Dysembryoplastic Neuroepithelial Tumors (DNET)
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Disease Entity
Dysembryoplastic neuroepithelial tumor (DNET)
Disease
Dysembryoplastic neuroepithelial tumors (DNETs) are low-grade glioneuronal neoplasms that are typically present in children and young adults. They account for around 1.5% of all primary brain tumors and are usually characterized by a benign clinical course and good prognosis. Previously DNET was considered a hamartomatous lesion, but it has since been confirmed to have a neoplastic nature.[1]
Epidemiology
DNETs account for only 1.5% of all childhood brain tumors but approximately 30% of pediatric mixed glioneuronal tumors[1]. The frequency of these tumors is slightly higher in males and an association with Noonan syndrome has been proposed.[2]
Anatomy
DNETs can present in any area of the brain, but most commonly present in the temporal lobe (around 66%).[3][4] The next most common sites include the frontal lobe (20%), parietal lobe (11%) and the occipital lobe (3%).[3]
Diagnosis
The new 2021 WHO diagnostic criteria required for to make the diagnosis of DNET include: 1) tumor must be a cortical glioneuronal tumor AND 2) must have specific glionuronal elements AND 3) must have the FGFR1 gene alteration OR the methylation profile of DNET.[1] Diagnostic testing includes neurological exams, CT scans, MRI, and lab-based studies.[5]
History
DNET’s are low-grade neoplasms that are typically present in children and young adults with a history of seizures.
Symptoms
Focal seizures are the most common symptoms of DNET. Headache is an uncommon symptom that only occurs with extensive tumors.[1] Motor weakness is also rarely seen unless the tumor is near the primary motor cortex.
Neuro-Ophthalmic Symptoms
Ophthalmic symptoms are rare in DNETs but when located in the occipital lobe, optic radiation, optic tract, or lateral geniculate nucleus DNETs can cause homonymous hemianopsia. Tumors located near the cranial nerves or brainstem can cause diplopia or ocular misalignment but most DNET are supratentorial (e.g., temporal and frontal lobe).
General Pathology and Genetics
The pathology of DNET is characterized by glioneuronal elements and “floating neurons”. DNETs are classified as World Health Organization (WHO) grade I tumors and are composed of multi-nodular lesions with a characteristic intranodular and internodular pattern. Biopsy of DNETs show uniform round cells with oligodendroglial-like morphology and internodular mucinous material with “floating neurons”.[3] Somatic and germline mutations in FGFR1 have been associated with the pathogenesis of DNETs. [6]
Management
Medical therapy
DNET is typically stable from a clinical perspective.[1] Many patients are treated with antiepileptic drugs, however many patients seizures are poorly controlled with medication alone and may require surgery.
Surgical therapy
Resection of the tumor is considered for patients with uncontrolled seizures despite medical management. The extent of resection beyond the DNET margin to achieve a good seizure outcome has been controversial. It is argued that a wider corticectomy beyond the tumor boundary is required for DNETs for adequate seizure control because DNETs are accompanied by a surrounding rim of the dysplastic cortex where the ictal onset zone is located .[1] However, seizures often stop even after incomplete resection. Most patients are cured of their disease after the first surgery, even if the entire tumor isn't removed. After resection prognosis is good because DNETs are benign and don't grow quickly.
Types of Surgical Therapy
Complete neurosurgical resection remains the best treatment option. Radiation and chemotherapy are not typically used to treat DNETs and they treatments may have harmful side affects that will follow children throughout life.[5] Gamma knife radiosurgery (GKRS) has however also been used in selected cases.[7]
Complications
Complete resection of DNETs is often hampered by ill-defined borders, multi-gyral involvement, tumor location in the eloquent cortex, and the presence of satellite lesions .
