Dysembryoplastic Neuroepithelial Tumor

Dysembryoplastic neuroepithelial tumor (DNT) is a recently described pathologically benign unique tumor arising within the supratentorial cortex and having a 100% association with partial complex seizures(1). Due to the paucity of literature on this condition and its heterogeneous cellular composition, DNT can present difficulties in diagnosis and is often confused with glial neoplasms(2). We are reporting a case of DNT in a 15 year old girl who presented with intractable partial complex seizures and who recovered completely after surgical excision of the tumor.


Dysembryoplastic neuroepithelial tumor
Dysembryoplastic neuroepithelial tumors (DNTs) commonly abbreviated DNT or DNET was first coined by Daumas-Duport and colleagues to describe a cortical lesion presenting in childhood 1) . According to Daumas-Duport and colleagues, the criteria for the diagnosis of DNET should include: (1) partial seizures, with or without secondary generalization beginning before age 20 (2) no neurological deficit or presence of a stable and likely congenital neurological deficit The vast majority are centered in cortical grey matter, arise from secondary germinal layers and are frequently associated with cortical dysplasia (up to 80% of cases).
Classically, DNETs have been described to have a benign course with cortical dysplasia rather than true neoplasias.
Rare midline neoplasms with similar histological features to those found in DNETs have been described near the septum pellucidum and termed 'DNET-like neoplasms of the septum pellucidum'. Due to their rarity, these tumors have been described in just a few reports and their genetic alterations sought only in small series 3) .

Epidemiology
Dysembryoplastic neuroepithelial tumors (DNETs) are uncommon neural tumors presenting most often in children and young adults.

Immunophenotype
The stellate astrocytes within the specific glioneuronal element (SGNE) are positive for GFAP The oligodendrocyte-like cells are typically S100 and OLIG2 positive, and may also express NOGO-A and myelin-oligodendrocyte glycoprotein.
The floating neurons are positive for NeuN.

Clinical Features
They are common causes of intractable epilepsy in pediatric epilepsy patients.
Defined as "an usually supratentorial glial-neuronal neoplasm occurring in children and young adults and characterized by a predominantly cortical location and by drug-resistant partial seizures".
It appears similar to oligodendroglioma, but with visible neurons.

Radiographic features
DNETs are typically predominantly cortical and well circumscribed tumours.
CT if cortical may scallop the inner table of of the skull vault (44-60%), but no erosion the cranial fossa can be minimally enlarged at times calcification in ~30% (more common histologically) low density no enhancement MRI Typically seen as a cortical lesion with hardly any surrounding vasogenic oedema.

T1
generally hypointense c.f adjacent brain T1 C+ (Gd) may show enhancement in ~20-30% of cases, enhancement may be heterogeneous or a mural nodule T2 generally high signal high signal 'bubbly appearance' FLAIR mixed signal intensity with bright rim sign partial suppression of some of the "bubbles" FLAIR is helpful in identifying the small peripheral lesions with similar intensity to CSF T2* calcification relatively frequent haemosiderin staining uncommon as bleeding into DNETs is only occasional DWI no restricted diffusion MR spectroscopy non-specific although lactate may be present

Differential diagnosis
A 29-year-old male from Bolivia, who lived in Spain, presented seizures and a multicystic brain lesion, initially suspected to be a dysembryoplastic neuroepithelial tumor (DNET). He underwent gross total resection of the mixed solid/cystic lesion. Pathology revealed gliosis, multiple interconnected cystic cavities with fibrous walls, inflammatory cell infiltration and no necrotizing granulomatous reaction. Inside the cavities, a parasitic form was identified as the larva of the cestode Spirometra mansoni. At 1-year follow-up, the patient had no deficits and was seizure free. Clinicians should be alerted to the possible existence of this rare entity in Europe, especially in patients from endemic areas with a possible infection history as well as "wandering lesions" on the MRI 5) .

Case series
DNTs patients who were admitted to the Department of Neurosurgery of Xiangya Hospital between 1 January 2010 and 31 December 2018 and underwent surgical resection were retrospectively analyzed. Clinical, neuroimaging, and pathological features of DNTs were compared among patients with different outcomes and analyzed using the Kaplan-Meier curves and univariable Cox regression analysis.
Results: Thirty-three DNTs patients were included finally, of which the average age at seizure onset was 11.59 ± 7.46 years old and the average duration of seizures prior to surgical resection was 3.00 ± 4.68 years. After surgical resection, the patients were followed up for 2.39 ± 1.97 years, and 28 patients (84.85%) were seizure-free (class I of the Engel Outcome Scale) while five patients (15.15%) were seizure-continuous (class II or III of the Engel Outcome Scale). When compared with seizure-free patients, seizure-continuous patients had greater age at seizure onset and longer duration of seizures before surgical resection (p < .05). No variables were found to be statistically significantly associated with prognosis in univariable Cox regression analysis, but patients with extra-temporal DNTs were found to have better prognosis than those with temporal DNTs (log-rank test p = .048).
Elder seizure onset age, longer duration of seizures prior to surgical resection, and a temporal location may be risk factors of poor prognosis for DNTs patients after surgical resection 6) .

