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Skull base neurocytoma: case report and review of the literature of extraventricular neurocytomas.

We report a rare skull base neurocytoma. A 44-year-old female with a history of focal seizure and progressive right-sided weakness sought treatment at an outside institution, where she underwent total resection of a "left medial sphenoid wing paraganglioma" in 1984. In 1995 after experiencing intense left-sided headaches for 3 weeks, the patient presented to our institution. Magnetic resonance imaging revealed a large local recurrence. She had deficits dating to her initial surgery, including moderate right-sided hemiparesis, complete left ophthalmoplegia, and left facial numbness.The patient underwent a craniotomy with extensive removal of the involved sphenoid bone and a subtotal resection of the tumor. Neurocytoma was diagnosed based on strong immunohistochemical staining for synaptophysin and no reactivity for glial fibrillary acidic protein. Postoperatively, her headaches resolved completely and her neurologic status remained at baseline. The residual tumor was treated with radiation therapy. After 5 years, she remains clinically and radiographically stable.Although typically located adjacent to the foramen of Monro, neurocytomas have now been reported in almost every subcompartment of the craniospinal axis. Finding neurocytomas in extraventricular locations may require revisiting the current theory that subependymal progenitor cells are the cells of origin for these tumors.

Case Reports↗

The biochemical analysis of neurotransmitters in central neurocytomas.

Central neurocytomas are rare benign intraventricular tumours composed of small round synaptophysin-positive cells, suggesting a neuronal origin of these tumour cells. Although past electron microscopic studies demonstrated synaptic vesicles in the synapse of central neurocytomas, the kinds of neurotransmitters in central neurocytomas have never been identified. In this study we analyzed neurotransmitters in an attempt to clarify the tumorigenesis of central neurocytomas. We studied frozen central neurocytoma specimens from four patients. The tissue levels of glutamate and GABA (gamma-aminobutyric acid) in the tumours were determined by gas chromatography-mass spectrometry (GC-MS) using a selected ion monitoring method. The tissue levels of acetylcholine, choline, catecholamines and metabolites of catecholamines in the tumours were measured by high-performance liquid chromatography combined with electrochemical detection. Choline was found in extremely high concentration in all central neurocytomas when compared with levels in controls. In one central neurocytoma, GABA was found in extremely high concentration compared with controls. In all central neurocytomas, glutamate was found in lower or identical concentrations compared with controls. In all central neurocytomas and controls, dopamine and catecholamine concentrations were extremely low. These results indicated that the histogenesis of central neurocytomas begins with the subependymal stem cells, which have the potential to differentiate into cholinergic or GABA neurons.

Adult↗

Value of postoperative stereotactic radiosurgery and conventional radiotherapy for incompletely resected typical neurocytomas.

BACKGROUND: Two groups of central neurocytomas have been identified: typical and atypical neurocytomas. The more benign typical neurocytomas have a better prognosis. Complete resection of typical neurocytomas results in significantly better outcome than incomplete resection. The current study investigated whether the outcome after incomplete resection can be improved by postoperative stereotactic radiosurgery (SRS) or by conventional radiotherapy. METHODS: The data of all neurocytoma patients reported since 1997, when the first neurocytoma patient treated with SRS was described, were reviewed. Patients who underwent complete resection or those with atypical neurocytoma were excluded from the analysis. Three different therapies were compared for overall survival (OS) and local control (LC): incomplete resection alone (ITR), ITR followed by conventional radiotherapy (ITR+cRT), and ITR followed by stereotactic radiosurgery (ITR+SRS). RESULTS: Data were complete in 121 patients (59 ITR, 41 ITR+cRT, and 21 ITR+SRS). The 5-year-LC after ITR was 51%. LC was significantly better after ITR+cRT (87%, P = 0.001) and after ITR+SRS (100%, P = 0.004). The difference between ITR+cRT and ITR+SRS was not significant (P = 0.45). The 5-year-OS was 93% after ITR, 100% after ITR+cRT, and 100% after ITR+SRS. The differences between the various groups were not significant. The P-values were 0.13 for ITR versus ITR+cRT, 0.29 for ITR versus ITR+SRS, and 1.0 for ITR+cRT versus ITR+SRS. CONCLUSIONS: After ITR of typical neurocytomas, LC is significantly improved by both conventional radiotherapy and SRS. The results of both radiation treatments were similar. SRS is a reasonable alternative to conventional radiotherapy in selected patients.

