Spinal Cord Ependymoma Research Articles

Prognostic value of H3K27me3 in children with ependymoma.

To investigate the expression of H3K27me3 in different anatomical sites and analyze its prognostic value in children with ependymoma. A total of 188 children diagnosed with ependymoma were admitted to the Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, between 2012 and 2017, and regular follow-up was conducted. Expression of H3K27me3 was analyzed by immunohistochemistry and scored semiquantitatively. The prognostic correlation was analyzed by Kaplan-Meier and Cox regression survival analyses. Of the 188 children with ependymoma, 61.7% were male, and the median and average age was five years (0-17 years) and 6.26 years, respectively. There were 65 cases of supratentorial ependymoma, 115 cases of infratentorial ependymoma, and 8 cases of spinal cord ependymoma. The median follow-up time was 39.95 months (0.3-90.19 months). Five-year progression-free survival (PFS) and overall survival (OS) were 48.5% and 61.4%, respectively. Kaplan-Meier univariate survival analysis showed that H3K27me3 expression had significant effects on PFS (P=0.0003) and OS (P<0.0001) in infratentorial ependymoma, but only affected OS (P=0.03) in supratentorial ependymoma. In Chinese children, infratentorial ependymoma with incomplete resection and no adjuvant radiotherapy is associated with poor OS. On the other hand, low expression of H3K27me3 indicates poor prognosis of infratentorial ependymoma, but it has no significant prognostic value for supratentorial ependymoma. In addition, high expression of H3K27me3 in spinal ependymoma may indicate a better prognosis.

Genomic Landscape of Intramedullary Spinal Cord Gliomas

Intramedullary spinal cord tumors (IMSCTs) are rare neoplasms that have limited treatment options and are associated with high rates of morbidity and mortality. To better understand the genetic basis of these tumors we performed whole exome sequencing on 45 tumors and matched germline DNA, including twenty-nine spinal cord ependymomas and sixteen astrocytomas. Though recurrent somatic mutations in IMSCTs were rare, we identified NF2 mutations in 15.7% of tumors (ependymoma, N = 7; astrocytoma, N = 1), RP1 mutations in 5.9% of tumors (ependymoma, N = 3), and ESX1 mutations in 5.9% of tumors (ependymoma, N = 3). We further identified copy number amplifications in CTU1 in 25% of myxopapillary ependymomas. Given the paucity of somatic driver mutations, we further performed whole-genome sequencing of 12 tumors (ependymoma, N = 9; astrocytoma, N = 3). Overall, we observed that IMSCTs with intracranial histologic counterparts (e.g. glioblastoma) did not harbor the canonical mutations associated with their intracranial counterparts. Our findings suggest that the origin of IMSCTs may be distinct from tumors arising within other compartments of the central nervous system and provides the framework to begin more biologically based therapeutic strategies.

PATH-66. THE GENOMIC LANDSCAPE OF SPINAL CORD EPENDYMOMA

Abstract INTRODUCTION Ependymomas are seen throughout the neural axis but spinal cord is most common in adults. A subset arises in the setting of neurofibromatosis 2, whereas most are sporadic, potentially with somatic NF2 inactivation. The genetic drivers in NF2 wildtype tumors are unknown, as is the spectrum of cooperating genetic alterations. METHODS We performed targeted next-generation sequencing (NGS) to assess mutations, rearrangements, and chromosomal copy number alterations in 46 adult spinal cord ependymomas. RESULTS The 24 females and 22 males ranged from 20–73 (median 46) years of age. Tumors were in the cervical (n=24), thoracic (n=12), and lumbar (n=10) spinal cord. Nine tumors (20%) harbored truncating NF2 mutations with loss of the remaining wildtype allele, with frequent monosomy 13q. Thirteen NF2-wildtype tumors (28%) showed monosomy 22q with frequent monosomy 13q and trisomy 7, 9, and 12. Seventeen tumors (37%) carried a near-tetraploid genome, likely due to genomic reduplication with frequent preservation of diploidy in chromosomes 13q (77%), 14q (88%), 21q (53%) and 22q (65%). Remaining cases did not show a recurrent pattern, but one harbored focal high-level MYCN amplification. Three of the six recurrences were seen in the last subgroup; however, there was no significant difference for progression-free survival between four subgroups. None of the NF2-mutant tumors were in lumbar spinal cord, but there was no difference for tumor location or patient age between four subgroups. DISCUSSION Biallelic NF2 mutational inactivation characterizes only a subset of spinal cord ependymomas, and MYCN amplification is likely a genetic driver in a small subset of NF2 wildtype cases. The high frequency of chromosome 22q loss even in NF2-wildtype tumors raises the possibility of cryptic alterations in the NF2 gene not detected by our panel, or perhaps implicates the presence of another as yet unidentified tumor suppressor gene on chromosome 22q.

