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
(3) cortical topography of the lesion as best demonstrated on MRI
(4) no mass effect on CT or MRI (except if related to a cyst) 2).
The World Health Organization (WHO) has categorized it under grade 1 tumors.
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).
Dysembryoplastic neuroepithelial tumors (DNETs) are uncommon neural tumors presenting most often in children and young adults
It is a mixed glial-neural neoplasm a multinodular architecture and a heterogeneous cellular composition. Three histological forms are recognized:
specific glioneuronal element (SGNE)
with glial nodules and a multinodular architecture
a component of associated focal cortical dysplasia is common (Blumcke classification IIIb)
simple specific glioneuronal element (SGNE) only
same clinical and neuroimaging features as complex DNET, but… no specific glioneuronal element (SGNE)
There have been isolated case reports of astrocytic (malignant) transformation of a histologically proven DNET.
Perhaps one with gemistocytic differentiation. The mechanism of development of a gemistocytic astrocytoma in a proven DNET remains a matter of debate. Its proposed mechanism is as either a collision tumor or the neoplastic change within DNET.
These reports of malignant transformation lend credence to the theory that there is at least a subgroup of lesions amongst DNETs, which have a malignant behavior and require adjunct treatment strategies. The issue is to identify this specific subset. How to do this? Whether some special characteristics on histopathologic examination or the genetic analysis hold the key remains unanswered. Till then, the need for lifelong surveillance in a case of DNET cannot be over emphasized 4).
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.
Molecular studies are needed to better understand the biological nature of GNTs and to refine their classification system 5).
DNETs are typically predominantly cortical and well circumscribed tumours.
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.
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
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 6).
The optimal surgical treatment of DNT is controversial. Some authors consider lesionectomy to be sufficient for good seizure control, whereas others advocate that additional resection of the epileptogenic zone beside the tumor improves outcome.
Further research is clearly needed to address this and other crucial questions 7).
Because the epileptogenic location of DNT varies among cases, it is important to identify its location by preoperative multimodal examinations, including chronic subdural ECoG recordings 8).
Dysembryoplastic neuroepithelial tumors (DNET) are benign, localized lesions that typically cause localization-related epilepsy of childhood onset. Although excellent seizure outcomes are expected following surgical resection of focal, benign lesions, reports in pediatric epilepsy series suggest that this may not be the case with DNETs, which may exhibit complex and often multifocal epileptogenesis.
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 9).
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 10).
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 11).
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 BAF47-negative 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 follow-up of these lesions 12).
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 13).
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 14).