A Cohort Study of CNS Tumors in Multiple Endocrine Neoplasia Type 1.

PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is thought to increase the risk of meningioma and ependymoma. Thus, we aimed to describe the frequency, incidence, and specific clinical and histological features of central nervous system (CNS) tumors in the MEN1 population (except pituitary tumors). EXPERIMENTAL DESIGN: The study population included patients harboring CNS tumors diagnosed with MEN1 syndrome after 1990 and followed up in the French MEN1 national cohort. The standardized incidence ratio (SIR) was calculated based on the French Gironde CNS Tumor Registry. Genomic analyses were performed on somatic DNA from seven CNS tumors, including meningiomas and ependymomas from patients with MEN1, and then on 50 sporadic meningiomas and ependymomas. RESULTS: A total of 29 CNS tumors were found among the 1,498 symptomatic patients (2%; incidence = 47.4/100,000 person-years; SIR = 4.5), including 12 meningiomas (0.8%; incidence = 16.2/100,000; SIR = 2.5), 8 ependymomas (0.5%; incidence = 10.8/100,000; SIR = 17.6), 5 astrocytomas (0.3%; incidence = 6.7/100,000; SIR = 5.8), and 4 schwannomas (0.3%; incidence = 5.4/100,000; SIR = 12.7). Meningiomas in patients with MEN1 were benign, mostly meningothelial, with 11 years earlier onset compared with the sporadic population and an F/M ratio of 1/1. Spinal and cranial ependymomas were mostly classified as World Health Organization grade 2. A biallelic MEN1 inactivation was observed in 4/5 ependymomas and 1/2 meningiomas from patients with MEN1, whereas MEN1 deletion in one allele was present in 3/41 and 0/9 sporadic meningiomas and ependymomas, respectively. CONCLUSIONS: The incidence of each CNS tumor was higher in the MEN1 population than in the French general population. Meningiomas and ependymomas should be considered part of the MEN1 syndrome, but somatic molecular data are missing to conclude for astrocytomas and schwannomas.

Association Between Urbanicity and Outcomes Among Patients with Spinal Cord Ependymomas in the United States.

BACKGROUND: Spinal cord ependymomas (SCEs) represent the most common intramedullary spinal cord tumors among adults. Research shows that access to neurosurgical care and patient outcomes can be greatly influenced by patient location. This study investigates the association between the outcomes of patients with SCE in metropolitan and nonmetropolitan areas. METHODS: Cases of SCE between 2004 and 2019 were identified within the Central Brain Tumor Registry of the United States, a combined dataset including the Centers for Disease Control and Prevention's National Program of Cancer Registries and National Cancer Institute's Surveillance, Epidemiology, and End Results Program data. Multivariable logistic regression models were constructed to evaluate the association between urbanicity and SCE treatment, adjusted for age at diagnosis, sex, race and ethnicity. Survival data was available from 42 National Program of Cancer Registries (excluding Kansas and Minnesota, for which county data are unavailable), and Cox proportional hazard models were used to understand the effect of surgical treatment, county urbanicity, age at diagnosis, and the interaction effect between age at diagnosis and surgery, on the survival time of patients. RESULTS: Overall, 7577 patients were identified, with 6454 (85%) residing in metropolitan and 1223 (15%) in nonmetropolitan counties. Metropolitan and nonmetropolitan counties had different age, sex, and race/ethnicity compositions; however, demographics were not associated with differences in the type of surgery received when stratified by urbanicity. Irrespective of metropolitan status, individuals who were American Indian/Alaska Native non-Hispanic and Hispanic (all races) were associated with reduced odds of receiving surgery. Individuals who were Black non-Hispanic and Hispanic were associated with increased odds of receiving comprehensive treatment. Diagnosis of SCE at later ages was linked with elevated mortality (hazard ratio = 4.85, P < 0.001). Gross total resection was associated with reduced risk of death (hazard ratio = 0.37, P = 0.004), and age did not interact with gross total resection to influence risk of death. CONCLUSIONS: The relationship between patients' residential location and access to neurosurgical care is critical to ensuring equitable distribution of care. This study represents an important step in delineating areas of existing disparities.

