Anaplastic Ependymoma Research Articles

Novel fusion genes and chimeric transcripts in ependymal tumors

We have previously identified two ALK rearrangements in a subset of ependymal tumors using a combination of cytogenetic data and RNA sequencing. The aim of this study was to perform an unbiased search for fusion transcripts in our entire series of ependymal tumors. Fusion analysis was performed using the FusionCatcher algorithm on 12 RNA-sequenced ependymal tumors. Candidate transcripts were prioritized based on the software's filtering and manual visualization using the BLAST (Basic Local Alignment Search Tool) and BLAT (BLAST-like alignment tool) tools. Genomic and reverse transcriptase PCR with subsequent Sanger sequencing was used to validate the potential fusions. Fluorescent in situ hybridization (FISH) using locus-specific probes was also performed. A total of 841 candidate chimeric transcripts were identified in the 12 tumors, with an average of 49 unique candidate fusions per tumor. After algorithmic and manual filtering, the final list consisted of 24 potential fusion events. Raw RNA-seq read sequences and PCR validation supports two novel fusion genes: a reciprocal fusion gene involving UQCR10 and C1orf194 in an adult spinal ependymoma and a TSPAN4-CD151 fusion gene in a pediatric infratentorial anaplastic ependymoma. Our previously reported ALK rearrangements and the RELA and YAP1 fusions found in supratentorial ependymomas were until now the only known fusion genes present in ependymal tumors. The chimeric transcripts presented here are the first to be reported in infratentorial or spinal ependymomas. Further studies are required to characterize the genomic rearrangements causing these fusion genes, as well as the frequency and functional importance of the fusions. © 2016 Wiley Periodicals, Inc.

Evaluating the apparent diffusion coefficient in MRI studies as a means of determining paediatric brain tumour stages

BackgroundThe apparent diffusion coefficient (ADC) in MRI seems to be related to cellularity in brain tumours. Its utility as a tool for distinguishing between histological types and tumour stages remains controversial. ProceduresWe retrospectively evaluated children diagnosed with CNS tumours between January 2008 and December 2013. Data collected were age, sex, histological diagnosis, and location of the tumour. We evaluated the ADC and ADC ratio and correlated those values with histological diagnoses. ResultsThe study included 55 patients with a median age of 6 years. Histological diagnoses were pilocytic astrocytoma (40%), anaplastic ependymoma (16.4%), ganglioglioma (10.9%), glioblastoma (7.3%), medulloblastoma (5.5%), and other (20%). Tumours could also be classified as low-grade (64%) or high-grade (36%). Mean ADC was 1.3 for low-grade tumours and 0.9 for high-grade tumours (P=.004). Mean ADC ratios were 1.5 and 1.2 for low and high-grade tumours respectively (P=.025). There were no significant differences in ADC/ADC ratio between different histological types. ConclusionADC and ADC ratio may be useful in imaging-study based differential diagnosis of low and high-grade tumours, but they are not a substitute for an anatomical pathology study.

Magnetic resonance imaging findings of extraventricular anaplastic ependymoma: A report of 11 cases.

Anaplastic ependymomas are rare malignant tumors of the central nervous system. Few studies are available regarding their neuroradiological characteristics. The present study aimed to retrospectively review a series of patients with extraventricular anaplastic ependymoma and to analyze the magnetic resonance imaging (MRI) characteristics to distinguish anaplastic ependymoma from other intracranial tumors. The clinical and pathological images of 11 patients who presented with histologically proven anaplastic ependymoma at Nanfang Hospital (Southern Medical University, Guangzhou, Guangdong, China) between September 2004 and March 2015 were retrospectively reviewed. MRI scans were obtained in all 11 cases. Computed tomography scans were obtained in only 3 cases. In total, 8 tumors were located at the supratentorial parenchyma, and 3 tumors were derived from the cerebellar hemisphere. Images displayed quasi-circular (4/11), irregularly-lobulated (7/11) variable-intensity masses. The masses presented with cysts or necrosis (8/11), hemorrhage (7/11), marked (9/11) or mild (2/11) enhancement, and moderate (4/11), mild (3/11) or absent (4/11) peritumoral edema. The tumors were also frequently closely associated with the lateral ventricle (6/11). Tumors appeared isointense to hypointense on T1-weighted imaging (T1WI) and heterogeneously hyperintense or hypointense on T2WI, demonstrating wreath-like and ring-like characteristics, with intratumoral nodules (3/11) or marked flake-like inhomogeneous (6/11) enhancement on post-contrast MRI. Only 2 solid lesions showed mild enhancement (2/11). Although the MRI features of the extraventricular anaplastic ependymomas varied and were non-specific, these characteristic MRI findings, combined with the locations of the lesions, the age of onset and the short disease course, could be useful in differentiating anaplastic ependymomas from other intracranial neoplasms in the future.

