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Brain Pathology (Zurich, Switzerland) Jan 2021The molecular biology of ependymomas is not well understood and this is particularly true for ependymoma relapses. We aimed at finding out if and to which extent,...
The molecular biology of ependymomas is not well understood and this is particularly true for ependymoma relapses. We aimed at finding out if and to which extent, relapses differ from their corresponding primary tumors on the morphological, chromosomal and epigenetic level. We investigated 24 matched ependymoma primary and relapsed tumor samples and, as a first step, compared cell density, necrosis, vessel proliferation, Ki67 proliferative index, trimethylation at H3K27 and expression of CXorf67. For the investigation of global methylation profiles, we used public data in order to analyze copy number variation profiles, differential methylation, methylation status and fractions of hypo- and hypermethylated CpGs in different epigenomic substructures. Morphologically, we found a significant increase with relapse in cell density and proliferation. H3K27 trimethylation and CXorf67 expression remained stable between primary and relapse tumor samples, and the analysis of DNA methylation profiles neither revealed significant differences in copy number variations nor differentially methylated regions. Significant differences in the methylation status were found for CpG islands, but also in N Shelves or S Shelves, depending on the molecular subgroup. The fraction of probes changing their methylation in the epigenomic substructures appeared subgroup-specific. Most changes occur in CpG islands, for which relapsed tumors demonstrate higher methylation values than primary tumors. The morphological differences reflect increased aggressiveness upon ependymoma relapse, but, despite slight changes, this observation does not appear to be sufficiently explained by epigenetic changes.
Topics: Adolescent; Adult; Brain Neoplasms; Child; Ependymoma; Epigenome; Female; Humans; Infant; Male; Middle Aged; Neoplasm Recurrence, Local; Young Adult
PubMed: 32633004
DOI: 10.1111/bpa.12875 -
Oncology Reports Aug 2014Ependymomas are rare tumors of the central nervous system (CNS). They are classified based on tumor histology and grade, but the prognostic value of the WHO grading...
Ependymomas are rare tumors of the central nervous system (CNS). They are classified based on tumor histology and grade, but the prognostic value of the WHO grading system remains controversial. Treatment is mainly surgical and by radiation. An improved knowledge of ependymoma biology is important to elucidate the pathogenesis, to improve classification schemes, and to identify novel potential treatment targets. Only 113 ependymoma karyotypes with chromosome aberrations are registered in the Mitelman database. We present the first study of ependymoma genomes combining karyotyping and high resolution comparative genomic hybridization (HR-CGH). Nineteen tumor samples were collected from three pediatric and 15 adult patients treated at Oslo University Hospital between 2005 and 2012. Histological diagnoses included subependymoma and myxopapillary ependymoma (WHO grade I), ependymoma (WHO grade II) and anaplastic ependymoma (WHO grade III). Four tumors were intraspinal and 15 were intracranial. Seventeen samples were successfully karyotyped, HR-CGH analysis was undertaken on 17 samples, and 15 of 19 tumors were analyzed using both methods. Twelve tumors had karyotypic abnormalities, mostly gains or losses of whole chromosomes. Structural rearrangements were found in four tumors, in two of which 2p23 was identified as a breakpoint region. Twelve tumors displayed genomic imbalances by HR-CGH analysis with loss of material at 6q as the most common. 6q loss, which was detected by one or both methods in seven of 12 (58%) abnormal tumors, and 5p gain (observed in five tumors; 42%) were the most common genomic aberrations in this series.
Topics: Adolescent; Adult; Aged; Brain Neoplasms; Child; Child, Preschool; Chromosome Aberrations; Chromosome Deletion; Chromosomes, Human, Pair 5; Chromosomes, Human, Pair 6; Comparative Genomic Hybridization; Ependymoma; Genome, Human; Humans; Infant; Karyotyping; Male; Middle Aged; Norway; Spinal Neoplasms; Young Adult
PubMed: 24939246
DOI: 10.3892/or.2014.3271 -
Scientific Reports Jul 2019Three of the hallmarks of poor prognosis in paediatric ependymoma are drug resistance, local invasion and recurrence. We hypothesised that these hallmarks were due to...
