Case of the Month: December 2025 
Diagnosis and Discussion 

Answers to Questions:

- The differential diagnosis includes multinodular and vacuolating neuronal tumor (MVNT), dysembryoplastic neuroepithelial tumor (DNT), low-grade glioneuronal tumors, and focal cortical dysplasia. The combination of multinodular T2/FLAIR hyperintense lesions, vacuolated neuronal cells, and synaptophysin positivity supports MVNT.

- OLIG2 is a marker of oligodendroglial lineage but is also expressed in MVNT tumor cells, reflecting early neuronal differentiation and supporting a diagnosis of MVNT when interpreted alongside morphology and other markers.

Expanded History:

The patient had drug-resistant epilepsy since his teenage years, with no other neurological deficits. Imaging was performed due to worsening seizure frequency. There is no family history of epilepsy or CNS tumors.

Radiology:

MRI demonstrated multiple, non-enhancing, subcortical nodules in the right frontal lobe, hyperintense on T2 and FLAIR, with no mass effect or edema. These features are characteristic of MVNT and help distinguish it from other low-grade tumors.

Histology:

Multiple, sharply demarcated nodules in deep cortex and superficial white matter. Vacuolated, intermediate-to-large neuronal cells with round nuclei, open chromatin, and distinct nucleoli. No mitoses or increased glial cellularity.

Differential Diagnosis:

- MVNT (favored)

- DNT

- Focal cortical dysplasia

- Low-grade glioneuronal tumor

- Ganglioglioma

Immunohistochemistry:

- Synaptophysin, HuC/HuD, or non-phosphorylated 200-kDa NFP: Positive in lesional cells (neuronal origin)

- Neurofilament, MAP2: Variable positivity, supporting neuronal differentiation

- OLIG2, Doublecortin: Positive expression of early neuronal markers, suggesting maturation arrest

- CD34: Positive ramified neural elements in adjacent cortex

- GFAP: Negative in tumor cells, positive in reactive astrocytes

- NeuN, chromogranin: Negative

Molecular/Methylation Information:

- No consistent mutations in BRAF V600E, IDH1/2, FGFR1, or mTOR pathway genes

- MAPK pathway-activating mutations, commonly indels and hotspot mutations in MAP2K1

- FGFR2-ZMYND11 fusion has been reported in some cases

- Methylation profiling is not diagnostic, possibly due to small number of cases currently included in classifiers, but supports the benign nature.

Discussion:

MVNT is a rare, benign CNS WHO grade 1 lesion, typically presenting in adults with late-onset, drug-resistant epilepsy or headaches. Lesions are most often supratentorial, involving the temporal or frontal lobes, and show characteristic multinodular, non-enhancing, T2/FLAIR hyperintense appearance on MRI. These tumors usually involve deep cortex and superficial white matter as opposed to DNT which is predominantly cortical in location. Histologically, MVNT consists of vacuolated neuronal cells in well-demarcated nodules, with staining for synaptophysin and variable early/intermediate neuronal marker expression, suggesting maturation arrest. The natural history is indolent, with no recurrence or progression after resection or during surveillance. Surgery is reserved for refractory epilepsy or progressive symptoms; most cases can be managed conservatively. The pathogenesis remains unclear, with features overlapping malformative and neoplastic processes.

References

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