Altered MicroRNA Expression Is Associated with Tumor Grade, Molecular Background and Outcome in Childhood Infratentorial Ependymoma.

BackgroundEpendymal tumors are the third most common group of brain tumors in children, accounting for about 10% of all primary brain neoplasms. According to the current WHO classification, they comprise four entities with the most frequent ependymoma and anaplastic ependymoma. The most of pediatric tumors are located within the posterior fossa, with a tendency to infiltrate the vital brain structures. This limits surgical resection and poses a considerable clinical problem. Moreover, there are no appropriate outcome prognostic factors besides the extent of surgical resection. Despite definition of molecular subgroups, the majority of childhood ependymomas present a balanced genome, which makes it difficult to establish molecular prognostic factors.MethodsThe purpose of our study was to explore whether miRNA expression could be used as prognostic markers in pediatric infratentorial ependymomas. We also performed a mRNA expression pattern analysis of NELL2 and LAMA2 genes, with immunohistochemical illustrations of representative cases. The miRNA and mRNA expression was measured in 53 pediatric infratentorial ependymomas using a real-time quantitative PCR.ResultsThree miRNAs were shown to efficiently differentiate between grade II and III ependymomas: miR-17-5p, miR-19a-3p, and miR-106b-5p. Survival analysis showed that the probabilities of overall (p = 0.036) and event-free survival (p = 0.002) were reduced with higher than median miRNA expression levels of miR-17-5p. Using multivariate analysis adjusted for patient's age, sex, tumor grade and localization, we showed statistically significant associations with event-free survival (p = 0004) and borderline statistical significance with overall survival (p = 0.057) for miR-17-5p. Correlation analysis of miR-19a, miR-17-5p, miR-106b revealed that their expression levels were significantly correlated with EZH2 expression, suggested marker of PFA ependymomas. Furthermore, lower expression level of LAMA2 mRNA was shown to be associated with an increased risk of death in covariate-adjusted analyses.ConclusionsOur data provide a better understanding of pediatric ependymoma and suggests the presence of plausible molecular biomarkers connected with the outcome.

PNR-32UPDATE OF DIAGNOSTICS OF PRIMITIVE NEUROECTODERMAL TUMOURS OF THE CNS - NEUROPATHOLOGICAL RE-EVALUATION OF 99 CASES

PNR-32. UPDATE OF DIAGNOSTICS OF PRIMITIVE NEUROECTODERMAL TUMOURS OF THE CNS NEUROPATHOLOGICAL RE-EVALUATION OF 99 CASES Torsten Pietsch1, Dominique Figarella-Branger2, Cynthia Hawkins3, Felice Giangaspero4, Thomas S. Jacques5, Marco Gessi1, Peter Burger6, Christine Haberler7, and for the Internatonal CNS-PNET working group1; University of Bonn, Bonn, Germany; University of Marseille, Marseille, France; The Hospital for Sick Children, Toronto, Canada; University of Rome, Rome, Italy; University of London, London, UK; Johns Hopkins University, Baltimore, USA; University of Vienna, Vienna, Austria Recent analysis of tumours historically diagnosed as CNS-PNET by epigenetic profiling has led to the hypothesis that such cases may represent morphological mimics of CNS-PNET but can be largely assigned to other tumour entities, and that CNS-PNET are frequently misclassified by neuropathological diagnostics. As part of an international effort to collect and re-analyze CNS-PNET, 99 tumours diagnosed as CNS-PNET or pineoblastoma in the last 2 decades in 9 European countries were reviewed according to today’s standards of neuropathological diagnostics. 46% of cases were confirmed as CNS-PNET; of these, 68% were diagnosed as ETMR (including ependymoblastoma/ medulloepithelioma), and 32% as other CNS-PNET (CNS-PNET, NOS (n 1⁄4 11), CNSneuroblastoma (n 1⁄4 3) and CNS-ganglioneuroblastoma (n 1⁄4 2)). 54% of tumours were defined as other entities includingpineal parenchymal tumours (pineoblastoma/PPID; n 1⁄4 12), (anaplastic) ependymomas (n 1⁄4 7), PXA (n 1⁄4 2), diffuse high-grade gliomas (n 1⁄4 15), ATRT (n 1⁄4 3), mesenchymal tumours /sarcomas (n 1⁄4 7), germ cell tumour (n 1⁄4 1) and medulloblastoma (n 1⁄4 1), and 5 tumours were not classifiable, mostly because of insufficient biopsy material. A marker panel was defined for an optimized approach for the assessment of CNS-PNETs and tumours mimicking these neoplasms in routine neuropathological diagnostic workup. This study shows that (1) today’s diagnostic repertoire allows assignment of CNS-PNET cases, and (2) retrospective cohorts treated in neuro-oncological studies have to be re-analyzed to allow meaningful conclusions on effectiveness of specific treatment modalities. This cohort will be used to cross-validate assignment to tumour entities by epigenetic profiling and the associated clinical datawill be re-analyzed inan internationalmeta-analysis. Supported by the German Children’s Cancer Foundation. Neuro-Oncology 18:iii7–iii15, 2016. doi:10.1093/neuonc/now067.27 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

