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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 -
Journal of Neurosurgery Dec 2023Mutations in NF2 are the most common somatic driver mutation in sporadic meningiomas. NF2 mutant meningiomas preferentially arise along the cerebral convexities-however,...
OBJECTIVE
Mutations in NF2 are the most common somatic driver mutation in sporadic meningiomas. NF2 mutant meningiomas preferentially arise along the cerebral convexities-however, they can also be found in the posterior fossa. The authors investigated whether NF2 mutant meningiomas differ in clinical and genomic features based on their location relative to the tentorium.
METHODS
Clinical and whole exome sequencing (WES) data for patients who underwent resection of sporadic NF2 mutant meningiomas were reviewed and analyzed.
RESULTS
A total of 191 NF2 mutant meningiomas were included (165 supratentorial, 26 infratentorial). Supratentorial NF2 mutant meningiomas were significantly associated with edema (64.0% vs 28.0%, p < 0.001); higher grade-i.e., WHO grade II or III (41.8% vs 3.9%, p < 0.001); elevated Ki-67 (55.0% vs 13.6%, p < 0.001); and larger volume (mean 45.5 cm3 vs 14.9 cm3, p < 0.001). Furthermore, supratentorial tumors were more likely to harbor the higher-risk feature of chromosome 1p deletion (p = 0.038) and had a larger fraction of the genome altered with loss of heterozygosity (p < 0.001). Infratentorial meningiomas were more likely to undergo subtotal resection than supratentorial tumors (37.5% vs 15.8%, p = 0.021); however, there was no significant difference in overall (p = 0.2) or progression-free (p = 0.4) survival.
CONCLUSIONS
Supratentorial NF2 mutant meningiomas are associated with more aggressive clinical and genomic features as compared with their infratentorial counterparts. Although infratentorial tumors have higher rates of subtotal resection, there is no associated difference in survival or recurrence. These findings help to better inform surgical decision-making in the management of NF2 mutant meningiomas based on location, and may guide postoperative management of these tumors.
Topics: Humans; Meningioma; Meningeal Neoplasms; Mutation; Genomics; Supratentorial Neoplasms
PubMed: 37243548
DOI: 10.3171/2023.4.JNS222929 -
ZFTA-RELA Dictates Oncogenic Transcriptional Programs to Drive Aggressive Supratentorial Ependymoma.Cancer Discovery Sep 2021More than 60% of supratentorial ependymomas harbor a (ZR) gene fusion (formerly ). To study the biology of ZR, we developed an autochthonous mouse tumor model using...
More than 60% of supratentorial ependymomas harbor a (ZR) gene fusion (formerly ). To study the biology of ZR, we developed an autochthonous mouse tumor model using electroporation (IUE) of the embryonic mouse brain. Integrative epigenomic and transcriptomic mapping was performed on IUE-driven ZR tumors by CUT&RUN, chromatin immunoprecipitation sequencing, assay for transposase-accessible chromatin sequencing, and RNA sequencing and compared with human ZR-driven ependymoma. In addition to direct canonical NFκB pathway activation, ZR dictates a neoplastic transcriptional program and binds to thousands of unique sites across the genome that are enriched with PLAGL family transcription factor (TF) motifs. ZR activates gene expression programs through recruitment of transcriptional coactivators (Brd4, Ep300, Cbp, Pol2) that are amenable to pharmacologic inhibition. Downstream ZR target genes converge on developmental programs marked by PLAGL TF proteins, and activate neoplastic programs enriched in Mapk, focal adhesion, and gene imprinting networks. SIGNIFICANCE: Ependymomas are aggressive brain tumors. Although drivers of supratentorial ependymoma (- and -associated gene fusions) have been discovered, their functions remain unclear. Our study investigates the biology of -driven ependymoma, specifically mechanisms of transcriptional deregulation and direct downstream gene networks that may be leveraged for potential therapeutic testing..
