Rosette-forming Glioneuronal Tumor: A Rare Posterior Fossa Tumor in an Adolescent.

Rosette-forming glioneuronal tumor (RGNT) is a rare variety of slow growing mixed glioneuronal tumor involving primarily fourth ventricular region and occurring predominantly in young adults. We present a case of a 16-year-old boy who presented with dizziness and occipital headache. On radiological evaluation, a fairly large hypodense posterior fossa mass lesion in relation to the left side of the vermis, with a large cystic component was found. Surgical resection of the tumor was performed. Histopathological examination showed a biphasic tumor composed of bland neurocytic cells, arranged in the form of neurocytic rosettes along with glial areas resembling low-grade glioma. The neurocytic rich region shows strong synaptophysin positivity in the neuropil-rich core of the rosettes. Methylation-inhibited binding proliferative index was low (<1%). Based on these features, a diagnosis of RGNT was made. RGNT of the fourth ventricle should be considered in differential diagnosis of posterior fossa lesions, especially in relation to fourth ventricle and vermis in young adults.

INTRODUCTION

Rosette-forming glioneuronal tumor (RGNT) is a recently described, rare variety of mixed glioneuronal tumor of central nervous system (CNS). Initially, it was described as dysembryoplastic neuroepithelial tumor (DNT) of cerebellum.[1] In 2002, in a series of 11 cases, Komori et al. first described RGNT as a distinct variant of mixed glioneuronal tumor arising in relation to the fourth ventricle.[2] Later, it was included as a low grade (Grade I) tumor in the last edition of the WHO classification of CNS tumor (2007).[3] Although initially, it was described as a tumor arising in relation to the fourth ventricle with possible extension into surrounding structures, cases involving other sites of CNS including pineal gland region, optic chiasm, hypothalamus and even, cervical spinal cord have been reported.

CASE REPORT

A 16-year-old adolescent boy presented with a history of dizziness and occipital headache for less than a week. On examination, mild truncal ataxia was noticed. No other neurological deficits were apparent.

He was evaluated radiologically initially with contrast enhanced computed tomography (CT) scan followed by contrast enhanced magnetic resonance imaging (MRI) of the brain. His initial CT scan revealed a fairly large hypodense posterior fossa mass lesion in relation to the left side of the vermis, with a large cystic component pushing the fourth ventricle anteriorly. Upstream hydrocephalus was also noticed. On contrast films, solid component of the tumor showed patchy enhancement. Contrast MRI confirmed the findings of CT scan. It revealed heterogeneously enhancing mural nodule in the left side of vermis with a large cystic component pushing the fourth ventricle anteriorly and thus causing upstream hydrocephalus. Minimal perilesional edema was seen on T2-weighted MR scan. Radiological differential diagnosis included pilocytic astrocytoma and hemangioblastoma [Figure 1].

Figure 1

Preoperative gadolinium-enhanced T1 axial image showing partly solid and partly cystic tumor

With the above clinicoradiological findings surgical resection was planned. Initially, the right frontal external ventricular drain was placed. Then, he was repositioned to prone position with neck flexed and head kept on 3pin system. Midline posterior fossa craniectomy was done. Solid part of the tumor was exposed through vermian split approach. Intraoperative findings were suggestive of an intraaxial solid tumor arising from the left side of the vermis. It was grayish pink in appearance, moderately vascular, soft and suckable. Gross total removal of the solid part was done.

The postoperative period was uneventful, and no fresh neurological deficit occurred. The external ventricular drain was removed after 2 days. He was discharged in a stable condition after 9 days.

Postoperative CT scan of the brain showed complete removal of the tumor with no evidence of hydrocephalus.

Microscopically, the tumor was biphasic and composed of bland neurocytic cells arranged in the form of neurocytic rosettes along with glial areas resembling pilocytic astrocytoma. The neurocytic rich region showed strong synaptophysin positivity in the neuropil-rich core of the rosettes. The surrounding glial tissue showed glial fibrillary acidic protein (GFAP) positivity. Methylation-inhibited binding (MIB-1) proliferative index was low (<1%) [Figure 2]. Based on these features, a diagnosis of RGNT was made.

Figure 2

(a) Low power view showing rosettes lined by a single layer of bland neurocytic cells. (b) High power view of the neurocytic rosette. (c) Immunohistochemistry for synaptophysin highlights the neuropil-rich core of the rosette. The inset shows high power view of the same. (d) The rosettes are negative for glial fibrillary acidic protein immunostain

On 1 year follow-up, he was asymptomatic. Check MR scan showed no residual tumor [Figure 3].

