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→Primary Author(s)*
==Primary Author(s)*==
==Primary Author(s)*==
Dr Leila Moayed Alaei, Royal Prince Alfred Hospital
__TOC__
__TOC__
==Cancer Category/Type==
==Cancer Category/Type==
Glioneuronal tumour
==Cancer Sub-Classification / Subtype==
==Cancer Sub-Classification / Subtype==
Ganglioglioma
==Definition / Description of Disease==
==Definition / Description of 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>.
==Synonyms / Terminology==
==Synonyms / Terminology==
None
==Epidemiology / Prevalence==
==Epidemiology / Prevalence==
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>.
==Clinical Features==
==Clinical Features==
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"
|'''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>
|-
|'''Imaging 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" />
|}
==Sites of Involvement==
==Sites of Involvement==
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==
==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==
==Immunophenotype==
<br />
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
! Finding !! Marker
!Finding!!Marker
|-
|-
|Positive (universal) || EXAMPLE CD1
|Positive (universal)
|CD34 expressed in expressed in ramified tumor cells[21]
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)[1, 20]
Neoplastic glial component – GFAP, OLIG2 (MAP2 -)
* Ki-67 <5%[5]
|-
|-
|Positive (subset) || EXAMPLE CD2
|Positive (subset)
|BRAF VE1 (+ in BRAF-mutant gangliogliomas)
|-
|-
|Negative (universal) || EXAMPLE CD3
|Negative (universal)
| IDH1 R132H, ATRX (normal retained pattern of staining)
|-
|-
|Negative (subset) || EXAMPLE CD4
|Negative (subset)
|BRAF VE1 (- in BRAF-wildtype gangliogliomas)
|}
|}
==Chromosomal Rearrangements (Gene Fusions)==
==Chromosomal Rearrangements (Gene Fusions)==
{| class="wikitable"
|'''Chromosomal Rearrangement'''
|'''Genes in Fusion'''
'''(5’ or 3’ Segments)'''
|'''Structural variation'''
|'''Prevalence'''
|'''Diagnostic Significance (Yes, No or Unknown)'''
|'''Prognostic Significance (Yes, No or Unknown)'''
|'''Therapeutic Significance (Yes, No or Unknown)'''
|'''Notes'''
|-
|t(7;7)(q34;q34)[8,13]
|''KIAA1549::BRAF [8, 9]''
|duplication
|16.7 % [9]
|Yes[1,8]
|No
|Yes[22]
|<nowiki>- also seen in PLNTY, ganglioglioma, and pilocytic astrocytoma; can distinguish by methylation signature[1] </nowiki>
- in-frame fusion[8]
|-
|t(8;8)(p11.23;p11.22)
|''FGFR1::TACC1 [8]''
|inversion
|2.5% (1/40)[8]
|Unknown
|Unknown
|Unknown
|<nowiki>- in-frame fusion[8] </nowiki>
- no FDA-approved anti-FGFR therapy for ganglioglioma at present
|-
|t(10;10)(q26.13;q25.3) [8,13]
|''FGFR2::KIAA1598 [8]''
|deletion
|2.5% (1/40)[8]
|Unknown
|Unknown
|Unknown
|<nowiki>- in-frame fusion[8] </nowiki>
<br />
|-
|t(10;10) (q26.13;q24.3)[8,13]
|''FGFR2::INA[8]''
|inversion
|2.5% (1/40) [8]
|Unknown
|Unknown
|Unknown
|<nowiki>- in-frame fusion[8] </nowiki>
<br />
|-
|t(3;3)(p14.3;p25.2) [8,13]
|''ERC2::RAF1[8]''
|deletion
|2.5%(1/40) [8]
|Unknown
|Unknown
|Yes (potential) [22]
|<nowiki>- in-frame fusion[8] </nowiki>
<br />
|-
|-
|t(14;7)(q32.32;7q34) [8,13]
|''CDC42BPB::BRAF [8]''
|translocation
|2.5% (1/40) [8]
|Unknown
|Unknown
|Yes (potential) [22]
|<nowiki>- in-frame fusion[8] </nowiki>
<br />
|-
|-
|EXAMPLE t(9;22)(q34;q11.2) || EXAMPLE 3'ABL1 / 5'BCR || EXAMPLE der(22) || EXAMPLE 5%
|t(7;7)(p15.3;q34) [8,13]
|''KLHL7::BRAF[8]''
|inversion
|2.5% (1/40) [8]
<br />
|Unknown
|Unknown
|Yes (potential) [22]
|<nowiki>- in-frame fusion[8] </nowiki>
<br />
|-
|-
|EXAMPLE t(8;21)(q22;q22) || EXAMPLE 5'RUNX1 / 3'RUNXT1 || EXAMPLE der(8) || EXAMPLE 5%
|t(1;11)(q25.2;q14.1) [8,13]
|}
|''ABL2::GAB2[8]''
|translocation
|2.5% (1/40) [8]
<br />
|Unknown
|Unknown
|Yes (potential) [22]
|<nowiki>- in-frame fusion[8] </nowiki>
<br />
|}
==Characteristic Chromosomal Aberrations / Patterns==
==Characteristic Chromosomal Aberrations / Patterns==
None
==Genomic Gain/Loss/LOH==
==Genomic Gain/Loss/LOH==
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
! Chromosome Number !! Gain/Loss/Amp/LOH !! Region
!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
|-
|-
|EXAMPLE 8 || EXAMPLE Gain || EXAMPLE chr8:0-1000000
|EXAMPLE 8||EXAMPLE Gain||EXAMPLE chr8:0-1000000
|-
|-
|EXAMPLE 7 || EXAMPLE Loss || EXAMPLE chr7:0-1000000
|EXAMPLE 7||EXAMPLE Loss||EXAMPLE chr7:0-1000000
|}
|}
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
! Gene !! Mutation !! Oncogene/Tumor Suppressor/Other !! Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) !! Prevalence (COSMIC/TCGA/Other)
!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
|-
|-
| EXAMPLE TP53 || EXAMPLE R273H || EXAMPLE Tumor Suppressor || EXAMPLE LOF || EXAMPLE 20%
|EXAMPLE TP53||EXAMPLE R273H||EXAMPLE Tumor Suppressor||EXAMPLE LOF||EXAMPLE 20%
|}
|}
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
! Type !! Gene/Region/Other
!Type!!Gene/Region/Other
|-
|-
| Concomitant Mutations || EXAMPLE IDH1 R123H
|Concomitant Mutations||EXAMPLE IDH1 R123H
|-
|-
| Secondary Mutations || EXAMPLE Trisomy 7
|Secondary Mutations||EXAMPLE Trisomy 7
|-
|-
|Mutually Exclusive || EXAMPLE EGFR Amplification
|Mutually Exclusive||EXAMPLE EGFR Amplification
|}
|}
==References==
==References==
=== EXAMPLE Book ===
===EXAMPLE Book===
#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.
#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 ===
===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.
#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 ==
==Notes==
<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.
<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.