Neuro-Oncology

Updated 09.18.2024
Released 01.16.2024
Expires For CME 09.18.2027

Glioneuronal and neuronal tumors [Brief]

Authors: Pouya Jamshidi MD, Nicolas Kostelecky MD

Editor: Rimas V Lukas MD

Introduction

Key points

	• Glioneuronal and neuronal tumors are a diverse group of tumors with frequent MAPK alterations.
	• They generally have a good prognosis among the collective group of brain tumors.

Discussion

Glioneuronal and neuronal tumors are a collection of tumors that are generally low grade and show indolent behavior; many are driven by MAPK pathway alterations. They frequently occur as histologic and molecular differentials with one another, and their diagnosis requires careful integration of all relevant ancillary studies. Common clinical presentations relate to local mass effect or seizure activity.

Ganglioglioma. Gangliogliomas are MAPK pathway-driven tumors histologically notable for two cell populations: ganglion cells and glial cells. These may be closely admixed or geographically distinct within the tumor. They most often carry a BRAF V600E mutation (23) and typically arise in the temporal lobe, though they may occur anywhere (31). They carry a wide differential diagnosis of other neuroepithelial tumors, some of which are described below, with the most prominent among them being diffuse gliomas, dysembryoplastic neuroepithelial tumors, polymorphous low-grade neuroepithelial tumors of the young, and multinodular and vacuolating neuronal tumors. Additionally, focal cortical dysplasia may be in the differential diagnosis, particularly in epileptogenic cases. Overall, they have an excellent prognosis (10).

Gangliocytoma. Gangliocytomas, in contrast to the similarly named gangliogliomas described above, histologically show exclusively enlarged ganglion-like cells. Exceedingly rare, these tumors affect mostly children and may occur anywhere in the neuraxis, though, like ganglioglioma, they occur most frequently in the temporal lobe. They may also occur in the pituitary gland, where they are thought to arise through transdifferentiation from neoplastic neuroendocrine cells. Unlike ganglioglioma, they have no specific molecular alteration ascribed to them. Nonetheless, they show an excellent prognosis (31; 06).

Dysplastic cerebellar gangliocytoma. Dysplastic cerebellar gangliocytomas (ie, Lhermitte-Duclos disease) morphologically overlap with the gangliocytomas described above but have a strong association with Cowden syndrome (PTEN hamartoma syndrome) and are restricted to the cerebellar molecular and internal granular cell layers (01; 19).

Desmoplastic infantile ganglioglioma or desmoplastic infantile astrocytoma. Desmoplastic infantile ganglioglioma or desmoplastic infantile astrocytomas are benign MAPK pathway-driven tumors that occur most frequently before 24 months of age in the cerebral hemispheres. They may show a broad spectrum of morphologies, depending on the extent of the gangliocytic and astrocytic components. Both types show a desmoplastic leptomeningeal stroma, BRAF or RAF1 mutations or fusions are the most common alterations, and they have an excellent prognosis (04; 05).

Dysembryoplastic neuroepithelial tumor. Dysembryoplastic neuroepithelial tumor is an FGFR1 or BRAF V600E-driven tumor of childhood and young adulthood. Typically located in the cortex, and most frequently in the temporal lobe, these tumors have a characteristic histologic finding of “floating neurons,” normal-appearing neurons embedded in a myxoid matrix with intervening columns of oligodendroglial-like cells. Dysembryoplastic neuroepithelial tumors have a favorable prognosis (11; 30; 32; 25).

Myxoid glioneuronal tumor. Myxoid glioneuronal tumors show a near identical histologic appearance to dysembryoplastic neuroepithelial tumors, hence the original (now discouraged) name of “dysembryoplastic neuroepithelial tumor-like neoplasm of the septum pellucidum” (02). This tumor is distinctly located in the septum pellucidum, corpus callosum, or periventricular white matter and is defined by a mutation in PDGFRA. Myxoid glioneuronal tumors have a good prognosis (20).

Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters. Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters is a rare, DNA methylation-defined entity with a wide morphologic spectrum, including variable cellularity, oligodendroglioma-like cells, and multinucleated cells (24). In addition to their distinct DNA methylation profile, the monosomy of chromosome 14 is frequently described (08; 12). They are reported more frequently in children, though a broad age range has been noted. They show a favorable prognosis (12; 24; 03).

Papillary glioneuronal tumor. Papillary glioneuronal tumors are commonly supratentorial and show a predilection for young adults. They have a biphasic pattern, with a glial pseudopapillary component, cuboidal cells, and an interpapillary component of neurocytic and ganglioid cells. They show PRKCA fusions, with the most common partner being SLC44A1 (resulting in a SLC44A1::PRKCA fusion). They have a generally good prognosis (22; 15).

Rosette-forming glioneuronal tumor. Rosette-forming glioneuronal tumors are biphasic tumors composed of a rosette-forming neurocytic component and a glial component (18). They are midline in nature and often carry alterations in FGFR1, with a coinciding PIK3CA or PIK3R1 mutation (28). Though they are indolent in nature, given their typical location in the midline (eg, cerebellar vermis, 4th ventricle, and brainstem), postoperative complications are not uncommon.

Diffuse leptomeningeal glioneuronal tumor. Diffuse leptomeningeal glioneuronal tumor is a leptomeningeal-based tumor, unique in this category, which frequently shows a KIAA1549::BRAF fusion (the same as seen in pilocytic astrocytoma) (27). The affected leptomeninges can be either in the spinal cord or cerebrum. Mostly affecting pediatric patients, these tumors show a more waxing and waning clinical course as compared to other glioneuronal tumors, with variable rates of 5-year survival reported (26).

Multinodular and vacuolating neuronal tumor. Multinodular and vacuolating neuronal tumors are uncommon, cerebral-based tumors at the deep cortical ribbon or superficial white matter that harbor MAPK alterations. They have a nodular architecture with vacuolated tumor cells. They show a wide age of presentation but often have an excellent prognosis (16; 09).

Central neurocytoma and extraventricular neurocytoma. Central neurocytomas and extraventricular neurocytomas are neuroepithelial tumors with overlapping histomorphology, namely round cells with speckled chromatin. The most typical architectural finding is that of fibrillary areas, though extraventricular neurocytomas show a more diverse morphologic spectrum (14; 07). Key differences between these entities, though they share a name and some histologic findings, include their localization (intraventricular in central neurocytoma, intraparenchymal for extraventricular) and distinct molecular features. Central neurocytomas show a distinct DNA methylation profile but no other recurrent features (17). Extraventricular neurocytomas have their own separate DNA methylation profile and frequently harbor FGFR1::TACC1 fusions (29). These tumors have the potential to follow a more aggressive course than many of the entities described above.

Cerebellar liponeurocytoma. Cerebellar liponeurocytomas, as the name implies, are tumors of the cerebellum showing two morphologic populations: neurocytic cells arranged in sheets and adipocyte-like cells that are, in fact, lipid-laden neuroepithelial cells. It has a good prognosis, typically occurs in late-to-middle-aged adults, and may recur. At recurrence, the tumor may show a marked reduction in the lipid-rich cells and, in turn, may show more atypical histomorphology (21; 13).

References

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33: References especially recommended by the author or editor for general reading.

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Glioneuronal and neuronal tumors …

Glioneuronal and neuronal tumors [Brief]

Introduction

Key points

Discussion

References

Contributors

Authors

Editor

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

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Cerebellar astrocytoma

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Glioneuronal and neuronal tumors [Brief]

Introduction

Key points

Discussion

References

Contributors

Authors

Editor

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Anti-LGI1 encephalitis

CNS germinoma

Circumscribed astrocytic gliomas [Brief]

Pediatric-type diffuse high-grade gliomas [Brief]

Adult-type diffuse gliomas [Brief]

Mesenchymal non-meningothelial tumors [Brief]

Cerebellar astrocytoma

Neurolymphomatosis

This is an article preview.
Start a Free Account
to access the full version.