Definition
- Essential:
- Intra-axial low-grade glioneuronal tumour AND
- Combination of neoplastic ganglion and glial cells
- AND (for unresolved lesions)
- BRAF V600E mutation or other МАРК pathway alteration OR
- Methylation profile of ganglioglioma
- Desirable:
- Absence of IDH mutation
WHO Grade
- Grade 1
- If has anaplastic features then grade 3
- No criteria for grade 2 have been established yet
Localisation
- Can occur throughout CNS
Cranial
- >70% temporal lobe
- Based on 602 surgical specimens submitted to the German Neuropathological Reference Center for Epilepsy Surgery.
Localisation | Number of specimens | Tumours |
Temporal | 509 | 84% |
Frontal | 28 | 5% |
Parietal | 17 | 3% |
Occipital | 12 | 2% |
Multiple lobes | 30 | 5% |
Other | 6 | 1% |
Spinal
- More common in children
- 2nd most common intramedullary spinal cord tumour in paeds
- Long tumor length
- Presence of tumoral cysts
- Absence of edema and syrinx formation
- Patchy postcontrast enhancement is usually seen, and there may be enhancement of the pial surface of the cord
- Common occur in the Cervicothoracic region.
- Tumour can extend into medulla
- Low-grade tumors and have a low potential for malignant degeneration but a high propensity for local recurrence.
Numbers
- Gangliogliomas and gangliocytomas together account for
- 0.4% of all CNS tumours
- 1.3% of all brain tumours
- Incidence
- 0.3– 5.2% in adult tumour
- 14% in paediatric tumours
- Mean/median patient age at diagnosis of 8.5-25 years.
- Male to female ratio is 1.1-1.9:1
- The mean patient age at surgery when presented with epilepsy was 9.9 years and 48% of the patients were girls.
Clinical presentation
- Chronic temporal lobe epilepsy
- Most common tumour associated with epilepsy
- Gangliogliomas have been reported in 15-25% of patients undergoing surgery for control of seizures
- Pharmacoresistant epilepsy.
- A non- epileptic presentation in a case with a presumed ganglioglioma should alert the treating clinician to the possibility of a non- benign clinical course.
Radiological
CT
- Iso- or hypodense
- Frequently calcified ~35%
- Bony remodelling or thinning can indicate the slow growing nature of a tumour (scalloping)
- Enhancement is seen in approximately 50% of cases
MRI
- T1
- Solid component iso to hypointense
- T1 C+ (Gd)
- Solid component variable contrast enhancement
- T2
- Hyperintense solid component
- Variable signal in the cystic component depending on the amount of proteinaceous material or the presence of blood products
- Peritumoural FLAIR/T2 oedema is distinctly uncommon
- T2* (GE/SWI)
- Calcified areas (common) will show blooming signal loss
Images
Histopathology
Macroscopic
- Well-delineated solid or cystic lesions, usually with little mass effect
- Calcification may be present
- Necrosis and haemorrhage rare
Microscopy
- Combination of neuronal and glial cell elements, which may exhibit marked heterogeneity
- Can be dominant glial or neuronal
- Dysplastic Ganglion cells (neurons) component
- Clustering, a lack of cytoarchitectural organization,
- Cytomegaly
- Well differentiated hence called ganglion (large cells seen in image)
- Perimembranous aggregation of Nissl substance,
- The presence of binucleated forms (seen in < 50% of cases). The glial component of gangliogliomas
- Neoplastic glial component
- Substantial variability, but constitutes the proliferative cell population of the tumour
- Include cell types resembling fibrillary astrocytoma, oligodendroglioma, or pilocytic astrocytoma
- Rarefaction of white matter is another common feature
- May develop a reticulin fibre network apart from the vasculature
- Dystrophic calcification, either within the matrix or as neuronal/capillary incrustation
- Extensive lymphoid infiltrates along perivascular spaces or within the tumour/brain parenchyma
- A prominent capillary network
- Focal cortical dysplasia is an uncommon finding in gangliogliomas
- Ki-67 proliferation index: 1.1% to 2.7%
Immunophenotype
- Similar to gangliocytoma
- Positive
- Neuronal component
- Synaptophysin
- Neurofilament
- Chromogranin-A
- MAP2
- CD34 (80%)
- Not present in neurons in adult brain
- Consistently expressed in 70-80% of gangliogliomas, especially when located in temporal lobe
- Prominent not only in confluent areas of the tumour, and also in peritumoural satellite lesions
- Glial component
- GFAP
- BRAF V600E mutation stain
- Negative
- NeuN (weakly expressed or negative)
Genetic profile
- BRAF V600E mutation occurs in approximately 50% of gangliogliomas
- Ganglion cells might carry this mutation and be stained up
- Presence of a BRAF V600E mutation was associated with (Poorer prognosis) shorter recurrence-free survival in paeds gangliogliomas
- IDH mutation or combined loss of chromosomal arms 1p and 19q exclude a diagnosis of a ganglioglioma
- Gain of chromosome 7
- Detection of TP53 or PTEN mutations or CDK4 or EGFR amplification does not support a diagnosis of ganglioglioma.
- Been associated with
- Peutz-jegher syndrome
- NF1 and 2
Treatment
Surgery
- Low complications rates
- Tumour location
- Young age
- Not comorbid
- The epileptological results following surgical treatment are also very good.
- Luyken et al., 2003:
- Engel class I outcomes (seizure- free or only occasional non- disabling seizures) in approximately 80% of LEAT cases during a 10 yrs follow- up in a cohort of 207 patients (including 86 gangliogliomas) undergoing surgery for drug- resistant epilepsy of more than 2 years
- Luyken et al., 2004
- A complete tumour resection will cure all but the very occasional patient with a ganglioglioma WHO grade I
- Presentation with long- term or refractory epilepsy is an immensely important clinical prognostic marker (Majores et al., 2008).
- A recent report of 88 such cases detailed a 5 yrs. progression- free survival rate of only 58% following surgery (Compton et al., 2012).
Prognosis
- The prognosis is favourable, with a recurrence-free survival rate as high as 97% at 7.5 years.
- Good prognosis is associated
- Temporal lobe
- Complete surgical resection
- Chronic epilepsy
- Poor prognosis marker
- High Ki67 index
- Presence of p53 labelling
- Inconsistent histological association with outcome
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