Brainstem ganglioglioma in an infant: Case report and review of literature.

Gangliogliomas are well differentiated, usually low grade, neuroepithelial tumors that comprise of neoplastic ganglion cells in combination with neoplastic glial cells. Occasionally, glial cells may show anaplastic features and are then labeled as anaplastic gangliogliomas. Most of the reported gangliogliomas are supratentorial tumors, predominantly in the temporal lobe. Brainstem location has been reported infrequently. As with cortically based gangliogliomas, though the primary treatment is resection, this is often not possible due to the eloquence of surrounding involved parenchyma. Here, we report a case of brainstem tumor in an 8-month-old child that was substantially resected and was histopathologically Grade 1 ganglioglioma. As per review of English literature, there has been no case of brainstem ganglioglioma reported in an infant (less than 1 year age). We discuss the surgical difficulties in the radical excision of such benign tumors and review literature on pediatric brainstem gangliogliomas.

Introduction

Gangliogliomas are usually low-grade, slow growing neoplasms of the central nervous system that have biphasic histological features of neoplastic neural and glial elements. Comprising approximately 0.4% of all central nervous system tumors and less than 2% of all intracranial tumors, they are mostly supratentorial with a predilection for the temporal lobes.[1] Nevertheless, there are reports of gangliogliomas in the third ventricle, thalamus, optic nerve, spinal cord, cerebellum, brainstem, pituitary, and pineal glands. Gangliogliomas present usually in first three decades of life and both sexes are equally affected.[23] In this report, we present a rare case of a brainstem ganglioglioma in an infant and discuss published literature on this entity.

Case Report

An 8-month-old boy presented with complaints of incessant cry and vomiting. A computed tomography (CT) scan brain at a local hospital revealed a posterior fossa tumor and obstructive hydrocephalus. In view of raised intracranial pressure (ICP), a ventriculoperitoneal shunt was performed, and the child was referred to our hospital for further management. On admission, the child was alert and did not have any clinical features suggestive of increased ICP. The child′s neurological examination was normal. Magnetic resonance imaging revealed a heterogeneously enhancing large solid-cystic tumor in the fourth ventricle compressing the cervicomedullary junction dorsally [Figure 1]. A well-defined plane from the floor of the fourth ventricle or inferior cerebellar vermis could not be discerned. Differential diagnosis of exophytic cervicomedullary glioma or a vermian astrocytoma was considered. The child underwent a midline suboccipital craniectomy. The tumor was a moderately vascular grey tissue that was variably soft to firm, and was dorsally exophytic from the medulla into the fourth ventricle. A near total excision of the tumor was attempted to spare the medullary tissues, which had no clear plane from the tumor.

Figure 1

Axial T1-weighted (a) shows a hypointense tumor predominantly in the midline with a cystic component situated anteriorly and to the right abutting the brainstem. Axial (b) and sagittal (c) T2-weighted images demonstrate the poor demarcation of the tumor from the brainstem. Post contrast axial (d), coronal (e) and sagittal (f) T1-weighted images show the heterogeneous nature of the tumor with enhancement of the solid component and the cyst wall

Histopathological examination [Figure 2] revealed a combination of neoplastic ganglion cells mixed with neoplastic astrocytic cells. Immunohistochemical staining demonstrated that the pleomorphic glial cells were positive for glial fibrillary acid protein, and the neoplastic ganglion cells and the intervening stroma were intensely positive for neurofilament protein and synaptophysin.

Figure 2

Histology. (a) Conventional H and E staining showing neoplasm with an admixture of glial cells and ganglion cells. The ganglion cells characteristically contain abundant eosinophilic cytoplasm and large vesicular nuclei with prominent nucleoli. The glial cells with small dark nuclei are seen scattered in between (×400). (b) The glial tumor cells strongly express glial fibrillary acidic protein (GFAP; ×400); ganglion cell cytoplasm and intervening stroma demonstrating strong positivity for neurofilament protein and synaptophysin (c and d respectively; avidin biotin ×400)

After surgery, the child had no new neurological deficits but developed high grade fever from the third post-operative day. A cerebrospinal fluid (CSF) study confirmed meningitis and the child were started on intravenous antibiotics based on sensitivity pattern. In view of persistent fever, it was decided to remove the shunt. Following shunt removal, fever subsided, and the child was continued on oral antibiotics. Ten days after surgery, the child became irritable. Examination revealed a tense anterior fontanelle and CT scan showed gross hydrocephalus with periventricular lucency. Suspecting raised ICP; the child underwent a repeat ventriculoperitoneal shunt. After this procedure, the child had an uneventful course in the hospital and was discharged 2 weeks after admission. Post-operative imaging showed minimal enhancement in the left side of the medulla bordering the cerebellomedullary fissure, and it was decided to keep the child on imaging follow-up.

