Astrocytoma, IDH-mutant - Revision history

Jensflorian: /* Molecular */ image text updated

2022-04-14T09:10:49Z

Molecular: image text updated

← Older revision		Revision as of 09:10, 14 April 2022
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	File:Astrocytoma whoII HE.jpg \| Astrocytoma, fibrillary type (WC/jensflorian)		File:Astrocytoma whoII HE.jpg \| Astrocytoma, fibrillary type (WC/jensflorian)
	File:Neuropathology case II 02.jpg \| Astrocytoma, protoplasmatic type (WC/jensflorian)		File:Neuropathology case II 02.jpg \| Astrocytoma, protoplasmatic type (WC/jensflorian)
	File:Gemistocytic astrocytoma.jpg \| ~~Gemistocytic astrocytoma~~ (WC/jensflorian)		File:Gemistocytic astrocytoma.jpg \| Astrocytoma, gemistocytic cells (WC/jensflorian)
	File:Mitoses_astro_III.jpg \| Marked mitotic activity in ~~anaplastic~~ astrocytoma (WC/jensflorian).		File:Mitoses_astro_III.jpg \| Marked mitotic activity in astrocytoma grade 3 (WC/jensflorian).
	File:405551M-ANAPLASTIC_ASTROCYTOMA.jpg \| Marked nuclear pleomorphism (AFIP).		File:405551M-ANAPLASTIC_ASTROCYTOMA.jpg \| Marked nuclear pleomorphism (AFIP).
	File:GFAP astrocytoma.jpg\| GFAP staining in astrocytoma (WC/jensflorian)		File:GFAP astrocytoma.jpg\| GFAP staining in astrocytoma (WC/jensflorian)

Jensflorian: /* Molecular */ moved from GBM

2022-04-14T09:09:56Z

Molecular: moved from GBM

← Older revision		Revision as of 09:09, 14 April 2022
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	<gallery>		<gallery>
	~~File:GFAP astrocytoma.jpg\| GFAP in astrocytoma (WC/jensflorian)~~		File:Diffuse_astrocytoma_HE_stain.jpg \| Astrocytoma, grade 2 [[H&E]] (WC/jensflorian)
	~~File:Neuropathology case II 04.jpg \| ATRX loss in astrocytoma (WC/jensflorian)~~		File:Image NP T2a 0002.JPG \| Astrocytoma, grade 2 [[H&E]] (WC/jensflorian)
	File:Diffuse_astrocytoma_HE_stain.jpg \| ~~Diffuse astrocytoma~~, [[H&E]] (WC/jensflorian)
	File:Image NP T2a 0002.JPG \| ~~Diffuse astrocytoma~~, [[H&E]] (WC/jensflorian)
	File:Astrocytoma whoII HE.jpg \| Astrocytoma, fibrillary type (WC/jensflorian)		File:Astrocytoma whoII HE.jpg \| Astrocytoma, fibrillary type (WC/jensflorian)
	File:Neuropathology case II 02.jpg \| Astrocytoma, protoplasmatic type (WC/jensflorian)		File:Neuropathology case II 02.jpg \| Astrocytoma, protoplasmatic type (WC/jensflorian)
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	File:Mitoses_astro_III.jpg \| Marked mitotic activity in anaplastic astrocytoma (WC/jensflorian).		File:Mitoses_astro_III.jpg \| Marked mitotic activity in anaplastic astrocytoma (WC/jensflorian).
	File:405551M-ANAPLASTIC_ASTROCYTOMA.jpg \| Marked nuclear pleomorphism (AFIP).		File:405551M-ANAPLASTIC_ASTROCYTOMA.jpg \| Marked nuclear pleomorphism (AFIP).
			File:GFAP astrocytoma.jpg\| GFAP staining in astrocytoma (WC/jensflorian)
			File:Neuropathology case II 04.jpg \| ATRX loss in astrocytoma (WC/jensflorian)
			File:IDH1 GBM 20x.jpg \| IDH1 R132H immunreactivity in a Grade 4 astrocytoma (WC/Marvin101)
	</gallery>		</gallery>

