Tiirkish Neiirosiirgery 10: 61 - 64, 2000 To/ilI/iiy: Dysembryopliistic Neiiroepitheliiil TIIl/1or

Dysembryoplastic NeuroepitheliaI Tumor: A Case Report

Disembriyoplastik Nöroepitelyol Tümör: Olgu Sunumu

SAHSINE TOLUNAY, AHMET BEKAR

Departments of Pathology (ST) and Neurosurgery (AB), Uludag University School of Medicine, Bursa, Turkey

Received: 3.8.1999 <:::> Accepted: 24.2.2000

Abstract: A 14-year-old male patient presented with thechief complaint of tremors in his left arm and leg, and ahistory of seizures since age 3. The patient had beendiagnosed with partial epilepsy, and had been takinganticonvulsant medication for 6 years. He had been havingfour to five seizures a day in the year prior to presentationat our center. Sin ce the patient's condition had notimproved with the drug treatment, he was referred to theNeurosurgery Outpatient Clinic. A neurologicalexamination revealed no pathological findings.Computerized tomography and magnetic resonanceimaging showed a 2x1x1cm space-occupying lesionlocated in the cortical and subcortical regions of the rightparietal lobe. The mass did not enhance with contrastinjection. Digital subtraction-angiography findings werenormaL. The patient's electraencephalogram showedepileptic discharges that started in the right hemisphereand then rapidly generalized. The preliminary diagnosiswas a low-grade glial tumor, and the patient underwentsurgery. The mass was easily reached with the stereotacticlaser beam. The tumor was gray-white, had minimal bloodsupply, and its borders were not easily distinguishablefrom the surraunding normal tissue. The tumor wascompletely removed. The patient experienced no seizuresduring 4 years of postoperative follow-up, and hiselectroencephalogram findings were normal in the fourthyear.Key Words: Brain tumor, congenital tumor, partialcomplex epilepsy

INTRODUCTION

Dysembryoplastic neuroepithelial tumor (DNT)is a very rare neoplasm that was first described in

Özet: 14 yasinda erkek, 3 yasinda baslayan sol kol vesol bacakta titreme, kasilma tarzinda nöbet geçirmeyakinmasi ile basvurdu. 6 yil süreyle parsiyel epilepsitanisi ile antiepileptik tedavi görmüs. Bir yil öncegünde 4-5 kez nöbeti olmaya baslamis. Antiepileptiktedaviye ragmen yakinmasinin devam etmesi üzerineNörosirürji poliklinigine sevk edildi. Nörolojikmuayenesinde patolojik bulgu saptanmadi. Radyolojikincelenmesinde CT ve MRI' da sag parietalde kortikalve subkortikal bölgede 2x1x1 cm boyutlarinda belirginkontrast tutulumu olmayan, yer kaplayan lezyonsaptandi. DSA normaldi. EEG'de sag hemisferdenbaslayip hizla jeneralize olan epileptik bozuklukbulundu. Düsük gradeli glial tümör ön tanisi ile hastaopere edildi. Kitleye stereotaktik lazer önderligindekolayca ulasildi. Gri beyaz renkli normal dokudangüçlükle ayirdedilen, vaskülaritesi az kitle totalçikarildi. Postoperatif dört yillik takipte epileptiknöbeti olmayan hastanin, son 1 yildir EEG bulgularinormaldi.

Anahtar Kelimeler: Beyin tümörü, konjenital tümör,parsiyel kompleks epilepsi

1988 (1). Only a few cases have been published inthe literature. Diagnosis is difficult due to theheterogeneous cellular composition of DNT, and thistumor is often confused with other glial neoplasms.

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Affected patients usuaIly have history of partialcomplex seizures that do not respond to medicaltr·eatment. Patient age at onset of epilepsy rangesfrom 1 to 19 years, the mean age being 9 years. Theseizure activity usuaIly occurs for long period s beforethe diagnosis is made, ranging from 2 to 18 years'duration (mean, 9 years) (1). Since excision of DNTis curative, it is essential that these tumors bedistinguished from other neoplasms that arehistologicaiiy similar but behave differently.

