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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 -
CNS Oncology Jan 2024Atypical teratoid rhabdoid tumors (AT/RT) are rare and highly malignant CNS neoplasms primarily affecting children. Adult cases are extremely uncommon, with only...
Atypical teratoid rhabdoid tumors (AT/RT) are rare and highly malignant CNS neoplasms primarily affecting children. Adult cases are extremely uncommon, with only approximately 92 reported. Spinal AT/RT in adults is particularly rare. Here, we present the case of a 50-year-old patient diagnosed with AT/RT of the spine. Initially, they were diagnosed and treated for a spinal ependymoma. However, after 10 years, a recurrence was detected through magnetic resonance imaging (MRI) and the tumor was reclassified as AT/RT. We discuss the significance of gene mutations in diagnosing AT/RT and describe our unique treatment approach involving surgery, radiation and anti-PD1 therapy in this patient.
Topics: Humans; Middle Aged; Central Nervous System Neoplasms; Rhabdoid Tumor; SMARCB1 Protein; Teratoma
PubMed: 38380555
DOI: 10.2217/cns-2023-0017 -
Journal of Medical Case Reports Feb 2024Ependymomas are the third most common central nervous system tumor in the pediatric population; however, spinal ependymomas in children are rare. Ependymomas affecting... (Review)
Review
BACKGROUND
Ependymomas are the third most common central nervous system tumor in the pediatric population; however, spinal ependymomas in children are rare. Ependymomas affecting the spinal cord most frequently occur in adults of 20-40 years of age. The current World Health Organization classification system for ependymomas is now composed of ten different entities based on histopathology, location, and molecular studies, with evidence that the new classification system more accurately predicts clinical outcomes.
CASE PRESENTATION
We present the case of a 16-year-old Caucasian female patient with a history of type 2 neurofibromatosis with multiple schwannomas, meningioma, and spinal ependymoma. Chromosome analysis of the harvested spinal ependymoma tumor sample revealed a 46,XX,-6,+7,-22,+mar[16]/46,XX[4] karyotype. Subsequent OncoScan microarray analysis of the formalin-fixed paraffin-embedded tumor sample confirmed + 7, -22 and clarified that the marker chromosome represents chromothripsis of the entire chromosome 6 with more than 100 breakpoints. Fluorescent in situ hybridization and microarray analysis showed no evidence of MYCN amplification. The final integrated pathology diagnosis was spinal ependymoma (central nervous system World Health Organization grade 2 with no MYCN amplification.
CONCLUSION
This case adds to the existing literature of pediatric patients with spinal ependymomas and expands the cytogenetic findings that may be seen in patients with this tumor type. This case also highlights the value of cytogenetics and microarray analysis in solid tumors to provide a more accurate molecular diagnosis.
Topics: Adult; Humans; Child; Female; Adolescent; Chromothripsis; Chromosomes, Human, Pair 6; In Situ Hybridization, Fluorescence; Spinal Cord Neoplasms; Ependymoma; Meningeal Neoplasms
PubMed: 38351155
DOI: 10.1186/s13256-023-04283-4 -
Frontiers in Neurology 2023Anomalous origin of the middle meningeal artery (MMA) from the basilar artery is a rare congenital neurological variant that has been detected in both children and...
BACKGROUND
Anomalous origin of the middle meningeal artery (MMA) from the basilar artery is a rare congenital neurological variant that has been detected in both children and adults with diagnoses ranging from intracranial haemorrhage to ependymoma. This review aims to investigate the anatomical course of an anomalous basilar-middle meningeal artery and its clinical presentation.
METHODS
A systematic search was performed in PubMed using the keywords (middle meningeal artery) and (basilar artery). Ninety-four papers were identified, of which seven were included. One paper was further identified through cross-referencing.
RESULTS
The average age of presentation was 43 years with a male predominance (7/9). In most cases, the MMA arose between the superior cerebellar artery and the anterior inferior cerebellar artery (8/9) (versus 1 case between the anterior inferior cerebellar artery and the posterior inferior cerebellar artery). The anomaly mostly presented on the left side (6/11), but was bilateral in one case. Most of the cases showed a pontine artery branching from the basilar artery arising 5 mm to 10 mm proximal to the superior cerebellar artery, which would then assume the trajectory of the MMA. In three cases, the vessel increased in calibre near the trigeminal ganglion. Foramen spinosum absence in the anomalous side was noted in 3/6 of the patients.
CONCLUSION
To avoid unexpected complications during neurosurgical and neuroradiointerventional procedures, it is essential to have a clear understanding of the anomalous routes of the MMA. This is especially important when it proves to be the only available route for embolization.
PubMed: 38322796
DOI: 10.3389/fneur.2023.1301426 -
Radiology Case Reports Apr 2024Myxopapillary ependymoma, a rare variant of ependymoma, commonly occurs in the conus medullaris or filum terminale. The rarity of these tumors can make their diagnosis...
