Oligodendroglioma pathophysiology: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Oligodendroglioma}} | {{Oligodendroglioma}} | ||
{{CMG}}{{AE}}{{S.M.}}{{SR}} | |||
==Overview== | ==Overview== | ||
[[Oligodendroglioma]] arises from the tripotential [[Glial cell|glial precursor cells]] and ''not'' from the [[bipotential]] [[Oligodendrocyte|oligodendrocytes]]. [[Genes]] [[Association (statistics)|associated]] with the [[pathogenesis]] of [[oligodendroglioma]] include [[Translocation|t[1;19][q10;p10]]], [[ATRX]], ''[[Mutation|NJDS]]'', ''[[Isocitrate dehydrogenase|IDH1]]'', ''[[IDH2]]'', [[TERT]] [[promoter]], [[H3F3A|H3]] K27M (''[[H3F3A]], [[HIST1H3B]]/[[HIST1H3C|C]]),'' ''[[CIC (gene)|CIC]]'', ''[[Far upstream element-binding protein 1|FUBP1]]'', ''[[p53]]'', ''[[CD57|Leu-7]]'', ''[[TCF12|TCF-12]]'', ''[[TP53]],[[Ogt|MGMT]]'', ''[[P73|TP73]]'', [[BRAF]], ''[[EGFR]]'', and ''[[PTEN]]''. Common intracranial sites involved by [[oligodendroglioma]] include [[Cerebral hemisphere|cerebral hemispheres]], [[posterior fossa]], and [[Spinal cord|intramedullary spinal cord]]. On [[gross pathology]], [[oligodendroglioma]] is characterized by a well-circumscribed, gelatinous, [[Calcified lesion|calcified]], [[cystic]], [[gray]] [[mass]] with focal [[hemorrhage]] which may expand a [[gyrus]] and remodel the [[skull]]. On [[microscopic]] [[histopathological]] [[analysis]], [[oligodendroglioma]] is characterized by [[diffuse]] [[growth]][[pattern]] of highly [[cellular]] [[lesion]] of monomorphic [[Cells (biology)|cells]] having rounded [[nucleus]] with [[atypia]], speckled "''[[salt]]-and-[[Pepper spray|pepper]]''" [[chromatin]] [[pattern]] and [[Perinuclear space|perinuclear]] [[Halo (medicine)|halo]]<nowiki/>resembling ''fried [[Egg (biology)|eggs]]'', [[Distinctive feature|distinct]] [[Cell (biology)|cell]] borders, clear [[cytoplasm]], abundant [[calcification]] and "''chicken-wire''" like [[vascularity]] [[pattern]]. [[Oligodendroglioma]] is demonstrated by [[Positivity effect|positivity]] to [[tumor markers]] such as [[Isocitrate dehydrogenase|IDH1-R132H]], [[Microtubule-associated protein|MAP2]], [[GFAP]], [[S100 calcium binding protein A8|S-100]], [[SOX10]], EMA, [[ATRX]], [[Ki-67 (Biology)|Ki-67]], [[Neuron-Specific Enolase (NSE)|NSE]], [[synaptophysin]], [[OLIG1]], and [[OLIG2]]. | |||
==Pathophysiology== | ==Pathophysiology== | ||
===Pathogenesis=== | ===Pathogenesis=== | ||
*Oligodendroglioma does ''not'' arise from the bipotential [[oligodendrocyte]]s, although [[tumor]] cells look very similiar.<ref name=pathogenesis>General features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma#cite_note-1</ref> | *[[Oligodendroglioma]] does ''not'' arise from the [[bipotential]] [[oligodendrocyte]]s, although the [[tumor]] [[Cells (biology)|cells]] look very similiar.<ref name="pathogenesis">General features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma#cite_note-1</ref> | ||
*Oligodendroglioma arises from the tripotential [[glial cell|glial precursor cells]]. | *[[Oligodendroglioma]] arises from the tripotential [[glial cell|glial precursor cells]]. | ||
===Genetics=== | ===Genetics=== | ||
*Development of oligodendroglioma is the result | *[[Development]] of [[oligodendroglioma]] is the [[result]] of multiple [[mutation|genetic mutations.]]<ref name="pmid25848751">{{cite journal| author=Suzuki H, Aoki K, Chiba K, Sato Y, Shiozawa Y, Shiraishi Y et al.| title=Mutational landscape and clonal architecture in grade II and III gliomas. | journal=Nat Genet | year= 2015 | volume= 47 | issue= 5 | pages= 458-68 | pmid=25848751 | doi=10.1038/ng.3273 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25848751 }} </ref><ref name="pmid26210286">{{cite journal| author=Leeper HE, Caron AA, Decker PA, Jenkins RB, Lachance DH, Giannini C| title=IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas. | journal=Oncotarget | year= 2015 | volume= 6 | issue= 30 | pages= 30295-305 | pmid=26210286 | doi=10.18632/oncotarget.4497 | pmc=4745799 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26210286 }} </ref><ref name="pmid24470545">{{cite journal| author=Sabha N, Knobbe CB, Maganti M, Al Omar S, Bernstein M, Cairns R et al.| title=Analysis of IDH mutation, 1p/19q deletion, and PTEN loss delineates prognosis in clinical low-grade diffuse gliomas. | journal=Neuro Oncol | year= 2014 | volume= 16 | issue= 7 | pages= 914-23 | pmid=24470545 | doi=10.1093/neuonc/not299 | pmc=4057130 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24470545 }} </ref><ref name="pmid23583981">{{cite journal| author=Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B et al.| title=Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. | journal=Nat Genet | year= 2013 | volume= 45 | issue= 6 | pages= 602-12 | pmid=23583981 | doi=10.1038/ng.2611 | pmc=3727232 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23583981 }} </ref><ref name="pmid24705251">{{cite journal| author=Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y et al.| title=The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. | journal=Nat Genet | year= 2014 | volume= 46 | issue= 5 | pages= 444-450 | pmid=24705251 | doi=10.1038/ng.2938 | pmc=4056452 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24705251 }} </ref><ref name="pmid26671986">{{cite journal| author=Tanboon J, Williams EA, Louis DN| title=The Diagnostic Use of Immunohistochemical Surrogates for Signature Molecular Genetic Alterations in Gliomas. | journal=J Neuropathol Exp Neurol | year= 2016 | volume= 75 | issue= 1 | pages= 4-18 | pmid=26671986 | doi=10.1093/jnen/nlv009 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26671986 }} </ref><ref name="pmid22869205">{{cite journal| author=Jiao Y, Killela PJ, Reitman ZJ, Rasheed AB, Heaphy CM, de Wilde RF et al.| title=Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas. | journal=Oncotarget | year= 2012 | volume= 3 | issue= 7 | pages= 709-22 | pmid=22869205 | doi=10.18632/oncotarget.588 | pmc=3443254 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22869205 }} </ref><ref name="pmid22588899">{{cite journal| author=Sahm F, Koelsche C, Meyer J, Pusch S, Lindenberg K, Mueller W et al.| title=CIC and FUBP1 mutations in oligodendrogliomas, oligoastrocytomas and astrocytomas. | journal=Acta Neuropathol | year= 2012 | volume= 123 | issue= 6 | pages= 853-60 | pmid=22588899 | doi=10.1007/s00401-012-0993-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22588899 }} </ref><ref name="pmid15709179">{{cite journal| author=Barbashina V, Salazar P, Holland EC, Rosenblum MK, Ladanyi M| title=Allelic losses at 1p36 and 19q13 in gliomas: correlation with histologic classification, definition of a 150-kb minimal deleted region on 1p36, and evaluation of CAMTA1 as a candidate tumor suppressor gene. | journal=Clin Cancer Res | year= 2005 | volume= 11 | issue= 3 | pages= 1119-28 | pmid=15709179 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15709179 }} </ref><ref name="pmid23681562">{{cite journal| author=Frenel JS, Leux C, Loussouarn D, Le Loupp AG, Leclair F, Aumont M et al.| title=Combining two biomarkers, IDH1/2 mutations and 1p/19q codeletion, to stratify anaplastic oligodendroglioma in three groups: a single-center experience. | journal=J Neurooncol | year= 2013 | volume= 114 | issue= 1 | pages= 85-91 | pmid=23681562 | doi=10.1007/s11060-013-1152-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23681562 }} </ref><ref name="pmid27651340">{{cite journal| author=Hacisalihoglu P, Kucukodaci Z, Gundogdu G, Bilgic B| title=The Correlation Between 1p/19q Codeletion, IDH1 Mutation, p53 Overexpression and Their Prognostic Roles in 41 Turkish Anaplastic Oligodendroglioma Patients. | journal=Turk Neurosurg | year= 2017 | volume= 27 | issue= 5 | pages= 682-689 | pmid=27651340 | doi=10.5137/1019-5149.JTN.16832-15.1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27651340 }} </ref> | ||
