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Myxopapillary ependymoma (MPE) is a unique slow-growing benign (WHO grade 1) subtype of spinal cord ependymoma arising predominantly in the filum terminale. Despite its benign nature, it occasionally disseminates through the cerebrospinal fluid and metastasizes to distant sites. Here, we report an extremely rare case of MPE with interval CSF seeding and metachronous metastasis in a 47 -year-old female presented as a gradually increasing low back pain for three months with bilateral radiculopathy down to the knees. Magnetic resonance imaging (MRI) showed an intradural extramedullary spinal mass of iso-intense signal to the cord on T1 weighted-images (WIs), heterogeneous, predominantly hyperintense signal on T2WIs with homogenous enhancement after contrast administration. L2 laminectomy with gross total resection (GTR) was performed, and histopathological results confirmed the diagnosis of MPE. Adjuvant radiotherapy was administered, followed by series of MRI scans. 28 months after GTR, Lumbar MRI showed multiple tiny enhancing nodules in the cauda equina. 44 months follow-up whole spine MRI revealed multiple intradural extramedullary nodules throughout the entire spine. The largest one measures about 1.5cm opposite to T3 -T4 intervertebral disc space. The patient underwent T3 and T4 laminectomy and GTR under general anesthesia using microsurgical techniques, and the histopathological result came with the diagnosis of MPE.

Neurofibromatosis type 2 (NF2) is a rare, hereditary tumor syndrome, often requiring repeated surgeries for multiple lesions with significant cumulative morbidity. As such, non-operative management should be considered when possible for this patient population. The aim of this study is to provide a systematic review of the literature regarding this treatment strategy. A descriptive case of a patient in whom bevacizumab treatments enabled over 15 years of surgical postponement for a symptomatic spinal cord ependymoma is also provided. Evidence suggests that bevacizumab is a reasonable surgery-deferring option for cystic lesions, and it may be especially useful in NF2 patients to reduce cumulative morbidity.

Background No standard medical treatment exists for adult patients with recurrent ependymoma, and prospective clinical trials in this population have not succeeded because of its rarity and challenges in accruing patients. The Collaborative Ependymoma Research Network conducted a prospective phase II clinical trial of dose-dense temozolomide (TMZ) and lapatinib, targeting the unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter status and increased expression of ErbB2 (human epidermal growth factor receptor 2) and ErbB1 (epidermal growth factor receptor) in ependymomas. Methods Patients age 18 or older with histologically proven and progressive ependymoma or anaplastic ependymoma were eligible and received dose-dense TMZ and daily lapatinib. The primary outcome measure was median progression-free survival (PFS). Landmark 6- and 12-month PFS and objective response were measured. Serial assessments of symptom burden using the MD Anderson Symptom Inventory Brain Tumor (MDASI-BT)/MDASI–Spine Tumor modules were collected. Results The 50 patients enrolled had a median age of 43.5 years, median Karnofsky performance status of 90, and a median of 2 prior relapses. Twenty patients had grade III, 16 grade II, and 8 grade I ependymoma. Half had spinal cord tumors; 15 had a supratentorial tumor, 8 infratentorial, and 2 had disseminated disease. Treatment was well tolerated. The median PFS was 7.8 months (95% CI: 5.5,12.2); the 6- and 12-month PFS rates were 55% and 38%, with 2 complete and 6 partial responses. Measures of symptom burden showed reduction in moderate-severe pain and other disease-related symptoms in most patients. Conclusions This treatment, with demonstrated clinical activity with objective responses and prolonged disease control associated with disease-related symptom improvements, is an option as a salvage regimen for adult patients with recurrent ependymoma.

We report a novel group of clinically aggressive spinal cord ependymomas characterized by Grade III histology, MYCN amplification, an absence of NF2 alterations or other recurrent pathogenic mutations, and a unique methylation classifier profile. Seven cases were found to have MYCN amplification in the course of routine mutational profiling of 552 patients with central nervous system tumors between December 2016 and July of 2019 and an eighth patient was identified from an unrelated set of cases. Methylation array analysis revealed that none of the 8 cases clustered with any of the nine previously described ependymoma methylation subgroups, and 7 of 8 formed their own tight unique cluster. Histologically all cases showed grade III features, and all demonstrated aggressive clinical behavior. These findings are presented in the context of data from three other studies describing similar cases. Therefore, a combined total of 27 MYCN amplified spinal cord ependymoma cases have now been reported in the literature, warranting their consideration as a distinctive subtype of spinal cord ependymoma (SP-EPN-MYCN) with their unique molecular characteristics and 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.

