Introduction. Clinical manifestations

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1 Dysembryoplastic neuroepithelial tumor Scott Mintzer MD ( Dr. Mintzer of Thomas Jefferson University has no relevant financial relationships to disclose. ) Edward J Dropcho MD, editor. ( Dr. Dropcho of Indiana University Medical Center has no relevant financial relationships to disclose.) Originally released February 16, 1999; last updated November 14, 2014; expires November 14, 2017 Notice: This article has expired and is therefore not available for CME credit. Introduction This article includes discussion of dysembryoplastic neuroepithelial tumor, DNT, and DNET. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations. Key points Dysembryoplastic neuroepithelial tumor is a highly indolent (WHO grade I) glial tumor usually found in children and young adults. It is most commonly found in the temporal lobe and occasionally in frontal or other locations. The vast majority of tumors present with chronic epilepsy. Tumors appear on imaging as an expansion of a cortical gyrus, usually nonenhancing. Treatment is exclusively by resection, if necessary for seizure control. Prognosis for seizure control following resection is excellent. Historical note and terminology Dysembryoplastic neuroepithelial tumor is a rare but well-recognized tumor of children and young adults that most often results in chronic epilepsy. In 1988, the pathology and clinical syndrome were first elucidated by Daumas-Duport and colleagues, who found tumors in 20 patients undergoing epilepsy surgery at St. Anne Hospital in Paris for which existing tumor classification seemed inadequate (Daumas-Duport et al 1988). These multinodular tumors, composed of both glial and neuronal elements, were remarkably similar to each other and resulted in a distinct clinical picture. In retrospect, these tumors resembled "certain small tumours encountered in the temporal lobe" by Cavanagh 30 years earlier, although the tumors described by Cavanagh were microscopic in scale and were considered by the author to be hamartomatous in nature (Cavanagh 1958). Review of the Mayo Clinic Tissue Registry identified 19 additional cases, and the original report of 39 patients remains the most thorough and authoritative account of this tumor to date (Daumas-Duport et al 1988). Several other patient series have confirmed the findings of the original report (Raymond et al 1994; Taraturo et al 1995; Prayson et al 1996), and further study has expanded the pathologic recognition and understanding of this tumor (Daumas-Duport 1993; Daumas-Duport et al 1999; Honavar et al 1999). Though it remains uncommon, with just over 300 cases reported fully in the literature to date, this tumor has gained increasing recognition and is now well-known to neurologists in 2 subspecialties, as these patients are more likely to present to the refractory epilepsy clinic than to the neuro-oncology clinic. Clinical manifestations Presentation and course Dysembryoplastic neuroepithelial tumor occurs almost exclusively in the cerebral cortex. In the 10 large series that have been published to date, comprising 346 patients (Daumas-Duport et al 1988; Daumas-Duport 1993; Daumas- Duport 1999; Raymond et al 1994; Taraturo et al 1995; Wolf et al 1995; Prayson et al 1996; Honavar et al 1999; Nolan et al 2004; Thom et al 2011), the tumor involved the temporal lobe in 252 patients (73%) and the frontal lobe in 64 (18%). Parietal and occipital tumors made up the remainder. One series described 10 patients with tumors in the region of the septum pellucidum (Baisden et al 2001). There are also scattered case reports of solitary or multifocal occurrence in the basal ganglia and posterior fossa (Leung et al 1994; Cervera-Pierot et al 1997; Fujimoto et al 2000). About 60% of patients are male, with every case series showing a male predominance. The age at surgical diagnosis in these 346 patients ranged from 1 week to 55 years, with symptoms present for 1 month to 39 years prior to diagnosis.