Adolescent↗

Central neurocytomas. Critical evaluation of a small-cell neuronal tumor.

We report herein the clinical and pathological features of 20 patients with central neurocytomas. Investigations for various differentiation antigens and cell type-specific markers were performed by immunohistochemistry using paraffin-embedded tissue. In addition, the expression of L1 adhesion molecule and of the various N.CAM (neural cell adhesion molecule) isoforms were investigated by immunoblotting studies in two frozen specimens. Central neurocytomas are clinically characterized by their intraventricular localization, occurrence in young adults, and good prognosis. It rarely occurs in patients over 50, but such cases have a poor prognosis. Total surgical excision is the best treatment. Radiotherapy is appropriate if surgery is incomplete or contraindicated. Histologically, central neurocytomas display the following features: an oligo-like pattern, usually associated with large fibrillary rosettes or perivascular arrangement, and a rich endocrine-type vasculature. Central neurocytomas have a remarkably homogeneous antigenic profile. GFAP expression is only found in scattered reactive astrocytes, S100 protein in reactive astrocytes and rare tumor cells. Among the pan-neuroendocrine markers, central neurocytomas always express neuron-specific enolase; they frequently express synaptophysin but never chromogranin A. Synaptophysin is the most reliable immunohistological marker for central neurocytomas; however, immunoreactivity could be lost with long formalin fixation. In these cases, electron microscopy is used to support the neuronal nature of the tumor cells. The expression of L1 adhesion molecule and the isoform 180 of N.CAM, indicates that central neurocytomas are formed by cells committed to neuronal phenotype. Nevertheless, advanced neuronal differentiation may be absent, as suggested by the persistence of embryonic N.CAM, the nonexpression of neurofilament proteins, and the absence of mature synapses in numerous cases. Central neurocytomas and neuroblastomas share some biochemical properties, but their respective clinicopathological features and biological behavior are dramatically different.

Adolescent↗

Blood flow and metabolism of central neurocytoma: a positron emission tomography study.

BACKGROUND: New World Health Organization classifications have categorized central neurocytomas as neuronal tumors. The differential diagnosis between central neurocytomas and other tumors is important for selection of the optimal therapy modality for the management of intraventricular tumors. To characterize the pathophysiology and proliferating activity of central neurocytoma accurately, cerebral blood flow and metabolism in five patients with central neurocytoma were studied using positron emission tomography (PET). METHODS: Tracers used for the present study included C15O2, C15O, 15O2, and 18F-fluorodeoxyglucose (FDG). Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), cerebral metabolic rate of oxygen (rCMRO2), and cerebral metabolic rate of glucose (rCMRGl) were quantitatively analyzed in tumor lesions and the contralateral gray matter. Four patients with central neurocytoma underwent a complete PET study, including all circulatory and metabolic parameters; one patient was studied with 11C-methyl-L-methionine and FDG tracers. RESULTS: Tumor rCBF and rCBV were higher than comparable values in the contralateral gray matter in three of four patients. This high level of perfusion corresponds to angiographic findings that show intense tumor staining in tumors fed by perforated arteries. Tumor rOEF and rCMRO2 were significantly lower than corresponding values in the gray matter (rOEF, P < 0.01; rCMRO2, P < 0.05 by Student's t test). Tumor rCMRGl ranged from 2.68 to 6.26 mg/100 ml/minutes and did not exceed contralateral gray matter values in any of the five patients. Tumor rCMRGl was significantly lower (P < 0.02) than the gray matter rCMRGl. One tumor exhibited a relatively high value of rCMRGl (comparable to gray matter rCMRGl), and increased in size 4 months after partial resection. No other tumors appeared during postoperative follow-up periods that ranged from 4 to 135 months. CONCLUSIONS: Circulation and metabolism parameters measured by PET offer insight into the biologic characteristics of central neurocytoma. Tumor rCMRGl may be an indicator of the proliferating activity in central neurocytoma.

