Central Neurocytoma Research Articles

Central Neurocytomas: A Comprehensive Review with Special Emphasis on the Role of Gamma Knife Stereotactic Radiosurgery

Central Neurocytomas (CNs) are uncommon tumors of central nervous system, arising from neuronal cells. Mostly these tumors are intraventricular and commonly occurs at the level of the “Foramen of Monro”. However, recently cases of “Extraventricular Neurocytoma” have also been reported. Typically, CNs are associated with favorable outcome. Best long term prognosis, in terms of local control and survival is achieved by maximal safe surgical resection, which is considered as ideal therapeutic option. However, management of recurrent or residual CNs remains controversial. Treatment options for patients with recurrent or residual CNs includes reoperation, radiotherapy or chemotherapy. Use of conventional radiotherapy in recurrent or residual CNs is associated with long term complications in the form of cognitive abnormalities and risk of developing secondary malignancies. Recently, Gamma Knife Radiosurgery is used in patients with recurrent or residual CNs as an alternative treatment option to conventional radiotherapy. Studies have reported that Gamma Knife Radiosurgery provides safe and effective alternative treatment option for recurrent or residual CNs, by eliminating the long term side effects of conventional radiotherapy. However, these are based on results of limited number of studies, with small sample sizes, with no control groups. Randomized control trials or larger studies are required to confirm the effectiveness of Gamma knife Radiosurgery in recurrent or residual CNs. This paper reviews the findings of case series and case reports that contribute to the effectiveness of Gamma knife Radiosurgery in CNs.

Differential Hypermethylation of Death-Associated Protein Kinase Promoter in Central Neurocytoma and Oligodendroglioma

Background. Central neurocytoma and oligodendroglioma are rare tumors of the central nervous system. However, diagnosis between these two types of tumors is challenging due to their many cytological and histological similarities. Death-associated protein kinase (DAPK) is a calcium/calmodulin-regulated serine/threonine protein kinase involved in many apoptosis pathways, and repressed expression of DAPK by promoter hypermethylation has been found in a variety of human cancers. The purpose of this study was to assess DAPK protein expression and promoter hypermethylation in central neurocytoma and oligodendroglioma. Method. Central neurocytoma and oligodendroglioma samples were obtained from age- and sex-matched patients. DAPK protein expression was performed using immunohistochemical assays in formalin-fixed, paraffin-embedded sections. DAPK promoter hypermethylation was carried out using bisulfite-modified genomic DNA in methylation-specific PCR followed by separation in agarose gels. Findings. A statistically significant difference (P = 0.021) in DAPK promoter hypermethylation between central neurocytoma (76.9%) and oligodendroglioma (20%) was observed. High levels of DAPK protein expression were generally found in oligodendroglioma (90%), compared with 38.5% in central neurocytoma (P = 0.054; not statistically significant). There was an inverse correlation between DAPK protein expression and DAPK promoter hypermethylation in the cohort of 23 patients (P = 0.002). Conclusions. The results show that DAPK promoter hypermethylation and repressed expression of DAPK protein were more common in central neurocytoma than in oligodendroglioma. Thus, DAPK promoter hypermethylation could be useful for differential diagnosis between these two types of tumors, whereas DAPK protein expression might be less predictive. The role of DAPK promoter hypermethylation in the pathogenesis of central neurocytoma warrants further study.

Central Neurocytoma and Epidermoid Tumor Occurring as Collision Tumors: A Rare Association

Different brain tumors of distinct histology can co-exist in the setting of phakomatoses or as a complication of radiotherapy. In the absence of these predisposing factors, this phenomenon is uncommon. When the lesions are in close proximity they are described as collision tumors and are extremely rare. A 58-year-old woman presented with persistent headache and cognitive decline for three months. Magnetic resonance imaging revealed a tumor arising from the atrium of the left lateral ventricle with heterogeneous contrast enhancement. This intraventricular lesion was adjacent to another extensive infiltrating tumor of the basal cisterns. Operative findings revealed a vascular ventricular tumor and gross total resection was achieved. An adjacent avascular basal cistern tumor with a pearly white sheen was encountered and partial excision was performed. The histopathological diagnosis was central neurocytoma and epidermoid tumor. There is only one documented description of a central neurocytoma co-existing with a tumor of different pathology. To our knowledge, this is the first reported collision tumor case involving central neurocytoma. Since the incidence of both lesions co-existing juxtaposed is extremely low, a chronic oncogenetic inflammatory process stimulated by the epidermoid tumor to the subventricular region is suggested. Other mechanisms for tumor collision are discussed and we suggest a classification system for this rare association to reflect their pathogenesis.

