Table 1.

Main characteristics of some rare predominantly glioneuronal and neuronal tumours (WHO grade 1 and 2).

Tumour	Median Age (Years)/ Sex	Localisation	Immunohisto Chemistry	Specific Mutations	Histology	Symptoms	Treatment	MRI Particularities
Multinodular and vacuolating neuronal tumours	40 y, M > F [31]	Temporal/frontal lobes,	OLIG2+, synaptophysin-, CD34-, GFAP-. NeuN- [32]	MAPK pathway mutations of MAP2K1 and of BRAF (excluding BRAFV600E) [33]. FGFR2 fusion	Purely neuronal (non-neurocytic and no neoplastic glial cells). Absence of mitoses.	Mainly seizures [34] Sometimes incidental finding.	Observation preferred. Surgery only if refractory epilepsy [35]. Molecular targeted therapy *.	Small superficial cortical cystic lesions, sometimes in clusters [31].
Rosette-forming glioneuronal tumour (Figure 2)	20 y	Midline structures in proximity of the 4th ventricle and the aqueduct of Sylvius	Neurocytes: Olig2+, rosettes: synaptophysin+, Glial cells: GFAP+, S100+	FGFR1 mutations are very common, associated with PIK3CA, PIK3R1 or NF1 mutations [36]	Biphasic tumour with a component of neurocytes forming rosettes and/or pseudorosettes, and a glial component (often pilocytic astrocytes).	Progressive brainstem/cerebellar signs and visual disturbance.	Surgical resection is preferred [37]. If aggressive features and/or leptomeningeal infiltration, spinal metastasis: RT and chemotherapy [38] can be discussed in an adjuvant manner after surgery. Molecular targeted therapy*.	Mix of cystic and solid lesions, strong gadolinium enhancement. “Green bell pepper sign” [39].
Papillary glioneuronal tumour	25 y	Supratentorial: mainly temporal and frontal lobes	Neurocytes: Olig2+, synaptophysin+, Astrocytic cells of papilla: GFAP+	PRKCA gene fusions, mostly SLC44A1:PRKCA fusion [40,41]	biphasic organisation with astrocytic papillas around hyalinized vessels and a neuronal component (most often neurocytic).	Headaches [42] and seizures. Incidental finding if small enough. Often characterized by an indolent course [43].	Surgical resection alone is preferred: with very rare recurrences [44]. RT and/or chemotherapy if high Ki-67 in recurrence or other features of aggressiveness [45].	Solid and a cystic component [46]. Septations can be quite specific. Calcifications are frequent.
Myxoid glioneuronal tumour (previously DNT of the septum pellucidum)	20–25 years	Septum pellucidum, periventricular locations, corpus callosum [47].	OLIG2+, SOX10+, GFAP+	dinucleotide mutation at codon p.K385 in the PDGFRA gene [47]	Histologically similar to DNT or RGNT.	Hydrocephalus the most frequent initial clinical presentation, incidental findings not rare.	Gross surgical resection alone is preferred. In case of relapse and/or dissemination, RT [48] and/or chemotherapy (TMZ, CCNU) [47] can be considered.	No contrast enhancement, nor diffusion restriction. Partially suppressed Flair in centre, no oedema [48,49].
Gangliocytoma	Children, young adults	Mainly temporal lobe [50]. Sellar locations also seen [51].	chromogranin A+, synaptophysin+, neurofilament+, GFAP-	BRAFV600E mutation of alternative MAPK pathway alterations [52].	multinucleated ganglionic neuronal tumour cells.	Seizures due to temporal/cortical locations [50,53]. Sometimes headaches, brainstem signs.	Surgical resection [53]. Relapse after resection remains very rare [54]. Chemotherapy has no place, neither radiotherapy. Molecular targeted therapy*.	Strong Gd enhancement, cystic images, perilesional oedema, calcifications [54].
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters	Young adults, children	Supratentorial locations.	Synaptophysin+, NeuN+, MAP2+, Olig2+, GFAP-	Monosomy 14. Distinct methylation profile [55].	Pseudo-oligodendroglial cells infiltrating cerebral cortex and forming nuclear clusters. Low number of mitosis.	Unspecific.	No standard treatment. Gross total surgery followed by radiotherapy may be a good option [56].	None or only discrete Gd enhancement, no oedema.

Molecular targeted therapy *: Molecular targeted therapy is an option if druggable molecular alteration is detected (e.g., BRAF or FGFR inhibitor).