Supra-tentorial Ependymomas with ZFTA Fusion, YAP1 Fusion, and Astroblastomas, MN1-altered: Characteristic Imaging Features.

PURPOSE: Supratentorial (ST) ependymoma subgroups are defined by two different fusions with different prognoses. Astroblastomas, MN1-altered, have ependymal-like histopathologic features and represent a differential diagnosis in children. We hypothesized that ZFTA-fused ependymoma and YAP1-fused ependymoma on the one hand, and astroblastoma, MN1-altered, on the other hand, show different MRI characteristics. METHODS: We retrospectively analyzed the preoperative imaging of 45 patients with ST ependymoma or astroblastoma between January 2000 and September 2020, blinded to histomolecular grouping. Several characteristics, such as location, tumor volume, calcifications, solid/cystic component, and signal enhancement or diffusion were evaluated. We compared imaging characteristics according to their molecular subtype (ZFTA-fused, YAP1-fused, and astroblastoma, MN1-altered). RESULTS: Thirty-nine patients were classified as having an ependymoma, 35 with a ZFTA fusion and four with a YAP1 fusion, and six as having an astroblastoma, MN1-altered. YAP1-fused ependymomas were more likely to involve at least 3 lobes than ZFTA-fused ependymomas. Astroblastomas were located in the frontal lobe in 100% of the tumors versus 49% of the ependymomas. Cerebral blood flow by arterial spin labeling was higher in astroblastomas than in ependymomas. There were no differences in the other characteristics between the molecular groups. All the tumors showed common features: intra-axial extra-ventricular tumors, very frequent contrast enhancement (39/43, 91%), a cystic/necrotic component (41/45, 91%), restricted diffusion (32/36, 89%), calcifications (15/18, 83%), and peri-tumoral edema (38/44, 86%). CONCLUSION: The distinction between ST ependymoma subtypes and astroblastomas can be guided by several imaging features. These tumors share common imaging features that may help to differentiate ST ependymomas and astroblastomas from other pediatric ST tumors.

Identification and validation of miRNA-target genes network in pediatric brain tumors.

Alterations in miRNA levels have been observed in various types of cancer, impacting numerous cellular processes and increasing their potential usefulness in combination therapies also in brain tumors. Recent advances in understanding the genetics and epigenetics of brain tumours point to new aberrations and associations, making it essential to continually update knowledge and classification. Here we conducted molecular analysis of 123 samples of childhood brain tumors (pilocytic astrocytoma, medulloblastoma, ependymoma), focusing on identification of genes that could potentially be regulated by crucial representatives of OncomiR-1: miR-17-5p and miR-20a-5p. On the basis of microarray gene expression analysis and qRTPCR profiling, we selected six (WEE1, CCND1, VEGFA, PTPRO, TP53INP1, BCL2L11) the most promising target genes for further experiments. The WEE1, CCND1, PTPRO, TP53INP1 genes showed increased expression levels in all tested entities with the lowest increase in the pilocytic astrocytoma compared to the ependymoma and medulloblastoma. The obtained results indicate a correlation between gene expression and the WHO grade and subtype. Furthermore, our analysis showed that the integration between genomic and epigenetic pathways should now point the way to further molecular research.

Microsurgery resection of giant cervicothoracic spinal ependymoma: Two-dimensional operative video.

Background: Ependymomas, rare glial brain tumors, account for <5% of all brain tumors. Interestingly, over 60% of ependymomas occur in the spinal cord of adults, including those originating from the filum terminale, while the rest are found within the brain. The World Health Organization (WHO) categorizes ependymomas into three grades: subependymomas and myxopapillary ependymomas ([MEPNs]; WHO grade I), classic ependymomas (WHO grade II), and anaplastic ependymomas (WHO grade III). Spinal ependymomas generally exhibit a more favorable prognosis compared to their intracranial counterparts and are primarily treated through gross total resection, which is considered the most effective surgical approach. As such, they are recognized as a distinct clinical entity that demands tailored management strategies. MEPNs, which constitute 13% of ependymomas, typically occur in the cauda equina and sometimes extend into the conus medullaris. Most other spinal ependymomas are of the classic type and predominantly arise in the cervical and thoracic regions of the spine. The mean age at diagnosis is 45 years of age. While prognosis varies based on molecular subtypes, complete resection is associated with improved survival. Case Description: Here, we demonstrate the technical nuances to safely achieve gross total resection of a giant spinal ependymoma in a 29-year-old female with a medical history notable for sept-optic dysplasia, and panhypopituitarism. The patient presented with progressive neck pain, upper and lower extremity weakness, and numbness for 1 year. On physical examination, she demonstrated mild weakness in her left arm. The preoperative magnetic resonance imaging revealed a cervicothoracic intramedullary mass extending from C4 to T2 with an associated syrinx at C4. Under intraoperative neural monitoring (somatosensory evoked potentials, motor-evoked potentials, and epidural direct wave recordings), the patient underwent a C4 - T2 laminectomy. In addition, spinal ultrasonography helped differentiate solid tumor mass from syrinx formation, thus guiding the focus and extent of the decompression . Conclusion: Gross total resection was achieved; at 18 postoperative months, the patient had mild residual motor deficit. The pathological evaluation revealed a WHO grade II ependymoma. Subsequent sequential enhanced MR studies at 3, 6, and 12 months confirmed no tumor recurrence.

