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

Author: John DeWitt, M.D., Ph.D.
Editorial Board Member Review: Maria Martinez-Lage Alvarez, M.D.
Editor-in-Chief Review: Debra Zynger, M.D.

Revised: 26 November 2018, last major update October 2018

Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: Anaplastic oligodendroglioma IDH-mutant 1p / 19q-codeleted

Cite this page: DeWitt, J. Anaplastic oligodendroglioma, IDH-mutant and 1p / 19q-codeleted. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cnstumoranaplasticoli.html. Accessed December 12th, 2018.
Definition / general
  • WHO 2016 definition: An IDH-mutant and 1p / 19q-codeleted oligodendroglioma with focal or diffuse histological features of anaplasia (in particular, pathological microvascular proliferation or brisk mitotic activity)
Essential features
  • IDH1 or IDH2 mutation and 1p / 19q-codeletion is required for the diagnosis
  • Necrosis, palisaded or otherwise, may be seen and does not indicate progression to glioblastoma
  • Grade III of IV
  • An astrocytic component is compatible with this diagnosis when the appropriate molecular alterations are present (IDH mutation, 1p / 19q-codeletion)
  • Preferentially occur in adult patients, arising in the cerebral hemispheres
ICD coding
Epidemiology
  • Epidemiologic data mostly based on previous WHO histologic classifications
  • Incidence rate of 0.11 cases per 100,000 population (Neuro Oncol 2014;Suppl 4:iv1)
  • 0.5% of primary brain tumors, 2.5% of all gliomas
  • Median age at diagnosis of 49 years (approximately 6 years older than WHO grade II oligodendrogliomas)
  • Rare in children
  • 1.2:1 male to female ratio
Sites
  • Most commonly found in the cortex and white matter of the cerebral hemispheres
  • Frontal lobe the most common location, followed by the temporal lobe
  • Rare cases of spinal intramedullary anaplastic oligodendroglioma have been reported (J Craniovertebr Junction Spine 2017;8:253)
Clinical features
Grading
  • Grade III of IV, note that oligodendrogliomas can only be assigned WHO grade II or III, as WHO grade IV in infiltrating gliomas is restricted to astrocytomas
  • Prognostic value of grading within IDH-mutant, 1p / 19q-codeleted tumors is not entirely clear given that historical studies did not restrict the studied population to tumors only containing these molecular characteristics
  • Histological features historically characteristic of anaplasia include high cellularity, marked cytological atypia, high mitotic activity, microvascular proliferation and necrosis with or without palisading
  • Microvascular proliferation and brisk mitotic activity (> 5 mitoses per 10 high power fields) have been suggested to be of particular importance (J Neuropathol Exp Neurol 2001;60:248)
Radiology description
  • Often show a heterogeneous appearance due to the variable presence of calcifications, cystic degeneration, hemorrhage or necrosis
  • Contrast enhancement on CT or MRI is often present and can be homogeneous or patchy (Handb Clin Neurol 2012;105:467)
  • Ring enhancement may be rarely seen, but is more common in high grade astrocytoma (glioblastoma)
Radiology images

