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Brain Pathology (Zurich, Switzerland) Mar 2021Pediatric ependymomas frequently develop in the cerebellum and are currently treated using non-specific therapies, in part, because few somatically mutated driver genes...
Pediatric ependymomas frequently develop in the cerebellum and are currently treated using non-specific therapies, in part, because few somatically mutated driver genes are present, and the underlying pathobiology is poorly described. Circular RNAs (circRNAs) constitute as a large class of primarily non-coding RNAs with important roles in tumorigenesis, but they have not been described in pediatric ependymomas. To advance our molecular understanding of ependymomas, we performed Next Generation Sequencing of rRNA-depleted total RNA of 10 primary ependymoma and three control samples. CircRNA expression patterns were correlated to disease stage, outcome, age, and gender. We found a profound global downregulation of circRNAs in ependymoma relative to control samples. Many differentially expressed circRNAs were discovered and circSMARCA5 and circ-FBXW7, which are described as tumor suppressors in glioma and glioblastomas in adults, were among the most downregulated. Moreover, patients with a dismal outcome clustered separately from patients with a good prognosis in unsupervised hierarchical cluster analyses. Next, NanoString nCounter experiments were performed, using a custom-designed panel targeting 66 selected circRNAs, on a larger cohort that also included medulloblastomas and pilocytic astrocytomas. These experiments indicated that circRNA expression profiles are different among distinct pediatric brain tumor subtypes. In particular, circRNAs derived from RMST, LRBA, WDR78, DRC1 and BBS9 genes were specifically upregulated in ependymomas. In conclusion, circRNAs have different expression profiles in ependymomas relative to controls and between survivors and patients with a dismal outcome, suggesting that circRNAs could be exerted as diagnostic and prognostic biomarkers in the future if further validated in larger cohorts.
Topics: Adolescent; Brain Neoplasms; Child; Child, Preschool; Ependymoma; Female; High-Throughput Nucleotide Sequencing; Humans; Infant; Male; RNA, Circular; Sequence Analysis, RNA
PubMed: 33247464
DOI: 10.1111/bpa.12922 -
Turkish Neurosurgery 2012Intramedullary tumors affecting the entire cord from the cervicomedullary junction to the conus are termed "holocord tumors". Ependymomas are the most frequent...
Intramedullary tumors affecting the entire cord from the cervicomedullary junction to the conus are termed "holocord tumors". Ependymomas are the most frequent intramedullary tumor in adults. Holocord ependymoma is an exceedingly rare condition. An extensive review of the literature revealed that only five other cases have been reported. We report the sixth case of holocord ependymoma. In this article, we present a case of holocord ependymoma in a 19-year-old girl which was totally resected in a two-stage approach. A two-staged operation is recommended for the aim of total resection for this disease. Besides, cysts are common feature of all spinal ependymomas. There was a solid mass not accompanied by a cyst a any level in our patient's tumor. To the authors' best knowledge, a pure solid mass not accompanied by a cyst has not been previously reported with holocord ependymoma cases.
Topics: Ependymoma; Female; Humans; Magnetic Resonance Imaging; Neurosurgical Procedures; Spinal Cord; Spinal Cord Neoplasms; Young Adult
PubMed: 22437304
DOI: 10.5137/1019-5149.JTN.3281-10.1 -
JPMA. the Journal of the Pakistan... Nov 2022To enumerate the burden of ependymoma in our region and identify the demographic, tumoural, surgical, clinical characteristics, and outcomes of patients diagnosed with...
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.
Topics: Child; Humans; Child, Preschool; Adolescent; Young Adult; Adult; Retrospective Studies; Cross-Sectional Studies; Brain Neoplasms; Ependymoma; Time
PubMed: 36591627
DOI: 10.47391/JPMA.11-S4-AKUB07 -
Turk Patoloji Dergisi 2022Ependymomas are neuroepithelial tumors of the central nervous system with heterogeneous biology and clinical course. The aim of the present study is to investigate the...