Three of the hallmarks of poor prognosis in paediatric ependymoma are drug resistance, local invasion and recurrence. We hypothesised that these hallmarks were due to the presence of a sub-population of cancer stem cells expressing the multi-drug efflux transporter ABCB1. ABCB1 gene expression was observed in 4 out of 5 paediatric ependymoma cell lines and increased in stem cell enriched neurospheres. Functional inhibition of ABCB1 using vardenafil or verapamil significantly (p ≤ 0.05-0.001) potentiated the response to three chemotherapeutic drugs (vincristine, etoposide and methotrexate). Both inhibitors were also able to significantly reduce migration (p ≤ 0.001) and invasion (p ≤ 0.001). We demonstrate that ABCB1 positive patients from an infant chemotherapy-led trial (CNS9204) had a shorter mean event free survival (EFS) (2.7 versus 8.6 years; p = 0.007 log-rank analysis) and overall survival (OS) (5.4 versus 12 years; p = 0.009 log-rank analysis). ABCB1 positivity also correlated with reduced event free survival in patients with incompletely resected tumours who received chemotherapy across CNS9204 and CNS9904 (a radiotherapy-led SIOP 1999-04 trial cohort; p = 0.03). ABCB1 is a predictive marker of chemotherapy response in ependymoma patients and vardenafil, currently used to treat paediatric pulmonary hypertension in children, could be repurposed to reduce chemoresistance, migration and invasion in paediatric ependymoma patients at non-toxic concentrations.
Topics: ATP Binding Cassette Transporter, Subfamily B; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Child, Preschool; Drug Resistance, Neoplasm; Drug Synergism; Ependymoma; Etoposide; Gene Expression Regulation, Neoplastic; Humans; Infant; Methotrexate; Neoplasm Invasiveness; Neoplastic Stem Cells; Prognosis; Survival Analysis; Up-Regulation; Vardenafil Dihydrochloride; Verapamil; Vincristine
PubMed: 31311995
DOI: 10.1038/s41598-019-46700-z -
Journal of Neurosurgery Apr 2011Supratentorial cortical ependymomas (CE) are rare, with 7 cases reported. The lesions, typically occurring in the superficial cortex in young adults and associated with...
OBJECT
Supratentorial cortical ependymomas (CE) are rare, with 7 cases reported. The lesions, typically occurring in the superficial cortex in young adults and associated with a history of seizures, are not fully characterized. Furthermore, their relationship with the recently described angiocentric glioma (AG) is still being debated. This study was undertaken to summarize the authors' experience with CEs.
METHODS
Between 1997 and 2009, 202 cases of ependymoma were surgically treated at the Mayo Clinic, 49 of which were supratentorial. Among these, 9 CE cases were retrospectively identified. Clinical, imaging, and pathological features of each case were reviewed.
RESULTS
Tumors arose from the frontal (5 cases), parietal (3), and occipital (1) lobes. No tumor occurred in the temporal lobe, despite its reported association with seizures. The mean age at presentation was 27 ± 19 years (± SD) and age at resection was 36 ± 16 years. The mean size of the lesion was 16 ± 14 cm(3). Seizures were the presenting symptom in 78%. Cross-sectional imaging in 8 cases was characterized by a heterogeneous mass with multiple cystlike areas and enhancement of the soft-tissue component. Gross-total resection was achieved in 8 of 9 tumors. Pathologically, 6 were low-grade (WHO Grade II) and 3 were anaplastic (WHO Grade III) ependymomas. All tumors exhibited the focal presence of perivascular pseudorosettes, but only 1 (11%) exhibited the focal presence of a true rosette. A bipolar spindle cell component resembling AG was present in 3 (33%) and "Schwannian-like" nodules in 2 (22%). Subpial aggregation and peripheral infiltration were present in 4 cases (44%). With a mean postsurgery follow-up of 62 ± 38 months, only 2 lesions recurred locally after imaging-confirmed gross-total resection, both being Grade III. In 5 (71%) of 7 patients presenting with seizures an Engel Class I outcome was achieved.
CONCLUSIONS
Cortical ependymomas represent a rare type of ependymoma occurring superficially in the cortex. Morphologically, these tumors are protean, varying from classic to epithelioid, clear cell, and tanycytic. Some also exhibited features typical of AG. Most tumors were low grade and cured with resection. Anaplastic tumors occur and may recur locally despite provision of radiation therapy. Cortical ependymomas frequently, but not always, present with seizures, but despite their high association with epilepsy, none occurred in the temporal lobe in any of the authors' 9 patients. Overall, CEs appear to have a relatively favorable prognosis compared with other supratentorial ependymomas.