2 However, because this tumor appears to be extremely indolent and stable for years to decades, there is no reason why it cannot be diagnosed at any age; in fact, there are reports of postmortem diagnosis at the ages of 50 and 75 years (Gottschalk et al 1993; Leung et al 1994). The latter patient had epilepsy for 60 years. The most salient clinical point is that onset of symptoms occurs almost exclusively in childhood or early adulthood, usually between the ages of 1 month and 17 years, with mean age of symptom onset being 9 years. Onset of symptoms in adulthood is less common, though in a series of patients who had undergone epilepsy surgery, more than 40% had adult onset of seizures (Burneo et al 2008). Almost every patient with dysembryoplastic neuroepithelial tumor presents with epilepsy, which, as mentioned above, may be of substantial duration. The seizures are complex partial in type, though simple partial seizures and secondary generalization of partial seizures may also occur. Most patients are medically refractory. Some patients have been reported whose sole presenting symptoms were headache, vomiting, and increased intracranial pressure or hydrocephalus, particularly when the tumor occurs in a periventricular location and obstructs the foramen of Monro (Raymond et al 1994; Cervera-Pierot et al 1997; Baisden et al 2001). Focal neurologic deficits were reported in only 3 of 69 patients (4%). Occasionally there is protrusion of the skull overlying the lesion. One report describes occurrence of this lesion in 2 (and possibly 3) members of a family (Hasselblatt et al 2004). Prognosis and complications The overall prognosis for patients with dysembryoplastic neuroepithelial tumor is excellent. Follow-up studies in patients whose tumor was not resected have shown no growth for periods of 2 to 12 years with CT or MR imaging (Daumas-Duport 1993; Cervera-Pierot et al 1997; Daumas-Duport et al 1999). After resection, recurrent tumor is rare, with most studies reporting no recurrence in any patient (Raymond et al 1994; Taraturo et al 1995; Daumas-Duport et al 1999; Honavar et al 1999). Two patients who died from other causes 6 to 15 years after resection had no evidence of recurrent tumor at autopsy (Daumas-Duport et al 1988; Honavar et al 1999). A minority of patients do experience recurrence, however (Prayson et al 1996; Nolan et al 2004), and there is a single case report to date of malignant transformation of a dysembryoplastic neuroepithelial tumor following subtotal resection (Hammond et al 2000). The prognosis for patients' epilepsy is also excellent overall. The literature regarding intermediate-term outcome (more than 6 months of follow-up) of glioneuronal tumors, including dysembryoplastic neuroepithelial tumors and gangliogliomas, comprising 39 studies, was recently summarized (Englot et al 2012). A total of 80% of patients were free of disabling seizures after surgery, with outcome predicted by less than 1-year duration of epilepsy, absence of generalized tonic-clonic seizures, and gross total (as opposed to subtotal) resection. However, this 80% seizurefreedom rate is limited by the fact that the authors required only 6-month outcomes to include studies in their review; epilepsy surgery studies traditionally look at outcomes of 2 years or longer. Two more investigations yielded conflicting results regarding long-term outcome. The Toronto group found that while 85% of children were free from disabling seizures at 1 year after resection, this proportion dropped considerably over the ensuing 2 years, with only 62% being seizure-free at last follow-up (Nolan et al 2004). The only factor found to be associated with long-term seizure freedom was complete tumor resection. On the other hand, Chan and colleagues found that freedom from disabling seizures was seen in 78% of patients and that this outcome was maintained over a prolonged follow-up period of 8 years or more. They also found that, for tumors in the temporal lobe, temporal lobectomy yielded superior results to mere lesionectomy. This might be due to the coexisting cortical dysplasia typically found adjacent to these tumors (Chan et al 2006). Clinical vignette A 16-year-old girl presented to the clinic with a 13-year history of seizures. Her first seizure, occurring at 3 years of age, was generalized. Subsequent seizures were predominantly nocturnal and involved unresponsiveness with clonic movements of the right arm, twisting of the torso to the right, and right-beating nystagmoid eye movements, occasionally preceded by an aura of hand numbness and dizziness. MRI of the brain at 12 