CNS tumor
Diffuse astrocytic and oligodendroglial tumors
Oligodendroglioma, IDH mutant and 1p/19q codeleted

Author: John DeWitt, M.D., Ph.D. (see Authors page)
Editor: Maria Martinez-Lage, M.D.
Deputy Editor Review: Debra Zynger, M.D.

Revised: 9 August 2018, last major update July 2018

Copyright: (c) 2018, PathologyOutlines.com, Inc.

PubMed Search: Oligodendroglioma (IDH mutant OR 1p/19q codeleted)

Cite this page: DeWitt, J. Oligodendroglioma, IDH mutant and 1p/19q codeleted. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cnstumoroligodendrogliomaidhmutant.html. Accessed August 19th, 2018.
Definition / general
Essential features
  • IDH1 or IDH2 mutation and 1p/19q codeletion are required for the diagnosis
  • Morphology typically resembles that of oligodendrocytes with rounded nuclei and artifactually clear surrounding cytoplasm on routinely processed specimens
  • Histologic features often include a branching capillary pattern and microcalcifications
  • Astrocytic appearance does not preclude this diagnosis when the appropriate molecular alterations are present (IDH mutation, 1p/19q codeletion)
  • Preferentially occurs in adult patients within the cerebral hemispheres
ICD-10 coding
Epidemiology
  • Epidemiologic data is mostly based on previous WHO histologic classifications
  • Incidence rate of 0.26 cases per 100,000 population (Neuro Oncol 2014;16:iv1)
  • 1.2% of primary brain tumors, 5.9% of all gliomas
  • Peak incidence age 35 - 44 years
  • Rare in patients younger than 16 years
  • Male to female ratio 1.3:1
Sites
  • Most commonly found in the cortex and white matter of the cerebral hemispheres
  • Frontal lobe is the most common location (> 50% of cases)
  • Primary spinal cord location is rare, representing 1.5% of oligodendrogliomas
Clinical features
  • About two - thirds of cases present with seizure (Epilepsy Res 2011;94:39)
  • Other common presenting symptoms include headache, focal neurologic deficits or mental status change
Grading
  • Grade II of IV
  • These tumors are well differentiated and lack or have minimal anaplastic features
  • Prominent anaplastic features such as necrosis or microvascular proliferation are compatible with anaplastic oligodendroglioma, IDH mutant and 1p/19q codeleted
Radiology description
  • CT scan typically shows a hypodense or isodense mass lesion that is well demarcated and located in the cerebral hemispheres - either the cortex or subcortical white matter (Br J Radiol 2011;84:S90)
  • Calcifications can be present
  • On MRI, tumors are often T2 hyperintense and T1 hypointense
  • Heterogenous appearance may indicate areas of hemorrhage or cystic change within the tumor
  • Contrast enhancement is uncommon in WHO grade II tumors (< 20%) and is associated with a more aggressive course
Radiology images

Images hosted on PathOut server:

Contributed by John DeWitt, M.D., Ph.D.

