Mixed Neuronal-glial Tumor Research Articles

FET PET provides adjunctive value to FDG PET in distinction of spinal cord tumors

ObjectiveThis study aimed to compare the diagnostic efficacy of O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) PET and 2-deoxy-2-[18F]fluoro-d-deoxyglucose (18F-FDG) PET for spinal cord lesions. Materials and methodsPaired preoperative 18F-FDG PET/MRI and 18F-FET PET/MRI scans were conducted on patients with suspected spinal cord tumors. Clinical manifestations and PET performance, including SUVmean, SUVmax, TBRmean, TBRmax, metabolic tumor volume (MTV), and total lesion metabolism (TLM), and tumor volume, were compared using group analysis and receiver operating characteristic (ROC) curves. ResultsThirty-five patients were categorized into three groups based on their pathological diagnosis: high-grade tumors (HGTs, n = 6), low-grade tumors (LGTs, n = 19), and non-tumor diseases (NTDs, n = 10). The background SUVmean of 18F-FET PET was significantly lower than that of 18F-FDG PET (p < 0.0001), while the delineated tumor volumes showed no significant difference (p > 0.05). The mass SUVmean, SUVmax, MTV, and TLM values of both 18F-FDG PET and 18F-FET PET were statistically different between HGTs and LGTs (p < 0.05). Similarly, the mass SUVmax, TBRmax, MTV, and TLM values of both 18F-FDG PET and 18F-FET PET, as well as the mass SUVmean of 18F-FET PET, exhibited statistical differences between HGTs and NTDs (p < 0.05). But none were able to distinguish LGTs and NTDs (p > 0.05). Notably, 18F-FET PET provided valuable supporting diagnostic evidence in 1 case of mixed neuronal-glial tumor (MNGT) and 2 cases of intramedullary inflammatory lesions. Optimal cut-off values of all measured parameters for distinguishing tumors and NTDs were determined through ROC analysis. Conclusion18F-FET PET presented comparable diagnostic performance to 18F-FDG PET in differentiating HGTs, LGTs, and NTDs, but exhibited particular utility in MNGT and inflammatory lesions.

Dysembryoplastic Neuroepithelial Tumor (Dnet) in a Young Female: A Rare Case Presentation

Dysembryoplastic neuroepithelial tumor (DNET) is a recently described, morphologically unique, and surgically curable low grade brain tumor which is included in the WHO CNS classification as neuronal and mixed neuronal glial tumor. It is usually seen in children and young adults. This entity first described by Damas-Duport in 1998 is usually non-recurring with an excellent prognosis. We present a case of 30 year old female experiencing seizures with well defined space occupying lesion in the frontal region of brain. Contrast enhanced Magnetic Resonance Imaging was done which revealed well defined multilobulated solid cystic mass lesion in cortical/ subcortical region of left frontal lobe. Histological features suggested dysembryoplastic neuroepithelial tumor which was subsequently confirmed on immunohistochemistry by GFAP and S-100 positivity. The principal differential diagnosis is oligodendrogliomas and gangliogliomas. Patient did not receive any adjuvant therapy post operatively and showed no signs of residual disease or recurrence on magnetic resonance imaging during follow up. Patient is on phenytoin for prophylaxis of seizures.

Desmoplastic Infantile Astrocytoma in a 47-day Old Male Infant with Four-year Follow-up: A Rare Case Report and Literature Review

Desmoplastic infantile astrocytoma/ganglioglioma (DIA/DIG) is a rare mixed neuronalglial solid cystic brain tumor found in infantile cerebral hemispheres. The main presentation of the tumor is the rapidly enlarging of the head circumference with hydrocephalus and seizure. DIA is classified as a WHO Grade 1 brain tumor but, due to the rarity of the tumor, few studies are available on tumor survival and prognosis. Herein, we report a 47-day-old male infant diagnosed with DIA and the four-year follow-up.

Predictors of mortality and tumor recurrence in desmoplastic infantile ganglioglioma and astrocytoma-and individual participant data meta-analysis (IPDMA).

Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are classified together as grade I neuronal and mixed neuronal-glial tumor of the central nervous system by the World Health Organization (WHO). These tumors are rare and have not been well characterized in terms of clinical outcomes. We aimed to identify clinical predictors of mortality and tumor recurrence/progression by performing an individual patient data meta-analysis (IPDMA) of the literature. A systematic literature review from 1970 to 2020 was performed, and individualized clinical data for patients diagnosed with DIA/DIG were extracted. Aggregated data were excluded from collection. Outcome measures of interest were mortality and tumor recurrence/progression, as well as time-to-event (TTE) for each of these. Participants without information on these outcome measures were excluded. Cox regression survival analyses were performed to determine predictors of mortality and tumor recurrence / progression. We identified 98 articles and extracted individual patient data from 188 patients. The cohort consisted of 58.9% males with a median age of 7months. The majority (68.1%) were DIGs, while 24.5% were DIAs and 7.5% were non-specific desmoplastic infantile tumors; DIAs presented more commonly in deep locations (p = 0.001), with leptomeningeal metastasis (p = 0.001), and was associated with decreased probability of gross total resection (GTR; p = 0.001). Gender, age, and tumor pathology were not statistically significant predictors of either mortality or tumor recurrence/progression. On multivariate survival analysis, GTR was a predictor of survival (HR = 0.058; p = 0.007) while leptomeningeal metastasis at presentation was a predictor of mortality (HR = 3.27; p = 0.025). Deep tumor location (HR = 2.93; p = 0.001) and chemotherapy administration (HR = 2.02; p = 0.017) were associated with tumor recurrence/progression. Our IPDMA of DIA/DIG cases reported in the literature revealed that GTR was a predictor of survival while leptomeningeal metastasis at presentation was associated with mortality. Deep tumor location and chemotherapy were associated with tumor recurrence / progression.

Magnetic resonance imaging findings of mixed neuronal-glial tumors with pathologic correlation: a review.

Mixed neuronal-glial tumors are rare, and MRI diagnosis of them presents a challenge. In this review, we discuss the MRI findings of ganglioglioma, anaplastic ganglioglioma, desmoplastic infantile ganglioglioma, papillary glioneuronal tumor, rosette-forming glioneuronal tumor, and primary diffuse leptomeningeal glioneuronal tumor with clinicopathologic correlation. There is overlap of imaging features both with each other and some other tumors, which complicates diagnosis. The combination of imaging findings and the age, location, and appropriate clinical picture should allow the radiologist and the clinicians to raise a provisional diagnosis of a mixed neuronal glial tumor, and guide patient management.

Comprehensive genetic characterization of rosette-forming glioneuronal tumors: independent component analysis by tissue microdissection.

A rosette-forming glioneuronal tumor (RGNT) is a rare mixed neuronal-glial tumor characterized by biphasic architecture of glial and neurocytic components. The number of reports of genetic analyses of RGNTs is few. Additionally, the genetic background of the unique biphasic pathological characteristics of such mixed neuronal-glial tumors remains unclear. To clarify the genetic background of RGNTs, we performed separate comprehensive genetic analyses of glial and neurocytic components of five RGNTs, by tissue microdissection. Two missense mutations in FGFR1 in both components of two cases, and one mutation in PIK3CA in both components of one case, were detected. In the latter case with PIK3CA mutation, the additional FGFR1 mutation was detected only in the glial component. Moreover, the loss of chromosome 13q in only the neurocytic component was observed in one other case. Their results suggested that RGNTs, which are tumors harboring two divergent differentiations that arose from a single clone, have a diverse genetic background. Although previous studies have suggested that RGNTs and pilocytic astrocytomas (PAs) represent the same tumor entity, their results confirm that the genetic background of RGNTs is not identical to that of PA.

The clinicopathological characteristics of non-specific variant of dysembryoplastic neuroepithelial tumor

Background Dysembryoplastic neuroepithelial tumor (DNT) is a benign neuronal and mixed neuronal-glial tumor (WHOⅠ) and may present 3 histological subtypes: simple, complex and non-specfic. Non-specific DNT is very difficult to be diagnosed because of the lack of specific glioneuronal element. Herein we describe one case of non-specific DNT in frontal lobe. The radiological and clinicopathological features of this lesion, as well as its diagnosis and differential diagnosis are discussed. Methods The clinical data of one patient with non-specific DNT was presented retrospectively. Gross totally resected mass was routinely paraffin embedded and stained with hematoxylin and eosin. Immunohistochemical staining was used to detect antigen expression. 1p/19q co-deletion was also detected by fluorescence in situ hybridization (FISH) utilizing Vysis dual-color probe. Results A 16-year-old boy presented with recurrent headache and dizziness. He had a history of at least two complex seizures over the previous 3 years. MRI revealed a small, well-demarcated cystic lesion within the cortex of right frontal lobe with hypointense on T 1 WI and hyperintense on T 2 WI. There was no obvious peritumoral edema or enhancement. The tumor was removed totally. The histological sections revealed cystic area with neuroglial nodule attached on the cyst wall. The nodule was mainly composed of oligodendrocytic-like components and scattered neuronal cells. Typical specific glioneuronal element was not seen. Microcolumnar arrangement was found in the adjacent cortex of lesion, which conformed with the histological features of focal cortical dysplasia (FCD) typeⅠ a. Immunohistochemically, the oligodendrocytic-like component was diffusely positive for synaptophysin (Syn) in cytoplasm and oligodendrocytes transcription factor-2 (Olig-2) in nuclei, focally positive for CD34, S-100 protein (S-100) and BRAF V600E in cytoplasm. However, there was no positive signal found for detection of glial fibrillary acidic protein (GFAP) and isocitrate dehydrogenase 1 (IDH1) R132H. Ki-67 labeling index was 2%. FISH showed that there was no 1p/19q co-deletion. Based on clinical presentation and histological findings, a final diagnosis of non-specific variant of DNT, WHO Ⅰ, accompanied by FCD Ⅲ b, was made. Accessory treatment was not given postsurgically. The patient was regularly followed-up for one year. Head MRI was reexamined 3 and 6 months after operation. No recurrence or seizure occurred. Conclusions In clinical practice, non-specific variant of DNT is diagnostic challenging and may be confused with other low-grade gliomas even if there are typical clinical manifestations and radiological appearance of DNT exhibited in lesion. The accurate diagnosis of this tumor is obtained from carefully histological inspection and a panel of immunohistochemical and molecular study for CD34, IDH1 R132H, BRAF V600E and 1p/19q co-deletion. DOI: 10.3969/j.issn.1672-6731.2016.12.008

