Dysembryoplastic Neuroepithelial Tumor (DNET)

Key Points at a Glance

Key Points of This Disease

• Dysembryoplastic neuroepithelial tumor (DNET) is a low-grade glioneuronal tumor that commonly occurs in children and young adults, classified as WHO grade 1.
• It accounts for approximately 1.5% of all primary brain tumors and most frequently occurs in the temporal lobe (about 66–70%).
• Drug-resistant focal seizures are the most common initial symptom.
• When occurring in the occipital lobe, optic radiation, optic tract, or lateral geniculate body, it may present with contralateral homonymous hemianopia.
• MRI findings, histopathological examination, and confirmation of FGFR1 gene mutation are important for definitive diagnosis.
• Complete resection is the standard treatment, and seizures disappear in 80–100% of cases postoperatively.
• Malignant transformation is extremely rare, but long-term imaging follow-up is recommended.

1. What is dysembryoplastic neuroepithelial tumor (DNET)?

Dysembryoplastic neuroepithelial tumor (DNET) is a low-grade mixed glioneuronal tumor. It is classified as grade 1 in the 2021 WHO classification of central nervous system tumors. In 1988, Daumas-Duport et al. reported 39 young patients with drug-resistant partial epilepsy, establishing it as an independent disease entity. ²⁾

They account for approximately 1.5% of all primary brain tumors. They represent about 30% of mixed glioneuronal tumors in children. About 6% of epilepsy cases are associated with DNET. ⁶⁾ DNET accounts for about 20% of surgical cases of drug-resistant epilepsy. ²⁾

The peak age of onset is 10–14 years, with an average age of onset around 19 years. ^{1, 2)} There is a slight male predominance, with a male-to-female ratio of 6:1 in some case series. ¹⁾ An association with Noonan syndrome has also been reported. Previously considered a hamartomatous lesion, it is now recognized as having neoplastic properties.

The most common location is the temporal lobe, accounting for about 66–70% of cases. This is followed by the frontal lobe (about 20–29%), parietal lobe (about 11%), and occipital lobe (about 3%). ¹⁾ Rarely, it can also occur in the cerebellum ⁶⁾ or within the ventricles. ³⁾

Q How rare is DNET as a brain tumor?

A

It is a rare tumor, accounting for about 1.5% of all primary brain tumors. However, it accounts for about 30% of mixed glioneuronal tumors in children and is relatively common among epilepsy-associated tumors. The peak age of onset is 10–14 years, with a slight male predominance.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

Focal seizures (partial seizures) are the most common initial symptom of DNET. The most frequent seizure type is complex partial seizure, followed by generalized tonic-clonic seizure and simple partial seizure. ²⁾ Most patients experience their first seizure before the age of 20. ²⁾

• Focal seizures: Often present as drug-resistant epilepsy. Seizures typically last about 2 minutes. ³⁾
• Headache: Occurs only when the tumor is extensive. This is a rare symptom.
• Motor paralysis: Appears only when the tumor is near the primary motor cortex.
• Gait instability and strabismus: Reported in atypical DNET arising in the cerebellum. ⁶⁾

Clinical Findings (Findings Confirmed by Physician Examination)

Ophthalmic findings are rare in DNET. Since most tumors occur supratentorially (temporal or frontal lobes), their impact on the visual system is limited.

• Homonymous hemianopia: Can occur with tumors located in the occipital lobe, optic radiation, optic tract, or lateral geniculate body. A case of right homonymous hemianopia has been reported in a 10-year-old boy with a left occipital DNET. ⁵⁾
• Diplopia or ocular misalignment: May occur with tumors near cranial nerves or the brainstem, but is extremely rare.
• Papilledema: May be observed in large tumors accompanied by headache. ²⁾

When the optic tract is damaged, it results in homonymous hemianopia on the side opposite the lesion and a relative afferent pupillary defect (RAPD) in the contralateral eye. The optic disc on the affected side shows hourglass atrophy, while the contralateral eye shows band atrophy. Damage to the lateral geniculate body causes homonymous hemianopia, but since the afferent pathway for the light reflex does not pass through the lateral geniculate body, RAPD does not occur.

Q Can DNET cause ophthalmic symptoms?

A

Most DNETs occur in the temporal or frontal lobes, so ophthalmic symptoms are rare. However, when located in the occipital lobe, optic radiation, optic tract, or lateral geniculate body, they can cause contralateral homonymous hemianopia. Tumors near the brainstem may also present with diplopia.