years of age revealed a left medial temporal lobe mass. Stereotactic biopsy revealed what was felt to be a low-grade glioma. Her parents opted for conservative management out of concern for postsurgical neurologic deficit. Subsequently, her seizures occurred more often during the daytime and increased in frequency to 1 to 2 per day despite multiple attempts at anticonvulsant monotherapy and polytherapy. Repeat MRI redemonstrated the left temporal mass, which appeared unchanged over 4 years. Long-term video-eeg monitoring suggested left temporal seizure onset, and left anterior temporal lobectomy was performed 5 months after initial presentation to the clinic. Pathologic examination revealed dysembryoplastic neuroepithelial tumor as well as hippocampal sclerosis. She was admitted 10 days later with a flurry of seizures and a

3 subtherapeutic valproate level. In the ensuing 2 months after discharge, she had 2 more seizures, prompting a change in her anticonvulsant regimen from gabapentin and valproate to gabapentin and carbamazepine. She remained seizure-free for 5 months and was lost to follow-up. Biological basis Etiology and pathogenesis The etiology of this tumor is unknown. Dysembryoplastic neuroepithelial tumor appears in situ as enlargement of a cortical gyrus, which exceeds the thickness of the surrounding normal cortex. Macroscopically, the tumor is often contained within the cortical ribbon, with involvement of the underlying white matter typically only in mesial temporal locations (Lantos et al 1997), though a different series suggested much more frequent white matter involvement than had previously been thought (Honavar et al 1999). The lesion has a mucinous or semi-liquid consistency with macroscopic nodules visible within. The soft consistency of this tumor renders it prone to damage during removal, and great care must be taken in handling the pathologic specimen or diagnosis may be hindered (Daumas-Duport et al 1988). Meningeal involvement occurs occasionally. Classically, the dysembryoplastic neuroepithelial tumor displays 3 distinct pathologic features. The one that is most specific for this tumor type is the oddly named "specific glioneuronal element," consisting of columns of monotonous, small, round cells with little cytoplasm that resemble oligodendrocytes. These columns are oriented perpendicular to the cortical surface and typically form an alveolar pattern, with the interstitial spaces filled with pale, mucinous fluid. Thin capillaries run through these columns, and cytologically normal neurons give the appearance of floating within the fluid matrix. Mitotic figures are rare. Ultrastructural studies demonstrate that the columns are made up of bundles of axons to which are attached the cell processes of the presumptive oligodendrocytes (Daumas-Duport 1993; Taraturo et al 1995). These small round cells stain positively for S-100 (an oligodendroglial marker), and in a series, the majority of tumors showed staining of a significant fraction of these cells with myelin oligodendrocyte glycoprotein, a marker for mature oligodendrocytes (Gyure et al 2000). These cells stain only rarely with GFAP (an astrocytic marker); however, multiple reports also demonstrate that in 7% to 40% of cases, small fractions of these cells stain positively for neurofilament protein, synaptophysin, neuron-specific enolase, or class III beta-tubulin, suggesting early neuronal differentiation. In addition, electron microscopy has demonstrated dense-core granules (a characteristic of neuronal differentiation) in a few of these cells and occasional synapse formation involving them (Hirose et al 1994; Leung et al 1994; Taraturo et al 1995; Prayson et al 1996). This evidence suggests origin from an early glioneuronal precursor rather than from an oligodendroglial cell. The second, more variable, histologic characteristic of this tumor is that of glial nodules. These sharply demarcated regions are most often situated at the edge of the specific glioneuronal element, bordering the white matter. They are composed variously of astrocytes (usually pilocytic, but sometimes fibrillary or even anaplastic), small round oligodendrocyte-like cells, and mature neurons, with astrocytic nodules being most common. Occasionally, nodules may be composed of cells of glioneuronal lineage that cannot be further characterized (Daumas-Duport et al 1988). The third pathologic element of this tumor type is that of cortical dysplasia, which is present in a graded fashion at the edges of the specific glioneuronal element, shading off into normal cortex at either end. Neurons do not