Oligodendroglioma pathophysiology: Difference between revisions

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==Overview==
==Overview==
Oligodendroglioma arises from the tripotential [[glial cell|glial precursor cells]] and ''not'' from the bipotential [[oligodendrocyte]]s. Genes associated with the pathogenesis of oligodendroglioma include [[translocation|t[1;19][q10;p10]]], ''[[mutation|NJDS]]'', ''[[Isocitrate dehydrogenase|IDH1]]'', ''[[IDH2]]'', ''CIC'', ''[[Far upstream element-binding protein 1|FUBP1]]'', ''[[p53]]'', ''[[CD57|Leu-7]]'', ''[[TCF12|TCF-12]]'', ''[[Ogt|MGMT]]'', ''[[P73|TP73]]'', ''[[EGFR]]'', and ''[[PTEN]]''. On gross pathology, oligodendroglioma is characterized by a well-circumscribed, gelatinous, calcified, gray mass which may expand a [[gyrus]] and remodel the [[skull]]. On microscopic histopathological analysis, oligodendroglioma is characterized by diffuse growth pattern of highly cellular lesion with rounded nucleus with [[atypia]] and perinuclear halo resembling ''fried eggs'', distinct cell borders, clear cytoplasm, and abundant [[calcification]]. Oligodendroglioma is demonstrated by positivity to tumor markers such as [[Microtubule-associated protein|MAP2]], [[GFAP]], [[S100 calcium binding protein A8|S-100]], EMA, [[isocitrate dehydrogenase|IDH1-R132H]], ATRX, [[Ki-67 (Biology)|Ki-67]], [[Neuron-Specific Enolase (NSE)|NSE]], [[Synaptophysin]], [[OLIG1]], and [[OLIG2]].
[[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 the [[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 of multiple [
*[[Development]] of [[oligodendroglioma
:*''[[Far upstream element-binding protein 1|FUBP1]]''
:*''[[Far upstream element-binding protein 1|FUBP1]]''
:*''[[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>
:*''[[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  
:*[[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>
:**''KIAA1549''-''BRAF'' fusion  
:**''[[KIAA1549L (gene)|KIAA1549]]''-''[[BRAF (gene)|BRAF]]'' [[Fusion gene|fusion]]
:**''BRAF'' V600E mutation  
:**''[[BRAF]]'' V600E [[mutation]]
:*''[[CD57|Leu-7]]''
:*''[[CD57|Leu-7]]''
:*''[[TCF12|TCF-12]]''
:*''[[TCF12|TCF-12]]''
Line 33: 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]]<ref name="grosspa">Gross appearance of oligodendroglioma. Dr Henry Knipe and Dr Frank Gaillard et al. http://radiopaedia.org/articles/oligodendroglioma</ref>
*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]])
:*[[Calcification]] (70-90%; one of the most frequently calcifying tumors)
**[[Hemorrhage|Focal hemorrhage]]
:*[[Hemorrhage|Focal hemorrhage]]
**[[cyst|Cystic]] (20%)
:*[[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.
:*[[Cerebral hemisphere]]s (cortex and white matter) - 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]])
:*[[Posterior fossa]] (rare)
**[[spinal cord|Intramedullary spinal cord]] (very [[rare]], only 1.5% of [[oligodendrogliomas]]).
:*[[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]]]
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[[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><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>
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>
*Diffusely growing, infiltrative tumor
*[[Diffuse|Diffusely]] [[Growth|growing]], [[Infiltration (medical)|infiltrative]] [[tumor]]
*Moderate cellularity
*Moderate [[Cellular|cellularity]]
*Highly cellular lesion composed of typically monomorphic 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]]
**Inconspicuous nucleoli
**Inconspicuous [[nucleoli]]
**[[cytoplasm|Clear cytoplasm]]  (artifactual retraction of the cytoplasm on routinely processed formalin fixed, paraffin embedded material, leading to the characteristic "fried egg" appearance)
**[[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 clearing
***Some [[oligodendrogliomas]] have [[eosinophilic]] [[cytoplasm]] with focal [[Perinuclear space|perinuclear]] clearing.
**Dense network of acutely fine branched capillary sized vessels -classically referred to as a "''chicken-wire''" like appearance/pattern<ref name="microscope">Images of microscopic appearance of oligodendroglioma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligodendroglioma</ref>
**[[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 appearing; may vaguely resemble a [[paraganglioma]] at low power
***Abundant and delicate [[Appearance|appearing]]; may [[Vagueness|vaguely]] resemble a [[paraganglioma]] at low [[Power nap|power]].
*Small punctate [[Calcification]]s, particularly along the blood vessels is a striking feature (but not a specific finding)
