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.

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: [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.


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%.

Molecular

  • IDH1 R132- or IDH2 R172-point mutations classify the tumors as Diffuse astrocytoma, IDH-mutant.
  • Absence of LOH 1p/19q.
  • Tp53 mutations in approx. 60% (80-90% in gemistocytic, 50% in fibrillary types).
  • MGMT promotor methylated in approx. 50%.
  • The existence of diffuse astrocytoma, IDH wildtype is challenged.[4]
    • Most cases show genetic alterations compatible with glioblastoma.[5]

DDx


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. 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.
  5. 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.