CASE REPORT

Suprasellar ganglioglioma presenting with diabetes insipidusin a young boy: a rare clinical presentation

Ruchika Gupta & Vaishali Suri & Raman Arora &

Mehar C. Sharma & Shashwat Mishra &

Manmohan Singh & Chitra Sarkar

Received: 7 July 2009 /Revised: 8 August 2009 /Published online: 9 September 2009# Springer-Verlag 2009

AbstractObjective Gangliogliomas are rare tumors composed of anadmixture of glial and neuronal components. These usuallyoccur in young patients, who present with therapy-resistantseizures. Clinical presentation of ganglioglioma withdiabetes insipidus is extremely rare with only one casereported earlier in the available literature. Due to this rarity,ganglioglioma is not considered in the differential diagnosisin a patient with diabetes insipidus.Case A 7-year boy presented with polyuria, polydipsia,and progressive visual loss for 18 months. Investigationsrevealed diabetes insipidus. Radiographic studies of thebrain showed a solid and cystic mass in the suprasellarregion effacing the third ventricle. Intraoperatively,diffuse thickening of bilateral optic nerves and opticchiasma was noted and a diagnosis of optic glioma wasconsidered. A biopsy of the mass was taken, which onhistopathological examination showed features of gan-glioglioma. The patient was referred for further radio-therapy but was lost to follow-up.Conclusion Diabetes insipidus as a presenting symptom ofganglioglioma is extremely rare. This benign tumor shouldbe kept in mind in patients with central diabetes insipidusand a suprasellar mass lesion. This report describes thesecond such case in the literature.

Keywords Ganglioglioma . Suprasellar . Optico-chiasmal .

Diabetes insipidus . Histopathology

Introduction

Gangliogliomas are rare low-grade mixed tumors com-posed of neuronal and glial elements, both exhibitingneoplastic features [3, 9]. They usually present inchildren and young adults with intractable seizures [10].Diabetes insipidus (DI) as a presenting symptom ofganglioglioma has been reported in only one report inthe literature [13]. In the case described by Shono et al.,the tumor involved the suprasellar region [13]. Ganglio-gliomas occurring in the suprasellar region may extendalong the optico-chiasmal pathway. In such cases, radio-logic differentiation from optic glioma is not possible [5].Due to the rarity of suprasellar location of ganglioglioma,other more common tumors like germinoma or eosino-philic granuloma are considered clinically. An accuratediagnosis, mostly by histopathological examination ofexcised tumor or biopsy, is essential for appropriatemanagement and prognostication.

We describe a case of suprasellar gangliogliomapresenting as DI in a young child, where the diagnosiswas made on histopathology. To the best of ourknowledge, this is the second report of gangliogliomapresenting with DI.

Case report

A 7-year-old boy presented to the neurosurgery outpa-tient department with an 18-month history of abnormalweight gain, excessive thirst, and urination and progres-

R. Gupta :V. Suri (*) : R. Arora :M. C. Sharma : C. SarkarDepartment of Pathology, All India Institute of Medical Sciences,Ansari Nagar,New Delhi 110029, Indiae-mail: surivaishali@yahoo.co.in

S. Mishra :M. SinghDepartment of Neurosurgery,All India Institute of Medical Sciences,Ansari Nagar,New Delhi, India

Childs Nerv Syst (2010) 26:255–258DOI 10.1007/s00381-009-0989-1

sive diminution of vision in both eyes. His generalcondition was stable. Cardiovascular, respiratory, andabdominal examinations were unremarkable. Centralnervous system examination was also unremarkable forhigher mental functions, cranial nerves, and motor andsensory functions. Visual acuity was markedly reduced tothree feet in the left eye and one feet in the right eye;there was however no restriction in the range ofmovement of both eyes.

