Dysembryoplastic Neuroepithelial Tumor Presenting As a Hypothalamic Hamartoma in a Child with Gelastic Seizures: Case Report

CASE REPORT J Neurosurg Pediatr 26:34–37, 2020

Dysembryoplastic neuroepithelial tumor presenting as a hypothalamic hamartoma in a child with gelastic seizures: case report

Yuxiang Cai, MD, Yanjin Wang, MD, and Zhiquan Yang, MD

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

Dysembryoplastic neuroepithelial tumors (DNETs) are benign intracranial tumors of neuroglial origin, mostly located in the supratentorial regions and particularly in the temporal lobe. Few cases of DNETs in the hypothalamus have been described. The authors present the case of a DNET in the hypothalamus. The 5-year-old girl with complaints of limb and gelastic seizures was admitted to the neurosurgical department of Xiangya Hospital. Neurological examination findings were unremarkable. MRI showed isointensity without significant enhancement on T1- and T2-weighted images. The lesion exhibited clearly defined borders on the sagittal, coronal, and axial images. The preliminary diagnosis was hypothalamic hamartoma (HH); however, the lesion was surgically removed, and histopathological examination confirmed the diagnosis of a DNET. Hypothalamic DNETs are extremely rare. Based on their clinical manifestation and imaging, DNETs are easily misdiagnosed as HHs. Diagnoses apart from HHs must be entertained when a hypothalamic lesion is being investigated. https://thejns.org/doi/abs/10.3171/2020.2.PEDS19764 KEYWORDS dysembryoplastic neuroepithelial tumor; seizure; hypothalamus; epilepsy

ysembryoplastic neuroepithelial tumors (DNETs) lasted approximately 5 minutes and typically included con- are benign, glioneuronal neoplasms that are in- vulsions, eye turning, frothing at the mouth, facial cyano- cluded in the group of neuronal and mixed neu- sis, and limb stiffness, and they were alleviated spontane- Dronal-glial tumors.1 DNETs often manifest as medically ously. This seizure type occurred only twice. The second intractable epilepsy, and they primarily occur in children form was more common in this child; it lasted only a few and adolescents. Since the first report by Daumas-Duport seconds and was marked by uncontrolled laughter, but no et al. in 1988,2 the rate of accurately diagnosed DNETs in loss of consciousness. Although the patient had used ox- patients with seizures has increased due to developments carbazepine for a number of years (beginning at a dose of in pathology and imaging. DNETs most often occur in the 100 mg/day and gradually increasing to 450 mg/day), the temporal lobe, followed by other supratentorial cortical lo- seizures were not well controlled. Findings on neurologi- cations, including the frontal, parietal, and occipital lobes.3 cal examination were unremarkable. Her hormone func- DNETs have also been reported in the cerebellum, brain- tion was assessed, but no obvious abnormity was observed. stem, and thalamus.4,5 In this report, we present the case of a hypothalamic DNET. Examination The seizures were recorded twice by video electro- Case Report encephalography (EEG) and lasted 30–40 seconds. The events included sudden and involuntary laughter accompa- Presentation nied by slight rigidity and spasming of her limbs. Initially, A 5-year-old girl presented with a 4.6-year history of the EEG showed wide low voltage. Subsequently, spike seizures. Her seizures had two main forms and would be- waves and slow waves appeared in the full set of leads. gin without obvious inducement. Seizures of the first form The spike waves decreased, and the amplitude of the slow

ABBREVIATIONS DNET = dysembryoplastic neuroepithelial tumor; EEG = electroencephalography; HH = hypothalamic hamartoma. SUBMITTED December 21, 2019. ACCEPTED February 4, 2020. INCLUDE WHEN CITING Published online April 10, 2020; DOI: 10.3171/2020.2.PEDS19764.