demonstrate any cytologic atypia. Tumors containing all 3 of the aforementioned elements were subsequently labeled the "complex form" of dysembryoplastic neuroepithelial tumor, as further studies by Daumas-Duport unearthed many cases in which only the specific glioneuronal element was present, with none of the other features. These patients shared the clinical profile of the previously reported patients and were, therefore, considered to have the "simple form" of dysembryoplastic neuroepithelial tumor (Daumas-Duport 1993). The existence of cases featuring only nodules and dysplasia without the specific element was also documented in 40% of cases in the original report and has been found by others as well (Iwanaga et al 1995). In light of these findings, Daumas-Duport considered either the specific glioneuronal element alone or the glial nodules with surrounding cortical dysplasia to be sufficient to make a diagnosis of dysembryoplastic neuroepithelial tumor (Daumas-Duport 1993). Two reports have suggested further expansion of the diagnostic criteria. Honavar and colleagues, in a large series,

4 described 46 tumors with the same cellular components as the "complex" form but having only a single glial nodule or a diffuse architecture with blurring of anatomical landmarks rather than multiple nodules. These authors concluded that the diagnosis of dysembryoplastic neuroepithelial tumor may be made in any neoplasm composed of oligodendroglial-like cells, astrocytes, and mature neurons (Honavar et al 1999). Daumas-Duport and colleagues went still further, examining all glial tumors removed in epilepsy surgery procedures at St. Anne Hospital that did not conform to established histological criteria for ganglioglioma or dysembryoplastic neuroepithelial tumor. They found cortical dysplasia adjacent to the tumor in nearly half the cases and also found that clinical presentation, neuroimaging, and long-term prognosis were almost identical to that of established dysembryoplastic neuroepithelial tumors. They concluded that these cases also represented a form of dysembryoplastic neuroepithelial tumor, and such a diagnosis should be a major consideration in any glial tumor, regardless of histologic appearance in a patient with early-onset focal epilepsy and minimal neurologic deficits if the tumor is intracortical in location and without edema or mass effect on imaging studies (Daumas-Duport et al 1999). A recent report revealed that the oligodendroglial-like cells of these tumors stain only for glial markers, not neuronal ones (Komori and Arai 2013). The authors also found that cells staining for neuronal markers were much less common when the tumor was embedded in the white matter. The authors posited that these tumors are therefore purely glial in origin, rather than glioneuronal, with the floating neurons representing trapped nonneoplastic cortical neurons. They suggested that they might even be considered the Grade I (noninfiltrating) form of oligodendroglioma. It is apparent that the definition of this tumor is in flux and that further expansion or refinement of the concept should be expected in the future, especially in view of the therapeutic importance of making the proper diagnosis. Several cases have been reported in which glial nodules with surrounding dysplasia contained atypical neurons, with tumors having the macroscopic appearance of a cyst with mural nodules, a picture suggestive of ganglioglioma (Daumas-Duport 1993; Shimbo et al 1997). These tumors may represent a transition between ganglioglioma and dysembryoplastic neuroepithelial tumor, suggesting a common origin of these neoplasms, which share many clinical features with each other as well as with other tumor types such as pleomorphic xanthoastrocytoma (eg, young age, glioneuronal composition, temporal lobe location, indolent nature, or presentation with epilepsy) (Iwanaga et al 1995). In fact, there has been a report of a dysembryoplastic neuroepithelial tumor mixed with anaplastic elements of a pleomorphic xanthoastrocytoma (Ishizawa 2007). The most likely cellular origin of this tumor is the subpial granular layer of the cortex, one of the secondary germinal layers of the nervous system. These cells are believed to migrate into the cerebral cortex in the middle to late stages of gestation and then to mature into cortical glial cells. This hypothesis could account for the consistent supratentorial and cortical location of this tumor, and the fact that migration of these cells occurs after the predominant neuronal migration could explain why the axons of the specific glioneuronal element