Case Of Rosette-forming Glioneuronal Tumor Research Articles

Rosette-forming glioneuronal tumor of the fourth ventricle

Objective To explore the clinicopathological features of rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle. Methods The clinical manifestations, neuroimaging, histopathological and immunohistochemical features were analysed in one case of RGNT of the fourth ventricle, and related literatures were reviewed. Results A 24-year-old female presented with progressive dizziness under no obvious predisposing causes and dyskinesia such as stumbling. MRI revealed expansion of the fourth ventricle, and a mass with long T 1 WI and T 2 WI signal and clear boundary could be seen within the fourth ventricle. The border of tumor showed slight enhancement. At surgery, it was observed that the solitary tumor arised from the fourth ventricle and appeared well demarcated with rhomboid fossa. The tumor was blocking the aqueduct of sylvius before it was removed. Microscopically, the tumor exhibited both neuronic and astrocytic components. In the neuronic components, neurocytes formed neurocytic rosettes and perivascular pseudorosettes. At the center of the neurocytic rosettes, there was an eosinophilic core and some region consisted of microcysts. While the astrocytic components of the tumor revealed typical pilocytic astrocytoma structure. The center of neuronic rosettes and perivascular pseudorosettes displayed strong positive staining with synaptophysin (Syn) and oligodendrocytes transcription factor-2 (Olig-2). The astrocytic components showed positive immunostaining of glial fibrillary acidic protein (GFAP). There were focal and partial positive immunostaining of neuron-specific enolase (NSE) in both components of the tumor. The Ki-67 labeling index was 1.50%-2.00% in two components. Conclusions Rosette-forming glioneuronal tumor of the fourth ventricle is an unusual neuronal and mixed neuronal-glial tumors. The imaging examination showed solid or mixed solid-cystic mass at the fourth ventricle with well demarcated border. The lesion has two characteristic components and the distinctive immunostaining of GFAP and Syn expression will help the differential diagnosis. DOI: 10.3969/j.issn.1672-6731.2015.11.013

Analysis of a Novel Translocation, T(9;17)(Q31;Q24), in Rosette-Forming Glioneuronal Tumors

ABSTRACT Aim: Papillary glioneuronal tumor (PGNT) and rosette-forming glioneuronal tumor (RGNT) were recently established unusual glioneuronal phenotypes and were categorized as a novel tumor entity in the 2007 World Health Organization classification. The molecular background of these glioneuronal tumors remains poorly understood due to a paucity of reports. Recently, the SLC44A1-PRKCA fusion has been identified in 3 cases of PGNT. Methods: The aim of this study was to confirm it in our 3 cases of PGNT and analyze the presence of specific fusion in 2 cases of RGNT, using fluorescence in situ hybridization. Results: Two out of three PGNT cases showed one adjacent red-green signal pair representing the rearrangement on chromosome 9 and 17, but not a complete fused yellow signal. Normal signal pattern was observed in the other PGNT case. Neither of two RGNT cases revealed adjacent red-green signal pair or yellow signal. Conclusions: The SLC44A1-PRKCA fusion is a characteristic alteration in PGNT but not in RGNT, and is suggested as a potential biomarker of PGNT. One adjacent red-green signal pair observed in the PGNTs may imply the presence of different breakpoints from those previously reported in the 9q31 and 17q24 genes. Disclosure: All authors have declared no conflicts of interest.

