Neurosurgery notes/Tumours/Gliomas, Glioneuronal Tumors, and Neuronal Tumors/Adult type diffuse astrocytoma/Low grade gliomas/Astrocytoma, IDH mutant/Grade 2 Astrocytoma IDH mutant

Grade 2 Astrocytoma IDH mutant

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Astrocytoma, IDH mutant

Definition

  • A diffusely infiltrative astrocytic glioma with an IDH1 or IDH2 mutation that is well differentiated and lacks histological features of anaplasia AND
  • Mitotic activity is not detected or very low AND
  • Absent
    • Microvascular proliferation
    • Necrosis
    • Homozygous deletions of CDKN2A and/or CDKN2B

Numbers

  • 30 yrs
  • Men
  • Frontal lobes
  • Grade 2
  • 11 - 15% of all astrocytic brain tumors
  • Recurrent with frequent progression to higher grades

Imaging

  • CT:
      • A left frontal region of low density is present with mass effect.
      • Non contrast enhancing
       
      CT
      CT
      CT+C
      CT+C
  • MRI
      • Images
      T1
      T1
      DWI
      DWI
      T1+C
      T1+C
      ADC
      ADC
      T2
      T2
      Gradient Echo
      Gradient Echo
      Flair
      Flair
    • Examples
        • 60-year-old man
        • WHO 2016
          • Grade II diffuse astrocytoma, IDHmut.
        • WHO 2021 integrated diagnosis
          • (Molecular: IDHmut, 1p/19q retained, no CDKN2A deletion): Astrocytoma, IDH-mutant, CNS WHO grade 2.
        • MRI shows moderately homogenous high T2w signal (A) which suppresses on FLAIR (B) with faint intrinsic enhancement on T1w-CE (C).
        notion image
    • T2-FLAIR mismatch with FLAIR hyperintense rim
        • Suggest it is IDH mutant non 1p19q co-deleted (Astrocytoma) meaning it can differentiate Astrocytoma from oligoodendrooglioma
        • High signal seen on T2w sequences with comparatively hypointense signal seen on FLAIR in these tumours; often with a persisting FLAIR hyperintense rim
        • Contrast enhancement is uncommon in grade 2 IDH-mutant astrocytoma but is seen at increasing frequency in the higher-grade lesions
        • Perilesional signal abnormality is more typically seen around higher-grade lesions.
        FLAIR
        FLAIR
        T2
        T2

Pathology

Macroscopic

  • 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
 
notion image
 

Microscopic

  • Infiltrative, diffuse growth pattern with the formation of secondary structures of Scherer:
    • Gliomas infiltrate around blood vessels (outside virchow-robin spaces) and along white matter tracts rather than infiltrating directly through these structures
  • Variable calcification
  • 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
Diffuse astrocytoma. A Moderately cellular tumour composed of uniform neoplastic fibrillary astrocytic cells. B Extensive microcyst formation.
Diffuse astrocytoma. A Moderately cellular tumour composed of uniform neoplastic fibrillary astrocytic cells. B Extensive microcyst formation.
 
  • Histological subtype
    • Gemistocytic astrocytoma IDH mutant:
        • Variant of IDH-mutant diffuse astrocytoma characterized by the presence of a recognizable population of neoplastic gemistocytes (> 20%)
        • Numbers
          • 10% of all grade 2 diffuse astrocytoma
          • 40 yrs
          • Men
        • Localisation
          • Frontal and temporal lobes
        • Grade 2
        • Prognosis
          • Early progression to Grade 3 and less favorable outcome
        • Microscopic
          • Presence of gemistocytes - large tumour cells with abundant dense eosinophilic, GFAP-positive cytoplasm displacing the nucleus eccentrically.
        notion image

Molecular phenotype

  • Mutations in IDH genes: either IDH1 or IDH2
  • Loss of function mutations in p53 and ATRX
  • No co-deletion of chromosomes 1p and 19q
  • Gain of chromosome 7
  • Ki67 index < 4%

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
    • Also more common in frontal lobes
    • Has many similar associations with astrocytomas that people think they originate from the same stem cell
  • 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

Prognosis

  • Median survival 6-8 yr survival
  • Inferior outcome by EORTC
    • >40yrs
    • Astrocytoma histology
    • Largest tumour diameter >6cm
      • 13% inc in size per year
      • Last 6months of growth before transformation increases to 26%
    • Tumour cross midline
    • Had neurological deficits prior to surgery
      • NOT SEIZURES
  • IDH mutant diffuse astrocytomas have significantly better prognosis than IDH-wildtype tumours, which tend to exhibit a more aggressive clinical behaviour
  • Growth rates
    • Annual growth rates of non transforming Low grade gliomas on volumetric scans
      • 13%
    • One year before progression, growth rates of low grade gliomas on volumetric scans
      • 26%
  • Progression free survival vs overall survival
    • 2 yrs advantage for progression free survival with radiotherapy not overall survival
  • 90% low grade glioma will transform to high grade
    • 50% will transform in 5yrs
      • Median survival of 6 yrs: Takes 5 yrs to transforms to high grade in 50% then have 14months left to live