Myxopapillary ependymoma, a rare variant of ependymoma, commonly occurs in the conus medullaris or filum terminale. The rarity of these tumors can make their diagnosis and treatment challenging. This case report presents an atypical occurrence of myxopapillary ependymoma within the sacrum in a 68-year-old patient presented with a 3-month history of persistent left-sided low back pain radiating to the legs and fecal dysfunction. The patient underwent a sacral laminectomy and subtotal excision of the tumor, followed by adjuvant radiotherapy with favorable outcomes. This report highlights the significance of tailored approaches for unconventional tumor locations emphasizes the potential benefits of multimodal treatment strategies and provides insights from a comprehensive literature review on similar cases.
PubMed: 38312753
DOI: 10.1016/j.radcr.2023.12.010 -
Frontiers in Oncology 2023Ependymomas are central nervous system tumors that significantly impact the quality of life and carry a high mortality rate. Both the disease itself and its treatment...
BACKGROUND
Ependymomas are central nervous system tumors that significantly impact the quality of life and carry a high mortality rate. Both the disease itself and its treatment cause significant morbidity. At a national level in Peru, there are no reports on clinical characteristics of the disease.
METHODS
This retrospective study captured patient aged less than 19 years with a diagnosis of ependymoma from 2012 to 2022 at a tertiary center in Lima.
RESULTS
85 patients were included with a median follow-up time was 51.6 months. The 5-year overall survival and progression-free survival were 55.89% (95% CI: 44.28 - 65.99) and 37.71% (95% CI: 26,21-49,16) respectively. The main prognostic factors identified were completed treatment (p=0.019), adjuvant chemotherapy (p=0.048), presence of metastasis (p=0.012), and disease recurrence (p=0.02).
CONCLUSIONS
The survival of patients with ependymoma is below that reported in high-income countries. Incomplete treatment and treatment abandonment are factors that negatively impact the prognosis. Further studies are needed to identify barriers in the referral and treatment process for patients with ependymoma.
PubMed: 38298447
DOI: 10.3389/fonc.2023.1331790 -
Journal of Neuro-oncology Mar 2024Central nervous system (CNS) tumours account for around 25% of childhood neoplasms. With multi-modal therapy, 5-year survival is at around 75% in the UK. Conventional... (Review)
Review
BACKGROUND
Central nervous system (CNS) tumours account for around 25% of childhood neoplasms. With multi-modal therapy, 5-year survival is at around 75% in the UK. Conventional photon radiotherapy has made significant contributions to survival, but can be associated with long-term side effects. Proton beam radiotherapy (PBT) reduces the volume of irradiated tissue outside the tumour target volume which may potentially reduce toxicity. Our aim was to assess the effectiveness and safety of PBT and make recommendations for future research for this evolving treatment.
METHODS
A systematic review assessing the effects of PBT for treating CNS tumours in children/young adults was undertaken using methods recommended by Cochrane and reported using PRISMA guidelines. Any study design was included where clinical and toxicity outcomes were reported. Searches were to May 2021, with a narrative synthesis employed.
RESULTS
Thirty-one case series studies involving 1731 patients from 10 PBT centres were included. Eleven studies involved children with medulloblastoma / primitive neuroectodermal tumours (n = 712), five ependymoma (n = 398), four atypical teratoid/rhabdoid tumour (n = 72), six craniopharyngioma (n = 272), three low-grade gliomas (n = 233), one germ cell tumours (n = 22) and one pineoblastoma (n = 22). Clinical outcomes were the most frequently reported with overall survival values ranging from 100 to 28% depending on the tumour type. Endocrine outcomes were the most frequently reported toxicity outcomes with quality of life the least reported.
CONCLUSIONS
This review highlights areas of uncertainty in this research area. A well-defined, well-funded research agenda is needed to best maximise the potential of PBT.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO-CRD42016036802.
Topics: Child; Humans; Young Adult; Proton Therapy; Quality of Life; Central Nervous System Neoplasms; Central Nervous System; Pituitary Neoplasms; Cerebellar Neoplasms
PubMed: 38294638
DOI: 10.1007/s11060-023-04510-4 -
The American Journal of Case Reports Jan 2024BACKGROUND Myxopapillary ependymoma is a rare type of slow-growing tumor that mainly occurs in the spinal cord, particularly in the region of the conus medullaris and...