*[[Genes]] [[Association (statistics)|associated]] with the [[pathogenesis]] of [[oligodendroglioma]] include:<ref name="transloc">Molecular genetics of oligodendroglioma. https://en.wikipedia.org/wiki/Oligodendroglioma</ref><ref name="pmid21817013">{{cite journal| author=Bettegowda C, Agrawal N, Jiao Y, Sausen M, Wood LD, Hruban RH et al.| title=Mutations in CIC and FUBP1 contribute to human oligodendroglioma. | journal=Science | year= 2011 | volume= 333 | issue= 6048 | pages= 1453-5 | pmid=21817013 | doi=10.1126/science.1210557 | pmc=PMC3170506 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21817013 }} </ref><ref name="prog">Prognosis and treatment of oligodendroglioma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligodendroglioma</ref><ref name="pmid22072542">{{cite journal| author=Yip S, Butterfield YS, Morozova O, Chittaranjan S, Blough MD, An J et al.| title=Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers. | journal=J Pathol | year= 2012 | volume= 226 | issue= 1 | pages= 7-16 | pmid=22072542 | doi=10.1002/path.2995 | pmc=PMC3246739 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22072542 }} </ref><ref name="pmid26068201">{{cite journal| author=Labreche K, Simeonova I, Kamoun A, Gleize V, Chubb D, Letouzé E et al.| title=TCF12 is mutated in anaplastic oligodendroglioma. | journal=Nat Commun | year= 2015 | volume= 6 | issue= | pages= 7207 | pmid=26068201 | doi=10.1038/ncomms8207 | pmc=PMC4490400 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26068201 }} </ref><ref name="pmid21937591">{{cite journal| author=Suri V, Jha P, Agarwal S, Pathak P, Sharma MC, Sharma V et al.| title=Molecular profile of oligodendrogliomas in young patients. | journal=Neuro Oncol | year= 2011 | volume= 13 | issue= 10 | pages= 1099-106 | pmid=21937591 | doi=10.1093/neuonc/nor146 | pmc=PMC3177666 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21937591 }} </ref><ref name="pmid9038605">{{cite journal| author=Hagel C, Laking G, Laas R, Scheil S, Jung R, Milde-Langosch K et al.| title=Demonstration of p53 protein and TP53 gene mutations in oligodendrogliomas. | journal=Eur J Cancer | year= 1996 | volume= 32A | issue= 13 | pages= 2242-8 | pmid=9038605 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9038605 }} </ref><ref name="von DeimlingHartmann2005">{{cite journal|last1=von Deimling|first1=A|last2=Hartmann|first2=C|title=Oligodendrogliomas: Impact of molecular genetics on treatment|journal=Neurology India|volume=53|issue=2|year=2005|pages=140|issn=0028-3886|doi=10.4103/0028-3886.16394}}</ref><ref name="pmid26061751">{{cite journal| author=Cancer Genome Atlas Research Network. Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR et al.| title=Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. | journal=N Engl J Med | year= 2015 | volume= 372 | issue= 26 | pages= 2481-98 | pmid=26061751 | doi=10.1056/NEJMoa1402121 | pmc=4530011 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26061751 }} </ref><ref name="pmid26061753">{{cite journal| author=Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H et al.| title=Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. | journal=N Engl J Med | year= 2015 | volume= 372 | issue= 26 | pages= 2499-508 | pmid=26061753 | doi=10.1056/NEJMoa1407279 | pmc=4489704 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26061753 }} </ref><ref name="pmid11801559">{{cite journal| author=Ueki K, Nishikawa R, Nakazato Y, Hirose T, Hirato J, Funada N et al.| title=Correlation of histology and molecular genetic analysis of 1p, 19q, 10q, TP53, EGFR, CDK4, and CDKN2A in 91 astrocytic and oligodendroglial tumors. | journal=Clin Cancer Res | year= 2002 | volume= 8 | issue= 1 | pages= 196-201 | pmid=11801559 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11801559 }} </ref><ref name="pmid25150284">{{cite journal| author=Labussière M, Boisselier B, Mokhtari K, Di Stefano AL, Rahimian A, Rossetto M et al.| title=Combined analysis of TERT, EGFR, and IDH status defines distinct prognostic glioblastoma classes. | journal=Neurology | year= 2014 | volume= 83 | issue= 13 | pages= 1200-6 | pmid=25150284 | doi=10.1212/WNL.0000000000000814 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25150284 }} </ref><ref name="pmid30030640">{{cite journal| author=Nambirajan A, Suri V, Kedia S, Goyal K, Malgulwar PB, Khanna G et al.| title=Paediatric diffuse leptomeningeal tumor with glial and neuronal differentiation harbouring chromosome 1p/19q co-deletion and H3.3 K27M mutation: unusual molecular profile and its therapeutic implications. | journal=Brain Tumor Pathol | year= 2018 | volume= 35 | issue= 3 | pages= 186-191 | pmid=30030640 | doi=10.1007/s10014-018-0325-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30030640 }} </ref> | |||
:*[[translocation|t(1;19)(q10;p10)]] (co-[[Deletion (genetics)|deletion]] of [[chromosomal]] arms [[chromosome 1|1p]]36 and [[chromosome 19|19q]]13; most common)<ref name="pmid16088966">{{cite journal| author=McDonald JM, See SJ, Tremont IW, Colman H, Gilbert MR, Groves M et al.| title=The prognostic impact of histology and 1p/19q status in anaplastic oligodendroglial tumors. | journal=Cancer | year= 2005 | volume= 104 | issue= 7 | pages= 1468-77 | pmid=16088966 | doi=10.1002/cncr.21338 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16088966 }} </ref><ref name="pmid15709179">{{cite journal| author=Barbashina V, Salazar P, Holland EC, Rosenblum MK, Ladanyi M| title=Allelic losses at 1p36 and 19q13 in gliomas: correlation with histologic classification, definition of a 150-kb minimal deleted region on 1p36, and evaluation of CAMTA1 as a candidate tumor suppressor gene. | journal=Clin Cancer Res | year= 2005 | volume= 11 | issue= 3 | pages= 1119-28 | pmid=15709179 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15709179 }} </ref><ref name="pmid7977648">{{cite journal| author=Reifenberger J, Reifenberger G, Liu L, James CD, Wechsler W, Collins VP| title=Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. | journal=Am J Pathol | year= 1994 | volume= 145 | issue= 5 | pages= 1175-90 | pmid=7977648 | doi= | pmc=1887413 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7977648 }} </ref> | |||
:*[[ATRX]]<ref name="pmid25427834">{{cite journal| author=Reuss DE, Sahm F, Schrimpf D, Wiestler B, Capper D, Koelsche C et al.| title=ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an "integrated" diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. | journal=Acta Neuropathol | year= 2015 | volume= 129 | issue= 1 | pages= 133-46 | pmid=25427834 | doi=10.1007/s00401-014-1370-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25427834 }} </ref> | |||
:*''[[Isocitrate dehydrogenase|IDH1]]''<ref name="pmid27780605">{{cite journal| author=Chen N, Yu T, Gong J, Nie L, Chen X, Zhang M et al.| title=IDH1/2 gene hotspot mutations in central nervous system tumours: analysis of 922 Chinese patients. | journal=Pathology | year= 2016 | volume= 48 | issue= 7 | pages= 675-683 | pmid=27780605 | doi=10.1016/j.pathol.2016.07.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27780605 }} </ref><ref name="pmid22113362">{{cite journal| author=Zhou YX, Wang JX, Feng M, Sun CM, Sun T, Chen GL et al.| title=Analysis of isocitrate dehydrogenase 1 mutation in 97 patients with glioma. | journal=J Mol Neurosci | year= 2012 | volume= 47 | issue= 3 | pages= 442-7 | pmid=22113362 | doi=10.1007/s12031-011-9681-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22113362 }} </ref><ref name="pmid19903171">{{cite journal| author=Capper D, Weissert S, Balss J, Habel A, Meyer J, Jäger D et al.| title=Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. | journal=Brain Pathol | year= 2010 | volume= 20 | issue= 1 | pages= 245-54 | pmid=19903171 | doi=10.1111/j.1750-3639.2009.00352.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19903171 }} </ref><ref name="pmid19228619">{{cite journal| author=Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W et al.| title=IDH1 and IDH2 mutations in gliomas. | journal=N Engl J Med | year= 2009 | volume= 360 | issue= 8 | pages= 765-73 | pmid=19228619 | doi=10.1056/NEJMoa0808710 | pmc=2820383 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19228619 }} </ref><ref name="pmid18985363">{{cite journal| author=Balss J, Meyer J, Mueller W, Korshunov A, Hartmann C, von Deimling A| title=Analysis of the IDH1 codon 132 mutation in brain tumors. | journal=Acta Neuropathol | year= 2008 | volume= 116 | issue= 6 | pages= 597-602 | pmid=18985363 | doi=10.1007/s00401-008-0455-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18985363 }} </ref><ref name="pmid24748374">{{cite journal| author=Arita H, Narita Y, Matsushita Y, Fukushima S, Yoshida A, Takami H et al.| title=Development of a robust and sensitive pyrosequencing assay for the detection of IDH1/2 mutations in gliomas. | journal=Brain Tumor Pathol | year= 2015 | volume= 32 | issue= 1 | pages= 22-30 | pmid=24748374 | doi=10.1007/s10014-014-0186-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24748374 }} </ref><ref name="pmid20847279">{{cite journal| author=Setty P, Hammes J, Rothämel T, Vladimirova V, Kramm CM, Pietsch T et al.| title=A pyrosequencing-based assay for the rapid detection of IDH1 mutations in clinical samples. | journal=J Mol Diagn | year= 2010 | volume= 12 | issue= 6 | pages= 750-6 | pmid=20847279 | doi=10.2353/jmoldx.2010.090237 | pmc=2963913 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20847279 }} </ref><ref name="pmid23370430">{{cite journal| author=Pang B, Durso MB, Hamilton RL, Nikiforova MN| title=A novel COLD-PCR/FMCA assay enhances the detection of low-abundance IDH1 mutations in gliomas. | journal=Diagn Mol Pathol | year= 2013 | volume= 22 | issue= 1 | pages= 28-34 | pmid=23370430 | doi=10.1097/PDM.0b013e31826c7ff8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23370430 }} </ref><ref name="pmid20886613">{{cite journal| author=Boisselier B, Marie Y, Labussière M, Ciccarino P, Desestret V, Wang X et al.| title=COLD PCR HRM: a highly sensitive detection method for IDH1 mutations. | journal=Hum Mutat | year= 2010 | volume= 31 | issue= 12 | pages= 1360-5 | pmid=20886613 | doi=10.1002/humu.21365 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20886613 }} </ref> | |||
