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WHO 2016 categorization combines morphology and genetics into following groups:<ref>{{Cite journal | last1 = Louis | first1 = DN. | last2 = Perry | first2 = A. | last3 = Reifenberger | first3 = G. | last4 = von Deimling | first4 = A. | last5 = Figarella-Branger | first5 = D. | last6 = Cavenee | first6 = WK. | last7 = Ohgaki | first7 = H. | last8 = Wiestler | first8 = OD. | last9 = Kleihues | first9 = P. | title = The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. | journal = Acta Neuropathol | volume = 131 | issue = 6 | pages = 803-20 | month = Jun | year = 2016 | doi = 10.1007/s00401-016-1545-1 | PMID = 27157931 }}</ref> | WHO 2016 categorization combines morphology and genetics into following groups:<ref>{{Cite journal | last1 = Louis | first1 = DN. | last2 = Perry | first2 = A. | last3 = Reifenberger | first3 = G. | last4 = von Deimling | first4 = A. | last5 = Figarella-Branger | first5 = D. | last6 = Cavenee | first6 = WK. | last7 = Ohgaki | first7 = H. | last8 = Wiestler | first8 = OD. | last9 = Kleihues | first9 = P. | title = The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. | journal = Acta Neuropathol | volume = 131 | issue = 6 | pages = 803-20 | month = Jun | year = 2016 | doi = 10.1007/s00401-016-1545-1 | PMID = 27157931 }}</ref> | ||
*Anaplastic astrocytoma, IDH-mutant (ICD-O: 9401/3). | *Anaplastic astrocytoma, IDH-mutant (ICD-O: 9401/3). | ||
*Anaplastic astrocytoma, IDH-wildtype (ICD-O: | *Anaplastic astrocytoma, IDH-wildtype (ICD-O: 9401/3). | ||
*Anaplastic astrocytoma,NOS (ICD-O: | *Anaplastic astrocytoma,NOS (ICD-O: 9401/3) - genetic data missing. | ||
==Radiology/Clinic== | ==Radiology/Clinic== | ||
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*The majority are contrast-enhanching, T2 bright. | *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.<ref>{{Cite journal | last1 = Reuss | first1 = DE. | last2 = Mamatjan | first2 = Y. | last3 = Schrimpf | first3 = D. | last4 = Capper | first4 = D. | last5 = Hovestadt | first5 = V. | last6 = Kratz | first6 = A. | last7 = Sahm | first7 = F. | last8 = Koelsche | first8 = C. | last9 = Korshunov | first9 = A. | title = IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO. | journal = Acta Neuropathol | volume = 129 | issue = 6 | pages = 867-73 | month = Jun | year = 2015 | doi = 10.1007/s00401-015-1438-8 | PMID = 25962792 }}</ref> | |||
*Anaplastic astrocytoma, IDH-wildtype perform worse than glioblastoma, IDH-mutant despite grading differences.<ref>{{Cite journal | last1 = Hartmann | first1 = C. | last2 = Hentschel | first2 = B. | last3 = Wick | first3 = W. | last4 = Capper | first4 = D. | last5 = Felsberg | first5 = J. | last6 = Simon | first6 = M. | last7 = Westphal | first7 = M. | last8 = Schackert | first8 = G. | last9 = Meyermann | first9 = R. | title = 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. | journal = Acta Neuropathol | volume = 120 | issue = 6 | pages = 707-18 | month = Dec | year = 2010 | doi = 10.1007/s00401-010-0781-z | PMID = 21088844 }}</ref> | |||
==Macroscopy== | ==Macroscopy== | ||
*No clear demarcation from white matter. | *No clear demarcation from white matter. | ||
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*Softer consistency and opacity. | *Softer consistency and opacity. | ||
*No necrosis. | *No necrosis. | ||
==Histology== | |||
Features: <ref name=AFIP2007>{{Ref AFIP2007|34}}</ref> | |||
*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. | |||
<gallery> | |||
File:Mitoses_astro_III.jpg | Marked mitotic activity in anaplastic astrocytoma (WC/jensflorian). | |||
File:405551M-ANAPLASTIC_ASTROCYTOMA.jpg | Marked nuclear pleomorphism (AFIP). | |||
</gallery> | |||
==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%<ref>{{Cite journal | last1 = Lee | first1 = Y. | last2 = Koh | first2 = J. | last3 = Kim | first3 = SI. | last4 = Won | first4 = JK. | last5 = Park | first5 = CK. | last6 = Choi | first6 = SH. | last7 = Park | first7 = SH. | title = The frequency and prognostic effect of TERT promoter mutation in diffuse gliomas. | journal = Acta Neuropathol Commun | volume = 5 | issue = 1 | pages = 62 | month = Aug | year = 2017 | doi = 10.1186/s40478-017-0465-1 | PMID = 28851427 }}</ref><ref>{{Cite journal | last1 = Koelsche | first1 = C. | last2 = Sahm | first2 = F. | last3 = Capper | first3 = D. | last4 = Reuss | first4 = D. | last5 = Sturm | first5 = D. | last6 = Jones | first6 = DT. | last7 = Kool | first7 = M. | last8 = Northcott | first8 = PA. | last9 = Wiestler | first9 = B. | title = Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system. | journal = Acta Neuropathol | volume = 126 | issue = 6 | pages = 907-15 | month = Dec | year = 2013 | doi = 10.1007/s00401-013-1195-5 | PMID = 24154961 }}</ref> | |||
*Approximately 80 % of IDH wildtype astrocytomas in fact represent underdiagnosed GBM.<ref>{{Cite journal | last1 = Reuss | first1 = DE. | last2 = Kratz | first2 = A. | last3 = Sahm | first3 = F. | last4 = Capper | first4 = D. | last5 = Schrimpf | first5 = D. | last6 = Koelsche | first6 = C. | last7 = Hovestadt | first7 = V. | last8 = Bewerunge-Hudler | first8 = M. | last9 = Jones | first9 = DT. | title = Adult IDH wild type astrocytomas biologically and clinically resolve into other tumor entities. | journal = Acta Neuropathol | volume = 130 | issue = 3 | pages = 407-17 | month = Sep | year = 2015 | doi = 10.1007/s00401-015-1454-8 | PMID = 26087904 }}</ref> | |||
==DDx== | |||
*[[Diffuse astrocytoma]] - absent or very low mitotic activity. | |||
*Anaplastic [[Oligoastrocytoma]], NOS - esp. when genetic data on IDH and LOH 1p/19q are lacking. | |||
*Anaplastic [[Oligodendroglioma]], when LOH 1p/19q is present. | |||
*[[Glioblastoma]] - vascular proliferations and / or necrosis. | |||