A peculiar histopathological form of dysembryoplastic neuroepithelial tumor with separated pilocytic astrocytoma and rosette‐forming glioneuronal tumor components

Dysembryoplastic neuroepithelial tumors (DNTs) mostly display typical clinical, neuroimaging and histopathological features, but sometimes they reveal heterogeneous or non‐specific morphology, which results in diagnostic dilemmas. We present a case of a young adult with longstanding, intractable epilepsy associated with a multinodular cystic lesion in the temporal lobe. The lesion consisted of morphologically different components. In particular, a few cortical nodules displayed a specific glioneuronal element with floating neurons typically found in DNT. Two large, well‐circumscribed nodules were entirely composed of biphasic, piloid, astroglial patterns that corresponded strictly to a pilocytic astrocytoma. The well‐defined areas, which contained numerous distinct neurocytic‐like rosettes, were identical with rosette‐forming glioneuronal tumors (RGNTs). This type of neurocytic rosette was widespread within the surrounding piloid background. Some solid nodules exhibited increased cellularity, oligodendroglioma‐like elements and a focal ribbon cell arrangement. The lesion was associated with advanced reactive gliosis and foci of dysplastic changes in the adjacent cortex. The clinico‐radiological and main histopathological features were consistent with a diagnosis of a complex variant of DNT composed of pilocytic and rosette‐forming glioneuronal components. Although both piloid tissue and rosette‐like formations have been occasionally mentioned in DNT lesions, the present case of DNT was unique in its well‐circumscribed, separate pilocytic and RGNT nodules. We concluded that it represented an unusual, mixed pilocytic/RGNT variant of DNT.     

Intractable epilepsy due to a rosette‐forming glioneuronal tumor with a dysembryoplastic neuroepithelial background

A rosette‐forming glioneuronal tumor (RGNT) was initially reported as an infratentorial tumor that comprised both small neurocytic rosettes and astrocytic components. However, a few studies have reported supratentorial RGNTs arising in the cerebral hemispheres. Here, we report an unusual case involving a 9‐year‐old boy with a supratentorial RGNT who presented with intractable epilepsy and behavioral changes. Brain MRI revealed a well‐circumscribed space‐occupying lesion with septae in the right inferomedial parietal lobe. Electroencephalography showed multifocal spikes over the right frontal, temporal and parietal regions. The seizure frequency decreased dramatically after tumorectomy. Histopathological examination revealed prominent neurocytic rosette formation appearing with the specific glioneuronal element of a dysembryoplastic neuroepithelial tumor (DNT). Although the pathogenesis has not been elucidated, a supratentorial RGNT presenting with epilepsy may exhibit a rosette component, which is the major feature of this tumor, against the background of a specific glioneuronal element mimicking DNT. However, RGNT arising in regions other than the fourth ventricle is rare, and the pathogenesis of epilepsy due to RGNT has not been fully elucidated. Further clinical and histological studies are required to understand the pathology underlying epilepsy caused by RGNT.     

SLC44A1–PRKCA fusion in papillary and rosette-forming glioneuronal tumors

We investigated the fused protein of solute carrier family 44 choline transporter member 1 (SLC44A1) and protein kinase C alpha (PRKCA) in three patients with papillary glioneuronal tumors (PGNT). PGNT and rosette-forming glioneuronal tumors (RGNT) are recently identified, unusual glioneuronal tumor variants which were categorized as novel tumor entities in the 2007 World Health Organization classification system. The molecular background of these tumors remains poorly understood due to the paucity of studies. The SLC44A1–PRKCA fusion was recently detected in three cases of PGNT. We invesitgated for the SLC44A1–PRKCA fusion protein in the three PGNT patients and a further two with RGNT using fluorescence in situ hybridization. Two out of the three PGNT patients had a fused signal (paired red–green signal) representing a rearrangement on chromosomes 9 and 17. A normal signal pattern was observed in the third PGNT patient. Neither of the two RGNT patients demonstrated a fused signal. This suggests that the SLC44A1–PRKCA fusion is a characteristic alteration in PGNT but not RGNT. Therefore, it is a potential biomarker of PGNT. The paired red–green signal that was observed in the PGNT patients implies the presence of a different breakpoint than that previously reported in the 9q31 and 17q24 genes.     

