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

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

ABBREVIATIONS

DNET = dysembryoplastic neuroepithelial tumor; EEG = electroencephalography; HH = hypothalamic hamartoma.

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.

ABBREVIATIONS

DNET = dysembryoplastic neuroepithelial tumor; EEG = electroencephalography; HH = hypothalamic hamartoma.

Dysembryoplastic neuroepithelial tumors (DNETs) are benign, glioneuronal neoplasms that are included in the group of neuronal and mixed neuronal-glial tumors.1 DNETs often manifest as medically intractable epilepsy, and they primarily occur in children and adolescents. Since the first report by Daumas-Duport et al. in 1988,2 the rate of accurately diagnosed DNETs in patients with seizures has increased due to developments in pathology and imaging. DNETs most often occur in the temporal lobe, followed by other supratentorial cortical locations, including the frontal, parietal, and occipital lobes.3 DNETs have also been reported in the cerebellum, brainstem, and thalamus.4,5 In this report, we present the case of a hypothalamic DNET.

Case Report

Presentation

A 5-year-old girl presented with a 4.6-year history of seizures. Her seizures had two main forms and would begin without obvious inducement. Seizures of the first form lasted approximately 5 minutes and typically included convulsions, eye turning, frothing at the mouth, facial cyanosis, and limb stiffness, and they were alleviated spontaneously. This seizure type occurred only twice. The second form was more common in this child; it lasted only a few seconds and was marked by uncontrolled laughter, but no loss of consciousness. Although the patient had used oxcarbazepine for a number of years (beginning at a dose of 100 mg/day and gradually increasing to 450 mg/day), the seizures were not well controlled. Findings on neurological examination were unremarkable. Her hormone function was assessed, but no obvious abnormity was observed.

Examination

The seizures were recorded twice by video electroencephalography (EEG) and lasted 30–40 seconds. The events included sudden and involuntary laughter accompanied by slight rigidity and spasming of her limbs. Initially, the EEG showed wide low voltage. Subsequently, spike waves and slow waves appeared in the full set of leads. The spike waves decreased, and the amplitude of the slow waves progressively increased. The frequency of slow waves lessened gradually. The seizure ceased when the frequency reached 1–2 Hz.

A noncontrast cerebral CT scan showed a circular lesion (32 Hounsfield units) about 4 mm in diameter in the left area of the suprasellar cistern. The lesion showed no calcification (Fig. 1). MRI showed a lesion in the hypothalamus that had isointensity without significant enhancement on T1-weighted, T2-weighted, and FLAIR images. The lesion had clearly defined borders on the sagittal, coronal, and axial views (Fig. 1). A hypothalamic hamartoma (HH) was the preliminary diagnosis.

FIG. 1.
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.

Operation and Follow-Up

The lesion was exposed via pterional approach. A gray tumor with dimensions of 1 × 0.8 × 0.8 cm could be seen. The lesion had clearly defined borders and abundant vascularity. Subtotal resection was performed using a microsurgical technique because the posterior portion of the lesion had close adhesion to the pedunculus cerebri and hypothalamus. The patient had an uneventful postoperative recovery. Over the 12-month follow-up period, the patient was neurologically intact and seizure free (Fig. 2). The results from the histopathological examination confirmed that the lesion was a hypothalamic DNET (Fig. 3). The histopathology showed isolated neurons with large nuclei characteristically floating within the mucoid substance, encircled by a glial component, which was composed mainly of oligodendroglia-like cells. Immunohistochemical staining demonstrated the following findings: negative p53 and isocitrate dehydrogenase 1 expression and positive glial fibrillary acidic protein, oligodendrocyte transcription factor 2, NeuN, and O6-methylguanine-DNA methyltransferase expression.

FIG. 2.
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.

FIG. 3.
FIG. 3.

The most distinctive pathological features of DNETs are their “specific glioneuronal elements” accompanied by numerous interspersed floating neurons. Specific glioneuronal elements are composed of ganglion cells suspended within a basophilic mucoid matrix encircled by oligodendroglia-like cells. H & E, original magnification ×200. Figure is available in color online only.