Adult↗

Is 50 Gy sufficient to achieve long-term local control after incomplete resection of typical neurocytomas?

BACKGROUND AND PURPOSE: Central neurocytomas are generally described as rare benign central nervous system tumors. They can be divided in two groups, typical and atypical neurocytomas. Typical neurocytomas are associated with better outcome. This study investigates whether a decrease in radiation dose from 54 Gy to 50 Gy for incompletely resected typical neurocytomas would jeopardize the outcome. PATIENTS AND METHODS: The data of all reported neurocytoma patients were reviewed. Tumors with an atypical histology or an MIB-1 labeling index > 3% were defined as atypical neurocytomas and excluded from this analysis. If the reported data were incomplete, the authors were contacted for additional relevant data. Two groups were created based on an EQD2 (equivalent dose in 2-Gy fractions) of < or = 50 Gy or > 50 Gy and compared for overall survival and local control. Additionally, the patients who received an EQD2 < 50 Gy were compared to those patients receiving an EQD2 = 50 Gy. RESULTS: The data were complete in 94 patients. The 10-year survival was 100% after < or = 50 Gy (n = 34) and 93% after > 50 Gy (n = 60; p = 0.51). The 10-year local control rates were 83% and 88%, respectively (p = 0.69). At 10 years, overall survival was 100% both after < 50 Gy and after 50 Gy (p = 1.0), local control was 71% and 90%, respectively (p = 0.029). CONCLUSION: After incomplete resection of typical neurocytomas, radiotherapy with 50 Gy (2-Gy fractions) appears sufficient, as it resulted in similar local control as doses > 50 Gy and insignificantly better local control than doses < 50 Gy.

Adolescent↗

Forskolin promotes astroglial differentiation of human central neurocytoma cells.

Human central neurocytoma is a kind of the brain tumors that are usually found in anterior part of the lateral ventricles. In this study, we established conditions that allowed proliferation of neurocytoma cells culture and analyzed characteristics of neurocytoma cells in vitro. For in vitro, a condition that used for culturing neural stem cells and contained basic fibroblast growth factor (bFGF) provided high proliferation. RT-PCR analaysis showed that nestin was found in neurocytoma cells, indicating that the neurocytomas possess neural stem cell properties. Interestingly, treatment of neurocytoma cells with forskolin increased expression of glial fibrillary acidic protein with a concomitant decrease in the nestin expression. Forskolin also induced morphological changes of neurocytoma cells to adopt an astrocyte-like phenotype. The results suggest that neurocyotma cells may have properties of multipotent neural stem cells.

Animals↗

Genetic differences between neurocytoma and dysembryoplastic neuroepithelial tumor and oligodendroglial tumors.

