Anaplastic astrocytoma

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Anaplastic astrocytoma (AKA: high-grade astrocytoma) is a infiltrating neoplasm of the diffuse astrocytic and oligodendroglial tumor group occurring in the CNS white matter.

  • Most common grade III WHO glioma in adults (peaks between 40-50 years).
  • Approx 5% of all gliomas.[1]
  • Usually shows progression to glioblastoma sooner or later.

WHO 2016 categorization combines morphology and genetics into following groups:[2]

  • Anaplastic astrocytoma, IDH-mutant (ICD-O: 9401/3).
  • Anaplastic astrocytoma, IDH-wildtype (ICD-O: 9401/3).
  • Anaplastic astrocytoma,NOS (ICD-O: 9401/3) - genetic data missing.

Radiology/Clinic

  • Mass effect.
  • Seizures.
  • Neurologic decifit.
  • The majority are contrast-enhanching, T2 bright.

Prognosis

  • Overall prognosis is rather poor (average survival 2-3 years).
  • IDH-mutant tumors share a similiar prognosis to grade II IDH-mutant tumors.[3]
  • Anaplastic astrocytoma, IDH-wildtype perform worse than glioblastoma, IDH-mutant despite grading differences.[4]

Macroscopy

  • No clear demarcation from white matter.
  • Invaded structures may appear enlarged.
  • Softer consistency and opacity.
  • No necrosis.

Histology

Features: [5]

  • Increased cellularity (compared to Diffuse Astrocytoma).
    • Specimens with low cellularity but plenty mitoses are also considered anaplastic.
  • Distinct nuclear atypia and pleomorphism.
    • May include multinucleated cells.
  • Cytoplasm highly variable (even within the same tumour).
  • Mitoses present (a single mitosis in a small specimen indicates a high-grade tumor).
  • Microcystic spaces of the background (none to extensive).
  • No necrosis, no vascular proliferations.
    • Except radiation necrosis after pretreatment.
  • Lymphocytic cuffing (mostly in gemistocytic type).
  • Rosenthal fibers usu. absent.

  • Marked mitotic activity in anaplastic astrocytoma (WC/jensflorian).

  • Marked nuclear pleomorphism (AFIP).

IHC

  • GFAP+ve.
  • MAP2+ve (especially in cell processes).
  • Vimentin+ve (often perinuclear).
  • S-100+ve.
  • MIB-1: usu. 5-10& (overlaps with grade II tumors).
  • IDH-1 (R132H)+ve in 60-70%.
    • 'Note: This antibody does not detect other rare IDH1/2 mutations.
  • ATRX nuclear loss in 70%.


Molecular

  • TERT promotor mutations in 20-25%[6][7]
  • Approximately 80 % of IDH wildtype astrocytomas in fact represent underdiagnosed GBM.[8]

DDx


  1. redirect Neuropathology_tumours#Infiltrative_astrocytomas
  1. ↑ Ohgaki, H.; Kleihues, P. (Jun 2005). "Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas.". J Neuropathol Exp Neurol 64 (6): 479-89. PMID 15977639.
  2. ↑ 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.
  3. ↑ Reuss, DE.; Mamatjan, Y.; Schrimpf, D.; Capper, D.; Hovestadt, V.; Kratz, A.; Sahm, F.; Koelsche, C. et al. (Jun 2015). "IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO.". Acta Neuropathol 129 (6): 867-73. doi:10.1007/s00401-015-1438-8. PMID 25962792.
  4. ↑ Hartmann, C.; Hentschel, B.; Wick, W.; Capper, D.; Felsberg, J.; Simon, M.; Westphal, M.; Schackert, G. et al. (Dec 2010). "Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas.". Acta Neuropathol 120 (6): 707-18. doi:10.1007/s00401-010-0781-z. PMID 21088844.
  5. ↑ 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.
  6. ↑ Lee, Y.; Koh, J.; Kim, SI.; Won, JK.; Park, CK.; Choi, SH.; Park, SH. (Aug 2017). "The frequency and prognostic effect of TERT promoter mutation in diffuse gliomas.". Acta Neuropathol Commun 5 (1): 62. doi:10.1186/s40478-017-0465-1. PMID 28851427.
  7. ↑ Koelsche, C.; Sahm, F.; Capper, D.; Reuss, D.; Sturm, D.; Jones, DT.; Kool, M.; Northcott, PA. et al. (Dec 2013). "Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system.". Acta Neuropathol 126 (6): 907-15. doi:10.1007/s00401-013-1195-5. PMID 24154961.
  8. ↑ 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.
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