Breastfeeding and risk of childhood brain tumors: a report from the Childhood Cancer and Leukemia International Consortium.

PURPOSE: Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence. METHODS: We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of CBT, astrocytoma, medulloblastoma/PNET, and ependymoma according to breastfeeding status, adjusting for study, sex, mode of delivery, birthweight, age at diagnosis/interview, maternal age at delivery, maternal educational attainment, and maternal race/ethnicity. We evaluated any breastfeeding versus none and breastfeeding ≥ 6 months versus none. We subsequently performed random effects meta-analysis to confirm our findings, identify potential sources of heterogeneity, and evaluate for outliers or influential studies. RESULTS: Breastfeeding was reported by 64.8% of control mothers and 64.5% of case mothers and was not associated with CBT (OR 1.04, 95% CI 0.94-1.15), astrocytoma (OR 1.01, 95% CI 0.87-1.17), medulloblastoma/PNET (OR 1.11, 95% CI 0.93-1.32), or ependymoma (OR 1.06, 95% CI 0.81-1.40). Results were similar when we restricted to breastfeeding ≥ 6 months and in meta-analyses. CONCLUSION: Our data suggest that breastfeeding does not protect against CBT.

Ependymoma: an epidemiological perspective from a low- and middle-income country.

OBJECTIVE: To enumerate the burden of ependymoma in our region and identify the demographic, tumoural, surgical, clinical characteristics, and outcomes of patients diagnosed with ependymoma. METHODS: This retrospective cross-sectional study included patients admitted under neurosurgical service between January 1 and December 31, 2019. The inclusion criterion for the study was a histopathological diagnosis of the brain lesion. The experience of the ependymal brain tumours observed at the 32 participating sites in Pakistan is presented. RESULTS: A total of 2750 patients with brain tumours were seen in 2019 at our centres of whom 58(2.1%) had a histopathological diagnosis of ependymoma. The median age at diagnosis was nine (IQR= 4.5-24.5) years. The median time to surgery from date of radiological diagnosis was 38.5 (IQR= 4-93.8) days. The median KPS score at presentation was 70 (IQR= 60-80), and post-surgery was 90 (IQR= 70-100), showing an average increase of 20. Our population's overall mortality rate for ependymoma was 31.1%, with the 30-day mortality rate being 2.2% (lower than the 4.5% on average for all brain tumours in our cohort). CONCLUSIONS: Ependymomas were predominantly found in the paediatric population in the presented cohort. While gender distribution and histopathological grading seemed to follow international trends, this study had a much higher mortality rate and a much lower gross total resection rate than centres in high-income countries.

The role of sex genotype in paediatric CNS tumour incidence and survival.

PURPOSE: Evidence exists, in CNS germinomas and medulloblastomas (MB), that patient sex significantly influences incidence and outcome. The role of sex genotype in other paediatric CNS tumours remains unclear. This study sought to examine the role of sex genotype in CNS tumour incidence and overall survival (OS). METHODS: Age-adjusted incidence and OS rates were collected from the Surveillance Epidemiology and End Result (SEER) registry between 2000 and 2011 for common paediatric (<=19 years) CNS tumours: pilocytic astrocytoma (PA), anaplastic astrocytoma, glioblastoma (GBM), medulloblastoma, supratentorial CNS embryonal tumour, ependymoma, and germinoma. All patients with histologically confirmed, ICD-03 coded, first tumours, were included. Kaplan-Meier and Cox regression analyses were used to calculate hazard ratios (HR). RESULTS: The total cases are as follows: males=3018 and females=2276. Highest incidence was seen in PA (n=2103). GBM displayed the worst OS, whilst PA displayed the best. Higher incidence was observed in males for all tumours, except PA. Females with ependymoma had significantly better OS compared to males, whereas males with germinomas had better OS compared to females. Females <1 year with AA had better OS than males. Increasing age significantly improved male and female survival in ependymoma and medulloblastoma. CONCLUSION: Interrogating population-based registries such as SEER minimises bias and provides credible data. Observed differences in incidence and OS between the sexes for different paediatric CNS tumours provide useful prognostic information for clinicians. Sex genotype was a significant independent prognostic factor in ependymomas and germinomas. Further investigation of possible epigenetic and hormonal differences may provide sex-specific vulnerabilities that may be exploitable for targeted therapy.