OBJECT: Because of their histological similarities, it is occasionally difficult to differentiate neurocytoma and dysembryoplastic neuroepithelial tumor (DNT) from oligodendroglial tumors. This study was conducted to investigate genetic differences among these tumor types in terms of loss of heterozygosity on chromosomes 1p and 19q, and p53 gene mutation. METHODS: A total of 24 tumors were analyzed, consisting of eight central neurocytomas, three DNTs, seven oligodendrogliomas, four oligoastrocytomas, and two undetermined extraventricular tumors with neurocytoma features (ETNFs). Allelic loss was determined using microsatellite markers that cover the common deletions on chromosomes 1p and 19q in oligodendrogliomas. A p53 gene mutation was identified using polymerase chain reaction-single-strand conformation polymorphism analysis and subsequent direct sequencing. Immunohistochemical studies with synaptophysin and electron microscopy investigations were also conducted. Allelic loss on 1p and 19q was detected in six oligodendrogliomas (86%) and in three oligoastrocytomas (75%), but in none of the central neurocytomas or DNTs. A p53 missense mutation was detected at codon 161 (GCC-->ACC, Ala-->Thr) in only one oligoastrocytoma without allelic loss. Synaptophysin was expressed in all central neurocytomas and DNTs, in three oligodendrogliomas (43%), and in three oligoastrocytomas (75%). Of the ETNFs, one demonstrated synaptophysin expression and neural ultrastructures but lacked genetic alterations, whereas the other showed allelic loss on 1p and 19q but was negative immunohistochemically and ultrastructurally. The former was diagnosed as a potential intraparenchymal neurocytoma and the latter as an oligodendroglioma. CONCLUSIONS: Despite histological similarities, central neurocytomas and DNTs are genetically distinct from oligodendroglial tumors. Examination for allelic loss on 1p and 19q and for p53 mutation can be useful for making this distinction.

Adolescent↗

Histogenesis and differentiation potential of central neurocytomas.

The central neurocytoma, a recently identified rare supratentorial brain tumor in young adults, is characterized by intraventricular location and a usually benign clinical course. In order to elucidate the histogenesis and differentiation potential of this neoplasm, we have undertaken an immunocytochemical and molecular biological study of four central neurocytomas. It was found by immunocytochemistry and immunoblotting that all tumors express neuron-specific enolase and synaptophysin. Western blots also revealed expression of the synaptic vesicle protein, synapsin I, neurofilament protein and glial fibrillary acidic protein in several neurocytomas which failed to exhibit immunoreactivity to these marker antigens on paraffin sections. Immunocytochemical reactions with antibodies to synaptophysin and glial fibrillary acidic protein on adjacent sections demonstrated coexpression in individual tumor cells. The neuronal form of the pp60src protein-tyrosine kinase, an oncogene-product specifically expressed in central nervous system neurons, was not detectable in two central neurocytomas investigated. N-myc, a proto-oncogene frequently amplified in childhood neuroblastomas, was present as a single copy gene in all central neurocytomas, indicating that amplification of this gene is not involved in the pathogenesis of the central neurocytoma. In accordance with ultrastructural evidence of synaptogenesis, we conclude that the central neurocytoma is a neuroectodermal tumor with consistent commitment for neuronal differentiation. Since these tumors retain a potential for additional glial differentiation, we propose an origin from bipotential progenitor cells in the periventricular matrix, which in the mammalian brain persists throughout adult life.

Adult↗

Neurocytoma: a comprehensive review.

Central neurocytomas (CN) are uncommon tumors of the central nervous system, most descriptions of which available in the literature are in the form of isolated case reports and small series. Owing to this rare incidence, diagnosis and management of this neoplasm remain controversial. Usually, these tumors affect lateral ventricles of young adults and display characteristic neuroimaging and histomorphologic findings. Neurocytomas often mimic oligodendrogliomas when confirmation of diagnosis rests on immunohistochemistry, ultrastructure, and genetic studies. Extraventricular neurocytomas, situated entirely within the brain parenchyma and spinal cord, have also been reported. Typically, CN are associated with a favorable outcome although cases with more aggressive clinical course with recurrences are not unknown. MIB-1 labeling index (LI) of >2% often heralds poor prognosis and tumour recurrence. Safe maximal resection is presently considered the ideal therapeutic option, with best long-term prognosis in terms of local control and survival. The role of adjuvant radiotherapy apparently seems to benefit patients with incomplete resection and in atypical neurocytoma. Utility of other therapeutic regimen, however, remains shrouded in controversy. Epidemiology, histogenesis, clinical profile, histology, neuroimaging and therapeutic modalities of neurocytomas have been comprehensively reviewed, with special emphasis on CN and extraventricular neurocytomas and their atypical counterparts.