BACKGROUND Myxopapillary ependymoma is a rare type of slow-growing tumor that mainly occurs in the spinal cord, particularly in the region of the conus medullaris and the cauda equina. It originates from the ependymal glial cells found in the filum terminale. CASE REPORT We present a clinical case of a 44-year-old male patient who presented with symptoms of non-specific pain in the lower back persisting for the past 2 years. He did not report any specific neurological deficits or radicular symptoms. Unenhanced MRI of the lumbar spine showed a giant intradural, extramedullary, heterogenous, expansive tumor at the level L1-S4 with erosion of the sacral bone and invasion of presacral tissue. Based on its characteristic localization and growth pattern, suspicion arose for myxopapillary ependymoma. Biopsy confirmed the initial diagnosis. Partial resection of the tumor with laminectomy and laminoplasty was deemed necessary. Preoperative neural axis MRI showed contrast-enhancing lesions in the cerebellum and the cervical and thoracic spine; therefore, adjuvant radiation therapy was administered. Following the surgery, the patient experienced intermittent episodes of neurological deficits and required physiotherapy. Control MRI a year after the operation showed tumor growth and more metastases along the neural axis. CONCLUSIONS Complete surgical excision of the tumor is the preferred treatment approach, but there is a risk of recurrence even after total excision, so radiotherapy is recommended to minimize the risk of recurrence. Prior to surgery, it is essential to conduct MRI/PET/CT of the head and spine to assess the possibility of metastases.
Topics: Male; Humans; Adult; Spinal Cord Neoplasms; Positron Emission Tomography Computed Tomography; Ependymoma; Cauda Equina; Laminectomy; Magnetic Resonance Imaging
PubMed: 38291726
DOI: 10.12659/AJCR.942392 -
Frontiers in Oncology 2023Recently, there has been growing interest in the presence and function of meningeal lymphatic vessels, with no direct evidence linking these vessels to primary brain...
Recently, there has been growing interest in the presence and function of meningeal lymphatic vessels, with no direct evidence linking these vessels to primary brain tumors. We report a unique case of recurrent ependymoma in the dura mater, showing histopathological signs of lymphatic proliferation at the tumor attachment site. The patient initially presented with a headache, and was diagnosed with fusion-positive supratentorial ependymoma, central nervous system WHO Grade 3. Following multiple dura mater recurrences and surgery, the fifth procedure revealed numerous tumors contralateral to the original site, with genetic testing confirming fusion positivity, indicating recurrent ependymoma. Immunohistochemical analysis showed D2-40 lymphatic vessel proliferation around tumor attachment sites within the dura mater. Elevated expression of , which is an epithelial-to-mesenchymal transition factor, was also observed, implicating potential involvement in the unique pathophysiology. The present case suggests a new process of metastasis through meningeal lymphatic vessels, although we were unable to visually confirm tumor cell infiltration into the lymphatic vessels. This case is the first report suggesting ependymoma metastasis through dural lymphatic vessels, underlining the need for further case accumulation and study to understand the mechanisms of this phenomenon.
PubMed: 38282673
DOI: 10.3389/fonc.2023.1340167 -
Acta Neuropathologica Jan 2024Posterior fossa type A (PF-EPN-A, PFA) ependymoma are aggressive tumors that mainly affect children and have a poor prognosis. Histopathology shows significant...
Posterior fossa type A (PF-EPN-A, PFA) ependymoma are aggressive tumors that mainly affect children and have a poor prognosis. Histopathology shows significant intratumoral heterogeneity, ranging from loose tissue to often sharply demarcated, extremely cell-dense tumor areas. To determine molecular differences in morphologically different areas and to understand their clinical significance, we analyzed 113 PF-EPN-A samples, including 40 corresponding relapse samples. Cell-dense areas ranged from 0 to 100% of the tumor area and displayed a higher proportion of proliferating tumor cells (p < 0.01). Clinically, cell density was associated with poor progression-free and overall survival (p = 0.0026, p < 0.01). Molecularly, tumor areas with low and high cell density showed diverging DNA methylation profiles regarding their similarity to distinct previously discovered PF-EPN-A subtypes in 9/21 cases. Prognostically relevant chromosomal changes at 1q and 6q showed spatial heterogeneity within single tumors and were significantly enriched in cell-dense tumor areas as shown by single-cell RNA (scRNA)-sequencing as well as copy number profiling and fluorescence in situ hybridization (FISH) analyses of different tumor areas. Finally, spatial transcriptomics revealed cell-dense areas of different tumors to be more similar than various different areas of the same tumor. High-density areas distinctly overexpressed genes encoding histone proteins, WNT5A, TGFB1, or IGF2. Relapsing tumors displayed a higher proportion of cell-dense areas (p = 0.036), a change in PF-EPN-A methylation subtypes (13/32 patients), and novel chromosome 1q gains and 6q losses (12/32 cases) compared to corresponding primary tumors. Our data suggest that PF-EPN-A ependymomas habor a previously unrecognized intratumoral heterogeneity with clinical implications, which has to be accounted for when selecting diagnostic material, inter alia, by histological evaluation of the proportion of cell-dense areas.
Topics: Child; Humans; In Situ Hybridization, Fluorescence; Neoplasm Recurrence, Local; Ependymoma; Histones; Gene Expression Profiling
PubMed: 38265527
DOI: 10.1007/s00401-023-02682-x