Topics: Animals; DNA-Binding Proteins; Disease Models, Animal; Ependymoma; Mice; Supratentorial Neoplasms; Transcription Factor RelA; Transcription Factors
PubMed: 33741710
DOI: 10.1158/2159-8290.CD-20-1066 -
Journal of Clinical Neuroscience :... Dec 2014Intracranial ependymomas are rare tumors in adults. Thus, factors affecting prognosis are poorly understood. We performed a study to investigate whether tumor location... (Review)
Review
Intracranial ependymomas are rare tumors in adults. Thus, factors affecting prognosis are poorly understood. We performed a study to investigate whether tumor location is an important prognostic factor in adults who undergo surgery for intracranial ependymomas. PubMed was searched to identify studies that reported clinical outcomes in adult patients with intracranial ependymoma. Data were extracted for patient and tumor characteristics, extent of resection, progression-free survival (PFS), and overall survival (OS). Tumors were categorized as supratentorial or infratentorial and extraventricular or intraventricular. Presenting clinical features and tumor characteristics were tabulated. Kaplan-Meier and multivariate Cox regression survival analyses were performed to determine PFS and OS by tumor location. Extent of resection was also analyzed by tumor location. A total of 183 patients were included in the meta-analysis. Patients presented at a mean of 8.2months with a myriad of clinical features. The mean tumor size was 3.38 cm, and 19.3% of tumors were cystic. Supratentorial tumors were most commonly located in the frontal and parietal lobes, and infratentorial tumors in the fourth ventricle. Supratentorial tumors demonstrated significantly poorer PFS (p<0.001) and OS (p=0.003) than infratentorial tumors, despite a higher rate of gross total resection (GTR) for the supratentorial tumors (72.6% versus 42.1%). Extraventricular ependymomas displayed significantly poorer PFS than intraventricular ependymomas (p=0.009). In summary, supratentorial ependymomas have significantly poorer PFS and OS than their infratentorial counterparts, despite being more conducive to GTR, suggesting increased clinical aggressiveness. Extraventricular location is also associated with significantly poorer PFS than intraventricular location.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain Neoplasms; Disease-Free Survival; Ependymoma; Female; Humans; Male; Meta-Analysis as Topic; Middle Aged; Prognosis; Proportional Hazards Models; Supratentorial Neoplasms; Young Adult
PubMed: 25037313
DOI: 10.1016/j.jocn.2014.05.011 -
World Neurosurgery Sep 2019Hemangioblastomas are benign vascular neoplasms that may be associated with von Hippel-Lindau disease. They are more common in men, with a mean age of 36 years, and...
BACKGROUND
Hemangioblastomas are benign vascular neoplasms that may be associated with von Hippel-Lindau disease. They are more common in men, with a mean age of 36 years, and rarely affect the supratentorial region and, when present in this topography, do not have meningeal impairment. Diagnosis by the radiologic and histopathologic study is difficult, since they are rare and, therefore, forgotten diagnosis, besides they are differential diagnoses with other supratentorial neoplasms.
CASE DESCRIPTION
The present report describes a case of a frontal hemangioblastoma in a 64-year-old woman who presented with seizures. Our imaging studies had as a main hypothesis a frontal meningioma because of dural tail sign, lack of edema, contrast enhancement pattern, and extra-axial location in the supratentorial region, in the frontal lobe, which is uncommon for a hemangioblastoma. The patient underwent microneurosurgery for tumor resection, and the excised tissue was submitted for anatomopathologic evaluation. This study clarified the diagnosis as hemangioblastoma. We followed up the patient at the outpatient clinic for 2 years, with clinical improvement, without tumor recurrence. We also compared the clinical, radiologic, epidemiologic, and anatomopathologic data of the reported case with data from a literature review conducted through the PubMed portal.
CONCLUSIONS
Definitive treatment for these lesions is surgical resection. Physicians should be aware that supratentorial meningeal hemangioblastomas can be developed in a patient without von Hippel-Lindau disease and regular follow-up is mandatory.
Topics: Dura Mater; Female; Hemangioblastoma; Humans; Meningeal Neoplasms; Middle Aged; Supratentorial Neoplasms
PubMed: 31150863
DOI: 10.1016/j.wneu.2019.05.175 -
Anesthesiology Clinics Mar 2021Understanding how anesthetics impact cerebral physiology, cerebral blood flow, brain metabolism, brain relaxation, and neurologic recovery is crucial for optimizing... (Review)
Review
Understanding how anesthetics impact cerebral physiology, cerebral blood flow, brain metabolism, brain relaxation, and neurologic recovery is crucial for optimizing anesthesia during supratentorial craniotomies. Intraoperative goals for supratentorial tumor resection include maintaining cerebral perfusion pressure and cerebral autoregulation, optimizing surgical access and neuromonitoring, and facilitating rapid, cooperative emergence. Evidence-based studies increasingly expand the impact of anesthetic care beyond immediate perioperative care into both preoperative optimization and minimizing postoperative consequences. New evidence is needed for neuroanesthesia's role in neurooncology, in preventing conversion from acute to chronic pain, and in decreasing risk of intraoperative ischemia and postoperative delirium.
Topics: Anesthesia; Anesthetics; Craniotomy; Humans; Supratentorial Neoplasms; Wakefulness
PubMed: 33563387
DOI: 10.1016/j.anclin.2020.11.007 -
RoFo : Fortschritte Auf Dem Gebiete Der... Mar 2019
Topics: Adolescent; Cell Proliferation; Collagen; Contrast Media; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Female; Humans; Ki-67 Antigen; Magnetic Resonance Imaging; Neoplasm Grading; Neurilemmoma; S100 Proteins; SOXE Transcription Factors; Supratentorial Neoplasms
PubMed: 30081423
DOI: 10.1055/a-0657-4061 -
Journal of Clinical Neuroscience :... Jun 2016Ependymoma is a rare primary brain or spinal cord tumor that arises from the ependyma, a tissue of the central nervous system. This study analyzed a large cohort of...