MRI: anterior temporal tumor

MRI: frontal lobe tumor with cystic change

Prognostic factors
  • Typically slow growing with a long overall survival
  • More favorable outcomes have been associated with younger age, location in the frontal lobe and greater extent of resection
  • Presence of anaplastic features such as necrosis, microvascular proliferation and mitoses have been historically associated with a worse prognosis (see anaplastic oligodendroglioma, IDH mutant and 1p/19q codeleted)
Case reports
Treatment
  • Complete resection as extensively as is safely possible (J Clin Oncol 2008;26:1338)
  • Chemotherapy or radiation therapy in some cases
Gross description
  • Typically a soft, relatively well defined, greyish pink mass arising in the cortex or subcortical white matter
  • Blurring of the gray-white junction is common
  • Calcifications may lead to a gritty texture; in extreme cases dense calcifications can present as intratumoral stones
  • Cystic degeneration and hemorrhage can be present and rare cases with abundant mucin can appear gelatinous
Microscopic (histologic) description
  • Diffusely infiltrating tumor with moderate cellularity (J Pathol Bacteriol 1929;32:735)
  • Tumor cells are typically monomorphic with round nuclei, salt and pepper chromatin pattern and inconspicuous nucleoli
  • Routinely processed formalin fixed, paraffin embedded material often shows artifactual retraction of the cytoplasm leading to the characteristic "fried egg" appearance of tumor cells
  • Dense network of fine branching capillaries, classically referred to as a "chicken wire" pattern, is often seen
  • Small punctate calcifications, particularly along blood vessels, may be present but this is not a specific finding
  • In surrounding infiltrated brain parenchyma, tumor cells may form secondary structures with perineuronal satellitosis and subpial accumulation; perivascular distribution is less common
  • Tumor cells can show a microgemistocytic appearance, with a rounded belly of eccentric GFAP+ eosinophilic cytoplasm (Cancer 1990;66:1204)
  • In the presence of the appropriate molecular findings (IDH mutation, 1p/19q codeletion), a predominant fibrillar astrocytic phenotype is compatible with the diagnosis (N Engl J Med 2015;372:2481)
  • Mitoses are allowed but should be infrequent and although rare foci of microvascular proliferation and necrosis can be seen, their presence should prompt the consideration of a diagnosis of anaplastic oligodendroglioma, IDH mutant and 1p/19q codeleted (J Neurooncol 2006;80:75)
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by John DeWitt, M.D., Ph.D.

"Fried egg" appearance

"Chicken wire" vessels

Infiltrating cortex


Calcifications

Microgemistocytic histology

Astrocytic histology


R132H-IDH1

ATRX

p53

Positive stains
Negative stains
  • p53 (rare weakly positive cells can be seen)
  • Keratins (although cocktails may show cross reactivity)
Molecular / cytogenetics description
  • Unbalanced translocation between chromosome 1 and 19 results in whole arm loss of 1p and 19q chromosomal material (Cancer Res 2006;66:9852)
  • IDH1 or IDH2 mutation necessary for the diagnosis, with R132H-IDH1 variant seen in > 90% of cases (Acta Neuropathol 2009;118:469)
  • TERT promoter mutation nearly always present
Differential diagnosis
  • Anaplastic oligodendroglioma, IDH mutant and 1p/19q codeleted: prominent anaplastic features such as necrosis, microvascular proliferation and brisk mitotic activity warrant this diagnosis
  • Astrocytoma, IDH mutant:
  • Macrophage rich lesion: positive for macrophage markers
  • Oligodendroglioma, NOS: a tumor that shows classical oligodendroglioma histology but molecular studies to confirm IDH mutation and 1p/19q codeletion are lacking or are inconclusive
  • Other lesions composed of oligodendroglial-like cells, such as clear cell ependymoma, dysembryoplastic neuroepithelial tumor, neurocytoma: these tumors lack IDH mutation and tend to be more circumscribed rather than infiltrative
Board review question #1
What is true about the entity shown in the photomicrograph?



  1. Nuclear expression of ATRX is most likely to be lost
  2. p53 immunohistochemistry is most likely to be strongly positive
  3. Presence of any mitotic activity makes this a grade III tumor
  4. Presence of necrosis or vascular proliferation would most likely be compatible with a histologic diagnosis of glioblastoma
  5. R132H-IDH1 mutation is most likely to be present if sequenced
Board review answer #1
E. R132H-IDH1 mutation is most likely to be present if sequenced
Board review question #2
You are working up a low grade, diffusely infiltrating glial tumor and find tumor cells are positive for R132H-IDH1, retain expression of nuclear ATRX and show weak expression of p53. What is the next appropriate step in the diagnostic workup?

  1. Order 1p/19q FISH
  2. Order Ki67
  3. Order Olig2 immunohistochemistry
  4. Send the tumor for next generation sequencing
  5. Sign the case out as astrocytoma, IDH mutant
Board review answer #2
A. Order 1p/19q FISH