Intracranial ependymomas in pediatric patients: patterns of care, disparities, and survival outcomes from the National Cancer Database.

OBJECTIVE: This study aimed to extract and analyze comprehensive data from the National Cancer Database (NCDB) to gain insights into the epidemiological prevalence, treatment patterns, and survival outcomes associated with intracranial ependymomas in pediatric patients. METHODS: The authors examined data extracted from the NCDB spanning the years 2010 to 2017, with a specific emphasis on intracranial ependymomas in individuals aged 0-21 years. The study used logistic and Poisson regression, along with Kaplan-Meier survival estimates and Cox proportional hazards models, for analysis. RESULTS: Among 908 included pediatric patients, 495 (54.5%) were male, and 702 (80.6%) were White. Kaplan-Meier analysis determined overall survival (OS) rates of 97.1% (95% CI 96%-98.2%) at 1 year postdiagnosis, 89% (95% CI 86.9%-91.1%) at 3 years, 82.9% (95% CI 80.3%-85.7%) at 5 years, and 74.5% (95% CI 69.8%-79.4%) at 10 years. Grade 3 tumors predicted a more than fourfold higher mortality hazard (p < 0.001; reference = grade 2). Infratentorial localization was also associated with a 1.7-fold increase in mortality hazard (p = 0.002; reference = supratentorial). Larger maximum tumor size (> 5 cm) correlated with a lower mortality hazard (HR 0.64, p = 0.011; reference ≤ 5 cm). The vast majority of patients (85.9%, n = 780) underwent resection. Uninsured patients had over fourfold higher prolonged length of stay (LOS) odds than those privately insured (OR 4.645, p = 0.007). Radiotherapy was received by 76.1% of patients, and the highest rates of radiotherapy occurred among children aged 5-12 years (p < 0.001). Only 25.6% received chemotherapy at any point during their treatment. Peak chemotherapy use emerged within ages 0-4 years, reaching 33.6% in this age group. Kaplan-Meier analysis indicated chemotherapy was associated with significantly worse OS (p = 0.041). CONCLUSIONS: This comprehensive analysis of the NCDB provides valuable insights into the epidemiology, treatment patterns, and survival outcomes of intracranial ependymomas in pediatric patients. Higher tumor grade, infratentorial localization, and chemotherapy use was associated with worse OS, while larger tumor size correlated with lower mortality hazard. Disparities in care were identified, with uninsured patients experiencing prolonged LOS. These findings underscore the need for tailored treatment strategies based on patient and tumor characteristics and highlight the importance of addressing socioeconomic barriers to optimize outcomes for children with ependymomas.

Histopathological Spectrum of Gliomas and Its Immunohistochemical Correlation in a Tertiary Care Setup.