PATH-20. INVESTIGATION OF CLINICALLY AGGRESSIVE SPINAL CORD EPENDYMOMA THROUGH METHYLATION ANALYSIS

Abstract Spinal ependymoma is a rare, often low-grade tumor, for which the clinical course and prognosis has been poorly defined. Classification has relied on histological criteria, as there are few defining molecular mutations, causing controversy in diagnosis and grading. DNA methylation analysis with the brain tumor classifier was used on tumor tissue from 37 patients identified from the Neuro-Oncology Branch Natural History Study and selected Collaborative Ependymoma Research Network (CERN) Tissue Repository. These were histologically diagnosed with non-myxopapillary spinal ependymoma (92% grade II and 8% grade III), with 12 designated “poor performers” (50% male, median age 30 years) defined by a progression free survival of less than two years (median 7 months) with at least one recurrence. Alternatively, the 25 “good performers” (56% male, median age 43 years) had no progression with a follow-up time greater than 5 years (median 84 months). Methylation classification matched to “spinal ependymoma” in 33% of the poor performer cases while 8% matched myxopapillary or RELA-fusion ependymoma and 50% were no-match. For the good performers, 52% agreed with histological diagnosis, 28% matched myxopapillary and 20% were no-match. Interestingly, we noted high-level MYCN amplification by copy number analysis in two (17%) cases, neither of which matched to a defined methylation class, and both of which were in the poor performers group. Overall, methylation results reveal complex biology in conventional spinal cord ependymomas, most evident in an increase of no-match cases in the poor performers group. Of importance, the no-match cases contain evidence of a potentially new diagnostic entity characterized by both a poor prognosis and MYCN amplification. For further elucidation of this entity, a larger cohort of patients with expanded clinical criteria has been identified for further testing.

OS2.1 Incidence patterns for primary spinal cord ependymomas in adults: a Surveillance, Epidemiology, and End Results study

Abstract BACKGROUND Ependymomas are the most common primary spinal cord tumors in adults. However, few population-based studies analyzed the epidemiological features for this tumor type. We explored Surveillance, Epidemiology, and End Results (SEER) database to evaluate the incidence patterns over time with regard to patient gender, race, age at diagnosis, and histological subtype for patients diagnosed with primary malignant spinal cord gliomas between 1973 and 2015. METHODS We queried SEER database to identify all adult patients (≥ 20 years of age) diagnosed with primary spinal cord ependymomas during 1973–2015. Variables of interest included gender, race, age at diagnosis, and histological subtype of tumor. The SEER*Stat 8.3.5 program was used to calculate frequencies, age-adjusted incidence rates (IR) with adjustment to the 2000 US Standard population and 95% confidence intervals (CI). An annual percentage change (APC) statistic with a 2-sided p-values was used to assess incidence patterns over time. RESULTS 1224 adult patients with primary spinal cord ependymomas were diagnosed between 1973 and 2015. Of the total population, 55.7% were males (n = 682) and 44.3% were females (n=542). Myxopapillary ependymomas (ICD-O-3 code 9394), papillary ependymomas (9393), ependymomas (9391) and anaplastic ependymomas (9392) accounts for 28.7% (n = 351), 0.5% (n = 6), 69.4% (n = 849) and 1.5% (n = 18) respectively. The overall age-adjusted IR for all adult primary spinal cord ependymomas was 0.16 per 100,000 (95%CI 0.15–0.17). The IR in male was higher than that in female (males 0.19 per 100,000 [95% CI 0.17–0.20], females 0.14 per 100,000 [95% CI 0.13–0.14]. Caucasians experienced higher IR (0.18 per 100,000 [95% CI 0.17–0.19]) compared to African Americans (0.19 per 100,000 [95% CI 0.07–0.12]) and the others (0.10 per 100,000 [95% CI 0.08–0.13]). Patients of age between 40 and 49 years experienced the highest IR (0.25 per 100,000 [95% CI 0.22–0.29]) than patients in the other age ranges. The most common histological subtypes were ependymomas (0.11 per 100,000 [95% CI 0.11–0.12]) and myxopapillary ependymomas (0.047 per 100,000 [95% CI 0.042–0.052]. The overall age-adjusted IR for all adult primary spinal cord ependymomas showed a statistically significant increase over time between 1973 and 2015 (APC=5.15, p&lt;0.01). The same increasing trend was found in Caucasians (APC=5.36, p&lt;0.01) and in both males (APC=5.13, p&lt;0.01) and females (APC=4.95, p&lt;0.01). CONCLUSION This study demonstrates an increasing IR of adult primary spinal cord ependymomas over the past four decades. Males, Caucasians and age between 40 and 49 years experienced a higher IR.

