CNS tumor

Diffuse astrocytic and oligodendroglial tumors

Anaplastic oligodendroglioma, IDH-mutant and 1p / 19q-codeleted

Editorial Board Member: Maria Martinez-Lage, M.D.

Deputy Editor-in-Chief: Debra L. Zynger, M.D.

Topic Completed: 1 October 2018

Minor changes: 25 September 2020

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

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Table of Contents

Cite this page: DeWitt J. Anaplastic oligodendroglioma, IDH-mutant and 1p / 19q-codeleted. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumoranaplasticoli.html. Accessed September 20th, 2021.

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

C71.9

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

Common presenting symptoms include headache, focal neurologic deficits or mental status change (Handb Clin Neurol 2012;105:467)
Presentation with seizure is less common than in WHO grade II oligodendrogliomas (Clin Neurol Neurosurg 2013;115:2336)

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:

Axial flair frontal lobe tumor

Axial flair large temporal lobe tumor

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

22 year old man with intracranial dissemination of primary spinal cord anaplastic oligodendroglioma (Eur J Neurol 2007;14:578)
34 year old man with an anaplastic oligodendroglioma resembling meningioma and arteriovenous malformation (Exp Ther Med 2015;10:1499)
48 year old man with secondary anaplastic oligodendroglioma after cranial irradiation (J Neurooncol 2008;88:299)
55 year old man with extracranial metastasis and 1p19q loss of heterozygosity (Neurol Med Chir (Tokyo) 2010;50:161)
67 year old woman responding favorably to intranasal delivery of perillyl alcohol (Surg Neurol 2006;66:611)

Treatment

Complete resection as extensively as is safely possible, followed by upfront concurrent radiotherapy and procarbazine, carmustine, vincristine (PCV) chemotherapy (J Clin Oncol 2013;31:337, J Clin Oncol 2013;31:344)

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

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

IDH1-R132H: majority of cases (Acta Neuropathol 2009;118:599)
ATRX
GFAP: positive in intermingled reactive astrocytes and minigemistocytes
Ki67 / MIB1: typically more than 5% of tumor cells
Olig2
SOX10
MAP2
S100

Negative stains

p53: rare positive cells can be seen
Keratin: 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 (N Engl J Med 2015;372:2481, Nat Genet 2015;47:458)
Concurrent polysomy of 1p and 19q is more common in anaplastic oligodendrogliomas than WHO grade II oligodendrogliomas and is associated with a high Ki67 proliferation index and less favorable outcome (J Neuropathol Exp Neurol 2009;68:274, J Neuropathol Exp Neurol 2012;71:618)
IDH1 or IDH2 mutation necessary for the diagnosis, with IDH1-R132H variant seen in > 90% of cases (N Engl J Med 2015;372:2481, Nat Genet 2015;47:458)
TERT promoter mutation nearly always present (N Engl J Med 2015;372:2481, Nat Genet 2015;47:458)

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

IARC: WHO Classification of Tumours of the Central Nervous System, 4th Edition, 2016, Acta Neuropathol 2016;131:803
Molecular background of oligodendroglioma: 1p / 19q, IDH, TERT, CIC and FUBP1 (CNS Oncol 2015;4:287)

Board review style question #1

IDH

A WHO grade of II is most appropriate
Grading is not possible
If necrosis is also found this is a WHO grade IV tumor
The presence of microvascular proliferation makes this tumor WHO grade IV
This is a WHO grade III tumor

Board review style answer #1

E. This is a WHO grade III tumor (anaplastic oligodendroglioma, IDH-mutant and 1p / 19q-codeleted)

Comment Here

Reference: Anaplastic oligodendroglioma, IDH-mutant and 1p / 19q-codeleted

Board review style question #2

IDH1-R132H

Anaplastic astrocytoma, WHO grade III
Anaplastic oligodendroglioma, WHO grade III
Glioblastoma, WHO grade IV
Malignant glioneuronal tumor, WHO grade IV
Oligodendroglioma, WHO grade II

Board review style answer #2

B. Anaplastic oligodendroglioma, WHO grade III

Comment Here

Reference: Anaplastic oligodendroglioma, IDH-mutant and 1p / 19q-codeleted