HG-77RADIATION-INDUCED HIGH GRADE GLIOMA FOLLOWING I-125 BRACHYTHERAPY IN A PEDIATRIC PATIENT

HG-77. RADIATION-INDUCED HIGH GRADE GLIOMA FOLLOWING I-125 BRACHYTHERAPY IN A PEDIATRIC PATIENT Daniela Garcez, Eduardo Netto, and Duarte Salgado; Instituto Portugues de Oncologia de Lisboa Francisco Gentil E.P.E., Lisboa, Portugal INTRODUCTION: Brachytherapy has been used in brain tumors since 1960. Only a few studies have been published about late occurence of second malignancies due to brachytherapy for brain tumors. Therefore, this procedureappears to be an attractive alternative in multimodality cancer management in selected pediatric cases. CASE PRESENTATION: We report the case of a 33 years old female patient diagnosed with an anaplastic ependymoma grade III (right frontal lobe) when she was 8 years old. After a total resection she underwent craniospinal radiotherapy (36Gy) with a focal boost (54Gy). A local relapse was identified three years later and pathological diagnosis, after total resection, was ependymoblastoma. She received I-125 brachytherapy for 3 months followed by 8 cycles of CCNU, cisplatin and vincristine. She remained in total remission for almost 20 years. In 2015 she was admitted due to progressive apathy. An MRI scan showed a large contrast enhancing tumor (8x7cm) in the right frontal lobewith mass effect and midline shift. After subtotal resection the pathological diagnosis was anaplastic oligodendroglioma. CONCLUSION: Despite the obvious advantages that I-125 brachytherapy presents, the use in the pediatric population remains controversial.Radiation-induced tumors area serious issue andareusuallyagressiveand sometimes fatal. The enhanced risk of associating standard external beam radiotherapy with brachytherapy should be carefully considered in the pediatric population. Neuro-Oncology 18:iii48–iii77, 2016. doi:10.1093/neuonc/now073.73 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Decreased FOXJ1 expression and its ciliogenesis programme in aggressive ependymoma and choroid plexus tumours.

Well-differentiated human cancers share transcriptional programmes with the normal tissue counterparts from which they arise. These programmes broadly influence cell behaviour and function and are integral modulators of malignancy. Here, we show that the master regulator of motile ciliogenesis, FOXJ1, is highly expressed in cells along the ventricular surface of the human brain. Strong expression is present in cells of the ependyma and the choroid plexus as well as in a subset of cells residing in the subventricular zone. Expression of FOXJ1 and its transcriptional programme is maintained in many well-differentiated human tumours that arise along the ventricle, including low-grade ependymal tumours and choroid plexus papillomas. Anaplastic ependymomas as well as choroid plexus carcinomas show decreased FOXJ1 expression and its associated ciliogenesis programme genes. In ependymomas and choroid plexus tumours, reduced expression of FOXJ1 and its ciliogenesis programme are markers of poor outcome and are therefore useful biomarkers for assessing these tumours. Transitions in ciliogenesis define distinct differentiation states in ependymal and choroid plexus tumours with important implications for patient care. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Erratum to: Re-irradiation of recurrent anaplastic ependymoma using radiosurgery or fractionated stereotactic radiotherapy

Purpose Recurrent ependymomas were retreated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). The efficacy, toxicities, and differences between SRS and FSRT were analyzed.