Topics: Adult; Brain; Child; Ependymoma; Epilepsy; Female; Follow-Up Studies; Humans; Infant; Magnetic Resonance Imaging; Male; Middle Aged; Neurosurgical Procedures; Retrospective Studies; Supratentorial Neoplasms; Tomography, X-Ray Computed
PubMed: 21235315
DOI: 10.3171/2010.12.JNS10846 -
Cancer Cell Jul 2020Ependymomas are aggressive central nervous system tumors that resist chemotherapy. In this issue of Cancer Cell, Gojo et al. dissect the single cell transcriptional...
Ependymomas are aggressive central nervous system tumors that resist chemotherapy. In this issue of Cancer Cell, Gojo et al. dissect the single cell transcriptional landscapes of ependymoma to define cellular programs that mediate therapeutic resistance, tumor aggressiveness, and potential targets for therapy.
Topics: Central Nervous System Neoplasms; Child; Ependymoma; Humans; RNA-Seq
PubMed: 32663463
DOI: 10.1016/j.ccell.2020.06.010 -
Journal of Neurosurgical Sciences Feb 2018
Topics: Brain Neoplasms; Central Nervous System Neoplasms; Ependymoma; Humans; Research
PubMed: 28945056
DOI: 10.23736/S0390-5616.17.04217-5 -
Diagnostic Pathology Mar 2017Imaging and histology of clear-cell ependymoma and cerebellum-based hemangioblastoma are similar; distinguishing between them is a diagnostic challenge. (Review)
Review
BACKGROUND
Imaging and histology of clear-cell ependymoma and cerebellum-based hemangioblastoma are similar; distinguishing between them is a diagnostic challenge.
CASE PRESENTATION
A 62-year-old Chinese woman presented with an intermittent headache of 8 years' duration. Computed tomography and magnetic resonance imaging revealed a mass in the cerebellum. Neurological imaging suggested hemangioblastoma (HB). Histologically, the tumor included cellular and paucicellular areas, in which cells were arranged in nests or diffusely distributed; and a highly vascular area, in which tumor cells were arranged in clusters and separated by capillaries. At low magnification, the tumor mimicked cellular HB, but at high magnification, tumor cells showed clear cytoplasm instead of the vacuolated cytoplasm typically observed in HB. Moreover, spindly, bipolar elements resembling tanycytes were observed within the nest structures. Although these features indicated the possibility of ependymoma, neither true ependymal rosettes nor an ependymal-lined profile was observed. The tumor was characterized by prominent vascularity, but glomeruloid formation was absent. We saw pleomorphism in foci of some tumor giant cells, but pathologic mitosis and palisaded necrosis were absent. Most tumor cells were positive for glial fibrillary acidic protein and S100. Epithelial membrane antigen was expressed with a paranuclear dot-like or a ring-like pattern. The Ki-67 index was approximately 2%. Considering the patient's symptom, neurological imaging, and pathological findings, she was diagnosed as cerebellar ependymoma (WHO grade II).
CONCLUSIONS
Here, we report a case of ependymoma with overlapping clear-cell and tanycytic features, and review the literature to evaluate its real incidence. Pathologists should consider this rare diagnosis when confronted with a similar presentation.
Topics: Biomarkers, Tumor; Biopsy; Cerebellar Neoplasms; Cerebral Angiography; Chromosome Deletion; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; Computed Tomography Angiography; Diagnosis, Differential; Ependymoglial Cells; Ependymoma; Female; Hemangioblastoma; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Middle Aged; Neoplasm Grading; Predictive Value of Tests
PubMed: 28320419
DOI: 10.1186/s13000-017-0619-2 -
British Journal of Cancer Jun 2013Ependymomas are rare primary gliomas that commonly affect both children and adults, but unique as survival is worse in children.
BACKGROUND
Ependymomas are rare primary gliomas that commonly affect both children and adults, but unique as survival is worse in children.
METHODS
Data on brain and central nervous system primary malignant and non-malignant ependymal tumours from the Central Brain Tumor Registry of the United States analytic data set and primary malignant ependymal tumours from the SEER 13 registries research data file were used to evaluate incidence and survival, respectively.