are properly oriented with respect to the cortical surface (Daumas-Duport 1993). Thinning of the inner table of the skull, a frequent radiologic finding in this tumor, and the surrounding cortical dysplasia seen histologically also attest to its development in the earliest stages of life. This hypothesis does not explain the remarkable stability of this lesion; it has been proposed that early control of the abnormal growth by embryonic tissues may be responsible (Daumas-Duport et al 1988). Others have suggested that this lesion is actually a complex hamartoma, with overgrowth of what may represent normal embryonic nervous system tissue, rather than true neoplastic cells (Prayson and Estes 1992; Hirose et al 1994); however, given the clinical and cytologic characteristics of the lesion, most authors consider this growth to be a benign tumor (Daumas-Duport et al 1988; Taraturo et al 1995), and the occasional recurrence or growth of the lesion support this. The reason for the male predominance of this lesion is not known. Proliferative indices seen in dysembryoplastic neuroepithelial tumor range from no labeling (about 25% to 40% of cases) to slight or intermediate labeling of less than 1% of nuclei (50% to 65% of cases) to a high labeling index that may reach the level of cell division seen in high-grade gliomas (10% to 20% of cases) (Daumas-Duport 1993; Taraturo et al 1995; Wolf et al 1995; Prayson et al 1996; Daumas-Duport et al 1999; Honavar et al 1999). The oligodendrocytic cells of the specific glioneuronal element are rarely labeled. The labeling index of the nodules does not correspond to the aggressiveness of their histologic appearance, nor does the clinical course of highly labeled tumors deviate from the usual indolence that is a constant feature of this entity, suggesting that cell loss keeps up with cell proliferation in these cases. Two genetic studies have demonstrated that deletions in chromosomal regions 1p and 19q, which are present in a majority of oligodendrogliomas and mixed oligoastrocytomas, are not seen at all in dysembryoplastic neuroepithelial tumors (Fujisawa et al 2002; Prayson et al 2002). This points to clear genetic differences in the tumor types and might,

5 in certain cases, be useful in distinguishing the tumors from each other when pathologic diagnosis is uncertain. As is the case for other causes of refractory epilepsy, it is not known why the seizures produced by this entity often appear to be drug resistant. Some evidence suggests that the same multidrug transporter proteins that may produce resistance to chemotherapy in tumors (such as p-glycoprotein, multidrug resistance-associated protein 1, and major vault protein) and that are present in other causes of refractory epilepsy (such as hippocampal sclerosis) are likewise present in dysembryoplastic neuroepithelial tumors and might contribute to their antiepileptic drug resistance (Sisodiya et al 2002; Sisodiya et al 2003). Epidemiology" Because this tumor has been described almost exclusively in patients undergoing epilepsy surgery, no data are available concerning its incidence or prevalence in the general population. Although these tumors may rarely be encountered incidentally (M Blaivas, written communication, December 1998), a study of 500 unselected brains at autopsy found no cases of dysembryoplastic neuroepithelial tumor (nor of cortical dysplasia) (Wolf et al 1995). Within the population of patients with chronic epilepsy seen at tertiary referral centers, the incidence of brain tumors is 15%; 6% of these tumors are dysembryoplastic neuroepithelial tumors, yielding an overall incidence of 0.9% in this patient group (Morris and Estes 1996). Two more case series, however, using expanded diagnostic criteria for the tumor, found that 18% to 19% of patients undergoing temporal lobe resection for refractory epilepsy had a dysembryoplastic neuroepithelial tumor (Daumas-Duport et al 1999; Honavar et al 1999). Prevention No means of preventing these tumors is available, nor is any particular population group known to be at risk. Differential diagnosis The differential diagnosis for this lesion consists of all of the low-grade glioma subtypes, including astrocytoma, oligodendroglioma, mixed oligoastrocytoma, pleomorphic xanthoastrocytoma, and ganglioglioma (Greenberg et al 1999). The latter 2 neoplasms usually appear as cystic lesions with enhancing mural nodules, and oligodendroglial tumors are often calcified. Hamartoma must also be considered in the differential diagnosis. Histologically, the specific glioneuronal element may be mistaken for oligodendroglioma