Ependymomas: A clinicopathologic study

Introduction: Ependymomas are glial neoplasms that account for 4-8% of primary CNS neoplasms. Considerable controversy exists with regards to their prognosis and management, owing to their rarity and heterogeneity. Objectives: To study the clinical and pathologic features of ependymomas and evaluate their important prognostic variables. Materials and Methods: A 10 year retrospective study was carried out. The age, sex, location, clinical presentation, radiologic findings, microscopy, type of excision and follow up findings were studied. Results: 168 ependymomas were identified in a total of 6628 biopsies((2.53%). Majority were seen in the second decade (42/168), M:F ratio was 2:1. 15.48% (26 cases) occurred in the supratentorial compartment, 36.92% (62 cases) infratentorially, and 47.61% (80 cases) in the spinal cord. 90% of the intracranial tumors presented with features of raised ICT while patients with spinal tumors had focal motor deficits. There were 146 classic grade II ependymomas(78.5%), most common location being the posterior fossa, 36 myxopapillary ependymomas(17.8%), all seen in the lumbosacral region and 6 anaplastic ependymomas(3.57%). Anaplastic ependymomas were seen supratentorially in children and young adults while the peak of myxopapillary tumours was in third and fourth decades. 105 patients underwent gross or near total excision while in 16 it was partial or subtotal. Follow up was available in 73 patients. 9 patients died in the immediate post – operative period. Follow up for the rest varied from 3 months to 9 years. Anaplastic ependymomas were associated with a poorer prognosis. In supratentorial and lumbosacral tumours there was no difference in survival between gross total and subtotal excision while in adult infratentorial grade II ependymomas and cervical ependymomas, gross total excision had a better three year survival. Conclusions: The prognosis of ependymomas is multifactorial and depends on histologic type and extent of surg

Supratentorial Extraventricular Anaplastic Ependymoma Presented With Headache in Pregnancy: Case Report and Review of the Literature

Supratentorial extraventricular anaplastic ependymoma (SEAE) is a rare type of ependymoma. On magnetic resonance imaging (MRI), generally it is noted with a solid appearance or a mixed solid and cystic pattern. A 28-year-old female was admitted to our clinic with a complaint of increasing headaches in the third trimester of pregnancy and epileptic seizures in the first week postpartum. A superficial cortical lesion was found in the left precentral gyrus anterior, showing as purely cystic on the MRI. Gross total microsurgical resection was performed. Histological and immunohistochemical examinations confirmed the finding of anaplastic ependymoma. In this article, the course of SEAE is described that starting with pregnancy. And SEAE in this patient was investigated regarding different features from other similar cases. Also, the effect of pregnancy on this tumor’s growth, which is known to have an embryonal origin, is discussed. J Med Cases. 2016;7(7):274-281 doi: https://doi.org/10.14740/jmc2306w

Re-irradiation of recurrent anaplastic ependymoma using radiosurgery or fractionated stereotactic radiotherapy.

Recurrent ependymomas were retreated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). The efficacy, toxicities, and differences between SRS and FSRT were analyzed. Eight patients with recurrent ependymomas fulfilling the criteria described below were evaluated. Inclusion criteria were: (1) the patient had previously undergone surgery and conventional radiotherapy as first-line treatment; (2) targets were located in or adjacent to the eloquent area or were deep-seated; and (3) the previously irradiated volume overlapped the target lesion. FSRT was delivered to 18 lesions, SRS to 20 lesions. A median follow-up period was 23 months. The local control rate was 76 % at 3 years. No significant differences in local control were observed due to tumor size or fractionation schedule. Lesions receiving >25 Gy/5 fr or 21 Gy/3 fr did not recur within 1 year, whereas no dose-response relationship was observed in those treated with SRS. No grade ≥2 toxicity was observed. Our treatment protocol provided an acceptable LC rate and minimal toxicities. Because local recurrence of tumors may result in patient death, a minimum dose of 21 Gy/3 fr or 25 Gy/5 fr or higher may be most suitable for treatment of these cases.

Radiation-induced anaplastic ependymoma mimicking a skull base meningioma: A case report.