Prognosis
These tumors normally do not grow quickly over time and have a good prognosis. Many patients usually undergo resection of the tumor due to difficulty in managing seizures medically.[2] Metastatic spread or leptomeningeal dissemination of DNETs is exceedingly rare, with only a handful of cases reported in the literature. However, DNETs resulting in a drop leptomeningeal metastasis and fatality have been reported two times.[4][8] While the exact mechanisms underlying leptomeningeal metastasis in DNETs is unknown, it is likely multifactorial. The proposed pathways include direct extension into the ventricular system or subarachnoid spaces, dissemination via cerebrospinal fluid (CSF) pathways, hematogenous spread, and perineural or perivascular invasion.[2]
Summary
DNET’s are low-grade flioneuronal neoplasms that are typically present in children and young adults with a good prognosis. They account for around 1.5% of all primary brain tumors and are usually located in the temporal lobe with the most common symptom at presentation being seizures. Patients may have a contralateral homonymous hemianopsia if there is involvement of retrochiasmal pathway (optic tract, lateral geniculate body, or temporal, parietal or occipital lobes) Although the seizures can be medically managed many patients undergo resection of the tumor due to poor response to anti-seizure medications. Given the benign nature of DNET’s after a successful resection many patients have complete resolution of their symptoms, however, there are cases of recurrence, metastasis, and even death from DNET tumors after resection. This is exceedingly rare and further research is needed to investigate why this happens and if there are factors that can predict the occurrence of these poor outcomes.
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Phi JH, Kim SH. Dysembryoplastic Neuroepithelial Tumor: A Benign but Complex Tumor of the Cerebral Cortex. Brain Tumor Res Treat. 2022 Jul;10(3):144-150. doi: 10.14791/btrt.2022.0015. PMID: 35929111; PMCID: PMC9353162.
- ↑ 2.0 2.1 2.2 Louis DN, Ohgaki H, Wiestler OD et-al. "WHO Classification of Tumours of the Central Nervous System. 4th Edition Revised" ISBN: 9789283244929
- ↑ 3.0 3.1 3.2 Campos, A.R., Clusmann, H., von Lehe, M. et al. Simple and complex dysembryoplastic neuroepithelial tumors (DNT) variants: clinical profile, MRI, and histopathology. Neuroradiology 51, 433–443 (2009). https://doi.org/10.1007/s00234-009-0511-1
- ↑ 4.0 4.1 Farkas A, Joyner D, Saad AG, Anderson M, Khan M. Lethal disseminated dysembryoplastic neuroepithelial tumor following West Nile virus: Report of a very unusual combination. Radiol Case Rep. 2018;13(3):555-558. doi:10.1016/j.radcr.2018.02.014
- ↑ 5.0 5.1 Sukheeja D, Mehta J. Dysembryoplastic neuroepithelial tumor: A rare brain tumor not to be misdiagnosed. Asian J Neurosurg. 2016 Apr-Jun;11(2):174. doi: 10.4103/1793-5482.175643. PMID: 27057233; PMCID: PMC4802948.
- ↑ Bale, T.A. FGFR- gene family alterations in low-grade neuroepithelial tumors. acta neuropathol commun 8, 21 (2020). https://doi.org/10.1186/s40478-020-00898-6
- ↑ Sinclair G, Martin H, Shamikh A, Samadi A, Cooray G, Bartek J Jr, Al-Saffar Y, Svensson M, Dodoo E. Salvage gamma knife radiosurgery in the management of dysembryoplastic neuroepithelial tumors: Long-term outcome in a single-institution case series. Surg Neurol Int. 2017 Aug 9;8:174. doi: 10.4103/sni.sni_482_16. PMID: 28868186; PMCID: PMC5569391.
- ↑ Kim SK, Jeong MY, Jung TY, Kang HK, Yoon W. Diffuse Ependymal Dysembryoplastic Neuroepithelial Tumor Causing Spinal Drop Metastases: A Case Report. Korean J Radiol. 2011;13(4):492-495. doi:10.3348/kjr.2012.13.4.492