Images hosted on other servers:
Missing Image

Axial flair frontal lobe tumor

Missing Image

Axial flair large temporal lobe tumor

Missing Image

Axial flair frontal lobe tumor with hemorrhage

Missing Image

Sagittal T1


Prognostic factors
  • Historical studies found a 5 and 10 year survival rate of 52% and 39% respectively in anaplastic oligodendroglioma, however these studies did not take the presence of IDH mutation or 1p / 19q-codeletion into account (Neuro Oncol 2014;16 Suppl 4:iv1)
  • More recent data has shown overall survival times of greater than 10 years for patients with IDH-mutant, 1p / 19q-codeleted anaplastic oligodendroglioma treated with combined radiotherapy and procarbazine, carmustine, vincristine (PCV) chemotherapy (J Clin Oncol 2013;31:337, J Clin Oncol 2013;31:344)
Case reports
Treatment
Gross description
  • Often a soft, relatively well defined, greyish-pink mass arising in the cortex or subcortical white matter
  • Blurring of the grey-white junction is common
  • Calcifications may lead to a gritty texture and 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
  • Areas of tumor necrosis may be present
Microscopic (histologic) description
  • Diffusely infiltrating gliomas with moderate to high cellularity and varying morphologic appearance (J Pathol 1929;32:735)
  • Most tumor cells typically show round nuclei, perinuclear haloes, and hyperchromatic chromatin reminiscent of normal oligodendroglial cells
  • Dense network of fine branching capillaries ("chicken wire" pattern) can be present but often prominent microvascular proliferation is also seen
  • Mitoses are often prominent, with one study suggesting a cut off of 6 mitoses per 10 high power fields for designation of WHO grade III (J Neuropathol Exp Neurol 2001;60:248)
  • Necrosis, either palisaded or not, may be seen
  • Microcalcifications are often present but are not a specific finding
  • A "microgemistocytic" appearance, with a rounded belly of eccentric GFAP+ cytoplasm may be prominent (Cancer 1990;66:1204)
  • Rare cases may show sarcoma-like areas (oligosarcoma) (Clin Neuropathol 2013;32:165, Am J Surg Pathol 2007;31:351)
  • In the presence of the appropriate molecular findings (IDH mutation, 1p / 19q-codeletion) a predominant fibrillar astrocytic component is compatible with the diagnosis
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Maria Martinez-Lage Alvarez, M.D.

Nuclear-cytoplasmic ratio

Nuclear atypia and calcification

Microvascular proliferation



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

Fried egg

Mitoses

Microvascular proliferation

Necrosis

Microgemistocytic histology


Mixed astrocytic histology

IDH1-R132H

ATRX

p53

Ki67 (MIB1)

Positive stains
Negative stains
  • p53: rare positive cells can be seen
  • Keratin: although cocktails may show cross reactivity
Molecular / cytogenetics description
Differential diagnosis
  • Anaplastic oligodendroglioma, NOS: when the tumor shows classical anaplastic oligodendroglioma histology but molecular studies to confirm IDH mutation and 1p / 19q-codeletion are lacking or are inconclusive
  • Malignant small cell astrocytic tumors, such as small cell glioblastoma: important differential due to the aggressive difference in clinical course; combined IDH mutation and 1p / 19q-codeletion will not be present (Cancer 2004;101:2318)
  • Oligodendroglioma, IDH-mutant and 1p / 19q-codeleted: prominent anaplastic features such as necrosis, microvascular proliferation and mitoses are lacking to fully support a diagnosis of an anaplastic WHO grade III tumor, lower Ki67 index; similar sites of involvement and gross appearance but no necrosis
  • Diffuse astrocytoma, IDH-mutant: ATRX usually negative, p53 usually strongly positive, TERT promoter mutation typically absent
  • Other lesions composed of oligodendroglial-like cells such as clear cell ependymoma, neurocytoma, dysembryoplastic neuroepithelial tumor: all these tumors lack IDH mutation
Additional references
Board review question #1

    What is true about grading in this cellular IDH-mutant, 1p / 19q-codeleted tumor?

  1. A WHO grade of II is most appropriate
  2. Grading is not possible
  3. If necrosis is also found this is a WHO grade IV tumor
  4. The presence of microvascular proliferation makes this tumor WHO grade IV
  5. This is a WHO grade III tumor
Board review answer #1
E. This is a WHO grade III tumor (anaplastic oligodendroglioma, IDH-mutant and 1p / 19q-codeleted)
Board review question #2
    You are working up a high grade, diffusely infiltrating glial tumor with microvascular proliferation and necrosis. Molecular testing shows tumor cells are positive for IDH1-R132H mutation and 1p / 19q-codeletion. What is the most accurate diagnosis?

  1. Anaplastic astrocytoma, WHO grade III
  2. Anaplastic oligodendroglioma, WHO grade III
  3. Glioblastoma, WHO grade IV
  4. Malignant glioneuronal tumor, WHO grade IV
  5. Oligodendroglioma, WHO grade II
Board review answer #2
B. Anaplastic oligodendroglioma, WHO grade III

Comment Here