3. Causes and Risk Factors

DNET is thought to originate from abnormal development of the cerebral cortex during the fetal period. ³⁾ It frequently coexists with focal cortical dysplasia (FCD), and approximately 29% of cases have adjacent glial tissue with cortical dysplasia. ¹⁾

• FGFR1 gene mutation: The most important molecular abnormality found in 58–82% of DNETs. ⁴⁾ The most frequent is internal tandem duplication (ITD) in the tyrosine kinase domain (40–60%), followed by missense mutations. ¹⁾ Both somatic and germline mutations have been reported.
• BRAF V600E mutation: Found in some reports, but less common in cases with specific glioneuronal elements of DNET, and frequency varies between studies. ¹⁾
• Noonan syndrome: Suggested association with DNET.
• Focal cortical dysplasia: Often found adjacent to DNET and contributes to the formation of epileptic foci. ¹⁾

Prevention of this disease

Since DNET is caused by developmental abnormalities during the fetal period, there is currently no established method of prevention. If drug-resistant epilepsy appears in childhood, it is important to undergo an early MRI examination.

4. Diagnosis and examination methods

2021 WHO diagnostic criteria

A definitive diagnosis of DNET requires the following three elements.

1. It is a cortical glioneuronal tumor.
2. It has characteristic glioneuronal elements.
3. It has an FGFR1 gene mutation or a methylation profile specific to DNET.

Imaging Diagnosis

MRI is the first-choice imaging test.

• T2-weighted imaging: Hyperintense lesions in the corticobasal region
• T1-weighted imaging: Hypo- to isointense
• FLAIR imaging: Mixed signal. The bright rim sign is considered specific¹⁾
• Contrast-enhanced MRI: Usually no to mild enhancement^{1, 4)}
• Peripheral edema/mass effect: Absence is an important distinguishing feature^{1, 6)}
• Often presents with a multicystic “soap bubble” appearance¹⁾

When optic tract lesions are suspected, OCT findings show selective thinning in the temporal region of the affected eye and the nasal region of the contralateral eye on macular inner retinal layer analysis. This is a characteristic homonymous hemianopic pattern corresponding to hemianopic optic atrophy.

Histopathological Examination

• Oligodendrocyte-like cells (OLCs): Uniform round cells. Strongly positive for S-100 protein and Olig-2²⁾
• Floating neurons: Neurons suspended in a mucoid matrix. Positive for synaptophysin and NeuN²⁾
• Multinodular structure: Columnar structures perpendicular to the cortical surface¹⁾
• Ki-67 proliferation index: Low (<2%). Reflects benign nature^{1, 2)}
• GFAP: OLC negative, only scattered astrocytes positive¹⁾

DNET has three subtypes.⁶⁾

Subtype	Features
Simple type	Only glioneuronal elements
Mixed type	Glioneuronal elements + glial nodules
Diffuse type	Lacking glioneuronal elements

Differential diagnosis

The main tumors requiring differentiation are listed below. ²⁾

• Oligodendroglioma: Has IDH mutation and 1p19q co-deletion. DNET does not have these ¹⁾
• Ganglioglioma: Contains dysplastic neurons and inflammatory infiltration. Contrast enhancement is clear
• Pilocytic astrocytoma: Commonly occurs infratentorially. Biphasic pattern
• Pleomorphic xanthoastrocytoma: Contains pleomorphic tumor cells

5. Standard Treatment

Medical Treatment

Antiepileptic drugs: Although often drug-resistant, medical management is attempted first. Valproic acid, etc., are used.

Observation: If clinically stable, regular imaging follow-up may be sufficient.

Surgical Treatment

Complete resection: The best treatment option, with seizure freedom in 80–100% of cases. ²⁾

Cortical resection: Extensive resection including dysplastic cortex around the tumor may be necessary.

Factors that make complete resection difficult include unclear tumor borders, involvement of multiple gyri, proximity to functional cortex, and satellite lesions. However, even incomplete resection may lead to seizure freedom in many cases. Due to its benign and slow-growing nature, most patients are cured by initial surgery.

Radiation therapy and chemotherapy are not typically used to treat DNET. In children, these treatments may cause long-term adverse effects. There are reports of gamma knife radiosurgery being used in selected cases.

Surgical Considerations

Because the epileptogenic zone is located in the dysplastic cortex surrounding the tumor, resection of the tumor alone may result in persistent seizures. Complete resection of adjacent cortical dysplasia may be key to seizure freedom. ¹⁾ Longer duration of seizures has been reported to be associated with poorer postoperative seizure control. ¹⁾

Q Can surgery cure epilepsy seizures?

