Ganglioglioma (GG) is a mixed tumor containing both dysplastic neurons and glial cells. The majority are low-grade tumors classified as WHO Grade 1 or 2.
They account for 0.4–1.7% of all central nervous system tumors, with an annual incidence of approximately 0.06–0.02 per million for the common type, making them extremely rare. 1, 2) About 19% of adult GGs occur in the posterior cranial fossa. 3)
Neuro-ophthalmic signs may arise when the tumor directly compresses or infiltrates structures involved in the visual pathway or eye movement, or via increased intracranial pressure. Understanding the relationship between tumor location and ocular symptoms is key to diagnosis.
It tends to occur more often in children and young adults, but cases in adults and the elderly have also been reported. Cerebellar GGs have been reported at ages 75 2) and 76 3), with no upper age limit. They can grow extremely slowly; some GGs discovered in childhood have remained asymptomatic for about 60 years. 3)
Neuro-ophthalmologic subjective symptoms of ganglioglioma vary depending on the location.
Ophthalmologic findings vary depending on the site of occurrence.
Suprasellar Lesions
Optic nerve infiltration: Decreased visual acuity and concentric visual field constriction. Direct infiltration has been reported in 5 cases. 7)
Optic chiasm infiltration: Bitemporal hemianopsia. Confirmed in 9 of 19 cases of suprasellar GG in a review. 7)
Optic tract infiltration: Homonymous hemianopsia pattern. One case reported in the literature. 7)
Pineal Region Lesions
Parinaud syndrome: Presents with upward gaze palsy, convergence insufficiency, and light-near dissociation. Caused by dorsal midbrain compression due to pineal region tumors.
Bilateral papilledema: Mainly due to increased intracranial pressure from obstructive hydrocephalus. May be accompanied by seizures. 4)
Posterior Fossa Lesions
Papilledema: Bilateral papilledema associated with obstructive hydrocephalus.
Abducens nerve palsy: Occurs as a false localizing sign due to increased intracranial pressure. Diplopia is the main complaint.
Li et al. reviewed 19 cases of suprasellar GG in the literature and reported visual dysfunction in 15/19 cases (79%). 7) The breakdown was 5 cases of optic nerve infiltration, 9 cases of optic chiasm infiltration, and 1 case of optic tract infiltration, indicating that direct tumor invasion of the visual pathway is the main cause of visual acuity and visual field deficits.
Parinaud syndrome is caused by compression or damage to the dorsal midbrain (superior colliculus) and presents with the triad of upward gaze palsy, convergence disorder, and light-near dissociation. It is a characteristic ophthalmologic finding in pineal region tumors, and in pineal region tumors including ganglioglioma, it often coexists with obstructive hydrocephalus. 4)
Established environmental risk factors for ganglioglioma are not clear. Genetic mutations have been shown to be involved in tumor formation.
The rate of anaplastic transformation varies by report, ranging from 0.6% to 14.5%. 1) Anaplastic GG has a high risk of recurrence and metastasis.
The diagnosis of ganglioglioma is based on a combination of neuroimaging and histopathological examination.
MRI is the mainstay of diagnosis.
The following are performed as part of the neuro-ophthalmic evaluation.
In cerebellar ganglioglioma, differentiation from pilocytic astrocytoma is particularly difficult, and histopathological confirmation is required. 6)
| Location | Main differential diagnoses |
|---|---|
| Suprasellar | Craniopharyngioma, optic pathway glioma |
| Pineal region | Germ cell tumor, pineocytoma |
| Cerebellum | Pilocytic astrocytoma, medulloblastoma |
Definitive diagnosis is made by histopathology. Confirmation of the BRAF V600E mutation is now considered an essential test item because it directly affects treatment selection. 5)
Gross total resection (GTR) is the first choice.
Postoperative radiotherapy is performed for anaplastic GG or cases with residual tumor.
The survival time for anaplastic GG is shown below.
| Condition | Median survival time or survival rate |
|---|---|
| Anaplastic GG overall | 24.7–29 months1, 8) |
| After GTR (anaplastic GG) | 44 months1) |
| 2-year survival rate (anaplastic GG) | Approximately 40%2) |
| 2-year survival rate (typical GG) | Approximately 90%2) |
The median survival time for anaplastic GG is reported to be 24.7 to 29 months. 1, 8) When gross total resection is achieved, it is reported to extend to 44 months. 1) While the 2-year survival rate for low-grade GG is about 90%, that for anaplastic GG is about 40%, showing a significant difference in prognosis. 2)
Ganglioglioma is a tumor composed of differentiated neuronal and glial cells, and its neuro-ophthalmic effects occur through the following mechanisms.
At the molecular level, the BRAF V600E mutation constitutively activates the RAF-MEK-ERK pathway, promoting tumor cell proliferation. Low-grade gliomas with only this mutation often follow an indolent course. Additional mutations such as CDKN2A/B deletion are implicated in anaplastic transformation5), and this mechanism is of interest in malignant progression.
Vizcaino et al. analyzed three cases of anaplastic transformation of BRAF V600E-mutant gliomas from pathological, molecular, and epigenetic perspectives, showing that acquisition of CDKN2A/B deletion is important for transformation.5)
Molecular targeted therapy targeting the BRAF V600E mutation has been applied to anaplastic GG.
Vizcaino et al. reported that three cases of anaplastic transformed GG with BRAF V600E mutation were treated with combination therapy of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor), achieving disease stabilization for 17 to 31 months. 5)
Vemurafenib (another BRAF inhibitor) has also been mentioned for application to anaplastic GG. 2) Research on these molecular targeted drugs as new treatment options for unresectable or recurrent cases is ongoing.
Currently at the research stage and not standard treatment. The combination of dabrafenib and trametinib has been reported to achieve disease stabilization for 17–31 months in 3 cases of anaplastic transformation of GG 5), but verification through large-scale clinical trials is needed. Confirmation of BRAF V600E mutation is a prerequisite.