Discussion

DNETs are benign tumors that belong to neuronal and mixed neuronal-glial tumors. The tumors typically manifest as medically intractable, partial complex seizures in children and adolescents.6 Consistent with the characteristics of DNETs, our patient was a 5-year-old child who presented with a 4.6-year history of seizures without known precipitating events. DNETs typically occur within the supratentorial cortex and most commonly in the temporal lobe.3 On MRI, DNETs are characterized by a multinodular structure, rendering a bubbly appearance. Mass effect and perilesional edema are usually absent even in voluminous lesions.7 A triangular pattern distribution and a FLAIR rim are typical imaging findings that can be observed in cases of DNETs.8 In the current case, MRI on FLAIR and contrast enhancement imaging had an isointense signal, and the patient presented with gelastic seizures, together rendering the mass diagnostically indistinguishable from an HH. HHs are masses that consist of well-differentiated ectopic neurons interspersed with glial cells, and they are located in the tuber cinereum of the hypothalamus.9 They are congenital malformations rather than cancerous tumors. Prototypical clinical presentations of HHs include precocious puberty and gelastic seizures that begin in infancy.10 The signal intensity of HH lesions on MRI is hypointense on T1-weighted sequences and hyperintense on T2-weighted sequences.11 Therefore, based on age, clinical manifestations, and imaging, the preoperative diagnosis was HH. Only after performing histopathological examination was the diagnosis of a DNET confirmed. DNETs have intracortical nodules within a microcystic, vacuolated background. The structure additionally contains columnar architecture of uniform oligodendrocyte-like cells, which are lined around variously shaped and sized microcysts. This morphology is called “specific glioneuronal elements,” which, accompanied by numerous interspersed floating neurons, is the most distinctive pathological feature of DNETs.12 However, not all DNETs have specific glioneuronal elements, and some DNETs exhibit a growth pattern similar to that of diffuse 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, epidermoid cysts, Rathke’s cleft cysts, and colloid cysts. Some lesions are simply located in the hypothalamus, masquerading 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 region of the tuber cinereum. The patient presented with an ovarian cyst and signs of precocious puberty. A DNET located in the hypothalamus has also been described in a previous case report.18 That case involved a 50-year-old man with a 9-year history of generalized tonic-clonic seizures, who had multifocal involvement of diverse sites in the central nervous system, including the temporal lobe, third ventricle, and basal ganglia, as well as partial involvement of the hypothalamus. The patient did not undergo aggressive therapy and died of acute myocardial infarction.18 A DNET simply located in the hypothalamus has not been reported yet.

Our patient was initially diagnosed with an HH. She presented with medically intractable epilepsy without precocious puberty. Thus, we did not consider continuing antiepileptic medication treatment or using gonadotropin-releasing hormone agonists. Resection, endoscopic resection, laser ablation, and Gamma Knife radiosurgery were viable options. Due to the long medical history and poor family finances, her parents were eager for a cure to her illness in an expeditious and economic way. Thus, we decided to perform resection. However, we need to point out that if the clinical manifestations and imaging findings do not match the typical HH, we recommend doing a biopsy before a nonresective intervention.

Complete tumor resection is considered to be a major prognostic factor for DNETs in most studies. However, whether DNETs need lesionectomy only, rather than extended resection, is a matter of debate, especially when the lesion is located within the temporal lobe.6 Some studies recommend surgical planning based on intraoperative electrocorticography combined with MRI.6,19 However, one study reported a case in which intraoperative monitoring with electrocorticography and tailored resection did not improve seizure outcome.20 In the current case, the tumor was located in an area of the hypothalamus atypical for common DNETs. The lesion was adherent to important surrounding nerve and vessel structures, such as the optic tract, pituitary stalk, and superior hypophyseal artery. The lesion was carefully surgically separated from normal tissue. Subsequently, the lesion was also found to be adherent to the pedunculus cerebri and hypothalamus. To avoid severe postoperative functional impairment and homeostatic disturbances, the lesion was not removed completely. At the 12-month follow-up visit, the patient was seizure free and was not taking antiepileptic drugs. Incomplete resection is usually regarded as the major cause of surgical failure. Some studies suggest that the follow-up should continue for a minimum of 3 years to reliably assess seizure outcomes, as some children may only achieve short-term remission.20,21 Therefore, our case requires longer follow-up to fully evaluate the therapeutic effects.