*Small punctate [[calcification]]s, particularly along the [[blood vessels]] is a striking [[Features (pattern recognition)|feature]] (but not a [[Specific activity|specific]] finding).
*Perifocal [[edema]] - rare
*Perifocal [[edema]] - [[rare]]
*Few tumors may exhibit [[eosinophilic]] granular bodies
*[[Fewmets|Few]] [[tumors]] may [[Exhibitionism|exhibit]] [[eosinophilic]] [[Granular cell|granular]] [[Body|bodies]]
*Some tumors may show a spongioblastoma-like growth pattern
*Some [[tumors]] may show a [[spongioblastoma]]-like [[growth]] [[pattern]]
*Tumor cells may form following secondary structures in the surrounding infiltrated brain parenchyma:
*[[Tumor cell|Tumor cells]] may form following [[Secondary structure|secondary structures]] in the surrounding [[Infiltration (medical)|infiltrated]] [[brain]] [[parenchyma]]:
**Perineuronal satellitosis
**Perineuronal satellitosis
**Subpial accumulation
**[[Subpial space|Subpial]] accumulation
**Perivascular distribution (less common)
**[[Perivascular cell|Perivascular]] [[Distribution (pharmacology)|distribution]] (less common)
*Microgemistocytic appearance of tumor cells with a rounded belly of eccentric 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>
*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 fibrillar astrocytic phenotype is compatible with the diagnosis when following 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>
*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>
**''IDH'' mutation
**''[[IDH1|IDH]]'' [[mutation]]
**1p/19q codeletion
**[[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]]]
|
[[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]]]
|
|}
====Microscopic histopathological findings in anaplastic oligodendroglioma====
====Microscopic histopathological findings in anaplastic oligodendroglioma====
On microscopic histopathological analysis, [[anaplastic|anaplastic oligodendroglioma]], ''IDH'' mutant and 1p/19q codeleted, is characterized by:<ref name="micro">Microscopic features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma</ref>
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 diffusely increased cell density
*Focal or [[Diffuse|diffusely]] increased [[cell]] [[density]]
*Atypical to frankly [[pleomorphic]] cells or [[multinucleated giant cells]]
*Atypical to [[Frank Newhook|frankly]] [[pleomorphic]] [[Cells (biology)|cells]] or [[multinucleated giant cells]]
*Tumor cells may be plasmacytoid (i.e. have a [[plasma cell]]-like appearance)
*[[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/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>
*[[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>
*Rare foci of:
*[[Rare]] foci of:
**[[Necrosis]]
**[[Necrosis]]
**[[apoptosis|Apoptotic cells]]
**[[apoptosis|Apoptotic cells]]
**[[vascular|Microvacular proliferation]] either in the form of:
**[[vascular|Microvacular proliferation]] either in the form of:
***Glomeruloid' vessels or
***[[Glomerular|Glomeruloid]]' [[vessels]] or
***Endothelial [[hyperplasia]]
***[[Endothelial]] [[hyperplasia]]
{|
|
[[File:Brisk mitotic rate.jpg|thumb|250px|none|Brisk mitotic rate in anaplastic oligodendroglioma [http://www.pathologyoutlines.com/topic/cnstumoranaplasticoligodendroglioma.html]]]
|
[[File:Vascularproliferationoligo.jpg|thumb|250px|none| Vascularproliferation [https://emedicine.medscape.com/article/1743896-overview Source: Roger E McLendon, MD et al.]]]
|
[[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]]]
|
[[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.]]]
|
|}
{|
|
[[File:Chickenwire vessels.jpg|thumb|250px|none| Chicken wire vessels [http://www.pathologyoutlines.com/topic/cnstumoroligodendrogliomaidhmutant.html Source: John DeWitt, M.D., Ph.D.]]]
|
[[File:Friedeggoligo.jpg|thumb|250px|none| "Fried egg" appearance [http://www.pathologyoutlines.com/topic/cnstumoroligodendrogliomaidhmutant.html Source: John DeWitt, M.D., Ph.D.]]]
|
[[File:Infilcortex.jpg|thumb|250px|none| Infiltrating cortex [http://www.pathologyoutlines.com/topic/cnstumoroligodendrogliomaidhmutant.html Source: John DeWitt, M.D., Ph.D.]]]
|
[[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]]]
|
[[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]]]
|
|}


