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Radiologia 2016Rhabdomyosarcoma is the most common soft-tissue sarcoma in children; it can appear in any part of the body. Its biological behavior varies widely, and despite the... (Review)
Review
Rhabdomyosarcoma is the most common soft-tissue sarcoma in children; it can appear in any part of the body. Its biological behavior varies widely, and despite the absence of specific clinical or radiological characteristics, rhabdomyosarcoma should be taken into account in the differential diagnosis of solid tumors in children. This review focuses primarily on the imaging findings and anatomical distribution of the histological subtypes of childhood rhabdomyosarcoma and secondarily on the differential findings in histological studies.
Topics: Child; Humans; Rhabdomyosarcoma, Embryonal
PubMed: 27810092
DOI: 10.1016/j.rx.2016.09.003 -
Journal of Medical Case Reports Jan 2021The importance of this paper is to help to emphasize the importance of chemotherapy for children with pure intratesticular rhabdomyosarcoma after radical inguinal... (Review)
Review
BACKGROUND
The importance of this paper is to help to emphasize the importance of chemotherapy for children with pure intratesticular rhabdomyosarcoma after radical inguinal orchiectomy is done as first treatment of rhabdomyosarcoma. The information provided in this paper about the follow-up outcomes of the patient described in this paper, it highlights that, recurrence and even metastasis of intratesticular rhabdomyosarcoma in children are more likely to occur if surgery it not combined with chemotherapy.
CASE PRESENTATION
Herein, we present a 6-year old African male child with a 3 months history of a painless right intratesticular tumour. The tumour was poorly vascularized and was in continuity with the spermatic cord. Pelvic computer tomography (CT) scan showed a heterogeneous mass with well-defined margins without microcalcification and multiple bilateral inguinal enlarged lymph nodes were noticed without pelvic lymphadenopathy. The tumour measured 3.8 × 2.8 × 3.9 cm. The tumour marker panel showed: lactate dehydrogenase of (472 UI/l), alpha-fetoprotein (1.43 UI/ml) and human chorionic gonadotrophin beta (2.9 mUI/ml). Microscopically, the tumour was composed of small to medium size undifferentiated cells. These were oval to spindle, hyperchromatic cells to stromal myxoid degeneration were noted. Tunica albuginea and rete testis both were infiltrated by tumour. The tumour showed high mitotic count which measured 50 mitoses per 10 High Power Field (HPF). The diagnosis of rhabdomyosarcoma (RMS) was confirmed by immunohistochemistry (IHC) testing using myoD antibody which showed strong and diffuse intranuclear staining of the tumour cells. Currently, he is on cyclophosphamide and vincristine chemotherapy regime and his condition has improved much.
CONCLUSIONS
The experience obtained from the index case is crucial for the management of patients with intratesticular rhabdomyosarcoma which should always make sure that radical inguinal orchiectomy is covered by chemotherapy and/or radiotherapy. This will potentially lower the possibilities of recurrence and/or metastasis of the tumour, hence improving the prognosis of the patients. We report the clinical, radiological, and laboratory characteristics as well as the outcome of the patient.
Topics: Child; Cyclophosphamide; Humans; Male; Neoplasm Recurrence, Local; Orchiectomy; Rhabdomyosarcoma; Rhabdomyosarcoma, Embryonal; Testicular Neoplasms
PubMed: 33516251
DOI: 10.1186/s13256-020-02599-z -
Pediatric Blood & Cancer Apr 2022Children and adolescents with rhabdomyosarcoma (RMS) comprise a heterogeneous population with variable overall survival rates ranging between approximately 6% and 100%... (Review)
Review
Children and adolescents with rhabdomyosarcoma (RMS) comprise a heterogeneous population with variable overall survival rates ranging between approximately 6% and 100% depending on defined risk factors. Although the risk stratification of patients has been refined across five decades of collaborative group studies, molecular prognostic biomarkers beyond FOXO1 fusion status have yet to be incorporated prospectively in upfront risk-based therapy assignments. This review describes the evolution of risk-based therapy and the current risk stratification, defines a new risk stratification incorporating novel biomarkers, and provides the rationale for the current and upcoming Children's Oncology Group RMS studies.
Topics: Adolescent; Child; Gene Fusion; Humans; Rhabdomyosarcoma; Rhabdomyosarcoma, Embryonal; Risk Assessment; Risk Factors
PubMed: 35129294
DOI: 10.1002/pbc.29511 -
Journal of Clinical Oncology : Official... Sep 2021Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent...