Clinicopathological analysis of unusual rosette-forming glioneuronal tumor in brain parenchyma

Background Rosette-forming glioneuronal tumor (RGNT) is a rare and novel brain tumor. It affects mainly young adults and arises in the midline, primarily involving the cerebellum, and the walls or floor of the fourth ventricle. The tumor is composed of distinctive histological components, uniform neurocytes forming rosettes and (or) perivascular pseudorosettes, as well as astrocytic component resembling pilocytic astrocytoma. To our best knowledge, no more than 50 cases of RGNT have been described in the literatures to date and found commonly in association with the ventricular system. Only a few cases have been known to occur at sites outside of its usual location. Herein, we present a rare case of RGNT of brain parenchyma. Due to its rarity and non-specific appearance in radiological examination, it is a diagnostic challenge for radiologists and histopathologists to differentiate RGNT in unusual sites from other intracranial lesions because of its similarities in radiological and histological findings. The aim of this study is to summarize the clinicopathological features of RGNT and discuss the differential diagnosis of histologically similar tumors in brain. Methods The clinical manifestation of a patient with RGNT occurring in left frontal lobe was presented retrospectively. Resected mass was routinely paraffin-embedded and stained with Hematoxylin and Eosin. Dako EnVision immunohistochemical staining system was used to detect the tumor antigen expressions, including glial fibrillary acidic protein (GFAP), S-100 protein (S-100), cytokeratin (CK), neuronal nuclear antigen (NeuN), synaptophysin (Syn), neuron-specific enolase (NSE), chromogranin A (CgA), oligodendrocytes transcription factor-2 (Olig-2), epithelial membrane antigen (EMA) and Ki-67 (MIB-1). Results A 12-year-old girl presented with 2-year history of twitches and mild headache. MRI revealed a solid well-circumscribed lesion in left frontal lobe with mild heterogeneous enhancement. The lesion was observed to locate in brain parenchyma and there was no evidence of tumor infiltrating in ventricular system. Craniotomy was performed and the tumor was removed totally. Histological examination revealed that the tumor was distinctive in its juxtaposition of patterned neurocytic and pilocytic astroglial components. The neurocytic component showed the tumor cells had small, uniform round nuclei with scant cytoplasm and formed narrow perivascular pseudorosettes or Homer-Wright-like rosettes arrays of neurocytic nuclei around delicate eosinophilic neuropil cores. The glial component tended to exhibit pilocytic astrocytoma-like morphology with long, hair-like processes and Rosenthal fibers. Immunohistochemical staining showed that the tumor cells in glial component were diffusely positive for GFAP and S-100, but negative for NeuN, Syn and NSE. However, perivascular pseudorosettes or Homer-Wright-like rosettes were positive for Syn and Olig-2, and negative for GFAP. Ki-67 index was low and less than 1%. Based on clinical presentation and histological findings, a final histological diagnosis of RGNT in brain parenchyma, WHO grade Ⅰ, was made according to the criteria of WHO classification. The patient has not received chemotherapy and attended follow-up for 12 months, without any neurological deficit or signs of recurrence. Conclusions RGNT is a rare tumor and classified as mixed neuronal-glial tumor. RGNT probably derives from a common progenitor cell originated from subependymal plate or brain parenchyma, able to differentiate toward both glial and neuronal phenotype. RGNT in brain parenchyma is also observed to have the similar biological behaviors and histopathological characteristics with its intra-ventricular counterpart. With similarities in histological findings, it may be difficult to differentiate RGNT from extraventricular neurocytoma, dysembry oplastic neuroepithelial tumor (DNT), and ependymoma with neuronal differentiation or neuropil-like islands. The presence of distinct low-grade glial component in the tumor and appropriate immunohistochemical profile are necessary for correct diagnosis. doi: 10.3969/j.issn.1672-6731.2014.03.014

Rosette forming glioneuronal tumor of the fourth ventricle in squash cytology smear

Rosette forming glioneuronal tumor (RGNT) is a recently recognized and extremely rare glioneuronal tumor occurring in the fourth ventricle. It is crucial for the cytopathologist to be aware of this entity as it can be easily mistaken for more common neoplasms occurring at this site. We present here the cytology of such a rare case of RGNT that was misdiagnosed as ependymoma. The varying cytological features of this entity, as well as the common diagnostic difficulties encountered in cytology, are highlighted in this report.