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

Mixed neuronal-glial tumor in the temporal lobe of an infant: a case report

BackgroundTumors that arise in the temporal lobes of infants and spread to the neural system are limited to several diagnoses. Herein, we present an infantile case of a temporal tumor showing neuronal and glial differentiation.Case presentationThe patient was a 9-month-old boy with low body weight due to intrauterine growth retardation. At 9 months after birth, he presented partial seizures. Computed tomography scanning revealed a mass (35 * 40 mm) in the left temporal lobe. Isointensity was noted on magnetic resonance T1-weighted images and fluid attenuation inversion recovery images. The tumor was heterogeneously enhanced with gadolinium. Positron emission tomography showed high methionine uptake in the tumor. During surgery, the tumor, which was elastic and soft and bled easily, was gross totally resected. A moderately clear boundary was noted between the tumor and normal brain parenchyma. Histologically, the tumor mainly comprised a ganglioglioma-like portion and short spindle cells at different densities. The former was immunohistochemically positive for some kinds of neuronal markers including synaptophysin. The spindle cells were positive for glial fibrillary acidic protein, but desmoplasia was not observed.DiscussionThe tumor contained both neuronal and glial elements; the former were the main constituents of the tumor and included several ganglion-like cells. Because neuronal elements gradually transited to glial cells, a mixed neuronal-glial tumor was diagnosed.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2045126100982604

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.

Bilateral non-contiguous atypical papillary glioneuronal tumor: case report

Papillary glioneuronal tumor (PGNT) was first described as a distinct clinic-pathological entity by Komori et al. in 1998. Since then it has been included as a mixed neuronal-glial tumor in the revised WHO (2007) classification of central nervous system tumors. On brain imaging, it appears as a demarcated, solid to cystic, contrast-enhancing mass usually located in the temporal lobe. Histologically, it is considered a biphasic tumor characterized by small cuboidal GFAP-positive astrocytes around hyalinised blood vessels and synaptophysin-positive interpapillary collections of neurocytes, large neurons and intermediate-sized "ganglioid cells". Although they are generally regarded as benign WHO Grade I tumors, recent reports have described more pathologically aggressive features. To date, these reports have all been single lesions.

Expression and diagnostic significance of CD34 in brain tumors of patients with refractory epilepsy

To study the immunohistochemical expression and diagnostic significance of CD34 in brain tumors of patients with refractory epilepsy. Immunohistochemical study for CD34 was performed on formalin-fixed paraffin-embedded tissue blocks of 54 cases of brain tumors occurring in patients with refractory epilepsy. The tumor types included ganglioglioma (GG, number = 21), dysembryoplastic neuroepithelial tumor (DNT, number = 8), tumors/lesions which had the transitional features that between glioneuronal hamartia and mixed neuronal-glial tumor (number = 21) and pleomorphic xanthoastrocytoma (PXA, number = 4). Cases of glioblastoma (number = 4) and oligoastrocytoma (number = 5) were used as controls. Twenty of the 21 cases of GG, 1 of the 8 cases of DNT, 16 of the 21 cases of tumors/lesions which had the transitional features and 3 of the 4 cases of PXA showed cytoplasmic and membranous positivity for CD34. The adjoining brain tissues in 9 of the 18 cases of GG, 6 of the 16 cases of tumors/lesions which had the transitional features and 1 of the 3 cases of PXA also expressed CD34. In contrast, only 1 case of glioblastoma showed membranous positivity for CD34. CD34 preferred to staining for GG and PXA. Which represent a valuable tool for distinguishing GG, PXA and DNT, oligoastrocytoma, glioblastoma.