Operative Management of Intraventricular Central Neurocytomas: An Analysis of a Surgical Experience with 32 Cases.

To better understand the clinical characteristics of central neurocytoma (CN), as well as to assess the optimum therapeutic schedule. This was a retrospective study of 32 patients with CN who visited our department between January 2008 and January 2013. We analyzed the clinical and radiological presentations, tumor characteristics, surgical strategies, and the prognosis. We performed operation guided by combined intraoperative magnetic resonance imaging (iMRI) and neuronavigation in 25 patients. The iMRI detected residual tumor in 9 cases, and further resection was performed in 5 cases. Total and nearly total tumor resection was achieved in 29 cases (91%). There was no significant difference between transcortical and transcallosal approaches in complications. Two cases (6%) with recurrence received respectively repeat salvage surgery and radiosurgery at 46 and 50 months after surgery. Thirty patients (94%) had excellent functional outcome (Karnofsky Performance Score ≥80) and 28 patients (88%) resumed their occupations. Our study demonstrates radical surgery with excellent neurological outcomes is the primary treatment of CN. The techniques of resection guided by combined iMRI and neuronavigation seems to enable a higher complete resection rate and reduce the morbidity rate during surgery. We suggest careful clinical observation after initial surgery, and repeat salvage surgery or radiosurgery for recurrent CN.

Extraventricular neurocytoma, a comprehensive review

Extra ventricular neurocytoms (EVN) are a rare parenchymal brain tumour distinct from central neurocytomas. This review attempts to analyze a series of seven cases of EVN from a single institute against the background of available literature. Retrospective analysis of the clinical manifestation, pathological features, imaging findings, microsurgical treatment effectiveness and progression free survival of seven cases of EVN operated between 2000-2012. The study group included five females and two males in the age group 7-65 years (mean 30.71 yrs). The distribution of the lesion was as follows Lobar 4, Cerebellum 1, Pineal 1, spinal 1. The duration of clinical symptoms ranged from three months to seven years and the presentation was site and size specific. Cystic Changes (71 %), perilesional oedema (57 %) and heterogeneous contrast enhancement (85.7 %), and calcification (42 %) were a few distinct imaging characteristics. Increased perfusion correlated with atypical histology in two patients. Surgical resection remains the main management strategy for longer outcome and patients with STR + RT and GTR had comparable follow-up. Extremes of age and atypical histological features were adverse prognostic factors. EVN are rare tumors with either glial or neuronal differentiation or a potential for atypical changes. Both, GTR and STR combined with RT, offer reasonably good outcome with overall comparable survival. The available literature of EVN is limited, larger series with long term follow-ups are needed to dictate the management protocol. The role of adjuvant therapy is still debatable and needs further validation.

Primary Spinal Neurocytoma Involving the Medulla Oblongata: Two Case Reports and a Literature Review

Central neurocytoma is a rare neuroectodermal tumor found in young adults. These tumors are generally located in the lateral or third ventricles. Extraventricular neurocytoma in the spinal cord is extremely rare. We report on two patients with primary spinal neurocytomas who presented with progressive numbness and weakness in the limbs. Both patients had intramedullary masses between the medulla and the upper thoracic levels. The clinical, radiological, surgical, and pathological features of this abnormality are discussed, and all 20 reported cases were reviewed. In conclusion, neurocytoma should be included in the differential diagnosis of a spinal intramedullary tumor, and subtotal resection is acceptable for a relatively favorable prognosis if gross total removal is unachievable. The efficacy of adjuvant radiochemotherapy to control tumor recurrence is unknown.