Microsurgical Resection of Low-Grade Spinal Cord Astrocytoma: 2-Dimensional Operative Video.

This video demonstrates microsurgical resection of low-grade (Grade I) thoracic spinal cord astrocytoma. Astrocytomas are the most common pediatric intramedullary tumors and occur secondary to ependymomas in adults.1,2 The treatment goal should be radical gross total resection while preserving neurological function with intraoperative neuromonitoring.2-4 To our knowledge, this is the first video report on microsurgical resection of low-grade spinal cord astrocytoma. A 58-yr-old female presented with gait disturbances has been featured in this video. A spinal MRI revealed T1/T2 hyperintense intramedullary tumor at T4, suggesting spinal cord astrocytoma versus ependymoma. Dura was opened in the midline and tacked to the surrounding muscle tissue with tacking sutures. The arachnoid was opened separately with microscissors, keeping it intact for closure at the end of surgery. Liga clips were applied to hold the arachnoid to the dura. Myelotomy was done in the midline,5 opening the posterior median sulcus over the length of the tumor and extending proximally and distally a few millimeters beyond the tumor.3,5 The tumor reduction was achieved by coagulation or debulking. Once sufficient debulking was achieved, dissection of the tumor margins toward surrounding cord was performed. Preoperative recording of motor-evoked potentials (MEPs) compared with continuous intraoperative MEPs were essential for preserving the neurological function and quality of life. The intraoperative finding of a clear tumor plane of resection carries positive prognostic significance and reduces the risk of complications.2,3,6 A pathohistological diagnosis showed a low-grade (Grade I) spinal cord astrocytoma (pilocytic). Follow-up MRI showed no sign of tumor or recurrence. The patient recovered fully and was neurologically intact.Written consent was obtained directly from the patient.

Spinal Cord Ependymomas With MYCN Amplification Show Aggressive Clinical Behavior.

Adult spinal cord ependymomas are typically low grade and have a relatively favorable clinical course following gross total resection. We report 4 cases of anaplastic spinal cord ependymoma with MYCN amplification, an exceptionally rare finding. All cases occurred in the spinal cord of adolescent and young adult women and had morphological and immunohistochemical features of anaplastic ependymomas (World Health Organization grade III). Chromosomal microarray analysis demonstrated amplification of 2p24 (including MYCN) in all cases. One patient died 6 months after surgery. Another patient recently had removal of metastatic nodules in the thoracic region, following gross total resection and adjuvant radiation therapy of a lumbar ependymoma 1 year previously. One patient responded well after chemotherapy but died after multiple relapses 82 months after diagnosis. We found MYCN amplification reported in 2 other ependymomas, both anaplastic and arising in the spinal cord of adult females (Brain Pathol 2001;11:133-43). One patient had multiple recurrences in the spinal cord and an intracranial metastasis. Although MYCN amplification is rare in ependymomas, the current and previously reported cases suggest that this is associated with higher-grade histology, spinal location, and often unfavorable prognosis. The clinical significance and therapeutic implications of MYCN amplification in ependymomas require further evaluation.