Background: Ependymoma is a common primary neoplasm of the spinal cord and filum terminale. Patients with spinal ependymoma usually experience gradual symptoms due to slow progression of the tumor; thus, early diagnosis can be challenging to make. Objective: The objective of this study was to report 5 years’ experience in treating spinal intramedullary ependymomas and to illustrate the advantage of aggressive complete resection whenever possible. Patients and Methods: Retrospective medical notes of all patients with spinal ependymoma treated surgically over a 5-year period between January 2003 and January 2008 were recorded. Clinical presentation, spinal level, extent of resection, and complications were recorded. A prolonged follow-up was documented. Results: There were 20 patients – 11 males, and nine females –included in this study. Their median age was 48 years (range 3–75 years). In 18 patients, total gross resection was achieved. Subtotal resection was only possible in one patient due to surgical difficulty. One patient underwent biopsy and referred for further surgery and subsequently had total resection. Conclusions: Radical total resection is achievable in spinal ependymomas, with minimal resultant morbidity.

Purpose Few studies report outcomes in children treated with radiation for nonmyxopapillary ependymoma of the spinal cord, and little evidence exists to inform decisions regarding target volume and prescription dose. Moreover, virtually no mature outcome data exist on proton therapy for this tumor. We describe our combined institutional experience treating pediatric classical/anaplastic ependymoma of the spinal cord with proton therapy. Methods and Materials Between 2008 and 2019, 14 pediatric patients with nonmetastatic nonmyxopapillary grade II (n = 6) and grade III (n = 8) spinal ependymoma received proton therapy. The median age at radiation was 14 years (range, 1.5-18 years). Five tumors arose within the cervical cord, 3 within the thoracic cord, and 6 within the lumbosacral cord. Before radiation therapy, 3 patients underwent subtotal resection, and 11 underwent gross-total or near total resection. Two patients received chemotherapy. For radiation, the clinical target volume received 50.4 Gy (n = 8), 52.2 (n = 1), or 54 Gy (n = 5), with the latter receiving a boost to the gross tumor volume after the initial 50.4 Gy, modified to respect spinal cord tolerance. Results With a median follow-up of 6.3 years (range, 1.5-14.8 years), no tumors progressed. Although most patients experienced neurologic sequela after surgery, only 1 developed additional neurologic deficits after radiation: An 18-year-old male who received 54 Gy after gross total resection of a lumbosacral tumor developed grade 2 erectile dysfunction. There were 2 cases of musculoskeletal toxicity attributable to surgery and radiation. At analysis, no patient had developed cardiac, pulmonary, or other visceral organ complications or a second malignancy. Conclusion Radiation to a total dose of 50 to 54 Gy can be safely delivered and plays a beneficial role in the multidisciplinary management of children with nonmyxopapillary spinal cord ependymoma. Proton therapy may reduce late radiation effects and is not associated with unexpected spinal cord toxicity.

Spinal ependymomas are the most common intramedullary spinal cord tumors in adults.1-4 They are benign histologically, and maximum safe surgical resection should be pursued with the goal of maintaining neurological integrity.4 Spinal ependymoma resections have been described in the operative video literature, including those using techniques of laminoplasty to prevent postlaminectomy kyphosis.1-3,5 Defining the planes between tumor and normal spinal cord is critical to achieving safe maximum resection.3 This video will illustrate the microsurgical techniques used in the resection of a large spinal cord ependymoma in a patient who presented with progressive lower extremity paraparesis and incontinence and was found to have a large intradural, intramedullary C4-T3 lesion with a rostral glial tumor cyst. The patient consented to surgical intervention. The patient was placed prone in MAYFIELD 3-point pin fixation (Integra LifeSciences, Plainsboro Township, New Jersey). Intraoperative neurophysiological electrodes were placed for somatosensory evoked potentials, motor evoked potentials, and D-wave monitoring of corticospinal tracts.6,7 C3-T4 replacement laminoplasties were performed. A midline dural incision spanning C4-T4 was made. A midline myelotomy preserving the pial venous plexus was performed with a 69 Beaver blade.2 The attachments of the tumor to the normal white matter of the spinal cord were microsurgically defined, coagulated, and divided. Tumor debulking was performed with an ultrasonic aspirator. Once gross total resection was achieved, the pial edges of the spinal cord were reapproximated. The dura was closed in a watertight fashion. The patient recovered from surgery well with preservation of her motor function with a continued T7 sensory level.