Genetic predisposition to longer telomere length and risk of childhood, adolescent and adult-onset ependymoma.

Ependymoma is the third most common brain tumor in children, with well-described molecular characterization but poorly understood underlying germline risk factors. To investigate whether genetic predisposition to longer telomere length influences ependymoma risk, we utilized case-control data from three studies: a population-based pediatric and adolescent ependymoma case-control sample from California (153 cases, 696 controls), a hospital-based pediatric posterior fossa type A (EPN-PF-A) ependymoma case-control study from Toronto's Hospital for Sick Children and the Children's Hospital of Philadelphia (83 cases, 332 controls), and a multicenter adult-onset ependymoma case-control dataset nested within the Glioma International Case-Control Consortium (GICC) (103 cases, 3287 controls). In the California case-control sample, a polygenic score for longer telomere length was significantly associated with increased risk of ependymoma diagnosed at ages 12-19 (P = 4.0 × 10-3), but not with ependymoma in children under 12 years of age (P = 0.94). Mendelian randomization supported this observation, identifying a significant association between genetic predisposition to longer telomere length and increased risk of adolescent-onset ependymoma (ORPRS = 1.67; 95% CI 1.18-2.37; P = 3.97 × 10-3) and adult-onset ependymoma (PMR-Egger = 0.042), but not with risk of ependymoma diagnosed before age 12 (OR = 1.12; 95% CI 0.94-1.34; P = 0.21), nor with EPN-PF-A (PMR-Egger = 0.59). These findings complement emerging literature suggesting that augmented telomere maintenance is important in ependymoma pathogenesis and progression, and that longer telomere length is a risk factor for diverse nervous system malignancies.

Ependimoma intracraneal: apuntes clínicos, moleculares y anatomopatológicos / Intracranial ependymoma: clinical, molecular and pathological notes

RESUMEN Los ependimomas surgen de las células ependimarias que revisten los ventrículos y los pasajes en el encéfalo y el centro de la médula espinal. Las células ependimarias producen líquido cefalorraquídeo. Se decidió la realización de una revisión acerca del ependimoma intracraneal teniendo en cuenta que no existe artículo nacional que trate este tema, siendo la mayoría de los trabajos consultados referentes a la misma variante histológica pero en localización espinal, cuyo objetivo es describir la características clínicas, moleculares y anatomopatológicas del ependimoma intracraneal. Se realizó la búsqueda de artículos en revistas de las bases de datos: PubMed, Scielo y EBSCO. La búsqueda se limitó a artículos con el texto completo, publicados fundamentalmente en los últimos cinco años. El ependimoma intracraneal es un tumor frecuente en la edad pediátrica, sus manifestaciones clínicas dependen de su localización, presenta una gran diversidad molecular y anatomoptológica (AU).

SUMMARY Ependymomas arise from ependymal cells that line the ventricles and passages in the brain and center of the spinal cord. Ependymal cells produce cerebrospinal fluid. It was decided to conduct a review about intracranial ependymoma taking into account that there is no national article dealing with this issue, with most of the works consulted referring to the same histological variant but in spinal location, whose objective is to describe the clinical characteristics, Molecular and pathological pathways of intracranial ependymoma. We searched articles in journals of the databases: PubMed, Scielo and EBSCO. The search was limited to articles with the full text, published mainly in the last five years. Intracranial ependymoma is a frequent tumor in the pediatric age, its clinical manifestations depend on its location, it has a great molecular and anatomoptological diversity (AU).