Surgical treatment of spinal ependymomas

Introduction Spinal ependymom as are rare tumors and present mainly around 40 years of age. Total resection is claimed to be the best option for the treatment, but it carries some risk and it needs good evaluation and may be some proper facilities to get satisfactory results. Aim The aim of this study was to investigate the surgical strategies and outcomes for spinal ependymomas of different lengths and locations. We present our surgical experience in Al-Zahraa University Hospital (Al-Azhar University) for managing spinal cord ependymomas. Patients and methods We report the results of eight patients over a 2-year period (2016–2018). All cases were managed in Al-Zahraa University Hospital. Surgery was recommended for all patients who have symptoms. Preoperative and postoperative clinical assessments were done for all cases. Results There were six men and two women. The mean age was 36.4 years (range, 24–60 years). The follow-up period ranged from 1 month to 2 years. Gross total resection was done in six (75%) cases. Near-total resection was done in one case, and partial resection was done in one cervical case. The overall postoperative complications rate was 12%. Seven of the eight cases improved clinically. Pain improved in seven (87.5%) cases. All three cases with weakness improved within the first week of surgery or during the first 6 months (postoperative follow-up period). Sphincters improved in three out four cases that had been presented with sphincters. Conclusion Most spinal ependymomas can be managed by gross total resection without significant morbidity. Neurological deficit occurred more in tumors that extend more than two spinal levels. Some cases have early postoperative neurological functions declination, but these cases improved during follow-up. It is better to use neurophysiological monitoring, but it is not essential for achieving good outcome.

Intramedullary spinal cord ependymoma and astrocytoma: intraoperative frozen-section diagnosis, extent of resection, and outcomes.

OBJECTIVEThe intraoperative differentiation of ependymomas from astrocytomas is important because neurosurgical strategies differ between these two tumor groups. Previous studies have reported that the diagnostic accuracy of intraoperative frozen sections of intracranial central nervous system (CNS) tumors is higher than 83%-97%, whereas that for spinal intramedullary tumors remains unknown. Herein, authors tested the hypothesis that intraoperative frozen-section diagnosis is the gold standard for a differential diagnosis of intramedullary spinal cord tumors.METHODSThe clinical characteristics, intraoperative histological diagnosis from frozen sections, extent of tumor resection, progression-free survival (PFS), and overall survival (OS) of 49 cases of intramedullary spinal cord ependymomas (n = 32) and astrocytomas (n = 17) were retrospectively evaluated.RESULTSThe frozen-section diagnosis and final diagnosis with permanent sections agreed in 23 (72%) of 32 cases of ependymoma. Of the 9 cases of ependymoma in which the frozen-section diagnosis disagreed with the final diagnosis, 4 were incorrectly diagnosed as astrocytoma and the other 5 cases had a nonspecific diagnosis, such as glioma. Nonetheless, gross-total resection was achieved in 6 of these 9 cases given the presence of a dissection plane. The frozen-section diagnosis and final diagnosis agreed in 12 (71%) of 17 cases of astrocytoma. Of the 5 cases of astrocytoma in which the frozen-section diagnosis disagreed with the final diagnosis, 1 was incorrectly diagnosed as ependymoma and the other 4 had a nonspecific diagnosis. Gross-total resection was achieved in only 1 of these 5 cases.A relationship between the size of tumor specimens and the diagnostic accuracy of frozen sections was not observed. Ependymal rosettes and perivascular pseudorosettes were observed in 30% and 57% of ependymomas, respectively, but were absent in astrocytomas.Progression-free survival and OS were both significantly longer in cases of ependymoma than in cases of astrocytoma (p < 0.001). Gross-total resection was achieved in 69% of ependymomas and was associated with longer PFS (p = 0.041). In the astrocytoma group, gross-total resection was achieved in only 12% and there was no relationship between extent of resection and OS. Tumor grades tended to correlate with OS in astrocytomas (p = 0.079).CONCLUSIONSThe diagnostic accuracy of intraoperative frozen sections was lower for intramedullary spinal cord ependymomas and astrocytomas in the present study than that for intracranial CNS tumors reported on in the literature. Surgical strategies need to be selected based on multiple factors, such as clinical characteristics, preoperative imaging, frozen-section diagnosis, and intraoperative findings of the tumor plane.

