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Neurosurgical Focus: Video Oct 2023A 58-year-old male was admitted to the authors' department due to cervicothoracic pain and disequilibrium. Physical examination evidenced sensory and motor deficits in...
A 58-year-old male was admitted to the authors' department due to cervicothoracic pain and disequilibrium. Physical examination evidenced sensory and motor deficits in the lower limbs. MRI evidenced an expansive intramedullary lesion compatible with ependymoma. The nuances of this surgical access and the management of intradural tumors are discussed.
PubMed: 37854644
DOI: 10.3171/2023.6.FOCVID2390 -
Neuro-oncology Jul 2022
Topics: Brain Neoplasms; Child; Ependymoma; Humans; Prospective Studies; Proton Therapy; Protons
PubMed: 35294554
DOI: 10.1093/neuonc/noac066 -
Nature Communications Jul 2022Pediatric ependymoma is a devastating brain cancer marked by its relapsing pattern and lack of effective chemotherapies. This shortage of treatments is due to limited...
Pediatric ependymoma is a devastating brain cancer marked by its relapsing pattern and lack of effective chemotherapies. This shortage of treatments is due to limited knowledge about ependymoma tumorigenic mechanisms. By means of single-nucleus chromatin accessibility and gene expression profiling of posterior fossa primary tumors and distal metastases, we reveal key transcription factors and enhancers associated with the differentiation of ependymoma tumor cells into tumor-derived cell lineages and their transition into a mesenchymal-like state. We identify NFκB, AP-1, and MYC as mediators of this transition, and show that the gene expression profiles of tumor cells and infiltrating microglia are consistent with abundant pro-inflammatory signaling between these populations. In line with these results, both TGF-β1 and TNF-α induce the expression of mesenchymal genes on a patient-derived cell model, and TGF-β1 leads to an invasive phenotype. Altogether, these data suggest that tumor gliosis induced by inflammatory cytokines and oxidative stress underlies the mesenchymal phenotype of posterior fossa ependymoma.
Topics: Cytokines; Ependymoma; Epithelial-Mesenchymal Transition; Humans; Neoplasm Recurrence, Local; Transforming Growth Factor beta1
PubMed: 35803925
DOI: 10.1038/s41467-022-31683-9 -
Molecular and Clinical Oncology May 2021Ependymomas are tumors of the central nervous system that can occur in patients of all ages. Guidelines from the World Health Organization (WHO) for the grading of...
Ependymomas are tumors of the central nervous system that can occur in patients of all ages. Guidelines from the World Health Organization (WHO) for the grading of ependymomas consider patient age, tumor resection range, tumor location and histopathological grade. However, recent studies have suggested that a greater focus on both tumor location and patient age in terms of transcriptomic, genetic, and epigenetic analyses may provide a more accurate assessment of clinical prognosis than the grading system proposed by WHO guidelines. The current study identified the differences and similarities in ependymoma characteristics using three different molecular analyses and methylation arrays. Primary intracranial ependymoma tissues were obtained from 13 Korean patients (9 adults and 4 children), after which whole-exome sequencing (WES), ion-proton comprehensive cancer panel (CCP) analysis, RNA sequencing, and Infinium HumanMethylation450 BeadChip array analysis was performed. Somatic mutations, copy number variations, and fusion genes were identified. It was observed that the methylation status and differentially expressed genes were significantly different according to tumor location and patient age. Several novel gene fusions and somatic mutations were identified, including a fusion mutation in a child with a good prognosis. Moreover, the methylation microarray revealed that genes associated with neurogenesis and neuron differentiation were hypermethylated in the adult group, whereas genes in the homeobox gene family were hypermethylated in the supratentorial (ST) group. The results confirmed the existence of significantly differentially expressed tumor-specific genes based on tumor location and patient age. These results provided valuable insight into the epigenetic and genetic profiles of intracranial ependymomas and uncovered potential strategies for the identification of location- and age-based ependymoma-related prognostic factors.
