WC)

• 

  Discrete invasion in a oligodendroglioma. (WC/jensflorian)

• 

  Minigemistocytes and mitoses. (WC/jensflorian)

• 

  Perinuclear MAP2 immunoreactivity in oligodendroglioma. (WC/jensflorian)

• 

  Demonstration of IDH1 R132H mutation in oligodendroglioma. (WC/jensflorian)

www:

• Oligodendroglioma - several images (upmc.edu).
• Oligodendroglioma with plasmacytoid cells (frontalcortex.com).

Histologic grading

Come in two flavours:

1. WHO CNS grade 2
   • This is most oligodendrogliomas.
   • Without genetic testing for IDH-1/2 and LOH 1p/19q, the tumor is called Oligodendroglioma, NOS.
2. WHO CNS grade 3
   • Features for calling high grade:
     • Endothelial hypertrophy.
       • Plump/large endothelial cells.
     • Necrosis.
     • High mitotic rate (6 mitoses/10 HPF for whatever "HPF" means, see HPFitis).
   • Without genetic testing for IDH-1/2 and LOH 1p/19q, the tumor is called Anaplastic oligodendroglioma, NOS.

IHC

Features:

• MAP2 +ve.
• GFAP +ve (variable).
  • Some subtypes +ve - should not be used to distinguish.
• EMA +ve.
• IDH-1 (R132H) +ve (approx 85%).
  • 18% +ve in one series of children, 23% +ve in another series.
• ATRX +ve (nuclear retention).
  • Useful for differentiating astrocytoma vs. oligodendroglioma.
• H3K27me3 -ve (nuclear loss).
• SOX10 +ve (up to 80%).
• p53 -ve or low expressed.
• Ki-67 (usu. >5% in grade II).
• May have neuronal "islands" (Synapto +ve, NeuN +ve).

Molecular pathology

Combined losses of 1p and 19q both and presence of IDH1/2 mutation is required for final diagnosis and is prognostic and therapeutic relevant:

• Greater chemosensitivity to PCV regimen.
• Better prognosis compared to astrocytic tumors.

Note:

• Consider underdiagnosed Glioblastoma, IDH-wildtype when tumor is IDH1/2 wildtype and has no LOH 1p/19q and no ATRX loss.
• IDH-1 mutant, but non-codeleted tumors are no longer classified as oligodendrogliomas on molecular basis. These tumors are classified as IDH-mutant astrocytoma.

See also

• Neuropathology tumours.
• Neuropathology.