The rosette-forming glioneuronal tumor mimicked cerebral cysticercosis: a case report

The rosette-forming glioneuronal tumor (RGNT) was first described by Komori et al. in 2002. As it was initially thought as dysembryoplastic neuroepithelial tumor (DNT) of the cerebellum [1]. In 2007, it was classified as grade I glioma by World Health Organization (WHO). RGNT occurs most often in young women with mean age of onset at 23.57 years [2]. There are few literatures regarding the imaging features and prognosis of RGNT. For most of the literatures on RGNT are case reports. RGNT is most commonly located in the fourth ventricle; however, recent reports demonstrated that RGNT can also occur at sites outside its usual locations. The lesions are mostly comprised of cystic-solid or solid, and the solid components present heterogenous enhancement. Here, we describe a rare case of a 22-year-old woman with RGNT in bilateral cerebellar hemisphere, brain stem, and left thalamus who was misdiagnosed as cerebral cysticercosis before biopsy.

A 22-year-old woman presented with a history of transient dizziness, nausea, and vomiting. No neurological deficits were apparent; however, on further evaluation, initially with computed tomography (CT) scan, revealed multiple cystic hypo-dense mass lesions in bilateral cerebellar hemisphere, brain stem, and left thalamus with unclear boundary (Fig. 1a–c). Magnetic resonance imaging (MRI) confirmed these lesions presented as hyper-intense in axial T2-weighted images and hypo-intense in axial T1-weighted images (Fig. 1d, e). The solid components were visible in some of the lesions in axial T2-weighted images (Fig. 1d). In addition, axial T2 FLAIR revealed iso-hyperintense (Fig. 1f). Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) showed no restricted diffusion (Fig. 1g, h). After contrast, one of the tumors showed mild peripheral enhancement, while others presented no enhancement (Fig. 1i), and small nodule-like higher signals in T2-weighted images were present (Fig. 1d). While, on perfusion-weighted imaging, the lesions were hypo-perfused (Fig. 1j, k).

Based on the above radiological findings, the woman was initially diagnosed with cerebral cysticercosis most possibly. Naturally, primary tumors of the central nervous system and metastatic tumors were differential diagnoses. Subsequently, she was admitted to the infectious diseases department to conduct empirical anti-infective therapy in addition to a follow-up post 2 weeks of MRI examination. Over the course of 2 weeks, she underwent further laboratory examinations, including serologies (specifically enzyme-linked immunotransfer blots (EITBs)); however, the results were negative. Meanwhile, eosinophilic cells and lymphocytes were neither found in cerebrospinal fluid (CSF). Other parasite antibodies were not discovered either. Most importantly, there were no significant changes in the MRI findings after 15 days (Fig. 1m–o). Finally, to determine an ultimate diagnosis, she underwent a biopsy of the right cerebellar hemisphere lesions in which the histopathological results confirmed a WHO grade I RGNT ultimately. Microscopically, the tumors showed that small round nuclear tumor cells were distributed in a network and arranged into a chrysanthemum-shaped cluster surrounding the nerve with single permutation. Synaptophysin immunopositivity in the pericapillary area of a perivascular pseudorosette was shown, along with scattered neurons in the focal areas were also visible. In addition, glial fibrillary acidic protein (GFAP) in the astrocytic component of the tumor was diffuse distribution. (Fig. 2a–e).

RGNT is an unusual disease, and it is considered an independent entity of glioma, which is categorized as grade I by World Health Organization (WHO) due to its characteristics of containing both neural and glial components [3]. It is generally considered to be benign, but there have been reports that some can be invasive [4]. The disease was initially thought to only occur in the fourth ventricle, and the typical imaging characteristics are mid-line lesions which appeared in the fourth ventricle and extended to adjacent structures [5]. On MRI, RGNT typical imaging findings are relatively well circumscribed, with both solid and cystic components with T1-hypo-intense and T2-hyper-intense located in or around the fourth ventricle. Gadolinium-based contrast enhancement could show variable or no enhancement, but with increasing reports of the disease, other positions have also been reported, including the pineal region, pons, thalamus, spinal cord, optic chiasm, cerebellar hemisphere, optic pathway, lateral ventricle, septum pellucidum, cerebellar vermis, and even temporal lobe [6‐9].