Laboratory investigations indicated hypopituitarism (cor-tisol 2.7 µg/dl, growth hormone 0.05 ng/ml) and DI. Bloodsugar levels, both fasting and postprandial, were withinreference ranges. Contrast-enhanced computed tomography(CECT) scan and magnetic resonance imaging (MRI) bothshowed a suprasellar solid cystic mass lesion measuring4.2×4×4.5 cm. The lesion was effacing the anterior thirdventricle with splaying of superior cerebral peduncle,obstructive hydrocephalus, and widening of both opticnerves (Fig. 1). Considering the age and suprasellarlocation of the tumor, a clinico-radiological diagnosis ofsuprasellar germinoma was considered.

After hospital admission, the patient complained ofpersistent headache and vomiting, indicating hydrocepha-lus. He underwent ventriculoperitoneal shunt surgery torelieve the intracranial tension. Subsequently, bifrontalcraniotomy was undertaken. Intraoperatively, a suprasellarfirm tumor with diffuse thickening and infiltration ofbilateral optic nerves and chiasma was detected, and adiagnosis of optico-chiasmal glioma was considered. Abiopsy was taken since surgical extirpation was notpossible.

Histopathological examination showed a low-grademixed glioneuronal tumor (Fig. 2) composed of pilocytic

astrocytoma-like areas (glial component) with scatteredganglion cells (neuronal component). The ganglion cellswere irregular, dysplastic, and dysmorphic. Focal micro-cystic change was also noted. No conspicuous perivascularlymphoid aggregate was seen. There was no microvascularproliferation, mitotic activity, or necrosis in the astrocyticcomponent. For confirmation of the nature of cells,immunohistochemistry was performed using the followingmonoclonal antibodies: glial acidic fibrillary protein(GFAP), synaptophysin, NeuN, neurofilament, and MIB-1.The astrocytic cells stained positively with GFAP, whileganglion cells were positive for synaptophysin, NeuN, andneurofilament. MIB-1 labeling index in the astrocyticcomponent was low (1–2%).

Thus, a final diagnosis of ganglioglioma (WorldHealth Organization (WHO) grade I) was rendered. Inview of the extent of infiltration of the tumor, the childwas referred for radiotherapy since surgical excision ofthe tumor was not possible. However, he was subse-quently lost to follow-up.

Discussion

Gangliogliomas are rare mixed glioneuronal tumors with anincidence of around 1–1.5% in large series [7]. They occurpredominantly in young males presenting with pharmacor-esistant epilepsy and tumors in temporal or frontal lobes[10]. However, symptoms vary according to the location ofthe tumor. Occurrence of ganglioglioma in the ventricularsystem is rare and includes involvement of lateral ventriclefrom septum pellucidum, fourth ventricle from its floor, andthird ventricle from thalamus and hypothalamus [2, 6, 8].

Fig. 1 MRI images of the brainshowing a suprasellar mass,which is isointense on T1Wimage (a, arrow) and demon-strating contrast enhancement(b, arrow). Bilateral optic nervesare seen to be widened, more onthe right side (b, arrowheads)

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Involvement of sellar and suprasellar areas is rare with veryfew reported cases [11]. Our patient also had a suprasellarmass with involvement of the third ventricle, hydrocepha-lus, and infiltration along the optic chiasmal pathway. Dueto this pattern of infiltration, an intraoperative diagnosis ofoptic glioma was considered. Gangliogliomas involving theoptic chiasma are extremely rare with only a few casesreported in the available literature. In majority of thesecases, a clinico-radiologic diagnosis of pilocytic astrocyto-ma was considered. The involvement of optic chiasmadiffers from the usual location of ganglioglioma in that acomplete surgical excision is often not possible [14]. OnCECT, ganglioglioma may be seen either as an isodense orhypodense cystic lesion with enhancing mural nodule, acystic mass with ring enhancement or as a solid masslesion. Calcification may also be noted in some cases [13].