Jensflorian: /* Molecular */ typo

2022-04-06T13:11:28Z

Molecular: typo

← Older revision		Revision as of 13:11, 6 April 2022
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	*MGMT promotor methylated in approx. 50%.		*MGMT promotor methylated in approx. 50%.
	*CDKN2A/B homozygous deletion results in CNS grade 4<ref>{{Cite journal \| last1 = Shirahata \| first1 = M. \| last2 = Ono \| first2 = T. \| last3 = Stichel \| first3 = D. \| last4 = Schrimpf \| first4 = D. \| last5 = Reuss \| first5 = DE. \| last6 = Sahm \| first6 = F. \| last7 = Koelsche \| first7 = C. \| last8 = Wefers \| first8 = A. \| last9 = Reinhardt \| first9 = A. \| title = Novel, improved grading system(s) for IDH-mutant astrocytic gliomas. \| journal = Acta Neuropathol \| volume = 136 \| issue = 1 \| pages = 153-166 \| month = Jul \| year = 2018 \| doi = 10.1007/s00401-018-1849-4 \| PMID = 29687258 }}</ref><ref>{{Cite journal \| last1 = Aoki \| first1 = K. \| last2 = Nakamura \| first2 = H. \| last3 = Suzuki \| first3 = H. \| last4 = Matsuo \| first4 = K. \| last5 = Kataoka \| first5 = K. \| last6 = Shimamura \| first6 = T. \| last7 = Motomura \| first7 = K. \| last8 = Ohka \| first8 = F. \| last9 = Shiina \| first9 = S. \| title = Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. \| journal = Neuro Oncol \| volume = 20 \| issue = 1 \| pages = 66-77 \| month = 01 \| year = 2018 \| doi = 10.1093/neuonc/nox132 \| PMID = 29016839 }}</ref>		*CDKN2A/B homozygous deletion results in CNS grade 4<ref>{{Cite journal \| last1 = Shirahata \| first1 = M. \| last2 = Ono \| first2 = T. \| last3 = Stichel \| first3 = D. \| last4 = Schrimpf \| first4 = D. \| last5 = Reuss \| first5 = DE. \| last6 = Sahm \| first6 = F. \| last7 = Koelsche \| first7 = C. \| last8 = Wefers \| first8 = A. \| last9 = Reinhardt \| first9 = A. \| title = Novel, improved grading system(s) for IDH-mutant astrocytic gliomas. \| journal = Acta Neuropathol \| volume = 136 \| issue = 1 \| pages = 153-166 \| month = Jul \| year = 2018 \| doi = 10.1007/s00401-018-1849-4 \| PMID = 29687258 }}</ref><ref>{{Cite journal \| last1 = Aoki \| first1 = K. \| last2 = Nakamura \| first2 = H. \| last3 = Suzuki \| first3 = H. \| last4 = Matsuo \| first4 = K. \| last5 = Kataoka \| first5 = K. \| last6 = Shimamura \| first6 = T. \| last7 = Motomura \| first7 = K. \| last8 = Ohka \| first8 = F. \| last9 = Shiina \| first9 = S. \| title = Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. \| journal = Neuro Oncol \| volume = 20 \| issue = 1 \| pages = 66-77 \| month = 01 \| year = 2018 \| doi = 10.1093/neuonc/nox132 \| PMID = 29016839 }}</ref>
	~~Note:~~
	*Usu. no EGFR amplification, no combined whole chromosome 7 gain and whole chromosome 10 loss (+ 7/− 10).		*Usu. no EGFR amplification, no combined whole chromosome 7 gain and whole chromosome 10 loss (+ 7/− 10).
	*Absence of TERT promoter mutation (if present in IDH-mutant tumour, consider ~~oligodendroglionma~~).<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>		*Absence of TERT promoter mutation (if present in IDH-mutant tumour, consider oligodendroglioma).<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>

	<gallery>		<gallery>

Jensflorian: Merging complete

2022-04-06T13:10:28Z

Merging complete

← Older revision		Revision as of 13:10, 6 April 2022
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	* Astrocytoma, IDH mutant grade 4 (ICD-O: 9445/3)		* Astrocytoma, IDH mutant grade 4 (ICD-O: 9445/3)
	* Diffuse astrocytoma,NOS (ICD-O 9400/3) - genetic testing still missing.		* Diffuse astrocytoma,NOS (ICD-O 9400/3) - genetic testing still missing.