Age Factors↗

Oligodendroglioma with neurocytic differentiation versus atypical extraventricular neurocytoma: a case report of unusual pathologic findings of a spinal cord tumor.

Differentiating oligodendroglioma from extraventricular neurocytoma by conventional light microscopy alone can present a diagnostic challenge. We report pathologic findings of an unusual spinal cord tumor from a 33-year-old male patient which showed hybrid features of oligodendroglioma and extraventricular neurocytoma. Magnetic resonance imaging (MRI) showed an enhancing intramedullary mass in the cervicothoracic region (C7 through T6). Histologic examination revealed a clear cell neoplasm containing ganglion-like cells and calcifications, prompting the differential diagnosis of oligodendroglioma and extraventricular neurocytoma. The immunohistochemical analysis disclosed neural differentiation of the neoplastic cells with strong synaptophysin and neurofilament staining consistent with extraventricular neurocytoma, as well as strong S-100 and glial fibrillary acidic protein (GFAP) expression. Molecular studies with fluorescent in situ hybridization (FISH) revealed chromosome 1p/(partial) 19q deletions, a finding commonly observed in oligodendroglioma. The proliferation index (using antibody MIB1) of the tumor was approximately 30%. The morphologic findings and these results strengthen the hypothesis that these tumors may share a common progenitor cell, which has also been observed by others. Because there are differences in patient management and long-term prognosis, it is important to attempt to distinguish between oligodendroglioma and neurocytoma. This unusual case and similar rare reported cases support the need to reclassify tumors showing pathologic features common to both neurocytoma and oligodendroglioma as a unique entity, while the effort continues to identify the cell of origin.

Adult↗

Management of neurocytomas: case report and review of the literature.

The purpose of this report is to review the available literature on the presentation, pathology, and treatment of central nervous system (CNS) neurocytomas. A case report of an extraventricular neurocytoma is presented along with a comprehensive literature search of patients with a diagnosis of CNS neurocytoma. CNS neurocytomas are rare neoplasms, with fewer than 240 cases reported in the literature. The majority of neurocytomas are found in the ventricular system of the brain. Immunohistochemistry is frequently used to help distinguish this tumor from other CNS neoplasms. MIB-1 proliferation index is commonly used in an attempt to predict biologic behavior. Little is known about the management of patients with this tumor, because most reports are from the pathologic literature and contain sparse information regarding clinical management. Neurocytomas are rare CNS tumors with varied biologic behavior. MIB-1 index may help direct adjuvant therapy. An excellent prognosis can be expected if a gross total resection is achieved. Postoperative radiation therapy (RT) may be considered after subtotal resection. Otherwise, RT is an option for medically inoperable or recurrent disease.

Aged↗

Detection of chromosomal imbalances in central neurocytomas by using comparative genomic hybridization.

OBJECT: Central neurocytomas are rare neuronal tumors commonly found in the intraventricular regions. Little is known about the tumorigenesis of these neoplasms. The aim of this study was to provide an overview of genetic imbalances in central neurocytomas. METHODS: In this study, comparative genomic hybridization was used to identify DNA sequence copy number changes (losses and gains) in a series of 10 central neurocytomas. Tumor DNA and normal reference DNA were differentially labeled and allowed to cohybridize to normal metaphase chromosomes. After hybridization and fluorescent staining of the bound DNA, regions of gain or of loss of DNA sequences were detected as changes in the tumor/normal fluorescence intensity ratio along the target metaphase chromosomes. A gain of DNA sequence was detected in chromosomes 2p, 10q, and 18q. A protooncogene, Bcl2, which maps to 18q21, was evaluated by immunohistochemical analysis to determine its role in the formation of central neurocytomas. CONCLUSIONS: In this study the authors identified recurrent genetic changes on chromosomes 2p, 10q, and 18q in central neurocytomas and highlighted chromosomal regions for additional mapping and cloning of candidate genes that are important in the development of central neurocytomas.

