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Cancers Dec 2023Congenital tumors are rare and, owing to this rarity, there is limited information on many of them. A total of 839 fetal and postnatal MRI studies performed in the first...
Congenital tumors are rare and, owing to this rarity, there is limited information on many of them. A total of 839 fetal and postnatal MRI studies performed in the first 3 months of life were retrospectively reviewed. They were performed with the use of 1.5 T scanners. Seventy-six tumors were diagnosed based on fetal MRI between 20 and 37 gestational weeks, and 27 were found after birth, from 1 day of age to 3 months of life. Teratomas were the most common tumors in our dataset, mainly in the sacrococcygeal region (SCT), followed by cardiac rhabdomyomas and subependymal giant cell astrocytomas (SEGA) associated with TSC, and neuroblastomas. The group of less common tumors consisted of infantile fibrosarcomas, malignant rhabdoid tumors, mesoblastic nephromas and Wilms tumor, craniopharyngiomas, brain stem gliomas, desmoplastic infantile astrocytoma, choroid plexus carcinoma, glioblastoma, hemangiopericytoma, rhabdomyosarcoma, melanoma, mesenchymal hamartomas of the chest wall and the liver, and juvenile xanthogranuloma, with special consideration of blue rubber bleb nevus syndrome. MRI plays a significant role in further and better characterization of congenital tumors, leading to a correct diagnosis in many cases, which is crucial for pregnancy and neonatal management and psychological preparation of the parents. No diagnosis is impossible and can be absolutely excluded.
PubMed: 38201471
DOI: 10.3390/cancers16010043 -
Free Neuropathology Jan 2023Pilocytic astrocytoma (PA) is one of the most common primary intracranial neoplasms in childhood with an overall favorable prognosis. Despite decades of experience,...
Pathological perspectives in pilocytic astrocytomas: Extent of resection as the sole critical factor for recurrence-free survival, and the challenge of evaluating conclusions derived from limited data.
Pilocytic astrocytoma (PA) is one of the most common primary intracranial neoplasms in childhood with an overall favorable prognosis. Despite decades of experience, there are still diagnostic and treatment challenges and unresolved issues regarding risk factors associated with recurrence, most often due to conclusions of publications with limited data. We analyzed 499 patients with PA diagnosed in a single institution over 30 years in order to provide answers to some of the unresolved issues. We identified pilocytic astrocytomas diagnosed at the University of California, San Francisco, between 1989 and 2019, confirmed the diagnoses using the WHO 2021 essential and desirable criteria, and performed a retrospective review of the demographic and clinical features of the patients and the radiological, pathologic and molecular features of the tumors. Among the patients identified from pathology archives, 499 cases fulfilled the inclusion criteria. Median age at presentation was 12 years (range 3.5 months - 73 years) and the median follow-up was 78.5 months. Tumors were predominantly located in the posterior fossa (52.6%). There were six deaths, but there were confounding factors that prevented a clear association of death to tumor progression. Extent of resection was the only significant factor for recurrence-free survival. Recurrence-free survival time was 321.0 months for gross total resection, compared to 160.9 months for subtotal resection (log rank, p <0.001). Multivariate analysis was able to identify extent of resection as the only significant variable to influence recurrence-free survival. We did not find a statistically significant association between age, status, tumor location, molecular alterations, and outcome. Smaller series with apparently significant results may have suffered from limited sample size, limited variables, acceptance of univariate analysis findings as well as a larger p value for biological significance. PA still remains a predominantly surgical disease and every attempt should be made to achieve gross total resection since this appears to be the most reliable predictor of recurrence-free survival.
PubMed: 37901684
DOI: 10.17879/freeneuropathology-2023-5116 -
Pathologica Dec 2022The WHO 2021 classification of central nervous system cancers distinguishes diffuse gliomas that arise in adults (referred to as the "adult type") and those that arise... (Review)
Review
The WHO 2021 classification of central nervous system cancers distinguishes diffuse gliomas that arise in adults (referred to as the "adult type") and those that arise in children (defined as "paediatric") based on clinical and molecular characteristics."). However, paediatric-type gliomas may occasionally be present in younger adults and occasionally adult-type gliomas may occur in children. Diffuse low-grade paediatric glioma includes diffuse astrocytoma altered by MYB or MYBL1, low-grade polymorphic juvenile neuroepithelial tumour, angiocentric glioma, and diffuse low-grade glioma with an altered MAPK pathway. Here, we examine these newly recognised entities according to WHO diagnostic criteria and propose an integrated diagnostic approach that can be used to separate these clinically and biologically distinct tumor groups.