:*''[[IDH2]]''<ref name="pmid24004584">{{cite journal| author=Pan Y, Qi XL, Wang LM, Dong RF, Zhang M, Zheng DF et al.| title=[Mutation of isocitrate dehydrogenase gene in Chinese patients with glioma]. | journal=Zhonghua Bing Li Xue Za Zhi | year= 2013 | volume= 42 | issue= 5 | pages= 292-8 | pmid=24004584 | doi=10.3760/cma.j.issn.0529-5807.2013.05.002 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24004584 }} </ref><ref name="pmid19554337">{{cite journal| author=Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A et al.| title=Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. | journal=Acta Neuropathol | year= 2009 | volume= 118 | issue= 4 | pages= 469-74 | pmid=19554337 | doi=10.1007/s00401-009-0561-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19554337 }} </ref><ref name="pmid19765000">{{cite journal| author=Sonoda Y, Kumabe T, Nakamura T, Saito R, Kanamori M, Yamashita Y et al.| title=Analysis of IDH1 and IDH2 mutations in Japanese glioma patients. | journal=Cancer Sci | year= 2009 | volume= 100 | issue= 10 | pages= 1996-8 | pmid=19765000 | doi=10.1111/j.1349-7006.2009.01270.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19765000 }} </ref><ref name="pmid25008158">{{cite journal| author=Arita H, Narita Y, Yoshida A, Hashimoto N, Yoshimine T, Ichimura K| title=IDH1/2 mutation detection in gliomas. | journal=Brain Tumor Pathol | year= 2015 | volume= 32 | issue= 2 | pages= 79-89 | pmid=25008158 | doi=10.1007/s10014-014-0197-x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25008158 }} </ref><ref name="pmid20160062">{{cite journal| author=van den Bent MJ, Dubbink HJ, Marie Y, Brandes AA, Taphoorn MJ, Wesseling P et al.| title=IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. | journal=Clin Cancer Res | year= 2010 | volume= 16 | issue= 5 | pages= 1597-604 | pmid=20160062 | doi=10.1158/1078-0432.CCR-09-2902 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20160062 }} </ref><ref name="pmid24889502">{{cite journal| author=Catteau A, Girardi H, Monville F, Poggionovo C, Carpentier S, Frayssinet V et al.| title=A new sensitive PCR assay for one-step detection of 12 IDH1/2 mutations in glioma. | journal=Acta Neuropathol Commun | year= 2014 | volume= 2 | issue= | pages= 58 | pmid=24889502 | doi=10.1186/2051-5960-2-58 | pmc=4229941 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24889502 }} </ref> | |||
: | :*[[TERT]] [[promoter]]<ref name="pmid26061753">{{cite journal| author=Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H et al.| title=Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. | journal=N Engl J Med | year= 2015 | volume= 372 | issue= 26 | pages= 2499-508 | pmid=26061753 | doi=10.1056/NEJMoa1407279 | pmc=4489704 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26061753 }} </ref><ref name="pmid30346624">{{cite journal| author=Diplas BH, Liu H, Yang R, Hansen LJ, Zachem AL, Zhao F et al.| title=Sensitive and rapid detection of TERT promoter and IDH mutations in diffuse gliomas. | journal=Neuro Oncol | year= 2019 | volume= 21 | issue= 4 | pages= 440-450 | pmid=30346624 | doi=10.1093/neuonc/noy167 | pmc=6422442 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30346624 }} </ref><ref name="pmid26617880">{{cite journal| author=Sun ZL, Chan AK, Chen LC, Tang C, Zhang ZY, Ding XJ et al.| title=TERT promoter mutated WHO grades II and III gliomas are located preferentially in the frontal lobe and avoid the midline. | journal=Int J Clin Exp Pathol | year= 2015 | volume= 8 | issue= 9 | pages= 11485-94 | pmid=26617880 | doi= | pmc=4637696 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26617880 }} </ref><ref name="pmid26957363">{{cite journal| author=Yang P, Cai J, Yan W, Zhang W, Wang Y, Chen B et al.| title=Classification based on mutations of TERT promoter and IDH characterizes subtypes in grade II/III gliomas. | journal=Neuro Oncol | year= 2016 | volume= 18 | issue= 8 | pages= 1099-108 | pmid=26957363 | doi=10.1093/neuonc/now021 | pmc=4933482 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26957363 }} </ref><ref name="pmid25314060">{{cite journal| author=Labussière M, Di Stefano AL, Gleize V, Boisselier B, Giry M, Mangesius S et al.| title=TERT promoter mutations in gliomas, genetic associations and clinico-pathological correlations. | journal=Br J Cancer | year= 2014 | volume= 111 | issue= 10 | pages= 2024-32 | pmid=25314060 | doi=10.1038/bjc.2014.538 | pmc=4229642 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25314060 }} </ref><ref name="pmid26608520">{{cite journal| author=Nencha U, Rahimian A, Giry M, Sechi A, Mokhtari K, Polivka M et al.| title=TERT promoter mutations and rs2853669 polymorphism: prognostic impact and interactions with common alterations in glioblastomas. | journal=J Neurooncol | year= 2016 | volume= 126 | issue= 3 | pages= 441-6 | pmid=26608520 | doi=10.1007/s11060-015-1999-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26608520 }} </ref> | ||
:*[[H3F3A|H3]] K27M [[mutations]] in either ''[[H3F3A]]'' (one of two [[genes]] [[Encoding (memory)|encoding]] the [[histone]] H3.3 variant) or ''[[HIST1H3B]]/[[HIST1H3C|C]]'' ([[Encoding (memory)|encoding]] the [[histone]] H3.1 variant).<ref name="pmid22661320">{{cite journal| author=Khuong-Quang DA, Buczkowicz P, Rakopoulos P, Liu XY, Fontebasso AM, Bouffet E et al.| title=K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. | journal=Acta Neuropathol | year= 2012 | volume= 124 | issue= 3 | pages= 439-47 | pmid=22661320 | doi=10.1007/s00401-012-0998-0 | pmc=3422615 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22661320 }} </ref><ref name="pmid30890717">{{cite journal| author=Harutyunyan AS, Krug B, Chen H, Papillon-Cavanagh S, Zeinieh M, De Jay N et al.| title=H3K27M induces defective chromatin spread of PRC2-mediated repressive H3K27me2/me3 and is essential for glioma tumorigenesis. | journal=Nat Commun | year= 2019 | volume= 10 | issue= 1 | pages= 1262 | pmid=30890717 | doi=10.1038/s41467-019-09140-x | pmc=6425035 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30890717 }} </ref><ref name="pmid22286216">{{cite journal| author=Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J et al.| title=Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. | journal=Nat Genet | year= 2012 | volume= 44 | issue= 3 | pages= 251-3 | pmid=22286216 | doi=10.1038/ng.1102 | pmc=3288377 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22286216 }} </ref><ref name="pmid26399631">{{cite journal| author=Castel D, Philippe C, Calmon R, Le Dret L, Truffaux N, Boddaert N et al.| title=Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. | journal=Acta Neuropathol | year= 2015 | volume= 130 | issue= 6 | pages= 815-27 | pmid=26399631 | doi=10.1007/s00401-015-1478-0 | pmc=4654747 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26399631 }} </ref><ref name="pmid27038188">{{cite journal| author=Castel D, Grill J, Debily MA| title=Histone H3 genotyping refines clinico-radiological diagnostic and prognostic criteria in DIPG. | journal=Acta Neuropathol | year= 2016 | volume= 131 | issue= 5 | pages= 795-6 | pmid=27038188 | doi=10.1007/s00401-016-1568-7 | pmc=4835508 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27038188 }} </ref><ref name="pmid28522693">{{cite journal| author=Cordero FJ, Huang Z, Grenier C, He X, Hu G, McLendon RE et al.| title=Histone H3.3K27M Represses p16 to Accelerate Gliomagenesis in a Murine Model of DIPG. | journal=Mol Cancer Res | year= 2017 | volume= 15 | issue= 9 | pages= 1243-1254 | pmid=28522693 | doi=10.1158/1541-7786.MCR-16-0389 | pmc=5581686 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28522693 }} </ref> | |||
:*''[[mutation|NJDS]]'' (A 2009 [[Oxford Forum|Oxford]] Neurosymposium [[Study design|study]] illustrated that there's a 69% [[correlation]] between NJDS [[gene mutation]] and [[tumor]] [[Initiation (chemistry)|initiation]]). | |||
:*''[[CIC (gene)|CIC]]''<ref name="pmid24086756">{{cite journal| author=Eisenreich S, Abou-El-Ardat K, Szafranski K, Campos Valenzuela JA, Rump A, Nigro JM et al.| title=Novel CIC point mutations and an exon-spanning, homozygous deletion identified in oligodendroglial tumors by a comprehensive genomic approach including transcriptome sequencing. | journal=PLoS One | year= 2013 | volume= 8 | issue= 9 | pages= e76623 | pmid=24086756 | doi=10.1371/journal.pone.0076623 | pmc=3785522 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24086756 }} </ref><ref name="pmid22072542">{{cite journal| author=Yip S, Butterfield YS, Morozova O, Chittaranjan S, Blough MD, An J et al.| title=Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers. | journal=J Pathol | year= 2012 | volume= 226 | issue= 1 | pages= 7-16 | pmid=22072542 | doi=10.1002/path.2995 | pmc=3246739 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22072542 }} </ref> | |||
:*''[[Far upstream element-binding protein 1|FUBP1]]'' | :*''[[Far upstream element-binding protein 1|FUBP1]]'' | ||
:*''[[p53]]'' | :*''[[TP53]]'' | ||
:*''[[p53]]''<ref name="pmid24590827">{{cite journal| author=Gillet E, Alentorn A, Doukouré B, Mundwiller E, van Thuijl HF, van Thuij H et al.| title=TP53 and p53 statuses and their clinical impact in diffuse low grade gliomas. | journal=J Neurooncol | year= 2014 | volume= 118 | issue= 1 | pages= 131-9 | pmid=24590827 | doi=10.1007/s11060-014-1407-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24590827 }} </ref> | |||