Diffusion weighted MR imaging and proton MR spectroscopy findings of central Neurocytoma with Pathological Correlation

Three cases of histopathologically confirmed central neurocytoma (CN) are presented, emphasizing diagnostic imaging issues: conventional magnetic resonance imaging with Proton magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) findings of CN. Patients age ranged from 17 to 32 years, Imaging include a CT scan and MR examination with DWI and proton MRS on a 1.5-T system. DWI and subsequent apparent diffusion coefficient (ADC) were obtained in all. Single voxel MRS was performed prior to surgery using a point resolved spectroscopy sequence (PRESS) with short 35ms and long echotime (TE) 144ms, associated with a two-dimensional chemical Shift Imaging (2D-CSI) with 144ms TE (one case). Histopathological examination included immunostaining with synaptophysin. With the long TE, a variable amount of glycine with markedly increased choline, very small to almost complete loss of N-acetylaspartate and creatine, and inverted triplet of alanine-lactate were observed in all three patients. Increased glutamate and glutamine complex (Glx) was also observed in all with short TE. DWI demonstrated variable low ADC which appeared well correlated with the tumor signal intensity and cell density: the most homogeneous and highly dense cellular tumor with increased nucleus to cytoplasm ratio demonstrated the lower ADC. Histological pattern was typical in two cases and demonstrated an oligodendroglioma-like pattern in one case. Positivity for synaptophysin confirmed the neuronal origin in all. The demonstration within an intraventricular tumor of both glycine and alanine on MRS along with high choline, bulky Glx and restricted diffusion appear diagnostic of CN.

Clinical Course of Central Neurocytoma with Malignant Transformation—An Indication for Craniospinal Irradiation

Central neurocytoma is generally considered to be a benign tumor and the literature suggests that a cure may be attained by surgery ± adjuvant focal irradiation. However, there is a need for change in the therapeutic strategy for the subgroup of patients with aggressive central neurocytoma. An example case is presented and the literature on central neurocytoma cases with malignant features and dissemination via the cerebrospinal fluid is reviewed and the radiotherapeutic strategies available for central neurocytoma treatment is discussed. Nineteen cases including the present report with a malignant course and cerebrospinal fluid dissemination have been described to date, most of them involving an elevated MIB-1 labeling index. Our case exhibited atypical central neurocytoma with an initially elevated MIB-1 labeling index (25-30 %). The primary treatment included surgery and focal radiotherapy. Three years later the disease had disseminated throughout the craniospinal axis. A good tumor response and symptom relief were achieved with repeated radiation and temozolomide chemotherapy. Central neurocytoma with an initially high proliferation activity has a high tendency to spread via the cerebrospinal fluid. The chemo- and radiosensitivity of the tumor suggest a more aggressive adjuvant therapy approach. Cases with a potential for malignant transformation should be identified and treated appropriately, including irradiation of the entire neuroaxis and adjuvant chemotherapy may be considered.

Radiosurgery for central neurocytoma: long-term outcome and failure pattern

Despite the favorable outcomes of radiosurgery for central neurocytoma (CN), these results are based on case series that included a limited number of patients and short follow-up periods because of the scarcity of CN. Because CN is a benign tumor with an indolent clinical course, long-term follow-up and analysis of failure pattern are required for the establishment of the role of radiosurgery in the management of CN. Twenty consecutive patients (10 patients who received Gamma Knife radiosurgery (GKRS) as a primary treatment and 10 patients who received GKRS as a secondary treatment) with a radiological follow-up period ≥36 months were included in this study. The mean radiological follow-up duration was 100 months (range 43-149 months). The mean tumor volume was 10.4 cm(3) (range 0.4-36.4 cm(3)) and the mean marginal dose was 15.4 Gy (range 9-20 Gy). Local control failure was found in six patients at the last radiological follow-up. Overall actuarial local control rates were 89.5 % at 5 years and 83.1 % at 10 years. The primary GKRS group included two cases with local failure, with cyst formation or local recurrence. In contrast, in the secondary GKRS group, local control failure was found in four cases (including three cases with an "out-of-field recurrence" pattern) and occurred earlier compared with the primary GKRS group. Our study suggests that GKRS could be a primary or secondary treatment option for CN. However, long-term radiological follow-up is mandatory. In particular, more careful consideration during margin delineation and planning procedure is required in the secondary GKRS group.

