Compendium of Cancer Genome Aberrations

CNS5:Ganglioglioma: Difference between revisions

[unchecked revision][checked revision]
← Older edit
VisualWikitext
No edit summary
 
(16 intermediate revisions by 3 users not shown)
Line 1: Line 1:
==Primary Author(s)*==
{{DISPLAYTITLE:Ganglioglioma}}
Dr Leila Moayed Alaei, Royal Prince Alfred Hospital


__TOC__
[[CNS5:Table_of_Contents|Central Nervous System Tumours (WHO Classification, 5th ed.)]]
==Cancer Category/Type==


Glioneuronal tumour  
{{Under Construction}}


==Cancer Sub-Classification / Subtype==
<span style="color:#0070C0">(''General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)''</span>
==Primary Author(s)*==
Dr Leila Moayed Alaei, Royal Prince Alfred Hospital
==WHO Classification of Disease==


Ganglioglioma
{| class="wikitable"
 
!Structure
==Definition / Description of Disease==
!Disease
 
|-
This is a distinct entity in the World Health Organization (WHO) classification system within the section of Gliomas, Glioneuronal and neuronal tumours. This is a well-differentiated glioneuronal tumour with low proliferative activity, comprised of mixed neoplastic neuronal and glial cell components. It is molecularly characterized by genomic aberrations causing MAPK pathway activation (CNS WHO grade 1)<ref name=":0">Solomon D.A. et al. (2021). Ganglioglioma, in "World Health Organization Classification of Central Nervous System Tumours" (5th edition). pp.111-115. </ref>.
|Book
 
|Central Nervous System Tumours (5th ed.)
==Synonyms / Terminology==
|-
 
|Category
None
|Gliomas, glioneuronal tumours, and neuronal tumours
 
|-
==Epidemiology / Prevalence==
|Family
 
|Gliomas, glioneuronal tumours, and neuronal tumours
Gangliogliomas are generally tumours of adolescent/young adults with a median age of 12 years at the time of diagnosis. However, the tumour has been reported in wider range of age from 0 to 70 years of age<ref>{{Cite journal|last=Lang|first=Shih-Shan|last2=Beslow|first2=Lauren A.|last3=Gabel|first3=Brandon|last4=Judkins|first4=Alex R.|last5=Fisher|first5=Michael J.|last6=Sutton|first6=Leslie N.|last7=Storm|first7=Phillip B.|last8=Heuer|first8=Gregory G.|date=2012-07|title=Surgical treatment of brain tumors in infants younger than six months of age and review of the literature|url=https://pubmed.ncbi.nlm.nih.gov/22120270|journal=World Neurosurgery|volume=78|issue=1-2|pages=137–144|doi=10.1016/j.wneu.2011.09.012|issn=1878-8769|pmc=3292637|pmid=22120270}}</ref><ref>{{Cite journal|last=Blumcke|first=Ingmar|last2=Spreafico|first2=Roberto|last3=Haaker|first3=Gerrit|last4=Coras|first4=Roland|last5=Kobow|first5=Katja|last6=Bien|first6=Christian G.|last7=Pfäfflin|first7=Margarete|last8=Elger|first8=Christian|last9=Widman|first9=Guido|date=2017-10-26|title=Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery|url=https://pubmed.ncbi.nlm.nih.gov/29069555|journal=The New England Journal of Medicine|volume=377|issue=17|pages=1648–1656|doi=10.1056/NEJMoa1703784|issn=1533-4406|pmid=29069555}}</ref>. The tumour is more prevalent in male patients (59.8%) than in female patients (40.2%)<ref>{{Cite journal|last=Dudley|first=Roy W. R.|last2=Torok|first2=Michelle R.|last3=Gallegos|first3=Danielle R.|last4=Mulcahy-Levy|first4=Jean M.|last5=Hoffman|first5=Lindsey M.|last6=Liu|first6=Arthur K.|last7=Handler|first7=Michael H.|last8=Hankinson|first8=Todd C.|date=2015-03|title=Pediatric low-grade ganglioglioma: epidemiology, treatments, and outcome analysis on 348 children from the surveillance, epidemiology, and end results database|url=https://pubmed.ncbi.nlm.nih.gov/25603107|journal=Neurosurgery|volume=76|issue=3|pages=313–319; discussion 319; quiz 319–320|doi=10.1227/NEU.0000000000000619|issn=1524-4040|pmc=4333003|pmid=25603107}}</ref>.
|-
|Type
|Glioneuronal and neuronal tumours
|-
|Subtype(s)
|Ganglioglioma
|}