PubMed: 33767857
DOI: 10.3892/mco.2021.2250 -
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 -
Brain Pathology (Zurich, Switzerland) Jan 2020Ependymomas are primary central nervous system tumors (CNS), arising within the posterior fossa and supratentorial regions of the brain, and in the spine. Over the last... (Review)
Review
Ependymomas are primary central nervous system tumors (CNS), arising within the posterior fossa and supratentorial regions of the brain, and in the spine. Over the last decade, research has resulted in substantial insights into the molecular characteristics of ependymomas, and significant advances have been made in the establishment of a molecular classification system. Ependymomas both within and between the three CNS regions in which they arise, have been shown to contain distinct genetic, epigenetic and cytogenic aberrations, with at least three molecularly distinct subgroups identified within each region. However, these advances in molecular characterization have yet to be translated into clinical practice, with the standard treatment for ependymoma patients largely unchanged. This review summarizes the advances made in the molecular characterization of intracranial ependymomas, outlines the progress made in establishing preclinical models and proposes strategies for moving toward subgroup-specific preclinical investigations and treatment.
Topics: Brain Neoplasms; Central Nervous System Neoplasms; Ependymoma; Humans; Infratentorial Neoplasms; Spinal Neoplasms; Supratentorial Neoplasms
PubMed: 31433520
DOI: 10.1111/bpa.12781 -
Child's Nervous System : ChNS :... Aug 2021Pediatric ependymomas comprise biologically distinct tumor entities with different (epi)genetics, age distribution and localization, as well as a different prognosis.... (Review)
Review
Pediatric ependymomas comprise biologically distinct tumor entities with different (epi)genetics, age distribution and localization, as well as a different prognosis. Regarding risk stratification within these biologically defined entities, histopathological features still seem to be relevant. The mainstay of treatment is gross total resection (GTR) if possible, achieved with intraoperative monitoring and neuronavigation-and if necessary second surgery-followed by adjuvant radiation therapy. However, there is growing evidence that some ependymal tumors may be cured by surgery alone, while others relapse despite adjuvant treatment. To date, the role of chemotherapy is not clear. Current therapy achieves reasonable survival rates for the majority of ependymoma patients. The next challenge is to go beyond initial tumor control and use risk-adapted therapy to reduce secondary effect and therapy-induced morbidity for low-risk patients and to intensify treatment for high-risk patients. With identification of specific alterations, targeted therapy may represent an option for individualized treatment modalities in the future.
Topics: Child; Ependymoma; Humans; Morbidity; Neoplasm Recurrence, Local; Prognosis; Survival Rate
PubMed: 34008056
DOI: 10.1007/s00381-021-05207-7 -
Acta Neuropathologica Jan 2024The diagnosis of ependymoma has moved from a purely histopathological review with limited prognostic value to an integrated diagnosis, relying heavily on molecular...
The diagnosis of ependymoma has moved from a purely histopathological review with limited prognostic value to an integrated diagnosis, relying heavily on molecular information. However, as the integrated approach is still novel and some molecular ependymoma subtypes are quite rare, few studies have correlated integrated pathology and clinical outcome, often focusing on small series of single molecular types. We collected data from 2023 ependymomas as classified by DNA methylation profiling, consisting of 1736 previously published and 287 unpublished methylation profiles. Methylation data and clinical information were correlated, and an integrated model was developed to predict progression-free survival. Patients with EPN-PFA, EPN-ZFTA, and EPN-MYCN tumors showed the worst outcome with 10-year overall survival rates of 56%, 62%, and 32%, respectively. EPN-PFA harbored chromosome 1q gains and/or 6q losses as markers for worse survival. In supratentorial EPN-ZFTA, a combined loss of CDKN2A and B indicated worse survival, whereas a single loss did not. Twelve out of 200 EPN-ZFTA (6%) were located in the posterior fossa, and these tumors relapsed or progressed even earlier than supratentorial tumors with a combined loss of CDKN2A/B. Patients with MPE and PF-SE, generally regarded as non-aggressive tumors, only had a 10-year progression-free survival of 59% and 65%, respectively. For the prediction of the 5-year progression-free survival, Kaplan-Meier estimators based on the molecular subtype, a Support Vector Machine based on methylation, and an integrated model based on clinical factors, CNV data, and predicted methylation scores achieved balanced accuracies of 66%, 68%, and 73%, respectively. Excluding samples with low prediction scores resulted in balanced accuracies of over 80%. In sum, our large-scale analysis of ependymomas provides robust information about molecular features and their clinical meaning. Our data are particularly relevant for rare and hardly explored tumor subtypes and seemingly benign variants that display higher recurrence rates than previously believed.