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 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.

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 2.2 years 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.

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 50.4 Gy (range 44.0–59.4 Gy). The median follow-up was 49 months (range 9–321 months), 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.

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.

Objective A spinal cord subependymoma is an uncommon, indolent, benign spinal cord tumor. It is radiologically similar to a spinal cord ependymoma, but surgical findings and outcomes differ. Gross total resection of the tumor is not always feasible. The present study was done to determine the clinical, radiological and pathological characteristics of spinal cord subependymomas. Methods We retrospectively reviewed the medical records of ten spinal cord subependymoma patients (M : F=4 : 6; median 38 years; range, 21-77) from four institutions. Results The most common symptoms were sensory changes and/or pain in eight patients, followed by motor weakness in six. The median duration of symptoms was 9.5 months. Preoperative radiological diagnosis was ependymoma in seven and astrocytoma in three. The tumors were located eccentrically in six and were not enhanced in six. Gross total resection of the tumor was achieved in five patients, whereas subtotal or partial resection was inevitable in the other five patients due to a poor dissection plane. Adjuvant radiotherapy was performed in two patients. Neurological deterioration occurred in two patients; transient weakness in one after subtotal resection and permanent weakness after gross total resection in the other. Recurrence or regrowth of the tumor was not observed during the median 31.5 months follow-up period (range, 8-89). Conclusion Spinal cord subependymoma should be considered when the tumor is located eccentrically and is not dissected easily from the spinal cord. Considering the rather indolent nature of spinal cord subependymomas, subtotal removal without the risk of neurological deficit is another option.

The paper describes long-term results of surgical treatment of a female patient with intramedullary ependymoma at the cervical level. Long relapse-free period was reported after the radical removal of intramedullary ependymoma. A complication developed after multilevel laminectomy required anterior fusion. Analysis of patient’s neurological symptoms and level of long-term social adaptation showed her full independence and preservation of working capacity.

BACKGROUND Ependymomas are currently classified into 9 subgroups by DNA methylation profiles. Although spinal cord ependymoma (SP-EPN) is distinct from other tumors, diversity within SP-EPN is still unclear. Here, we used transcriptomic and epigenomic profiles to investigate the diversity among Japanese SP-EPN cases. MATERIALS AND METHODS We analyzed 57 SP-EPN patients (32 males and 25 females, aged from 18 to 78 years, median: 52), including two cases of neurofibromatosis type 2, five cases of grade 3 (WHO grade). We obtained transcriptome (RNA-seq) and DNA methylation (Infinium Methylation EPIC array) data from fresh frozen specimens of SP-EPN resected at the University of Tokyo Hospital and our collaborative groups. RESULTS Three cases had a previous intracranial ependymoma operation. Hierarchical clustering of the DNA methylation data showed that these three cases of intracranial origin as a different cluster from spinal origin. The 45 grade 2 spinal ependymoma showed a relatively homogenous methylation pattern. However, the methylation status of HOX gene cluster regions is compatible with the segment of origin, which reflects the cells of origins are derived after the determination of segment identity. RNA sequencing of 57 cases revealed two subgroups within grade 2. Gene ontology analysis of differentially expressed genes suggested the difference in metabolic state such as rRNA translation and mitochondrial respiration between the two expression subgroups. CONCLUSION Epigenetic analysis indicated the accurate body segment origin of SP-EPN. We observed that metabolic states could divide grade 2 spinal cord ependymoma into 2 subgroups and will present the relationship to clinicopathological information.