CASE REPORT

A 14-year-old boy presented with tremors ofthe left arm and leg, and a history of seizures sinceage 3. He was originaIly diagnosed with partialcomplex epilepsy, and had been on anticonvulsanttreatment for 6 years. He had been having seizuresfour to five times daily in the year prior to hispresentation at our center. Since the medicaltreatment had produced no improvement in hiscondition, the patient was referred to theNeurosurgery Outpatient Clinic at UludagUniversity Medical SchooL. A neurologicalexamination revealed no pathological findings.Cranial computerized tomography (CT) andmagnetic resonance imaging (MRI) revealed a 2x1x1cm space-occupying lesi on in the cortex andsubcortex of the right parietal lobe. The lesion didnot enhance with contrast injection (Figure 1).Digital

Figure 1: The MRI appearance of the space-occupyinglesion located in the cortex and subcortex of the

right parietallobe.

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Tolimay: Dysel1lbryoplaslic Neuroepil/ielial Tiiiiior

subtraction angiography (DSA) findings wereunremarkable. An electroencephalogram (EEG)showed epileptic derangement that started in theright hemisphere and rapidly generalized.

The preliminary diagnosis was glial tumor, andthe patient underwent surgery. The mass was easilyreached with the stereotactic laser be am (Steiner­Lindquist Stereotactic Guide). At surgery, we founda gray-white mass with minimal blood supply thatwas not well-delineated from the surroundingnormal tissue. The tumor was aspirated easily, andwas totaiiy excised.

The excised specimen consisted of gray-whitetissue fragments that measured approximately2x1.5x1cm when pieced together. Histologicalexamination of sections stained with hematoxylin­eosin (HE) revealed a tumor composed of nodularstructures within the gray and the white matter. Onenodule contained calcified material (Figure 2). Thenodules were comprised of oligodendrocytes,neurons and astrocytes. Some containedpredominantly oligodendrocytes (Figure 3), whereasothers were rich in astrocytes (Figure 4). Most of theceiis in the nodules were uniform in size and shape,but a smaIl minority showed pleomorphism withlarger nuclei, and some ceIls had multiple nuclei.Occasional neurons stained positive for neurol1­specific enolase (NSE). Some ceIls that appeared tobe floating within clear spaces in the nodulescontained nuclei that were similar to those ofneurons; however, since they did not stain with NSE,these ceIls were considered immature neurons.

Pilocytic astrocytes and a few granular eosinophilic

Figure 2: Nodules containing neurons, oligodendrocytesand astrocytes surrounded by abnormal cortextissue. (HE x100)

Tiirkis/i Neurosiirgery 10: 61 - 64, 2000

Figure 3: High-magnification examination of the nodulesrevealed large disordered neurons and lack ofperineuronal satellitosis. (HE x200)

Figure 4: The cortex tissue between the nodules exhibitsoligodendroglioma-like hypercellularity, but noperineuronal satellitosis. (HE x200)

bodies were noted surrounding the microcysts withinthe nodules. These cells stained positively for glialfibrillary acidie protein (GFAP). The cartical tissuebetween the nodules contained foci of cortical

dysplasia characterized by distortion of normal tissuestructure and lamination. CompiIing all thesefindings led to the diagnosis of DNT.

The patient experienced no seizurespostoperatively, and was discharged on a regimenofCarbamazepin (Tegretol, CIBA) 200 mg four timesdaiIy and Fenitoin (Epdantoin, EMBIL) 100 mg twicedaily. During 4 years of follow-up, he experiencedno seizures. The anticonvulsant medication wasdiscontinued in the fourth year postsurgery becausethe patiene s EEG findings were normaL.

To/wiay: Dysembryop/astic Neiiroepit/ielia/ TimlOr

DISCUSSION

In 1988, it was recognized that 20 cases of adistinct brain tumor diagnosed at Sainte AnneHospital in France and retrospectively examined byDoumas-Douport, and 19 cases from the archives ofthe Mayo CIinic in the United States had similarcharacteristics (2). The neoplasm was named"d ysembryoplastic neuroepi thelial tumor",highlighting its possible dysembryogenic origin.

Almost all patients with this form of neoplasiasuffer partial complex seizures, with onset early inchildhood. At the time of DNT diagnosis, affectedindividuals generally have a long history of seizureactivity that has not responded to medical therapy.One-third of DNT patients have a focal cranial lesion.CT generally reveals a solitary, well-circumscribed,pseudocystic, low-density lesion. Some DNTs showfocal contrast enhancement (18%) or hyperdenseareas of calcification (23%). The tumor is usuallylocated in the temporal (62%), frontal (31%), orparietooccipital lobe (7%). it also frequently affectsthe caudate nucleus (1).