The present study describes the case of a 63-year-old woman presenting with headache, dizziness and vomiting due to a an ovoid mass in the left pre-bulbar cistern, apparently arising from the lower clivus and the foramen magnum. The clinical history revealed the subtotal removal of a right cerebellar low-grade glioma 15 years previously and subsequent conventional 60-Gy radiotherapy. Notably, following gross total resection, histopathological examination showed microscopic features that resulted in a diagnosis of anaplastic ependymoma. The patient underwent surgery to remove the mass and post-operative chemotherapy with temozolomide. A progressive improvement of neurological signs and symptoms was observed during the postoperative course. At the 6-month follow-up, the patient was free from clinical and radiological recurrence. The unusual features of this rare secondary brain tumor were the extrassial location in the posterior fossa, the unusual age-associated location of the histological subtype and the fact that it closely mimicked a skull-base meningioma.

The rare case of a combination two brain tumors with total colon polyposis

Objectives of publication: Presentation of a rare clinical observation from our own practice. Key points: The combination of brain tumors and colon polyposis often described in the literature as a syndrome Turcot. Turcot's syndrome is a genetic disease with different clinical manifestations. This is a rare syndrome (a little more than 150 cases are described), and therefore, the standardization of approaches to diagnosis and treatment is not currently defined. We present the clinical case of manifestations of the Turcot’s syndrome of our practice. Сlinical observation: Male patients, from birth to the skin marked multiple cafe-au-lait spots. At age 14 years, according to a magnetic resonance imaging multiple brain tumors are revealed, two different histologically tumor brains (one of which is benign (pilocytic astrocytoma), the other is malignant (anaplastic ependymoma)) and total colon adenomatous polyposis were diagnosed. Currently, syndromic pathology is not verified. Receives one of polychemotherapy protocols for treating tumors of the central nervous system. It is planned to conduct additional studies aimed at clarifying the genetic defect, with a view to a possible optimization of the therapy (modification of the plane of polychemotherapy, use of an option of radiation therapy, use of a target therapy). Conclusions: The results of a comprehensive survey of the use of modern techniques of molecular biology and cytogenetics affect the prognosis of the disease and treatment strategy.

Nucleolin overexpression is associated with an unfavorable outcome for ependymoma: a multifactorial analysis of 176 patients.

Ependymoma typically has a better overall survival rate than most gliomas. Only a few comprehensive clinical studies have been published, but these are mostly from Western countries and use small sample sizes. Histopathological classification is not sufficient to show variable outcomes, and fails to show prognostic markers of the diverse outcomes; hence, it is essential to understand biological mechanisms. In this study, 176 ependymoma samples (World Health Organization grade II and III) were reviewed at Huashan Hospital. Both children and adults were included. We performed multifactorial analyses of clinical prognostic factors and the biomolecular marker expressions of nucleolin, epidermal growth factor receptor (EGFR) and caveolae-associated protein caveolin-1 by immunohistochemistry. We identified the probabilities of progression-free survival and overall survival using univariate and multivariate statistical methods. The participants were diagnosed with ependymomas between 2002 and 2010, including distributions of tumor locations in intracranial and extracranial regions. Nucleolin was overexpressed in 67% of our samples, demonstrating a subgroup with poor outcome; particularly infratentorial and anaplastic ependymomas. There was no significant correlation between the expression of EGFR and caveolin-1 and clinical outcomes. Clinically, inferior prognosis was observed with regard to age (<18years), intracranial location, high grade ependymomas, and incomplete resection. We found that nucleolin was an unfavorable prognostic predictor for ependymomas. Moreover, our findings show a subset of aggravating outcomes in high-grade and posterior fossa tumors.