==Clinical Features==
==Related Terminology==


The clinical features are dependent on the tumour location and size. If located in the cerebrum, the most common presentation is with focal seizures<ref name=":0" /><ref name=":1">{{Cite journal|last=Prayson|first=R. A.|last2=Khajavi|first2=K.|last3=Comair|first3=Y. G.|date=1995-07|title=Cortical architectural abnormalities and MIB1 immunoreactivity in gangliogliomas: a study of 60 patients with intracranial tumors|url=https://pubmed.ncbi.nlm.nih.gov/7541447|journal=Journal of Neuropathology and Experimental Neurology|volume=54|issue=4|pages=513–520|doi=10.1097/00005072-199507000-00005|issn=0022-3069|pmid=7541447}}</ref>, with up to 23.6% of surgical epilepsy specimens harbouring gangliogliomas<ref>{{Cite journal|last=Blumcke|first=Ingmar|last2=Spreafico|first2=Roberto|last3=Haaker|first3=Gerrit|last4=Coras|first4=Roland|last5=Kobow|first5=Katja|last6=Bien|first6=Christian G.|last7=Pfäfflin|first7=Margarete|last8=Elger|first8=Christian|last9=Widman|first9=Guido|date=2017-10-26|title=Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery|url=https://pubmed.ncbi.nlm.nih.gov/29069555|journal=The New England Journal of Medicine|volume=377|issue=17|pages=1648–1656|doi=10.1056/NEJMoa1703784|issn=1533-4406|pmid=29069555}}</ref>. The mean duration of symptoms prior to diagnosis is also dependent on location. For tumours located in the cerebrum, the duration of symptoms prior to diagnosis ranges between 5 and 10 years, whereas in the brainstem and spinal cord, the mean duration of symptoms pre-diagnosis ranges between 1.25 years and 1.4 years, respectively<ref name=":1" /><ref>{{Cite journal|last=Lang|first=F. F.|last2=Epstein|first2=F. J.|last3=Ransohoff|first3=J.|last4=Allen|first4=J. C.|last5=Wisoff|first5=J.|last6=Abbott|first6=I. R.|last7=Miller|first7=D. C.|date=1993-12|title=Central nervous system gangliogliomas. Part 2: Clinical outcome|url=https://pubmed.ncbi.nlm.nih.gov/8246055|journal=Journal of Neurosurgery|volume=79|issue=6|pages=867–873|doi=10.3171/jns.1993.79.6.0867|issn=0022-3085|pmid=8246055}}</ref>.
The archetypal radiological features are of a circumscribed, solid/cystic mass, although varied appearances are the norm, ranging from presentation as a small cyst to a solid mass<ref name=":2">{{Cite journal|last=Zhang|first=D.|last2=Henning|first2=T. D.|last3=Zou|first3=L.-G.|last4=Hu|first4=L.-B.|last5=Wen|first5=L.|last6=Feng|first6=X.-Y.|last7=Dai|first7=S.-H.|last8=Wang|first8=W.-X.|last9=Sun|first9=Q.-R.|date=2008-01|title=Intracranial ganglioglioma: clinicopathological and MRI findings in 16 patients|url=https://pubmed.ncbi.nlm.nih.gov/18068794|journal=Clinical Radiology|volume=63|issue=1|pages=80–91|doi=10.1016/j.crad.2007.06.010|issn=0009-9260|pmid=18068794}}</ref>.  Patterns of contrast enhancement can also vary, including enhancement of the cystic wall to a markedly enhanced nodule<ref name=":2" />.
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|+
|Intracerebral ganglioglioma: Seizure; chronic temporal lobe epilepsy<ref name=":1" />
|Acceptable
 
|N/A
Brain stem ganglioglioma: blurry vision, loss of memory, syncope spells, cranial nerve deficits, headache, and gait instability<ref>{{Cite journal|last=Mpairamidis|first=Evriviadis|last2=Alexiou|first2=George A.|last3=Stefanaki|first3=Kalliopi|last4=Sfakianos|first4=George|last5=Prodromou|first5=Neofytos|date=2008-12|title=Brainstem ganglioglioma|url=https://pubmed.ncbi.nlm.nih.gov/19073857|journal=Journal of Child Neurology|volume=23|issue=12|pages=1481–1483|doi=10.1177/0883073808319316|issn=1708-8283|pmid=19073857}}</ref>
 
Spinal cord ganglioglioma:  acute onset paraparesis<ref>{{Cite journal|last=Cruz|first=Thainá Zanon|last2=Ferreira-Pinto|first2=Pedro Henrique Costa|last3=Brito|first3=Ana Carolina Gonçalves|last4=Ururahy|first4=Leandro|last5=Sanchez|first5=Jefferson Trivino|last6=Nigri|first6=Flavio|date=2021|title=Ganglioglioma of the cervicothoracic spinal cord in a patient with neurofibromatosis type 1: A case report|url=https://pubmed.ncbi.nlm.nih.gov/34345454|journal=Surgical Neurology International|volume=12|pages=313|doi=10.25259/SNI_192_2021|issn=2229-5097|pmc=8326088|pmid=34345454}}</ref>
|-
|-
|'''Imaging Findings'''
|Not Recommended
|Classic imaging features: T1 iso- to hypointense solid component,  T2-hyperintense solid component with varied signal within the cystic component; nodule and cyst wall show variable contrast enhancement<ref name=":2" />
|N/A
|}
|}


==Sites of Involvement==
==Gene Rearrangements==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
Most common location: temporal lobes (>70%)[5,6,18]
 
Other locations: cerebrum, brainstem, cerebellum, spinal cord, and optic nerves, lateral ventricle[3,5,6,18]
 
==Morphologic Features==
 
Ganglioglioma is a biphasic tumour composed of a neoplastic neuronal and a neoplastic glial component [3,18]. The neoplastic neuronal component is comprised of dysmorphic ganglion cells showing cytomegaly, binucleation and perimembranous aggregation of Nissl substance. Disorganised cytoarchitecture is also observed, with clustering of neurons. The neoplastic glial component can resemble a diffuse glioma or pilocytic astrocytoma; the glial component harbours the proliferative component of the tumour, which can show infiltration on microscopy. Proliferative activity is usually low to absent. The two components can be intermingled or geographically distinct. Other pertinent histological features include Rosenthal fibres, eosinophilic granular bodies and perivascular lymphoid infiltration[3,18]. An association with focal cortical dysplasia is a commonly reported finding[19].  
 
==Immunophenotype==
 
<br />
 
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|<span class="blue-text">EXAMPLE:</span>
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
|-
|-
|Positive (universal)  
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|CD34 expressed in expressed in ramified tumor cells[21]
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|<span class="blue-text">EXAMPLE:</span> D
|
|<span class="blue-text">EXAMPLE:</span>


Neoplastic neuronal component – MAP2, neurofilament, synaptophysin, chromogranin A
''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''


* No definitive markers for neoplastic neuronal component
* Typical profile: chromogranin A+, NeuN-, synaptophysin+, neurofilament+, MAP2+ (but MAP2 - in glial component)[1, 20]


Neoplastic glial component – GFAP, OLIG2 (MAP2 -)  
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|<span class="blue-text">EXAMPLE:</span>


* Ki-67 <5%[5]
Both balanced and unbalanced forms are observed by FISH (add references).
|-
|Positive (subset)
|BRAF VE1 (+ in BRAF-mutant gangliogliomas)  
|-
|-
|Negative (universal)  
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
| IDH1 R132H, ATRX (normal retained pattern of staining)
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|
|-
|-
|Negative (subset)
|
|BRAF VE1 (- in BRAF-wildtype gangliogliomas)
|
|
|
|
|
|
|
|}
|}