Rosette-forming Glioneuronal Tumors in the Posterior Third Ventricle

Rosette-forming glioneuronal tumor (RGNT) is a rare brain tumor found almost exclusively within the fourth ventricle. These grade I tumors were first included in the World Health Organization (WHO) Classification for the central nervous system in 20071. Since then, approximately 49 cases have been published.There are no reported cases of RGNT within the third ventricle, although this tumor has also been described in the pineal region, the tectum and within the aqueduct. Supratentorial localization is quite rare, with only three published: one was found in the septum pellucidum, another within the optic nerve in neurofibromatosis type 1 (NF1) patient and one in a patient with multiple RGNT in the lateral ventricle. The authors report the first case series in the literature of RGNT occurring within the posterior third ventricle.

Tumor glioneuronal formador de rosetas del cuarto ventrículo. Presentación de un caso y revisión de la literatura

Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a rare tumor that has been recently characterized. RGNT was included as a new glioneuronal tumor in 2007 by the World Health Organization (WHO) in classification of tumors of the central nervous system. Within this group we found 34 documented cases. We present a new case of RGNT of the fourth ventricle with intratumoral posttraumatic bleeding and review the existing literature of this new entity.A 30-year-old patient was admitted after suffering mild traumatic brain injury (TBI) had headache, diplopia and ataxia. Studies of computed tomography and magnetic resonance imaging revealed a tumor at the fourth ventricle with intralesional bleeding and areas of calcification. She was operated performing macroscopically complete tumor resection. Pathologic examination showed a rosette-forming glioneuronal tumor of the fourth ventricle.The RGNT of the fourth ventricle are rare and affect young adults. The evidence shows that the prognosis is usually favorable but there is the possibility of progression and recurrence. Intratumoral hemorrhage is a very unusual presentation that involves risk to the patient's life. Surgical resection should be careful due to the location of these lesions and their extension into critical areas, all patients regardless of extent of resection achieved require a long-term monitoring of the risk of late relapse.

A rare posterior cranial fossa tumor

Among tumors of the central nervous system, tumors of the mixed glioneuronal type form an important recognized subset. Some of the examples for mixed glioneuronal tumors include gangliocytoma, dysembryoplastic neuroepithelial tumor (DNT), ganglioglioma, anaplastic ganglioglioma, and central neurocytoma. The rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a new entity that has only slowly emerged in the literature due to its prior classification with other low-grade mixed glial and neuronal tumors. These tumors are relatively infrequent lesions, and therefore, they can be challenging to diagnose for the practicing pathologist. This is a rare biphasic tumor with clearly defined neurocytic and glial components. The tumor is found exclusively in the posterior fossa, where it arises in the midline, usually occupying a substantial fraction of the fourth ventricle, and it is observed by magnetic resonance imaging (MRI) as a circumscribed, solid mass with heterogeneous contrast enhancement. We describe here a case of RGNT occurring in a 22-year-old male.

Rosette‐forming glioneuronal tumor of the septum pellucidum with extension to the supratentorial ventricles: Rare case with genetic analysis

In the original description, rosette-forming glioneuronal tumors (RGNTs) were restricted to the fourth ventricle and/or posterior fossa. Here, we first report an unusual case of RGNT centered in the septum pellucidum and associated with multiple masses occupying the wall of the bilateral lateral ventricles and the third ventricle. No mass was found in the fourth ventricle. Histological and immunohistochemical examination revealed that the tumor presented biphasic differentiation characterized by predominantly neurocytic rosettes and pilocytic astrocytoma-like components with obvious microvascular proliferation. Chromosome 1p/19q deletions and isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations were not identified. Because this case exhibited a worrisome growth pattern, further studies and long-term follow-up are needed to determine the true nature of these tumors.