European genetic ancestry associated with risk of childhood ependymoma.

BACKGROUND: Ependymoma is a histologically defined central nervous system tumor most commonly occurring in childhood. Population-level incidence differences by race/ethnicity are observed, with individuals of European ancestry at highest risk. We aimed to determine whether extent of European genetic ancestry is associated with ependymoma risk in US populations. METHODS: In a multi-ethnic study of Californian children (327 cases, 1970 controls), we estimated the proportions of European, African, and Native American ancestry among recently admixed Hispanic and African American subjects and estimated European admixture among non-Hispanic white subjects using genome-wide data. We tested whether genome-wide ancestry differences were associated with ependymoma risk and performed admixture mapping to identify associations with local ancestry. We also evaluated race/ethnicity-stratified ependymoma incidence data from the Central Brain Tumor Registry of the United States (CBTRUS). RESULTS: CBTRUS data revealed that African American and Native American children have 33% and 36%, respectively, reduced incidence of ependymoma compared with non-Hispanic whites. In genetic analyses, a 20% increase in European ancestry was associated with a 1.31-fold higher odds of ependymoma among self-reported Hispanics and African Americans (95% CI: 1.08-1.59, Pmeta = 6.7 × 10-3). Additionally, eastern European ancestral substructure was associated with increased ependymoma risk in non-Hispanic whites (P = 0.030) and in Hispanics (P = 0.043). Admixture mapping revealed a peak at 20p13 associated with increased local European ancestry, and targeted fine-mapping identified a lead variant at rs6039499 near RSPO4 (odds ratio = 1.99; 95% CI: 1.45-2.73; P = 2.2 × 10-5) but which was not validated in an independent set of posterior fossa type A patients. CONCLUSIONS: Interethnic differences in ependymoma risk are recapitulated in the genomic ancestry of ependymoma patients, implicating regions to target in future association studies.

Caracterización de los pacientes con ependimoma intracraneal en el hospital pediátrico Juan Manuel Márquez. 2012-2017 / Characterization of patients with intracranial ependymoma in the pediatric hospital Juan Manuel Márquez. 2012-2017

RESUMEN Introducción: los ependimomas constituyen aproximadamente del 3-5 % de los tumores intracraneales y del 5-10 % de los tumores cerebrales, en la edad pediátrica. Objetivo: caracterizar los pacientes con ependimomas intracraneales intervenidos quirúrgicamente, en el Hospital Pediátrico ¨Juan Manuel Márquez. ¨ Materiales y método: estudio descriptivo, retrospectivo, a pacientes en edad pediátrica con diagnóstico histológico de ependimoma de localización intracraneal. En el período de enero 2012 a diciembre 2017. El universo quedó conformado por todos los pacientes en edad pediátrica operados con diagnóstico histológico de ependimoma intracraneal en el lugar y período antes mencionado (N=22). Resultados: la edad media fue 2,75 años con límites entre 1 y 17 y una desviación estándar de 3,65. Los pacientes del sexo masculino representaron el 63,64 %, la relación con el sexo femenino en los primeros 4 años fue de 1:1. En cuanto al cuadro clínico, se observó predominio de la hidrocefalia en el 72,73 % de los pacientes. Los ependimomas intracraneales de localización infratentorial, (63,64 %) predominaron. El 45,45 % de las lesiones estudiadas se correspondían con el subtipo histológico de ependimoma anaplásico. Conclusiones: la combinación de cirugía, radioterapia y quimioterapia se empleó en la mayoría de los casos. Predominó el abordaje directo de la lesión a través de craneotomía y exéresis adecuada a la localización del ependimoma, sin embargo, en la mayoría solo se logró resección entre el 50 y 90 %. En la mayoría de los pacientes la evolución luego del diagnóstico, evidenció una tendencia hacia la estabilidad (AU).

