Histopathological, molecular, clinical and radiological characterization of rosette-forming glioneuronal tumor in the central nervous system

Abstract

Objective: A rosette-forming glioneuronal tumor (RGNT) is a rare entity originally described in the fourth ventricle. Recently, RGNTs occurring in extraventricular sites and those with malignant behaviors have been reported. The purpose of this study was to analyze the clinicoradiological and histopathological features, therapeutic strategies, and outcomes of RGNTs.

Methods: We enrolled 38 patients diagnosed with RGNTs pathologically between August 2009 and June 2016. CT and MRI, including diffusion-weighted imaging and spectroscopy, were performed. The surgical treatment and histopathological and molecular features were assessed. Additionally, we searched the relevant literatures and performed a pooled analysis of individual patient data. The potential risk factors of prognosis were analyzed.

Results: Our case series included 22 male and 16 female patients, with a mean age of 25.9 years. RGNTs involved the fourth ventricle (26.3%), cerebella (34.2%), supratentorial ventricular system (13.2%), spinal cord (10.5%), temporal lobe (10.5%), thalamus (7.9%), brain stem (7.9%), frontal lobe (5.3%), pineal region (5.3%), suprasellar region (2.6%), and basal ganglia (2.6%). Statistical analyses showed that pediatric age, purely solid appearance of the tumor, and inadequate resection (only partial removal or biopsy) were risk factors associated with progression events. Patients with subtotal resection appeared to do as well as those with gross total resection.

Conclusions: RGNTs can occur nearly anywhere in the CNS, at both supratentorial and infratentorial sites. Maximal safe surgical resection should be emphasized for treatment; whilst aggressive resection with the goal of complete resection may be unnecessary.

Keywords: brain tumor; central nervous system; rosette-forming glioneuronal tumor; spinal cord tumor; treatment.

Figure 1. Rosette-forming glioneuronal tumor in the frontal lobe involving the lateral ventricle and rosette-forming glioneuronal tumor in the spinal cord

(A) CT reveals a hypodense lesion (arrowhead) in the right frontal lobe involving the lateral ventricle, and focal calcification is visible. (B and C) MRI shows a cystic-sold lesion (arrowheads) with hypointensity on axial T1WI (B) and hyperintensity on axial T2WI (C). (D–F) The axial (D), sagittal (E), and coronal (F) contrast T1WI show heterogeneously remarkable enhancement in the solid portion of the tumor. (G and H) The apparent diffusion coefficient (ADC) map (G) and DWI (H) show facilitated diffusion. (I and J) MRS demonstrates an elevated choline value, reduced NAA value, and absence of lactate or lipid peaks. (K–M) MRI of another patient reveals an intramedullary mass (arrows) in the spinal cord, with hypointensity on sagittal T1WI (K), hyperintensity on sagittal (L) and axial (N) T2WI, and heterogeneous enhancement on sagittal contrasted T1WI (M).

Figure 2. Rosette-forming glioneuronal tumor in the pineal region involving the tectum

(A) CT reveals a slight hypodense lesion (arrowhead) in the pineal region involving the tectum, without calcification. (B and C) MRI shows a cystic-sold lesion (arrowheads) with hypointensity on axial T1WI (B) and hyperintensity on axial T2WI (C). (D–F) Axial (D), sagittal (E), and coronal (F) contrast T1WI show no significant enhancement. (G and H) The ADC map (G) and DWI (H) show facilitated diffusion. (I and J) MRS demonstrates an elevated choline value, reduced NAA value, and absence of lactate or lipid peaks.