Introduction Central nervous system (CNS) tumors pose significant diagnostic challenges due to their varied morphological and differentiating characteristics. Modern advancements in immunohistochemistry (IHC) and molecular pathology have greatly enhanced prognostication, screening, and therapeutic management. Gliomas, a type of tumor originating from glial cells in the CNS, can develop from astrocytes, oligodendrocytes, or ependymal cells. According to the 2021 update, the classification of diffuse gliomas is primarily based on the presence or absence of isocitrate dehydrogenase (IDH1/2) mutations. IDH-wildtype gliomas (glioblastomas) have a significantly poorer prognosis compared to IDH-mutant gliomas (astrocytomas and oligodendrogliomas). Gliomas are highly infiltrative and resistant to treatment, making them largely incurable regardless of their grade and prognosis. Objective This study aimed to determine the histopathological diversity of gliomas and its correlation with protein expressions of IDH, ATRX gene (α-thalassemia/mental retardation syndrome X-linked), Ki-67, and p53 mutations (tumor suppressor gene-53), according to the 2021 World Health Organization (WHO) Classification of CNS Tumors, Fifth Edition. Methods This descriptive cross-sectional study was carried out in the Department of Pathology at a tertiary care center, focusing on various types of gliomas received over a two-year period. A total of 54 specimens of gliomas received from the Department of Neurosurgery were subjected to histopathological examination. Sections were stained using hematoxylin and eosin (H&E), and IHC was performed using four markers (IDH, ATRX, p53, Ki-67) in each case. Results were analyzed according to the 2021 WHO Classification of CNS Tumors, Fifth Edition. Results The majority of individuals were between the age group of 40 and 60 years, showing a male predominance (65%). The most common site was the frontal lobe. Glioblastoma constituted the largest proportion (46.2%) of the total cases, followed by astrocytoma (20.3%), oligodendroglioma (18.5%), pilocytic astrocytoma (7.4%), and ependymoma (7.4%). All 11 cases of astrocytoma exhibited IDH mutation and ATRX loss, with p53 positive in the majority of cases. Strong nuclear p53 immunohistochemical positivity in >10% of tumor nuclei correlates with TP53 mutations. Among 25 cases of glioblastoma, IDH was negative, ATRX was retained in all cases, and 11 cases were positive for p53 mutation. For oligodendroglioma, out of 10 cases, IDH mutation was positive, and ATRX was retained in all cases. p53 mutation was not seen in any case. All cases of pilocytic astrocytoma were negative for IDH and p53 mutations, with ATRX retained in all cases. In all cases of ependymoma, IDH and p53 mutations were negative, and ATRX was retained in all cases. Glioblastomas exhibited the highest Ki-67 expression. Conclusion The 2021 WHO Classification of CNS Tumors, Fifth Edition, was updated, building on previously established concepts and continuing to evolve. The final diagnosis of gliomas relies on a comprehensive combination of clinical evaluation, neuroimaging, pathological examination, and molecular analysis. Nonetheless, histopathological examination, along with IHC, remains the cornerstone of diagnosis.

Transcranial motor-evoked potentials disappear with pons transection.

Motor-evoked potential (MEP) monitoring by transcranial electrical stimulation (TES) is important for intraoperative motor function assessment in neurosurgery; however, false-negative results sometimes occur, and these findings should be interpreted with caution. Herein, we report an interesting MEP change resulting from a pons transection. The patient was a boy aged 5 years and 2 months. He underwent multiple craniotomies for cerebellar anaplastic ependymoma and was already paralyzed in the right upper and lower limbs. Therefore, we decided to remove the recurrent lesion from the left anterior pons. MEPs were recorded on both the right and left sides after the start of surgery but disappeared 1 h 30 min after the start of surgery in the TES on the operative side, even when the stimulation intensity was increased. The contralateral TES consistently recorded stable MEPs throughout the surgery. The tumor was completely resected on imaging. Immediately postoperatively, the patient experienced flaccid paralysis on the right side of the body, which recovered to preoperative levels over time. A transcranial MEP cannot be derived if the corticospinal tract is transected at the pons. Transcranial MEP findings may accurately reflect the corticospinal tract function if the injury is caudal to the pons.

Ensemble learning-based pretreatment MRI radiomic model for distinguishing intracranial extraventricular ependymoma from glioblastoma multiforme.

This study aims to develop an ensemble learning (EL) method based on magnetic resonance (MR) radiomic features to preoperatively differentiate intracranial extraventricular ependymoma (IEE) from glioblastoma (GBM). This retrospective study enrolled patients with histopathologically confirmed IEE and GBM from June 2016 to June 2021. Radiomics features were extracted from T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) sequence images, and classification models were constructed using EL methods and logistic regression (LR). The efficiency of the models was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. The combined EL model, based on clinical parameters and radiomic features from T1WI and T2WI images, demonstrated good discriminative ability, achieving an area under the receiver operating characteristics curve (AUC) of 0.96 (95% CI 0.94-0.98), a specificity of 0.84, an accuracy of 0.92, and a sensitivity of 0.95 in the training set, and an AUC of 0.89 (95% CI 0.83-0.94), a specificity of 0.83, an accuracy of 0.81, and a sensitivity of 0.74 in the validation set. The discriminative efficacy of the EL model was significantly higher than that of the LR model. Favorable calibration performance and clinical applicability for the EL model were observed. The EL model combining preoperative MR-based tumor radiomics and clinical data showed high accuracy and sensitivity in differentiating IEE from GBM preoperatively, which may potentially assist in clinical management of these brain tumors.