==Chromosomal Rearrangements (Gene Fusions)==
 
'''Add content below into table above''' -  
{| class="wikitable"
{| class="wikitable"
|'''Chromosomal Rearrangement'''  
|'''Chromosomal Rearrangement'''
|'''Genes in Fusion'''  
|'''Genes in Fusion'''  


'''(5’ or 3’ Segments)'''  
'''(5’ or 3’ Segments)'''
|'''Structural variation'''  
|'''Structural variation'''
|'''Prevalence'''  
|'''Prevalence'''
|'''Diagnostic Significance (Yes, No or Unknown)'''  
|'''Diagnostic Significance (Yes, No or Unknown)'''
|'''Prognostic Significance (Yes, No or Unknown)'''  
|'''Prognostic Significance (Yes, No or Unknown)'''
|'''Therapeutic Significance (Yes, No or Unknown)'''  
|'''Therapeutic Significance (Yes, No or Unknown)'''
|'''Notes'''  
|'''Notes'''
|-
|-
|t(7;7)(q34;q34)[8,13]
|t(7;7)(q34;q34)<ref name=":6">{{Cite journal|last=Pekmezci|first=Melike|last2=Villanueva-Meyer|first2=Javier E.|last3=Goode|first3=Benjamin|last4=Van Ziffle|first4=Jessica|last5=Onodera|first5=Courtney|last6=Grenert|first6=James P.|last7=Bastian|first7=Boris C.|last8=Chamyan|first8=Gabriel|last9=Maher|first9=Ossama M.|date=2018-06-07|title=The genetic landscape of ganglioglioma|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992851/|journal=Acta Neuropathologica Communications|volume=6|pages=47|doi=10.1186/s40478-018-0551-z|issn=2051-5960|pmc=5992851|pmid=29880043}}</ref><ref name=":7">{{Cite journal|last=Kim|first=Pora|last2=Zhou|first2=Xiaobo|date=2018-11-08|title=FusionGDB: fusion gene annotation DataBase|url=http://dx.doi.org/10.1093/nar/gky1067|journal=Nucleic Acids Research|volume=47|issue=D1|pages=D994–D1004|doi=10.1093/nar/gky1067|issn=0305-1048}}</ref>
|''KIAA1549::BRAF [8, 9]''
|''KIAA1549::BRAF''<ref name=":6" /><ref name=":8">{{Cite journal|last=Appay|first=Romain|last2=Fina|first2=Frédéric|last3=Macagno|first3=Nicolas|last4=Padovani|first4=Laëtitia|last5=Colin|first5=Carole|last6=Barets|first6=Doriane|last7=Ordioni|first7=Joanna|last8=Scavarda|first8=Didier|last9=Giangaspero|first9=Felice|date=2018-10|title=Duplications of KIAA1549 and BRAF screening by Droplet Digital PCR from formalin-fixed paraffin-embedded DNA is an accurate alternative for KIAA1549-BRAF fusion detection in pilocytic astrocytomas|url=https://pubmed.ncbi.nlm.nih.gov/29802359|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=31|issue=10|pages=1490–1501|doi=10.1038/s41379-018-0050-6|issn=1530-0285|pmid=29802359}}</ref>
|duplication  
|duplication  
|16.7 % [9]
|16.7%<ref name=":8" />
|Yes[1,8]
|Yes<ref name=":0">Solomon D.A. et al. (2021). Ganglioglioma, in "World Health Organization Classification of Central Nervous System Tumours" (5th edition). pp.111-115. </ref><ref name=":6" />
|No  
|No
|Yes[22]
|Yes<ref name=":9">{{Cite journal|last=Schreck|first=Karisa C.|last2=Grossman|first2=Stuart A.|last3=Pratilas|first3=Christine A.|date=2019-08-28|title=BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors|url=https://pubmed.ncbi.nlm.nih.gov/31466300|journal=Cancers|volume=11|issue=9|pages=E1262|doi=10.3390/cancers11091262|issn=2072-6694|pmc=6769482|pmid=31466300}}</ref>
|<nowiki>- also seen in PLNTY, ganglioglioma, and pilocytic astrocytoma; can distinguish by methylation signature[1] </nowiki>
| - also seen in PLNTY, ganglioglioma, and pilocytic astrocytoma; can distinguish by methylation signature<ref name=":0" />


- in-frame fusion[8]
- in-frame fusion<ref name=":6" />
|-
|-
|t(8;8)(p11.23;p11.22)  
|t(8;8)(p11.23;p11.22)<ref name=":6" /><ref name=":7" />
|''FGFR1::TACC1 [8]''  
|''FGFR1::TACC1''<ref name=":6" />
|inversion  
|inversion
|2.5% (1/40)[8]
|2.5% (1/40)<ref name=":6" />
|Unknown  
|Unknown
|Unknown  
|Unknown
|Unknown  
|Unknown  
|<nowiki>- in-frame fusion[8] </nowiki>
| - in-frame fusion<ref name=":6" />