			The existence of diffuse astrocytoma, IDH wildtype is challenged.<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> Most adult IDH wildtype cases show genetic alterations identical to glioblastoma.<ref>{{Cite journal \| last1 = Hasselblatt \| first1 = M. \| last2 = Jaber \| first2 = M. \| last3 = Reuss \| first3 = D. \| last4 = Grauer \| first4 = O. \| last5 = Bibo \| first5 = A. \| last6 = Terwey \| first6 = S. \| last7 = Schick \| first7 = U. \| last8 = Ebel \| first8 = H. \| last9 = Niederstadt \| first9 = T. \| title = Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis. \| journal = J Neuropathol Exp Neurol \| volume = \| issue = \| pages = \| month = Feb \| year = 2018 \| doi = 10.1093/jnen/nly012 \| PMID = 29444314 }}</ref>

	==Astrocytoma, IDH mutant grade 2==		==Astrocytoma, IDH mutant grade 2==
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	*CDKN2A/B homozygous deletion results in CNS grade 4<ref>{{Cite journal \| last1 = Shirahata \| first1 = M. \| last2 = Ono \| first2 = T. \| last3 = Stichel \| first3 = D. \| last4 = Schrimpf \| first4 = D. \| last5 = Reuss \| first5 = DE. \| last6 = Sahm \| first6 = F. \| last7 = Koelsche \| first7 = C. \| last8 = Wefers \| first8 = A. \| last9 = Reinhardt \| first9 = A. \| title = Novel, improved grading system(s) for IDH-mutant astrocytic gliomas. \| journal = Acta Neuropathol \| volume = 136 \| issue = 1 \| pages = 153-166 \| month = Jul \| year = 2018 \| doi = 10.1007/s00401-018-1849-4 \| PMID = 29687258 }}</ref><ref>{{Cite journal \| last1 = Aoki \| first1 = K. \| last2 = Nakamura \| first2 = H. \| last3 = Suzuki \| first3 = H. \| last4 = Matsuo \| first4 = K. \| last5 = Kataoka \| first5 = K. \| last6 = Shimamura \| first6 = T. \| last7 = Motomura \| first7 = K. \| last8 = Ohka \| first8 = F. \| last9 = Shiina \| first9 = S. \| title = Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. \| journal = Neuro Oncol \| volume = 20 \| issue = 1 \| pages = 66-77 \| month = 01 \| year = 2018 \| doi = 10.1093/neuonc/nox132 \| PMID = 29016839 }}</ref>		*CDKN2A/B homozygous deletion results in CNS grade 4<ref>{{Cite journal \| last1 = Shirahata \| first1 = M. \| last2 = Ono \| first2 = T. \| last3 = Stichel \| first3 = D. \| last4 = Schrimpf \| first4 = D. \| last5 = Reuss \| first5 = DE. \| last6 = Sahm \| first6 = F. \| last7 = Koelsche \| first7 = C. \| last8 = Wefers \| first8 = A. \| last9 = Reinhardt \| first9 = A. \| title = Novel, improved grading system(s) for IDH-mutant astrocytic gliomas. \| journal = Acta Neuropathol \| volume = 136 \| issue = 1 \| pages = 153-166 \| month = Jul \| year = 2018 \| doi = 10.1007/s00401-018-1849-4 \| PMID = 29687258 }}</ref><ref>{{Cite journal \| last1 = Aoki \| first1 = K. \| last2 = Nakamura \| first2 = H. \| last3 = Suzuki \| first3 = H. \| last4 = Matsuo \| first4 = K. \| last5 = Kataoka \| first5 = K. \| last6 = Shimamura \| first6 = T. \| last7 = Motomura \| first7 = K. \| last8 = Ohka \| first8 = F. \| last9 = Shiina \| first9 = S. \| title = Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. \| journal = Neuro Oncol \| volume = 20 \| issue = 1 \| pages = 66-77 \| month = 01 \| year = 2018 \| doi = 10.1093/neuonc/nox132 \| PMID = 29016839 }}</ref>