or mixed oligoastrocytoma due to the appearance of the predominant cell type. The nodules may be mistaken for astrocytoma. Biopsy may yield only one of the components, setting up ready misdiagnosis. During gross resection, the semi-liquid consistency of the tumor may cause distortion during handling, obscuring the architecture and producing diagnostic confusion. In the original report of this tumor, all 19 cases from the Mayo Clinic were initially diagnosed as astrocytoma, oligodendroglioma, or mixed oligoastrocytoma. Ganglioglioma is also considered within the pathologic differential but is distinguished by extracortical location or extension, lack of nodules, lack of neighboring dysplasia, and the presence of atypical neuronal cells and abundant connective tissue matrix (Daumas-Duport et al 1988). Proper diagnosis of this entity is crucial for patient care, as the treatment is different than that for grade 2 gliomas. Diagnostic workup As with all neoplasms, the workup for this tumor includes cerebral imaging to identify and pinpoint the lesion followed by operation to obtain tissue for pathologic analysis. On CT scanning, dysembryoplastic neuroepithelial tumor appears as a hypodense lesion, with calcification in about 25% of patients and contrast enhancement in 15% (Daumas-Duport et al 1988; Daumas-Duport 1993; Raymond et al 1994; Kuroiwa et al 1995; Taraturo et al 1995). Perhaps 5% of cases are CT occult. Thinning of the overlying skull is apparent on CT in approximately one third of cases, particularly when the tumor has a superficial location. In early studies, cystic appearance was reported in 28% to 50% of cases with CT or MRI (Daumas-Duport et al 1988; Daumas-Duport et al 1999; Raymond et al 1994; Taraturo et al 1995). However, a series using contemporary MRI techniques noted small cysts, sometimes separated from the main tumor mass, in 100% of 37 cases and found that these pseudocysts actually corresponded pathologically to the specific glioneuronal element (Campos et al 2009). MRI reveals the lesion to have hyperintense signal on T2-weighted images and hypointense signal on T1-weighted images in the large majority of cases. The intracortical location of the tumor is seen much more clearly on MRI than on CT. Neither mass effect nor edema is seen. Contrast enhancement, generally focal or punctate in appearance, was seen in about 40% of cases in early series (Daumas-Duport 1993; Raymond et al 1994;

6 Kuroiwa et al 1995; Taraturo et al 1995) but in only 22% of cases in a more recent series (Campos et al 2009). Interestingly, there is 1 report of a patient who developed new contrast enhancement with serial scans yet was nonetheless found to have a pathologically typical dysembryoplastic neuroepithelial tumor on resection (Jensen et al 2005). Thinning of the skull was described in 60% of cases in a report. The same report found that thick gyriform or nodular configuration, often with well-demarcated tumor lobules, was seen in all patients and appeared to be highly specific for dysembryoplastic neuroepithelial tumor (Kuroiwa et al 1995). Angiography is often normal but may show neovascularization or an avascular mass with shift of normal structures. On FDG-PET, the tumors have decreased uptake, which is in common with other low-grade neoplasms (Kaplan et al 1999). Another study in 5 patients (3 histologically verified) using PET with radiolabeled flumazenil demonstrated a decrease in binding in the region of the tumor, suggesting lower benzodiazepine receptor density (Richardson et al 2001). Several separate studies using methionine PET have demonstrated that dysembryoplastic neuroepithelial tumors have very low or no uptake, whereas gangliogliomas and other low-grade gliomas have high uptake (Kaplan et al 1999; Maehara et al 2004; Rosenberg et al 2005). This might make methionine PET a useful noninvasive tool for differential diagnosis. In a similar vein, proton MR spectroscopy, a tool more widely available, was also reported to demonstrate a different profile in dysembryoplastic neuroepithelial tumors than in other low-grade gliomas (Vuori et al 2004). Two studies have shown that patients with these tumors frequently have discordant or bilateral interictal epileptiform activity on EEG. However, this does not correlate with seizure outcome after surgery and, thus, need not be a source of concern (Raymond et al 1994; Labate et al 2004). Management Because patients with dysembryoplastic neuroepithelial tumor neither die nor become disabled as a consequence of neoplastic growth, active management is indicated only to treat tumor symptoms, particularly