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Human Cell May 2024MYCN (master regulator of cell cycle entry and proliferative metabolism) gene amplification defines a molecular subgroup of spinal cord ependymomas that show high-grade...
MYCN (master regulator of cell cycle entry and proliferative metabolism) gene amplification defines a molecular subgroup of spinal cord ependymomas that show high-grade morphology and aggressive behavior. Demonstration of MYCN amplification by DNA methylation or fluorescence-in situ hybridization (FISH) is required for diagnosis. We aimed to (i) assess prevalence and clinicopathological features of MYCN-amplified spinal ependymomas and (ii) evaluate utility of immunohistochemistry (IHC) for MYCN protein as a surrogate for molecular testing. A combined retrospective-prospective study spanning 8 years was designed during which all spinal cord ependymomas with adequate tissue were subjected to MYCN FISH and MYCN IHC. Among 77 spinal cord ependymomas included, MYCN amplification was identified in 4 samples from 3 patients (3/74, 4%) including two (1st and 2nd recurrences) from the same patient. All patients were adults (median age at diagnosis of 32 years) including two females and one male. The index tumors were located in thoracic (n = 2) and lumbar (n = 1) spinal cord. One of the female patients had neurofibromatosis type 2 (NF2). All four tumors showed anaplastic histology. Diffuse expression of MYCN protein was seen in all four MYCN-amplified samples but in none of the non-amplified cases, thus showing 100% concordance with FISH results. On follow-up, the NF2 patient developed widespread spinal dissemination while another developed recurrence proximal to the site of previous excision. To conclude, MYCN-amplified spinal ependymomas are rare tumors, accounting for ~ 4% of spinal cord ependymomas. Within the limitation of small sample size, MYCN IHC showed excellent concordance with MYCN gene amplification.
Topics: Adult; Humans; Male; Female; N-Myc Proto-Oncogene Protein; Retrospective Studies; Immunohistochemistry; Prospective Studies; Ependymoma; Spinal Cord Neoplasms; Biomarkers
PubMed: 38411836
DOI: 10.1007/s13577-024-01037-2 -
Neuropathology : Official Journal of... Feb 2024Astroblastoma is an uncommon circumscribed glial tumor mostly involving the cerebral hemisphere. The characteristic molecular alteration is meningioma (disrupted in...
Astroblastoma is an uncommon circumscribed glial tumor mostly involving the cerebral hemisphere. The characteristic molecular alteration is meningioma (disrupted in balanced translocation) 1 (MN1) rearrangement. No definite World Health Organization grade has been assigned as both low- and high-grade tumors are known to occur. Tumors in the spine are extremely rare; to date only three cases have been reported in the literature. A vigilant microscopy and ancillary testing aid in diagnosis when the tumors present in unusual locations, as in our case. The prompt differentiation of this tumor from its mimickers is a mandate as modalities of management are different and not clearly established.
PubMed: 38409890
DOI: 10.1111/neup.12965 -
Advances in Radiation Oncology Feb 2024Volumetric modulated arc therapy (VMAT) is a relatively new treatment technique in sub-Saharan Africa. Although craniospinal irradiation (CSI) in the pediatric...
PURPOSE
Volumetric modulated arc therapy (VMAT) is a relatively new treatment technique in sub-Saharan Africa. Although craniospinal irradiation (CSI) in the pediatric population has been practiced in Nigeria for many years, the use of VMAT to deliver this treatment is previously undocumented. We reviewed the first set of patients to undergo CSI at a cancer center in Nigeria, detailing the treatment technique, the progress experienced, dose statistics achieved, treatment toxicities, and cancer outcomes to date.
METHODS AND MATERIALS
This was a prospective case series of 5 children with histologically diagnosed cancers requiring CSI whose parents consented to the study. They were recruited at evaluation and followed through the process of their therapy. Toxicity was monitored at weekly review appointments using the Common Terminology Criteria for Adverse Events version 5.0. Follow-up of the children will continue in the long-term effects clinic.