Purpose/Objective(s) There is limited information published on the outcome of children treated with radiation for high-grade ependymoma of the spinal cord. Thus, little evidence is available to inform decisions of target volume or prescription dose. Moreover, there is virtually no mature outcome data on proton therapy, despite theoretical advantages in normal tissue exposure. We therefore performed a bicentric retrospective study to better inform treatment of this rare tumor in children. Materials/Methods Between 2008 and 2019, 14 consecutive pediatric patients with a non-metastatic grade II or III spinal ependymoma were treated with proton therapy at the University of Florida and Massachusetts General Hospital. The median age of the children at the time of radiation was 14 years old (range, 1.5-18 years). Five tumors arose within the cervical cord (C1-5, C1-2, C1-T1, C3-T1, C4-C6), 3 within the thoracic spine (C7-T4, T7-L1, T11-T12), and 6 within the lumbosacral spine (L3-L5, L3-L5, L4-S2, S2-S5, L2-L3, L2-L3). Six tumors were grade II histology and 8 were grade III. Prior to radiotherapy, 3 patients had undergone a subtotal resection while the other 11 had a gross total or near total resection. One patient received chemotherapy according to the International Society of Pediatric Oncology (SIOP) infant regimen and 1 patient received chemotherapy according to Children's Oncology Group (COG) ACNS0831. For radiation, the gross tumor volume (GTV) was defined by the gross disease and/or tumor bed at the time of radiation. The CTV was defined by the GTV + 5-10 mm. The CTV received 50.4 Gy (n = 8), 52.2 (n = 1), or 54 Gy (n = 5), with the latter undergoing boost to just the GTV following the initial 50.4 Gy to respect spinal cord tolerance. For the cohort, the median maximum point dose to the spinal cord was 52.4 Gy (range, 0-53.9 Gy). The median maximum dose to 0.1 cc of spinal cord was 51.3 Gy (range, 0-52.5 Gy). The median volume of cord receiving ≥50.4 Gy was 3.4 cc (range, 0-17.1 cc). Results With a median follow-up of 6.3 years (range, 1.5 – 14.8 years), no tumors have progressed and all patients are alive. Serious acute toxicity was limited to 1 case of grade 2 nausea. While most patients experienced neurologic sequela following surgery, only 1 patient developed additional neurologic deficits following radiation: An 18-year-old male who received 54 Gy following gross total resection of a lumbosacral tumor developed grade 2 erectile dysfunction. There were 2 cases of chronic musculoskeletal toxicity attributable to surgery and radiation in survivors. No patients have developed cardiac, pulmonary, or other visceral organ complications, nor has any patient developed a second malignancy. Conclusion These outcomes suggest that radiation to a dose of 50-54 Gy can be safely delivered and plays a beneficial role in the multidisciplinary management of children with grade II/III spinal cord ependymoma. Proton therapy may reduce the late radiation effects and is not associated with unexpected spinal cord toxicity.

PURPOSE Pediatric Spinal cord ependymoma (SCE) is rare, and the management is often heterogeneous across centers. We evaluated the impact of clinical, pathologic, and treatment-related factors on outcomes in a multi-institutional, international cohort. METHODS SCE patients age RESULTS 125 patients were identified, 18 (14.4%) with metastases. Initial surgery was GTR, and STR in 44, 56% of patients respectively. Histology was grade 1, 2, and 3 in 55, 17.7 and 23.2% respectively. 55 patients with initial GTR were observed (52.7%) or irradiated (43.6%); 60 patients had STR and were observed (40%) or irradiated (60%). The 7-year event-free (EFS) and overall survival (OS) was 60% (95% CI 51.5–71.4) and 79% (95% CI 71.1–87.8) respectively. STR and metastasis increased the hazard for death [HR 1.87, 95% CI 1.02–3.57, p=0.05 (vs. GTR)] and [HR 2.28, 95% CI 1.1–5.2, p=0.048 (vs. localized)] respectively. Across 43 failures, local failure predominated (48.8%). Distant and combined failure occurred in 30.2 and 13.9% respectively. Adjuvant RT offered a 20% absolute improvement (vs. observation) in EFS at 5 years regardless of extent of resection. RPA identified thoracic (vs. non-thoracic), grade (1 & 3 vs. 2), STR (vs. GTR) and metastases as determinants of inferior EFS. CONCLUSIONS Tumor and treatment-related factors are predictive of EFS. OS is favorable despite diverse schema and frequent distant failures.

