Diffuse astrocytoma

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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:[1]

  • 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)[2] This subtyping is no longer in use. These tumors are now classified according their IDH mutation status.


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


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


Features: [3]

  • 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.


  • 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%.


  • 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.[4][5]


  • The existence of diffuse astrocytoma, IDH wildtype is challenged.[6]
    • Most adult cases show genetic alterations compatible with glioblastoma.[7]
    • Molecular upgrade according to cIMPACT-NOW Update 3 consensus (one of these is sufficient):[8]
      • 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.[9]
      • 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.


See also

  1. Louis, DN.; Perry, A.; Reifenberger, G.; von Deimling, A.; Figarella-Branger, D.; Cavenee, WK.; Ohgaki, H.; Wiestler, OD. et al. (Jun 2016). "The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary.". Acta Neuropathol 131 (6): 803-20. doi:10.1007/s00401-016-1545-1. PMID 27157931.
  2. The International Agency for Research on Cancer (Editors: Louis, D.N.; Ohgaki, H.; Wiestler, O.D.; Cavenee, W.K.) (2007). Pathology and Genetics of Tumours of Tumors of the Central Nervous System (IARC WHO Classification of Tumours) (4th ed.). Lyon: World Health Organization. pp. 25. doi:10.1007/s00401-007-0243-4. ISBN 978-9283224303.
  3. Burger, P.C.; Scheithauer, B.W. (2007). Tumors of the Central Nervous System (Afip Atlas of Tumor Pathology) (4th ed.). Washington: American Registry of Pathology. pp. 34. ISBN 1933477016.
  4. Shirahata, M.; Ono, T.; Stichel, D.; Schrimpf, D.; Reuss, DE.; Sahm, F.; Koelsche, C.; Wefers, A. et al. (Jul 2018). "Novel, improved grading system(s) for IDH-mutant astrocytic gliomas.". Acta Neuropathol 136 (1): 153-166. doi:10.1007/s00401-018-1849-4. PMID 29687258.
  5. Aoki, K.; Nakamura, H.; Suzuki, H.; Matsuo, K.; Kataoka, K.; Shimamura, T.; Motomura, K.; Ohka, F. et al. (01 2018). "Prognostic relevance of genetic alterations in diffuse lower-grade gliomas.". Neuro Oncol 20 (1): 66-77. doi:10.1093/neuonc/nox132. PMID 29016839.
  6. Reuss, DE.; Kratz, A.; Sahm, F.; Capper, D.; Schrimpf, D.; Koelsche, C.; Hovestadt, V.; Bewerunge-Hudler, M. et al. (Sep 2015). "Adult IDH wild type astrocytomas biologically and clinically resolve into other tumor entities.". Acta Neuropathol 130 (3): 407-17. doi:10.1007/s00401-015-1454-8. PMID 26087904.
  7. Hasselblatt, M.; Jaber, M.; Reuss, D.; Grauer, O.; Bibo, A.; Terwey, S.; Schick, U.; Ebel, H. et al. (Feb 2018). "Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis.". J Neuropathol Exp Neurol. doi:10.1093/jnen/nly012. PMID 29444314.
  8. Brat, DJ.; Aldape, K.; Colman, H.; Holland, EC.; Louis, DN.; Jenkins, RB.; Kleinschmidt-DeMasters, BK.; Perry, A. et al. (Nov 2018). "cIMPACT-NOW update 3: recommended diagnostic criteria for "Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV".". Acta Neuropathol 136 (5): 805-810. doi:10.1007/s00401-018-1913-0. PMID 30259105.
  9. Ellison, DW.; Hawkins, C.; Jones, DTW.; Onar-Thomas, A.; Pfister, SM.; Reifenberger, G.; Louis, DN. (Apr 2019). "cIMPACT-NOW update 4: diffuse gliomas characterized by MYB, MYBL1, or FGFR1 alterations or BRAF". Acta Neuropathol 137 (4): 683-687. doi:10.1007/s00401-019-01987-0. PMID 30848347.