The medical and functional burden of surviving childhood ependymoma: A population-based study in Ontario, Canada.

BACKGROUND: Few studies have characterized the burden of late effects among childhood ependymoma survivors. To address this gap, we examined these sequelae using real-world health services data in a population-based ependymoma survivor cohort. METHODS: All individuals younger than 18 years diagnosed with an ependymoma in Ontario, Canada between 1987 and 2015 who had survived at least 5 years from their latest pediatric cancer event (index date) were matched 1:5 with population controls. Following linkage with provincial health services data, the cumulative incidences of multiple medical and functional outcomes between survivors and controls were compared. RESULTS: Among 96 survivors, 77.1% had been irradiated and 9.4% had received cisplatin. At 10 years post-index, survivors were at significantly higher risk of all-cause mortality (7.1%, 95% confidence interval [CI]: 1.0-13.3 vs. 0.3%, 95% CI: 0.0-1.0; p = .0002), non-obstetric hospitalization (45.1%, 95% CI: 32.6-56.7 vs. 10.6%, 95% CI: 7.6-14.1; p < .0001), stroke (6.5%, 95% CI: 2.3-13.7 vs. 0%; p < .0001), severe hearing loss requiring an amplification device (7.5%, 95% CI: 2.7-15.7 vs. 0%; p < .0001), receiving homecare service (27.6%, 95% CI: 18.5-37.5 vs. 7.7%, 95% CI: 5.3-10.7; p < .0001), and submitting a disability support prescription claim (24.0%, 95% CI: 14.8-34.3 vs. 5.4%, 95% CI: 3.5-7.8; p < .0001) compared to controls. CONCLUSIONS: Pediatric ependymoma survivors are highly vulnerable to severe late sequelae, including death, stroke, severe hearing loss, and disability. Urgent efforts are needed to improve risk-stratification approaches that mitigate exposure to toxic therapies for children with lower risk disease. Interventions to prevent or decrease the risk of developing late sequelae are critical to optimizing survivor long-term health.

Radiotherapy dosing in intracranial ependymoma using the national cancer database.

PURPOSE: To determine the dose-dependent effect of adjuvant radiotherapy on survival for pediatric intracranial ependymomas and explore patient and disease characteristics that experience survival benefit from higher doses. METHODS: Data was accessed from the National Cancer Database. Inclusion criteria was comprised of a diagnosis of non-metastatic intracranial ependymoma, World Health Organization (WHO) grade 2 or 3, surgical resection, adjuvant radiotherapy between 4500-6300 cGy, and non-missing survivorship data. Crude and adjusted Cox proportional hazard ratios (HRs) were calculated to estimate the associations of patient, tumor, and treatment characteristics with overall survival (OS). Kaplan-Meier (KM) estimations were used to visualize survival curves for dosing for the general cohort and by subgroups (age, resection extent, and grade). RESULTS: Of the 1154 patients who met inclusion criteria, 405 received ≤ 5400 cGy and 749 received > 5400 cGy. We found no difference in OS crude (0.95, 95% CI 0.72-1.06) or adjusted (0.88, 95% CI 0.46-1.69) HR for those receiving ≤ 5400 cGy. KM curves showed no difference in OS for dosing for the general cohort based on age, surgical extent, and grade. However, there was better OS in those with WHO grade 2 tumors compared to grade 3 regardless of dose received. CONCLUSIONS: There was no difference in OS between patients who received ≤ 5400 cGy compared to > 5400 cGy. We found improved OS in those with grade 2 tumors compared to grade 3, however there was no difference in OS based on dose received by tumor grade, age, or resection extent. Limitations in data available prevent exploring other outcomes or toxicity.

Treatment of Extraneural Metastases of Myxopapillary Ependymomas With Dose-Dense Temozolomide and Lapatinib.