Although DNETs are typically benign, the presence of such tumors can result in refractory epilepsy that interferes with a patient’s daily life. Surgery is the most effective treatment. Patients have experienced favorable outcomes following complete resection. Preoperative assessments are necessary to accurately diagnose the lesion from a range of similarly presenting lesions. Complete resection of the DNET is crucial to achieve a favorable long-term outcome, but severe postoperative complications must be prevented.

Acknowledgments

We thank Jingbo Li, MD, for critically revising the article.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Cai. Acquisition of data: Cai. Analysis and interpretation of data: Wang. Drafting the article: Cai. Critically revising the article: Yang, Wang. Reviewed submitted version of manuscript: Yang, Wang. Approved the final version of the manuscript on behalf of all authors: Yang.

References

  • 1

    Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131(6):803820.

    • Search Google Scholar
    • Export Citation
  • 2

    Daumas-Duport C, Scheithauer BW, Chodkiewicz JP, et al. Dysembryoplastic neuroepithelial tumor: a surgically curable tumor of young patients with intractable partial seizures. Report of thirty-nine cases. Neurosurgery. 1988;23(5):545556.

    • Search Google Scholar
    • Export Citation
  • 3

    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):859878.

    • Search Google Scholar
    • Export Citation
  • 4

    Stark J, Friedman E, Thompson S, et al. Atypical presentations of dysembryoplastic neuroepithelial tumors. Epilepsia. 2018;59(1):e14e17.

  • 5

    Sunwoo JS, Kim JS. Cerebellar dysembryoplastic neuroepithelial tumor: report of a case and review of the literature. J Neurol. 2017;264(11):23182321.

    • Search Google Scholar
    • Export Citation
  • 6

    Bilginer B, Yalnizoglu D, Soylemezoglu F, et al. Surgery for epilepsy in children with dysembryoplastic neuroepithelial tumor: clinical spectrum, seizure outcome, neuroradiology, and pathology. Childs Nerv Syst. 2009;25(4):485491.

    • Search Google Scholar
    • Export Citation
  • 7

    Chassoux F, Daumas-Duport C. Dysembryoplastic neuroepithelial tumors: where are we now? Epilepsia. 2013;54(suppl 9):129134.

  • 8

    Paudel K, Borofsky S, Jones RV, Levy LM. Dysembryoplastic neuroepithelial tumor with atypical presentation: MRI and diffusion tensor characteristics. J Radiol Case Rep. 2013;7(11):714.

    • Search Google Scholar
    • Export Citation
  • 9

    Harrison VS, Oatman O, Kerrigan JF. Hypothalamic hamartoma with epilepsy: review of endocrine comorbidity. Epilepsia. 2017;58(suppl 2):5059.

    • Search Google Scholar
    • Export Citation
  • 10

    Khawaja AM, Pati S, Ng YT. Management of epilepsy due to hypothalamic hamartomas. Pediatr Neurol. 2017;75:2942.

  • 11

    Amstutz DR, Coons SW, Kerrigan JF, et al. Hypothalamic hamartomas: correlation of MR imaging and spectroscopic findings with tumor glial content. AJNR Am J Neuroradiol. 2006;27(4):794798.

    • Search Google Scholar
    • Export Citation
  • 12

    Chassoux F, Landré E, Mellerio C, et al. Dysembryoplastic neuroepithelial tumors: epileptogenicity related to histologic subtypes. Clin Neurophysiol. 2013;124(6):10681078.

    • Search Google Scholar
    • Export Citation
  • 13

    O’Brien DF, Farrell M, Delanty N, et al. The Children’s Cancer and Leukaemia Group guidelines for the diagnosis and management of dysembryoplastic neuroepithelial tumours. Br J Neurosurg. 2007;21(6):539549.