:*[[BRAF]] alterations:<ref name="pmid25720745">{{cite journal| author=Rodriguez FJ, Schniederjan MJ, Nicolaides T, Tihan T, Burger PC, Perry A| title=High rate of concurrent BRAF-KIAA1549 gene fusion and 1p deletion in disseminated oligodendroglioma-like leptomeningeal neoplasms (DOLN). | journal=Acta Neuropathol | year= 2015 | volume= 129 | issue= 4 | pages= 609-610 | pmid=25720745 | doi=10.1007/s00401-015-1400-9 | pmc=4696044 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25720745 }} </ref> | |||
:**''[[KIAA1549L (gene)|KIAA1549]]''-''[[BRAF (gene)|BRAF]]'' [[Fusion gene|fusion]] | |||
:**''[[BRAF]]'' V600E [[mutation]] | |||
:*''[[CD57|Leu-7]]'' | :*''[[CD57|Leu-7]]'' | ||
:*''[[TCF12|TCF-12]]'' | :*''[[TCF12|TCF-12]]'' | ||
| Line 26: | Line 34: | ||
:*''[[EGFR]]'' | :*''[[EGFR]]'' | ||
:*''[[PTEN]]'' | :*''[[PTEN]]'' | ||
*There is a strong association of oligodendroglioma with expression of receptor tyrosine kinases that activate PI3K/AKT, RAS/MAP, and PLC/PKC pathways.<ref name="von DeimlingHartmann2005">{{cite journal|last1=von Deimling|first1=A|last2=Hartmann|first2=C|title=Oligodendrogliomas: Impact of molecular genetics on treatment|journal=Neurology India|volume=53|issue=2|year=2005|pages=140|issn=0028-3886|doi=10.4103/0028-3886.16394}}</ref> | *There is a [[strong]] [[Association (statistics)|association]] of [[oligodendroglioma]] with [[expression]] of [[receptor tyrosine kinases]] that activate [[Phosphoinositide 3-kinase|PI3K]]/[[AKT]], [[RAS]]/[[MAP]], and [[PLC]]/[[PKC alpha|PKC]] pathways.<ref name="von DeimlingHartmann2005">{{cite journal|last1=von Deimling|first1=A|last2=Hartmann|first2=C|title=Oligodendrogliomas: Impact of molecular genetics on treatment|journal=Neurology India|volume=53|issue=2|year=2005|pages=140|issn=0028-3886|doi=10.4103/0028-3886.16394}}</ref> | ||
===Gross Pathology=== | ===Gross Pathology=== | ||
*On gross pathology, oligodendroglioma is characterized by a well-circumscribed, gelatinous, gray mass which may expand a [[gyrus]] and remodel the [[skull]] | *On [[gross pathology]], [[oligodendroglioma]] is characterized by a well-circumscribed, [[Gelatinase|gelatinous]], [[gray]] [[mass]] which may [[Expanded access|expand]] a [[gyrus]] and remodel the [[skull|skul.l]]<ref name="grosspa">Gross appearance of oligodendroglioma. Dr Henry Knipe and Dr Frank Gaillard et al. http://radiopaedia.org/articles/oligodendroglioma</ref> | ||
*Other characteristic gross pathological features associated with oligodendroglioma include:<ref name=grosspa>Gross appearance of oligodendroglioma. Dr Henry Knipe and Dr Frank Gaillard et al. http://radiopaedia.org/articles/oligodendroglioma</ref><ref name="von DeimlingHartmann2005">{{cite journal|last1=von Deimling|first1=A|last2=Hartmann|first2=C|title=Oligodendrogliomas: Impact of molecular genetics on treatment|journal=Neurology India|volume=53|issue=2|year=2005|pages=140|issn=0028-3886|doi=10.4103/0028-3886.16394}}</ref> | *Other [[Characteristic function (probability theory)|characteristic]] [[Gross pathology|gross pathological]] [[Features (pattern recognition)|features]] [[Association (statistics)|associated]] with [[oligodendroglioma]] include:<ref name="grosspa">Gross appearance of oligodendroglioma. Dr Henry Knipe and Dr Frank Gaillard et al. http://radiopaedia.org/articles/oligodendroglioma</ref><ref name="von DeimlingHartmann2005">{{cite journal|last1=von Deimling|first1=A|last2=Hartmann|first2=C|title=Oligodendrogliomas: Impact of molecular genetics on treatment|journal=Neurology India|volume=53|issue=2|year=2005|pages=140|issn=0028-3886|doi=10.4103/0028-3886.16394}}</ref> | ||
**[[Calcification]] (70-90%; one of the most [[Frequentism|frequently]] [[Calcification|calcifying]] [[tumors]]) | |||
**[[Hemorrhage|Focal hemorrhage]] | |||
**[[cyst|Cystic]] (20%) | |||
*Common intracranial sites [[Association (statistics)|associated]] with [[oligodendroglioma]] include:<ref name="gross">Gross/radiologic findings of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref> | |||
*Common intracranial sites associated with oligodendroglioma include:<ref name=gross>Gross/radiologic findings of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref> | **[[Cerebral hemisphere]]s ([[cortex]] and [[white matter]]) - [[Distribution (pharmacology)|distribution]] between [[frontal lobe|frontal]] (most common, > 50% of cases), [[parietal lobe|parietal]], [[temporal lobe|temporal]], and [[occipital lobe]] approximates 3:2:2:1. | ||
**[[Posterior fossa]] ([[rare]]) | |||
**[[spinal cord|Intramedullary spinal cord]] (very [[rare]], only 1.5% of [[oligodendrogliomas]]). | |||
{| | |||
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[[File:Oligogross.jpg|thumb|250px|none| Oligodendroglioma involving frontal lobe [http://peir.path.uab.edu/library/picture.php?/18102]]] | |||
| | |||
[[File:Mixedoligo.jpg|thumb|250px|none| Mixed astrocytoma and oligodendroglioma [http://peir.path.uab.edu/library/picture.php?/18103/categories]]] | |||
| | |||
[[File:Oliggross.jpg|thumb|250px|none| Oligodendroglioma gross appearance [http://peir.path.uab.edu/library/picture.php?/18104/categories]]] | |||
|} | |||
===Microscopic Pathology=== | ===Microscopic Pathology=== | ||
On microscopic histopathological analysis, oligodendroglioma is characterized by:<ref name="von DeimlingHartmann2005">{{cite journal|last1=von Deimling|first1=A|last2=Hartmann|first2=C|title=Oligodendrogliomas: Impact of molecular genetics on treatment|journal=Neurology India|volume=53|issue=2|year=2005|pages=140|issn=0028-3886|doi=10.4103/0028-3886.16394}}</ref> | On [[microscopic]] [[histopathological]] [[analysis]], [[oligodendroglioma]] is characterized by:<ref name="von DeimlingHartmann2005">{{cite journal|last1=von Deimling|first1=A|last2=Hartmann|first2=C|title=Oligodendrogliomas: Impact of molecular genetics on treatment|journal=Neurology India|volume=53|issue=2|year=2005|pages=140|issn=0028-3886|doi=10.4103/0028-3886.16394}}</ref><ref name="micro">Microscopic features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref><ref name="turk">{{Citation |last=Ersen |first=Ayca|year=2008 |title=Pathology of malignant gliomas: Challenges of everyday practice and the WHO 2007 |publisher=Turkish Journal of Pathology |publication-place= |page= |url=http://www.turkjpath.org/text.php3?id=645 |accessdate=9 October, 2015 }}</ref><ref name="pmid15509821">{{cite journal| author=Eskandar EN, Loeffler JS, O'Neill AM, Hunter GJ, Louis DN| title=Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 33-2004. A 34-year-old man with a seizure and a frontal-lobe brain lesion. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 18 | pages= 1875-82 | pmid=15509821 | doi=10.1056/NEJMcpc049025 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15509821 }} </ref><ref name="pmid22941225">{{cite journal| author=Rodriguez FJ, Perry A, Rosenblum MK, Krawitz S, Cohen KJ, Lin D et al.| title=Disseminated oligodendroglial-like leptomeningeal tumor of childhood: a distinctive clinicopathologic entity. | journal=Acta Neuropathol | year= 2012 | volume= 124 | issue= 5 | pages= 627-41 | pmid=22941225 | doi=10.1007/s00401-012-1037-x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22941225 }} </ref> | ||
<ref name=micro>Microscopic features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref><ref name=turk>{{Citation | *[[Diffuse|Diffusely]] [[Growth|growing]], [[Infiltration (medical)|infiltrative]] [[tumor]] | ||
*Diffusely growing tumor | *Moderate [[Cellular|cellularity]] | ||
*Highly cellular lesion composed of cells resembling ''fried eggs'' with: | *Highly [[cellular]] [[lesion]] composed of [[Typical set|typically]] monomorphic [[Cells (biology)|cells]] resembling ''fried [[Egg (biology)|eggs]]'' with: | ||
**[[nucleus|Round nucleus]] - key feature | **[[nucleus|Round nucleus]] - key [[Features (pattern recognition)|feature]] | ||
**Distinct cell borders | **[[Distinctive feature|Distinct]] [[Cell (biology)|cell]] borders | ||
**Moderate-to-marked [[atypia|nuclear atypia]] with speckled "''salt-and-pepper''" chromatin pattern | **Moderate-to-marked [[atypia|nuclear atypia]] with [[Speckle pattern|speckled]] "''[[salt]]-and-[[Pepper spray|pepper]]''" [[chromatin]] [[pattern]] | ||
**[[cytoplasm|Clear cytoplasm]] | **Inconspicuous [[nucleoli]] | ||
***Some oligodendrogliomas have [[eosinophilic]] cytoplasm with focal perinuclear clearing | **[[cytoplasm|Clear cytoplasm]] (artifactual [[retraction]] of the [[cytoplasm]] on routinely [[Process (anatomy)|processed]] [[formalin]] [[Fixed effects|fixed]], [[paraffin]] [[Embedded value|embedded]] [[Materials science|material]], [[Leading strand|leading]] to the [[Characteristic function (probability theory)|characteristic]] "fried [[Egg (biology)|egg]]" [[appearance]]). | ||
** | ***Some [[oligodendrogliomas]] have [[eosinophilic]] [[cytoplasm]] with focal [[Perinuclear space|perinuclear]] clearing. | ||
***Abundant | **[[Dense]] [[Network motif|network]] of [[Acute|acutely]] fine branched [[capillary]] [[Size consistency|sized]] [[vessels]] -classically [[Reference|referred]] to as a "''chicken-wire''" like [[appearance]]/[[pattern|pattern.]]<ref name="microscope">Images of microscopic appearance of oligodendroglioma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligodendroglioma</ref> | ||
*[[ | ***Abundant and delicate [[Appearance|appearing]]; may [[Vagueness|vaguely]] resemble a [[paraganglioma]] at low [[Power nap|power]]. | ||