RESULTS
Five patients with a median age of 6 were recruited. Diagnoses were intracranial germ cell tumor (n = 2), medulloblastoma (n = 1), pineoblastoma (n = 1), and ependymoma (n = 1). For all patients, a dose of 36.0 Gy in 1.8 Gy daily fractions was prescribed to the entire neuraxis. A subsequent boost of 18 Gy (n = 4) to 19.8 Gy (n = 1) in 10 daily fractions to the primary tumor bed (n = 2) and posterior fossa (n = 2) was delivered. Four patients had chemotherapy before, during, or after radiation therapy. No patient experienced grade 3 or greater toxicity.
CONCLUSIONS
Our results indicate great progress has been made in the delivery of CSI in Nigeria, demonstrating tolerable acute side effects using VMAT. This series suggests the feasibility of implementing VMAT technology in low- or middle-income countries. Additional follow-up will be needed to determine whether survival rates and chronic toxicity rates are similar to those reported in the literature.
PubMed: 38405304
DOI: 10.1016/j.adro.2023.101325 -
Neuroradiology Apr 2024To investigate the value of histogram analysis of postcontrast T1-weighted (T1C) and apparent diffusion coefficient (ADC) images in predicting the grade and...
Whole-tumor histogram analysis of postcontrast T1-weighted and apparent diffusion coefficient in predicting the grade and proliferative activity of adult intracranial ependymomas.
PURPOSE
To investigate the value of histogram analysis of postcontrast T1-weighted (T1C) and apparent diffusion coefficient (ADC) images in predicting the grade and proliferative activity of adult intracranial ependymomas.
METHODS
Forty-seven adult intracranial ependymomas were enrolled and underwent histogram parameters extraction (including minimum, maximum, mean, 1st percentile (Perc.01), Perc.05, Perc.10, Perc.25, Perc.50, Perc.75, Perc.90, Perc.95, Perc.99, standard deviation (SD), variance, coefficient of variation (CV), skewness, kurtosis, and entropy of T1C and ADC) using FireVoxel software. Differences in histogram parameters between grade 2 and grade 3 adult intracranial ependymomas were compared. Receiver operating characteristic curves and logistic regression analyses were conducted to evaluate the diagnostic performance. Spearman's correlation analysis was used to evaluate the relationship between histogram parameters and Ki-67 proliferation index.
RESULTS
Grade 3 intracranial ependymomas group showed significantly higher Perc.95, Perc.99, SD, variance, CV, and entropy of T1C; lower minimum, mean, Perc.01, Perc.05, Perc.10, Perc.25, Perc.50 of ADC; and higher CV and entropy of ADC than grade 2 intracranial ependymomas group (all p < 0.05). Entropy (T1C) and Perc.10 (ADC) had a higher diagnostic performance with AUCs of 0.805 and 0.827 among the histogram parameters of T1C and ADC, respectively. The diagnostic performance was improved by combining entropy (T1C) and Perc.10 (ADC), with an AUC of 0.857. Significant correlations were observed between significant histogram parameters of T1C (r = 0.296-0.417, p = 0.001-0.044) and ADC (r = -0.428-0.395, p = 0.003-0.038).
CONCLUSION
Whole-tumor histogram analysis of T1C and ADC may be a promising approach for predicting the grade and proliferative activity of adult intracranial ependymomas.
Topics: Adult; Humans; Diffusion Magnetic Resonance Imaging; Ependymoma; ROC Curve; Brain Neoplasms; Retrospective Studies
PubMed: 38400953
DOI: 10.1007/s00234-024-03319-w -
NPJ Precision Oncology Feb 2024Pre-surgery differential diagnosis is valuable for personalized treatment planning in intramedullary spinal cord tumors. This study assessed the performance of...