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.

OBJECTIVE To investigate the expression of H3K27me3 in different anatomical sites and analyze its prognostic value in children with ependymoma. METHODS 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. RESULTS 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

STUDY DESIGN A retrospective study of preoperative and postoperative magnetic resonance imaging (MRI) findings in spinal ependymoma. OBJECTIVE The goal of the study was to examine MRI features, including the syrinx component volume, after surgical resection of spinal ependymoma, and to relate these features to extent of resection and improvement of postoperative neurological status. SUMMARY OF BACKGROUND DATA Spinal ependymomas have a variety of MRI findings preoperatively, including a hemorrhage cap sign, gadolinium enhancement, and a spinal tumor cyst. However, little is known about these features on postoperative MRI after tumor resection. MATERIALS AND METHODS The subjects were 38 patients treated for spinal cord ependymoma of World Health Organization grade II at our hospital. All had a spinal tumor cyst on preoperative MRI. All cases were followed with MRI for >1 year after surgery, including imaging at postoperative months (POM) 1 and 12. The maximum diameter of the syrinx was measured on mid-sagittal MRI. The extent of tumor resection was categorized as gross total resection (GTR) and subtotal resection (STR). RESULTS The mean age of the 38 patients (22 male and 16 female individuals) was 50.9 years (range, 21-71 y) at the time of surgery. The mean preoperative duration from disease onset was 14.9 months (range, 2-47 mo). GTR was achieved in 28 patients (74%) and STR in 10 (26%). The mean syrinx sizes preoperatively and at POM 1 and POM 12 were 7.5±2.3, 4.1±1.9, and 2.5±1.8 mm, respectively, with significant differences among the time points (P

Introduction Spinal cord tumors are a rare cause of spinal cord disorder (SCD). Early diagnosis can be challenging, especially in patient populations with other potential etiologies for back pain, such as pregnant women. Case presentation A 28-year-old female presented at 8 weeks gestation with thoracic back pain initially diagnosed as gestational low back pain. Her symptoms progressed to lower extremity weakness. After diagnosis and resection of a spinal cord ependymoma, we collaborated with the inpatient interdisciplinary team to devise a rehabilitation program focused on minimizing pregnancy-related complications and optimizing care of a newborn in the setting of a new paraplegia. Discussion Providers should not assume all pregnant women with low back pain have gestational back pain, as it can be due to more insidious causes. The rehabilitation course for women who develop an SCD during gestation should be carefully tailored toward their pre- and post-natal care and with the education of how the disorder can affect pregnancy and parenting.

The histopathology of intramedullary spinal cord tumors (IMSCT) can be suspected from the MRI features and characteristics. Ultimately, the confirmation of diagnosis requires surgery. This retrospective study addresses MRI features including homogeneity of enhancement, margination, and associated syrinx in intramedullary astrocytomas (IMA) and ependymomas (IME) that assist in diagnosis and predict resectability of these tumors.Single-center retrospective analysis of IMA and IME cases since 2005 extracted from the departmental registry/electronic medical records post IRB approval (IRB 201,710,760). We compared imaging findings (enhancement, margination, homogeneity, and associated syrinxes) between tumor types and examined patient outcomes.There were 18 IME and 21 IMA. On preoperative MRI, IME was favored to have homogenous enhancement (OR 1.8, p = 0.0001), well-marginated (p 0.0001, OR 0.019 [95 % CI 0.002-0.184]), and associated syrinx (p = 0.015, OR 0.192 [95 % CI 0.049-0.760]). Total excision, subtotal excision, and biopsy were performed in 12, 5, and 1 patients in the IME cohort, respectively. In the IMA group, tumors were heterogeneous and poorly marginated in 20 of the 21 patients. Total excision, subtotal excision, and biopsy were undertaken in 2, 13, and 6 patients, respectively. The success of excision was predicted by MRI, with a significant difference in the extent of resection between IME and IMA (XThe imaging characteristics of IME and IMA have meaningful clinical significance. Homogeneity, margination, and associated syrinxes in IME can predict resectability and complexity of surgery.