ABSTRACT Introduction: ependymoma are almost 3-5 % of the intracranial tumors and 5-10 % of the brain tumors in pediatric age. Objective: to characterize the patients with intracranial ependymoma who underwent surgery in the Pediatric Hospital ¨Juan Manuel Márquez.¨ Materials and method: retrospective, descriptive study of patients in pediatric age with histological diagnosis of ependymoma of intracranial location in the period January 2012-December 2017. The universe was formed by all patients of pediatric age who underwent surgery with histological diagnosis of intracranial ependymoma in the before-mentioned place and period (N=22). Results: the average age was 2.75 years with limits between 1 and 17 years old. Male patients represented 63.64 %; the relation with female sex during the first 4 years was 1:1. Regarding the clinical characteristics, hydrocephaly predominated in 72.73 % of patients. Intracranial ependymoma of infratentorial location (63.64 %) predominated. 45.45 % of the studied lesions corresponded to the histological subtype of anaplastic ependymoma. Conclusions: the combination of surgery, radiotherapy and chemotherapy was used in most of the cases. The direct approach of the lesion through craniotomy and a removal adequate to ependymoma location predominated. However, in most of them just the resection of 50-90 % was achieved. The evolution of most of patients after the diagnosis evidenced a tendency to the stability (AU).

Poor academic performance in offspring of survivors with childhood or adolescent central nervous system tumor in Sweden.

The number of children who were born after their parents were diagnosed with central nervous system (CNS) tumor is increasing, but it remains largely unknown regarding the academic performance of these children. We aimed to investigate whether children of survivors with childhood or adolescent CNS tumor were associated with poor academic performance. Children of survivors of CNS tumor were identified by combining the nationwide Swedish Cancer Register and the Multi-Generation Register, and those who have completed compulsory education in Sweden between 1989 and 2015 were included in our study. "Poor academic performance" was defined as a z-score of the academic performance below the 10th percentile. Conditional logistic regression and quantile regression were used to examine the association. A total of 655 children were born after their parental diagnosis of CNS tumor and they had 1.39 times higher risk of achieving poor academic performance as compared to the matched comparisons (95% CI = 1.10-1.76). The poor academic performance was even more pronounced in boys, among those with a paternal diagnosis of CNS tumor and those with a parental ependymoma. The observed association differed depending on preterm birth. In addition, the strength of the association declined with the increased quantiles of academic performance z-score. Our data suggest that parental CNS tumor affects the subsequent academic achievements among children born after the parental tumor.

The TP53 p.R337H mutation is uncommon in a Brazilian cohort of pediatric patients diagnosed with ependymoma.

BACKGROUND: Ependymoma (EPN) is the third most common childhood cancer of the central nervous system. RELA fusion-positive EPN accounts for approximately 70% of all childhood supratentorial tumors and shows the worst prognosis among the supratentorial EPNs. TP53 mutation is infrequent in RELA fusions EPNs. In the population from the Southern region of Brazil, there is a high incidence of the germline TP53 p.R337H mutation that predisposes carriers to develop early-onset tumors. However, despite this high incidence, the frequency of this mutation among EPN patients remains to be determined. Here, we investigated the presence of the TP53 p.R337H mutation in a larger cohort of pediatric EPNs of three institutions located in the state of São Paulo, Brazil. METHODS: The TP53 p.R337H mutation was screened by conventional RT-PCR and Sanger sequencing in 49 pediatric EPNs diagnosed during the period from 1995 to 2016. RESULTS: We described for the first time a case of a 5-year-old girl with RELA fusion EPN with a heterozygous TP53 p.R337H mutation. CONCLUSIONS: The present finding indicates that the TP53 p.R337H germline mutation is uncommon in patients with EPN in Brazil and screening of pediatric patients RELA fusion EPN may be informative to better understand the role of TP53 germline mutations in the development and prognosis of these tumors.

