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Cureus Dec 2021Ependymomas are commonly reported at an intradural intramedullary location and more frequently at the conus medullaris or filum terminale. In comparison to this, the...
Ependymomas are commonly reported at an intradural intramedullary location and more frequently at the conus medullaris or filum terminale. In comparison to this, the incidence of spinal tumors being reported at an intradural extramedullary site is less. We describe a young patient who presented with urinary retention and a long-standing history of back pain radiating to the right lower limb. Imaging revealed an intradural ependymoma extending from D11 to S1 and measuring 21 cm in length. The patient underwent D10 to S1 laminectomy. Although the tumor originated from the conus medullaris, the histological evaluation revealed a WHO grade II ependymoma, which is rare, as only 30% of tumors in this location are non-myxopapillary.
PubMed: 34909355
DOI: 10.7759/cureus.20329 -
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 -
Nature Neuroscience May 2023The spatiotemporal regulation of cell fate specification in the human developing spinal cord remains largely unknown. In this study, by performing integrated analysis of...
The spatiotemporal regulation of cell fate specification in the human developing spinal cord remains largely unknown. In this study, by performing integrated analysis of single-cell and spatial multi-omics data, we used 16 prenatal human samples to create a comprehensive developmental cell atlas of the spinal cord during post-conceptional weeks 5-12. This revealed how the cell fate commitment of neural progenitor cells and their spatial positioning are spatiotemporally regulated by specific gene sets. We identified unique events in human spinal cord development relative to rodents, including earlier quiescence of active neural stem cells, differential regulation of cell differentiation and distinct spatiotemporal genetic regulation of cell fate choices. In addition, by integrating our atlas with pediatric ependymomas data, we identified specific molecular signatures and lineage-specific genes of cancer stem cells during progression. Thus, we delineate spatiotemporal genetic regulation of human spinal cord development and leverage these data to gain disease insight.
Topics: Child; Female; Pregnancy; Humans; Spinal Cord; Ependymoma; Cell Differentiation; Neural Stem Cells; Gene Expression; Gene Expression Profiling; Gene Expression Regulation, Developmental
PubMed: 37095395
DOI: 10.1038/s41593-023-01312-9 -
International Journal of Molecular... Oct 2022The ubiquitin proteasome system (UPS) is critically important for cellular homeostasis and affects virtually all key functions in normal and neoplastic cells. Currently,... (Review)
Review
The ubiquitin proteasome system (UPS) is critically important for cellular homeostasis and affects virtually all key functions in normal and neoplastic cells. Currently, a comprehensive review of the role of the UPS in ependymoma (EPN) brain tumors is lacking but may provide valuable new information on cellular networks specific to different EPN subtypes and reveal future therapeutic targets. We have reviewed publicly available EPN gene transcription datasets encoding components of the UPS pathway. Reactome analysis of these data revealed genes and pathways that were able to distinguish different EPN subtypes with high significance. We identified differential transcription of several genes encoding ubiquitin E2 conjugases associated with EPN subtypes. The expression of the E2 conjugase genes , , and was elevated in the ST_EPN_RELA subtype. The UBE2C and UBE2S enzymes are associated with the ubiquitin ligase anaphase promoting complex (APC/c), which regulates the degradation of substrates associated with cell cycle progression, whereas UBE2I is a Sumo-conjugating enzyme. Additionally, elevated in ST_EPN_RELA were genes for the E3 ligase and histone deacetylase and the F-box cullin ring ligase adaptor . Cluster analysis demonstrated several genes encoding E3 ligases and their substrate adaptors as EPN subtype specific genetic markers. The most significant Reactome associated with differentially expressed genes for E3 ligases and their adaptors included antigen presentation, neddylation, sumoylation, and the APC/c complex. Our analysis provides several UPS associated factors that may be attractive markers and future therapeutic targets for the subtype-specific treatment of EPN patients.