- no FDA-approved anti-FGFR therapy for ganglioglioma at present  
- no FDA-approved anti-FGFR therapy for ganglioglioma at present  
|-
|-
|t(10;10)(q26.13;q25.3) [8,13]
|t(10;10)(q26.13;q25.3)<ref name=":6" /><ref name=":7" />
|''FGFR2::KIAA1598 [8]''  
|''FGFR2::KIAA1598''<ref name=":6" />
|deletion  
|deletion
|2.5% (1/40)[8]
|2.5% (1/40)<ref name=":6" />
|Unknown  
|Unknown
|Unknown  
|Unknown
|Unknown  
|Unknown
|<nowiki>- in-frame fusion[8] </nowiki>
| - in-frame fusion<ref name=":6" />  
<br />
<br />
|-
|-
|t(10;10) (q26.13;q24.3)[8,13]
|t(10;10) (q26.13;q24.3)<ref name=":6" /><ref name=":7" />
|''FGFR2::INA[8]''  
|''FGFR2::INA''<ref name=":6" />
|inversion  
|inversion
|2.5% (1/40) [8]
|2.5% (1/40)<ref name=":6" />
|Unknown  
|Unknown
|Unknown  
|Unknown
|Unknown  
|Unknown
|<nowiki>- in-frame fusion[8] </nowiki>
| - in-frame fusion<ref name=":6" />  
<br />
<br />
|-
|-
|t(3;3)(p14.3;p25.2) [8,13]
|t(3;3)(p14.3;p25.2)<ref name=":6" /><ref name=":7" />
|''ERC2::RAF1[8]''  
|''ERC2::RAF1''<ref name=":6" />
|deletion  
|deletion
|2.5%(1/40) [8]
|2.5%(1/40)<ref name=":6" />
|Unknown  
|Unknown
|Unknown  
|Unknown
|Yes (potential) [22]
|Yes (potential)<ref name=":9" />
|<nowiki>- in-frame fusion[8] </nowiki>
| - in-frame fusion<ref name=":6" />  
<br />
<br />
|-
|-
|t(14;7)(q32.32;7q34) [8,13]  
|t(14;7)(q32.32;7q34)<ref name=":6" /><ref name=":7" />
|''CDC42BPB::BRAF [8]''
|''CDC42BPB::BRAF''<ref name=":6" />
|translocation  
|translocation
|2.5% (1/40) [8]
|2.5% (1/40)<ref name=":6" />
|Unknown  
|Unknown
|Unknown  
|Unknown
|Yes (potential) [22]
|Yes (potential)<ref name=":9" />
|<nowiki>- in-frame fusion[8] </nowiki>
| - in-frame fusion<ref name=":6" />
<br />
<br />
|-
|-
|t(7;7)(p15.3;q34) [8,13]
|t(7;7)(p15.3;q34)<ref name=":6" /><ref name=":7" />
|''KLHL7::BRAF[8]''  
|''KLHL7::BRAF''<ref name=":6" />
|inversion  
|inversion
|2.5% (1/40) [8]
|2.5% (1/40) <ref name=":6" />
<br />
<br />
|Unknown  
|Unknown
|Unknown  
|Unknown
|Yes (potential) [22]
|Yes (potential)<ref name=":9" />
|<nowiki>- in-frame fusion[8] </nowiki>
| - in-frame fusion<ref name=":6" />
<br />
<br />
|-
|-
|t(1;11)(q25.2;q14.1) [8,13]
|t(1;11)(q25.2;q14.1)<ref name=":6" /><ref name=":7" />
|''ABL2::GAB2[8]''  
|''ABL2::GAB2''<ref name=":6" />
|translocation  
|translocation
|2.5% (1/40) [8]
|2.5% (1/40)<ref name=":6" />
<br />
<br />
|Unknown  
|Unknown
|Unknown  
|Unknown
|Yes (potential) [22]
|Yes (potential)<ref name=":9" />
|<nowiki>- in-frame fusion[8] </nowiki>
| - in-frame fusion<ref name=":6" />
<br />
<br />
|}
|}


==Characteristic Chromosomal Aberrations / Patterns==


None
==Individual Region Genomic Gain/Loss/LOH==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
|-
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|<span class="blue-text">EXAMPLE:</span>
7
|<span class="blue-text">EXAMPLE:</span> Loss
|<span class="blue-text">EXAMPLE:</span>
chr7
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<span class="blue-text">EXAMPLE:</span> D, P
|<span class="blue-text">EXAMPLE:</span> No
|<span class="blue-text">EXAMPLE:</span>
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
|-
|<span class="blue-text">EXAMPLE:</span>
8
|<span class="blue-text">EXAMPLE:</span> Gain
|<span class="blue-text">EXAMPLE:</span>
chr8
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<span class="blue-text">EXAMPLE:</span> D, P
|
|<span class="blue-text">EXAMPLE:</span>
Common recurrent secondary finding for t(8;21) (add references).
|-
|<span class="blue-text">EXAMPLE:</span>
17
|<span class="blue-text">EXAMPLE:</span> Amp
|<span class="blue-text">EXAMPLE:</span>
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|<span class="blue-text">EXAMPLE:</span>
''ERBB2''
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|<span class="blue-text">EXAMPLE:</span>
Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
|-
|
|
|
|
|
|
|
|}
'''Add content below into table above''' -  
{| class="wikitable"
|'''Chr #  '''
|'''Gain/Loss/Amp/LOH'''
|'''Minimal Region Genomic Coordinates [Genome Build]'''
|'''Minimal Region Cytoband'''
|'''Diagnostic Significance (Yes, No or Unknown)'''
|'''Prognostic Significance'''
 
'''(Yes, No or Unknown)  '''
|'''Therapeutic Significance'''


==Genomic Gain/Loss/LOH==
'''(Yes, No or Unknown)'''
|'''Notes'''
|-
|1
|loss
|Chr1:1- 248956422
<br />
|Chr1
|Unknown
|Unknown
|Unknown
| colspan="1" rowspan="20" |This constellation of chromosomal abnormalities was found in a case series of 40 gangliogliomas[8].


Put your text here and/or fill in the table
It is unknown if the abnormalities are either diagnostic, prognostic or therapeutic.  
|-
|3
|gain
|Chr3:1- 198295559
<br />
|Chr3
|Unknown
|Unknown
|Unknown
|-
|4
|gain
|Chr4:1- 190214555
|Chr4
|Unknown
|Unknown
|Unknown
|-
|5
|gain
|Chr5:1- 181538259
|Chr5
|Unknown
|Unknown
|Unknown
|-
|6
|gain
|Chr6:1- 170805979
|Chr6
|Unknown
|Unknown
|Unknown
|-
|7
|gain
|Chr7:1- 159345973
|Chr7
|Unknown
|Unknown
|Unknown
|-
|8
|gain
|Chr8:1- 145138636
|Chr8
|Unknown
|Unknown
|Unknown
|-
|9
|gain
|Chr9:1- 138394717
|Chr9
|Unknown
|Unknown
|Unknown
|-
|10
|loss (segmental)
|Chr10:1- 133797422
|Chr10
|Unknown
|Unknown
|Unknown
|-
|11
|gain
|Chr11:1- 135086622
|Chr11
|Unknown
|Unknown
|Unknown
|-
|12
|gain
|Chr12:1- 133275309
|Chr12
|Unknown
|Unknown
|Unknown
|-
|15
|gain
|Chr15: 1- 101991189
|Chr15
|Unknown
|Unknown
|Unknown
|-
|16
|Gain  
|Chr16:1-90338345
<br />
|Chr16
|Unknown
|Unknown
|Unknown
|-
|16
|loss
|Chr16:1-90338345
<br />
|Chr16
|Unknown
|Unknown
|Unknown
|-
|17
|loss
|Chr17:1- 83257441
|Chr17
|Unknown
|Unknown
|Unknown
|-
|18
|gain
|Chr18:1- 80373285
|Chr18
|Unknown
|Unknown
|Unknown
|-
|19
|gain
|Chr19:1- 58617616
|Chr19
|Unknown
|Unknown
|Unknown
|-
|20
|gain
|Chr20:1- 64444167
|Chr20
|Unknown
|Unknown
|Unknown
|-
|21
|gain
|Chr21:1- 46709983
|Chr21
|Unknown
|Unknown
|Unknown
|-
|22
|gain
|Chr22:1- 50818468
|Chr22
|Unknown
|Unknown
|Unknown
|}
<br />