    • Search Google Scholar
    • Export Citation
  • 14

    Fukunaga A, Tajima S, Sasayama T, et al. Hypothalamic-pituitary germinoma presenting as generalized hypohidrosis. Eur J Dermatol. 2017;27(3):297299.

    • Search Google Scholar
    • Export Citation
  • 15

    Wang J, Jia J, Hou Z, et al. Endoscopic transsphenoidal surgery for an adult patient with giant exophytic chiasmatic/hypothalamic glioma. J Craniofac Surg. 2018;29(5):e499e502.

    • Search Google Scholar
    • Export Citation
  • 16

    Yamamoto T, Matsubara T, Satomi K, et al. Rosette-forming glioneuronal tumor originating in the hypothalamus. Brain Tumor Pathol. 2015;32(4):291296.

    • Search Google Scholar
    • Export Citation
  • 17

    Bognár L, Bálint K, Bárdóczy Z. Symptomatic osteolipoma of the tuber cinereum. Case report. J Neurosurg. 2002;96(2):361363.

  • 18

    Leung SY, Gwi E, Ng HK, et al. Dysembryoplastic neuroepithelial tumor. A tumor with small neuronal cells resembling oligodendroglioma. Am J Surg Pathol. 1994;18(6):604614.

    • Search Google Scholar
    • Export Citation
  • 19

    Chassoux F, Rodrigo S, Mellerio C, et al. Dysembryoplastic neuroepithelial tumors: an MRI-based scheme for epilepsy surgery. Neurology. 2012;79(16):16991707.

    • Search Google Scholar
    • Export Citation
  • 20

    Nolan MA, Sakuta R, Chuang N, et al. Dysembryoplastic neuroepithelial tumors in childhood: long-term outcome and prognostic features. Neurology. 2004;62(12):22702276.

    • Search Google Scholar
    • Export Citation
  • 21

    Nguyen HS, Doan N, Gelsomino M, Shabani S. Dysembryoplastic neuroectodermal tumor: an analysis from the Surveillance, Epidemiology, and End Results Program, 2004-2013. World Neurosurg. 2017;103:380385.

    • Search Google Scholar
    • Export Citation

Contributor Notes

Correspondence Zhiquan Yang: Xiangya Hospital, Central South University, Hunan, P.R. China. yangzqneuro@163.com.

INCLUDE WHEN CITING Published online April 10, 2020; DOI: 10.3171/2020.2.PEDS19764.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

  • View in gallery

    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.

  • View in gallery

    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.

  • View in gallery

    The most distinctive pathological features of DNETs are their “specific glioneuronal elements” accompanied by numerous interspersed floating neurons. Specific glioneuronal elements are composed of ganglion cells suspended within a basophilic mucoid matrix encircled by oligodendroglia-like cells. H & E, original magnification ×200. Figure is available in color online only.

  • 1

    Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131(6):803820.

    • Search Google Scholar
    • Export Citation
  • 2

    Daumas-Duport C, Scheithauer BW, Chodkiewicz JP, et al. Dysembryoplastic neuroepithelial tumor: a surgically curable tumor of young patients with intractable partial seizures. Report of thirty-nine cases. Neurosurgery. 1988;23(5):545556.

    • Search Google Scholar
    • Export Citation
  • 3

    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):859878.

    • Search Google Scholar
    • Export Citation
  • 4

    Stark J, Friedman E, Thompson S, et al. Atypical presentations of dysembryoplastic neuroepithelial tumors. Epilepsia. 2018;59(1):e14e17.

  • 5

    Sunwoo JS, Kim JS. Cerebellar dysembryoplastic neuroepithelial tumor: report of a case and review of the literature. J Neurol. 2017;264(11):23182321.

    • Search Google Scholar
    • Export Citation
  • 6

    Bilginer B, Yalnizoglu D, Soylemezoglu F, et al. Surgery for epilepsy in children with dysembryoplastic neuroepithelial tumor: clinical spectrum, seizure outcome, neuroradiology, and pathology. Childs Nerv Syst. 2009;25(4):485491.