Ependymoma with Intraorbital Extracerebral Recurrence: Case Report

Ependymomas are rare neuroepithelial tumors that originate from a type of glial cell called ependymal cell. In general, they correspond to 1.2 to 7.8% of all intracranial neoplasms, and to2 to 6%of all gliomas. Although it corresponds only to2 to 3%of all primary brain tumors, ependymoma is the fourthmost common cerebral neoplasmin children, especially in children younger than 3 years of age.1,2 In patients younger than 20 years of age, the majority (90%) of ependymomas are infratentorial,more precisely from the IV ventricle. In spite of this, in adults, medullary ependymomas are more frequent (60%). In this context, supratentorial and extraventricular ependymomas, as in the case reported in the present article, are infrequent in both adults and children.1,2 Both sexes are equally affected.3 Recurrence of intracranial ependymomas occurs in almost 50% of the cases, and the followup outcome is not favorable.4 In another perspective, the recurrence of extracerebral ependymomas is extremely rare, and even more unusual in the intraorbital site, as it occurred in the case in question.

Improved risk-stratification for posterior fossa ependymoma of childhood considering clinical, histological and genetic features - a retrospective analysis of the HIT ependymoma trial cohort.

INTRODUCTION: Risk stratification of children with ependymomas of the posterior fossa in current therapeutic protocols is mainly based on clinical criteria. We aimed to identify independent outcome predictors for this disease entity by a systematic integrated analysis of clinical, histological and genetic information in a defined cohort of patients treated according to the German HIT protocols. METHODS: Tumor samples of 134 patients aged 0.2-15.9 years treated between 1999 and 2010 according to HIT protocols were analyzed for histological features including mitotic activity, necrosis and vascular proliferation and genomic alterations by SNP and molecular inversion probe analysis. Survival analysis was performed by Kaplan-Meier method with log rank test and multivariate Cox regression analysis. RESULTS: Residual tumor after surgery, chromosome 1q gain and structural genomic alterations were identified as predictors of significantly shorter event-free (EFS) and overall survival (OS). Furthermore, specific histological features including vascular proliferation, necrosis and high mitotic activity were predictive for shorter OS. Multivariate Cox regression revealed residual tumor, chromosome 1q gain and mitotic activity as independent predictors of both EFS and OS. Using these independent predictors of outcome, we were able to build a 3-tiered risk stratification model that separates patients with standard, intermediate and high risk, and which outperforms current stratification procedures. CONCLUSION: The integration of defined clinical, histological and genetic parameters led to an improved risk-stratification model for posterior fossa ependymoma of childhood. After validation in independent cohorts this model may provide the basis for risk-adapted treatment of children with ependymomas of the posterior fossa.

Disparities among racial/ethnic groups of patients diagnosed with ependymoma: analyses from the Surveillance, Epidemiology and End Results (SEER) registry.

PURPOSE: The aim of this study was to identify racial/ethnic disparities with regard to survival among patients with ependymoma. METHODS: Data from the Surveillance, Epidemiology and End Results (SEER) registry between the years of 1973-2015 which included 4821 patients diagnosed with ependymoma were analyzed. Multivariable cox proportional hazard ratios were performed to examine overall survival across racial/ethnic groups of patients with ependymoma, mortality risks across specified age groups, and mortality during specified time intervals, all with corresponding 95% confidence intervals. RESULTS: Non-Hispanic black patients (n = 421) have higher risk of overall mortality when compared to non-Hispanic white patients (n = 3255) with ependymoma (HR 1.48, CI 1.17-1.87). Risk of mortality was highest when comparing non-Hispanic black children under the age of 3 to non-Hispanic white children of the same age group (HR 3.05, CI 1.55-5.99). Mortality risk has increased among pediatric non-Hispanic black patients compared to pediatric non-Hispanic white patients between the years of 2006-2015, from previous rates between the years 1973-2005 (HR 1.95, CI 1.15-3.33 and HR 2.35, CI 1.24-4.44). Hispanic patients under 3 years had an increased risk of mortality compared to non-Hispanic white patients of this age group (HR 2.49, CI 1.37-4.53). Asian/Pacific Islander patients (n = 282) had no significant difference in outcomes when compared to non-Hispanic white patients. CONCLUSIONS: Our findings showed higher risk of mortality among non-Hispanic black patients compared to non-Hispanic white patients with ependymoma, with highest risk among pediatric patients. These results demonstrate significant need for research in survival outcomes for this disease.