	Note:		Note:
	*The existence of diffuse astrocytoma, IDH wildtype is challenged.<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>		*Usu. no EGFR amplification, no combined whole chromosome 7 gain and whole chromosome 10 loss (+ 7/− 10).
	**Most adult cases show genetic alterations compatible with glioblastoma.<ref>{{Cite journal \| last1 = Hasselblatt \| first1 = M. \| last2 = Jaber \| first2 = M. \| last3 = Reuss \| first3 = D. \| last4 = Grauer \| first4 = O. \| last5 = Bibo \| first5 = A. \| last6 = Terwey \| first6 = S. \| last7 = Schick \| first7 = U. \| last8 = Ebel \| first8 = H. \| last9 = Niederstadt \| first9 = T. \| title = Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis. \| journal = J Neuropathol Exp Neurol \| volume = \| issue = \| pages = \| month = Feb \| year = 2018 \| doi = 10.1093/jnen/nly012 \| PMID = 29444314 }}</ref>		*Absence of TERT promoter mutation (if present in IDH-mutant tumour, consider oligodendroglionma).<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>
	**Molecular upgrade according to cIMPACT-NOW Update 3 consensus (one of these is sufficient):<ref>{{Cite journal \| last1 = Brat \| first1 = DJ. \| last2 = Aldape \| first2 = K. \| last3 = Colman \| first3 = H. \| last4 = Holland \| first4 = EC. \| last5 = Louis \| first5 = DN. \| last6 = Jenkins \| first6 = RB. \| last7 = Kleinschmidt-DeMasters \| first7 = BK. \| last8 = Perry \| first8 = A. \| last9 = Reifenberger \| first9 = G. \| title = cIMPACT-NOW update 3: recommended diagnostic criteria for "Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV". \| journal = Acta Neuropathol \| volume = 136 \| issue = 5 \| pages = 805-810 \| month = Nov \| year = 2018 \| doi = 10.~~1007/s00401-018-1913-0 \| PMID = 30259105 }}</ref>~~
	~~***~~EGFR amplification
	***Combined whole chromosome 7 gain and whole chromosome 10 loss (+ 7/− 10)
	***TERT promoter mutation
	**Suggested Sign-out: <pre> Diffuse astrocytic glioma, IDH-~~wildtype~~, ~~with molecular features of glioblastoma, WHO grade IV</pre>~~
	**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.<ref>{{Cite journal \| last1 = Ellison \| first1 = DW. \| last2 = Hawkins \| first2 = C. \| last3 = Jones \| first3 = DTW. \| last4 = Onar-Thomas \| first4 = A. \| last5 = Pfister \| first5 = SM. \| last6 = Reifenberger \| first6 = G. \| last7 = Louis \| first7 = DN. \| title = cIMPACT-NOW update 4: diffuse gliomas characterized by MYB, MYBL1, or FGFR1 alterations or BRAF \| journal = Acta Neuropathol \| volume = 137 \| issue = 4 \| pages = 683-687 \| month = Apr \| year = 2019 \| doi = 10.1007/s00401-019-01987-0 \| PMID = 30848347 }}</ref>
	***Glial morphology can be astrocytic or oligodendrocytic.

	~~==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>

	<gallery>		<gallery>

Jensflorian: ...further merging

2022-04-06T13:05:50Z

...further merging

Show changes

Jensflorian: Merging...

2022-04-06T12:58:32Z

Merging...

