Dysembryoplastic neuroepithelial tumor: a clinicopathological study of 32 cases

Abstract

Dysembryoplastic neuroepithelial tumor (DNT) is a relatively newly described entity and is an important cause of intractable epilepsy. We report 32 cases of DNT who were operated and treated in our hospital over a period of 12 years. Immunostaining for various proliferative markers and tumor suppressor gene proteins was done to assess the proliferative potential of these tumors. The most common presentation was partial complex seizures followed by generalized tonic–clonic seizures, focal motor seizures, and myoclonus. The most common location was temporal lobe followed by frontal and in one patient lesion was multifocal. All patients were seizure free at the last postoperative follow-up which varies from 12 to 96 months with mean of 33.7 months. Microscopic examination showed classical histology comprising of intracortical multinodular microcystic lesions with floating neurons. Proliferative indices were very low (<1%) and tumor suppressor gene protein expression was not seen in the present study. Cortical dysplasia of the surrounding brain was observed in 37.3% of cases.

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Correspondence to Mehar Chand Sharma.

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Carlo Schaller, Geneva, Switzerland

This is a clinicopathological study from the epilepsy surgical program at the All Indian Institute in New Delhi. Among the series of n = 330 epileptic patients, who were operated between 1995 and 2006, DNTs were found in n = 32. All patients had state-of-the-art diagnostic workup which included noninvasive diagnostics with scalp and video EEG and elaborate MRI. Twenty of the patients had additional SPECT imaging. Radical resection was performed in all, with n = 26 patients remaining seizure free without medication after a mean of 34-month follow-up time for the whole group. It is concluded that DNTs are a relatively recently described entity, requiring clear workup and long-term follow-up, where malignant transformation cannot be excluded.

The paper refers to an important issue in lesional epilepsy surgery.

The ongoing debate as to whether and where there is a linkage between malformations of corticoneural development, e.g., focal cortical dysplasias, and neuroglial tumors such as DNTs. The authors have performed an elaborate workup of their clinicopathological series of DNTs. Apart from excellent surgical results with 75% having remained completely seizure free, six other patients who suffered very rarely from auras or seizures had a good outcome as well. The importance of excellent presurgical epileptological workup, including intraoperative electrocorticography (ECoG) for delineation of the epileptogenic zone, cannot be overestimated, as with DNTs there is almost always involvement of neighboring gray and white matter. With epileptogenicity of scattered glioneural elements being postulated by various groups, the success of surgery depends on resection of these epileptogenic areas as well. In their series, no patient had invasive brain mapping. I personally prefer extraoperative mapping with intracranial electrodes over intraoperative ECoG whenever this is feasible due to the multiple factors which may disturb intraoperative recording. Furthermore, it would be interesting to know how they had dealt with epileptogenic areas which extended into eloquent cortex, e.g., did they perform multiple subpial transections? To my knowledge, there is no study yet comparing ECoG-guided lesional epilepsy surgery with and without multiple subpial transections in eloquent cortex.

Analysis of pathological specimens revealed only one case with increased microvascular proliferation and no increase of other proliferative indices such as MIB or p53 in any of the others. On the rare occasion of evidence for proliferation or of oligoastrocytic components, as it was reported by other groups as well, regular follow-up by MRI is certainly warranted. The authors are to be congratulated to their structured workup—this is the way it should be done in multidisciplinary diagnosis and treatment of epilepsy.

Basant K. Misra, Vrajesh Udani, Mumbai, India

Since the first pathologic description of DNTs by Daumas-Duport [2] in 1988, several large series have crystallized our knowledge of this developmental glioneuronal tumor. Though rare, it is the most common tumor in children and young adults with pharmaco-resistant epilepsy [7]. Large series [3, 11] have characterized the imaging and pathologic features of this tumor which in some atypical cases can be confused with other tumors especially the oligodendroglioma. MR techniques like magnetic resonance spectroscopy, diffusion-weighted imaging, and MR perfusion may help in differentiating these two tumors [1] as can cytogenetic analysis of resected tumor tissue [8].

What has become clear over the years is the high incidence (up to 69–83%) of associated peritumoral cortical dysplasia [9, 12], especially type 1 cortical dysplasia which can affect long-term seizure prognosis after resection. Extraoperative electrocorticography has confirmed that the ictal onset zone may in fact be from this peritumoral [10] location and functional imaging like the subtraction ictal SPECT coregistered with MRI (SISCOM) [13] also highlights the importance of the peritumoral area in the genesis of seizures. The earlier concept of doing only a lesionectomy for these patients is now slowly changing into an extended lesionectomy with additional removal of surrounding dysplastic tissue, identified by MR and intraoperative electrocorticography. Though initial studies suggested excellent seizure freedom rates after surgery, recent studies with longer follow-up [5] suggest that seizure freedom rates decline over time. Also, as DNTs can recur several years after surgery [5] and in fact may rarely undergo malignant transformation [4, 5], it is best to do total resection with a close surveillance over a long time.

In this issue, Sharma and colleagues have presented a series of 32 patients with pharmaco-resistant epilepsy due to DNTs. By and large, the results are consistent with the literature. Surgery was mainly in the adult years and there were no lesions in the parietal or occipital lobes. The high seizure freedom rates that were achieved could be partly attributed to the radical resection of the tumor and the surrounding area as well as the comparatively short follow-up. Though surrounding cortical dysplasia was seen in fewer patients, it seemed to play a role in the persistence of seizures in a few patients. Pathologic analysis of tumor tissue confirmed the low malignant potential of this tumor.

In summary, the biologic behavior of DNTs appears homogenous in the majority of patients over many continents. A consensus seems to have evolved now that extended lesionectomy [6] is the best surgical strategy in the long term.

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2. Daumas-Duport C, Scheithauer BW, Chodkiewicz JP, Laws ER Jr, Vedrenne C (1988) Dysembryoplastic neuroepithelial tumor: a surgically curable tumor of young patients with intractable partial seizures. Report of thirty-nine cases. Neurosurgery 23:545–556

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12. Takahashi A, Hong SC, Seo DW, Hong SB, Lee M, Suh YL (2005) Frequent association of cortical dysplasia in dysembryoplastic neuroepithelial tumor treated by epilepsy surgery. Surg Neurol 64:419–427

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Sharma, M.C., Jain, D., Gupta, A. et al. Dysembryoplastic neuroepithelial tumor: a clinicopathological study of 32 cases. Neurosurg Rev 32, 161 (2009). https://doi.org/10.1007/s10143-008-0181-1

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Keywords

  • Epilepsy
  • DNET
  • Dysembryoplastic neuroepithelial tumor
  • Proliferative indices
  • Tumor suppressor gene
  • Epilepsy surgery