OBJECTIVE
Ependymomas are neuroepithelial tumors of the central nervous system with heterogeneous biology and clinical course. The aim of the present study is to investigate the relationship between the methylation status and clinicopathological parameters in ependymomas.
MATERIAL AND METHOD
DNA methylation status of CDKN2A, RASSF1A, KLF4 and ZIC2 genes were quantitatively analyzed with pyrosequencing in 44 ependymoma tumor tissues. The relationship of methylation profiles with tumor subtype, histological grade and patient age was statistically analyzed.
RESULTS
DNA methylation analyses for CDKN2A revealed no difference in methylation levels. Of the 31 included samples for optimal ZIC2 methylation analysis, 10 were hypermethylated (32.3%) and this change was significantly found in the adult spinal ependymomas (p=0.01). KLF4 hypermethylation was observed in 6 of the overall included 35 samples (17.1%); however, there was no statistically significant relation of the methylation status with tumor subtype, histological grade or age group. RASSF1A hypermethylation was observed in overall 40 included samples with varying methylation levels. Higher levels of hypermethylation were significantly related to the grade 3 histology (p=0.01) and spinal ependymomas (p=0.006). The pediatric cases with grade 3 ependymomas and ependymomas of adulthood showed significantly increased RASSF1A hypermethylation levels (p < 0.001 and p=0.001, respectively).
CONCLUSION
DNA methylation changes are likely to have biological importance in ependymomas. Both ZIC2 and RASSF1A methylation status may be useful parameters in the subclassification of these tumors.
Topics: Adult; Child; DNA Methylation; Ependymoma; Humans
PubMed: 34854470
DOI: 10.5146/tjpath.2021.01565 -
Cancer Medicine Sep 2021The prognostic factors for survival in patients with ependymoma (EPN) remain controversial. The aim of this study was to establish a prognostic model for 5- and 10-year...
BACKGROUND
The prognostic factors for survival in patients with ependymoma (EPN) remain controversial. The aim of this study was to establish a prognostic model for 5- and 10-year survival probability nomograms for patients with EPN.
METHODS
Clinical data from the Surveillance, Epidemiology, and End Results (SEER) database were used for patients diagnosed with ependymoma between 2000 and 2018 and were randomized 7:3 into a development set and a validation set. Factors significantly associated with prognosis were screened out using the least absolute shrinkage and selection operator (LASSO) regression. The calibration chart and consistency index (C-index) are used to evaluate the discrimination and consistency of the prediction model. Decision curve analysis (DCA) was used to further evaluate the established model. Finally, prognostic factors selected by LASSO regression were evaluated using Kaplan-Meier (KM) survival curves.
RESULTS
A total of 3820 patients were included in the prognostic model. Seven survival predictors were obtained by LASSO regression screening, including age, gender, morphology, location, size, laterality, and resection. The prognostic model of the nomogram showed moderate discriminative ability in the development group and the validation group, with a C-index of 0.642 and 0.615, respectively. In the development set and validation set survival curves, the prognosis index of high risk was less effective than low risk (p < 0.001).
CONCLUSIONS
Our nomograms may play an important role in predicting 5 and 10-year outcomes for patients with ependymoma. This will help assist clinicians in personalized medicine.
Topics: Adult; Ependymoma; Humans; Middle Aged; Nomograms; Prognosis; Retrospective Studies; Risk Factors; SEER Program; Survival Analysis; Young Adult
PubMed: 34342153
DOI: 10.1002/cam4.4151 -
BMJ Case Reports Jan 2021This report presents the longest spanning intradural myxopapillary ependymoma consisting of 23 vertebral segments in the literature. An 11-year-old boy presented with... (Review)
Review
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.