Fluorescence Guided Surgery with 5-Aminolevulinic Acid for Resection of Spinal Cord Ependymomas.

Study DesignA retrospective study.PurposeWe report our experience with 5-aminolevulinic acid (5-ALA)–assisted resection of spinal cord ependymomas in adults.Overview of LiteratureEpendymoma is the most frequent primary spinal cord tumor in adults. Surgery is the treatment of choice in most cases. However, while complete resection is achieved in approximately 80% of cases, clinical improvement is achieved in 15% only. Five-ALA fluorescence–guided surgery seems to be useful for this tumor type.MethodsWe studied 14 patients undergoing 5-ALA fluorescence-guided surgery for spinal cord ependymomas in our service. The modified McCormick classification was used to determine clinical status and the degree of resection was assessed with magnetic resonance imaging.ResultsOf the 14 patients, the tumor showed an intense emission of fluorescence in 12 and the fluorescence was weak and nonuniform in two. Complete resection was achieved in 11 cases. According to the McCormick classification, 10 patients improved, two remained the same, and two deteriorated.ConclusionsOur results confirm that 5-ALA fluorescence-guided resection is useful in spinal cord ependymoma resection. Although the rate of complete resections is similar to that in published series without 5-ALA, clinical results are better when using 5-ALA with a lower percentage of clinical deterioration.

The Clinical Results of Radiation Therapy for Spinal Cord Ependymoma with Adverse Prognostic Features: A Single-Institution Experience

The primary treatment for spinal ependymoma is surgical resection. However, some cases cannot achieve complete resection because of either neurological compromise or disseminated feature. In these cases, radiotherapy (RT) is generally recommended, however, the role of RT has not been fully elucidated. This study evaluated the clinical outcome of RT on spinal ependymoma with the adverse feature, such as incomplete resection or disseminated disease. Between 1991 and 2016, 25 patients with spinal cord ependymoma treated with radiotherapy (RT) in a single institution were retrospectively reviewed. All except one patient with anaplastic ependymoma had gross disease in spinal MRI before RT. Eighteen (64%) underwent subtotal resection, while 6 (24%) did not undergo surgical resection. Six (24%) had multiple disseminated diseases. World Health Organization grade was I in 12 patients, II in 12 patients, and III in 1 patient. Nineteen (76%), 5 (20%), and 1 (4%) patients received RT to the localized disease, craniospinal area, and whole spinal cord with posterior cranial fossa, respectively. Median RT dose was 50.4 Gy (range, 44.0–59.4). With a median follow-up period of 49 months (range, 9–321 months), disease progression was observed in 4 patients, of whom 2 had clear cell ependymoma (grade II), and 2 had classic ependymoma (grade II). There was no failure or death in 12 patients with grade I ependymoma. Of 6 patients with disseminated disease, 3 had not experienced disease progression with follow-up of 111 months, 45 months, and 49 months, respectively. Of 18 patients with localized disease, 16 had not experienced disease progression until the last follow-up. In all patients, the 2- and 5-year progression-free survival rates were 91.7% and 79.6%, respectively, and overall survival rates were 95.7% and 83.7% respectively. Of patients with grade I ependymoma, the 2- and 5-year overall survival rates were 100%, while those were 91.7% and 69.4%, respectively, in patients with grade II or III ependymoma. Twelve (48%) showed improved neurologic function after RT. Late toxicity (hypopituitarism) occurred in 1 patient who received craniospinal irradiation. Favorable PFS and OS could be achieved with RT in spinal ependymoma with adverse features. RT appears to be an effective treatment option for spinal ependymoma in cases when complete tumor removal cannot be achieved.

Variety of preoperative MRI changes in spinal cord ependymoma of WHO grade II: a case series.