Postoperative Complications of Central Neurocytoma

Six patients with central neurocytoma were retrospectively examined, including diagnosis and treatment process as well as postoperative complications. Clinical follow-ups were performed through telephone calls or outpatient service. Of the 6 patients, a total of 5 patients had 1 or more postoperative complications. The postoperative complications included hydrocephalus, basal ganglia edema, epidural hematoma of the operated region and the remote region, and intracranial infection; 5 patients underwent the cortical fistulization approach and 1 underwent the longitudinal fissure-corpus callosum approach. The neoplasms of 3 patients were totally resected and those of the other 3 patients were subtotally resected. Preoperative accurate diagnosis of central neurocytoma is of great importance for the drawing up of the operation strategy; in addition to magnetic resonance imaging and computed tomography, digital subtraction angiography and magnetic resonance spectroscopy could be helpful for the preoperative diagnosis of central neurocytoma. Subtotal resection of the lesion and the longitudinal fissure-corpus callosum approach may be useful for the reduction of postoperative complications.

Cytologic Features of Central and Extraventricular Neurocytoma on Squash Preparations

Intraoperative cytologic evaluation of brain tumors is utilized as an adjunct technique to frozen section because it provides comparatively better nuclear and cytoplasmic details. We undertook a retrospective study to further define the cytologic features of central and extraventricular neurocytomas, rare well-differentiated entities which are classified according to their locations but are morphologically similar. These tumors may be difficult …

Primary central neurocytoma of the mesencephalic tectum in a pediatric patient

Neurocytomas are tumors or neuronal differentiation, typically located within the supratentorial ventricular system. The extraventricular location is uncommon. A limited number of cases involving the brainstem have been reported and may be misdiagnosed as brainstem gliomas. Furthermore, midbrain neurocytomas are extremely rare, and no similar cases in pediatric patients have been reported in the literature to date. Brainstem location of neurocytomas often precludes gross total removal of the lesion, and in these cases, adjuvant therapies may be helpful. We report a case of a 16-year-old child who presented with signs and symptoms of increased intracranial pressure. The magnetic resonance imaging study demonstrated the presence of a primary mesencephalic tectum lesion causing obstructive hydrocephalus. The patient underwent emergent ventriculoperitoneal shunt implantation, resolving the hydrocephalus and the clinical symptoms. The lesion was partially removed through a suboccipital craniotomy and supracerebellar infratentorial approach to the mesencephalic tectum, without intraoperative complications. Histological examination of the lesion was consistent with the diagnosis of extraventricular neurocytoma. The patient was referred to the oncology department for additional treatment with Gamma Knife radiosurgery. Although brainstem neurocytoma is rare, this case demonstrates that it should be included in the differential diagnosis of brainstem gliomas. Because of brainstem tumor location, complete surgical removal may be challenging or not possible, with a high risk of postoperative neurological deficits. Adjuvant therapies may prevent local tumor growth in cases of tumor remnants or recurrences following microsurgery in selected cases.

30 Year-Old Male with Headaches

30 Year-Old Male with Headaches

FDG PET Differentiation of Tumor Recurrence From Post-Stereotactic Radiosurgical Scar in a Central Neurocytoma

Central neurocytoma is a rare benign tumor of neuronal origin. The tumor is often located in the ventricular system and can proliferate within the ventricle. Five months after stereotactic radiosurgery for recurrent neurocytoma, a 33-year-old woman had a 2.0-cm lesion in the right third ventricle on the MRI. FDG PET demonstrated intense uptake of the lesion. The subsequent MRI follow-up showed growth of the lesion and confirmed recurrence.

Diagnostic Challenges of Primary Thalamic Gliomas—Identification of a Minimally Enhancing Neuroradiological Subtype with Aggressive Neuropathology and Poor Clinical Outcome