Myxopapillary ependymomas (MPEs) are rare tumors of the central nervous system, and outcomes are generally worse with recurrent disease. These tumors can rarely metastasize outside the neuraxis. We present a case of a 35-year-old female with a history of MPEs who developed extraneural metastases 11 years after her initial gross total resection. Sites of metastases included multiple bilateral intrapulmonary and pleural-based masses with pleural effusion and a pelvic mass. The patient was treated with dose-dense TMZ and lapatinib and had a mixed radiographic response after 12 cycles of treatment. This is the first known case of extraneural metastases of MPEs to demonstrate a radiographic response to dose-dense TMZ and lapatinib. This case presentation discusses the need to establish optimal treatment of extraneural ependymal metastases, duration of treatment, and strategy for the management of recurrent diseases.

Distinct relapse pattern across molecular ependymoma types.

BACKGROUND: Ependymoma (EPN) is not a uniform disease but represents different disease types with biological and clinical heterogeneity. However, the pattern of when and where different types of EPN relapse is not yet comprehensively described. METHODS: We assembled 269 relapsed intracranial EPN from pediatric (n=233) and adult (n=36) patients from European and Northern American cohorts and correlated DNA methylation patterns and copy-number alterations with clinical information. RESULTS: The cohort comprised the following molecular EPN types: PF-EPN-A (n=177), ST-EPN-ZFTA (n=45), PF-EPN-B (n=31), PF-EPN-SE (n=12), and ST-EPN-YAP (n=4). First relapses of PF-EPN-B (PF: posterior-fossa) and PF-EPN-SE (SE: subependymoma) occurred later than of PF-EPN-A, ST-EPN-YAP (ST: supratentorial), or ST-EPN-ZFTA (median time to relapse: 4.3 and 6.0 years vs. 1.9/1.0/2.4 years; p<0.01). Metastatic or combined recurrences in PF-EPN-B and -A more often involved the spinal cord than in ST-EPN-ZFTA (72.7% and 40.0 vs. 12.5%; p<0.01). No distant relapses were observed in ST-EPN-YAP (n=4) or PF-EPN-SE (n=12). Post-relapse survival (PRS) was poor for PF-EPN-A and ST-EPN-ZFTA (5-year PRS: 44.5±4.4/47.8±9.1%), whereas PF-EPN-B and PF-EPN-SE displayed a 5-year PRS of 89.5±7.1/90.0±9.5% (p=0.03). However, 10-year PRS for PF-EPN-B dropped to 45.8±17.3%. Neither between radiation field and relapse pattern nor between radiation field and spinal involvement at relapse an impact was identified. Notably, all patients with relapsed ST-EPN-YAP did not receive upfront radiotherapy, but were successfully salvaged using irradiation at relapse. CONCLUSIONS: Relapse patterns of specific EPN types are different. Future clinical trials, treatment adaptions, duration of surveillance and diagnostics should be planned incorporating entity-specific relapse information.

Cytological features of ependymal and choroid plexus tumours.

Ependymal and choroid plexus tumours arise in anatomically related regions. Their intraoperative differential diagnosis is large and depends on factors such as age, tumour site and clinical presentation. Squash cytology can provide valuable information in this context. Cytological features of conventional ependymomas, subependymomas and myxopapillary ependymomas as well as choroid plexus tumours are reviewed and illustrated. Differential diagnostic considerations integrating morphological and clinical information are discussed.

Cauda equina myxopapillary ependymoma in von Hippel-Lindau disease: A case report.

Background: Patients affected by Von Hippel-Lindau (VHL) are prone to develop central nervous system neoplasms such as hemangioblastomas (HBs). Myxopapillary ependymoma (MPE) is not commonly associated with VHL disease. Case Description: We present the first case of a VHL patient affected by simultaneous silent cauda equina MPE and a symptomatic conus medullaris HB. The patient was first operated for systemic tumors and followed for asymptomatic HBs. Simple surveillance was maintained until neurological symptoms appeared. Regular follow-up demonstrated objective growth of the cystic conus medullaris tumor while the cauda equina lesion remained stable. Surgery was performed to avoid further neurological worsening. Histopathological examination showed conus medullaris HB and a nearby cauda equina MPE. Conclusion: Simultaneous spinal HBs and isolated MPE may exceptionally occur in VHL patients.

Imaging of supratentorial ependymomas with radio-pathological correlation.