*Perifocal [[edema]] - rare | *Small punctate [[calcification]]s, particularly along the [[blood vessels]] is a striking [[Features (pattern recognition)|feature]] (but not a [[Specific activity|specific]] finding). | ||
*Few tumors may exhibit [[eosinophilic]] granular bodies | *Perifocal [[edema]] - [[rare]] | ||
*Some tumors may show a spongioblastoma-like growth pattern | *[[Fewmets|Few]] [[tumors]] may [[Exhibitionism|exhibit]] [[eosinophilic]] [[Granular cell|granular]] [[Body|bodies]] | ||
*Some [[tumors]] may show a [[spongioblastoma]]-like [[growth]] [[pattern]] | |||
On microscopic histopathological analysis, [[anaplastic|anaplastic oligodendroglioma]] is characterized by:<ref name=micro>Microscopic features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref> | *[[Tumor cell|Tumor cells]] may form following [[Secondary structure|secondary structures]] in the surrounding [[Infiltration (medical)|infiltrated]] [[brain]] [[parenchyma]]: | ||
*Focal or diffusely increased cell density | **Perineuronal satellitosis | ||
*Atypical to frankly [[pleomorphic]] cells or [[multinucleated giant cells]] | **[[Subpial space|Subpial]] accumulation | ||
*Tumor cells may be plasmacytoid (i.e. have a [[plasma cell]]-like appearance) | **[[Perivascular cell|Perivascular]] [[Distribution (pharmacology)|distribution]] (less common) | ||
*Microgemistocytic [[appearance]] of [[Tumor cell|tumor cells]] with a rounded [[belly]] of [[Eccentricity (mathematics)|eccentric]] [[Glial fibrillary acidic protein|GFAP]]+ [[eosinophilic]] [[cytoplasm]] (maybe present).<ref name="pmid2205356">{{cite journal| author=Kros JM, Van Eden CG, Stefanko SZ, Waayer-Van Batenburg M, van der Kwast TH| title=Prognostic implications of glial fibrillary acidic protein containing cell types in oligodendrogliomas. | journal=Cancer | year= 1990 | volume= 66 | issue= 6 | pages= 1204-12 | pmid=2205356 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2205356 }} </ref> | |||
*A predominant [[Fibrillarin|fibrillar]] [[astrocytic]] [[phenotype]] is compatible with the [[diagnosis]] when following [[Appropriate Use Criteria|appropriate]] [[molecular]] findings are present:<ref name="pmid26061751">{{cite journal| author=Cancer Genome Atlas Research Network. Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR et al.| title=Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. | journal=N Engl J Med | year= 2015 | volume= 372 | issue= 26 | pages= 2481-98 | pmid=26061751 | doi=10.1056/NEJMoa1402121 | pmc=4530011 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26061751 }} </ref> | |||
**''[[IDH1|IDH]]'' [[mutation]] | |||
**[[1p36 deletion syndrome|1p]]/19q codeletion | |||
{| | |||
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[[File:Olighe.jpg|thumb|250px|none| Oligodendroglioma HE stain [https://commons.wikimedia.org/wiki/Category:Histopathology_of_oligodendroglioma#/media/File:Image_NP_T4a1_0004.JPG]]] | |||
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[[File:1200px-Oligodendroglioma discrete invasion HE.jpg|thumb|250px|none|Low power magnification of a Oligodendroglioma biopsy specimen showing discrete infiltration of the surrounding brain [https://librepathology.org/wiki/File:Oligodendroglioma_discrete_invasion_HE.jpg]]] | |||
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[[File:Oligo hee.jpg|thumb|250px|none| Oligodendroglioma HE stain [https://commons.wikimedia.org/wiki/Category:Histopathology_of_oligodendroglioma#/media/File:Image_NP_T4a1_0002.JPG]]] | |||
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[[File:Oligo hne.jpg|thumb|250px|none| Oligodendroglioma HE stain [https://commons.wikimedia.org/wiki/Category:Histopathology_of_oligodendroglioma#/media/File:Image_NP_T4a1_0001.JPG]]] | |||
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[[File:Oligohe.jpg|thumb|250px|none| Oligodendroglioma HE stain [https://commons.wikimedia.org/wiki/Category:Histopathology_of_oligodendroglioma#/media/File:Image_NP_T4a1_0003.JPG]]] | |||
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[[File:Oligodendorglioma GFAP.jpg|thumb|250px|none| GFAP immunohistochemistry in a histopathology specimen of oligodendroglioma grade II WHO [https://commons.wikimedia.org/wiki/Category:Histopathology_of_oligodendroglioma#/media/File:Oligodendorglioma_GFAP.jpg]]] | |||
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[[File:Oligodendroglioma histo.jpg|thumb|250px|none| High magnification micrograph of an oligodendroglioma showing the characteristic branching, small, chicken wire-like blood vessels and fried egg-like cells, with clear cytoplasm and well-defined cell borders. H&E stain. [https://commons.wikimedia.org/wiki/File:Oligodendroglioma1_high_mag.jpg]]] | |||
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[[File:Oligo low mag.jpg|thumb|250px|none|Low magnification micrograph of an oligodendroglioma showing the characteristic, small, branching, chicken wire-like blood vessels. H&E stain. [https://commons.wikimedia.org/wiki/File:Oligodendroglioma1_low_mag.jpg]]] | |||
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====Microscopic histopathological findings in anaplastic oligodendroglioma==== | |||
On [[microscopic]] [[histopathological]] [[analysis]], [[anaplastic|anaplastic oligodendroglioma]], ''[[IDH1|IDH]]'' [[mutant]] and [[1p36 deletion syndrome|1p]]/19q codeleted, is characterized by:<ref name="micro">Microscopic features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref> | |||
*Focal or [[Diffuse|diffusely]] increased [[cell]] [[density]] | |||
*Atypical to [[Frank Newhook|frankly]] [[pleomorphic]] [[Cells (biology)|cells]] or [[multinucleated giant cells]] | |||
*[[Tumor cell|Tumor cells]] may be [[plasmacytoid]] (i.e. have a [[plasma cell]]-like [[appearance]]) | |||
**Also called as [[astrocyte|minigemistocytes]] | **Also called as [[astrocyte|minigemistocytes]] | ||
*Significant | *[[Significant figure|Significant]]/brisk infrequent [[mitoses|mitotic activity]] (≥ 6 [[mitoses]] per 10 [[Medical Abbreviations|HPF]])<ref name="LP">Images of oligodendroglioma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref><ref name="pmid16794749">{{cite journal| author=Smith SF, Simpson JM, Brewer JA, Sekhon LH, Biggs MT, Cook RJ et al.| title=The presence of necrosis and/or microvascular proliferation does not influence survival of patients with anaplastic oligodendroglial tumours: review of 98 patients. | journal=J Neurooncol | year= 2006 | volume= 80 | issue= 1 | pages= 75-82 | pmid=16794749 | doi=10.1007/s11060-006-9158-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16794749 }} </ref> | ||
*[[Necrosis]] | *[[Rare]] foci of: | ||
** | **[[Necrosis]] | ||
*[[vascular|Microvacular proliferation]] | **[[apoptosis|Apoptotic cells]] | ||
**[[vascular|Microvacular proliferation]] either in the form of: | |||
***[[Glomerular|Glomeruloid]]' [[vessels]] or | |||
***[[Endothelial]] [[hyperplasia]] | |||
{| | |||
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[[File:Brisk mitotic rate.jpg|thumb|250px|none|Brisk mitotic rate in anaplastic oligodendroglioma [http://www.pathologyoutlines.com/topic/cnstumoranaplasticoligodendroglioma.html]]] | |||
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[[File:Vascularproliferationoligo.jpg|thumb|250px|none| Vascularproliferation [https://emedicine.medscape.com/article/1743896-overview Source: Roger E McLendon, MD et al.]]] | |||
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[[File:1200px-MAP2 anaplastic oligodendroglioma.jpg|thumb|250px|none|Histopathology of anaplastic oligodendroglioma (MAP2 staining) showing perinuclear immunoreactivity of tumor cells[https://librepathology.org/wiki/File:MAP2_anaplastic_oligodendroglioma.jpg]]] | |||
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[[File:Fried egg app.jpg|thumb|250px|none| "Fried egg" appearance [http://www.pathologyoutlines.com/topic/cnstumoroligodendrogliomaidhmutant.html Source: John DeWitt, M.D., Ph.D.]]] | |||
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[[File:Chickenwire vessels.jpg|thumb|250px|none| Chicken wire vessels [http://www.pathologyoutlines.com/topic/cnstumoroligodendrogliomaidhmutant.html Source: John DeWitt, M.D., Ph.D.]]] | |||
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[[File:Friedeggoligo.jpg|thumb|250px|none| "Fried egg" appearance [http://www.pathologyoutlines.com/topic/cnstumoroligodendrogliomaidhmutant.html Source: John DeWitt, M.D., Ph.D.]]] | |||
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[[File:Infilcortex.jpg|thumb|250px|none| Infiltrating cortex [http://www.pathologyoutlines.com/topic/cnstumoroligodendrogliomaidhmutant.html Source: John DeWitt, M.D., Ph.D.]]] | |||