Topics: Adult; Child; Humans; Brain Neoplasms; Glioma
PubMed: 36534420
DOI: 10.32074/1591-951X-828 -
BMC Cancer Dec 2022Juvenile Pilocytic Astrocytomas (JPAs) are one of the most common pediatric brain tumors, and they are driven by aberrant activation of the mitogen-activated protein...
BACKGROUND
Juvenile Pilocytic Astrocytomas (JPAs) are one of the most common pediatric brain tumors, and they are driven by aberrant activation of the mitogen-activated protein kinase (MAPK) signaling pathway. RAF-fusions are the most common genetic alterations identified in JPAs, with the prototypical KIAA1549-BRAF fusion leading to loss of BRAF's auto-inhibitory domain and subsequent constitutive kinase activation. JPAs are highly vascular and show pervasive immune infiltration, which can lead to low tumor cell purity in clinical samples. This can result in gene fusions that are difficult to detect with conventional omics approaches including RNA-Seq.
METHODS
To this effect, we applied RNA-Seq as well as linked-read whole-genome sequencing and in situ Hi-C as new approaches to detect and characterize low-frequency gene fusions at the genomic, transcriptomic and spatial level.
RESULTS
Integration of these datasets allowed the identification and detailed characterization of two novel BRAF fusion partners, PTPRZ1 and TOP2B, in addition to the canonical fusion with partner KIAA1549. Additionally, our Hi-C datasets enabled investigations of 3D genome architecture in JPAs which showed a high level of correlation in 3D compartment annotations between JPAs compared to other pediatric tumors, and high similarity to normal adult astrocytes. We detected interactions between BRAF and its fusion partners exclusively in tumor samples containing BRAF fusions.
CONCLUSIONS
We demonstrate the power of integrating multi-omic datasets to identify low frequency fusions and characterize the JPA genome at high resolution. We suggest that linked-reads and Hi-C could be used in clinic for the detection and characterization of JPAs.
Topics: Child; Adult; Humans; Multiomics; Proto-Oncogene Proteins B-raf; Oncogene Proteins, Fusion; Astrocytoma; Brain Neoplasms; Receptor-Like Protein Tyrosine Phosphatases, Class 5
PubMed: 36503484
DOI: 10.1186/s12885-022-10359-z -
La Clinica Terapeutica 2022Histograms can be determined throughout tumors, relying partly on existing tumor microstructure knowledge and the sampling effect from area of interest analyses. We...
PURPOSE
Histograms can be determined throughout tumors, relying partly on existing tumor microstructure knowledge and the sampling effect from area of interest analyses. We aimed to investigate the impact of ADC histogram parameters in discriminating medulloblastoma, ependymoma, and pilocytic astrocytoma.
METHODS
This study received approval from the Institutional Ethics Review Committee of Children's Hospital 02. Processes were conducted according to relevant laws and regulations, and requirements for written informed consent were fulfilled. The study involved 24 patients at Children's Hospital 02 from February-December 2019. Group 1 included 12 children with medulloblastoma, group 2 included 5 with ependymoma, and group 3 included 7 with pilocytic astrocytoma. All patients underwent MRI followed by surgery or biopsy to obtain histopathological confirmations.
RESULTS
Our analysis indicated that AUC, sensitivity, and specificity were 96.7%, 91.7%, and 100%, respectively when ADCkurtosis (cut-off point = 2.34) was taken to differentiate between medulloblasto-mas and ependymomas. To distinguish between medulloblastomas and pilocytic astrocytomas, the cut-off points of ADCmean, ADCmedian, ADCmax, ADCmin, rADCmean, rADCmax, and rADCmin of 0.985, 0.910, 1.305, 0.710, 1.349, 1.738, and 1.251, were taken respectively with AUC, sensitivity, and specificity elicited at 100%. To discriminate between ependymomas and pilocytic astrocytomas, the cut-off points of ADCmean, ADCmedian, ADCmax, ADCmin, rADCmean, rADC-median, rADCmax and rADCmin were 1.010, 0.930, 1.270, 0.735, 1.346, 1.324, 1.676, and 1.273, respectively, with AUC, sensitivity, and specificity at 100%.
CONCLUSION
ADC histograms can facilitate differentiation among juvenile medulloblastoma, ependymoma, and pilocytic astrocytoma, providing reliable, objective evidence of tumor differentiation.
Topics: Astrocytoma; Cerebellar Neoplasms; Child; Diffusion Magnetic Resonance Imaging; Ependymoma; Humans; Medulloblastoma; Retrospective Studies
PubMed: 35857056
DOI: 10.7417/CT.2022.2448 -
Neuro-oncology Advances 2022Pediatric gliomas comprise a diverse set of brain tumor entities that have substantial long-term ramifications for patient survival and quality of life. However, the...
