Diffuse astrocytoma IDH mutant

CNS tumor

Diffuse astrocytic and oligodendroglial tumors

Author: Eman Abdelzaher, M.D., Ph.D.

Topic Completed: 1 February 2018

Minor changes: 25 September 2020

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PubMed Search: Diffuse astrocytoma IDH-mutant

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Table of Contents

Cite this page: Abdelzaher E. Diffuse astrocytoma IDH mutant. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumordiffuseastrocytomaIDHmut.html. Accessed January 24th, 2021.

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

Contributed by Eman Abdelzaher, M.D., Ph.D.

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 style answer #1

B. IDH-mutant diffuse astrocytomas have significantly better prognosis than IDH-wildtype tumors

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Reference: Diffuse astrocytoma IDH mutant