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[[File:1200px-Anaplastic oligodendroglioma minigemistocytes.jpg|thumb|250px|none|Histopathology of anaplastic oligodendroglioma (HE stain) showing minigemistocytes and mitoses among tumor cells with perinuclear halo.[https://librepathology.org/wiki/File:Anaplastic_oligodendroglioma_minigemistocytes.jpg]]] | |||
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[[File:1200px-IDH1 R132H in anaplastic ologodendroglioma.jpg|thumb|250px|none| Histopathology of anaplastic oligodendroglioma (IDH1 R132H staining) showing immunoreactivity of tumor cells idicating presence of the isocitrate dehydrogenase 1 R132H mutation [https://librepathology.org/wiki/File:IDH1_R132H_in_anaplastic_ologodendroglioma.jpg]]] | |||
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===Immunohistochemistry=== | ===Immunohistochemistry=== | ||
Oligodendroglioma is demonstrated by positivity to tumor markers such as:<ref name=IHC>IHC of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref><ref name="pmid16622556">{{cite journal| author=Hilbig A, Barbosa-Coutinho LM, Netto GC, Bleil CB, Toscani NV| title=[Immunohistochemistry in oligodendrogliomas]. | journal=Arq Neuropsiquiatr | year= 2006 | volume= 64 | issue= 1 | pages= 67-71 | pmid=16622556 | doi=/S0004-282X2006000100014 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16622556 }} </ref><ref name="von DeimlingHartmann2005">{{cite journal|last1=von Deimling|first1=A|last2=Hartmann|first2=C|title=Oligodendrogliomas: Impact of molecular genetics on treatment|journal=Neurology India|volume=53|issue=2|year=2005|pages=140|issn=0028-3886|doi=10.4103/0028-3886.16394}}</ref> | [[Oligodendroglioma]] is demonstrated by [[Positivity effect|positivity]] to [[tumor markers]] such as:<ref name="IHC">IHC of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref><ref name="pmid16622556">{{cite journal| author=Hilbig A, Barbosa-Coutinho LM, Netto GC, Bleil CB, Toscani NV| title=[Immunohistochemistry in oligodendrogliomas]. | journal=Arq Neuropsiquiatr | year= 2006 | volume= 64 | issue= 1 | pages= 67-71 | pmid=16622556 | doi=/S0004-282X2006000100014 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16622556 }} </ref><ref name="von DeimlingHartmann2005">{{cite journal|last1=von Deimling|first1=A|last2=Hartmann|first2=C|title=Oligodendrogliomas: Impact of molecular genetics on treatment|journal=Neurology India|volume=53|issue=2|year=2005|pages=140|issn=0028-3886|doi=10.4103/0028-3886.16394}}</ref><ref name="pmid26671986">{{cite journal| author=Tanboon J, Williams EA, Louis DN| title=The Diagnostic Use of Immunohistochemical Surrogates for Signature Molecular Genetic Alterations in Gliomas. | journal=J Neuropathol Exp Neurol | year= 2016 | volume= 75 | issue= 1 | pages= 4-18 | pmid=26671986 | doi=10.1093/jnen/nlv009 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26671986 }} </ref> | ||
*[[isocitrate dehydrogenase|IDH1-R132H]] (majority of cases)<ref name="pmid25324168">{{cite journal| author=Kato Y| title=Specific monoclonal antibodies against IDH1/2 mutations as diagnostic tools for gliomas. | journal=Brain Tumor Pathol | year= 2015 | volume= 32 | issue= 1 | pages= 3-11 | pmid=25324168 | doi=10.1007/s10014-014-0202-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25324168 }} </ref> | |||
*[[Microtubule-associated protein|MAP2]] | *[[Microtubule-associated protein|MAP2]] | ||
*[[GFAP]] | *[[GFAP]] (positive in intermingled [[Reactivity|reactive]] [[astrocytes]] and minigemistocytes) | ||
*[[SOX10]] | |||
*[[S100 calcium binding protein A8|S-100]] | *[[S100 calcium binding protein A8|S-100]] | ||
*EMA | *EMA | ||
*[[ | *[[ATRX]] | ||
*[[Ki-67 (Biology)|Ki-67]] | *[[Ki-67 (Biology)|Ki-67]] | ||
*[[Neuron-Specific Enolase (NSE)|NSE]] | *[[Neuron-Specific Enolase (NSE)|NSE]] | ||
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*[[OLIG1]] | *[[OLIG1]] | ||
*[[OLIG2]] | *[[OLIG2]] | ||
[[Oligodendroglioma]] [[Stain|stains]] negative for: | |||
*[[p53]] ([[rare]] weakly positive [[Cells (biology)|cells]] can be seen) | |||
*[[Keratins]] (although cocktails may show [[Cross-correlation|cross]] [[reactivity]]) | |||
==References== | ==References== | ||
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{{WikiDoc Sources}} | {{WikiDoc Sources}} | ||
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Latest revision as of 13:31, 13 August 2019
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Oligodendroglioma Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Oligodendroglioma pathophysiology On the Web |
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American Roentgen Ray Society Images of Oligodendroglioma pathophysiology |
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Risk calculators and risk factors for Oligodendroglioma pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [16]Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[17]Sujit Routray, M.D. [18]
Overview
Oligodendroglioma arises from the tripotential glial precursor cells and not from the bipotential oligodendrocytes. Genes associated with the pathogenesis of oligodendroglioma include t[1;19][q10;p10], ATRX, NJDS, IDH1, IDH2, TERT promoter, H3 K27M (H3F3A, HIST1H3B/C), CIC, FUBP1, p53, Leu-7, TCF-12, TP53,MGMT, TP73, BRAF, EGFR, and PTEN. Common intracranial sites involved by oligodendroglioma include cerebral hemispheres, posterior fossa, and intramedullary spinal cord. On gross pathology, oligodendroglioma is characterized by a well-circumscribed, gelatinous, calcified, cystic, gray mass with focal hemorrhage which may expand a gyrus and remodel the skull. On microscopic histopathological analysis, oligodendroglioma is characterized by diffuse growthpattern of highly cellular lesion of monomorphic cells having rounded nucleus with atypia, speckled "salt-and-pepper" chromatin pattern and perinuclear haloresembling fried eggs, distinct cell borders, clear cytoplasm, abundant calcification and "chicken-wire" like vascularity pattern. Oligodendroglioma is demonstrated by positivity to tumor markers such as IDH1-R132H, MAP2, GFAP, S-100, SOX10, EMA, ATRX, Ki-67, NSE, synaptophysin, OLIG1, and OLIG2.
Pathophysiology
Pathogenesis
- Oligodendroglioma does not arise from the bipotential oligodendrocytes, although the tumor cells look very similiar.[1]
- Oligodendroglioma arises from the tripotential glial precursor cells.
Genetics
- Development of oligodendroglioma is the result of multiple genetic mutations.[2][3][4][5][6][7][8][9][10][11][12]
- Genes associated with the pathogenesis of oligodendroglioma include:[13][14][15][16][17][18][19][20][21][22][23][24][25]
- t(1;19)(q10;p10) (co-deletion of chromosomal arms 1p36 and 19q13; most common)[26][10][27]
- ATRX[28]
- IDH1[29][30][31][32][33][34][35][36][37]
- IDH2[38][39][40][41][42][43]
- TERT promoter[22][44][45][46][47][48]
- H3 K27M mutations in either H3F3A (one of two genes encoding the histone H3.3 variant) or HIST1H3B/C (encoding the histone H3.1 variant).[49][50][51][52][53][54]
- NJDS (A 2009 Oxford Neurosymposium study illustrated that there's a 69% correlation between NJDS gene mutation and tumor initiation).
- CIC[55][16]
- FUBP1
- TP53
- p53[56]
- BRAF alterations:[57]
- Leu-7
- TCF-12
- MGMT
- TP73
- EGFR
- PTEN
- There is a strong association of oligodendroglioma with expression of receptor tyrosine kinases that activate PI3K/AKT, RAS/MAP, and PLC/PKC pathways.[20]
Gross Pathology
- On gross pathology, oligodendroglioma is characterized by a well-circumscribed, gelatinous, gray mass which may expand a gyrus and remodel the skul.l[58]
- Other characteristic gross pathological features associated with oligodendroglioma include:[58][20]
- Calcification (70-90%; one of the most frequently calcifying tumors)
- Focal hemorrhage
- Cystic (20%)
- Common intracranial sites associated with oligodendroglioma include:[59]
- Cerebral hemispheres (cortex and white matter) - distribution between frontal (most common, > 50% of cases), parietal, temporal, and occipital lobe approximates 3:2:2:1.
- Posterior fossa (rare)
- Intramedullary spinal cord (very rare, only 1.5% of oligodendrogliomas).
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Microscopic Pathology
On microscopic histopathological analysis, oligodendroglioma is characterized by:[20][60][61][62][63]
- Diffusely growing, infiltrative tumor
- Moderate cellularity
- Highly cellular lesion composed of typically monomorphic cells resembling fried eggs with:
- Round nucleus - key feature
- Distinct cell borders
- Moderate-to-marked nuclear atypia with speckled "salt-and-pepper" chromatin pattern
- Inconspicuous nucleoli
- Clear cytoplasm (artifactual retraction of the cytoplasm on routinely processed formalin fixed, paraffin embedded material, leading to the characteristic "fried egg" appearance).
- Some oligodendrogliomas have eosinophilic cytoplasm with focal perinuclear clearing.
- Dense network of acutely fine branched capillary sized vessels -classically referred to as a "chicken-wire" like appearance/pattern.[64]
- Abundant and delicate appearing; may vaguely resemble a paraganglioma at low power.
- Small punctate calcifications, particularly along the blood vessels is a striking feature (but not a specific finding).