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.     

Papillary glioneuronal tumor

Papillary glioneuronal tumor (PGNT) is a rare, recently recognized tumor type histologically characterized by pseudopapillary architecture associated with compact areas composed of neuronal elements in different maturation states. The histogenesis of this tumor type is still unclear. The immunophenotype of PGNT comprises expression of several glial and neuronal proteins. Recently, immunohistochemical expression of Olig2 in a fraction of tumor cells has been reported, suggesting an additional oligodendroglial or at least oligodendroglia‐like tumor cell component. We report a further case of papillary glioneuronal tumor in a 12‐year‐old boy with immunohistochemical expression of PDGFRα, Olig2 and Nestin in support of a postulated origin of this tumor type from common progenitor cells in the subependymal plate. Nevertheless, further studies are needed to clarify the histogenesis of PGNT.     

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

Neurological Sciences - Rosette-forming glioneuronal tumor (RGNT) is a rare variety of slow growing mixed glioneuronal tumor involving primarily fourth ventricular region. This is a comprehensive...     

Papillary glioneuronal tumor radiologically mimicking a cavernous hemangioma with hemorrhagic onset

Papillary glioneuronal tumor is a recently identified low‐grade brain neoplasm classified as variant of ganglioglioma. Its salient morphological characteristics are the presence of pseudopapillary structures composed of blood vessels, often hyalinized, lined by uniform small astrocytes and a proliferation of neurocytic cells, eventually admixed with ganglioid and ganglion cells. We present a case of papillary glioneuronal tumor occurring in a 15‐year‐old female with an unusual hemorrhagic onset. The clinical, morphological and immunohistochemical features are discussed and the published literature is reviewed. This article proposes that papillary glioneuronal tumor should be included in the differential diagnosis of patients with tumoral related brain hemorrhage.     

The ‘rosette‐forming glioneuronal tumor’ of the fourth ventricle

Tumors containing both neuronal and glial components are a rare heterogeneous group with unique features that require further subclassification. The rosette‐forming glioneuronal tumor of the fourth ventricle is one of a number of recently described glioneuronal tumors, which has been accorded official WHO nosologic status only in 2007. We describe the clinical and pathologic features of two patients with rare rosette‐forming glioneuronal tumors of the fourth ventricle, one of which was associated with dysgenetic tricho‐rhinopharyngeal type I syndrome.     

Papillary glioneuronal tumor: A clinicopathological and immunohistochemical study of two cases

Papillary glioneuronal tumor (PGNT) has recently been identified as a new variant of mixed neuronal‐glial tumors. We report the clinical and pathological features of PGNT in two Chinese patients. One patient was a 35‐year‐old man who suffered from intractable seizures for 16 years. Another was a 26‐year‐old woman who presented with headache for 2 years. In both patients, magnetic resonance imaging showed well demarcated, mixed cystic and solid tumor in the temporal lobe. Histology of the excised tumors revealed a pseudopapillary architecture surrounded by a glial component and intervening areas were occupied by neuronally differentiated cells. No cortical dysplasia was found in the neighboring cortex in one of them. The glial component showed immunoreactivity with glial fibrillary acidic protein and S‐100 protein. Neuronally differentiated cells were immunolabeled by antisynaptophysin, NF, NeuN and MAP2 antibodies. Some small cells surrounding the surface of the pseudopapillae and in the compact area were immunopositive for Olig2. The MIB‐1 labeling index was <3%. The tumor did not recur within the follow‐up periods of 50 months and 13 months, and the patient with temporal lobe epilepsy became seizure‐free after surgery.     

Dysembryoplastic neuroepithelial tumor

Dysembryoplastic neuroepithelial tumor (DNT) is a mixed neuronal-glial tumor associated with a history of partial complex seizures. This uncommon lesion must be disting-uished from other infiltrating gliomas with similar histo-logical features. DNT frequently affects the temporal and frontal lobes of adolescents and young adults. On neuroimaging, the tumor is well demarcated and located in the superficial layers of the cortex. The presence of intracortical nodules is a positive sign indicating DNT. DNT can be divided into complex and simple forms. Complex forms comprise specific glioneuronal elements, glial nodules and/or cortical dysplasia while the simple forms may be composed of glioneuronal elements only. Glioneuronal elements consist of oligodendroglial-like cells which often exhibit alveolar and microcystic patterns. In addition, mature neurons of varying size may be present within the mucinous matrix. Surgical resection is usually sufficient for the treatment of DNT. The heterogeneous histology of DNT supports the hypothesis that it is derived from cells in the subpial granular layer.     