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FIG. 1. The lesion is marked by the white arrow. Axial CT scan (A) showing a circular lesion without calcification in the left area of the suprasellar cistern. MR images showing a lesion in the hypothalamus that is isointense on T1-weighted (B) and T2-weighted (C) sequences. The lesion has no significant enhancement on the axial (D), sagittal (E), and coronal (F) images after gadolinium injection. waves progressively increased. The frequency of slow tochemical staining demonstrated the following findings: waves lessened gradually. The seizure ceased when the negative p53 and isocitrate dehydrogenase 1 expression frequency reached 1–2 Hz. and positive glial fibrillary acidic protein, oligodendrocyte A noncontrast cerebral CT scan showed a circular le- transcription factor 2, NeuN, and O6-methylguanine-DNA sion (32 Hounsfield units) about 4 mm in diameter in the methyltransferase expression. left area of the suprasellar cistern. The lesion showed no calcification (Fig. 1). MRI showed a lesion in the hypothal- Discussion amus that had isointensity without significant enhancement on T1-weighted, T2-weighted, and FLAIR images. DNETs are benign tumors that belong to neuronal and The lesion had clearly defined borders on the sagittal, cor- mixed neuronal-glial tumors. The tumors typically mani- onal, and axial views (Fig. 1). A hypothalamic hamartoma fest as medically intractable, partial complex seizures in (HH) was the preliminary diagnosis. children and adolescents.6 Consistent with the characteristics of DNETs, our patient was a 5-year-old child who pre- Operation and Follow-Up sented with a 4.6-year history of seizures without known The lesion was exposed via pterional approach. A gray precipitating events. DNETs typically occur within the tumor with dimensions of 1 × 0.8 × 0.8 cm could be seen. supratentorial cortex and most commonly in the tempo- The lesion had clearly defined borders and abundant vas- ral lobe.3 On MRI, DNETs are characterized by a multi- cularity. Subtotal resection was performed using a micro- nodular structure, rendering a bubbly appearance. Mass surgical technique because the posterior portion of the effect and perilesional edema are usually absent even in lesion had close adhesion to the pedunculus cerebri and voluminous lesions.7 A triangular pattern distribution and hypothalamus. The patient had an uneventful postoper- a FLAIR rim are typical imaging findings that can be ative recovery. Over the 12-month follow-up period, the observed in cases of DNETs.8 In the current case, MRI patient was neurologically intact and seizure free (Fig. 2). on FLAIR and contrast enhancement imaging had an The results from the histopathological examination con- isointense signal, and the patient presented with gelastic firmed that the lesion was a hypothalamic DNET (Fig. 3). seizures, together rendering the mass diagnostically indis- The histopathology showed isolated neurons with large tinguishable from an HH. HHs are masses that consist of nuclei characteristically floating within the mucoid sub- well-differentiated ectopic neurons interspersed with glial stance, encircled by a glial component, which was com- cells, and they are located in the tuber cinereum of the posed mainly of oligodendroglia-like cells. Immunohis- hypothalamus.9 They are congenital malformations rather

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FIG. 2. The lesion location is marked by the white arrow on axial (A), sagittal (B), and coronal (C) images. As the 12-month follow- up MRI examination shows, most of the tumor tissues have been removed. than cancerous tumors. Prototypical clinical presentations zures, who had multifocal involvement of diverse sites in of HHs include precocious puberty and gelastic seizures the central nervous system, including the temporal lobe, that begin in infancy.10 The signal intensity of HH lesions third ventricle, and basal ganglia, as well as partial involve- on MRI is hypointense on T1-weighted sequences and hy- ment of the hypothalamus. The patient did not undergo ag- perintense on T2-weighted sequences.11 Therefore, based gressive therapy and died of acute myocardial infarction.18 on age, clinical manifestations, and imaging, the preop- A DNET simply located in the hypothalamus has not been erative diagnosis was HH. Only after performing histo- reported yet. pathological examination was the diagnosis of a DNET Our patient was initially diagnosed with an HH. She confirmed. DNETs have intracortical nodules within a presented with medically intractable epilepsy without microcystic, vacuolated background. The structure ad- precocious puberty. Thus, we did not consider continuing ditionally contains columnar architecture of uniform oli- antiepileptic medication treatment or using gonadotropin- godendrocyte-like cells, which are lined around variously releasing hormone agonists. Resection, endoscopic resec- shaped and sized microcysts. This morphology is called tion, laser ablation, and Gamma Knife radiosurgery were “specific glioneuronal elements,” which, accompanied by viable options. Due to the long medical history and poor numerous interspersed floating neurons, is the most dis- family finances, her parents were eager for a cure to her tinctive pathological feature of DNETs.12 However, not all illness in an expeditious and economic way. Thus, we de- DNETs have specific glioneuronal elements, and some cided to perform resection. However, we need to point out DNETs exhibit a growth pattern similar to that of diffuse that if the clinical manifestations and imaging findings do gliomas. Therefore, the differential diagnosis includes gangliogliomas, low-grade diffuse gliomas, focal cortical dysplasia, oligodendrogliomas, pilocytic astrocytomas, and diffuse astrocytomas.3,13 For HH, there are various hypothalamic lesions that need a differential diagnosis. Some lesions originate from the suprasellar cistern or third ventricle, which can invade the hypothalamus, such as craniopharyngiomas, epider- moid cysts, Rathke’s cleft cysts, and colloid cysts. Some lesions are simply located in the hypothalamus, masquerad- ing as an HH. Fukunaga et al.14 reported a single case with hypothalamic-pituitary germinoma presenting as generalized hypohidrosis. Wang et al.15 reported a case with exophytic chiasmatic/hypothalamic glioma. The tumor was partially removed by endoscopic transsphenoidal surgery, with good preservation of hypothalamic and endocrine functions. A rosette-forming glioneuronal tumor originating in the hypothalamus and manifesting with precocious puberty has also been reported.16 Bognár et al.17 described a case of intracranial osteolipomas that occurred in the FIG. 3. The most distinctive pathological features of DNETs are their region of the tuber cinereum. The patient presented with “specific glioneuronal elements” accompanied by numerous inter- an ovarian cyst and signs of precocious puberty. A DNET spersed floating neurons. Specific glioneuronal elements are composed located in the hypothalamus has also been described in of ganglion cells suspended within a basophilic mucoid matrix encircled a previous case report.18 That case involved a 50-year-old by oligodendroglia-like cells. H & E, original magnification ×200. Figure man with a 9-year history of generalized tonic-clonic sei- is available in color online only.