    • Search Google Scholar
    • Export Citation
  • 7

    Chassoux F, Daumas-Duport C. Dysembryoplastic neuroepithelial tumors: where are we now? Epilepsia. 2013;54(suppl 9):129134.

  • 8

    Paudel K, Borofsky S, Jones RV, Levy LM. Dysembryoplastic neuroepithelial tumor with atypical presentation: MRI and diffusion tensor characteristics. J Radiol Case Rep. 2013;7(11):714.

    • Search Google Scholar
    • Export Citation
  • 9

    Harrison VS, Oatman O, Kerrigan JF. Hypothalamic hamartoma with epilepsy: review of endocrine comorbidity. Epilepsia. 2017;58(suppl 2):5059.

    • Search Google Scholar
    • Export Citation
  • 10

    Khawaja AM, Pati S, Ng YT. Management of epilepsy due to hypothalamic hamartomas. Pediatr Neurol. 2017;75:2942.

  • 11

    Amstutz DR, Coons SW, Kerrigan JF, et al. Hypothalamic hamartomas: correlation of MR imaging and spectroscopic findings with tumor glial content. AJNR Am J Neuroradiol. 2006;27(4):794798.

    • Search Google Scholar
    • Export Citation
  • 12

    Chassoux F, Landré E, Mellerio C, et al. Dysembryoplastic neuroepithelial tumors: epileptogenicity related to histologic subtypes. Clin Neurophysiol. 2013;124(6):10681078.

    • Search Google Scholar
    • Export Citation
  • 13

    O’Brien DF, Farrell M, Delanty N, et al. The Children’s Cancer and Leukaemia Group guidelines for the diagnosis and management of dysembryoplastic neuroepithelial tumours. Br J Neurosurg. 2007;21(6):539549.

    • Search Google Scholar
    • Export Citation
  • 14

    Fukunaga A, Tajima S, Sasayama T, et al. Hypothalamic-pituitary germinoma presenting as generalized hypohidrosis. Eur J Dermatol. 2017;27(3):297299.

    • Search Google Scholar
    • Export Citation
  • 15

    Wang J, Jia J, Hou Z, et al. Endoscopic transsphenoidal surgery for an adult patient with giant exophytic chiasmatic/hypothalamic glioma. J Craniofac Surg. 2018;29(5):e499e502.

    • Search Google Scholar
    • Export Citation
  • 16

    Yamamoto T, Matsubara T, Satomi K, et al. Rosette-forming glioneuronal tumor originating in the hypothalamus. Brain Tumor Pathol. 2015;32(4):291296.

    • Search Google Scholar
    • Export Citation
  • 17

    Bognár L, Bálint K, Bárdóczy Z. Symptomatic osteolipoma of the tuber cinereum. Case report. J Neurosurg. 2002;96(2):361363.

  • 18

    Leung SY, Gwi E, Ng HK, et al. Dysembryoplastic neuroepithelial tumor. A tumor with small neuronal cells resembling oligodendroglioma. Am J Surg Pathol. 1994;18(6):604614.

    • Search Google Scholar
    • Export Citation
  • 19

    Chassoux F, Rodrigo S, Mellerio C, et al. Dysembryoplastic neuroepithelial tumors: an MRI-based scheme for epilepsy surgery. Neurology. 2012;79(16):16991707.

    • Search Google Scholar
    • Export Citation
  • 20

    Nolan MA, Sakuta R, Chuang N, et al. Dysembryoplastic neuroepithelial tumors in childhood: long-term outcome and prognostic features. Neurology. 2004;62(12):22702276.

    • Search Google Scholar
    • Export Citation
  • 21

    Nguyen HS, Doan N, Gelsomino M, Shabani S. Dysembryoplastic neuroectodermal tumor: an analysis from the Surveillance, Epidemiology, and End Results Program, 2004-2013. World Neurosurg. 2017;103:380385.

    • Search Google Scholar
    • Export Citation

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