A

Complete resection results in seizure freedom in 80–100% of cases. ²⁾ Incomplete resection may also improve seizures. However, if cortical dysplasia surrounding the tumor remains, seizures may persist, so extensive resection including the epileptogenic zone is considered. For details, see the “Standard Treatment” section.

6. Pathophysiology and Detailed Mechanisms

The pathological features of DNET are glioneuronal elements forming columnar structures perpendicular to the cortical surface and “floating neurons” suspended in a mucoid matrix. Uniform round cells with oligodendrocyte-like morphology are surrounded by mucoid material, constituting a multinodular lesion.

At the molecular level, FGFR1 gene mutations are the main molecular driver of DNET. Internal tandem duplication of the tyrosine kinase domain (TKD) is found in 40-60% of cases, the most frequent genetic abnormality. ¹⁾FGFR1 mutations activate RAS/ERK, PI3K/AKT, and mTOR signaling pathways. ¹⁾

Metastatic spread and leptomeningeal dissemination are extremely rare, but two fatal cases due to drop metastasis to the spinal cord have been reported. The following routes of dissemination have been proposed:

• Direct extension into the ventricular system or subarachnoid space
• Dissemination via the cerebrospinal fluid (CSF) pathway
• Hematogenous metastasis
• Perineural or perivascular infiltration

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7. Latest Research and Future Prospects (Research Stage Reports)

For Patients: Please Read

The following content is currently in the research stage or under clinical trials and is not standard treatment available at general hospitals. It is reference information for professionals regarding future medical developments.

5-ALA Fluorescence-Guided Surgery

Beauchamp et al. (2021) performed 5-aminolevulinic acid (5-ALA) fluorescence-guided resection of a left occipital lobe DNET in a 10-year-old boy, achieving gross total resection. Although 5-ALA fluorescence positivity has traditionally been considered rare in low-grade tumors, this is the first report of fluorescence positivity in DNET. Seizures disappeared at 6 months postoperatively (Engel class I). ⁵⁾

Malignant transformation

Takita et al. (2022) summarized malignant transformation of DNET, with only 14 cases reported in the literature. 65% of malignant transformation cases occurred outside the temporal lobe, and 93% showed contrast enhancement on MRI. Post-malignant transformation pathological types included anaplastic astrocytoma, glioblastoma, and anaplastic oligoastrocytoma. FGFR1 mutations were detected even in malignant transformation cases. ⁴⁾

Habib Chorfa et al. (2024) reported transformation to a glial tumor (WHO grade 2 cortical ependymoma) 3 years after complete resection of a right temporal lobe DNET in a 19-year-old woman. The importance of long-term imaging follow-up is emphasized. ⁷⁾

Classification of posterior fossa DNET

Stoyanov et al. (2023) reported a cerebellar DNET in a 2-year-old girl. Posterior fossa DNET presented with a clinical picture different from classic DNET (gait instability, strabismus, hydrocephalus) and showed a complex histological pattern. Separation as an independent classification is being considered. ⁶⁾

Q Can DNET become malignant?

A

Malignant transformation is extremely rare, with only 14 cases reported in the literature. ⁴⁾ Cases occurring outside the temporal lobe or showing enhancement on contrast-enhanced MRI require consideration of malignant transformation. Long-term imaging follow-up is recommended.

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8. References

1. Rahim S, Din NU, AbdulGhafar J, et al. Clinicopathological features of dysembryoplastic neuroepithelial tumor: a case series. J Med Case Rep. 2023;17:327.
2. Yibirin M, De Oliveira D, Suarez I, et al. A case of dysembryoplastic neuroepithelial tumor in an adolescent male. Cureus. 2021;13(3):e13917.
3. Li L, Hu X, Li J, Zhang H. Intraventricular dysembryoplastic neuroepithelial tumor in the temporal horn with broad involvement of the ependyma. Clin Case Rep. 2021;9:e03852.
4. Takita H, Shimono T, Uda T, et al. Malignant transformation of a dysembryoplastic neuroepithelial tumor presenting with intraventricular hemorrhage. Radiol Case Rep. 2022;17:939-943.
5. Beauchamp LH, Bercu MM, Avellino AM. 5-Aminolevulinic acid-assisted resection of pediatric dysembryoplastic neuroepithelial tumor: illustrative case. J Neurosurg Case Lessons. 2021;2(4):CASE20153.
6. Stoyanov GS, Petkova L, Kondev T, et al. Posterior fossa dysembryoplastic neuroepithelial tumor: a neuropathological report. Cureus. 2023;15(1):e33525.
7. Habib Chorfa S, Graini S, Amsiguine N, et al. Glial transformation of a DNET: about a case. Radiol Case Rep. 2025;20:64-68.