Diffuse astrocytoma

Diffuse astrocytoma (AKA: diffuse, low-grade astrocytoma) is a infiltrating astrocytoma occurring in the CNS white matter.

• Most common grade II WHO glioma in adults (peaks between 30-40 years).
• 10-15% of all astrocytomas.
• Usually shows progression to glioblastoma sooner or later.

WHO 2016 categorization combines morphology and genetics into following groups:

• Diffuse astrocytoma, IDH-mutant ICD-O: 9400/3 - most frequent.
  • Gemistocytic astrocytoma, IDH-mutant ICD-O:9411/3
• Diffuse astrocytoma, IDH-wildtype ICD-O: 9400/3
• Diffuse astrocytoma,NOS ICD-O: 9400/3 - genetic data missing.

Note: Older terminologies included Fibrillary astrocytoma (ICD-O: 9420/3) and Protoplasmatic astrocytoma (ICD-O:9410/3) This subtyping is no longer in use. These tumors are now classified according their IDH mutation status.

Radiology/Clinic

• Mass effect.
• Seizures.
• Neurologic decifit.
• Usually not contrast-enhanching, T2 bright.

Macroscopy

• No clear demarcation from white matter
• May contain larger cysts
• No necrosis

Histology

Features:

• Cell density higher than normal brain.
• Mild to moderate nuclear pleomorphism.
  • Monotony of atypical nuclei and irregular distribution indicates neoplasm.
  • "naked nuclei" without recognizeable processes.
  • No prominent nucleolus.
• Cytoplasm highly variable (even within the same tumour).
  • In normal CNS the cytoplasm blends within the neuropil.
• Mitoses absent or very rare.
• Microcystic spaces of the background (none to extensive).
• No necrosis, no vascular proliferations.
  • Except radiation necrosis.
• Lymphocytic cuffing (mostly in gemistocytic type)
• Abent to few rosenthal fibers.

• 

  Diffuse astrocytoma, H&E (WC/jensflorian)

• 

  Diffuse astrocytoma, H&E (WC/jensflorian)

• 

  Astrocytoma, fibrillary type (WC/jensflorian)

• 

  Astrocytoma, protoplasmatic type (WC/jensflorian)

• 

  Gemistocytic astrocytoma (WC/jensflorian)

IHC

• GFAP+ve.
• MAP2+ve (especially in cell processes).
• Vimentin+ve (often perinuclear).
• S-100+ve.
• p53: Nuclear staining in 30% of the tumours (usually few cells).
• MIB-1: 0-5% (mean: 2%).
• IDH-1 (R132H)+ve in 60-70%.
  • 'Note: This antibody does not detect other rare IDH1/2 mutations.
• ATRX nuclear loss in 70%.

• 

  GFAP in astrocytoma (WC/jensflorian)

• 

  ATRX loss in astrocytoma (WC/jensflorian)

Molecular

• IDH1 R132- or IDH2 R172-hotsopt mutations classify the tumors as Diffuse astrocytoma, IDH-mutant.
• Absence of LOH 1p/19q (otherwise classify tumor as oligodendroglioma).
• Tp53 mutations in approx. 60% (80-90% in gemistocytic, 50% in fibrillary types).
• MGMT promotor methylated in approx. 50%.
• CDKN2A/B homozygous deletion in IDH mutant diffuse astrocytoma has unfavourable prognosis.

Note:

• The existence of diffuse astrocytoma, IDH wildtype is challenged.
  • Most adult cases show genetic alterations compatible with glioblastoma.
  • Molecular upgrade according to cIMPACT-NOW Update 3 consensus (one of these is sufficient):
    • EGFR amplification
    • Combined whole chromosome 7 gain and whole chromosome 10 loss (+ 7/− 10)
    • TERT promoter mutation
  • Suggested Sign-out:

     Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV

  • WHO grade II diffuse gliomas IDH-wt/H3-wt in children and adolescents have an indolent clinical behavior and rare anaplastic progression.
    • Most tumors show a BRAFV600E mutation, an FGFR alteration, or a MYB or MYBL1 rearrangement.
    • Glial morphology can be astrocytic or oligodendrocytic.
  • Suggested sign-out:

    Diffuse glioma, MYB-altered.
    Diffuse glioma, MYBL1-altered.
    Diffuse glioma, FGFR1 TKD-duplicated.
    Diffuse glioma, FGFR1-mutant.
    Diffuse glioma, BRAF V600E-mutant.
    Diffuse glioma, other MAPK pathway alteration.

DDx

• Reactive astrocytosis.
• Demyelinisation.
• Anaplastic astrocytoma - increased mitotic activity.
• Oligoastrocytoma, NOS - esp. when genetic data on IDH and LOH 1p/19q are lacking.
• Oligodendroglioma - esp. protoplasmatic forms. LOH 1p/19q testing required.
• SEGA - esp. gemistocytic forms.

See also

• Astrocytoma.
• Neuropathology_tumours#Infiltrative_astrocytomas