This report presents the longest spanning intradural myxopapillary ependymoma consisting of 23 vertebral segments in the literature. An 11-year-old boy presented with right arm pain, mid back pain and progressive paraparesis associated with urinary retention. On MRI, the patient was found to have an intradural lesion extending from C5 to S3. The patient underwent T7 and T8 laminectomies with an almost total resection except for a minimal residual adhering to the spinal cord. The patient with the largest spanning spinal cord ependymoma was managed satisfactorily without significant morbidity. A small laminectomy may be used in some occasions despite the tumour’s extensive size because it may have a single point of attachment to the cord.

Study design A retrospective study. Purpose We report our experience with 5-aminolevulinic acid (5-ALA)-assisted resection of spinal cord ependymomas in adults. Overview of literature Ependymoma 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. Methods We 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. Results Of 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. Conclusions Our 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.

Ependymomas of the spinal cord are glial tumors arising from ependymal cells along the central canal of the spinal cord. They are rare, typically have a long natural history, and behave differently than their intracranial counterparts. They are grouped based on the World Health Organization (WHO) classification from grade I to III, with grade II spinal cord ependymomas appearing to be the most indolent despite their intermediate grade. Myxopapillary ependymoma (MPE) is a distinct subset that occurs almost exclusively in the conus medullaris, cauda equina, or filum terminale. Spinal cord ependymomas often present insidiously with back pain or neurologic deficits that are dependent on their location within the cord. Management consists of surgical resection, with gross total resection (GTR) offering the best chance for long-term control and possible cure. The role of postoperative radiation is controversial, but in general, radiation is employed locally for subtotal resection (STR), grade III (anaplastic) ependymomas, or after re-resection for recurrent disease. Long-term survival is excellent with rates over 85% at 10 years. However, 17 to 30% will recur, often years following initial treatment. As such, continued follow-up with surveillance imaging is essential.

We aimed to examine the impact of demographic and treatment factors on overall survival among spinal ependymoma patients.Using data from Surveillance, Epidemiology, and End Results (SEER) from 1990-2008, we evaluated subjects with histologically confirmed spinal cord ependymoma.We identified 1,353 patients with spinal ependymoma (mean age 43.5 years). Among these, 26 had anaplastic ependymoma (AE), 374 had myxopapillary ependymoma (MPE), and 953 had other low-grade ependymoma (non-MPE). Median follow-up was 61 months. Overall survival at 5 years was 97% for MPE, 92% for low-grade non-MPE, and 73% for AE. Gross total resection (GTR) was achieved in 58% of subjects with MPE, 51% with low-grade non-MPE, and 50% with AE. Radiation occurred more often after subtotal resection (STR) than after GTR, and more often among those with anaplastic histology. Histology and extent of surgical resection were significant prognostic factors in multivariate analyses. Compared to MPE, subjects with low-grade non-MPE had a higher risk of mortality at 5 years (HR 2.35, P = 0.03), as did subjects with AE (HR 8.63, P 0.01). Compared to GTR, STR was associated with an increased risk of mortality at 5 years (HR 2.2, P = 0.01), as was biopsy only (HR 2.05, P = 0.03) and no surgery (HR 4.97, P 0.01). Among patients with either STR or GTR, adjuvant radiotherapy did not confer a survival benefit at 5 years (STR: HR 2.29, P = 0.07, and GTR: HR 2.2, P = 0.12).We found that lower grade histology and higher extent of surgical resection were significant prognostic factors for more favourable survival outcomes for spinal ependymoma patients.

