Introduction
Rosette-forming glioneuronal tumour (RGNT) of the fourth ventricle is one of the newly described primary tumours of the central nervous system [12]. Komori et al. [18] were the first who described this entity. They explained the characteristics of these tumours in terms of location, distinctive histological appearance with formation of neurocytic component and indolent biologic behaviour in a series of 11 cases report in 2002 [19]. Rosette-forming glioneuronal tumour was confirmed as a new type in the newly updated World Health Organization (WHO) classification of tumours of the central nervous system in 2007 [12]. Previously, these tumours assumed to be only infratentorial and located around fourth ventricle. Different locations of RGNT as chiasma [31], suprasellar region [30] and pineal region [10,13,19,32], septum pellucidum [36], intraventricular dissemination [35] and two spinal cord [5,28] were published later.
Although the histopathological features of these tumours are regarded as distinct and typical, they can show wide spectral clinical symptoms (Table I). We aimed to make a case addition to the limited clinical, radiological and pathological experience of this kind of rare and “poorly” described tumours.
Case report
A 29-year-man was admitted with an acute neurological deterioration and somnolence. His neurological examination was normal except a positive Babinski sign on his right side. In his medical history, there was a diagnosis of an incidental and asymptomatic hydrocephalus that was seen in his cranial computed tomography (CT) following a mild head injury three years before. A cranial CT showed a three ventricular hydrocephalus and a hypodensity around vermis in the posterior fossa (Fig. 1A). A cranial magnetic resonance imaging (MRI) revealed a partly cystic lesion located in vermis. It was hypointense on T1 and hyperintense on T2 weighted images and had no contrast enhancement (Fig. 1B-D). The lesion was hyperintense on flair sequences. The neurological status of the patient improved promptly following an emergent external ventricular drainage insertion. On the following day, the patient underwent an operation and a nearly gross total tumour removal was performed.
The resected tumour specimen was transferred to the pathology department after fixing in a phosphate buffered 4% solution of formalin. Serial sections of 5 µm thick paraffin-embedded tumour tissues were stained with hematoxylin and eosin (HE). Additionally, an immunohistochemical (IHC) staining with monoclonal antibodies against glial fibrillary acidic protein (GFAP) (1 : 75; Neomarkers, Fremont, CA, USA), synaptophysin (1 : 100; Neomarkers) and Ki 67 (1 : 50; Neomarkers) was performed. Immunohistochemical staining was performed using an enhancement method based on a repetitive microwave heating technique using sodium citrate buffer. In microscopic examination, the tumour consisted of two components and it was also well demarcated from cerebellar tissue. The tumour was characterized by glial and neuronal components (Fig. 2A). In the area of the glial component, the cytoplasmic processes formed a compact textured fibrillary background. Some areas resembled pilocytic astrocytoma and oligodendroglioma (Fig. 2D). There were a few Rosenthal fibres and hemosiderin deposits. The neurocytic component consisted of uniform neurocytes which are forming rosettes and pseudorosettes (Fig. 2B-C). Neurocytic tumour cells had ovoid or round nuclei with fine chromatin pattern, inconspicuous nucleoli and delicate cytoplasmic processes. Overall, cellularity was low. Mitosis, atypia, necrosis or vascular proliferations were not seen. In immunohistochemical examination, synaptophysin immunoreactivity was only restricted in the peripapillary area of perivascular pseudorosette and rosette (Fig. 3A). Staining with GFAP antibody was positive in the astrocytic component of the tumour (Fig. 3B). Ki 67 labelling index was very low (1% and below). The tumour was reported to be a rosette-forming glioneuronal tumour of the fourth ventricle.
The postoperative period was unremarkable. He was followed for 32 months without evidence of progressive clinical deterioration.
Discussion
Kuchelmeister et al. [20] reported a dysembryoplastic neuroepithelial tumour (DNT) in cerebellum which morphologically resembled RGNT in 1995. The term rosette-forming glioneuronal tumour was used to define the low-grade tumour of the fourth ventricle by Komori et al. [18] for the first time in 1998. The characteristic features of these tumours were explained as 1) its unique location, 2) neurocytic pseudo-rosette formation and 3) the presence of a pilocytic astrocytoma component. Until the publishing of two cases that were located in chiasma [31] and spinal cord [5], these tumours were believed to be found only in posterior fossa. So, the “unique location” of these tumours seems to need some change. Anan et al. [5] suggested that the lesion might derive from the gray matter or the middle motor nuclei in the spinal cord, so RGNT may not be limited in distribution [5]. Scheithauer et al. [31] reported that periventricular germinal matrix is the likely origin of RGNTs and so, they may be occurring in “ectopic” sites. Rosette-forming glioneuronal tumours may be located in different areas such as the pineal region [9,10] and lateral ventricles [35] and some satellite tumours may also be seen in the patients [6,18,27,33].
Rosette-forming glioneuronal tumour is encountered more frequently in females. Thirty-one of the 56 reported cases in the English literature, including the present case, up to date were seen in women. Patient age was 12-70 years with a mean of 29 years (Table I).