epilepsy. A substantial portion of patients with this tumor have epilepsy that is refractory to anticonvulsant medication (though there may be some ascertainment bias, with resection and diagnosis occurring more often in patients with intractable seizures). No studies examine the use of particular anticonvulsant agents in this population. The mainstay of management of this tumor is surgical resection. Total or subtotal resection resulted in elimination of seizures at follow-up of 1 year or more in about three quarters of patients in 5 studies (Daumas-Duport et al 1988; Daumas-Duport et al 1999; Raymond et al 1994; Prayson et al 1996; Burneo et al 2008). However, a subsequent study indicated that such seizure-free rates decline measurably over years 2 and 3 to around 60% (Nolan et al 2004). The latter investigation also pointed to the crucial importance of complete tumor resection for long-term seizure freedom, with results far better in the patients having complete resection than in those with residual tumor (40% seizure-free versus 88% seizure-free respectively). It is possible that this is due to the cortical dysplasia that frequently abuts this tumor and may suggest that tumor resection should be accomplished with an ample margin to remove such dysplastic regions. In fact, an investigation from a pediatric epilepsy surgery group demonstrated not only that patients with a residual MRI lesion after surgery had a poorer seizure prognosis but also that such lesions were almost always dysplastic in nature; in fact, the presence of dysplasia was significantly associated with worse seizure-free outcomes and a need for reoperation for seizure control (Sakuta et al 2005). Overall, 65% of patients in that cohort became seizure-free. Surgery is usually indicated to obtain tissue diagnosis. As a result of its impressive indolence, radiation therapy and chemotherapy have no place in the management of this tumor and should be avoided to prevent iatrogenic injury (Daumas-Duport et al 1988; Greenberg et al 1999). This makes the proper diagnosis of dysembryoplastic neuroepithelial tumor, and its distinction from grade II or higher gliomas, absolutely essential. References cited Baisden BL, Brat DJ, Melhem ER, Rosenblum MK, King AP, Burger PC. Dysembryoplastic neuroepithelial tumor-like neoplasm of the septum pellucidum: a lesion often misdiagnosed as glioma: report of 10 cases. Am J Surg Path 2001;25: PMID Burneo JG, Tellez-Zenteno J, Steven DA, et al. Adult-onset epilepsy associated with dysembryoplastic neuroepithelial tumors. Seizure 2008;17(6): PMID

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9 immunocytochemical, and deoxyribonucleic acid analyses in a pediatric series. Neurosurgery 1995;36: Thom M, Toma A, An S, et al. One hundred and one dysembryoplastic neuroepithelial tumors: an adult epilepsy series with immunohistochemical, molecular genetic, and clinical correlations and a review of the literature. J Neuropathol Exp Neurol 2011;70(10): PMID Vuori K, Kankaanranta L, Hakkinen A-M, et al. Low-grade gliomas and focal cortical developmental malformations: differentiation with proton MR spectroscopy. Neuroradiology 2004;230: Wolf HK, Wellmer J, Muller MB, Wiestler OD, Hufnagel A, Pietsch T. Glioneuronal malformative lesions and dysembryoplastic neuroepithelial tumors in patients with chronic pharmacoresistent epilepsies. J Neuropathol Exp Neurol 1995;54(2): PMID **References especially recommended by the author or editor for general reading. ICD and OMIM codes ICD codes ICD-9: Malignant neoplasm of brain unspecified site: Benign neoplasm of brain: Neoplasm of uncertain behavior of brain: ICD-10: Malignant neoplasm of cerebellum: C71.6 Benign neoplasm of brain, supratentorial: D33.0 Neoplasm of uncertain behavior of brain, supratentorial: D43.0 ICD-O-3: Dysembryoplastic neuroepithelial tumor: 9413/0 Profile Age range of presentation 0-01 month months years years years years Sex preponderance male>female, >1:1 Family history none Heredity none Population groups selectively affected none selectively affected Occupation groups selectively affected

10 none selectively affected Differential diagnosis list low-grade gliomas astrocytoma oligodendroglioma and oligoastrocytoma mixed oligoastrocytoma pleomorphic xanthoastrocytoma ganglioglioma hamartoma Associated disorders Cortical dysplasia Epilepsy Other topics to consider Brain tumors in infancy and early childhood Epilepsy Focal cortical dysplasia Molecular diagnosis of brain tumors Supratentorial hemispheric low-grade gliomas of childhood Copyright MedLink Corporation. All rights reserved.