BACKGROUND
Pediatric gliomas comprise a diverse set of brain tumor entities that have substantial long-term ramifications for patient survival and quality of life. However, the study of these tumors is currently limited due to a lack of authentic models. Additionally, many aspects of pediatric brain tumor biology, such as tumor cell invasiveness, have been difficult to study with currently available tools. To address these issues, we developed a synthetic extracellular matrix (sECM)-based culture system to grow and study primary pediatric brain tumor cells.
METHODS
We developed a brain-like sECM material as a supportive scaffold for the culture of primary, patient-derived pediatric glioma cells and established patient-derived cell lines. Primary juvenile brainstem-derived murine astrocytes were used as a feeder layer to support the growth of primary human tumor cells.
RESULTS
We found that our culture system facilitated the proliferation of various primary pediatric brain tumors, including low-grade gliomas, and enabled ex vivo testing of investigational therapeutics. Additionally, we found that tuning this sECM material allowed us to assess high-grade pediatric glioma cell invasion and evaluate therapeutic interventions targeting invasive behavior.
CONCLUSION
Our sECM culture platform provides a multipurpose tool for pediatric brain tumor researchers that enables both a wide breadth of biological assays and the cultivation of diverse tumor types.
PubMed: 35669012
DOI: 10.1093/noajnl/vdac049 -
Diagnostics (Basel, Switzerland) Apr 2022Primary brain tumors are the most common solid neoplasms in children and a leading cause of mortality in this population. MRI plays a central role in the diagnosis,... (Review)
Review
Primary brain tumors are the most common solid neoplasms in children and a leading cause of mortality in this population. MRI plays a central role in the diagnosis, characterization, treatment planning, and disease surveillance of intracranial tumors. The purpose of this review is to provide an overview of imaging methodology, including conventional and advanced MRI techniques, and illustrate the MRI appearances of common pediatric brain tumors.
PubMed: 35454009
DOI: 10.3390/diagnostics12040961 -
Translational Oncology Jun 2022Brain tumors are the leading cause of cancer-related deaths in children. Tailored therapies need preclinical brain tumor models representing a wide range of molecular...
Brain tumors are the leading cause of cancer-related deaths in children. Tailored therapies need preclinical brain tumor models representing a wide range of molecular subtypes. Here, we adapted a previously established brain tissue-model to fresh patient tumor cells with the goal of establishing3D in vitro culture conditions for each tumor type.Wereported our findings from 11 pediatric tumor cases, consisting of three medulloblastoma (MB) patients, three ependymoma (EPN) patients, one glioblastoma (GBM) patient, and four juvenile pilocytic astrocytoma (Ast) patients. Chemically defined media consisting of a mixture of pro-neural and pro-endothelial cell culture medium was found to support better growth than serum-containing medium for all the tumor cases we tested. 3D scaffold alone was found to support cell heterogeneity and tumor type-dependent spheroid-forming ability; both properties were lost in 2D or gel-only control cultures. Limited in vitro models showed that the number of differentially expressed genes between in vitro vs. primary tissues, are 104 (0.6%) of medulloblastoma, 3,392 (20.2%) of ependymoma, and 576 (3.4%) of astrocytoma, out of total 16,795 protein-coding genes and lincRNAs. Two models derived from a same medulloblastoma patient clustered together with the patient-matched primary tumor tissue; both models were 3D scaffold-only in Neurobasal and EGM 1:1 (v/v) mixture and differed by a 1-mo gap in culture (i.e., 6wk versus 10wk). The genes underlying the in vitrovs. in vivo tissue differences may provide mechanistic insights into the tumor microenvironment. This study is the first step towards establishing a pipeline from patient cells to models to personalized drug testing for brain cancer.
PubMed: 35381525
DOI: 10.1016/j.tranon.2022.101407 -
Surgical Neurology International 2021Many patients with spinal juvenile pilocytic astrocytoma can experience prolonged remission after resection. However, some reports suggest that pregnancy may be...
BACKGROUND
Many patients with spinal juvenile pilocytic astrocytoma can experience prolonged remission after resection. However, some reports suggest that pregnancy may be associated with progression.
CASE DESCRIPTION
The authors provide an image report highlighting a case of rapid and aggressive transformation of an intramedullary astrocytoma of the cervical spine in a pregnant patient. Over the course of 1 year, the lesion progressed from a juvenile pilocytic astrocytoma to an anaplastic astrocytoma. Genetic testing revealed mutations associated with aggressive behavior.
CONCLUSION
The case and associated imaging demonstrate the importance of close neurologic monitoring and counseling regarding risk of progression in pregnant patients with spinal gliomas.
PubMed: 34621581
DOI: 10.25259/SNI_759_2021