OBJECT Grade II spinal cord ependymomas occurring in pediatric patients are exceptionally rare neoplasms. In this paper the authors use a national cancer database to determine patient demographics, treatment patterns, and associated outcomes of this cohort. METHODS The Surveillance Epidemiology and End Results (SEER) database was used to analyze subjects younger than 18 years with histologically confirmed diagnoses of Grade II spinal cord ependymoma from the years 1973 to 2008. Descriptive data on the demographic characteristics of this cohort and the associated treatment patterns are shown. The Kaplan-Meier method was used to estimate overall survival at 1, 2, 5, and 10 years. RESULTS This cohort comprised 64 pediatric subjects with Grade II spinal ependymoma. The median age was 13 years, nearly half of the patients were male, and most were white (84%). The median follow-up was 9.2 years. Overall survival at 5 and 10 years was 86% and 83%, respectively. Gross-total resection was achieved in 57% of subjects, and radiation therapy was administered to 36%. Radiation therapy was administered to 78% of subjects after subtotal resection but only to 19% of patients after gross-total resection; this difference was significant (p < 0.001). In a multivariate regression model analyzing sex, age at diagnosis, year of diagnosis, radiotherapy, and extent of resection, female sex was found to be an independent predictor of decreased mortality (HR 0.15 [95% CI 0.02–0.94], p = 0.04). CONCLUSIONS These data show long-term outcomes for pediatric patients with Grade II spinal ependymoma. Radiotherapy was more likely to be administered in cases of subtotal resection than in cases of gross-total resection. Female sex is associated with decreased mortality, while other demographic or treatment modalities are not.

Purpose: This study used receiver operating characteristic curve to analyze Surveillance, Epidemiology and End Results (SEER) ependymoma data to identify predictive models and potential disparity in outcome. Materials and Methods: This study analyzed socio-economic, staging and treatment factors available in the SEER database for ependymoma. For the risk modeling, each factor was fitted by a Generalized Linear Model to predict the outcome (‘brain and other nervous systems’ specific death in yes/no). The area under the receiver operating characteristic curve (ROC) was computed. Similar strata were combined to construct the most parsimonious models. A random sampling algorithm was used to estimate the modeling errors. Risk of ependymoma death was computed for the predictors for comparison. Results: A total of 3,500 patients diagnosed from 1973 to 2009 were included in this study. The mean follow up time (S.D.) was 79.8 (82.3) months. Some 46% of the patients were female. The mean (S.D.) age was 34.4 (22.8) years. Age was the most predictive factor of outcome. Unknown grade demonstrated a 15% risk of cause specific death compared to 9% for grades I and II, and 36% for grades III and IV. A 5-tiered grade model (with a ROC area 0.48) was optimized to a 3-tiered model (with ROC area of 0.53). This ROC area tied for the second with that for surgery. African-American patients had 21.5% risk of death compared with 16.6% for the others. Some 72.7% of patient who did not get RT had cerebellar or spinal ependymoma. Patients undergoing surgery had 16.3% risk of death, as compared to 23.7% among those who did not have surgery. Conclusion: Grading ependymoma may dramatically improve modeling of data. RT is under used for cerebellum and spinal cord ependymoma and it may be a potential way to improve outcome.

Patients with neurofibromatosis 1 (NF1) are predisposed to develop central nervous system tumors, due to the loss of neurofibromin, an inactivator of proto-oncogene Ras. However, to our knowledge, only three cases of ependymomas with NF1 have been reported in the literature. The authors present a case of NF1 patient with a spinal cord ependymoma. She was referred for about half a year history of increasing numbness that progressed from her fingers to her entire body above the bellybutton. Magnetic resonance imaging revealed a relative-demarcated, heterogeneously enhanced mass lesion accompanied by perifocal edema in C5-7 level, a left-sided T11 spinous process heterogeneously enhanced mass in soft tissue, intervertebral disk hernia in L2-5 level, and widespread punctum enhancing lesion in her scalp and in T11-L5 level. The patient underwent C5-7 laminectomies and total excision of the tumor under operative microscope, and intraoperative ultrasonography and physiological monitoring were used during the surgery. Histopathologically, her tumor was found to be a ependymoma without malignant features (grade II in the World Health Organization classification). Therefore, no adjuvant therapy was applied. Following the operation, the patient showed an uneventful clinical recovery with no evidence of tumor recurrence after one year of follow-up.

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.