Figure 3

One-year postoperative, gadolinium-enhanced T1 axial image, showing complete removal of tumor

DISCUSSION

Until recently only about 47 cases of RGNT have been reported. Based on this limited data, it has been found that RGNT is a slow growing tumor involving primarily fourth ventricular region and occurring predominantly in young adults with mean age of about 31.9 years (range: 12–59 years).[4] There is a female preponderance (F:M ratio around 2:1).[5] No familial association has been described. However, a case of RGNT in a neurofibromatosis Type 1 patient has been reported, but no genetic link was identified.[6] It has also been described in a patient with dysgenetic trichorhinopharyngeal Type 1 syndrome.[7] Most patients present with chronic headache, ataxia and like other posterior fossa lesions.

Radiologically, RGNT presents as iso- to hypo-intense on T1-weighted and hyperintense on T2-weighted MRI images. Calcification may also be present. The tumor is relatively well circumscribed, with both solid and cystic component. The cysts may be single or multiple. Variable degrees of contrast enhancement may also be seen.[4] Secondary hydrocephalus may also be found. Satellite lesions have been detected in a small number of patients. The frequency of this feature may be underestimated due to a lack of optimal radiological work-up of reported cases.[8]

On pathological examination, grossly these tumors have been described to be soft, gelatinous, and generally well demarcated, and sometimes minor to moderate infiltration has been observed. Microscopic examination shows two distinct components. The neurocytic component consists of a uniform population of neurocytes forming neurocytic rosettes and/or perivascular pseudorosettes. Neurocytes are seen to radiate around central neuropil cores and are dispersed in a loose, mucoid, often microcystic manner. Second component is the glial component with spindle and piloid cells resembling pilocytic astrocytoma. Rosenthal fibers and granular bodies are rare. Thrombosis of vessels and evidence of endothelial proliferation have been described in some cases.[9] Significant cytologic atypia and mitotic activity are lacking. On immunostaining, synaptophysin labels the neuropil matrix of the neurocytic rosettes and the astrocytic component is labeled by GFAP and S-100. Although coexpression of neuronal and glial markers in the neurocytic component of RGNT has recently been described.[10] MIB-1 proliferation index is typically low (ranging from 0.35% to 3.07%).[2] Although RGNTs are benign tumors with the possibility of surgical cure and favorable prognosis, their location can complicate surgical removal and imparts a significant risk of neurologic injury. RGNT treated by surgical resection only without radiotherapy.

Differential diagnosis of RGNT includes pilocytic astrocytoma, DNT, oligodendroglioma, and central neurocytoma. Cases where neurocytic components are inconspicuous or not biopsied, RGNT may be incorrectly diagnosed as pilocytic astrocytoma. Pilocytic astrocytoma can be differentiated from RGNT by the absence of rosettes or perivascular pseudorosettes. DNT is typically a supratentorial tumor that presents in younger age group. Oligodendrogliomas with neurocytic differentiation may show neurocyte or even well-formed rosettes but occur in older age, generally, arise in frontal lobe, and include oligodendroglial components. Neurocytoma consists of small round cells forming rosettes can be differentiated from RGNT by the absence of astrocytic components.

The histogenesis of RGNT is still unclear. RGNTs have been postulated to arise from pluripotent cells of the subependymal plate (periventricular germinal matrix) which have also been suggested as the site of origin of DNTs of the cerebellum.[21011] Whether this finding reflects normal or aberrant developmental placement of precursor or stem cells is not known. As increasing numbers of RGNTs have been recognized in locations other than the fourth ventricle the alternate possibility of histologically similar tumors with underlying genetic differences cannot be excluded. Recent papers have described the molecular genetic features of RGNT. Although it may resemble pilocytic astrocytoma no BRAF alteration, fusion, as well as mutation, have been demonstrated.[12]

CONCLUSION

RGNT of the fourth ventricle should be considered in the differential diagnosis of a posterior fossa tumor, especially in relation to fourth ventricle and vermis in a young adult and has to be differentiated from other lesions for its indolent course and favourable prognosis. Surgical procedures should be carefully performed to avoid serious surgical morbidities associated with lesion invading vital structures such as cerebellum and brain stem. Further long-term follow-up and histological analysis of this rare lesion are warranted.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.