Topics: Cervical Vertebrae; Child; Ependymoma; Humans; Laminectomy; Lumbar Vertebrae; Magnetic Resonance Imaging; Male; Radiotherapy, Adjuvant; Sacrum; Spinal Cord Neoplasms; Thoracic Vertebrae; Tumor Burden
PubMed: 33509888
DOI: 10.1136/bcr-2020-239453 -
Medical Archives (Sarajevo, Bosnia and... Apr 2023Myxopapillary ependymoma is a rare type of primary spinal tumor, it is distinctly a slow-growing tumor that originates in the conus medullaris, cauda equina, or film... (Review)
Review
BACKGROUND
Myxopapillary ependymoma is a rare type of primary spinal tumor, it is distinctly a slow-growing tumor that originates in the conus medullaris, cauda equina, or film terminals and is rarely identified as a multicentric type. Myxopapillary ependymoma has a unique histological characteristic and is associated with a generally better prognosis.
OBJECTIVE
We present a case of a rare multicentric myxopapillary ependymoma.
CASE PRESENTATION
A 28-year-old male with 1-year history of low back pain and 3 months of radiating pain to left lower limb with perianal anesthesia. Magnetic resonance imaging (MRI) exhibited a large intradural intramedullary lesion from the level of the conus medullaris extending to the filum terminals at the level of T12 to L3 with smaller multiple enhancing lesions seen opposite to L4 and L5 level as well as within the exiting nerve roots, at the left side of L1/L2 and L2/L3 and right side of L3/L4 and L5/S1 level. The patient underwent surgical resection with significant improvement in symptoms and no tumor progression on follow up MRI scan.
CONCLUSION
We hereby present a case of multicentric myxopapillary ependymoma with a literature review of the previous reported cases. We believe that our study will make a significant contribution to the literature and will be of interest to the readership regarding of the rarity of multicentric Myxopapillary ependymoma and it will help in decision making for the proper surgical Intervention on these kinds of cases.
Topics: Male; Humans; Adult; Ependymoma; Cauda Equina; Spinal Cord Neoplasms; Low Back Pain; Magnetic Resonance Imaging
PubMed: 37260799
DOI: 10.5455/medarh.2023.77.150-154 -
Neuro-oncology Apr 2023The diverse cellular constituents of childhood brain tumor ependymoma, recently revealed by single cell RNA-sequencing, may underly therapeutic resistance. Here we use...
BACKGROUND
The diverse cellular constituents of childhood brain tumor ependymoma, recently revealed by single cell RNA-sequencing, may underly therapeutic resistance. Here we use spatial transcriptomics to further advance our understanding of the tumor microenvironment, mapping cellular subpopulations to the tumor architecture of ependymoma posterior fossa subgroup A (PFA), the commonest and most deadly childhood ependymoma variant.
METHODS
Spatial transcriptomics data from intact PFA sections was deconvoluted to resolve the histological arrangement of neoplastic and non-neoplastic cell types. Key findings were validated using immunohistochemistry, in vitro functional assays and outcome analysis in clinically-annotated PFA bulk transcriptomic data.
RESULTS
PFA are comprised of epithelial and mesenchymal histological zones containing a diversity of cellular states, each zone including co-existing and spatially distinct undifferentiated progenitor-like cells; a quiescent mesenchymal zone population, and a second highly mitotic progenitor population that is restricted to hypercellular epithelial zones and that is more abundant in progressive tumors. We show that myeloid cell interaction is the leading cause of mesenchymal transition in PFA, occurring in zones spatially distinct from hypoxia-induced mesenchymal transition, and these distinct EMT-initiating processes were replicated using in vitro models of PFA.
CONCLUSIONS
These insights demonstrate the utility of spatial transcriptomics to advance our understanding of ependymoma biology, revealing a clearer picture of the cellular constituents of PFA, their interactions and influence on tumor progression.
Topics: Humans; Transcriptome; Infratentorial Neoplasms; Brain Neoplasms; Ependymoma; Epithelial-Mesenchymal Transition; Tumor Microenvironment
PubMed: 36215273
DOI: 10.1093/neuonc/noac219 -
Spinal Cord Series and Cases Jan 2021Of the 23 cases of spinal intradural-extramedullary ependymomas which have been reported to date, 11 were diagnosed as anaplastic. Here we present a very rare case of a...