To report a case series of surgically proven spinal ependymomas of WHO grade II in which there were changes in the preoperative MRI characteristics over time. A total of 71 patients with spinal cord ependymoma of WHO grade II underwent surgery. There were ten cases in which surgery was performed at an average of 2.2years after the tumor was found. Cystic components, syringomyelia, hemorrhage "cap sign," Gd enhancement pattern, characteristic changes in MRI, MIB-1 index, and neurological assessment during the preoperative period were examined. Cases with a huge cyst showed further enlargement of the cyst on the caudal and rostral sides with hemosiderin formation over time and changes in the pattern of Gd enhancement. In contrast, cases without initial cyst did not show cyst formation, and nodular homogeneous lesion remained without changes in Gd enhancement. Regarding neurological status, two cases with cyst enlargement and hemosiderin formation had worsened non-independent gait preoperatively. MRI in cases of spinal ependymomas of WHO grade II showed characteristics such as hemorrhage and cyst formation that varied over time. In particular, cases with cyst and hemosiderin showed tumor enlargement, including enlargement of lesions on the caudal and rostral sides and enlargement of Gd-enhanced lesions. These characteristics might influence gait ability during preoperative period. We emphasize that early surgery is still the standard of care for cervical intramedullary ependymoma, and our findings in this study should not be interpreted to indicate that such early surgery is not necessary in symptomatic cases. These slides can be retrieved under electronic supplementary material.

Clinical outcomes of radiotherapy for spinal cord ependymoma with adverse prognostic features: a single-center study.

This study evaluated the outcomes of radiotherapy (RT) for spinal ependymoma with adverse features, such as incomplete resection or disseminated disease. Twenty-five patients underwent RT for spinal cord ependymoma during 1991-2016. Twenty-four patients had gross disease on the pre-RT spinal magnetic resonance images. Six patients (24%) had disseminated disease. The World Health Organization grades were I (12 patients), II (12 patients), and III (1 patient). The RT fields were the tumor bed plus margin in 19 patients (76%), the entire craniospinal axis in 5 patients (20%), and the entire spinal canal with posterior cranial fossa in 1 patient (4%). The median RT dose was 50.4Gy (range 44.0-59.4Gy). The median follow-up was 49months (range 9-321months), with 5-year overall and progression-free survival rates of 83.7% and 70.8%, respectively. Relative to patients with grade II/III ependymoma, patients with grade I ependymoma had higher 5-year rates of overall survival (100% vs. 69.4%, P = .088) and progression-free survival (100% vs. 42.3%, P = .02). Disease progression was observed in 4 patients who had grade II ependymoma, including 2 of 6 patients with disseminated disease and 2 of 19 patients with localized disease. Twelve patients (48%) exhibited improved neurological function. One patient who underwent craniospinal irradiation developed late hypopituitarism. No other RT-related late toxicities were observed. Favorable survival outcomes were achieved using RT for spinal ependymoma with adverse prognostic features. Thus, RT may be an effective treatment option when complete tumor removal cannot be achieved.

High-Grade Glioma is not a Feature of Neurofibromatosis Type 2 in the Unirradiated Patient.

The Manchester criteria for neurofibromatosis type 2 (NF2) include a range of tumors, and gliomas were incorporated in the original description. The gliomas are now widely accepted to be predominantly spinal cord ependymomas. To determine whether these gliomas include any cases of malignant glioma (WHO grade III and IV) through a database review. The prospective database consists of 1253 patients with NF2. 1009 are known to be alive at last follow-up. There was a single case of glioblastoma multiforme (GBM; World Health Organization grade IV) in the series and no WHO grade III gliomas. The GBM was in a patient who had previously undergone stereotactic radiosurgery for a vestibular schwannoma. High-grade gliomas are not a feature of NF2 in the unirradiated patient and should be excluded from the diagnostic criteria.

Case-based review: ependymomas in adults.

Ependymomas are rare primary central nervous system (CNS) tumors in adults. They occur most commonly in the spinal cord, and have classically been graded histologically into World Health Organization (WHO) grades I, II, or III based on the level of anaplasia. Recent data are showing that genetic heterogeneity occurs within the same histological subgroup and that ependymomas arising from different CNS locations have different molecular signatures. This has renewed interest in developing targeting therapies based on molecular profiles especially given the variable outcomes with radiation and the poor results with cytotoxic agents. In this paper, we present the case of a 46-year-old woman with a classic presentation of spinal cord ependymoma and discuss the current histopathological and molecular classification for ependymomas as well as current guidelines for patient management.