Topics: Humans; Ubiquitin; Proteasome Endopeptidase Complex; Cullin Proteins; Genetic Markers; gamma-Glutamyl Hydrolase; Anaphase-Promoting Complex-Cyclosome; Ubiquitin-Protein Ligases; Ependymoma; Brain Neoplasms; Histone Deacetylases; Ubiquitin-Conjugating Enzymes
PubMed: 36293188
DOI: 10.3390/ijms232012330 -
Turkish Neurosurgery 2021To investigate the underlying conditions in children with torticollis.
AIM
To investigate the underlying conditions in children with torticollis.
MATERIAL AND METHODS
Between May 2016 and December 2019, 24 patients (10 girls and 14 boys; mean age, 8 years) presenting with twisted neck, neck pain, weakness of extremities, imbalance, and gait disorder were evaluated retrospectively.
RESULTS
Five of the patients had cranial pathologies (cerebellar anaplastic ependymoma and medulloblastoma, brain stem glioma, atypical teratoid rhabdoid tumor, and acute disseminated encephalomyelitis), and five of the patients had spinal pathologies (idiopathic intervertebral disc calcification, vertebral hemangiomatosis, compression fracture, multiple hereditary exostoses, and Langerhans cell histiocytosis at C4). Six of the patients had ocular pathologies (strabismus, Duane syndrome, and Brown syndrome each in two patients). Four patients had otorhinolaryngological infections (Sandifer syndrome, esophageal atresia, reflux, and spasmus nutans, with one patient each). Detailed clinical physical examination and necessary laboratory investigation were performed for all patients.
CONCLUSION
Torticollis is a sign that is not always innocent and may herald an underlying severe disease. Misdiagnosis can lead to wrong and unnecessary surgical procedures and treatments, and sometimes, the results can be damaging due to underlying severe conditions if diagnosed late. In addition, we first report a case of vertebral hemangiomatosis and temporomandibular joint ankylosis that presented with torticollis in the English medical literature.
Topics: Adolescent; Brain Neoplasms; Calcinosis; Child; Child, Preschool; Ependymoma; Eye Diseases; Female; Humans; Infant; Male; Neck Pain; Physical Examination; Retrospective Studies; Spinal Diseases; Torticollis
PubMed: 33759163
DOI: 10.5137/1019-5149.JTN.31359-20.2 -
Journal of Neuro-oncology Mar 2023Intraventricular compartmental radioimmunotherapy (cRIT) with 131-I-omburtamab is a potential therapy for recurrent primary brain tumors that can seed the thecal space.... (Clinical Trial)
Clinical Trial
PURPOSE
Intraventricular compartmental radioimmunotherapy (cRIT) with 131-I-omburtamab is a potential therapy for recurrent primary brain tumors that can seed the thecal space. These patients often previously received external beam radiotherapy (EBRT) to a portion or full craniospinal axis (CSI) as part of upfront therapy. Little is known regarding outcomes after re-irradiation as part of multimodality therapy including cRIT. This study evaluates predictors of response, patterns of failure, and radiologic events after cRIT.
METHODS
Patients with recurrent medulloblastoma or ependymoma who received 131-I-omburtamab on a prospective clinical trial were included. Extent of disease at cRIT initiation (no evidence of disease [NED] vs measurable disease [MD]) was assessed as associated with progression-free (PFS) and overall survival (OS) by Kaplan-Meier analysis.
RESULTS
All 27 patients (20 medulloblastoma, 7 ependymoma) had EBRT preceding cRIT: most (22, 81%) included CSI (median dose 2340 cGy, boost to 5400 cGy). Twelve (44%) also received EBRT at relapse as bridging to cRIT. There were no cases of radionecrosis. At cRIT initiation, 11 (55%) medulloblastoma and 3 (43%) ependymoma patients were NED, associated with improved PFS (p = 0.002) and OS (p = 0.048) in medulloblastoma. Most relapses were multifocal. With medium follow-up of 3.0 years (95% confidence interval, 1.8-7.4), 6 patients remain alive with NED.