- Perifocal edema - rare
- Few tumors may exhibit eosinophilic granular bodies
- Some tumors may show a spongioblastoma-like growth pattern
- Tumor cells may form following secondary structures in the surrounding infiltrated brain parenchyma:
- Perineuronal satellitosis
- Subpial accumulation
- Perivascular distribution (less common)
- Microgemistocytic appearance of tumor cells with a rounded belly of eccentric GFAP+ eosinophilic cytoplasm (maybe present).[65]
- A predominant fibrillar astrocytic phenotype is compatible with the diagnosis when following appropriate molecular findings are present:[21]
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Microscopic histopathological findings in anaplastic oligodendroglioma
On microscopic histopathological analysis, anaplastic oligodendroglioma, IDH mutant and 1p/19q codeleted, is characterized by:[60]
- Focal or diffusely increased cell density
- Atypical to frankly pleomorphic cells or multinucleated giant cells
- Tumor cells may be plasmacytoid (i.e. have a plasma cell-like appearance)
- Also called as minigemistocytes
- Significant/brisk infrequent mitotic activity (≥ 6 mitoses per 10 HPF)[66][67]
- Rare foci of:
- Necrosis
- Apoptotic cells
- Microvacular proliferation either in the form of:
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![[13]](https://librepathology.org/wiki/File:MAP2_anaplastic_oligodendroglioma.jpg){kind=link}
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![[14]](https://librepathology.org/wiki/File:Anaplastic_oligodendroglioma_minigemistocytes.jpg){kind=link}
![[15]](https://librepathology.org/wiki/File:IDH1_R132H_in_anaplastic_ologodendroglioma.jpg){kind=link}
Immunohistochemistry
Oligodendroglioma is demonstrated by positivity to tumor markers such as:[68][69][20][7]
- IDH1-R132H (majority of cases)[70]
- MAP2
- GFAP (positive in intermingled reactive astrocytes and minigemistocytes)
- SOX10
- S-100
- EMA
- ATRX
- Ki-67
- NSE
- Synaptophysin
- OLIG1
- OLIG2
Oligodendroglioma stains negative for:
- p53 (rare weakly positive cells can be seen)
- Keratins (although cocktails may show cross reactivity)
References
- ↑ General features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma#cite_note-1
- ↑ Suzuki H, Aoki K, Chiba K, Sato Y, Shiozawa Y, Shiraishi Y; et al. (2015). "Mutational landscape and clonal architecture in grade II and III gliomas". Nat Genet. 47 (5): 458–68. doi:10.1038/ng.3273. PMID 25848751.
- ↑ Leeper HE, Caron AA, Decker PA, Jenkins RB, Lachance DH, Giannini C (2015). "IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas". Oncotarget. 6 (30): 30295–305. doi:10.18632/oncotarget.4497. PMC 4745799. PMID 26210286.
- ↑ Sabha N, Knobbe CB, Maganti M, Al Omar S, Bernstein M, Cairns R; et al. (2014). "Analysis of IDH mutation, 1p/19q deletion, and PTEN loss delineates prognosis in clinical low-grade diffuse gliomas". Neuro Oncol. 16 (7): 914–23. doi:10.1093/neuonc/not299. PMC 4057130. PMID 24470545.
- ↑ Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B; et al. (2013). "Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas". Nat Genet. 45 (6): 602–12. doi:10.1038/ng.2611. PMC 3727232. PMID 23583981.
- ↑ Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y; et al. (2014). "The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma". Nat Genet. 46 (5): 444–450. doi:10.1038/ng.2938. PMC 4056452. PMID 24705251.
- ↑ 7.0 7.1 Tanboon J, Williams EA, Louis DN (2016). "The Diagnostic Use of Immunohistochemical Surrogates for Signature Molecular Genetic Alterations in Gliomas". J Neuropathol Exp Neurol. 75 (1): 4–18. doi:10.1093/jnen/nlv009. PMID 26671986.
- ↑ Jiao Y, Killela PJ, Reitman ZJ, Rasheed AB, Heaphy CM, de Wilde RF; et al. (2012). "Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas". Oncotarget. 3 (7): 709–22. doi:10.18632/oncotarget.588. PMC 3443254. PMID 22869205.
- ↑ Sahm F, Koelsche C, Meyer J, Pusch S, Lindenberg K, Mueller W; et al. (2012). "CIC and FUBP1 mutations in oligodendrogliomas, oligoastrocytomas and astrocytomas". Acta Neuropathol. 123 (6): 853–60. doi:10.1007/s00401-012-0993-5. PMID 22588899.
- ↑ 10.0 10.1 Barbashina V, Salazar P, Holland EC, Rosenblum MK, Ladanyi M (2005). "Allelic losses at 1p36 and 19q13 in gliomas: correlation with histologic classification, definition of a 150-kb minimal deleted region on 1p36, and evaluation of CAMTA1 as a candidate tumor suppressor gene". Clin Cancer Res. 11 (3): 1119–28. PMID 15709179.
- ↑ Frenel JS, Leux C, Loussouarn D, Le Loupp AG, Leclair F, Aumont M; et al. (2013). "Combining two biomarkers, IDH1/2 mutations and 1p/19q codeletion, to stratify anaplastic oligodendroglioma in three groups: a single-center experience". J Neurooncol. 114 (1): 85–91. doi:10.1007/s11060-013-1152-0. PMID 23681562.
- ↑ Hacisalihoglu P, Kucukodaci Z, Gundogdu G, Bilgic B (2017). "The Correlation Between 1p/19q Codeletion, IDH1 Mutation, p53 Overexpression and Their Prognostic Roles in 41 Turkish Anaplastic Oligodendroglioma Patients". Turk Neurosurg. 27 (5): 682–689. doi:10.5137/1019-5149.JTN.16832-15.1. PMID 27651340.
- ↑ Molecular genetics of oligodendroglioma. https://en.wikipedia.org/wiki/Oligodendroglioma
- ↑ Bettegowda C, Agrawal N, Jiao Y, Sausen M, Wood LD, Hruban RH; et al. (2011). "Mutations in CIC and FUBP1 contribute to human oligodendroglioma". Science. 333 (6048): 1453–5. doi:10.1126/science.1210557. PMC 3170506. PMID 21817013.
- ↑ Prognosis and treatment of oligodendroglioma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligodendroglioma
- ↑ 16.0 16.1 Yip S, Butterfield YS, Morozova O, Chittaranjan S, Blough MD, An J; et al. (2012). "Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers". J Pathol. 226 (1): 7–16. doi:10.1002/path.2995. PMC 3246739. PMID 22072542.
- ↑ Labreche K, Simeonova I, Kamoun A, Gleize V, Chubb D, Letouzé E; et al. (2015). "TCF12 is mutated in anaplastic oligodendroglioma". Nat Commun. 6: 7207. doi:10.1038/ncomms8207. PMC 4490400. PMID 26068201.
- ↑ Suri V, Jha P, Agarwal S, Pathak P, Sharma MC, Sharma V; et al. (2011). "Molecular profile of oligodendrogliomas in young patients". Neuro Oncol. 13 (10): 1099–106. doi:10.1093/neuonc/nor146. PMC 3177666. PMID 21937591.
- ↑ Hagel C, Laking G, Laas R, Scheil S, Jung R, Milde-Langosch K; et al. (1996). "Demonstration of p53 protein and TP53 gene mutations in oligodendrogliomas". Eur J Cancer. 32A (13): 2242–8. PMID 9038605.
- ↑ 20.0 20.1 20.2 20.3 20.4 von Deimling, A; Hartmann, C (2005). "Oligodendrogliomas: Impact of molecular genetics on treatment". Neurology India. 53 (2): 140. doi:10.4103/0028-3886.16394. ISSN 0028-3886.
- ↑ 21.0 21.1 Cancer Genome Atlas Research Network. Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR; et al. (2015). "Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas". N Engl J Med. 372 (26): 2481–98. doi:10.1056/NEJMoa1402121. PMC 4530011. PMID 26061751.
- ↑ 22.0 22.1 Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H; et al. (2015). "Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors". N Engl J Med. 372 (26): 2499–508. doi:10.1056/NEJMoa1407279. PMC 4489704. PMID 26061753.
- ↑ Ueki K, Nishikawa R, Nakazato Y, Hirose T, Hirato J, Funada N; et al. (2002). "Correlation of histology and molecular genetic analysis of 1p, 19q, 10q, TP53, EGFR, CDK4, and CDKN2A in 91 astrocytic and oligodendroglial tumors". Clin Cancer Res. 8 (1): 196–201. PMID 11801559.
- ↑ Labussière M, Boisselier B, Mokhtari K, Di Stefano AL, Rahimian A, Rossetto M; et al. (2014). "Combined analysis of TERT, EGFR, and IDH status defines distinct prognostic glioblastoma classes". Neurology. 83 (13): 1200–6. doi:10.1212/WNL.0000000000000814. PMID 25150284.
- ↑ Nambirajan A, Suri V, Kedia S, Goyal K, Malgulwar PB, Khanna G; et al. (2018). "Paediatric diffuse leptomeningeal tumor with glial and neuronal differentiation harbouring chromosome 1p/19q co-deletion and H3.3 K27M mutation: unusual molecular profile and its therapeutic implications". Brain Tumor Pathol. 35 (3): 186–191. doi:10.1007/s10014-018-0325-0. PMID 30030640.
- ↑ McDonald JM, See SJ, Tremont IW, Colman H, Gilbert MR, Groves M; et al. (2005). "The prognostic impact of histology and 1p/19q status in anaplastic oligodendroglial tumors". Cancer. 104 (7): 1468–77. doi:10.1002/cncr.21338. PMID 16088966.
- ↑ Reifenberger J, Reifenberger G, Liu L, James CD, Wechsler W, Collins VP (1994). "Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p". Am J Pathol. 145 (5): 1175–90. PMC 1887413. PMID 7977648.
- ↑ Reuss DE, Sahm F, Schrimpf D, Wiestler B, Capper D, Koelsche C; et al. (2015). "ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an "integrated" diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma". Acta Neuropathol. 129 (1): 133–46. doi:10.1007/s00401-014-1370-3. PMID 25427834.
- ↑ Chen N, Yu T, Gong J, Nie L, Chen X, Zhang M; et al. (2016). "IDH1/2 gene hotspot mutations in central nervous system tumours: analysis of 922 Chinese patients". Pathology. 48 (7): 675–683. doi:10.1016/j.pathol.2016.07.010. PMID 27780605.
- ↑ Zhou YX, Wang JX, Feng M, Sun CM, Sun T, Chen GL; et al. (2012). "Analysis of isocitrate dehydrogenase 1 mutation in 97 patients with glioma". J Mol Neurosci. 47 (3): 442–7. doi:10.1007/s12031-011-9681-5. PMID 22113362.
- ↑ Capper D, Weissert S, Balss J, Habel A, Meyer J, Jäger D; et al. (2010). "Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors". Brain Pathol. 20 (1): 245–54. doi:10.1111/j.1750-3639.2009.00352.x. PMID 19903171.
- ↑ Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W; et al. (2009). "IDH1 and IDH2 mutations in gliomas". N Engl J Med. 360 (8): 765–73. doi:10.1056/NEJMoa0808710. PMC 2820383. PMID 19228619.