Characteristics and outcomes in patients with primary intraspinal tumours.

INTRODUCTION: We report a retrospective cohort study aimed at presenting data on incidence, patient char-ac-teristics, tumour type, level of pathology, clinical status before and after surgery and complications in patients with surgically treated primary intraspinal tumours (PIST) in Western Denmark. METHODS: Population-based data were retrieved from hospital files from 1 January 2010 to 31 December 2015. RESULTS: In total, 78 males and 88 females with PIST were included in the study. Incidence per 100,000 persons per year in the population-based cohort was 2.18. The incidence of malignant PIST was 0.14 and the incidence of non-malignant PIST was 2.03. We found 25 extradural tumours, 100 intradural extramedullary tumours and 41 intramedullary tumours. Eleven were malignant and 155 were benign tumours. Schwannoma, meningioma and ependymoma were more common in adults, whereas haemangioblastoma, neurofibroma and epidermoid cysts were seen in 14 paediatric cases. Motor function disturbances were found in 38% of cases. Sensory disturbances were found in 54% of cases, and worsening of sensory functions was the most frequent post-operative sequela. Ataxia and neurogenic bowel/bladder dysfunction seem to constitute the highest risk in cases of intramedullary tumours. Pain was found in 75% of cases and was the most common symptom among all patients with PITS with a 58% improvement after surgery. Complications were recorded in 12% of cases. CONCLUSIONS: The incidence of PIST seems to be higher in Western Denmark than in other European studies. PIST are rare in children. FUNDING: none. TRIAL REGISTRATION: not relevant.

Is NF2 a Key Player of the Differentially Expressed Gene Between Spinal Cord Ependymoma and Intracranial Ependymoma?

BACKGROUND: Although intracranial and spinal ependymomas are histopathologically similar, the molecular landscape is heterogeneous. An urgent need exists to identify differences in the genomic profiles to tailor treatment strategies. In the present study, we delineated differential gene expression patterns between intracranial and spinal ependymomas. METHODS: We searched the Gene Expression Omnibus database using the term "ependymoma" and analyzed the raw gene expression profiles of 292 ependymomas (31 spinal and 261 intracranial). The gene expression data were analyzed to find differentially expressed genes (DEGs) between 2 regions. The fold change (FC) and false discovery rate (FDR) were used to assess DEGs after gene integration (|log2FC|>2; FDR P < 0.01). Enrichment and pathway analysis was also performed. RESULTS: A total of 201 genes (105 upregulated and 96 downregulated) were significant DEGs in the data sets. The underexpression of NF2 in spinal ependymomas was statistically significant (FDR P = 7.91 × 10-9). However, the FC of NF2 did not exceed the cutoff value (log2FC, -1.2). The top 5 ranked upregulated genes were ARX, HOXC6, HOXA9, HOXA5, and HOXA3, which indicated that spinal ependymomas frequently demonstrate overexpression of HOX family genes, which play fundamental roles in specifying anterior/posterior body patterning. Moreover, the gene ontology enrichment analysis specified "anterior/posterior pattern specification" and "neuron migration" in spinal and intracranial ependymomas, respectively. CONCLUSIONS: The most substantial magnitude of DEGs in ependymoma might be HOX genes. However, whether the differential expression of these genes is the cause or consequence of the disease remains to be elucidated in a larger prospective study.

Surgical outcomes of spinal cord and cauda equina ependymoma: Postoperative motor status and recurrence for each WHO grade in a multicenter study.