To evaluate neuropathology and neuroradiology in the diagnosis and clinical outcome of a retrospective cohort of thalamic gliomas. Neuropathological and neuroradiological review was undertaken in 25 cases of radiologically suspected thalamic glioma (excluding childhood pilocytic astrocytoma) over an 8 year period (2004-2012) at Frenchay Hospital and compared to the clinical outcome. In 12/25 (48%) there was a difference in neuropathological and suspected neuroradiological grading of the lesion of one or more grades. In 5/12 (42%) cases, the neuroradiology was lower grade than the pathology. In 4/5 (80%) of these cases, we identified a minimally enhancing subtype where the neuroradiology was predicted to be of lower grade than neuropathology. In 4/12, (33%) the suspected neuroradiology grade was higher than the final pathology. In 3/4, (75%) of these cases the suspected neuroradiology grade was higher than the neuropathology possibly because of unusual differentiation within the thalamic glioma (central neurocytoma, anaplastic oligoastrocytoma, and diffuse astrocytoma with pilocytic features). In 3/12 (25%) the biopsy was non-diagnostic. Neuropathology was a better predictor of clinical outcome than neuroradiology. 9/10 (90%) WHO Grade 4 gliomas and 8/9 (88%) Grade 3 gliomas on neuropathology were dead between 3-7 years after diagnosis. 3/3 (100%) Grade 2 gliomas on neuropathology were alive 3-7 years after diagnosis. 2/3 (67%) of the non-diagnostic cases were alive 3-7 years after biopsy. In 1/3 (33%) of the non-diagnostic cases the outcome was unknown. Diagnosis of primary thalamic glioma is challenging. We have identified that in the thalamus, a pattern of diffuse infiltration with minimal enhancement on imaging may often represent high-grade glioma. Neuropathology is overall the best predictor of clinical outcome.

Outcomes after surgery for central neurocytoma: results of a French multicentre retrospective study

Central neurocytoma (CN) is a rare intraventricular tumour. Surgery has been highly recommended for CN, although it entails a significant chance to harm the patient. We aimed to provide new data that would support surgical decision-making and optimise patient information about outcomes after surgery. Under the auspices of the French Society of Neurosurgery, we conducted a multi-institutional database search in 23 academic hospitals. In all, we reviewed the relevant clinical and radiological data of 82 patients who were operated on for CN between 1984 and 2008, and had their diagnosis confirmed by central pathological review. The median follow-up was 61 months (range, 6-96 months). Gross total resection (GTR) was achieved in 48 % of the patients, and subtotal resection (STR) in 52 %. The 5-year overall survival rate was 93.8 % (95 % CI, 93.7-93.9). The 5-year progression-free survival rate was 92.1 % (95 % CI, 91.90-92.2) in patients who underwent GTR, compared with 55.3 % (95 % CI, 55.1-55.5) in patients who had STR (p = 0.01). The overall perioperative complication rate was 66 %. The main causes of postoperative disability were some degree of postoperative paresis and/or aphasia (39 %), memory difficulties (29 %) and temporary hydrocephalus (26 %). GTR was not associated with an increased rate of postoperative complications compared with STR. At last follow-up, Karnofsky Performance Score was at least equal to 80 for 90.6 % of the tested patients. Our series emphasised that maximal surgical resection of CNs offers favourable benefit-risk ratio. These data are of importance to properly counsel patients regarding expected outcomes, and to plan relevant preoperative and postoperative investigations like language and memory function evaluation.

Mystery Case: Central neurocytoma

A 29-year-old man presented with dizziness and headache for 2 months. MRI revealed a mass in the lateral ventricle with attachment of septum pellucidum (figure, A and B). Magnetic resonance spectroscopy (MRS) (repetition time 1,600 ms, echo time [TE] 135 ms) showed high glycine, decreased N -acetylaspartate, and increased choline (figure, C). Central neurocytoma was diagnosed by histologic examination (figure, D). The authors thank Hao-Wen Chuang, MD, for help in pathologic preparation.

Detection on clinical pathology features of central neurocytoma by using Syn, GFAP, S-100 and NSE

