Ganglioglioma: Gangliogliomas are the most common type of glioneuronal tumor, accounting for 1% of all primary CNS neoplasms. These tumors are often located in the temporal lobe and are strongly epileptogenic (LEAT group). They can be located in other locations with spinal cord involvement being associated with a higher risk of recurrence. Anaplastic ganglioglioma, once classified as a WHO Grade III tumor, is now considered a separate entity.
They are characterized by a mixture of ganglionic neurons and glial cells. BRAFV600E mutations are associated with a poorer prognosis.
Gangliogliomas usually appear as solid masses, which may have cystic or calcified areas in up to 50% of cases. On MRI, they are hypointense or isointense on T1WI and hyperintense on T2WI, with heterogeneous contrast enhancement.
Gangliocytoma is primarily composed of mature neurons. Unlike gangliomas, it is characterized by a predominance of mature neurons with minimal or no glial component. The differential diagnosis should include a wide spectrum of solid-cystic tumors, such as pleomorphic xanthoastrocytoma, dysplastic neuroepithelial tumor (DNET), pilocytic astrocytoma, and metastatic lesions.
Dysembryoplastic Neuroepithelial Tumors (DNET): DNETs are rare, low-grade (WHO Grade I) glioneuronal tumors predominantly affecting young individuals most commonly arising in the temporal lobes. Focal cortical dysplasia is often associated with DNETs (LEAT group).
DNETs are composed of parallel axes of pseudo-oligodendroglial cells arranged around capillaries or axonal bundles, separated by a myxoid matrix containing "floating neurons.” Molecularly, FGFR1 alterations are frequent.
DNETs typically appear as well-demarcated hypointense lesions on T1-WI, hyperintense lesions on FLAIR/T2W showing no contrast enhancement. They often exhibit a soap-bubble appearance and demonstrate high ADC values, reflecting low cellular density. Perilesional edema and mass effect are minimal.
DNETs are included in the differential diagnosis of cystic glioneuronal tumors, particularly when considering lesions in the temporal lobe. Key differential diagnoses include ganglioglioma and focal cortical dysplasia. The newly described MVNT also shares some imaging similarities with DNET.
Desmoplastic infantile ganglioglioma/astrocytoma (DIG/DIA): They are uncommon, low-grade glioneuronal tumors that manifest in children under two years of age with increased head circumference, bulging fontanelles, and seizures.
The histology of DIG and DIA tumors is characterized by a combination of neuronal and astrocytic components within a dense fibrous connective tissue stroma. This stroma is accompanied by leptomeningeal desmoplasia.
These tumors are large, solid-cystic masses involving the superficial cortex and meninges. The dura-based solid component shows marked restriction on DWI and significant contrast enhancement. Although these tumors exhibit minimal surrounding edema they can have a significant mass effect.
The main differential diagnosis should be made with supratentorial anaplastic ependymoma, another large solid-cystic tumor located in the supratentorial region. Calcifications and hemorrhage are typical of this tumor, while they are extremely rare in DIG/DIA.
Myxoid glioneuronal tumor: It is a rare neoplasm primarily affecting young adults aged 20-25 years. It is most commonly located in the septum pellucidum but can also be found in periventricular regions and the corpus callosum. The primary presentation is often hydrocephalus, although many cases are discovered incidentally.
Molecularly, these tumors express markers such as OLIG2, SOX10, and GFAP. A key genetic finding is a mutation in the PDGFRA gene, specifically at codon p.K385.
On imaging, the tumor may present as a solid/cystic mass or a combination of both. The cystic component typically appears hyperintense on T2-WI and may suppress partially on FLAIR (T2/FLAIR mismatch) The solid portion usually does not enhance after contrast showing low perfusion and no restricted diffusion.
The differential diagnosis includes other centrally located tumors such as colloid cysts, ependymomas, subependymomas, and central neurocytomas.
Central neurocytoma: They account for 0.1% to 0.5% of all primary brain tumors and are classified as WHO Grade II. They primarily affect young adults, typically in their third decade of life. Most patients present with symptoms of intracranial hypertension secondary to obstructive hydrocephalus.