BACKGROUND: The goals of the study are to analyze postoperative outcomes and recurrence in cases of spinal cord and cauda equina ependymoma in each World Health Organization (WHO) Grade, and to examine the influence of extent of surgical removal on prognosis. Spinal ependymoma has a relatively high frequency among intramedullary spinal cord tumors. The tumor is classified in WHO guidelines as grades I, II, and III, but few studies have examined postoperative prognosis based on these grades. METHODS: The records of 80 patients undergoing surgery for spinal cord and cauda equina ependymoma were examined in a multicenter study using a retrospective database. Neurological motor status, pathological type, extent of resection, and tumor recurrence were evaluated. RESULTS: The histopathological types were grade I in 23 cases (myxopapillary: 21, subependymoma: 2), grade II in 52 cases, and grade III in 5 cases (including all anaplastic cases). Total resection was performed in 60 cases (83%), and eight cases had recurrence, including 2 in WHO grade I, 2 in grade II, and 4 in grade III. The 5-year recurrence-free survival rates were 90%, 91%, and 20% in grades I, II and III, respectively. Adjuvant radiotherapy for the local site was performed in 8 cases, including 3 in grade I and 5 in grade III; however, 4 of the 5 grade III cases (80%) had recurrence after radiotherapy. Among 59 patients with normal ambulation or independence without external assistance (McCormick Grade I or II), 53 (90%) maintained the same mobility after surgery. In cases that underwent total resection, the recurrence rate was significantly lower (p < 0.01). A good preoperative motor status also resulted in significantly better postoperative recovery of motor status (p < 0.05). CONCLUSIONS: Total resection of spinal cord and cauda equina ependymoma leads to postoperative motor recovery and may reduce tumor recurrence. Therefore, early surgery for this tumor is recommended before aggravation of paralysis.

Pediatric Spinal Ependymomas: An Epidemiologic Study.

OBJECTIVE: Pediatric intramedullary spinal cord ependymomas represent a rare central nervous system neoplasm with few available data regarding incidence and outcomes. To this end, large population-based studies are needed to assess the epidemiology and survival risk factors associated with these tumors in the hope of better understanding these tumors as well as improving outcomes. This retrospective study was undertaken to explore factors that may influence survival in pediatric patients with intramedullary spinal cord ependymomas. METHODS: Using the SEER (Surveillance Epidemiology and End Results) database, a prospective cancer registry, we retrospectively assessed survival in histologically confirmed spinal ependymomas in patients 17 years of age and younger. Survival was described with Kaplan-Meier curves, and a multivariate regression analysis was used to assess the association of several variables with survival, controlling for confounding variables. RESULTS: Invasive tumor extension (P < 0.001) was associated with decreased survival, whereas gross total resection (P = 0.028) correlated with better rates of survival. Age, gender, tumor size, tumor extension, the use and sequence of radiation therapy, or use of chemotherapy were not found to have a statistically significant association with survival outcomes. CONCLUSIONS: Invasive ependymomas occurring in the spine have a worse prognosis, whereas higher tumor grades do not clearly show worse rates of survival. Early diagnosis and surgery seem to be associated with improved survival and outcomes, whereas radiation therapy and chemotherapy have an unclear role.

Ependymoma.

Ependymoma can arise throughout the whole neuraxis. In children, tumors predominantly occur intracranially, whereas the spine is the most prevalent location in adults. Significant variance in the grade II versus grade III distinction of ependymomas has led to the acknowledgment that the clinical utility of histopathological classification is limited. Epigenomic profiling efforts have identified molecularly distinct groups of ependymomas that adequately reflect the biological, clinical, and histopathological heterogeneities across anatomical compartments, age groups, and grades. The recent update of the World Health Organization classification of central nervous system tumors has already integrated one of these groups, and molecular classification will be part of future clinical trials to improve risk stratification. Clinical management of this rare disease is challenging, making professional experience and intensified multidisciplinary cooperation pivotal factors for treatment success. Novel research strategies are currently applied for target discovery in ependymomas since for most molecular groups, genetic drivers are unknown.