Objective To investigate the clinical and pathological features of central neurocytoma (CNC),diagnosis and differential diagnosis,tissue and clinical prognosis.Methods 37 cases of brain glial cell tumors,immunohistochemistry synaptophysin (Syn),neuron-specific enolase (NSE),glial fibrillary acidic protein (GFAP),S-100 detection,detection of 9 cases of CNC.7 cases were aecompanied by differentiation characteristics of CNC.Results 6 cases were male,3 female,mean age 38.Clinical manifestations of headache,dizziness,vomiting,convulsions,coma symptoms,limb weakness.Location:2 cases occurred in the lateral ventricles,7 cases occurred in the external ventricles.The size of the tumor diameter was 3-7.5 cm.Light microscopy of tumor cells with uniform rouud,less cytoplasm,transparent,nucleus was small and round,chromatin was uniform,stippling,nuclear center,nuclear Zhou Kong halo,resembling the oligodendrocyte,tumor cells diffusely arranged densely,visible with a chrysanthemum shape,cell free zone neuropil like structure,interstitial,abundant blood vessels,slender,branched,a few appeared hyperplasia,calcifications and cystic degeneration.A few cases had nuclear atypia,mitotic and focal necrosis visible.Immunohistochemistry:Syn (strong positive 7/9,positive 2/9),S-100(strong positive 4/9,positive 4/9),NSE (weak positive 6/9),GFAP (positive 3/9,weak positive 4/9),Vimentin (strong positive 2/9,positive 1/9,weak positive 1/9),Ki67(weak positive 9/9),NF (weak positive 3/9).Follow-up of 8 cases,6 cases died,2 cases survived.Conclusions CNC morphologic features have multiple differentiation,which can occur within the ventricles,are also found in the brain of outdoor,misdiagnosed as ependymoma,oligodendroglioma and medulloblastoma tumors.Immune phenotype with differentiation,ventricle external CNC may be a glial cell differentiation gene type of the tumor,but for a prompt accompanied by glial cell differentiation of CNC,with biological behavior instability,poor clinical prognosis.Immunohistochemical Syn,GFAP are helpful to the diagnosis and differential diagnosis.High expression of GFAP and Ki67,suggests poor clinical prognosis. Key words: Brain tumor; Neurocytoma; Glial cell differentiation; Central; Immunohistochemistry; Diagnosis; Prognosis

Pathologic features and clinical outcome of central neurocytoma: analysis of 15 cases.

To get better recognition of central neurocytoma and diminish misdiagnosis. A retrospective review identified 15 cases of central neurocytoma. All cases of central neurocytoma were analyzed for their clinical symptoms, pathologic changes, immunohistochemical staining, prognosis and differential diagnosis. Clinical follow up was performed. There were 8 males and 7 females aged 10-64 years (median 32.93 years). The most common presenting symptoms were those related to increased intracranial pressure (ICP), including headache (100%), papilledema (93%) and vomiting (80%). All tumors were located in the ventricular system. The tumors were composed of uniform cells with round nuclei and a fine chromatin pattern, and in some areas, small cells with perinuclear halo could be seen. In particular, the anuclear areas may have a fine fibrillary matrix (neuropil). Nuclear atypia and vascular proliferation appeared in two cases, respectively. Focal necrosis could be seen in one case. Immunohistochemical findings included expression of synaptophysin (15/15), neuron specific enolase (12/15) and glial fibrillary acidic protein (GFAP) (3/15). MIB-1 proliferation index ranged from 0.8-12.5%, and was more than 2% in 3 of 15 cases assessed. Follow-up information of 11 patients was available. Central neurocytoma has a favorable prognosis in general, but in some cases, the clinical course could be aggressive. Increase of GFAP positivity, proliferation index and vascular proliferation might suggest a more malignant process.

Clinical and imaging features of central neurocytomas

To describe the clinical and imaging characteristics of patients with central neurocytoma (CN), we reviewed data on 27 patients who had histologically confirmed CN and were treated in our institution between 1999 and 2010. Neuro-imaging findings on CT scan (n=18) and MRI (n=25) were retrospectively evaluated. There were 15 males and 12 females with a mean age of 29years (range, 11–46years). The most frequent presentations included headache (n=21) and vomiting (n=6). Tumor sites included bilateral lateral ventricles (n=10), right lateral ventricle (n=7), left lateral ventricle (n=7) and fourth ventricle (n=3). On MRI, the T1-weighted signal was hypointense in 12 patients and isointense in 13, and the T2-weighted signal was isointense in 8 patients and hyperintense in 15. CT scans/MRI revealed a cystic component in 18 patients. Tumors showed a mild to marked enhancement in 26 patients. Flow voids from tumor vessels on MRI were present in 14 patients, and calcification was noted in six of 18 patients with CT scans. All lateral ventricle tumors were resected through a transcortical or transcallosal approach. Gross total resection was achieved in 19 patients, near total in two and subtotal in six. One patient died of cerebral infarction in the perioperative period. At the last follow up, there were three known clinical recurrences in this series. However, no recurrence was noted in 17 patients who underwent gross total resection with no adjuvant therapy.