CNS & pituitary tumors

Gliomas, glioneuronal tumors, and neuronal tumors

Oligodendroglioma, IDH mutant and 1p / 19q codeleted



Last author update: 25 April 2022
Last staff update: 26 April 2022

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PubMed Search: Oligodendroglioma, IDH mutant, 1p / 19q codeleted

Jared T. Ahrendsen, M.D., Ph.D.
Sanda Alexandrescu, M.D.
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Cite this page: Ahrendsen JT, Alexandrescu S. Oligodendroglioma, IDH mutant and 1p / 19q codeleted. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumoroligodendrogliomaidhmutant.html. Accessed December 3rd, 2022.
Definition / general
  • CNS WHO 2021 definition: diffusely infiltrating glioma with IDH1 or IDH2 mutation and codeletion of chromosome arms 1p and 19q (CNS WHO grade 2 or 3)
Essential features
  • Diffusely infiltrating glial neoplasm with IDH1 or IDH2 mutation and 1p / 19q whole arm codeletion (both features are required for diagnosis)
  • Morphology resembles nonneoplastic oligodendrocytes with round monotonous nuclei and perinuclear halos
  • Chicken wire vasculature, microcalcifications and microcysts are characteristic (Neuro Oncol 2014;16:1244)
  • Astrocytic differentiation does not preclude diagnosis if molecular features are present
    • Small gemistocytes (mini gemistocytes) with rounded bellies of eosinophilic, eccentrically placed cytoplasm are occasionally seen, especially in grade 3 tumors (Acta Neuropathol 1984;64:265)
  • Presence of other atypical features (including multinucleated giant cells, sarcomatous features, neurocytic differentiation or ganglion-like cells) does not preclude a diagnosis of oligodendroglioma if the requisite molecular features are present (Acta Neuropathol 2010;120:237, J Neuropathol Exp Neurol 2002;61:947, Neuropathology 2014;34:323)
ICD coding
  • ICD-O:
    • 9450/3 - oligodendroglioma, NOS
    • 9451/3 - oligodendroglioma, anaplastic
Epidemiology
  • Most epidemiologic data is based on histologic, rather than molecular, classification of oligodendroglioma
  • Incidence of 0.23 cases per 100,000 population in the United States (Neuro Oncol 2019;21:v1)
    • Incidence of CNS WHO grade 3 oligodendroglioma is 0.11
  • Of all brain tumors in the United States:
    • 0.9% are oligodendroglioma WHO grade 2
    • 0.4% are oligodendroglioma WHO grade 3
  • Peak incidence in fourth and fifth decades of life (Neuro Oncol 2020;22:iv1)
  • Rare in infants and children (Am J Surg Pathol 2014;38:1058)
  • Slight male predominance (Neuro Oncol 2019;21:v1)
Sites
  • Infiltrative neoplasm involving the white and gray matter
  • Can occur anywhere in the neuraxis; most common locations (Neuro Oncol 2020;22:iv1):
    • Frontal lobes: 59%
    • Temporal lobes: 14%
    • Parietal lobes: 10%
    • Occipital lobes: 1%
  • Rarely observed in midline structures, brainstem, cerebellum or spinal cord
  • Leptomeningeal spread occasionally observed, particularly at recurrence (Neurology 2019;92:e2483)
Pathophysiology
  • Cell (or cells) of origin for oligodendroglioma remains unknown
  • IDH mutation is likely the initiating event (driver mutation), which precedes 1p / 19q codeletion (Adv Anat Pathol 2015;22:50, Biomed Res Int 2014;2014:540236)
  • IDH mutations give rise to metabolic alterations, with increased production of 2-hydroxyglutarate (2HG)
  • Increased 2HG inhibits histone demethylation, causing a hypermethylation phenotype in neoplastic cells: glioma CpG island methylated phenotype (G CIMP) (Nature 2012;483:479, Acta Neuropathol 2013;125:621)
Etiology
Clinical features
Grading
  • WHO grade 2:
    • Well differentiated tumor lacking anaplastic features (brisk mitotic activity, microvascular proliferation, necrosis)
  • WHO grade 3:
    • Prominent anaplastic features (necrosis, microvascular proliferation or brisk mitotic activity) are compatible with anaplastic oligodendroglioma, IDH mutant and 1p / 19q codeleted, WHO grade 3
    • Strict mitotic activity criteria do not currently exist
    • Some authors suggest ≥ 6 mitotic figures per 10 high power fields in resection specimens for grade 3 designation (J Neuropathol Exp Neurol 2001;60:248)
    • Fewer mitotic figures might be sufficient for grade 3 designation in small biopsy specimens if other anaplastic features (vascular proliferation or necrosis) or significant nuclear atypia are present
    • CDKN2A homozygous deletion may serve as a molecular marker of CNS WHO grade 3 in IDH mutant and 1p / 19q codeleted oligodendrogliomas (Neuro Oncol 2019;21:1519)
Diagnosis
  • Magnetic resonance imaging (MRI), followed by stereotactic brain biopsy or surgical resection
  • Methods to detect IDH gene mutation:
  • Methods to detect 1p / 19q codeletion:
    • Fluorescent in situ hybridization (FISH)
    • Array comparative genomic hybridization
    • Polymerase chain reaction (PCR)
Radiology description
Radiology images

Contributed by Jared T. Ahrendsen, M.D., Ph.D. and John DeWitt, M.D., Ph.D.
MRI, brain: T1 post

MRI, brain: T1 post

MRI, brain: T2

MRI, brain: T2

MRI: frontal lobe tumor with cystic change MRI: frontal lobe tumor with cystic change

MRI: frontal lobe tumor with cystic change



Images hosted on other servers:

Axial flair frontal lobe tumor

Axial flair large temporal lobe tumor

Prognostic factors
Case reports
Treatment
  • Gross total resection, if possible
  • Adjuvant chemotherapy (temozolomide) and radiotherapy
    • Given to patients with symptomatic or progressive tumors, tumors with CNS WHO grade 3 histology or those with large postoperative residual tumor
  • References: Crit Rev Oncol Hematol 2008;66:262, Lancet 2005;366:985
Gross description
  • Variably well defined, gray-pink mass
  • Mucoid change can give a gelatinous consistency
  • Areas of cystic degeneration, calcifications, hemorrhage or necrosis can be seen
Frozen section description
  • Moderately cellular, diffusely infiltrating neoplasm
  • Glia with mild to moderate nuclear atypia
  • Round nuclei with speckled chromatin
  • Calcifications, perineuronal satellitosis or perivascular accumulation of tumor cells may be seen
  • Will not see perinuclear halos on frozen section or smear preparations
  • Anaplastic features (necrosis, vascular proliferation, mitoses) may be seen in WHO grade 3 tumors
  • Reference: J Cytol 2011;28:147
Frozen section images

Contributed by Jared T. Ahrendsen, M.D., Ph.D.
Intraoperative smear preparation

Intraoperative smear preparation

Intraoperative frozen section

Microscopic (histologic) description
  • Closely packed cells with small, round, monotonous nuclei (slightly larger than a normal oligodendrocyte)
  • Perinuclear clearing (fried egg appearance)
    • Formalin fixation artifact
    • Will not be seen on frozen sections or smear preparations
  • Network of thin walled, branching blood vessels (chicken wire vasculature)
  • Microcalcifications (calcospherites) are characteristic
  • Presence of perineural, perivascular or subpial aggregates of tumor cells (secondary structures of Scherer)
  • Occasional mitoses and moderate nuclear atypia are still consistent with grade 2 designation (J Neuropathol Exp Neurol 2001;60:248)
  • Not uncommon to find well differentiated / fibrillary astrocytic morphology (Acta Neuropathol 1984;64:265)
  • Features of CNS WHO grade 3 oligodendroglioma:
    • Presence of microvascular proliferation
    • Presence of necrosis
    • Presence of brisk mitotic activity
      • Strict mitotic figure cutoffs do not currently exist; some authors suggest ≥ 6 mitoses per 10 high power fields for WHO grade 3 designation in tumors without necrosis or vascular proliferation (Neuro Oncol 2014;16:1244, Neuro Oncol 2016;18:888)
Microscopic (histologic) images

Contributed by Jared T. Ahrendsen, M.D., Ph.D. and John DeWitt, M.D., Ph.D.
Diffusely infiltrating glial neoplasm

Diffusely infiltrating glial neoplasm

Microcalcifications

Microcalcifications

Perinuclear halos Perinuclear halos

Perinuclear halos

Chicken wire vasculature

Chicken wire vasculature


Secondary structures of Scherer

Secondary structures of Scherer

Diffusely infiltrating glial neoplasm

Cellularity and vascular proliferation

Diffusely infiltrating glial neoplasm

Focal necrosis

Diffusely infiltrating glial neoplasm

Brisk mitotic activity

Mixed astrocytic histology


IDH1 R132H

IDH1 R132H

p53

ATRX

Virtual slides

Images hosted on other servers:

Oligodendroglioma,
resection

Oligodendroglioma,
IDH1 R132H,
resection

Positive stains
Negative stains
Electron microscopy description
  • Not routinely used for diagnostic purposes
Molecular / cytogenetics description
Sample pathology report
  • Brain, frontal lobe, left, tumor, resection:
    • Integrated diagnosis: oligodendroglioma, IDH1 R132H mutant and 1p / 19q codeleted
    • Histologic diagnosis: oligodendroglioma
    • CNS WHO grade: 3
    • Molecular information:
      • IDH1 R132H mutation
      • 1p / 19q codeletion
      • TERT promotor mutation
Differential diagnosis
  • Astrocytoma, IDH mutant:
    • Lacks 1p / 19q codeletion and TERT promotor mutations
    • Harbors p53 or ATRX mutations
      • p53 expression strong and diffuse in tumor cells
      • ATRX expression lost in tumor cells
  • Other tumors with oligo-like morphology:
  • Macrophage rich lesions:
    • Stain positive with macrophage markers
Board review style question #1

A 42 year old man presents to the emergency room with new onset seizures. Brain magnetic resonance imaging (MRI) reveals a nonenhancing infiltrative mass lesion in the right frontal lobe. A biopsy is performed, shown in the image above. What molecular features are most likely present?

  1. BRAF V600E mutation
  2. EGFR amplification
  3. IDH mutation and 1p / 19q codeletion
  4. IDH, p53 and ATRX mutations
  5. Polysomy 7 and monosomy 10 (+7 / -10)
Board review style answer #1
C. IDH mutation and 1p / 19q codeletion. The image shows an oligodendroglioma, which is defined by the presence of IDH mutation and 1p / 19q codeletion.

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Reference: Oligodendroglioma, IDH mutant and 1p / 19q codeleted
Board review style question #2
Which of the following is a common genetic alteration in oligodendroglioma, IDH mutant and 1p / 19q codeleted?

  1. ATRX mutation
  2. BRAF V600E
  3. EGFR amplification
  4. p53 mutation
  5. TERT promotor mutation
Board review style answer #2
E. TERT promotor mutation. TERT promotor mutations are commonly observed in oligodendroglioma.

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Reference: Oligodendroglioma, IDH mutant and 1p / 19q codeleted
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