RESULTS
The 2004-2009 average annual age-adjusted incidence rate of ependymal tumours was 0.41/100,000. Spinal cord/cauda equina was the primary site at diagnosis for 50-60% of ependymal tumours in adult age groups in contrast to about 20% in children and adolescents. Ependymoma was the most frequent histology in all age groups; however, anaplastic ependymoma comprised about 30% in cases 0-19 years of age compared with about 3-5% in adult age groups. Overall, relative survival was favourable with rates at ∼85% and 75% at 3 and 10 years post diagnosis, respectively. However, children and adolescents, the oldest adult age group, cases diagnosed with anaplastic ependymoma and/or tumour location in a brain site had lowest survival rates.
CONCLUSION
Paediatric cases had worse outcomes compared with adults for numerous reasons including having a higher percentage of anaplastic ependymomas and greater percentage of cases of intracranial disease.
Topics: Adolescent; Adult; Aged; Brain Neoplasms; Central Nervous System Neoplasms; Child; Child, Preschool; Ependymoma; Female; Humans; Incidence; Infant; Infant, Newborn; Male; Middle Aged; Registries; Survival Rate; United States; Young Adult
PubMed: 23660944
DOI: 10.1038/bjc.2013.221 -
Acta Bio-medica : Atenei Parmensis May 2021Ependymomas are glial neoplasms of central nervous system originated from the ependymal lining of the brain ventricles and spinal cord central canal, and rarely...
Ependymomas are glial neoplasms of central nervous system originated from the ependymal lining of the brain ventricles and spinal cord central canal, and rarely exfoliated into cerebrospinal fluid (CSF). In this case we report the cytomorphological and immunocytomorphological features of ependymoma in CSF and intraoperative squash preparations, confirmed by histology. Case report. The patient was a nineteen months old female presented at the University hospital of Heraklion, Crete, in a hemicoma, and was intubated. Computed tomography, scanning and magnetic resonance imaging (MRI), were performed and a mass in the posterior fossa was found. A sample of cerebrospinal fluid (CSF) was sent for cytologic evaluation. A diagnosis of ependymoma was rendered, followed by tumor resection, during which intraoperative squash smears for cytologic interpretation were obtained. Cytological consultation disclosed a grade II ependymoma (WHO grade II), with focally anaplastic features (WHO grade III).
Topics: Ependymoma; Female; Humans; Infant; Magnetic Resonance Imaging; Tomography, X-Ray Computed
PubMed: 33988164
DOI: 10.23750/abm.v92i2.9996 -
Pathology Oncology Research : POR Mar 2010to retrospectively determine the long-term outcome of adult intracranial ependymoma patients treated with surgery, reoperation, and postoperative radiation therapy.
PURPOSE
to retrospectively determine the long-term outcome of adult intracranial ependymoma patients treated with surgery, reoperation, and postoperative radiation therapy.
MATERIAL AND METHODS
61 patients were treated at our institution between 1980 and 2004. Forty patients had World Health Organization (WHO) Grade II ependymoma, and 21 patients had Grade III ependymoma. The median age was 34 years. The majority of patients were female (59%), and 35 had gross total resections (60%). Eighteen patients were reoperated, 15 only once but 2 twice and one six times. Survival times following reoperation was mostly short but some of them reached more than 5 or 10 years. Postoperative radiation therapy was delivered to 31 patients postoperative (55.4%) and to 5 after reoperation, a median total dose of 54 Gy.
RESULTS
The median follow-up of surviving patients was 10.6 years. The 5-year and 10-year disease free survival rates for all patients were 50% and 32.9% respectively. The 5-year and 10-year overall survival rates for all patients were 57.1% and 39.4%, respectively. A statistically significant effect on prognosis was observed with WHO tumour grade as well as with MIB-1 labelling index. Subtotal resection predicted a worse overall survival, but this failed to reach statistical significance. No statistically significant effect on prognosis was observed with tumour location and radiation therapy.
CONCLUSION
In our experience the use of radiotherapy in adult, intracranial WHO Grade II ependymoma patients had no significant effect on prognosis. Radical surgery and eventual reoperation seems to be more favorable.
Topics: Adolescent; Adult; Aged; Brain Neoplasms; Combined Modality Therapy; Disease-Free Survival; Ependymoma; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neurosurgical Procedures; Radiotherapy; Reoperation; Retrospective Studies; Young Adult
PubMed: 19728165
DOI: 10.1007/s12253-009-9194-5