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

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. 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. 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. 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.

Pediatric Spinal Ependymomas: An Epidemiologic Study

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. 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. 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. 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.

Neoplastic Myelopathies.

This article discusses the diagnosis and management of neoplasms that affect the spinal cord as well as spinal cord disorders that can occur due to cancer treatments. Neoplastic myelopathies are uncommon neurologic disorders but cause significant morbidity when they occur. Primary spinal cord tumors can be classified into intramedullary, intradural extramedullary, or extradural tumors. Diffuse gliomas and ependymal tumors are the most common intramedullary tumors. Diffuse gliomas include the World Health Organization (WHO) grade II and grade III astrocytomas, the grade II and grade III oligodendrogliomas, the grade IV glioblastomas, and newly recognized pediatric diffuse midline gliomas with H3 K27M mutation. The majority of diffuse and anaplastic astrocytomas are IDH-mutant tumors, whereas only 10% of glioblastomas are IDH-mutant. Oligodendrogliomas are typically IDH-mutant and are characterized by the molecular signature of 1p/19q codeletion. Nine distinct molecular subgroups of ependymomas have been identified based on their genetic features and location. NF2 mutations are frequently found in spinal cord ependymomas. Metastatic tumors are the most common tumors of the spine and can be extradural, leptomeningeal, or, rarely, intramedullary. Extradural metastatic spinal cord compression is a neurologic emergency and should be promptly diagnosed as pretreatment neurologic status dictates the posttreatment outcome. Neoplastic myelopathies encompass many diagnoses ranging from benign and malignant spinal tumors to paraneoplastic syndromes heralding cancers. The knowledge of the clinical features and management of neoplastic myelopathies is essential to practicing neurologists as early diagnosis and treatment can prevent devastating neurologic sequelae.

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

BackgroundThe 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. MethodsThe 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. ResultsThe 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). ConclusionsTotal 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.

LncRNA LINC00880 promotes cell proliferation, migration, and invasion while inhibiting apoptosis by targeting CACNG5 through the MAPK signaling pathway in spinal cord ependymoma.

The present study was to investigate the effect of lncRNA LINC00880 targeting CACNG5 on cell proliferation, migration, invasion, and apoptosis in spinal cord ependymoma (SCE) through the MAPK signaling pathway. GEO database was used to download gene expression data related with SCE (GSE50161 and GSE66354) and annotation file. LncRNA with differential expression was predicted by Multi Experiment Matrix website (MEM). The target gene was analyzed by KEGG pathway enrichment analysis. SCE tissues and adjacent tissues were collected. The positive expression of CACNG5 protein was tested by immunohistochemistry. Expression of LINC00880, CACNG5, and MAPK signaling pathway-related proteins was measured with qRT-PCR and Western blotting. Cell proliferation, migration, invasion, cycle, and apoptosis were detected using MTT, Transwell assay, Scratch test, and Flow cytometry. SCE tissues showed increased LINC00880 expression. CACNG5 was a target gene of LINC00880 and correlated with MAPK signaling pathway. Compared with adjacent tissues, SCE tissues showed lower positive expression of CACNG5. Compared with the blank group, LINC00880 expression was higher in the LINC00880 vector and LINC00880 vector + CACNG5 vector groups, and lower in the si-LINC00880 and si-LINC00880 + si-CACNG5 groups; in the LINC00880 vector and si-CACNG5 groups, expression of survivin, p38MAPK, ERK1/2, JNK1/2/3 increased and CACNG5 and Bax expression reduced, the proliferation, invasion and migration of tumor cells increased, and apoptosis rate decreased. Opposite results were found in the si-LINC00880 and CACNG5 vector groups. The findings indicate that lncRNA LINC00880 targeting CACNG5 inhibits cell apoptosis and promotes proliferation, migration, and invasion in SCE through the MAPK signaling pathway.