Brain tumors in patients with intractable epilepsy: a clinicopathologic study of 35 cases

To study the clinicopathologic features of brain tumors occurring in patients with medically intractable epilepsy. The clinical, radiologic and pathologic features of brain tumors occurring in 35 patients with intractable epilepsy encountered during the period from January, 2005 to April, 2008 in Xuanwu Hospital were retrospectively reviewed. The mean age of seizure onset and duration of disease were 14.3-year-old and 8.6 years, respectively. Abnormal signals were observed in 94.3% of cases (33/35) by magnetic resonance imaging. The histologic types of brain tumors included ganglioglioma (13/35, WHO grade I and 6/35, WHO grade II), dysembryoplastic neuroepithelial tumor (3/35, WHO grade I), pleomorphic xanthoastrocytoma (3/35, WHO grade II), diffuse astrocytoma (1/35, WHO grade II), oligoastrocytoma (1/35, WHO grade II), angiocentric glioma (1/35, WHO grade I) and meningioangiomatosis (1/35). The 6 remaining cases showed features seen in between glioneuronal hamartoma and mixed neuronal-glial tumor. Most of these tumors were located in the temporal lobe (27/35) and associated with focal cortical dysplasia. Immunohistochemical study showed a remarkable expression of CD34 in gangliogliomas. Brain tumors in patients with medically intractable epilepsy are almost always benign and located in the temporal lobe. Most of them represent mixed neuronal-glial tumors and some show transitional features in-between glioneuronal hamartoma and mixed neuronal-glial neoplasm. The similar morphologic pattern and biological behavior of glioneuronal hamartoma and mixed neuronal-glial tumor may suggest a common pathogenetic mechanism.

Mixed neuronal-glial tumor of the fourth ventricle and successful treatment of postoperative mutism with bromocriptine: case report

Background Tumors composed of both neurocytic and astrocytic cells are uncommon and poorly understood. We describe the clinicopathologic features of a very rare rosette-forming glioneuronal tumor of the fourth ventricle and propose bromocriptine as a useful therapeutic agent for cerebellar mutism after posterior fossa surgery. Case Description A fourth ventricle tumor was incidentally discovered in an 18-year-old woman. Magnetic resonance imaging revealed ventriculomegaly and a solid tumor with low-intensity signals on T1-weighted images and high-intensity signals on T2-weighted images. There was slight gadolinium enhancement. The tumor was subtotally resected. Although its lower half was well circumscribed, its upper half manifested invasive growth. Histologically, 2 components were identified, synaptophysin-positive neurocytic cells forming perivascular pseudorosettes and glial fibrillary acidic protein–positive astrocytic cells with Rosenthal fibers. Overall, cellular atypia was minimal and the MIB-1 labeling index was low. On the basis of these histologic findings, the tumor bore striking similarity to the recently described rosette-forming glioneuronal tumors of the fourth ventricle. Postoperatively, the patient manifested cerebellar mutism. The administration of bromocriptine improved her neurological status dramatically. Conclusion The natural history of rosette-forming glioneuronal tumors of the fourth ventricle is not yet fully understood. Therefore, careful and long-term follow-up monitoring of the tumor hosts is necessary. Bromocriptine therapy may promote recovery from mutism after posterior fossa surgery.

Papillary glioneuronal tumor: a new variant of mixed neuronal-glial neoplasm.

We describe the clinicopathologic features of nine cases of a unique papillary glioneuronal tumor (PGNT) exhibiting astrocytic as well as extensive and varied neuronal differentiation. The four male and five female patients studied ranged in age from 11 to 52 years (mean 27.7 years). They either presented with mild neurologic symptoms or were asymptomatic. Magnetic resonance imaging showed demarcated cystic, 1.5-cm to 7-cm contrast-enhancing masses; five involved the temporal lobe, two the parietal, and two the frontal. All but one were totally resected. No recurrence was noted despite a follow-up period of 3 years. Two microscopic components were evident: 1) compact pseudopapillae composed of hyalinized vessels covered by a single layer of glial fibrillary acid protein (GFAP)-positive astrocytes and 2) synaptophysin-positive neuronal cells of varying size, including neurocytes, ganglioid cells, and ganglion cells within neuropil. Immunostains for chromogranin-A were negative, as was in situ hybridization for chromogranin-A mRNA. Ultrastructurally, neuronal cells featured microtubule-containing processes and aberrant synaptic terminals, but dense core granules were rare. Overall, cellularity was moderate and atypia was minimal. No mitotic activity or necrosis was noted. The proportions of the two components varied, but essential morphologic findings were identical in all cases. In that the clinical, radiographic, and morphologic characteristics of PGNT are distinctive, it appears to represent a previously undescribed form of mixed neuronal-glial tumor of the central nervous system.