Histopathologically, gangliogliomas are classified asWHO grade I tumors (except for anaplastic variants). Theyare composed of a mixture of neoplastic astrocytes andganglion cells. The ganglion cells or neurons in ganglio-glioma are dysplastic due to cytoarchitectural disorganiza-tion, subcortical localization, clustering, cytomegaly, andperimembranous aggregates of Nissl substance [3]. Glialelements in ganglioglioma also show substantial variability,including fibrillary astrocytoma, oligodendroglioma, orpilocytic astrocytoma. In addition, calcification, perivascu-lar lymphoid aggregates, and eosinophilic granular bodiesmay be seen [3]. The glial component constitutes theproliferative population of the tumor and, hence, defines thebiologic behavior [12]. Gangliogliomas with high prolifer-

ative activity (MIB-1 labeling index>10%), microvascularproliferation, or necrosis are classified as anaplastic (WHOgrade III) [3, 4]. Immunohistochemistry for glial proteins(GFAP), S-100 protein, and neuronal markers (NeuN,neurofilaments, synaptophysin, MAP2) helps in definingthe neuronal and glial cell populations. Semiquantitativeestimation of Ki-67 labeling index assists in characteriza-tion of the biologic behavior of the tumor [15]. The variousentities to be considered in the histopathological differentialdiagnosis of ganglioglioma include low-grade gliomas likepilocytic astrocytoma (WHO grade I), diffuse fibrillaryastrocytoma (WHO grade II), oligodendroglioma (WHOgrade II), and entities like dysembryoplastic neuroepithelialtumor, dysembryoplastic neuroepithelial tumor (DNT;grade I), cortical dysplasia, and gangliocytoma. Of these,DNT is a close differential due to the similar clinicalpresentation with chronic epilepsy in young patients andsimilar radiologic features. These two entities can bedistinguished on histopathology since DNT is usuallyintracortical and exhibits multinodularity with foci ofcortical dysplasia in adjoining cortex and specific glio-neuronal element in simple or complex forms [9].

DI as a presenting symptom of ganglioglioma isextremely rare and has been described in only one earlierreport [13]. This rarity of ganglioglioma with DI may beattributed to the uncommon occurrence of this tumor in thesellar and suprasellar region. We describe the second caseof this rare association of ganglioglioma and central DI. Insuch cases, DI occurs due to the involvement of hypotha-lamic–pituitary axis with inadequate secretion of antidiu-

Fig. 2 Photomicrographs show-ing an admixture of glial ele-ment and ganglion cells(a H&E, ×40). Higher-powerview shows the admixture moreclearly (b H&E, ×100). Theganglion cells (arrows) aredysplastic due to their aggrega-tion and cytoplasmic features(c H&E, ×200). Focal micro-cystic change and cytoplasmicvacuolation was also noted(d H&E, ×200)

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retic hormone from posterior pituitary, leading to centralDI. This is usually associated with panhypopituitarism. SinceDI can be caused by a defect in renal concentration ability(nephrogenic DI) or a psychological disorder (psychogenicDI), these need to be excluded before considering central DI.This can be achieved by water deprivation test or vasopressinresponse test [1]. In patients with confirmed central DI, CTscan and/or MRI of the hypothalamic–pituitary region ismandatory to detect infective/neoplastic conditions. Amongthe neoplastic conditions, the most common causes of centralDI include germinoma and eosinophilic granuloma [14]. Aclinico-radiologic differentiation between these entities andganglioglioma is quite difficult, as also in our case where adiagnosis of germinoma was considered on clinical andradiologic features. In such a situation, pathologic examina-tion offers the only means of an accurate diagnosis, correctmanagement, and prognostication of an individual patient.

In conclusion, diabetes insipidus is a rare mode ofpresentation for suprasellar ganglioglioma. Radiologicaldifferentiation of ganglioglioma from glial tumors anddysembryoplastic neuroepithelial tumor is extremely diffi-cult. Since ganglioglioma is generally a low-grade tumor,histopathologic examination and an accurate diagnosis areessential for appropriate management decisions.

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