===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>
*[[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]] (positive in intermingled reactive astrocytes and minigemistocytes)
*[[GFAP]] (positive in intermingled [[Reactivity|reactive]] [[astrocytes]] and minigemistocytes)
*SOX10
*[[SOX10]]
*[[S100 calcium binding protein A8|S-100]]
*[[S100 calcium binding protein A8|S-100]]
*EMA
*EMA
*ATRX
*[[ATRX]]
*[[Ki-67 (Biology)|Ki-67]]
*[[Ki-67 (Biology)|Ki-67]]
*[[Neuron-Specific Enolase (NSE)|NSE]]  
*[[Neuron-Specific Enolase (NSE)|NSE]]  
Line 100: Line 154:
*[[OLIG1]]
*[[OLIG1]]
*[[OLIG2]]
*[[OLIG2]]
Oligodendroglioma stains negative for:
[[Oligodendroglioma]] [[Stain|stains]] negative for:
*p53 (rare weakly positive cells can be seen)
*[[p53]] ([[rare]] weakly positive [[Cells (biology)|cells]] can be seen)
*Keratins (although cocktails may show cross reactivity)
*[[Keratins]] (although cocktails may show [[Cross-correlation|cross]] [[reactivity]])


==References==
==References==

Latest revision as of 13:31, 13 August 2019

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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

Genetics

Gross Pathology

Oligodendroglioma involving frontal lobe [1]
Mixed astrocytoma and oligodendroglioma [2]
Oligodendroglioma gross appearance [3]

Microscopic Pathology

On microscopic histopathological analysis, oligodendroglioma is characterized by:[20][60][61][62][63]

Oligodendroglioma HE stain [4]
Low power magnification of a Oligodendroglioma biopsy specimen showing discrete infiltration of the surrounding brain [5]
Oligodendroglioma HE stain [6]
Oligodendroglioma HE stain [7]
Oligodendroglioma HE stain [8]
GFAP immunohistochemistry in a histopathology specimen of oligodendroglioma grade II WHO [9]
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. [10]
Low magnification micrograph of an oligodendroglioma showing the characteristic, small, branching, chicken wire-like blood vessels. H&E stain. [11]

Microscopic histopathological findings in anaplastic oligodendroglioma

On microscopic histopathological analysis, anaplastic oligodendroglioma, IDH mutant and 1p/19q codeleted, is characterized by:[60]

Brisk mitotic rate in anaplastic oligodendroglioma [12]
Vascularproliferation Source: Roger E McLendon, MD et al.
Histopathology of anaplastic oligodendroglioma (MAP2 staining) showing perinuclear immunoreactivity of tumor cells[13]
"Fried egg" appearance Source: John DeWitt, M.D., Ph.D.
Chicken wire vessels Source: John DeWitt, M.D., Ph.D.
"Fried egg" appearance Source: John DeWitt, M.D., Ph.D.
Infiltrating cortex Source: John DeWitt, M.D., Ph.D.
Histopathology of anaplastic oligodendroglioma (HE stain) showing minigemistocytes and mitoses among tumor cells with perinuclear halo.[14]
Histopathology of anaplastic oligodendroglioma (IDH1 R132H staining) showing immunoreactivity of tumor cells idicating presence of the isocitrate dehydrogenase 1 R132H mutation [15]

Immunohistochemistry

Oligodendroglioma is demonstrated by positivity to tumor markers such as:[68][69][20][7]

Oligodendroglioma stains negative for:

References

  1. ↑ General features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma#cite_note-1
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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. ↑ 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.
  8. ↑ 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.
  9. ↑ 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. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ Molecular genetics of oligodendroglioma. https://en.wikipedia.org/wiki/Oligodendroglioma
  14. ↑ 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.
  15. ↑ Prognosis and treatment of oligodendroglioma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligodendroglioma
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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. ↑ 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. ↑ 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. ↑ 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.
  23. ↑ 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.
  24. ↑ 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.
  25. ↑ 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.
  26. ↑ 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.
  27. ↑ 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.
  28. ↑ 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.
  29. ↑ 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.
  30. ↑ 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.
  31. ↑ 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.
  32. ↑ 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.
  33. ↑ 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.
  34. ↑ 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.
  35. ↑ 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.
  36. ↑ 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.
  37. ↑ 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.
  38. ↑ Pan Y, Qi XL, Wang LM, Dong RF, Zhang M, Zheng DF; et al. (2013). "[Mutation of isocitrate dehydrogenase gene in Chinese patients with glioma]". Zhonghua Bing Li Xue Za Zhi. 42 (5): 292–8. doi:10.3760/cma.j.issn.0529-5807.2013.05.002. PMID 24004584.
  39. ↑ 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.
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  56. ↑ 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.
  57. ↑ 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. ↑ 58.0 58.1 Gross appearance of oligodendroglioma. Dr Henry Knipe and Dr Frank Gaillard et al. http://radiopaedia.org/articles/oligodendroglioma
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  60. ↑ 60.0 60.1 Microscopic features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma
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  62. ↑ 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.
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  64. ↑ Images of microscopic appearance of oligodendroglioma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligodendroglioma
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  68. ↑ IHC of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma
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  70. ↑ 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.


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