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Jensflorian: 1st creation from diffuse and anaplastic astrocytoma

2022-04-06T12:45:39Z

1st creation from diffuse and anaplastic astrocytoma

New page

'''Astrocytoma, IDH-mutant''' is a diffusely-growing, infiltrating astrocytoma of the adult occurring in the CNS white matter. IDH1 codon 132 or IDH2 codon 172 mutations are frequently associated with ATRX and TP53 mutations.

=General=
The current WHO classification recognizes three tumour grades:
* Astrocytoma, IDH mutant grade 2 (ICD-O: 9400/3)
* Astrocytoma, IDH mutant grade 3 (ICD-O: 9401/3)
* Astrocytoma, IDH mutant grade 4 (ICD-O: 9445/3)
* Diffuse astrocytoma,NOS (ICD-O 9400/3) - genetic testing still missing.

==Astrocytoma, IDH mutant grade 2==
* Most common CNS grade 2 WHO glioma in adults (peaks between 30-40 years).
* 10-15% of all [[astrocytoma]]s.
* Usually shows progression to [[glioblastoma]] sooner or later.

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>
*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)<ref name=WHOCNS>{{Ref WHOCNS|25}}</ref> 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: <ref name=AFIP2007>{{Ref AFIP2007|34}}</ref>
*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.

<gallery>
File:Diffuse_astrocytoma_HE_stain.jpg | Diffuse astrocytoma, [[H&E]] (WC/jensflorian)
File:Image NP T2a 0002.JPG | Diffuse astrocytoma, [[H&E]] (WC/jensflorian)
File:Astrocytoma whoII HE.jpg | Astrocytoma, fibrillary type (WC/jensflorian)
File:Neuropathology case II 02.jpg | Astrocytoma, protoplasmatic type (WC/jensflorian)
File:Gemistocytic astrocytoma.jpg | Gemistocytic astrocytoma (WC/jensflorian)
</gallery>

==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%.

<gallery>
File:GFAP astrocytoma.jpg| GFAP in astrocytoma (WC/jensflorian)
File:Neuropathology case II 04.jpg | ATRX loss in astrocytoma (WC/jensflorian)
</gallery>