Discussion

Gangliogliomas are predominantly reported in children and young adults[45] and account for 1–4% of all central nervous system tumors in children.[5] These tumors have a biphasic morphologic pattern, ranging from a predominantly neuronal phenotype to variants with a prominent glial population.[6] The origin is thought to be from a single precursor cell in a hamartomatous glioneuronal lesion that further evolve into neoplastic neuronal and glial elements.[7]

Though, they have been reported in all locations throughout the central nervous system, including cerebral hemsipheres, brainstem, cerebellum, and spinal cord, less than 15% are reported in the posterior fossa.[8] Table 1 gives the summary of 34 previously reported cases of brainstem ganglioglioma among pediatric population (<18 years age) in English literature. None of these cases have been cited in infants (less than 1 year of age).

Table 1

Literature review of pediatric brainstem gangliogliomas

Since, majority of the gangliogliomas are located supratentorially, and the lesions are usually cortical based, seizures are the commonest mode of presentation.[26] This is especially, true of temporal gangliogliomas. When located in the posterior fossa the patient may present with hydrocephalus, multiple cranial nerve palsies and/or cerebellar symptoms.[8] A report of a posterior fossa ganglioglioma has mentioned developmental delay as the presenting complaint in a pediatric patient.[27]

Imaging of gangliogliomas

Radiologically,[21] gangliogliomas are similar to other low-grade gliomas with a predominantly supratentorial localization. They are usually not particularly well-defined and can vary from purely solid to cystic lesions with a mural nodule. On T1-weighted magnetic resonance images, the solid parts vary from being hypointense to isointense, whereas on T2-weighted images, they are predominantly hyperintense. Enhancement with contrast is also variable. Considering these features, the differential diagnosis usually includes, other low-grade lesions such as pleomorphic xanthoastrocytoma, oligodendroglioma, dysembryoplastic neuroepithelial tumor, and low grade gliomas.[8] However, considering the rare location in the brainstem, any lesion with these imaging features will usually be labeled as a low grade glioma. Furthermore, the imaging features of infratentorial gangliogliomas are different from those of a supratentorial location and show higher rates of contrast enhancement and tumor associated cysts.[23] Unlike supratentorially located gangliogliomas, enhancement following gadolinium administration is present in nearly half of the infratentorial cases, although the pattern varies from intensely homogenous to heterogeneous compared to the isolated enhancing mass seen in the supratentorial gangliogliomas.[8]

Management of gangliogliomas

As with other low grade gliomas, the treatment of choice for gangliogliomas is also total surgical extirpation whenever possible.[23] Contrasting supratentorial cortical based gangliogliomas where radical decompression is relatively possible with good long term outcomes, those located in brainstem cannot be subjected to gross total removal all the time due to the eloquence of the adjacent parenchyma.[20] However, considering their low grade nature even partial decompression offers long-term symptom relief with an adjuvant radiotherapy usually reserved for recurrent lesions.[28] Nevertheless, surgical treatment has to be tailored for each case. The exophytic potions of the brainstem tumors can be resected whereas the infiltrating component can only be biopsied. The need for CSF diversion in the form of a shunt or ventriculostomy is also to be made on an individual basis.[23] The issue of treatment for residual tumor is still unclear, and the various authors have adopted different strategies. Whereas some have not given any adjuvant therapy,[6-33] others have resorted to radiotherapy and or chemotherapy only if there was evidence of large residue or tumor progression.[242034] The outcomes with both have been mixed, and the current literature has limited reports about the use of adjuvant therapy in patients with gangliogliomas as the usual supratentorially located tumors are amenable to radical excision, leaving little need for adjuvant therapies.

Prognosis and long term outcome

Though, brainstem gangliogliomas are benign tumors, their exact behavior in the brainstem location is difficult to predict due to the scarcity of reports in the literature, especially in the pediatric population. However, still with the available data, a few speculations can be drawn. Farmer[35] and Martin[36] in their studies had concluded that patients with brainstem gliomas fare better if the histology points to a ganglioglioma than other glioma subtypes. In contrast to this Lange et al.[20] in their study mention that when compared to supratentorial location, brainstem gangliogliomas have five-fold increased risk of recurrence. Baussard et al.[23] in their series of 10 patients implicated that even though complete excision may not be possible, removal of the enhancing component of the tumor, when possible, reduces the likelihood of requiring further treatment. Finally, according to the authors the association of another benign tumor does not appear to have any impact on tumor progression.

Conclusion

Gangliogliomas are seldom considered in the pre-operative diagnosis of pediatric brainstem lesions and is usually a diagnostic surprise following histopathological examination of the specimen. This case report highlights the need to consider ganglioglioma as a differential possibility even in infants, though extremely rare. As in the supratentorial location, they portend a favorable prognosis if maximal excision is achieved with minimal morbidity.