==Characteristic Chromosomal or Other Global Mutational Patterns==
Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
!Chromosomal Pattern
!Molecular Pathogenesis
!Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|EXAMPLE 8||EXAMPLE Gain||EXAMPLE chr8:0-1000000
|<span class="blue-text">EXAMPLE:</span>
Co-deletion of 1p and 18q
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|<span class="blue-text">EXAMPLE:</span> D, P
|
|
|-
|-
|EXAMPLE 7||EXAMPLE Loss||EXAMPLE chr7:0-1000000
|<span class="blue-text">EXAMPLE:</span>
|}
Microsatellite instability - hypermutated
|
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|<span class="blue-text">EXAMPLE:</span> P, T
|
|
|-
|
|
|
|
|
|
|}
 
==Gene Mutations (SNV/INDEL)==
==Gene Mutations (SNV/INDEL)==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
|-
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
<br />
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|<span class="blue-text">EXAMPLE:</span> T
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
<br />
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|<span class="blue-text">EXAMPLE:</span> P
|
|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|
|-
|
|
|
|
|
|
|
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
'''Add content below into table above''' -  
{| class="wikitable"
|'''Gene; Genetic Alteration'''
|'''Presumed Mechanism (Tumor Suppressor Gene (TSG)/Oncogene/Other)'''
|'''Prevalence (COSMIC/ TCGA/Other)'''
|'''Concomitant Mutations'''
|'''Mutually Exclusive Mutations'''
|'''Diagnostic Significance (Yes, No or Unknown)'''
|'''Prognostic Significance'''
'''(Yes, No or Unknown)  '''
|'''Therapeutic Significance'''
'''(Yes, No or Unknown)'''
|'''Notes'''
|-
|''BRAF'' p.V600E<ref name=":0" /><ref name=":6" />
|oncogene
|10-60%<ref name=":0" />
|Homozygous deletion of CDKN2A<ref name=":6" />[8]


Put your text here and/or fill in the tables


{| class="wikitable sortable"
H3-3A p.K27M<ref>{{Cite journal|last=Pagès|first=Mélanie|last2=Beccaria|first2=Kevin|last3=Boddaert|first3=Nathalie|last4=Saffroy|first4=Raphaël|last5=Besnard|first5=Aurore|last6=Castel|first6=David|last7=Fina|first7=Frédéric|last8=Barets|first8=Doriane|last9=Barret|first9=Emilie|date=2018-01|title=Co-occurrence of histone H3 K27M and BRAF V600E mutations in paediatric midline grade I ganglioglioma|url=https://pubmed.ncbi.nlm.nih.gov/27984673|journal=Brain Pathology (Zurich, Switzerland)|volume=28|issue=1|pages=103–111|doi=10.1111/bpa.12473|issn=1750-3639|pmc=8028391|pmid=27984673}}</ref>
|''KRAS, RAF1, NF1, FGFR1, and FGFR2''<ref name=":6" />
|Yes<ref name=":0" /><ref name=":6" />
|Yes<ref name=":10">{{Cite journal|last=Ryall|first=Scott|last2=Zapotocky|first2=Michal|last3=Fukuoka|first3=Kohei|last4=Nobre|first4=Liana|last5=Guerreiro Stucklin|first5=Ana|last6=Bennett|first6=Julie|last7=Siddaway|first7=Robert|last8=Li|first8=Christopher|last9=Pajovic|first9=Sanja|date=2020-04-13|title=Integrated Molecular and Clinical Analysis of 1,000 Pediatric Low-Grade Gliomas|url=https://pubmed.ncbi.nlm.nih.gov/32289278|journal=Cancer Cell|volume=37|issue=4|pages=569–583.e5|doi=10.1016/j.ccell.2020.03.011|issn=1878-3686|pmc=7169997|pmid=32289278}}</ref>
|Yes<ref name=":11">{{Cite journal|last=Kowalewski|first=Adam|last2=Durślewicz|first2=Justyna|last3=Zdrenka|first3=Marek|last4=Grzanka|first4=Dariusz|last5=Szylberg|first5=Łukasz|date=2020-08|title=Clinical Relevance of BRAF V600E Mutation Status in Brain Tumors with a Focus on a Novel Management Algorithm|url=https://pubmed.ncbi.nlm.nih.gov/32648041|journal=Targeted Oncology|volume=15|issue=4|pages=531–540|doi=10.1007/s11523-020-00735-9|issn=1776-260X|pmc=7434793|pmid=32648041}}</ref>
|FDA-approved therapy includes dabrafenib-trametinib<ref name=":11" />
<br />
|-
|''BRAF'' indel events: p.L505delinsLEYLS p.R506delinsRVLR p.R506delinsRSTQ p.T599_W604delinsTDG) <ref name=":6" />
|oncogene
|10%<ref name=":6" />
|
|''KRAS, RAF1, NF1, FGFR1, and FGFR2''<ref name=":6" />
|Yes<ref name=":0" /><ref name=":6" />
|Unknown
|Unknown
| 
|-
|''KRAS'' p.Q61K<ref name=":6" />
|oncogene
|5%<ref name=":6" />
|
|''KRAS, RAF1, NF1, FGFR1, and FGFR2''<ref name=":6" />
|Yes<ref name=":0" /><ref name=":6" />
|No<ref name=":6" /><ref name=":10" />
|No
|
|-
|''FGFR2'' exon 17 splicesite mutation<ref name=":6" />
|oncogene
|2.5%<ref name=":6" />
<br />
|
|''KRAS, RAF1, NF1, FGFR1, and BRAF''<ref name=":6" />
|Yes<ref name=":0" /><ref name=":6" />
|No<ref name=":6" /><ref name=":10" />
|No
|<nowiki>- no FDA-approved anti-FGFR therapy for ganglioglioma at present </nowiki>
<br />
|-
|-
!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
|''FGFR1'' p.N546K<ref name=":6" />
|oncogene
|2.5%<ref name=":6" />
<br />
|
|''KRAS, RAF1,''
 