2016
Data from 35 patients diagnosed with glioneuronal tumors (GNTs), including 24 gangliogliomas and 11 dysembryoplastic neuroepithelial tumors, were retrospectively collected. DNA was extracted from GNTs tissues and BRAF V600E mutation was examined by DNA sequencing. The correlations between BRAF V600E mutation and clinical features were analyzed.
Totally, BRAF V600E mutations were detected in 11 patients with GNTs, the rate of mutation were 33.3% and 27.3% in GGs (8/24) and DNTs (3/11), respectively. The probability of BRAF V600E mutation in females (7/12, 58.3%) was significantly higher than that in males (4/23, 17.4%) (P=0.022). Moreover, patients with BRAF-mutated GNTs had a significantly wider variety of seizure types compared to GNTs with BRAF wild-type status (P=0.027). However, no significant correlation between the BRAF status and certain clinical features, such as age of seizure onset, duration of epilepsy, age at surgery, location of the tumor and postoperative seizure free, were observed.
Zhang et al., demonstrated the presence of BRAF V600E mutation in Chinese epileptic patients with GNTs, which was significantly correlated with gender and multiple seizure types. Large sample studies and long-term follow-up are required for further confirmation 7) . 27 patients with drug resistant epilepsy and brain tumor, aged up to 19 years at the time of surgery, were studied between 1996 and 2013 and followed up for at least one year. The mean interval between the onset of seizures and the diagnosis of the tumor was 3.6 years, and from diagnosis to the surgery, 18 months. The location of the tumor was in the temporal lobe in 16, with ganglioglioma and dysembryoplastic neuroepithelial tumors being the most frequent. Among the patients, 92.5% and 90.4% were seizure-free in the first and fifth year after surgery, respectively. Twelve of 16 children were successful in becoming drug-free, with complete withdrawal by 3.2 years. Surgery proved to be potentially curative and safe in these cases, suggesting that the tumor diagnosis and surgery cannot be postponed 8) .

2008
A retrospective cohort of 23 patients seen at two major epilepsy centers, with localization-related epilepsy associated with histopathologically demonstrated DNETs. We assessed clinical, electrographic and surgical outcome features in patients with adult-and childhood-onset epilepsy. We were particularly interested in the level of congruence of EEG and MRI data and the need for intracranial recordings. We evaluated seizure outcomes at last follow-up.
The mean age was 33.3 years (range: 5-56 years). Ten patients had adult-onset epilepsy. Thirteen patients (57%) had simple partial, 21 (91%) had complex partial, 16 (70%) had secondarily generalized seizures and 5 patients had only simple partial seizures. Status epilepticus did not occur. Non-enhancing lesions on MRI were located in the temporal lobe in 17 patients, the frontal lobe in 3 patients and the parietal/occipital region in 2 patients. One patient had a DNET that involved both frontal and temporal areas. Ictal scalp EEG and MRI were congruent in 17 patients (74%). Eleven patients (48%) underwent lesionectomies, while the rest required some resection of extralesional cortex as well. Five patients required intracranial EEG. There was no association with cortical dysplasia. Seventeen patients (74%) had an Engel class 1 outcome, in a follow-up period that ranging from 5 to 98 months.
Burneo et al found no difference in outcomes between adult-and childhood-onset cases. Although epileptogenicity was complex, congruence between electro-clinical and neuroimaging studies was high and allowed good surgical outcomes at 1 year of follow-up 9) .

Case reports 2016
A 8-year-old boy who presented with an incidental finding of a small right insular lesion which grew slowly over 3 years. The patient first underwent surgery with subtotal tumor resection at age 11. Pathology was consistent with DNET. Following surgery, further tumor growth was evident, requiring fractionated radiotherapy and eventually chemotherapy, but continued tumor growth was witnessed. Three years after radiation, imaging showed dramatic further tumor growth, and the patient underwent a second debulking surgery. The pathology revealed a malignant tumor with BAF47negative cells, suggestive of AT/RT. This report adds about the poorly understood behavior and natural history of DNETs and emphasizes the importance of lifelong clinical and neuroimaging followup of these lesions 10) .

2015
A pediatric patient with intractable epilepsy caused by a simple DNT located in the precentral gyrus. Intracranial electrodes were implanted and used in combination with magnetic resonance imaging, video-electroencephalography and electrical cortical stimulation to assess neurological function, and where the epileptogenic zone was located.
The results of intracranial electrode monitoring suggested that the epileptogenic zone was located in the tumor area and that cortical function had been reorganized. We completely resected the tumor based on these findings. The patient has been seizure free after the surgery and has not had any neurological deficits.
Simple form DNTs in the precentral gyrus can be completely resected with careful preoperative assessment of cortical function. Cortical reorganization could partly explain the functional preservation after surgery 11) .

1992
Prayson and Estes describe two cases of dysembryoplastic neuroepithelial tumor occurring in young patients (ages 8 and 19 years). Both tumors were located in the temporal lobe. Temporal lobectomy with excision of mesial structures resulted in resolution of the seizures. Differential diagnosis includes oligodendrogliomas, mixed gliomas, and gangliogliomas. Features of the dysembryoplastic neuroepithelial tumor that are useful in making the distinction include a multinodular and multicystic appearance, the presence of both neuronal and glial (oligodendrocytic and astrocytic) components with little if any cytologic atypia, the presence of accompanying cortical dysplasia, and the lack of an arcuate vascular pattern. Because dysembryoplastic neuroepithelial tumors are curable by excision, the recognition and correct diagnosis of this tumor is important 12) . 1) Daumas-Duport C, Scheithauer BW, Chodkiewicz JP, Laws ER Jr, Vedrenne C. Dysembryoplasic neuroepithelial tumor: A surgically curable tumor of young patients with intractablepartial seizure. Report of thirty-nine cases. Neurosurgery 1988;23:545-56. 2)