Recurrent PIK3CA mutations in rosette-forming glioneuronal tumor

Rosette-forming glioneuronal tumor (RGNT) is a recentlydescribed CNS neoplasm generally involving posteriormidline structures with frequent extension in the fourthventricle [5]. With only one case of postoperative recur-rence reported to date [8], RGNT is considered to havefavorable outcome and the current standard of care issurgical excision without adjuvant therapy. To date, nomolecular alterations have been reported for this tumor.Alterations in the PI3K/AKT pathway are frequent in manycancers [11] and have been reported in CNS tumors [1, 2,6, 7]. Here, we report the identification of frequent PIK3CAmutations in a series of RGNTs reviewed at our institution.We searched our medical record database and identifiedeight cases of RGNT. The mean age at diagnosis was26 years (range 15–50) and the male:female ratio was 1:1.Clinical data was available for seven patients, with amedian follow-up time of 5 years (range 1–13) (Table 1).Two patients had late recurrences despite gross totalresection. The first had a recurrence at 9 years and hasremained stable 1 year after repeat resection. The secondhad a recurrence at 4 years with sacral and intraventriculardissemination and has been stable 2 years after 12 cycles oftemozolomide and cis-retinoic acid. The remaining patientswere recurrence-free at last follow-up.All eight cases showed classic histologic features ofRGNT including rosette-forming oligodendroglia-likecells, localized synaptophysin immunoreactivity withinrosettes, and fibrillary glial background (Fig. 1a, b). Theidentification of two cases with recurrence in a relativelysmall series of patients was unexpected and prompted us totest these tumors for known oncogenic mutations. Archivedformalin-fixed paraffin-embedded tumor tissue, onlyavailable for four of eight cases, was submitted for massspectrometry array mutation profiling (MassARRAY sys-tem, Sequenom, San Diego, CA) with a panel covering 86single nucleotide variant (SNV) hotspots in 14 genes:AKT1 (3), AKT2 (2), AKT3 (2), BRAF (10), EGFR (1),GNAQ (3), GNAS (2), IDH1 (3), IDH2 (3), KRAS (9), MET(11), NRAS (7), PI3KCA (29, in exons 1, 4, 6, 7, 9, 18, and20) and RET (1). Sequenom

Analysis of KIAA1549-BRAF fusion status in a case of rosette-forming glioneuronal tumor of the fourth ventricle (RGNT)

Rosette-forming glioneuronal tumors (RGNT) of the fourth ventricle are rare mixed glio-neuronal tumors included in the revised WHO classification of CNS tumors and show histopathological features similar to pilocytic astrocytomas. To evaluate at molecular level potential affinities between these tumors, we investigated a case of RGNT, arising in the cerebellum of a young patient, for the presence of transcriptional products originating from the KIAA1549-BRAF fusion. However, the analysis did not show any fusion. Further studies in larger RGNT case series are needed in order to demonstrate the possible presence of KIAA1549-BRAF fusion and better delineate its relationship with pilocytic astrocytomas.

Rosette‐forming glioneuronal tumor of the fourth ventricle with advanced microvascular proliferation – a case report

Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a recently described novel type of primary brain tumor that was included into the current WHO classification of CNS tumors. It is a very rare, slowly growing, mixed neoplasm at cerebellar localization with distinctive morphological pattern. We present an unusual case of a 20-year-old patient with RNGT of the fourth ventricle with advanced microvascular proliferation. MRI revealed the solid-cystic tumor mass largely involving the cerebellar vermis and left hemisphere with compression of the fourth ventricle. Microscopically, the tumor showed classical architectural pattern with two distinctive components. The main component consisted of neurocytic rosettes formed by round, isomorphic nuclei arranged around eosinophilic, fibrillar cores with strong synaptophysin expression. The perivascular rosettes with cell arrangement along blood vessels were observed only sporadically. The second neoplastic component consisted of spindle or stellate astroglial cells with piloid process and Rosenthal fibers, strongly resembling pilocytic astrocytoma. Focally, the astroglial cells showed increased cellularity but without marked nuclear atypia. The glial part of the tumor revealed advanced proliferation of microvessels. The vessels of glomeruloid type exhibited multilayered endothelial proliferation and marked mitotic activity. MIB1 labelling index was generally low; however, in areas exhibiting microvascular proliferation its expression was significantly increased up to 20%. This report demonstrates the unique case of RGNT with conspicuous microvascular proliferation of glomeruloid type and extensive endothelial proliferation. As there is still limited clinical experience with RGNT, further studies are necessary to evaluate the biology of this type of tumor.

