What are the treatment options for Dysembryoplastic Neuroepithelial Tumors (DNETs)?

Dysembryoplastic Neuroepithelial Tumors (DNETs): Comprehensive Overview

What is DNET?

DNETs are benign, slow-growing brain tumors that primarily affect children and young adults, presenting almost exclusively with medically intractable epilepsy. These are indolent tumors with benign pathology that remain clinically stable over many years, with patients having a normal life expectancy 1.

Pathophysiology

• DNETs are glioneuronal tumors composed of oligodendroglial-like cells and neurons, classified as WHO Grade I lesions 2, 3
• Cortical dysplasia (CD) is present adjacent to DNETs in 52-83% of cases, which is critical because this surrounding dysplastic cortex is often the source of ongoing seizure activity 1, 3
• The tumor itself and adjacent dysplastic brain both contribute to epileptogenicity, explaining why incomplete resection leads to seizure recurrence 1
• DNETs occasionally occur in patients with neurofibromatosis type 1, warranting referral to genetic services 1

Epidemiology

• DNETs typically present in children and young adults with long-standing, medically intractable epilepsy 4
• The median age at surgery ranges from 11-21 years, though 24% may have adult-onset seizures 3, 5
• 86-100% of patients present with intractable epilepsy as their primary symptom 2, 3, 5
• Complex partial seizures are the most common seizure type (76%), followed by simple partial and generalized tonic-clonic seizures 5
• The median duration from seizure onset to surgery is approximately 6-8 years 3, 5

Treatment Options

Primary Treatment: Complete Surgical Resection

Complete surgical removal of all DNETs associated with epilepsy is strongly recommended, with complete seizure control without anticonvulsants as the primary therapeutic goal and avoidance of malignant transformation as the secondary goal 1.

Surgical Strategies:

Two main surgical approaches exist, with extended resection being superior:

1. Extended Resection (PREFERRED): Complete excision of the DNET together with a rim of surrounding dysplastic brain is the most efficient approach given its higher success rates and low morbidity 1, 4

2. Lesionectomy Alone: Complete excision of the DNET only, which has lower success rates 1

Evidence Supporting Extended Resection:

• In patients with DNET plus adjacent cortical dysplasia, 39% required reoperation for recurrent seizures when dysplastic cortex was not removed 1
• When radical resection (tumor plus surrounding epileptogenic tissue) was performed, 100% of patients were seizure-free at long-term follow-up 1
• Temporal lobectomy leads to better seizure outcomes than lesionectomy alone (83.3% vs 33.3% Engel Class I) 1, 6
• Complete or extended resection predicts seizure freedom (OR 1.68,95% CI 1.39-2.03; p < 0.0001) 3

Surgical Outcomes:

• Overall favorable seizure outcome is 85-94% at long-term follow-up (mean 5-10 years) 2, 3, 6
• Seizure freedom rates: 86% at 1 year and 85% at 5 years 3
• Complete drug withdrawal is achieved in 50% of patients 2
• Shorter duration of epilepsy, total resection, and absence of early postoperative seizures predict favorable outcomes 2, 6

Role of Intraoperative Electrocorticography:

• When extralesional spiking foci are detected and resected, 94% achieve seizure freedom compared to 43% when absent 3
• Electrocorticography identifies extralesional interictal activity in 70% of cases, guiding extended resection 3

Timing of Surgery:

The standard medical management trial is 2 years, but earlier surgery is reasonable when multiple appropriate antiepileptic drugs fail to establish control in a shorter time 1. Do not advocate prolonged therapeutic trials of AEDs in patients with potentially curable surgical lesions 1.

Observation Only (Limited Indications)

Observation with serial imaging is acceptable only in two specific scenarios:

1. Incidental DNET without epilepsy: Close surveillance with serial imaging alone has been used safely 1
2. Well-controlled epilepsy with minimal AED side effects: When educational, behavioral, and psychological development is normal, close clinical and radiological surveillance is acceptable 1

Whenever any radiological doubt exists, tumor resection is advisable 1.

Radiotherapy and Chemotherapy: NOT RECOMMENDED

Patients with DNET lesions have a normal life expectancy and should not undergo postoperative chemotherapy or radiotherapy without referral to an experienced epilepsy surgery program 1. These treatments are not indicated for this benign tumor 1.

Biopsy Only: NOT RECOMMENDED

Stereotactic biopsy is not advocated as it may generate an unrepresentative tissue sample consisting of an oligodendroglial component only, leading to incorrect diagnosis 1.

Critical Pitfalls to Avoid

• Incomplete resection dramatically increases seizure recurrence rates: Residual tumor is a major risk factor for seizure recurrence, with 11% requiring reoperation after incomplete lesionectomy 1, 6
• Failing to resect adjacent cortical dysplasia: 39% of patients with DNET plus CD required reoperation when dysplastic cortex was not removed 1
• Performing lesionectomy alone in temporal lobe cases: Temporal lobectomy provides superior outcomes (83.3% vs 33.3% seizure freedom) 6
• Delaying surgery with prolonged medical trials: DNETs are surgically curable lesions; early surgery prevents years of intractable epilepsy 1

Prognosis

• DNETs remain clinically stable over many years with stable disease on serial imaging over a mean of 4.5 years 1
• Recurrences after complete surgical resection have not been described 1
• Even following partial surgical resection, progressive disease was not observed 1
• Long-term seizure outcome after surgery is predictable based on short-term follow-up results 6
• Duration of epilepsy prior to resection does not affect epilepsy outcome 1

Diagnostic Workup

• MRI with epilepsy protocols is the standard investigation, showing hypointensity on T1-weighted images and increased signal intensity on T2-weighted and FLAIR images 4, 2
• MRI-based image guidance (neuronavigation) is very helpful to ensure extended lesionectomy includes visibly dysplastic cortex 1
• FDG-PET should be obtained when MRI is normal or shows nonspecific findings (sensitivity 63-67%) 4
• Concordance between multiple diagnostic modalities (MRI, EEG, PET, SPECT) is associated with better surgical outcomes 4, 7