The findings common to all DNT cases are thetumor's cartical location, muItinodular pattern, andheterogeneous cellular composition. Histologically,the tumor nodules are clearIy delineated from thecerebral cortex, and their expansion distorts thecortical tissue, causing cytoarchitecturaldisorganization. Each nodule is typically comprisedof oIigodendrocyte-Iike cells with perinuclear halos,and groups of neuron-Iike cells floating withinmicrocysts of basophilic myxoid matrix.OIigodendrogIial cells ten d to predominate, andthese cells form Iinear patterns parallel to thecapillaries that are present in the mass (1,2). Any glialcells that are observed generally show nuclear atypia.Capillary vessel proIiferation is common, althoughno endotheIial proIiferation is seen. Mitotic figuresare rare, and necrosis is not a feature of this neoplasm.DNTs are clinically and histopathologically benign,and do not appear similar to, or behave like, gIiomas.

Immunohistochemical techniques are useful inthe diagnosis of DNTs. Astrocytes can be identifiedusing GFAP, and neurons using NSEimmunohistochemical stain. There are generally fewGFAP-positive astrogIial elements; however, someDNTs contain pilocytic astrocytes. Negative GFAPstaining does not rule out astrocytic differentiation.Likewise, neurofilament protein (NF) and NSEnegativity do not exclude the possibiIity of neuronal

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differentiation.

The characteristic location of DNTs can be

explained by the histogenic origin of this tumor,which is the embryonic subglial granular layer thatpersists in the frontotemporal region in normalinfants (1,2).Other evidence for the dysembryoplasticorigin of DNTs includes the observed focal corticaldysplasia and cellular differentiation with multipledistinct lines in the tumor tissue, the early onset ofsymptoms, and the presence of cartical dysplasiaadjacent to the tumor.

Conceming diagnosis, DNTs are often confusedwith oligodendrogliomas. Nodular structures arefound in both these tumors, but oligodendrogliomashave conspicuous cellular atypia, whereas DNTscontain larger neurons and can also be distinguishedby cortical dysplasia and the lack of, orinconspicuousness of, perineuronal satellitosis. DNTsthat contain large populations of astrocytes mayeasily be confused with mixed oligoastrocytomas, butthe distinguishing feature here is the lack of largerneurons in the latter. To date, no reports in theliterature have documented confusion of DNT with

ganglioglioma. The distinction between these twotumors is of academic interest only, gangliogliomabeing characterized by a background rich inreticulum, inflammatory cells, and atypical neurons(1,2,3,4).

The treatment for DNT is surgical excision.Interestingly, even in cases where tumor excision hasbeen incomplete, long-term follow-up (1-18 years)has revealed no clinical or radiological recurrence(1,2). Thirteen of 39 patients underwent radiationtreatment, but 26 received no additional therapypostsurgery. Radiation treatment and chemotherapyhave not proven to be beneficial in the clinicalmanagement and treatment of patients with this typeof tumor.

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Patients with DNT present with intractablepartial complex seizures that can be cured withsurgical excision of the tumor. As stated earlier, sinceno addihonal treatment is required to achieve ahighly successful outcome, it is extremely importantthat DNTs be distinguished from other histologicallysimilar lesions (1,2,3,4). We present the clinical,radiological and histopathological findings in thiscase of DNT as the first account of this neoplasm inour archives.

Correspondence: Prof. Dr. Sahsine TolunayUludag ÜniversitesiTip Fakültesi Patoloji ABD,16059 - Görükle

Bursa, TürkiyeTel: (90-224) 4428850

(90-224) 4428400-1181Fax: (90-224) 4428018E-mail: tolunay@uludag.edu.tr

REFERENCES

1. Burger PC, Scheithauer BW: Atlas of Tumor Pathology.Tumors of the Central Nervous System. Washington,1994 184-87 pp.

2. Daumas-Duport C, Scheithauer BW, Chadkiewicz JP,Laws E, Vedrenne C: Dysembryoplastic neuroepithelialturnor: A surgically eurable turn or of young patientswith intraetable partial seizures. Neurosurgery 23; 545­556, 1988

3. Nelson JS, Parisi JE, Sehoehet SS:Principles and praeticeof neuropathology. St. Louis, Mosby, 1993 150-53 pp.

4. Prayson RA, Estes ML: Dysembryoplastieneuroepithelial turnor. Arn J Clin Pathol 97; 398-401,1992

This ease was presented as a poster at the XIII NationalPathology Symposium in Bursa, Turkey, 19-22November 1995.