Aim: Supratentorial ependymoma (STE) is a rare tumor with distinct genetic alterations, whose imaging features have been scarcely studied. This study aims to review the computed tomography (CT) and magnetic resonance imaging (MRI) features of a cohort of histopathologically proven STE to identify the distinguishing features of STE, and look for specific signs of zinc finger translocation associated (ZFTA) fused STEs. Methods: Ethical clearance was obtained from the institutional ethics committee. The magnetic resonance (MR) images, CT images when available, clinical details, and pathological reports of 25 patients from a single institute with histopathologically proven STE were retrospectively reviewed. Imaging features, demographic details, pathological and molecular features, and type of surgical resection were described and tabulated. Relevant associations with imaging features were computed and tabulated. Results: The study showed that STEs are common in the pediatric population with no sex predilection. The periventricular location was the most common. A significant association between periventricular location and the presence of a cystic component (P value = 0.023) and the presence of the periwinkle sign/stellate sign (P value = 0.045) was found. Common features of ZFTA fused STEs included periventricular or intraventricular location, cystic component, necrosis, and the periwinkle sign. A significant association was found between ZFTA fusion and cystic component (P value = 0.048). Conclusions: This study attempts to identify the imaging features of STEs and their associations with molecular pathology and surgical outcome, and the distinguishing features of ZFTA fused STEs.

Incidence and Survival of Patients With Malignant Primary Spinal Cord Tumors: A Population-Based Analysis.

OBJECTIVE: Epidemiological studies on spinal cord tumors are rare, and studies on primary intramedullary tumors are even rarer. The incidence and survival of patients with primary intramedullary spinal cord tumors have not been well documented. We aimed to study the incidence and survival of patients with primary spinal cord malignant and borderline malignant tumors based on data from the Surveillance, Epidemiology, and End Results (SEER) database and provide information for revealing the epidemiology and exploring the prognosis of patients with primary intramedullary tumors. METHODS: Patients in the SEER database with microscopically diagnosed malignant and borderline malignant primary spinal cord tumors from 2000 and 2019 were included in this study. We analyzed the distribution of patients according to the demographic and clinical characteristics. Then, we extracted the incidence rate and 5-year relative survival for the whole cohort and different subgroups of the cohort. Finally, multivariate Cox proportional hazards models were used to analyze the independent prognostic factors associated with overall survival. RESULTS: A total of 5,211 patients with malignant and borderline malignant primary spinal cord tumors were included in this cohort study. Ependymoma, astrocytoma (including oligodendrogliomas and glioblastoma), lymphoma and hemangioblastoma were the most common pathological types. The age-adjusted incidence rates of primary spinal cord ependymoma was 0.18 per 100,000. The incidence rate for females was significantly lower than that for males. The incidence rate was highest in Caucasian. The incidence rate of ependymoma was significantly higher than that of other pathological types. The incidence of astrocytoma was highest among people aged 0-19 years, the incidence of ependymoma was highest among people aged 40-59 years, and the incidence of lymphoma was highest among people aged 60 years or older. The 5-year observed survival and relative survival rates for the whole cohort were 82.80% and 86.00%, respectively. Patients diagnosed with ependymoma had significantly better survival than their counterparts. We also found the impact of surgery and chemotherapy on the prognosis of patients with different tumors varies a lot. CONCLUSION: We conducted a population-based analysis of malignant and borderline malignant primary spinal cord tumors with the aim of revealing the epidemiology and survival of patients with primary intramedullary spinal cord tumors. Despite some shortcomings, this study provides valuable information to help us better understand the epidemiological characteristics of primary intramedullary spinal cord tumors.

TULIPs decorate the three-dimensional genome of PFA ependymoma.

Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues. A remarkable feature exclusively present in PFA are type B ultra long-range interactions in PFAs (TULIPs), regions separated by great distances along the linear genome that interact with each other in the 3D nuclear space with surprising strength. TULIPs occur in all PFA samples and recur at predictable genomic coordinates, and their formation is induced by expression of EZHIP. The universality of TULIPs across PFA samples suggests a conservation of molecular principles that could be exploited therapeutically.

Insights into brain tumor diagnosis: exploring in situ hybridization techniques.