Figure 3. Rosette-forming glioneuronal tumor in the lateral ventricle and cerebellar rosette-forming glioneuronal tumor with a satellite lesion

(A-F) MRI demonstrates a solid mass (arrowheads) in the lateral ventricle, with hypointensity on axial T1WI (A) and hyperintensity on axial T2WI (B). (C and D) Axial (C) and sagittal (D) contrast T1WI show focal enhancement. (E and F) The ADC map (E) and DWI (F) show facilitated diffusion. (G–J) MRI of another patient reveals a solid mass in the cerebellar vermis (arrowheads) and a satellite lesion in the cerebellar hemisphere (arrows); both of these show hypointensity on axial T1WI (G and H) and hyperintensity on axial T2WI (I and J). (K–N) On axial (K and L) and sagittal (M and N) contrast T1WI, the vermis lesion exhibits rim enhancement (arrowheads) and the satellite lesion shows no enhancement (arrows). (O–R) The ADC map (O and P) and DWI (Q and R) show facilitated diffusion.

Figure 4. Radiological and histopathological profiles of a patient with concomitant rosette-forming glioneuronal tumor and schwannoma

MRI reveals a spinal extramedullary solid mass at the C1 level (arrowheads) and an intramedullary solid mass in the medulla oblongata (arrows). (A–C) The former mass shows isointensity on sagittal T1WI (A), slight hyperintensity on sagittal T2WI (B), and homogeneously remarkable enhancement on sagittal contrast T1WI (C). (E–G) The latter mass shows isointensity on sagittal T1WI (E), remarkable hyperintensity on sagittal T2WI (F), and no enhancement on sagittal contrast T1WI (G). (D and H) Histopathological examinations of these 2 lesions are consistent with schwannoma (D) and RGNT (H), respectively. (Original magnification: D: 100×; H: 200×).

Figure 5. Histopathology and immunohistochemistry of rosette-forming glioneuronal tumors

Microphotographs show characteristic histopathological features of RGNT consisting of biphasic glial and neurocytic architecture (A). The neurocytic component is characterized by a ring of tumor cells with scant cytoplasm and dense nuclei, forming rosettes around eosinophilic neuropil cores (B). The glial component consists of spindle- or stellate-shaped astrocytic cells forming a compact fibrillar meshwork with occasional Rosenthal fibers, resembling pilocytic astrocytoma (C). In focal areas of the glial component, oligodendroglial-like cells with round nuclei and perinuclear clear halos are observed (D). Vacuoles are present around the perivascular pseudorosettes (E). Focal microvascular proliferation is observed (F&G). Synaptophysin staining exhibits strong immunoreactivity within the neuropil-like cores of neurocytic rosettes (H). Staining for GFAP demonstrates strong immunoreactivity in the glial background (I) and in the oligodendroglial-like component (J). Staining for Olig-2 displays positivity in both the neurocytic rosettes (K) and the pilocytic-like glial background (L). NeuN shows focal immunoreactivity in both the neurocytic- and pilocytic-like components (M&N). Ki-67 labeling in both components is low (O&P). Dual-color FISH shows normal disomic status (two red target signals and two green reference signals) of the chromosomes 1p36 (Q) and 19q13 (R). In rare cases, the DNET-like component is present, and it consists of the “specific glioneuronal element” with oligodendroglial-like cells arranged in columns separated by microcystic spaces, floating neurons, and mucoid stroma (S). In one case, concomitant spinal schwannoma is found (T). (Stains: A–G = Hematoxylin-eosin stain; H = Synaptophysin immunohistochemistry; I and J = GFAP immunohistochemistry; K and L = Olig-2 immunohistochemistry; M and N = NeuN immunohistochemistry; O and P = Ki-67 immunohistochemistry; Q and R = Dual-color FISH; S and T = Hematoxylin-eosin stain. Original magnification: A, C, E–G, S, and T: 100×; B, D, and H-P: 200×)

Figure 6. Kaplan–Meier curves

Kaplan–Meier curves of progression-free survival for (A) age, (B) cystic component, (C) MRI contrast enhancement, and (D) extent of resection. p^a: the p-value of Log-rank analysis. p^b: the p-value of Cox proportion hazard multivariate analysis. Log-rank tests showed that age was significantly associated with the tumor progression. Multivariate analysis showed that pediatric age, absence of cystic components and inadequate resection extent were significantly associated with the tumor progression.