CONCLUSION
For patients with medulloblastoma, remission at time of cRIT was associated with significantly improved survival outcomes. Relapses are often multifocal, particularly in the setting of measurable disease at cRIT initiation. EBRT is a promising tool to achieve NED status at cRIT initiation, with no cases of radiation necrosis.
Topics: Humans; Antibodies, Monoclonal; Brain Neoplasms; Cerebellar Neoplasms; Chronic Disease; Ependymoma; Iodine Radioisotopes; Medulloblastoma; Neoplasm Recurrence, Local; Prospective Studies; Radiotherapy Dosage
PubMed: 36853490
DOI: 10.1007/s11060-022-04235-w -
Brain Tumor Pathology Jan 2022Although ependymomas (EPNs) have similar histopathology, they are heterogeneous tumors with diverse immunophenotypes, genetics, epigenetics, and different clinical...
Although ependymomas (EPNs) have similar histopathology, they are heterogeneous tumors with diverse immunophenotypes, genetics, epigenetics, and different clinical behavior according to anatomical locations. We reclassified 141 primary EPNs from a single institute with immunohistochemistry (IHC) and next-generation sequencing (NGS). Supratentorial (ST), posterior fossa (PF), and spinal (SP) EPNs comprised 12%, 41%, and 47% of our cohort, respectively. Fusion genes were found only in ST-EPNs except for one SP-EPN with ZFTA-YAP1 fusion, NF2 gene alterations were found in SP-EPNs, but no driver gene was present in PF-EPNs. Surrogate IHC markers revealed high concordance rates between L1CAM and ZFTA-fusion and H3K27me3 loss or EZHIP overexpression was used for PFA-EPNs. The 7% cut-off of Ki-67 was sufficient to classify EPNs into two-tiered grades at all anatomical locations. Multivariate analysis also delineated that a Ki-67 index was the only independent prognostic factor in both overall and progression-free survivals. The gain of chromosome 1q and CDKN2A/2B deletion were associated with poor outcomes, such as multiple recurrences or extracranial metastases. In this study, we propose a cost-effective schematic diagnostic flow of EPNs by the anatomical location, three biomarkers (L1CAM, H3K27me3, and EZHIP), and a cut-off of a 7% Ki-67 labeling index.
Topics: Ependymoma; Humans; Infratentorial Neoplasms; Ki-67 Antigen; Neural Cell Adhesion Molecule L1; Oncogene Proteins; Prognosis; Spinal Neoplasms; Supratentorial Neoplasms
PubMed: 34812989
DOI: 10.1007/s10014-021-00417-y -
Neuro-oncology Practice Mar 2020Anaplastic ependymoma with extraneural metastases is associated with a poor clinical outcome. Metastatic spread to the parotid gland is a rare clinical entity that...
BACKGROUND
Anaplastic ependymoma with extraneural metastases is associated with a poor clinical outcome. Metastatic spread to the parotid gland is a rare clinical entity that requires multidisciplinary intervention. Herein, we present a systematic review of anaplastic ependymoma with extraneural metastases and report on a case with metastases to both parotid glands.
METHODS
Electronic databases were searched from their inception to February 2019. Inclusion criteria included reports of anaplastic ependymoma with extraneural metastasis. Studies were excluded if the tumor grade was not reported. A case illustration is provided.
RESULTS
The search yielded 15 cases of anaplastic ependymoma with extraneural metastases, including the present case. Mean age at diagnosis was 15 years. The initial tumor location was predominantly supratentorial (93.3%). All cases demonstrated leptomeningeal seeding before extraneural metastasis. Mean survival from initial diagnosis was 4.5 years. Metastasis to the parotid gland occurred in 2 cases, including the present case. We present a 17-year-old female patient who underwent gross total resection of a supratentorial, paraventricular anaplastic ependymoma followed by adjuvant external beam radiation therapy. The patient developed recurrent leptomeningeal seeding, treated with Gamma Knife radiosurgery over a 5-year period. She returned with a parotid mass and cervical lymphadenopathy and underwent parotidectomy and modified radical neck dissection. She continued to experience recurrences, including the left parotid gland, and was ultimately placed in hospice care.