Adolescent↗

Histopathological variants of central neurocytoma: Report of 10 cases.

Central neurocytoma is a rare neuronal tumor affecting young adults and usually located in the lateral ventricles. Post-operative prognosis is generally good. Histologically, central neurocytoma is composed of isomorphous small round or ovoid cells alternating with irregularly shaped patches of fibrillary matrix similar to the neuropile. In a series of 10 cases, two central neurocytomas were histologically "atypical" at first examination. One was intra-ventricular, and the second had an intra-parenchymatous juxta-ventricular location. Both were highly cellular with mitotic activity, and tumor necrosis was seen in one. Neuronal differentiation was assessed by synaptophysin immunoreactivity in all 10 cases and by ultrastructural examination in four, including the two "atypical" forms. Neuronal differentiation was less marked in these "atypical" forms, one also presenting focal GFAP immunoreactivity. The proliferative potential was determined by MIB-1 labeling index and compared with clinical outcome. The eight classical central neurocytomas had a MIB-1 labeling index < 2.3%, whereas the two "atypical" forms had a MIB-1 labeling index > 5.2% and both recurred. We think that there is a spectrum of small-cell neuronal tumors. The two extremes could be the central neurocytoma and the primary cerebral neuroblastoma, while the intermediate forms might be qualified as "atypical neurocytoma". In our series, the histological and immunohistochemical criteria of biological aggressiveness appeared to be high mitotic activity, tumor necrosis, loss of neuronal differentiation and high MIB-1 labelling index.

Adult↗

Central neurocytomas express photoreceptor differentiation.

BACKGROUND: Central neurocytomas are composed of mature neuronal elements, frequently arranged in rosettes similar to those present in pineocytomas. This suggests the possibility of similar patterns of differentiation, including photoreceptor differentiation. The authors analyzed the immunoreactivity of central neurocytomas for retinal S-antigen, neuronal, glial, and neuroendocrine markers. METHODS: Thirty-three central neurocytomas were analyzed with reference to their clinicopathologic characteristics, immunoreactivity, and the possibility that anaplastic histologic features correlated with aggressive clinical behavior. RESULTS: There were 18 male and 15 female patients. The median age at diagnosis was 30 years (range, 3-69 years). All of the tumors with specified location were related to the ventricles. Thirty-two tumors were diagnosed at surgery and 1 at autopsy. Histologic features included mineralization (20 of 33), foci of necrosis (4 of 33), chronic inflammation (4 of 33), ganglion cell differentiation (1 of 33), and lipomatous differentiation (1 of 33). None of the lesions had significant nuclear pleomorphism, mitotic activity, or vascular endothelial proliferation. Immunohistochemistry included expression of synaptophysin (33 of 33), neuron specific enolase (31 of 33), S-100 protein (25 of 33), retinal S-antigen (14 of 24), somatostatin (8 of 27), glial fibrillary acidic protein (4 of 33), neurofilament protein (3 of 22), and leucine enkephalin (1 of 27). At follow-up, 15 of 23 patients were alive an average of 8.1 years (range, 0.91-35.9 years) after surgery. CONCLUSIONS: Central neurocytomas behave as slowly growing neoplasms that remain confined within one or several supratentorial ventricles and are associated with long survival after surgical excision. Malignant forms with aggressive clinical behavior were not found. The neoplastic cells can express photoreceptor differentiation possibly relating central neurocytomas to pineocytomas. Adipocyte differentiation may be present, and the possibility of a relation between the central neurocytoma and cerebellar liponeurocytoma should be entertained.

Adolescent↗

Extraventricular neurocytoma presenting with intratumoral hemorrhage.