Headache and cerebellar signs as ataxia and nystagmus are the most common initial clinical symptoms. Diplopia, ptosis [13], dysarthria [13,19], blurred vision [19], seizure [19,35], dizziness [25], vertigo [14,34], vomiting [21,34), clumsy walking [21,23] and neck pain and rigidity [2,19] are the other signs and symptoms of this tumour. Lethargy [13], somnolence, loss of conscious [35] and anisocoria [23] due to increased intracranial pressure may also be seen in these patients as in the presented case. However, there are some cases which are diagnosed incidentally [1,19,27], too.
A three ventricular hydrocephalus may be seen in RGNT patients. It can be so serious that a ventriculo-peritoneal shunt [13] or insertion of an external ventricular drainage (EVD) may be required [10,23]. We also performed an EVD in the emergency room for the presented case, because the patient was admitted with an acute neurological deterioration with somnolence. Fortunately, most of these tumours are slowly growing lesions. The development of ventriculomegaly can be chronic and may be clinically compensated [23].
The radiological findings of RGNTs may show some variations. These lesions are relatively circumscribed and heterogeneous, they may have some calcifications and cystic components [4,11,13,21,23,27]. Some smaller tumour nodules may accompany these tumours [19,23,27]. These tumours are usually hypointense on T1 and hyperintense or isointens on T2 weighted MRI sequences [10]. They may have no contrast enhancement as in our case or may have a ring shaped contrast enhancement that led to consideration of malignancy [24,27]. Low density on non-enhanced CT as in the presented case is also typical of these lesions [4]. These tumours may show evidence of previous intratumoral haemorrhage on MRI [21,30].
Rosette-forming glioneuronal tumours have two components of both neurocytic and glial areas, but usually the glial component of the tumour predominates [3]. Rosette-forming glioneuronal tumours are low-grade tumours with no histopathological signs of malignancy [1,27]. They have a low labelling index of Ki-67 antigen, minimal or no cellular atypia and there is no evidence of recurrence, increase in tumour size or metastasis until now [19]. Solis et al. [32] found mutations of isocitrate dehydrogenase 1 (IDH1) and IDH2 that are relatively specific of diffuse gliomas; but Xiong et al. [36] did not detect somatic mutations of IDH1 and IDH2 in their cases. PIK3CA mutations were other mutations reported in RGNT [7]. PIK3CA mutants are seen with high frequencies in glioblastomas and anaplastic oligodendrogliomas.
The recommended treatment modality of these tumours is surgery. As these tumours are accepted low-grade in nature, an aggressive approach can increase surgical morbidity [15]; so, subtotal removal or gross total removal may be chosen. Until now, 4 cases of recurrence have been reported. The recurrence time of the tumours was 10 years in 2 cases [13,19] and 9 and 4 years in the others [7].
The main differential diagnosis of RGNT includes pilocytic astrocytoma (PA), dysembryoplastic neuroepithelial tumour, central neurocytoma, plexus papilloma, oligodendroglioma, ependymoma, primitive neuroectodermal tumour (PNET), glioneuronal tumour with neuropil-like islands (rosette) glioneuronal tumour, papillary glioneuronal tumour and metastasis [3,15,19,29]. Pilocytic astrocytoma is the most difficult tumour type for differential diagnosis with RGNT. Pilocytic astrocytoma has small round cells as well as astrocytic cells but rosette structures like those of RGNT are not found in PA [17,19]. There is also no evidence of neural differentiation in the rounded cells of pilocytic astrocytoma [3]. Dysembryoplastic neuroepithelial tumour has mature neurons in mucinous pools that help for differentiating from RGNT. Rosette-forming glioneuronal tumour does not have “floating neurons” as is the case for the “specific glioneuronal element” of DNT [34]. Central neurocytoma is characterized by uniform round cells and has similar immunohistochemical features of neuronal differentiation as in RGNT, but it does not have biphasic architecture with a distinctly separate glial component and true neurocytic rosette formation [35]. Central neurocytomas have no astrocytic components as RGNTs. Although neurocytes or well-formed rosettes may be found in oligodendrogliomas, oligodendroglial components are not seen in RGNTs [6]. The distribution pattern of synaptophysin and GFAP staining in ependymomas are quite the opposite to that seen in RGNTs [34].
In conclusion, RGNTs are clinically slow-growing tumours and typically occur in the midline. They affect mainly young adults with a slight female predominance. They can be seen outside the posterior fossa as ectopic tumours. They have biphasic cytoarchitecture with two elements; neurocytic rosettes resembling Homer-Wright rosettes and astrocytic component resembling a pilocytic astrocytoma. Glioneuronal tumours are a heterogeneous entity; so, further pathologic and clinical subclassifications may be required for prognostication and treatment. Careful and long-term follow-up monitoring will be wise for these uncommon tumours.
Disclosure
Authors report no conflict of interest.
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