CONCLUSIONS
Anaplastic ependymoma with extraneural metastasis is rare. A combination of repeated surgical resection, radiation therapy, and chemotherapy can be used to manage recurrent and metastatic disease, but outcomes remain poor.
PubMed: 32626590
DOI: 10.1093/nop/npz041 -
Neuro-oncology Practice Oct 2020Ependymoma is a rare CNS tumor arising from the ependymal lining of the ventricular system. General differences in incidence and survival have been noted but not...
BACKGROUND
Ependymoma is a rare CNS tumor arising from the ependymal lining of the ventricular system. General differences in incidence and survival have been noted but not examined on a comprehensive scale for all ages and by histology. Despite the rarity of ependymomas, morbidity/mortality associated with an ependymoma diagnosis justifies closer examination.
METHODS
Incidence data were obtained from the Central Brain Tumor Registry of the United States in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, and survival data from Surveillance Epidemiology and End Results, from 2000 to 2016 for anaplastic ependymoma and ependymoma, not otherwise specified (NOS). Age-adjusted incidence rates (IRs) per 100 000 person-years were analyzed by age, sex, race, and location. Survival analysis was performed with Kaplan-Meier curves and multivariable Cox proportional hazards models.
RESULTS
Incidence of anaplastic ependymoma was highest in ages 0 to 4 years. African American populations had lower incidence but had a 78% increased risk of death compared to white populations (hazard ratio [HR]: 1.78 [95% CI, 1.30-2.44]). Incidence was highest for anaplastic ependymoma in the supratentorial region. Adults (age 40+ years) had almost twice the risk of death compared to children (ages 0-14 years) (HR: 1.97 [95% CI, 1.45-2.66]). For ependymoma, NOS, subtotal resection had a risk of mortality 1.86 times greater than gross total resection ([HR: 1.86 [95% CI, 1.32-2.63]).
CONCLUSIONS
African American populations experienced higher mortality rates despite lower incidence compared to white populations. Extent of resection is an important prognostic factor for survival. This highlights need for further evaluation of treatment patterns and racial disparities in the care of patients with ependymoma subtypes.
PubMed: 33014396
DOI: 10.1093/nop/npaa023 -
Cancer Causes & Control : CCC Nov 2023Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young... (Meta-Analysis)
Meta-Analysis
PURPOSE
Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence.
METHODS
We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of CBT, astrocytoma, medulloblastoma/PNET, and ependymoma according to breastfeeding status, adjusting for study, sex, mode of delivery, birthweight, age at diagnosis/interview, maternal age at delivery, maternal educational attainment, and maternal race/ethnicity. We evaluated any breastfeeding versus none and breastfeeding ≥ 6 months versus none. We subsequently performed random effects meta-analysis to confirm our findings, identify potential sources of heterogeneity, and evaluate for outliers or influential studies.
RESULTS
Breastfeeding was reported by 64.8% of control mothers and 64.5% of case mothers and was not associated with CBT (OR 1.04, 95% CI 0.94-1.15), astrocytoma (OR 1.01, 95% CI 0.87-1.17), medulloblastoma/PNET (OR 1.11, 95% CI 0.93-1.32), or ependymoma (OR 1.06, 95% CI 0.81-1.40). Results were similar when we restricted to breastfeeding ≥ 6 months and in meta-analyses.
CONCLUSION
Our data suggest that breastfeeding does not protect against CBT.
Topics: Child; Female; Humans; Infant; Astrocytoma; Brain Neoplasms; Breast Feeding; Case-Control Studies; Cerebellar Neoplasms; Ependymoma; Leukemia; Medulloblastoma; Neuroectodermal Tumors, Primitive; Risk Factors; Male
PubMed: 37421504
DOI: 10.1007/s10552-023-01746-3