Ependymoma is a rare primary brain or spinal cord tumor that arises from the ependyma, a tissue of the central nervous system. This study analyzed a large cohort of adult supratentorial and posterior fossa ependymoma tumors in order to elucidate factors associated with overall survival. We utilized the USA National Cancer Database to study adult World Health Organization grade II/III supratentorial and posterior fossa ependymoma patients treated between 1998 and 2011. Overall survival was estimated by the Kaplan-Meier method and factors associated with survival were determined using a multivariate Cox proportional hazards model. Among 1318 patients, 1055 (80.0%) had grade II and 263 (20.0%) anaplastic tumors located in the posterior fossa (64.3%) and supratentorial region (35.7%). Overall average age was 44.3years, 48.0% of patients were female, 86.5% were Caucasian, and 36.8% underwent near/gross total surgical resection. Radiotherapy was given to 662 patients (50.8%) and 75 (5.9%) received chemotherapy. Older age at diagnosis (hazard ratio [HR] 1.51, p<0.0001), high tumor grade (HR 1.82, p=0.005), and large tumor size (HR 1.66, p=0.008) were associated with poor survival. Females compared to males (HR 0.67, p=0.03) and patients with posterior fossa tumors versus supratentorial (HR 0.64, p=0.04) had a survival advantage. Our study showed that older patients, with supratentorial tumors, and high histological grade had an increased risk of mortality. A survival benefit was captured in females and patients with posterior fossa tumors. Adjuvant radiotherapy and chemotherapy did not confer a survival benefit among all patients, even after stratification by tumor grade or anatomical location.
Topics: Adult; Ependymoma; Female; Humans; Infratentorial Neoplasms; Male; Middle Aged; Prognosis; Supratentorial Neoplasms
PubMed: 26810473
DOI: 10.1016/j.jocn.2015.11.014 -
Brain Tumor Pathology Oct 2014Here, we review the recent literature on molecular discoveries in ependymomas and pediatric diffuse gliomas. Ependymomas can now be categorized into three... (Review)
Review
Here, we review the recent literature on molecular discoveries in ependymomas and pediatric diffuse gliomas. Ependymomas can now be categorized into three location-related subgroups according to their biological profile: posterior fossa ependymomas, group A (PFA) and B (PFB), and supratentorial ependymomas. Although no recurrently mutated genes were found throughout these groups of ependymomas, PFA exhibited a CpG island methylator phenotype, PFB was associated with extensive chromosomal aberrations, and the C11orf95-RELA fusion gene was frequently observed in supratentorial ependymomas. Meanwhile, it has now become apparent that pediatric diffuse gliomas have a distinct genetic status from their adult counterparts, even though they share an indistinguishable histology. In pediatric low-grade diffuse gliomas, an intragenic duplication of the portion of FGFR1 encoding the tyrosine kinase domain (TKD) and rearrangements of MYB/MYBL1 were found recurrently and mutually exclusively. As for non-brainstem high-grade tumors, in addition to H3F3A, TP53, and ATRX mutations, which were frequently observed in older children, recurrent fusions involving NTRK1, NTRK2, and NTRK3 were reported in infants younger than 3 years of age. Moreover, in diffuse intrinsic pontine gliomas (DIPG), recurrent somatic mutations of ACVR1 were found in association with HIST1H3B mutations.
Topics: Adolescent; Age Factors; Brain Neoplasms; Child; Child, Preschool; Chromosome Aberrations; DNA Helicases; DNA-Cytosine Methylases; Ependymoma; Gene Duplication; Gene Fusion; Gene Rearrangement; Glioma; Humans; Infant; Infratentorial Neoplasms; Membrane Glycoproteins; Mutation; Nuclear Proteins; Phenotype; Protein-Tyrosine Kinases; Proteins; Proto-Oncogene Proteins; Receptor, Fibroblast Growth Factor, Type 1; Receptor, trkB; Receptor, trkC; Supratentorial Neoplasms; Trans-Activators; Transcription Factor RelA; Tumor Suppressor Protein p53; X-linked Nuclear Protein; Young Adult
PubMed: 25182241
DOI: 10.1007/s10014-014-0200-6 -
Journal of Neurosurgical Sciences Jun 2015With the increasing strive for complete resections of supratentorial low or high-grade gliomas, the necessity for intraoperative electrical stimulation methods to map... (Review)
Review
With the increasing strive for complete resections of supratentorial low or high-grade gliomas, the necessity for intraoperative electrical stimulation methods to map and monitor functional important cortical or subcortical brain areas increased. While many brain functions can be assessed during awake surgery using electrical stimulation, motor function as well as visual function can be mapped and monitored in the asleep patient, as well. Several different methods reviewed in this article are available which lead to an improved functional outcome while increasing the extent of tumor resection and thereby potentially the oncological outcome of the patient.
Topics: Brain Mapping; Glioma; Humans; Intraoperative Neurophysiological Monitoring; Supratentorial Neoplasms
PubMed: 25690027
DOI: No ID Found