ATPS-53SURGICAL THERAPY FOR CEREBRAL VENTRICLE TUMOR IN INFANTS

BACKGROUND: Surgical treatment for infant ventricle tumors is a tough procedure. We summarize the clinical information, surgical experience and perioperative therapy for 14 patients. METHODS: The patients contained 8 males, 6 females and were treated from 2010-1 to 2014-12. The age ranged from 4 to 24 months with an average of 11.5 months. We used the approach of trigone area for 3 cases, interhemispheric transcallosal for 5 cases, and sub-occipital medline for 6 cases. RESULTS: Resection extent: 10 total resection (including 2 subtotal resection), 4 partial resection. Pathology categories: 5 choroid plexus papilomas (CPP), 1 choroid plexus carcinoma,1 mature teratoma, 1 anaplastic CPP, 3 anaplastic ependymoma (WHO III), 1 ependymoma (WHO I-II ), 1 glioma, 1 medulloblastoma. PROGNOSIS: 7 cases survive (4 cases survive with different complications); 5 infants died (all died for abandoning treatment); 1 case was lost. Overall, the prognosis is poor. CONCLUSIONS: 1. Infant cerebral ventricle tumors are often large before symptoms come up. Tumor's proximity to important brain regions makes it difficult for total resection. 2. Infants have a small blood volume and poor tolerance to operation, since great blood loss usually occurs intraoperation. Time-consuming operations, such as those for total resection, require a great deal of time under anaesthesia and blood loss. It's preferable to choose a stage operation when severe blood loss occurs. 3. Acute resection is a better choice to relieve hydrocephalus rather than drainage. 4. Close contact of qualified, specialist medical staff is necessary. Intensive care and nutritional support are important for postoperation therapy.

Multiomics approach showing genome-wide copy number alterations and differential gene expression in different types of North-Indian pediatric brain tumors

PurposeBased on copy number alterations and transcriptional profiles, the posterior fossa tumors (medulloblastoma (MB), ependymoma and pilocytic astrocytoma) have been classified into various subgroups. The study design was aimed to identify and catalog genome-wide copy number alterations and differential gene expression in different types of North-Indian pediatric posterior fossa tumors and matched control tissue through Molecular Inversion Probe (MIP) Based and Human Transcriptome Array. Experimental designMIP based OncoScan Array and Human Transcriptome Array 2.0 were used to molecularly-categorize histopathologically and immunohistochemically proven tumor samples on the basis of copy number variations and altered gene expression patterns and/or alternative splicing events. ResultsBased on molecular, histopathological/immunohistochemical and age-dependent factors MB was subgrouped into group-3 MB, Wnt and SHH; ependymoma into balanced, numerical and structural/anaplastic; and pilocytic astrocytoma was stratified age-dependently. Compared with the vermis tissue of MB, the vermis tissue of ependymoma showed higher levels of gain and losses compared with their counter tumor parts implicating metastasis within the confined region. Group-3 MB and anaplastic ependymoma represented highest differentially expressed genes both at gene and exon levels in the CN altered regions compared with other subgroups of MB and ependymoma respectively. ConclusionThis multiomics approach based molecular characterization of posterior fossa tumors together with clinical and histopathological factors may help us in the area of personalized medicine.

Posterior fossa tumors in infants and neonates

Management of posterior fossa tumors in infants and neonates is challenging. The characteristics of the young babies make surgery very difficult, sometimes precluding a safe complete removal. A review of the literature was undertaken to examine the incidence, histology, surgical aspects, and prognosis of posterior fossa tumors in the first year of life. Therapeutical strategies of the most frequent tumor types are also discussed in detail. Histology is dominated by tumors with aggressive behavior, such as medulloblastomas, atypical teratoid/rhabdoid tumors, and anaplastic ependymomas. The most important surgical considerations in small children are the small circulating blood volume; the poor thermoregulation; and incomplete maturation of the brain, of the skull, and of the soft tissue. Treatment toxicity is inversely related to the age of the patients. Radiation therapy is usually considered as contraindicated in young children, with few exceptions. Proton therapy is a promising tool, but access to this kind of treatment is still limited. The therapeutic limitations of irradiation render resection of this tumor and adjuvant chemotherapy often the only therapeutic strategy in many cases. The overall prognosis remains dismal because of the prevalent aggressive histologies, the surgical challenges, and the limitations of adjuvant treatment. Nevertheless, the impressive improvements in anesthesiology and surgical techniques allow, in the vast majority of the cases, complete removal of the lesions with minor sequelae in high-volume referral pediatric centers.