==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.<ref>{{Cite journal | last1 = Shirahata | first1 = M. | last2 = Ono | first2 = T. | last3 = Stichel | first3 = D. | last4 = Schrimpf | first4 = D. | last5 = Reuss | first5 = DE. | last6 = Sahm | first6 = F. | last7 = Koelsche | first7 = C. | last8 = Wefers | first8 = A. | last9 = Reinhardt | first9 = A. | title = Novel, improved grading system(s) for IDH-mutant astrocytic gliomas. | journal = Acta Neuropathol | volume = 136 | issue = 1 | pages = 153-166 | month = Jul | year = 2018 | doi = 10.1007/s00401-018-1849-4 | PMID = 29687258 }}</ref><ref>{{Cite journal | last1 = Aoki | first1 = K. | last2 = Nakamura | first2 = H. | last3 = Suzuki | first3 = H. | last4 = Matsuo | first4 = K. | last5 = Kataoka | first5 = K. | last6 = Shimamura | first6 = T. | last7 = Motomura | first7 = K. | last8 = Ohka | first8 = F. | last9 = Shiina | first9 = S. | title = Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. | journal = Neuro Oncol | volume = 20 | issue = 1 | pages = 66-77 | month = 01 | year = 2018 | doi = 10.1093/neuonc/nox132 | PMID = 29016839 }}</ref>
Note:
*The existence of diffuse astrocytoma, IDH wildtype is challenged.<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>
**Most adult cases show genetic alterations compatible with glioblastoma.<ref>{{Cite journal | last1 = Hasselblatt | first1 = M. | last2 = Jaber | first2 = M. | last3 = Reuss | first3 = D. | last4 = Grauer | first4 = O. | last5 = Bibo | first5 = A. | last6 = Terwey | first6 = S. | last7 = Schick | first7 = U. | last8 = Ebel | first8 = H. | last9 = Niederstadt | first9 = T. | title = Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis. | journal = J Neuropathol Exp Neurol | volume = | issue = | pages = | month = Feb | year = 2018 | doi = 10.1093/jnen/nly012 | PMID = 29444314 }}</ref>
**Molecular upgrade according to cIMPACT-NOW Update 3 consensus (one of these is sufficient):<ref>{{Cite journal | last1 = Brat | first1 = DJ. | last2 = Aldape | first2 = K. | last3 = Colman | first3 = H. | last4 = Holland | first4 = EC. | last5 = Louis | first5 = DN. | last6 = Jenkins | first6 = RB. | last7 = Kleinschmidt-DeMasters | first7 = BK. | last8 = Perry | first8 = A. | last9 = Reifenberger | first9 = G. | title = cIMPACT-NOW update 3: recommended diagnostic criteria for "Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV". | journal = Acta Neuropathol | volume = 136 | issue = 5 | pages = 805-810 | month = Nov | year = 2018 | doi = 10.1007/s00401-018-1913-0 | PMID = 30259105 }}</ref>
***EGFR amplification
***Combined whole chromosome 7 gain and whole chromosome 10 loss (+ 7/− 10)
***TERT promoter mutation
**Suggested Sign-out: <pre> Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV</pre>
**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.<ref>{{Cite journal | last1 = Ellison | first1 = DW. | last2 = Hawkins | first2 = C. | last3 = Jones | first3 = DTW. | last4 = Onar-Thomas | first4 = A. | last5 = Pfister | first5 = SM. | last6 = Reifenberger | first6 = G. | last7 = Louis | first7 = DN. | title = cIMPACT-NOW update 4: diffuse gliomas characterized by MYB, MYBL1, or FGFR1 alterations or BRAF | journal = Acta Neuropathol | volume = 137 | issue = 4 | pages = 683-687 | month = Apr | year = 2019 | doi = 10.1007/s00401-019-01987-0 | PMID = 30848347 }}</ref>
***Glial morphology can be astrocytic or oligodendrocytic.

==DDx==
For CNS grade 2 tumours:
*Reactive astrocytosis.
*Demyelinisation.
*Grade 3 astrocytoma, IDH mutant - increased mitotic activity.
*[[Oligodendroglioma]], IDH-mutant and 1p/19q codeleted - esp. protoplasmatic forms. LOH 1p/19q testing required.
*[[SEGA]] - esp. gemistocytic forms.
*Diffuse glioma, MYB- or MYBL1-altered.
For CNS grade 3 tumours:
*Anaplastic [[Oligodendroglioma]], when LOH 1p/19q is present.
*[[Glioblastoma]] - vascular proliferations and / or necrosis.

'''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 [[glioma]]s.<ref>{{Cite journal | last1 = Ohgaki | first1 = H. | last2 = Kleihues | first2 = P. | title = Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. | journal = J Neuropathol Exp Neurol | volume = 64 | issue = 6 | pages = 479-89 | month = Jun | year = 2005 | doi = | PMID = 15977639 }}</ref>
* Usually shows progression to [[glioblastoma]] sooner or later.

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-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.<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==
*No clear demarcation from white matter.
*Invaded structures may appear enlarged.
*Softer consistency and opacity.
*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>

==Outdated terminologies==
*Diffuse astrocytoma
*Gemistocytic astrocytoma
*Diffuse astrocytoma, IDH-wildtype

''Note:'' Older terminologies included Fibrillary astrocytoma (ICD-O: 9420/3) and Protoplasmatic astrocytoma (ICD-O:9410/3)<ref name=WHOCNS>{{Ref WHOCNS|25}}</ref> This subtyping is no longer in use. These tumors are now classified according their IDH mutation status.

=See also=
*[[Astrocytoma]].
*[[Neuropathology_tumours#Infiltrative_astrocytomas]]

{{Reflist|2}}

[[Category:Diagnosis]]