Rosette forming glioneuronal tumor pineal gland and tectum: An intraoperative diagnosis on smear Preparation

We present an extremely rare case of newly described entity called rosette forming glioneuronal tumor (RGNT), involving the pineal gland, tectum, and the adjacent thalamus in a 22-year-old male. Interestingly, the ventricular system was not involved in this case. The tumor was diagnosed intraoperatively on smear preparation on cytomorphology. If sampled adequately, it is fairly easy to diagnose RGNT on smear preparation as it has a very distinctive cytomorphology of being composed of two population of cell. One of the components is pilocytic astrocytoma and the other is composed of small cells with scant cytoplasm, vesicular nuclei, arranged around neuropil-like material forming "neurocytic rosettes." To the best of our knowledge, this is the first case of RGNT in this rare location being diagnosed intraoperatively on smear preparation.

Rosette-Forming Glioneuronal Tumor of the Fourth Ventricle -Case Report-

Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a rare tumor included as a novel glioneuronal neoplasm in the 2007 World Health Organization classification of brain tumors. A 15-year-old female patient presented with RGNT of the fourth ventricle manifesting as headache persisting for one month. Magnetic resonance imaging disclosed a nonenhanced solid mass in the fourth ventricle and vermis. The tumor was gross totally resected. Histological examination revealed biphasic neurocytic and glial architecture. The neurocytic component consisted of uniform neurocytes forming neurocytic rosettes and perivascular pseudorosettes. Only 31 cases of RGNT have been reported. RGNT of the fourth ventricle should be considered in the differential diagnosis of infratentorial lesions in young adults. The prognosis is benign, but relatively aggressive behaviors such as tumor growth, recurrence, and acute deterioration due to intratumoral hemorrhaging can occur. Surgical resection requires care to prevent major surgical morbidities associated with lesions invading the cerebellum or brainstem.

Rosette-forming glioneuronal tumor of the fourth ventricle: Report of two cases with a differential diagnostic overview

We report on clinicopathological findings in two cases of rosette-forming glioneuronal tumor of the fourth ventricle (RGNT) occurring in females aged 16 years (Case 1) and 30 years (Case 2). Symptoms included vertigo, nausea, cerebellar ataxia, as well as headaches, and had been present for 4-months and 1 week, respectively. Magnetic resonance imaging (MRI) indicated a cerebellar-based tumor of 1.8 cm (Case 1) and 5 cm (Case 2) diameter each, bulging into the fourth ventricle. Case 2 involved a cyst-mural-nodule configuration. In both instances, the solid component appeared isointense on T 1 sequences, hyperintense in the T 2 mode, and enhanced moderately. Gross total resection was achieved via suboccipital craniotomy. However, functional recovery was disappointing in Case 1. On microscopy, both tumors comprised an admixture of low-grade astrocytoma interspersed with circular aggregates of synaptophysin-expressing round cells harboring oligodendrocyte-like nuclei. The astrocytic moiety in Case 1 was nondescript, and overtly pilocytic in Case 2. The architecture of neuronal elements variously consisted of neurocytic rosettes, of pseudorosettes centered on a capillary core, as well as of concentric ribbons along irregular lumina. Gangliocytic maturation, especially “floating neurons”, or a corresponding immunoreactivity for neurofilament protein was absent. Neither of these populations exhibited atypia, mitotic activity, or a significant labeling for MIB-1. Cerebellar parenchyma included in the surgical specimen did not reveal any preexisting malformative anomaly. Despite sharing some overlapping histologic traits with dysembryoplastic neuroepithelial tumor (DNT), the presentation of RGNT with respect to both patient age and location is consistent enough for this lesion to be singled out as an autonomous entity.