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Unauthenticated | Downloaded 10/01/21 01:21 AM UTC Cai et al. not match the typical HH, we recommend doing a biopsy 6. Bilginer B, Yalnizoglu D, Soylemezoglu F, et al. Surgery for before a nonresective intervention. epilepsy in children with dysembryoplastic neuroepithelial Complete tumor resection is considered to be a major tumor: clinical spectrum, seizure outcome, neuroradiology, and pathology. Childs Nerv Syst. 2009;25(4):485–491. prognostic factor for DNETs in most studies. However, 7. Chassoux F, Daumas-Duport C. Dysembryoplastic neuroepi- whether DNETs need lesionectomy only, rather than ex- thelial tumors: where are we now? Epilepsia. 2013;54(suppl tended resection, is a matter of debate, especially when 9):129–134. the lesion is located within the temporal lobe.6 Some stud- 8. Paudel K, Borofsky S, Jones RV, Levy LM. Dysembryoplas- ies recommend surgical planning based on intraoperative tic neuroepithelial tumor with atypical presentation: MRI electrocorticography combined with MRI.6,19 However, and diffusion tensor characteristics. J Radiol Case Rep. one study reported a case in which intraoperative moni- 2013;7(11):7–14. toring with electrocorticography and tailored resection did 9. Harrison VS, Oatman O, Kerrigan JF. Hypothalamic hamar- 20 toma with epilepsy: review of endocrine comorbidity. Epilep- not improve seizure outcome. In the current case, the tu- sia. 2017;58(suppl 2):50–59. mor was located in an area of the hypothalamus atypical 10. Khawaja AM, Pati S, Ng YT. Management of epilepsy due to for common DNETs. The lesion was adherent to important hypothalamic hamartomas. Pediatr Neurol. 2017;75:29–42. surrounding nerve and vessel structures, such as the optic 11. Amstutz DR, Coons SW, Kerrigan JF, et al. Hypothalamic tract, pituitary stalk, and superior hypophyseal artery. The hamartomas: correlation of MR imaging and spectroscopic lesion was carefully surgically separated from normal tis- findings with tumor glial content. AJNR Am J Neuroradiol. sue. Subsequently, the lesion was also found to be adherent 2006;27(4):794–798. to the pedunculus cerebri and hypothalamus. To avoid se- 12. Chassoux F, Landré E, Mellerio C, et al. Dysembryoplastic neuroepithelial tumors: epileptogenicity related to histologic vere postoperative functional impairment and homeostatic subtypes. Clin Neurophysiol. 2013;124(6):1068–1078. disturbances, the lesion was not removed completely. At 13. O’Brien DF, Farrell M, Delanty N, et al. The Children’s Can- the 12-month follow-up visit, the patient was seizure free cer and Leukaemia Group guidelines for the diagnosis and and was not taking antiepileptic drugs. Incomplete resec- management of dysembryoplastic neuroepithelial tumours. tion is usually regarded as the major cause of surgical fail- Br J Neurosurg. 2007;21(6):539–549. ure. Some studies suggest that the follow-up should con- 14. Fukunaga A, Tajima S, Sasayama T, et al. Hypothalamic- tinue for a minimum of 3 years to reliably assess seizure pituitary germinoma presenting as generalized hypohidrosis. outcomes, as some children may only achieve short-term Eur J Dermatol. 2017;27(3):297–299. 