Objective: The purpose of this study was to determine characteristic imaging findings of intramedullary spinal cord tumor in magnetic resonance imaging (MRI). Material and Methods: We retrospectively analyzed MRI in 15 patients with histologicaly proven intramedullary spinal cord tumors. The demographic data, MRI findings with histological findings were recorded in terms of age, location, length, morphology, signal intensity, the presence or absence of cyst and hemorrhage, enhancement pattern, other associated findings, necrosis, vascular proliferation and WHO grading. Results: Among the 15 patients, spinal cord ependymomas were eccentric 75%, well-define border 62.5% and cervicothoracic spine located 37.5%. Spinal cord astrocytomas were eccentrically located and ill-define border 85.7%, cervicothoracic and thoracic spine located 28.5%. A cystic component was seen in 87.5% of spinal cord ependymoma and 71.5% of astrocytomas. Intratumoral hemorrhage occurred in 75% of spinal cord ependymomas, and 57.1% of astrocytomas. In 12.5% of spinal cord ependymomas, a curvilinear low T2 signal, suggesting marginal hemorrhage, was seen at the upper and/or lower margins of the tumors. Twenty-five percent of spinal cord ependymoma and 57.2% of astrocytomas showed heterogeneous enhancement, while in 12.5% of spinal cord ependymomas, enhancement was homogeneous. Conclusion: Although no statistically significant characteristic MRI feature to distinguish between ependymoma and astrocytoma is detected. By percentage we found that border, length and signal intensity of tumors may help diagnosis. With pathological correlation, all of spinal cord ependymomas are mark hypervascular tumor, but astrocytomas never showed.

Purpose A retrospective study was performed to evaluate the results of postoperative radiation therapy of spinal cord ependymoma in children. Methods and materials Between 1984 and 2005, 28 children with spinal cord ependymoma were treated with radiotherapy, after surgery and in three cases after chemotherapy as well. Median age at diagnosis was 13.3years (range from 4.7 to 16.2years). Ependymoma myxopapillare was identified in 13, ependymoma in 12 and anaplastic ependymoma in 3 cases. Results With a median follow-up of 8.7years (range from 3 to 25years) 22 patients were alive. The overall survival rate of 2, 5 and 10years was 93%, 85% and 77% respectively, whereas progression free survival rate was 82%, 74% and 74% respectively. Patients with myxopapillary ependymoma had significantly better 5-year overall survival rate 100% than those with other histopathological types 60% ( p =0.016). There were 2 relapse incidences observed among 13 patients with myxopapillary ependymoma, both underwent repeated surgery and reirradiation. In the group of 20 patients with gross total resection the overall 5-year survival rate was 100% in comparison with 62.5% with partial surgery, but it did not achieve statistical significance. Conclusions The histological type of ependymoma myxopapillary was a statistical significant favourable prognostic factor. The gross total resection with adjuvant radiotherapy allows obtaining a high total survival rate.

Spinal ependymomas are rare tumours, with total resection favoured where possible. Several case series assessing the outcome following neurosurgical treatment for spinal ependymoma advocate the usage of adjuvant radiotherapy in cases of subtotal resection, or in unencapsulated tumours. We assessed the outcome of 61 consecutive cases of spinal ependymoma in a single centre over a 20year period using a variety of outcome measures. Sex distribution was equal, with a mean age at surgery of 43.6years (range 5-76years). Overall, most tumours occurred in the lumbosacral region (70.5%), with fewer in the thoracic (27.9%) and cervical regions (18.0%). Myxopapillary features were seen in 41.0% of tumours, and were more common when occurring in the lumbar region (51.2%). Gross total resection was achieved in 52.5%, subtotal resection in 37.7% and biopsy alone in 9.8% of patients and 31.1% received adjuvant radiotherapy. Two-thirds of patients achieved an excellent post-operative neurological outcome (Frankel grade E). Tumour recurrence was rare. Gross total resection and good preoperative neurological condition were most strongly predictive of good outcome. Post-operative radiotherapy did not seem to confer survival benefit in this case series, even in cases of incomplete resection, leading us to question its utility for all cases of spinal cord ependymoma.