'' NF1, BRAF, and FGFR2''<ref name=":6" />
|Yes<ref name=":0" /><ref name=":6" />
|No<ref name=":6" /><ref name=":10" />
|No
|<nowiki>- no FDA-approved anti-FGFR therapy for ganglioglioma at present </nowiki>
<br />
|}
 
==Epigenomic Alterations==
 
Methylation profiling can be used in the diagnosis of ganglioglioma, however low tumour cellularity can impact on feasibility in the diagnostic setting<ref name=":0" />.
 
==Genes and Main Pathways Involved==
90% of gangliogliomas harbor genetic alterations activating the MAPK signaling pathway, with non-MAPK signaling seen in 10% of cases (e.g. ''ABL2::GAB2'' gene fusion)<ref name=":6" />.  
{| class="wikitable"
|'''Gene; Genetic Alteration'''
|'''Pathway'''
|'''Pathophysiologic Outcome'''
|-
|-
|EXAMPLE TP53||EXAMPLE R273H||EXAMPLE Tumor Suppressor||EXAMPLE LOF||EXAMPLE 20%
|BRAF; activating alterations
|}
|MAPK signaling
|Increased cell growth and proliferation
===Other Mutations===
{| class="wikitable sortable"
|-
|-
!Type!!Gene/Region/Other
|RAF1; activating alterations
|MAPK signaling
|Increase cell growth and proliferation
|-
|-
|Concomitant Mutations||EXAMPLE IDH1 R123H
|KRAS; activating mutations
|MAPK signaling
|Increase cell growth and proliferation
|-
|-
|Secondary Mutations||EXAMPLE Trisomy 7
|NF1; inactivating mutations
|MAPK signaling  
|Increase cell growth and proliferation
|-
|-
|Mutually Exclusive||EXAMPLE EGFR Amplification
|FGFR1/2/3; activating alterations
|MAPK signaling
|Increase cell growth and proliferation
|}
|}
==Genetic Diagnostic Testing Methods==
*Chromosome microarray  
*Next generation sequencing  
*DNA methylation profiling
==Familial Forms==
Inactivating germline mutations or deletions of ''NF1'', as occurs in neurofibromatosis type 1, can be associated with a minor proportion of gangliogliomas<ref name=":6" /><ref>{{Cite journal|last=Rodriguez|first=Fausto J.|last2=Perry|first2=Arie|last3=Gutmann|first3=David H.|last4=O'Neill|first4=Brian Patrick|last5=Leonard|first5=Jeffrey|last6=Bryant|first6=Sandra|last7=Giannini|first7=Caterina|date=2008-03|title=Gliomas in neurofibromatosis type 1: a clinicopathologic study of 100 patients|url=https://pubmed.ncbi.nlm.nih.gov/18344915|journal=Journal of Neuropathology and Experimental Neurology|volume=67|issue=3|pages=240–249|doi=10.1097/NEN.0b013e318165eb75|issn=0022-3069|pmc=3417064|pmid=18344915}}</ref>


==Epigenomics (Methylation)==
==Additional Information==
This disease is <u>defined/characterized</u> as detailed below:


Put your text here
*This is a distinct entity in the World Health Organization (WHO) classification system within the section of Gliomas, Glioneuronal and neuronal tumours. This is a well-differentiated glioneuronal tumour with low proliferative activity, comprised of mixed neoplastic neuronal and glial cell components. It is molecularly characterized by genomic aberrations causing MAPK pathway activation (CNS WHO grade 1)<ref name=":0" />.


==Genes and Main Pathways Involved==
The <u>epidemiology/prevalence</u> of this disease is detailed below:


Put your text here
*Gangliogliomas are generally tumours of adolescent/young adults with a median age of 12 years at the time of diagnosis. However, the tumour has been reported in wider range of age from 0 to 70 years of age<ref>{{Cite journal|last=Lang|first=Shih-Shan|last2=Beslow|first2=Lauren A.|last3=Gabel|first3=Brandon|last4=Judkins|first4=Alex R.|last5=Fisher|first5=Michael J.|last6=Sutton|first6=Leslie N.|last7=Storm|first7=Phillip B.|last8=Heuer|first8=Gregory G.|date=2012-07|title=Surgical treatment of brain tumors in infants younger than six months of age and review of the literature|url=https://pubmed.ncbi.nlm.nih.gov/22120270|journal=World Neurosurgery|volume=78|issue=1-2|pages=137–144|doi=10.1016/j.wneu.2011.09.012|issn=1878-8769|pmc=3292637|pmid=22120270}}</ref><ref name=":3">{{Cite journal|last=Blumcke|first=Ingmar|last2=Spreafico|first2=Roberto|last3=Haaker|first3=Gerrit|last4=Coras|first4=Roland|last5=Kobow|first5=Katja|last6=Bien|first6=Christian G.|last7=Pfäfflin|first7=Margarete|last8=Elger|first8=Christian|last9=Widman|first9=Guido|date=2017-10-26|title=Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery|url=https://pubmed.ncbi.nlm.nih.gov/29069555|journal=The New England Journal of Medicine|volume=377|issue=17|pages=1648–1656|doi=10.1056/NEJMoa1703784|issn=1533-4406|pmid=29069555}}</ref>. The tumour is more prevalent in male patients (59.8%) than in female patients (40.2%)<ref>{{Cite journal|last=Dudley|first=Roy W. R.|last2=Torok|first2=Michelle R.|last3=Gallegos|first3=Danielle R.|last4=Mulcahy-Levy|first4=Jean M.|last5=Hoffman|first5=Lindsey M.|last6=Liu|first6=Arthur K.|last7=Handler|first7=Michael H.|last8=Hankinson|first8=Todd C.|date=2015-03|title=Pediatric low-grade ganglioglioma: epidemiology, treatments, and outcome analysis on 348 children from the surveillance, epidemiology, and end results database|url=https://pubmed.ncbi.nlm.nih.gov/25603107|journal=Neurosurgery|volume=76|issue=3|pages=313–319; discussion 319; quiz 319–320|doi=10.1227/NEU.0000000000000619|issn=1524-4040|pmc=4333003|pmid=25603107}}</ref>.