Rosette-forming glioneuronal tumor of the fourth ventricle with neurocytoma component

Rosette-forming glioneuronal tumor (RGNT) was first published in 2002 and was described as a benign and indolent tumor. It was also included in the 2007 World Health Organization (WHO) classification of tumors as a grade 1 tumor for its benign clinical behavior and the possibility of surgical cure. Pathologically, RGNT is a mixed neuronal–glial tumor which consists of two distinct histological components—one with uniform neurocytes forming rosettes and/or perivascular pseudorosettes and the other being astrocytic in nature resembling pilocytic astrocytoma (biphasic pattern). We present the clinical course and pathological findings of two distinctively different cases. The first one was a 4-year-old girl with head trauma and a tumor which was incidentally found by CT. Pathology revealed that the tumor contained neurocytoma components and areas of relatively high proliferative ability with the first report of the presence of midsized bright elliptic cells. The other case was a 19-year-old girl whose imaging studies showed hydrocephalus and a brain stem tumor. She underwent endoscopic third ventriculostomy and biopsy, followed by observation. An MRI taken 6 months later showed progression of the tumor and she subsequently had the tumor excised. We are considering the possibility for our RGNT cases to correspond to a higher WHO grade as they have shown rapid progression, contrary to the already established, and their character, origin, differential diagnosis, and treatment plans have been discussed.     

A case of recurrent epilepsy‐associated rosette‐forming glioneuronal tumor with anaplastic transformation in the absence of therapy

Rosette‐forming glioneuronal tumor (RGNT) most commonly occurs adjacent to the fourth ventricle and therefore rarely presents with epilepsy. Recent reports describe RGNT occurrence in other anatomical locations with considerable morphologic and genetic overlap with the epilepsy‐associated dysembryoplastic neuroepithelial tumor (DNET). Examples of RGNT or DNET with anaplastic change are rare, and typically occur in the setting of radiation treatment. We present the case of a 5‐year‐old girl with seizures, who underwent near total resection of a cystic temporal lobe lesion. Pathology showed morphologic and immunohistochemical features of RGNT, albeit with focally overlapping DNET‐like patterns. Resections of residual or recurrent tumor were performed 1 year and 5 years after the initial resection, but no adjuvant radiation or chemotherapy was given. Ten years after the initial resection, surveillance imaging identified new and enhancing nodules, leading to another gross total resection. This specimen showed areas similar to the original tumor, but also high‐grade foci with oligodendroglial morphology, increased cellularity, palisading necrosis, microvascular proliferation, and up to 13 mitotic figures per 10 high power fields. Ancillary studies the status by sequencing showed wild‐type of the isocitrate dehydrogenase 1 (IDH1), IDH2, and human histone 3.3 (H3F3A) genes, and BRAF studies were negative for mutation or rearrangement. Fluorescence in situ hybridization (FISH) showed codeletion of 1p and 19q limited to the high‐grade regions. By immunohistochemistry there was loss of nuclear alpha‐thalassemia mental retardation syndrome, X‐linked (ATRX) expression only in the high‐grade region. Next‐generation sequencing showed an fibroblast growth factor receptor receptor 1 (FGFR1) kinase domain internal tandem duplication in three resection specimens. ATRX mutation in the high‐grade tumor was confirmed by sequencing which showed a frameshift mutation (p.R1427fs), while the apparent 1p/19q‐codeletion by FISH was due to loss of chromosome arm 1p and only partial loss of 19q. Exceptional features of this case include the temporal lobe location, 1p/19q loss by FISH without true whole‐arm codeletion, and anaplastic transformation associated with ATRX mutation without radiation or chemotherapy.     