Topics: Humans; Ependymoma; Progression-Free Survival; Protein Processing, Post-Translational
PubMed: 38265522
DOI: 10.1007/s00401-023-02674-x -
World Journal of Clinical Oncology Nov 2021Myxopapillary ependymoma (MPE) is a pathological grade I tumor that arises in the filum terminale. MPE with anaplastic features is extremely rare, and only 5 cases have...
BACKGROUND
Myxopapillary ependymoma (MPE) is a pathological grade I tumor that arises in the filum terminale. MPE with anaplastic features is extremely rare, and only 5 cases have shown malignancy at the time of recurrence.
CASE SUMMARY
The patient (a 46-year-old woman) had undergone a MPE operation 30 years ago. After subtotal resection of the tumor located in L4-S1, it had a solid component that extended to the adjacent subcutaneous region. Histologically, the tumor consisted of a typical MPE with anaplastic features. The anaplastic areas of the tumor showed hypercellularity, a rapid mitotic rate, vascular proliferation, and connective tissue proliferation. Pleomorphic cells and atypical mitotic figures were occasionally observed. The MIB-1 index in this area was 12.3%. The immunohistochemical study showed immunoreactivity for vimentin, glial fibrillary acidic protein and S100. The morphological pattern and immunohistochemical profile were consistent with anaplastic MPE. The patient tolerated surgery well without new neurological deficits. She underwent local irradiation for the residual tumor and rehabilitation.
CONCLUSION
Although extremely rare, anaplastic MPE occurs in both pediatric and adult patients, similar to other ependymomas. At a minimum, close monitoring is recommended, given concerns about aggressive biological potential. In the future, further study is needed to determine the WHO classification criteria and genetic indicators of tumor progression. The possibility of malignant transformation of MPE should be taken into account, and patients with MPE should be treated with care and follow-up.
PubMed: 34909401
DOI: 10.5306/wjco.v12.i11.1072 -
BMC Neurology Feb 2024Anaplastic ependymoma and H3K27M-mutant diffuse midline glioma are two common subtypes of brain tumors with poor long-term prognosis. The present study analyzed and...
BACKGROUND
Anaplastic ependymoma and H3K27M-mutant diffuse midline glioma are two common subtypes of brain tumors with poor long-term prognosis. The present study analyzed and compared the differences in cell types between two tumors by single-cell RNA sequencing (scRNA-seq) technology.
METHODS
ScRNA-seq was performed to profile cells from cancer tissue from anaplastic ependymoma patient and H3K27M-mutant diffuse midline glioma patient. Cell clustering, marker gene identification, cell type annotation, copy number variation analysis and function analysis of differentially expressed genes were then performed.
RESULTS
A total of 11,219 cells were obtained from anaplastic ependymoma and H3K27M mutant diffuse midline glioma, and these cells categorized into 12 distinct clusters. Each cell cluster could be characterized with specific cell markers to indicate cellular heterogeneity. Five cell types were annotated in each sample, including astrocyte, oligodendrocytes, microglial cell, neural progenitor cell and immune cell. The cluster types and proportion of cell types were not consistent between the two brain tumors. Functional analyses suggest that these cell clusters are involved in tumor-associated pathways, with slight differences in the cells of origin between the two tumors. In addition, cell communication analysis showed that the NRG3-ERBB4 pair is a key Ligand-receptor pair for anaplastic ependymoma, while in H3K27M-mutant diffuse midline glioma it is the PTN-PTPRZ1 pair that establishes contact with other cells.
CONCLUSION
There was intratumor heterogeneity in anaplastic ependymoma and H3K27M mutant diffuse midline glioma, and that the subtype differences may be due to differences in the origin of the cells.
Topics: Humans; Glioma; Histones; DNA Copy Number Variations; Mutation; Brain Neoplasms; Ependymoma; Sequence Analysis, RNA; Receptor-Like Protein Tyrosine Phosphatases, Class 5
PubMed: 38383423
DOI: 10.1186/s12883-024-03558-7