INTRODUCTION
Of the 23 cases of spinal intradural-extramedullary ependymomas which have been reported to date, 11 were diagnosed as anaplastic. Here we present a very rare case of a thoracic intradural-extramedullary (not intramedullary) anaplastic ependymoma in an adult along with a literature review.
CASE PRESENTATION
A 29-year-old man presented with rapidly progressive gait disturbance, a sensory-deficit below the trunk and urination disorders that had begun a few months earlier. Magnetic resonance imaging of his thoracic spine revealed a dorsal-located intradural-extramedullary tumor at T4-5. The rapid deterioration of his symptoms within several months led him to refer to our department for surgery. Within one month the size of tumor increased to involve the T4-6 level, consequently worsening his gait disturbance. He underwent surgery and tumor mass was resected. However, there was leptomeningeal dissemination of the tumor cells on the surface of cord. A near-total resection was therefore achieved. Histopathology revealed the resected specimen had immunoreactivity for EMA/Vimentin/CD56/CD99/S-100/GFAP, with a Ki-67 index of ~35%. These factors led to the diagnosis of anaplastic ependymoma. Seven weeks postoperatively he received adjuvant radiotherapy to the whole brain and the whole spinal cord. He recovered as an independent ambulator without recurrence 1 year postoperatively.
DISCUSSION
Because of their rarity, there are no clear treatment or adjuvant therapy guidelines for spinal anaplastic ependymoma. Adjuvant radiotherapy to the whole brain and spinal cord was necessarily indicated after near-total resection. Although the patient's condition has not recurred 1 year after surgery, careful and serial follow-up is necessary for this individual.
Topics: Adult; Ependymoma; Humans; Magnetic Resonance Imaging; Male; Radiotherapy, Adjuvant; Spinal Cord Neoplasms; Spine
PubMed: 33468988
DOI: 10.1038/s41394-020-00367-1 -
Neuro-oncology Jun 2022The risk profile for posterior fossa ependymoma (EP) depends on surgical and molecular status [Group A (PFA) versus Group B (PFB)]. While subtotal tumor resection is...
BACKGROUND
The risk profile for posterior fossa ependymoma (EP) depends on surgical and molecular status [Group A (PFA) versus Group B (PFB)]. While subtotal tumor resection is known to confer worse prognosis, MRI-based EP risk-profiling is unexplored. We aimed to apply machine learning strategies to link MRI-based biomarkers of high-risk EP and also to distinguish PFA from PFB.
METHODS
We extracted 1800 quantitative features from presurgical T2-weighted (T2-MRI) and gadolinium-enhanced T1-weighted (T1-MRI) imaging of 157 EP patients. We implemented nested cross-validation to identify features for risk score calculations and apply a Cox model for survival analysis. We conducted additional feature selection for PFA versus PFB and examined performance across three candidate classifiers.
RESULTS
For all EP patients with GTR, we identified four T2-MRI-based features and stratified patients into high- and low-risk groups, with 5-year overall survival rates of 62% and 100%, respectively (P < .0001). Among presumed PFA patients with GTR, four T1-MRI and five T2-MRI features predicted divergence of high- and low-risk groups, with 5-year overall survival rates of 62.7% and 96.7%, respectively (P = .002). T1-MRI-based features showed the best performance distinguishing PFA from PFB with an AUC of 0.86.
CONCLUSIONS
We present machine learning strategies to identify MRI phenotypes that distinguish PFA from PFB, as well as high- and low-risk PFA. We also describe quantitative image predictors of aggressive EP tumors that might assist risk-profiling after surgery. Future studies could examine translating radiomics as an adjunct to EP risk assessment when considering therapy strategies or trial candidacy.
Topics: Ependymoma; Humans; Machine Learning; Magnetic Resonance Imaging; Prognosis; Retrospective Studies
PubMed: 34850171
DOI: 10.1093/neuonc/noab272