A case of extraventricular neurocytoma with spontaneous intratumoral hemorrhage is reported. A 47-year-old man presented with sudden left-sided hemiparesis. Magnetic resonance imaging revealed a right parietal subcortical mass with intratumoral hemorrhagic transformation and without contact to the ventricular system. After complete microsurgical removal, the tumor was histologically diagnosed as neurocytoma. Usually, the term "central neurocytoma" is restricted to neurocytic neoplasms arising within the cerebral ventricles. In the majority of the cases, these slow-growing, generally circumscribed lesions become symptomatic by obstructive hydrocephalus. Hemorrhagic onset is sporadically reported in the literature. In contrast to central neurocytomas, neurocytic lesions located within the brain parenchyma, so-called "extraventricular neurocytomas" are very uncommon. To the knowledge of the authors, this is the first case of an extraventricular neurocytoma with histological classic features presenting with intratumoral hemorrhage in adults.

Biomarkers, Tumor↗

Patterns of differentiation in central neurocytoma. An immunohistochemical study of eleven biopsies.

Central neurocytoma has been characterised by its intraventricular localisation, predominant occurrence in young adults, oligodendroglioma-like histology, benign course and ultrastructural evidence for neuronal differentiation. Eleven intraventricular central neurocytomas were studied histopathologically, employing cell type-specific immunocytochemical markers and electron microscopic analysis. In the past, these lesions have caused diagnostic problems since central neurocytomas share basic histopathological features with other periventricular neoplasms. Accordingly, several tumours of this series had previously been classified as ependymomas of the foramen of Monro or oligodendrogliomas. Although generally regarded as benign lesions, two central neurocytomas of this series showed histopathological evidence of anaplasia, with focal necrosis, mitotic activity and vascular proliferation. All central neurocytomas exhibited immunoreactivity for neuron-specific enolase and synaptophysin, indicating consistent neuronal differentiation. Three tumours were studied by electron microscopy and contained synaptic vesicles, neuritic processes and neurosecretory granules. In addition, one tumour contained ganglioid cells and this was associated with focal immunoreactivity for neurofilament protein, suggesting that some central neurocytomas may, at least focally, continue to differentiate towards the formation of mature neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Tissue culture of human neurocytomas induces the expression of glial fibrilary acidic protein.

Cell cultures were established from three human neurocytoma specimens (primary and recurrent). The phenotypic evolution was analyzed by immunocytology in different culture conditions in the presence and absence of serum including the addition of epidermal growth factor, rat caudate extract, retinoic acid, and N-acetyl cystein. The cells were grown on glass cover slides or an extracellular matrix (ECM) from bovine corneal endothelial cells. Immunostainings were performed after overnight incubation and were repeated after 5 and 10 days of culture. The cultures were compared to an oligoastrocytoma also arising at the foramen of Monro and an ependymoma of the frontal lateral ventricle, two tumors supposedly originating from the same tissue matrix as the neurocytoma. After overnight incubation, 90% of the neurocytoma cells were positive for A2B5 and synaptophysin. GFAP reactivity appeared in the periphery of cell processes in less than 1% of the cells. The staining patterns and morphology were nearly identical under the different culture conditions. After 5 days, almost all cells were strongly positive for GFAP, while the number of cells remaining positive for synaptophysin and A2B5 was unchanged from the earlier time point. Again, there were no fundamental differences between the incubation conditions. At this point, cultures maintained on ECM were compared to their counterparts on untreated glass cover slides with identical staining results, although many fewer cells had attached. An identical immuno-reactive pattern was found on day 10. In contrast to the neurocytoma cultures, there was an immediate strong GFAP signal in both the mixed glioma and the ependymoma. A2B5 was also positive, but synaptophysin was absent. Because the neurocytoma specimens were synaptophysin positive but GFAP negative by immunohistochemistry, it is concluded that neurocytomas may represent a human neuronoglial precursor tumor that switches its phenotype in culture to astroglial differentiation despite very diverse culture conditions.

Adult↗