Pre-surgery differential diagnosis is valuable for personalized treatment planning in intramedullary spinal cord tumors. This study assessed the performance of sequencing cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) for differential diagnosis of these tumors. Prospectively enrolling 45 patients with intramedullary spinal cord lesions, including diffuse midline glioma (DMG), H3K27-altered (14/45), glioblastoma (1/45), H3-wildtype-astrocytoma (10/45), ependymoma (11/45), and other lesions (9/45), CSF samples were collected via lumbar puncture (41/45), intraoperative extraction (3/45), and Ommaya reservoir (1/45). Then, these samples underwent targeted sequencing along with paired tissue DNA. DMG, H3K27-altered patients exhibited a higher ctDNA positivity (85.7%, 12/14) compared to patients with H3-wildtype-astrocytoma (0/8, P = 0.0003), ependymoma (2/10, P = 0.003), and glioneuronal tumor (0/3, P = 0.009). The histological-grade-IV (P = 0.0027), Ki-67 index ≥10% (P = 0.014), and tumor reaching spinal cord surface (P = 0.012) are also associated with higher ctDNA positivity. Interestingly, for patients with TERT promoter mutant tumors, TERT mutation was detectable in the CSF cfDNA of one DMG case, but not other five cases with histological-grade-II tumors. Shared copy number variants were exclusively observed in DMG, H3K27-altered, and showed a strong correlation (Correlation = 0.95) between CSF and tissue. Finally, H3K27M mutations in CSF exhibited high diagnostic efficiency for DMG, H3K27-altered (Sensitivity = 85.7%, Specificity = 100.0%, AUC = 0.929). Notably, H3K27M was detectable in CSF from patients with recurrent tumors, making it easily applicable for postoperative monitoring. In conclusion, the molecular profile from ctDNA released into CSF of malignant tumors was more frequently detected compared to relatively benign ones. Sequencing of ctDNA in CSF exhibited high efficiency for the differential diagnosis of DMG, H3K27-altered.
PubMed: 38388726
DOI: 10.1038/s41698-024-00541-w -
Asian Journal of Surgery Jun 2024
Topics: Humans; Ependymoma; Pineal Gland; Pinealoma; Brain Neoplasms; Male; Magnetic Resonance Imaging; Female
PubMed: 38388272
DOI: 10.1016/j.asjsur.2024.02.027 -
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 -
BJU International Jul 2024
Topics: Humans; Urinary Bladder Neoplasms; Ependymoma; Male; Female
PubMed: 38379218
DOI: 10.1111/bju.16302 -
Radiotherapy and Oncology : Journal of... May 2024Ependymoma is the third most frequent childhood braintumor. Standard treatment is surgery followed by radiation therapy including proton therapy (PBT). Retrospective...
BACKGROUND AND PURPOSE
Ependymoma is the third most frequent childhood braintumor. Standard treatment is surgery followed by radiation therapy including proton therapy (PBT). Retrospective studies have reported higher rates of brainstem injury after PBT than after photon therapy (XRT). We report a national multicenter study of the incidence of brainstem injury after XRT versus PBT, and their correlations with dosimetric data.
MATERIAL AND METHODS
We included all patients aged < 25 years who were treated with PBT or XRT for intracranial ependymoma at five French pediatric oncology reference centers between 2007 and 2020. We reviewed pre-irradiation MRI, follow-up MRIs over the 12 months post-treatment and clinical data.
RESULTS
Of the 83 patients, 42 were treated with PBT, 37 with XRT, and 4 with both (median dose: 59.4 Gy, range: 53‑60). No new or progressive symptomatic brainstem injury was found. Four patients presented asymptomatic radiographic changes (punctiform brainstem enhancement and FLAIR hypersignal), with median onset at 3.5 months (range: 3.0‑9.4) after radiation therapy, and median offset at 7.6 months (range: 3.7‑7.9). Two had been treated with PBT, one with XRT, and one with mixed XRT-PBT. Prescribed doses were 59.4, 55.8, 59.4 and 54 Gy.
CONCLUSION
Asymptomatic radiographic changes occurred in 4.8% of patients with ependymoma in a large national series. There was no correlation with dose or technique. No symptomatic brainstem injury was identified.
Topics: Humans; Ependymoma; Proton Therapy; Retrospective Studies; Female; Male; Child; Brain Neoplasms; Adolescent; Child, Preschool; Brain Stem; Young Adult; France; Photons; Radiation Injuries; Magnetic Resonance Imaging; Infant; Radiotherapy Dosage
PubMed: 38367939
DOI: 10.1016/j.radonc.2024.110157