CNS tumor
Diffuse astrocytic and oligodendroglial tumors
Diffuse astrocytoma IDH mutant
Author: Eman Abdelzaher, M.D., Ph.D.
Topic Completed: 1 February 2018
Minor changes: 31 July 2020
Copyright: 2002-2020, PathologyOutlines.com, Inc.
PubMed Search: Diffuse astrocytoma IDH-mutant
Table of Contents
Definition / general | Epidemiology | Sites | Clinical features | Grading | Radiology description | Radiology images | Prognostic factors | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Board review style question #1 | Board review answer #1Cite this page: Abdelzaher E. Diffuse astrocytoma IDH mutant. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumordiffuseastrocytomaIDHmut.html. Accessed August 7th, 2020.
Definition / general
- IDH1 / 2 mutated well differentiated diffusely infiltrating glioma with astrocytic features without 1p / 19q codeletion and usually with p53 and / or ATRX mutations
- In the absence of 1p / 19q codeletion, a component morphologically resembling oligodendroglioma is compatible with this diagnosis
- Intrinsic capacity for malignant progression to IDH-mutant anaplastic astrocytoma and eventually to IDH-mutant glioblastoma (Glia 1995;15:211)
- Accounts for approximately 11 - 15% of all astrocytic brain tumors
Epidemiology
- Most commonly affects young adults in their mid 30s
- Slight predominance in men
Sites
- Occurs throughout the CNS but is preferentially located in the cerebral hemispheres especially the frontal lobes
Clinical features
- Gradual onset of symptoms
- Seizures are a common symptom in cerebral hemispheric lesions
- Changes in behavior or personality, especially in frontal lobe tumors
- Uncommonly, site dependent neurological deficits
- Manifestations of increased intracranial pressure
Grading
- WHO grade II
Radiology description
- Expanding intra-axial poorly defined mass of low signal
- Variable peritumoral edema and mass effect
- No contrast enhancement
- Variable calcification, best seen on CT
- Enhancement indicates tumor progression to higher grades
Radiology images
Images hosted on other servers:
35 year old man with diffuse
astrocytoma (multiple images)
Prognostic factors
- Recurrent with frequent progression to higher grades
- IDH1 / 2 mutant diffuse astrocytomas have significantly better prognosis than IDH-wildtype tumors, which tend to exhibit a more aggressive clinical behavior (Acta Neuropathol 2016;131:803)
- No substantial prognostic difference between WHO grades II and III IDH1 / 2 mutated astrocytomas (Acta Neuropathol 2015;129:867)
Gross description
- Ill defined neoplasm with blurring of gray white junction and expansion of the infiltrated brain areas
- Variable textures: firm, soft, gelatinous, granular
- Variable microcystic change imparting a spongy appearance
- Variable calcification with a gritty sensation
Gross images
Images hosted on other servers:
Glioma with cystic spaces in the cerebral hemisphere
Microscopic (histologic) description
- Infiltrative, diffuse growth pattern with the formation of secondary structures of Scherer (Nat Rev Neurosci 2014;15:455)
- Moderately cellular
- Irregular cell distribution
- Nuclear atypia is typical, yet variable: enlarged elongated hyperchromatic irregular nuclei
- Variable amount of cytoplasm: may be scant (naked nuclei) to moderate with processes creating a fibrillary background
- No mitotic activity (a single mitosis in a sizable specimen is allowed)
- No necrosis or microvascular proliferation
- Variable microcystic change
- Variable calcification
Microscopic (histologic) images
Images contributed by Eman Abdelzaher, M.D., Ph.D.
IDH status not assessed but likely IDH-mutant
Diffuse astrocytoma, NOS: low power
Diffuse astrocytoma, NOS: medium power
Subpial accumulation
Diffuse astrocytoma, NOS: high power
Perineuronal satellitosis
Perivascular accumulation
Cytology description
- Nuclear atypia
- Fibrillary background
Positive stains
- GFAP (variable)
- Vimentin (variable)
- Olig2
- IDH1
- Marker of infiltrating gliomas, both astrocytic or oligodendroglial (Curr Neurol Neurosci Rep 2013;13:345)
- Recognizes only the most common mutation (IDH-R132H which accounts for about 90% of all glioma associated IDH mutations, Neuro Oncol 2014;16:1478)
- In the absence of immunohistochemical evidence for IDH mutation, other IDH1 / 2 mutations must be diagnosed by mutational analysis (Neuro Oncol 2014;16:1478)
- Rare in children < 14 years (Childs Nerv Syst 2011;27:87)
- p53
- Ki67: low proliferation index (usually < 4%)
Negative stains
- ATRX
- Loss of nuclear ATRX is typical of diffuse astrocytomas, not oligodendrogliomas or reactive gliosis (Front Oncol 2017;7:236)
- Strong nuclear expression in nonneoplastic vasculature and cells serves as an internal control
Molecular / cytogenetics description
- Mutations in IDH genes: either IDH1 or IDH2
- Loss of function mutations in p53 and ATRX
- No codeletion of chromosomes 1p and 19q
- Gain of chromosome 7
Differential diagnosis
- Normal brain: beware of thick sections, no nuclear atypia, IDH1 negative, p53 negative
- Demyelinating disease: not infiltrative, numerous macrophages (CD68 positive), IDH1 negative
- Oligodendroglioma: uniform cell distribution and cytological features, rounded vesicular nuclei with small distinct nucleoli, perinuclear halos, chicken wire vessels, 1p / 19q codeletion
- Pilocytic astrocytoma: circumscribed and contrast enhancing, histologically compact biphasic architecture (alternating piloid and spongy areas), IDH1 negative
- Reactive gliosis: evenly distributed hypertrophic astrocytes, IDH1 negative
Board review style question #1
Which of the following is true about IDH-mutant diffuse astrocytoma?
- Codeletion of chromosomes 1p and 19q is a characteristic molecular alteration
- IDH-mutant diffuse astrocytomas have significantly better prognosis than IDH-wildtype tumors
- IDH protein expression is detected in astrocytic tumors only
- Malignant progression to higher grades does not occur
- Retained nuclear ATRX is typical of diffuse astrocytomas
Board review answer #1
B. IDH-mutant diffuse astrocytomas have significantly better prognosis than IDH-wildtype tumors