Anatomic locations in high grade glioma

Abstract The treatment options and prognosis in gliomas could be determined by anatomic topographic location, beside different subtypes of glioma. The aim of this study is to find if any correlation between anatomical location of a glioma and the different subtypes of high grade glioma exist, and if this differences exists, does this influence the treatment options in terms of surgery. To do this, a representative group of 318 adults with high grade glioma was used. The most frequent subtypes of high grade glioma were glioblastoma (76,1%) followed by anaplastic astrocytomas (19,1%), anaplastic oligodendrogliomas (2,2), anaplastic ependymomas (1,2%), anaplastic oligoastrocytomas (0,9%), and anaplastic oligoastrocyomas (0,3%). The most frequent locations of gliomas were in the right frontal lobe in 11,95% of the cases, followed by left frontal in 9,12%, left temporal in 9,12%, right parietal in 8,18%, left parietal in 6,60%, right temporal in 5,66% for one lobe location. For multiple lobe locations the left fronto-parietal and left temporo-parietal (5,03%) were the most frequent locations. Deep-seated locations were present in 1,56% of the cases, and brain stem location was in 3,46%. No significant difference was observed between left or right predominence. Regarding the results among different subtypes of high grade glioma we noted that the anaplastic astrocytomas were more frequently located at the right frontal lobe in 18,03% compare to left frontal and left parietal lobe in 9,83%. In glioblastoma we found no significant differences in anatomical location as seen in anaplastic astrocytomas. These data results from our study could affect the therapeutic strategy regarding the extent of tumors resection.

The Role of Fast Cell Cycle Analysis in Pediatric Brain Tumors

Cell cycle analysis by flow cytometry has not been adequately studied in pediatric brain tumors. We investigated the value of a modified rapid (within 6 min) cell cycle analysis protocol for the characterization of malignancy of pediatric brain tumors and for the differentiation of neoplastic from nonneoplastic tissue for possible intraoperative application. We retrospectively studied brain tumor specimens from patients treated at our institute over a 5-year period. All tumor samples were histopathologically verified before flow-cytometric analysis. The histopathological examination of permanent tissue sections was the gold standard. There were 68 brain tumor cases. All tumors had significantly lower G₀/G₁ and significantly higher S phase and mitosis fractions than normal brain tissue. Furthermore low-grade tumors could be differentiated from high-grade tumors. DNA aneuploidy was detected in 35 tumors. A correlation between S phase fraction and Ki-67 index was found in medulloblastomas and anaplastic ependymomas. Rapid cell cycle analysis by flow cytometry is a promising method for the identification of neoplastic tissue intraoperatively. Low-grade tumors could be differentiated from high-grade tumors. Thus, cell cycle analysis can be a valuable adjunct to the histopathological evaluation of pediatric brain tumors, whereas its intraoperative application warrants further investigation.

Qualitative analysis of spinal intramedullary lesions using PET/CT.

OBJECT Although the usefulness of PET for brain lesions has been established, few reports have examined the use of PET for spinal intramedullary lesions. This study investigated the diagnostic utility of PET/CT for spinal intramedullary lesions. METHODS l-[methyl-11C]-methionine (MET)- or [18F]-fluorodeoxyglucose (FDG)-PET/CT was performed in 26 patients with spinal intramedullary lesions. The region of interest (ROI) within the spinal cord parenchyma was placed manually in the axial plane. Maximum pixel counts in the ROIs were normalized to the maximum standardized uptake value (SUVmax) using subject body weight. For FDG-PET the SUVmax was corrected for lean body mass (SULmax) to exclude any influence of the patient's body shape. Each SUV was analyzed based on histopathological results after surgery. The diagnostic validity of the SUV was further compared with the tumor proliferation index using the MIB-1 monoclonal antibody (MIB-1 index). RESULTS A total of 16 patients underwent both FDG-PET and MET-PET, and the remaining 10 patients underwent either FDG-PET or MET-PET. Pathological diagnoses included high-grade malignancy such as glioblastoma multiforme, anaplastic astrocytoma, or anaplastic ependymoma in 5 patients; low-grade malignancy such as hemangioblastoma, diffuse astrocytoma, or ependymoma in 12 patients; and nonneoplastic lesion including cavernous malformation in 9 patients. Both FDG and MET accumulated significantly in high-grade malignancy, and the SULmax and SUVmax correlated with the tumor proliferation index. Therapeutic response after chemotherapy or radiation in high-grade malignancy was well monitored. However, a significant difference in SULmax and SUVmax for FDG-PET and MET-PET was not evident between low-grade malignancy and nonneoplastic lesions. CONCLUSIONS Spinal PET/CT using FDG or MET for spinal intramedullary lesions appears useful and practical, particularly for tumors with high-grade malignancy. Differentiation of tumors with low-grade malignancy from nonneoplastic lesions may still prove difficult. Further technological refinement, including the selection of radiotracer or analysis evaluation methods, is needed.