CNS tumor
Diffuse astrocytic and oligodendroglial tumors
Diffuse astrocytoma, IDH-mutant




Topic Completed: 1 February 2018

Revised: 8 April 2019

Copyright: 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: Diffuse astrocytoma IDH-mutant

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Cite this page: Abdelzaher E. Diffuse astrocytoma IDH-mutant. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cnstumordiffuseastrocytomaIDHmut.html. Accessed April 25th, 2019.
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 hosted on PathOut server:

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



Images hosted on other servers:

Increased cellularity and pleomorphism

Diffuse astrocytoma, WHO grade II

Cytology description
  • Nuclear atypia
  • Fibrillary background
Positive stains
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 question #1
Which of the following is true about IDH-mutant diffuse astrocytoma?



  1. Codeletion of chromosomes 1p and 19q is a characteristic molecular alteration
  2. IDH-mutant diffuse astrocytomas have significantly better prognosis than IDH-wildtype tumors
  3. IDH protein expression is detected in astrocytic tumors only
  4. Malignant progression to higher grades does not occur
  5. 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
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