==Diagnostic Testing Methods==
The <u>clinical features</u> of this disease are detailed below:


Put your text here
*The clinical features are dependent on the tumour location and size. If located in the cerebrum, the most common presentation is with focal seizures<ref name=":0" /><ref name=":1">{{Cite journal|last=Prayson|first=R. A.|last2=Khajavi|first2=K.|last3=Comair|first3=Y. G.|date=1995-07|title=Cortical architectural abnormalities and MIB1 immunoreactivity in gangliogliomas: a study of 60 patients with intracranial tumors|url=https://pubmed.ncbi.nlm.nih.gov/7541447|journal=Journal of Neuropathology and Experimental Neurology|volume=54|issue=4|pages=513–520|doi=10.1097/00005072-199507000-00005|issn=0022-3069|pmid=7541447}}</ref>, with up to 23.6% of surgical epilepsy specimens harbouring gangliogliomas<ref>{{Cite journal|last=Blumcke|first=Ingmar|last2=Spreafico|first2=Roberto|last3=Haaker|first3=Gerrit|last4=Coras|first4=Roland|last5=Kobow|first5=Katja|last6=Bien|first6=Christian G.|last7=Pfäfflin|first7=Margarete|last8=Elger|first8=Christian|last9=Widman|first9=Guido|date=2017-10-26|title=Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery|url=https://pubmed.ncbi.nlm.nih.gov/29069555|journal=The New England Journal of Medicine|volume=377|issue=17|pages=1648–1656|doi=10.1056/NEJMoa1703784|issn=1533-4406|pmid=29069555}}</ref>. The mean duration of symptoms prior to diagnosis is also dependent on location. For tumours located in the cerebrum, the duration of symptoms prior to diagnosis ranges between 5 and 10 years, whereas in the brainstem and spinal cord, the mean duration of symptoms pre-diagnosis ranges between 1.25 years and 1.4 years, respectively<ref name=":1" /><ref name=":4">{{Cite journal|last=Lang|first=F. F.|last2=Epstein|first2=F. J.|last3=Ransohoff|first3=J.|last4=Allen|first4=J. C.|last5=Wisoff|first5=J.|last6=Abbott|first6=I. R.|last7=Miller|first7=D. C.|date=1993-12|title=Central nervous system gangliogliomas. Part 2: Clinical outcome|url=https://pubmed.ncbi.nlm.nih.gov/8246055|journal=Journal of Neurosurgery|volume=79|issue=6|pages=867–873|doi=10.3171/jns.1993.79.6.0867|issn=0022-3085|pmid=8246055}}</ref>.
*The archetypal radiological features are of a circumscribed, solid/cystic mass, although varied appearances are the norm, ranging from presentation as a small cyst to a solid mass<ref name=":2">{{Cite journal|last=Zhang|first=D.|last2=Henning|first2=T. D.|last3=Zou|first3=L.-G.|last4=Hu|first4=L.-B.|last5=Wen|first5=L.|last6=Feng|first6=X.-Y.|last7=Dai|first7=S.-H.|last8=Wang|first8=W.-X.|last9=Sun|first9=Q.-R.|date=2008-01|title=Intracranial ganglioglioma: clinicopathological and MRI findings in 16 patients|url=https://pubmed.ncbi.nlm.nih.gov/18068794|journal=Clinical Radiology|volume=63|issue=1|pages=80–91|doi=10.1016/j.crad.2007.06.010|issn=0009-9260|pmid=18068794}}</ref>.  Patterns of contrast enhancement can also vary, including enhancement of the cystic wall to a markedly enhanced nodule<ref name=":2" />.
*Signs and symptoms - Intracerebral ganglioglioma: Seizure; chronic temporal lobe epilepsy<ref name=":1" />; Brain stem ganglioglioma: blurry vision, loss of memory, syncope spells, cranial nerve deficits, headache, and gait instability<ref>{{Cite journal|last=Mpairamidis|first=Evriviadis|last2=Alexiou|first2=George A.|last3=Stefanaki|first3=Kalliopi|last4=Sfakianos|first4=George|last5=Prodromou|first5=Neofytos|date=2008-12|title=Brainstem ganglioglioma|url=https://pubmed.ncbi.nlm.nih.gov/19073857|journal=Journal of Child Neurology|volume=23|issue=12|pages=1481–1483|doi=10.1177/0883073808319316|issn=1708-8283|pmid=19073857}}</ref>; Spinal cord ganglioglioma:  acute onset paraparesis<ref>{{Cite journal|last=Cruz|first=Thainá Zanon|last2=Ferreira-Pinto|first2=Pedro Henrique Costa|last3=Brito|first3=Ana Carolina Gonçalves|last4=Ururahy|first4=Leandro|last5=Sanchez|first5=Jefferson Trivino|last6=Nigri|first6=Flavio|date=2021|title=Ganglioglioma of the cervicothoracic spinal cord in a patient with neurofibromatosis type 1: A case report|url=https://pubmed.ncbi.nlm.nih.gov/34345454|journal=Surgical Neurology International|volume=12|pages=313|doi=10.25259/SNI_192_2021|issn=2229-5097|pmc=8326088|pmid=34345454}}</ref>
*Laboratory findings - Classic imaging features: T1 iso- to hypointense solid component, T2-hyperintense solid component with varied signal within the cystic component; nodule and cyst wall show variable contrast enhancement<ref name=":2" />