- ↑ Balss J, Meyer J, Mueller W, Korshunov A, Hartmann C, von Deimling A (2008). "Analysis of the IDH1 codon 132 mutation in brain tumors". Acta Neuropathol. 116 (6): 597–602. doi:10.1007/s00401-008-0455-2. PMID 18985363.
- ↑ Arita H, Narita Y, Matsushita Y, Fukushima S, Yoshida A, Takami H; et al. (2015). "Development of a robust and sensitive pyrosequencing assay for the detection of IDH1/2 mutations in gliomas". Brain Tumor Pathol. 32 (1): 22–30. doi:10.1007/s10014-014-0186-0. PMID 24748374.
- ↑ Setty P, Hammes J, Rothämel T, Vladimirova V, Kramm CM, Pietsch T; et al. (2010). "A pyrosequencing-based assay for the rapid detection of IDH1 mutations in clinical samples". J Mol Diagn. 12 (6): 750–6. doi:10.2353/jmoldx.2010.090237. PMC 2963913. PMID 20847279.
- ↑ Pang B, Durso MB, Hamilton RL, Nikiforova MN (2013). "A novel COLD-PCR/FMCA assay enhances the detection of low-abundance IDH1 mutations in gliomas". Diagn Mol Pathol. 22 (1): 28–34. doi:10.1097/PDM.0b013e31826c7ff8. PMID 23370430.
- ↑ Boisselier B, Marie Y, Labussière M, Ciccarino P, Desestret V, Wang X; et al. (2010). "COLD PCR HRM: a highly sensitive detection method for IDH1 mutations". Hum Mutat. 31 (12): 1360–5. doi:10.1002/humu.21365. PMID 20886613.
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- ↑ Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A; et al. (2009). "Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas". Acta Neuropathol. 118 (4): 469–74. doi:10.1007/s00401-009-0561-9. PMID 19554337.
- ↑ Sonoda Y, Kumabe T, Nakamura T, Saito R, Kanamori M, Yamashita Y; et al. (2009). "Analysis of IDH1 and IDH2 mutations in Japanese glioma patients". Cancer Sci. 100 (10): 1996–8. doi:10.1111/j.1349-7006.2009.01270.x. PMID 19765000.
- ↑ Arita H, Narita Y, Yoshida A, Hashimoto N, Yoshimine T, Ichimura K (2015). "IDH1/2 mutation detection in gliomas". Brain Tumor Pathol. 32 (2): 79–89. doi:10.1007/s10014-014-0197-x. PMID 25008158.
- ↑ van den Bent MJ, Dubbink HJ, Marie Y, Brandes AA, Taphoorn MJ, Wesseling P; et al. (2010). "IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group". Clin Cancer Res. 16 (5): 1597–604. doi:10.1158/1078-0432.CCR-09-2902. PMID 20160062.
- ↑ Catteau A, Girardi H, Monville F, Poggionovo C, Carpentier S, Frayssinet V; et al. (2014). "A new sensitive PCR assay for one-step detection of 12 IDH1/2 mutations in glioma". Acta Neuropathol Commun. 2: 58. doi:10.1186/2051-5960-2-58. PMC 4229941. PMID 24889502.
- ↑ Diplas BH, Liu H, Yang R, Hansen LJ, Zachem AL, Zhao F; et al. (2019). "Sensitive and rapid detection of TERT promoter and IDH mutations in diffuse gliomas". Neuro Oncol. 21 (4): 440–450. doi:10.1093/neuonc/noy167. PMC 6422442. PMID 30346624.
- ↑ Sun ZL, Chan AK, Chen LC, Tang C, Zhang ZY, Ding XJ; et al. (2015). "TERT promoter mutated WHO grades II and III gliomas are located preferentially in the frontal lobe and avoid the midline". Int J Clin Exp Pathol. 8 (9): 11485–94. PMC 4637696. PMID 26617880.
- ↑ Yang P, Cai J, Yan W, Zhang W, Wang Y, Chen B; et al. (2016). "Classification based on mutations of TERT promoter and IDH characterizes subtypes in grade II/III gliomas". Neuro Oncol. 18 (8): 1099–108. doi:10.1093/neuonc/now021. PMC 4933482. PMID 26957363.
- ↑ Labussière M, Di Stefano AL, Gleize V, Boisselier B, Giry M, Mangesius S; et al. (2014). "TERT promoter mutations in gliomas, genetic associations and clinico-pathological correlations". Br J Cancer. 111 (10): 2024–32. doi:10.1038/bjc.2014.538. PMC 4229642. PMID 25314060.
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- ↑ Khuong-Quang DA, Buczkowicz P, Rakopoulos P, Liu XY, Fontebasso AM, Bouffet E; et al. (2012). "K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas". Acta Neuropathol. 124 (3): 439–47. doi:10.1007/s00401-012-0998-0. PMC 3422615. PMID 22661320.
- ↑ Harutyunyan AS, Krug B, Chen H, Papillon-Cavanagh S, Zeinieh M, De Jay N; et al. (2019). "H3K27M induces defective chromatin spread of PRC2-mediated repressive H3K27me2/me3 and is essential for glioma tumorigenesis". Nat Commun. 10 (1): 1262. doi:10.1038/s41467-019-09140-x. PMC 6425035. PMID 30890717.
- ↑ Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J; et al. (2012). "Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas". Nat Genet. 44 (3): 251–3. doi:10.1038/ng.1102. PMC 3288377. PMID 22286216.
- ↑ Castel D, Philippe C, Calmon R, Le Dret L, Truffaux N, Boddaert N; et al. (2015). "Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes". Acta Neuropathol. 130 (6): 815–27. doi:10.1007/s00401-015-1478-0. PMC 4654747. PMID 26399631.
- ↑ Castel D, Grill J, Debily MA (2016). "Histone H3 genotyping refines clinico-radiological diagnostic and prognostic criteria in DIPG". Acta Neuropathol. 131 (5): 795–6. doi:10.1007/s00401-016-1568-7. PMC 4835508. PMID 27038188.
- ↑ Cordero FJ, Huang Z, Grenier C, He X, Hu G, McLendon RE; et al. (2017). "Histone H3.3K27M Represses p16 to Accelerate Gliomagenesis in a Murine Model of DIPG". Mol Cancer Res. 15 (9): 1243–1254. doi:10.1158/1541-7786.MCR-16-0389. PMC 5581686. PMID 28522693.
- ↑ Eisenreich S, Abou-El-Ardat K, Szafranski K, Campos Valenzuela JA, Rump A, Nigro JM; et al. (2013). "Novel CIC point mutations and an exon-spanning, homozygous deletion identified in oligodendroglial tumors by a comprehensive genomic approach including transcriptome sequencing". PLoS One. 8 (9): e76623. doi:10.1371/journal.pone.0076623. PMC 3785522. PMID 24086756.
- ↑ Gillet E, Alentorn A, Doukouré B, Mundwiller E, van Thuijl HF, van Thuij H; et al. (2014). "TP53 and p53 statuses and their clinical impact in diffuse low grade gliomas". J Neurooncol. 118 (1): 131–9. doi:10.1007/s11060-014-1407-4. PMID 24590827.
- ↑ Rodriguez FJ, Schniederjan MJ, Nicolaides T, Tihan T, Burger PC, Perry A (2015). "High rate of concurrent BRAF-KIAA1549 gene fusion and 1p deletion in disseminated oligodendroglioma-like leptomeningeal neoplasms (DOLN)". Acta Neuropathol. 129 (4): 609–610. doi:10.1007/s00401-015-1400-9. PMC 4696044. PMID 25720745.
- ↑ 58.0 58.1 Gross appearance of oligodendroglioma. Dr Henry Knipe and Dr Frank Gaillard et al. http://radiopaedia.org/articles/oligodendroglioma
- ↑ Gross/radiologic findings of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma
- ↑ 60.0 60.1 Microscopic features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma
- ↑ Ersen, Ayca (2008), Pathology of malignant gliomas: Challenges of everyday practice and the WHO 2007, Turkish Journal of Pathology, retrieved 9 October, 2015 Check date values in:
|accessdate=(help) - ↑ Eskandar EN, Loeffler JS, O'Neill AM, Hunter GJ, Louis DN (2004). "Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 33-2004. A 34-year-old man with a seizure and a frontal-lobe brain lesion". N Engl J Med. 351 (18): 1875–82. doi:10.1056/NEJMcpc049025. PMID 15509821.
- ↑ Rodriguez FJ, Perry A, Rosenblum MK, Krawitz S, Cohen KJ, Lin D; et al. (2012). "Disseminated oligodendroglial-like leptomeningeal tumor of childhood: a distinctive clinicopathologic entity". Acta Neuropathol. 124 (5): 627–41. doi:10.1007/s00401-012-1037-x. PMID 22941225.
- ↑ Images of microscopic appearance of oligodendroglioma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligodendroglioma
- ↑ Kros JM, Van Eden CG, Stefanko SZ, Waayer-Van Batenburg M, van der Kwast TH (1990). "Prognostic implications of glial fibrillary acidic protein containing cell types in oligodendrogliomas". Cancer. 66 (6): 1204–12. PMID 2205356.
- ↑ Images of oligodendroglioma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Oligodendroglioma
- ↑ Smith SF, Simpson JM, Brewer JA, Sekhon LH, Biggs MT, Cook RJ; et al. (2006). "The presence of necrosis and/or microvascular proliferation does not influence survival of patients with anaplastic oligodendroglial tumours: review of 98 patients". J Neurooncol. 80 (1): 75–82. doi:10.1007/s11060-006-9158-5. PMID 16794749.
- ↑ IHC of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma
- ↑ Hilbig A, Barbosa-Coutinho LM, Netto GC, Bleil CB, Toscani NV (2006). "[Immunohistochemistry in oligodendrogliomas]". Arq Neuropsiquiatr. 64 (1): 67–71. doi:/S0004-282X2006000100014 Check
|doi=value (help). PMID 16622556. - ↑ Kato Y (2015). "Specific monoclonal antibodies against IDH1/2 mutations as diagnostic tools for gliomas". Brain Tumor Pathol. 32 (1): 3–11. doi:10.1007/s10014-014-0202-4. PMID 25324168.