These tumors are composed of neurocytic cells with clear cytoplasm (salt and pepper appearance) similar to oligodendrogliomas. Genetic studies are crucial as central neurocytomas lack the IDH1/2 mutations and 1p/19q codeletion characteristic of oligodendrogliomas. They are mainly located in the lateral ventricles with < 3% occurring in the third and fourth ventricles.
On imaging, central neurocytomas typically appear as well-circumscribed, isointense, or slightly hyperintense masses on T1-WI and hyperintense on T2-WI. They often have a "soap-bubble" appearance due to cystic degeneration. Calcifications are common. Vascular voids and heterogeneous enhancement are frequently observed. Restricted diffusion is common, reflecting the high cellular density of these tumors.
Rosette-forming glioneuronal tumor (RGNT): is a rare, low-grade (WHO Grade I) neuroepithelial tumor that predominantly affects young adults. It is characterized by a distinctive histopathology, featuring a neurocytic component arranged in rosettes or perivascular pseudorosettes. The glial component often resembles that of pilocytic astrocytoma, with Rosenthal fibers and eosinophilic granular bodies.
These tumors primarily arise in the fourth ventricle, often involving the cerebellar vermis, midbrain, and cerebral aqueduct. Other less common locations include the cerebellar hemispheres, pineal region, lateral and third ventricles, and even the spinal cord.
RGNTs may appear solid or cystic. They typically demonstrate hypointensity on T1WI and hyperintensity on T2 WI. It shows a characteristic "ring enhancement" pattern, where the periphery of the tumor enhances more strongly than the central portion giving the appearance of a sectioned bell pepper. Calcifications and hemorrhage may be present in some cases.
Dysplastic cerebellar gangliocytoma (Lhermitte Duclos disease): it is a rare tumor of the cerebellum usually occurring in the setting of Cowden disease. Cowden disease is a rare autosomic dominant condition involving the PTEN gene. Patients present multiple hamartomas, breast, and thyroid neoplasm.
The tumor is considered to be hamartomatous rather than neoplastic and consists of an abnormal thickening of the external molecular layer of the cerebellum, depletion of the Purkinje cell layer, and infiltration of the granular layer by dysplastic ganglion cells.
Image features: The MRI showed cerebellar folia hypertrophy with a tiger stripe appearance, partial contrast enhancement, and venous proliferation between the folia.
Differential diagnosis includes cerebellar ischemia, cerebellitis, and medulloblastoma. Medulloblastoma is a more common and aggressive tumor, also seen in patients with Cowden syndrome. Unlike DGTP, it appears hypointense on imaging, enhances strongly, and shows restricted diffusion.
Diffuse leptomeningeal glioneuronal tumor (DLGNT): It is a rare oligodendroglial-derived disseminated tumor defined as an independent glioneuronal tumor on 2016 WHO classification. The WHO grade has not yet been determined. DLGNT involves diffusely the leptomeninges and mainly affects children.
Histomolecular pathology: Oligodendrocyte-like tumour cells. 1p/19q codeletion and MAPK signaling pathway activation. Two subtypes are defined based on methylation classes DLGNT-1 and DLGNT2. DLGNT2 and/or gain of 1q are associated with a worse prognosis.
Image features: Thickened leptomeninges with a leptomeningeal contrast enhancement and diffuse small subpial cysts.
Differential diagnoses induce Infectious, inflammatory, and carcinomatous meningitis.
Less common glioneuronal tumors:
Multinodular and vacuolating neuronal tumor (MVNT): New entity in the WHO 2021 classification. Juxtacortical tiny, well-defined T2 hyperintense nodules without mass effect located on temporal and parietal lobes.
Cerebellar liponeurocytoma: Upgrade to WHO grade II in 2016. It’s a well-defined hypoattenuating mass involving the cerebellar hemisphere. Because of the fatty component, it shows focal areas of hyperintensity on both T1 and T2-WI.
Diffuse glioneuronal tumor with oligodendroglial features (DGONC): Really rare tumor with oligodendroglioma-like features. Well-defined rounded mass iso/hyperintense on T2-WI. It may contain blood, calcium, and small cystic areas. It shows no contrast enhancement after contrast and restricted diffusion.
Papillary glioneuronal tumor: It is a tumor that originates from the germinal layer of the ependyma. It is located in supratentorial periventricular white matter. Features on imaging are very similar to ganglioglioma.