==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==
The <u>sites of involvement</u> of this disease are detailed below:


Put your text here
*Most common location: temporal lobes (>70%)<ref name=":1" /><ref name=":4" /><ref name=":5">{{Cite journal|last=Wolf|first=H. K.|last2=Müller|first2=M. B.|last3=Spänle|first3=M.|last4=Zentner|first4=J.|last5=Schramm|first5=J.|last6=Wiestler|first6=O. D.|date=1994|title=Ganglioglioma: a detailed histopathological and immunohistochemical analysis of 61 cases|url=https://pubmed.ncbi.nlm.nih.gov/7985497|journal=Acta Neuropathologica|volume=88|issue=2|pages=166–173|doi=10.1007/BF00294510|issn=0001-6322|pmid=7985497}}</ref>
*Other locations: cerebrum, brainstem, cerebellum, spinal cord, and optic nerves, lateral ventricle<ref name=":3" /><ref name=":1" /><ref name=":4" /><ref name=":5" />


==Familial Forms==
The <u>morphologic features</u> of this disease are detailed below:


Put your text here
*Ganglioglioma is a biphasic tumor composed of a neoplastic neuronal and a neoplastic glial component<ref name=":3" /><ref name=":5" />. The neoplastic neuronal component is comprised of dysmorphic ganglion cells showing cytomegaly, binucleation and perimembranous aggregation of Nissl substance. Disorganized cytoarchitecture is also observed, with clustering of neurons. The neoplastic glial component can resemble a diffuse glioma or pilocytic astrocytoma; the glial component harbors the proliferative component of the tumor, which can show infiltration on microscopy. Proliferative activity is usually low to absent. The two components can be intermingled or geographically distinct. Other pertinent histological features include Rosenthal fibres, eosinophilic granular bodies and perivascular lymphoid infiltration<ref name=":3" /><ref name=":5" />. An association with focal cortical dysplasia is a commonly reported finding<ref>{{Cite journal|last=Blümcke|first=Ingmar|last2=Thom|first2=Maria|last3=Aronica|first3=Eleonora|last4=Armstrong|first4=Dawna D.|last5=Vinters|first5=Harry V.|last6=Palmini|first6=Andre|last7=Jacques|first7=Thomas S.|last8=Avanzini|first8=Giuliano|last9=Barkovich|first9=A. James|date=2011-01|title=The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission|url=https://pubmed.ncbi.nlm.nih.gov/21219302|journal=Epilepsia|volume=52|issue=1|pages=158–174|doi=10.1111/j.1528-1167.2010.02777.x|issn=1528-1167|pmc=3058866|pmid=21219302}}</ref>.


==Other Information==
The <u>immunophenotype</u> of this disease is detailed below:


Put your text here
*Positive (universal) - CD34 expressed in expressed in ramified tumor cells<ref>{{Cite journal|last=Blümcke|first=Ingmar|last2=Wiestler|first2=Otmar D.|date=2002-07|title=Gangliogliomas: an intriguing tumor entity associated with focal epilepsies|url=https://pubmed.ncbi.nlm.nih.gov/12125736|journal=Journal of Neuropathology and Experimental Neurology|volume=61|issue=7|pages=575–584|doi=10.1093/jnen/61.7.575|issn=0022-3069|pmid=12125736}}</ref>
*Neoplastic neuronal component – MAP2, neurofilament, synaptophysin, chromogranin A (No definitive markers for neoplastic neuronal component; Typical profile: chromogranin A+, NeuN-, synaptophysin+, neurofilament+, MAP2+ (but MAP2 - in glial component)<ref name=":0" /><ref>{{Cite journal|last=Blümcke|first=Ingmar|last2=Wiestler|first2=Otmar D.|date=2002-07|title=Gangliogliomas: an intriguing tumor entity associated with focal epilepsies|url=https://pubmed.ncbi.nlm.nih.gov/12125736|journal=Journal of Neuropathology and Experimental Neurology|volume=61|issue=7|pages=575–584|doi=10.1093/jnen/61.7.575|issn=0022-3069|pmid=12125736}}</ref>)
*Neoplastic glial component – GFAP, OLIG2 (MAP2 -) (Ki-67 <5%<ref>{{Cite journal|last=Prayson|first=R. A.|last2=Khajavi|first2=K.|last3=Comair|first3=Y. G.|date=1995-07|title=Cortical architectural abnormalities and MIB1 immunoreactivity in gangliogliomas: a study of 60 patients with intracranial tumors|url=https://pubmed.ncbi.nlm.nih.gov/7541447|journal=Journal of Neuropathology and Experimental Neurology|volume=54|issue=4|pages=513–520|doi=10.1097/00005072-199507000-00005|issn=0022-3069|pmid=7541447}}</ref>)
*Positive (subset) - BRAF VE1 (+ in BRAF-mutant gangliogliomas)<ref name=":0" />
*Negative (universal) - IDH1 R132H, ATRX (normal retained pattern of staining)<ref name=":0" />
*Negative (subset) - BRAF VE1 (- in BRAF-wildtype gangliogliomas)<ref name=":0" />


==Links==
==Links==
Line 247: Line 679:


==References==
==References==
<references />
<br />


===EXAMPLE Book===
==Notes[edit | edit source]==
 
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''Associate Editor'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
#Arber DA, et al., (2008). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4thedition.Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p117-118.
 
===EXAMPLE Journal Article===
 
#Li Y, et al., (2001). Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet 28:220-221, PMID 11431691.


==Notes==
<nowiki>*</nowiki>''Citation of this Page'': “Ganglioglioma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/CNS5:Ganglioglioma</nowiki>.
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
[[Category:CNS5]]
[[Category:DISEASE]]
[[Category:Diseases G]]
Retrieved from "https://test.ccga.io/index.php/CNS5:Ganglioglioma"