Spinal glioneuronal tumor with neuropil‐like islands and meningeal dissemination: histopathological and radiological study of a pediatric case

Cerebral and spinal location of glioneuronal tumors have been recently described as a novel type of primary CNS neoplasia. A distinctive rare form of glioneuronal tumors with neuropil‐like islands (GTNI) have been reported to occur in the adult cerebrum, whereas spinal GTNI localization is extremely rare. In the present report we describe a case of a 15‐month‐old child with a spinal GTNI of the cervical region and meningeal dissemination. Histologically the tumor was composed of round, small neurocytic‐like cells arranged around eosinophilic neuropil cores and embedded in a diffuse fibrillar glial component forming prominent “rosetted” neuropil islands displaying strong immunoreactivity for neuronal markers. Cerebral GTNI shows abundant glial components not rarely exhibiting anaplastic features that justify their inclusion within the group of diffuse astrocytomas. In contrast, including our case, spinal GTNI do not show histological evidence of anaplastic features and exhibits a significant neuronal component that may imply considering these lesions in a separate group. Nevertheless, due to their exceptional rarity, the natural history of these lesions is not yet fully understood, but spinal GTNI seems to have an unfavorable clinical course despite their benign histopathological features, which must be taken into account for appropriate treatment and follow‐up of the patient.     

Cytogenetic study of glioneuronal tumor with neuropil‐like islands: A case report

Glioneuronal tumor with neuropil‐like islands (GTNI) is a recently recognized glioneuronal neoplasm but it was classified as an astrocytic tumor by the World Health Organization (WHO) in 2007. We performed a cytogenetic study in a case of GTNI arising in a 55‐year‐old man and analyzed its genetic alteration. It presented as a heterogeneously enhancing, multi‐lobulating solid mass on MRI. Histopathologically, the tumor showed the biphasic feature of the predominating micronodular neuropil‐like islands and the diffusely infiltrating glial component. In addition, the prominent blood vessels with perivascular hyalinization were observed. On cytogenetic study, loss of 4q, 5q, 11p and gain of 6p, 7, 8, 11q, 12p, 15q were found. The remaining tumor after subtotal resection progressed 7 months later, despite combined chemo‐ and radiotherapy. From the results, it seems that GTNI does not share pathologic or genetic features with conventional astrocytoma, suggesting a unique entity with aggressive behavior.     

Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle: Case report and review of literature

Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle has been identified as a novel and distinctive type of primary central nervous system neoplasm. In this report, we present a case with RGNT arising from the right cerebellar hemisphere. A 30-year-old female patient complained of headache for a five-year duration. Preoperative MRI revealed a well-circumscribed, cystic-solid lesion with hypo-intensity on T1-weighted image, hyper-intensity on T2-weighted image, and significant dot-like enhancement after IV contrast. Gross total resection was achieved in this case via suboccipital retro-sigmoidal approach, and RGNT was confirmed in the final histopathological diagnosis. RGNT of the fourth ventricle is a rare, benign tumor with an excellent prognosis. Operation is recommended as the prior protocol of treatment, and the follow-up MRI is necessary to evaluate the long-term prognostic effects. Currently, only one case of progression or recurrence has been reported in the postoperative course.     

Papillary glioneuronal tumor with a high proliferative component and minigemistocytes in a child

Papillary glioneuronal tumor (PGNT) is a rare type of primary brain tumor. Although PGNT has traditionally been defined as a clinically indolent neoplasm, several cases with high proliferative activity and tumor recurrence have recently been reported. We report a case of PGNT in a 12‐year‐old boy who presented with epilepsy and harbored a 64 mm cystic tumor with a high proliferative component in the right temporal lobe. ¹¹C‐methionine positron emission tomography (PET) showed high uptake in the solid mass. Gross total resection of the tumor mass was achieved and the patient became seizure‐free without any neurological deficits. Histologically, the tumor contained two distinct areas of a vasocentric papilliform structure and a desmoplastic component. Minigemistocytic cells and small necrotic regions were observed adjacent to the pseudopapillae. Immunohistochemical analyses revealed both glial and neuronal differentiation. The Ki‐67 proliferation index was high (14%) in the area corresponding to the high uptake region in the ¹¹C‐methionine PET. No tumor recurrence was observed 20 months after surgery. High proliferative PGNTs are rare and to our knowledge this is only the third pediatric case of PGNT with atypical features reported in the literature. Hence, we here review the reported cases of PGNT and discuss the clinical, radiological and histological features of this malignancy.