With regards to the English literature through a comprehensive search of Web of Science and PubMed using the search term “the rosette-forming glioneuronal tumor” nearly a decade, more than 100 articles have been published to date. After full text screening, excluding articles that were less relevant to the characteristics of RGNTs, nearly 70 articles were included by December 2020 finally. In general, 101 cases of RGNTs were reported located in the fourth ventricle, while 51 cases were located in atypical site. However, the imaging manifestations of RGNTs occurring outside the fourth ventricle are not specific; so, they are often misdiagnosed. Here, the characteristics of RGNTs located outside the fourth ventricle in 51 published cases were listed (Table 1). The lesions can be solid-cystic, cystic, or simple solid, and generally, the former is the most common. The average age of these published cases is 38 years old. Hemorrhage is rare in RGNTs, and only six cases presented positive for bleeding. Management of RGNTs has been accordant with the literatures. Surgery remains the primary treatment option, with gross total resection (GTR) recommended and subtotal resection (STR) as alternatives. The prognosis of RGNT is generally good, and recurrence is uncommon with a total of 4 cases recrudesced of the 51 cases. However, two patients died of these presented cases. Most of the tumors were single lesions with only 10 cases showed multiple lesions.

In summary, the misdiagnosis in the above case reflects how RGNT is under-emphasized and poorly researched. Thus, based on the analysis of the present case and limited data available from review of literature, we propose that the following two aspects may have contributed significantly in misdiagnosing RGNT. Firstly, the case we highlighted occurred in the brain parenchyma, while more than 69.7% of previously reported RGNTs involve the fourth ventricle [3]. And multiple lesions involving the bilateral cerebellar hemisphere, brain stem, and left thalamus at the same time are rarely reported. Secondly, the imaging findings of this case overlapped with cerebral cysticercosis. As we all know, cerebral cysticercosis is the most common parasitic disease of the central nervous system (CNS). The imaging manifestations of the parenchymal active phase are multiple cystic lesions. The enhancement is not obvious and the hypo-perfusion on perfusion imaging. For the above reasons, the tumors were misdiagnosed as cerebral cysticercosis deservedly.

Admittedly, there are distinct radiological signs which highlight uncertainties regarding the previous diagnosis: most notably include tiny spot-like hypo-intense in bilateral cerebellar hemisphere on the susceptibility weighted imaging (SWI) (Fig. 1l). After excluding tiny calcifications on CT (Fig. 1c), it can be assumed that there is minor hemorrhage within the lesions. Hemorrhage is almost invisible in cerebral cysticercosis, although there were also few reports of hemorrhages in RGNT. Two possible reasons may account for the latter. One being that the SWI sequence is rarely a routine sequence, and minor hemorrhages in many reported cases may go undetected because they are difficult to show on other sequences in MRI. On the other hand, it is generally assumed that RGNT is a benign tumor, microvascular proliferation is rare; therefore, the hemorrhages are infrequent as well. The evidence between microvascular endothelial proliferation and hemorrhages has been documented in RGNT [10, 11]. L. Gao et al. reported several cases of RGNTs with intratumoral hemorrhage in 2017. They summarized that intratumoral hemorrhage was one of the additional indications to the diagnosis of RGNT. Other indications included “green bell pepper sign,” CSF dissemination, and multiple satellite lesions. Medhi et al. also summed up that hemorrhage and CSF dissemination may be the characteristics of RGNT through the summary of 7 cases [12]. In our case, intratumoral hemorrhage and multiple satellite lesions are consistent with their conclusions. Therefore, the above signs may aid in diagnosing RGNTs. However, whether this microvascular proliferation and intratumoral hemorrhage are related to prognosis needs further research.

RGNT is an uncommon low-grade neuroglial tumor which is generally considered benign with slightly longer course [2]. Headache is the most recorded common symptom. Histopathologically, RGNT consists of two components: a neurocytic component that forms rosettes, and an astrocytic component that resembles a pilocytic astrocytoma [13]. Through the case we reported, we have discovered that RGNT can be multiple cystic lesions, and the brain parenchyma can be the major affected areas. The intratumoral hemorrhage shown by SWI sequence may have some significance for our diagnosis of it. In conclusion, RGNT often presents significant diagnostic dilemma, and hence, further knowledge of this tumor is essential as they are relatively slow growing and exhibit benign histological characteristics.