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: Maria Martinez-Lage, M.D.
Deputy Editor-in-Chief: Debra Zynger, M.D.
Topic Completed: 1 October 2018
Minor changes: 21 July 2020
Revised: 2 January 2019, last major update October 2018
Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.
PubMed Search: Anaplastic oligodendroglioma IDH-mutant 1p / 19q-codeleted
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Clinical features | Grading | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Additional references | Board review style question #1 | Board review answer #1 | Board review style question #2 | Board review answer #2Cite this page: DeWitt J. Anaplastic oligodendroglioma, IDH-mutant and 1p / 19q-codeleted. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumoranaplasticoli.html. Accessed August 7th, 2020.
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
- 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
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
- What is true about grading in this cellular IDH-mutant, 1p / 19q-codeleted tumor?
- 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 answer #1
E. This is a WHO grade III tumor (anaplastic oligodendroglioma, IDH-mutant and 1p / 19q-codeleted)
Board review style 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?
- 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 answer #2