20,21 15. Wang J, Jia J, Hou Z, et al. Endoscopic transsphenoidal sur- remission. Therefore, our case requires longer follow- gery for an adult patient with giant exophytic chiasmatic/hy- up to fully evaluate the therapeutic effects. pothalamic glioma. J Craniofac Surg. 2018;29(5):e499–e502. Although DNETs are typically benign, the presence of 16. Yamamoto T, Matsubara T, Satomi K, et al. Rosette-forming such tumors can result in refractory epilepsy that interferes glioneuronal tumor originating in the hypothalamus. Brain with a patient’s daily life. Surgery is the most effective Tumor Pathol. 2015;32(4):291–296. treatment. Patients have experienced favorable outcomes 17. Bognár L, Bálint K, Bárdóczy Z. Symptomatic osteoli- following complete resection. Preoperative assessments poma of the tuber cinereum. Case report. J Neurosurg. 2002;96(2):361–363. are necessary to accurately diagnose the lesion from a 18. Leung SY, Gwi E, Ng HK, et al. Dysembryoplastic neuroepi- range of similarly presenting lesions. Complete resection thelial tumor. A tumor with small neuronal cells resembling of the DNET is crucial to achieve a favorable long-term oligodendroglioma. Am J Surg Pathol. 1994;18(6):604–614. outcome, but severe postoperative complications must be 19. Chassoux F, Rodrigo S, Mellerio C, et al. Dysembryoplastic prevented. neuroepithelial tumors: an MRI-based scheme for epilepsy surgery. Neurology. 2012;79(16):1699–1707. 20. Nolan MA, Sakuta R, Chuang N, et al. Dysembryoplastic Acknowledgments neuroepithelial tumors in childhood: long-term outcome and We thank Jingbo Li, MD, for critically revising the article. prognostic features. Neurology. 2004;62(12):2270–2276. 21. Nguyen HS, Doan N, Gelsomino M, Shabani S. Dysembryo- plastic neuroectodermal tumor: an analysis from the Surveil- References lance, Epidemiology, and End Results Program, 2004-2013. 1. Louis DN, Perry A, Reifenberger G, et al. The 2016 World World Neurosurg. 2017;103:380–385. Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131(6):803–820. Disclosures 2. Daumas-Duport C, Scheithauer BW, Chodkiewicz JP, et al. The authors report no conflict of interest concerning the materi- Dysembryoplastic neuroepithelial tumor: a surgically curable als or methods used in this study or the findings specified in this tumor of young patients with intractable partial seizures. Re- paper. port of thirty-nine cases. Neurosurgery. 1988;23(5):545–556. 3. Thom M, Toma A, An S, et al. One hundred and one dysem- Author Contributions bryoplastic neuroepithelial tumors: an adult epilepsy series with immunohistochemical, molecular genetic, and clinical Conception and design: Cai. Acquisition of data: Cai. Analysis correlations and a review of the literature. J Neuropathol Exp and interpretation of data: Wang. Drafting the article: Cai. Neurol. 2011;70(10):859–878. Critically revising the article: Yang, Wang. Reviewed submitted 4. Stark J, Friedman E, Thompson S, et al. Atypical presenta- version of manuscript: Yang, Wang. Approved the final version of tions of dysembryoplastic neuroepithelial tumors. Epilepsia. the manuscript on behalf of all authors: Yang. 2018;59(1):e14–e17. 5. Sunwoo JS, Kim JS. Cerebellar dysembryoplastic neuroepi- Correspondence thelial tumor: report of a case and review of the literature. J Zhiquan Yang: Xiangya Hospital, Central South University, Neurol. 2017;264(11):2318–2321. Hunan, P.R. China. [email protected].

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