Objectives: Diagnosing brain tumors is critical due to their complex nature. This review explores the potential of in situ hybridization for diagnosing brain neoplasms, examining their attributes and applications in neurology and oncology. Methods: The review surveys literature and cross-references findings with the OMIM database, examining 513 records. It pinpoints mutations suitable for in situ hybridization and identifies common chromosomal and gene anomalies in brain tumors. Emphasis is placed on mutations' clinical implications, including prognosis and drug sensitivity. Results: Amplifications in EGFR, MDM2, and MDM4, along with Y chromosome loss, chromosome 7 polysomy, and deletions of PTEN, CDKN2/p16, TP53, and DMBT1, correlate with poor prognosis in glioma patients. Protective genetic changes in glioma include increased expression of ADGRB3/1, IL12B, DYRKA1, VEGFC, LRRC4, and BMP4. Elevated MMP24 expression worsens prognosis in glioma, oligodendroglioma, and meningioma patients. Meningioma exhibits common chromosomal anomalies like loss of chromosomes 1, 9, 17, and 22, with specific genes implicated in their development. Main occurrences in medulloblastoma include the formation of isochromosome 17q and SHH signaling pathway disruption. Increased expression of BARHL1 is associated with prolonged survival. Adenomas mutations were reviewed with a focus on adenoma-carcinoma transition and different subtypes, with MMP9 identified as the main metalloprotease implicated in tumor progression. Discussion: Molecular-genetic diagnostics for common brain tumors involve diverse genetic anomalies. In situ hybridization shows promise for diagnosing and prognosticating tumors. Detecting tumor-specific alterations is vital for prognosis and treatment. However, many mutations require other methods, hindering in situ hybridization from becoming the primary diagnostic method.

Doing more with less: surgical results of pediatric posterior fossa tumors from a single center in Latin America.

OBJECTIVE: We aim to report the epidemiology, surgical outcomes, and survival rates of pediatric patients with posterior fossa tumors in a large single-center case series. METHODS: A retrospective analysis was conducted on pediatric patients who underwent surgical treatment for posterior fossa tumors between January 2011 and January 2019. RESULTS: A total of 135 pediatric patients, with an average age of 7.5 years at diagnosis and a mean follow-up of 35.7 months, were included in the study. Most tumors were located within the midline, with ventriculomegaly observed in 71.4% of the patients. Pilocytic astrocytomas encompassed the majority of tumors (34.1%), followed by medulloblastomas (27.4%) and ependymomas (11.8%). Gross total resection (GTR) was achieved in 71.8% of the patients, with a recurrence rate of 20%. Surgical complications were observed in 25.9% of the patients. GTR significantly impacted 5-year overall survival (OS) and 4-year progression-free survival (PFS) in patients with posterior fossa tumors. Patients who underwent GTR had a 5-year OS of 89.7%, compared to 72.7% for near-total resection and 70.8% for subtotal resection. The 4-year PFS for patients who underwent GTR was 82.5%, whereas it was 63.6% for patients who underwent near-total resection and 54.2% for patients who underwent subtotal resection. CONCLUSION: Surgical resection remains the main treatment for pediatric posterior fossa tumors, and higher resection rates are linked to better survival outcomes. Despite limited resources for molecular diagnosis, our institution has demonstrated that a specialized neurooncological center with a high surgical volume can still achieve favorable survival outcomes for these patients.

Outcomes and Pattern of Care for Spinal Myxopapillary Ependymoma in the Modern Era-A Population-Based Observational Study.

(1) Background: Myxopapillary ependymoma (MPE) is a rare tumor of the spine, typically slow-growing and low-grade. Optimal management strategies remain unclear due to limited evidence given the low incidence of the disease. (2) Methods: We analyzed data from 1197 patients with spinal MPE from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2020). Patient demographics, treatment modalities, and survival outcomes were examined using statistical analyses. (3) Results: Most patients were White (89.9%) with a median age at diagnosis of 42 years. Surgical resection was performed in 95% of cases. The estimated 10-year overall survival was 91.4%. Younger age (hazard ratio (HR) = 1.09, p < 0.001) and receipt of surgery (HR = 0.43, p = 0.007) were associated with improved survival. Surprisingly, male sex was associated with worse survival (HR = 1.86, p = 0.008) and a younger age at diagnosis compared to females. (4) Conclusions: This study, the largest of its kind, underscores the importance of surgical resection in managing spinal MPE. The unexpected association between male sex and worse survival warrants further investigation into potential sex-specific pathophysiological factors influencing prognosis. Despite limitations, our findings contribute valuable insights for guiding clinical management strategies for spinal MPE.