PURPOSE
Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent disease remains poor, and beyond fusion status, no genomic markers are available for risk stratification. We present an international consortium study designed to determine the incidence of driver mutations and their association with clinical outcome.
PATIENTS AND METHODS
Tumor samples collected from patients enrolled on Children's Oncology Group trials (1998-2017) and UK patients enrolled on malignant mesenchymal tumor and RMS2005 (1995-2016) trials were subjected to custom-capture sequencing. Mutations, indels, gene deletions, and amplifications were identified, and survival analysis was performed.
RESULTS
DNA from 641 patients was suitable for analyses. A median of one mutation was found per tumor. In fusion-negative cases, mutation of any RAS pathway member was found in > 50% of cases, and 21% had no putative driver mutation identified. (15%), (15%), and (13%) mutations were found at a higher incidence than previously reported and mutations were associated with worse outcomes in both fusion-negative and fusion-positive cases. Interestingly, mutations in isoforms predominated in infants < 1 year (64% of cases). Mutation of was associated with histologic patterns beyond those previously described, older age, head and neck primary site, and a dismal survival. Finally, we provide a searchable companion database (ClinOmics), containing all genomic variants, and clinical annotation including survival data.
CONCLUSION
This is the largest genomic characterization of clinically annotated rhabdomyosarcoma tumors to date and provides prognostic genetic features that refine risk stratification and will be incorporated into prospective trials.
Topics: Adolescent; Adult; Biomarkers, Tumor; Child; Child, Preschool; DNA Mutational Analysis; Databases, Genetic; Disease Progression; Female; Gene Amplification; Gene Deletion; Gene Expression Profiling; Genetic Predisposition to Disease; Genomics; Humans; INDEL Mutation; Infant; Infant, Newborn; Male; Phenotype; Predictive Value of Tests; Progression-Free Survival; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma, Embryonal; Risk Assessment; Risk Factors; Time Factors; Transcriptome; United Kingdom; United States; Young Adult
PubMed: 34166060
DOI: 10.1200/JCO.20.03060 -
Developmental Cell May 2022Rhabdomyosarcoma (RMS) is a pediatric cancer with features of skeletal muscle; patients with unresectable or metastatic RMS fare poorly due to high rates of disease...
Rhabdomyosarcoma (RMS) is a pediatric cancer with features of skeletal muscle; patients with unresectable or metastatic RMS fare poorly due to high rates of disease recurrence. Here, we use single-cell and single-nucleus RNA sequencing to show that RMS tumors recapitulate the spectrum of embryonal myogenesis. Using matched patient samples from a clinical trial and orthotopic patient-derived xenografts (O-PDXs), we show that chemotherapy eliminates the most proliferative component with features of myoblasts within embryonal RMS; after treatment, the immature population with features of paraxial mesoderm expands to reconstitute the developmental hierarchy of the original tumor. We discovered that this paraxial mesoderm population is dependent on EGFR signaling and is sensitive to EGFR inhibitors. Taken together, these data serve as a proof of concept that targeting each developmental state in embryonal RMS is an effective strategy for improving outcomes by preventing disease recurrence.
Topics: Child; Drug Resistance; ErbB Receptors; Humans; Muscle Development; Neoplasm Recurrence, Local; Rhabdomyosarcoma; Rhabdomyosarcoma, Embryonal
PubMed: 35483358
DOI: 10.1016/j.devcel.2022.04.003 -
European Journal of Cancer (Oxford,... Sep 2022Rhabdomyosarcomas (RMSs) are the most common soft tissue sarcomas in children/adolescents less than 18 years of age with an annual incidence of 1-2/million.... (Review)
Review
Molecular testing of rhabdomyosarcoma in clinical trials to improve risk stratification and outcome: A consensus view from European paediatric Soft tissue sarcoma Study Group, Children's Oncology Group and Cooperative Weichteilsarkom-Studiengruppe.
Rhabdomyosarcomas (RMSs) are the most common soft tissue sarcomas in children/adolescents less than 18 years of age with an annual incidence of 1-2/million. Inter/intra-tumour heterogeneity raise challenges in clinical, pathological and biological research studies. Risk stratification in European and North American clinical trials previously relied on clinico-pathological features, but now, incorporates PAX3/7-FOXO1-fusion gene status in the place of alveolar histology. International working groups propose a coordinated approach through the INternational Soft Tissue SaRcoma ConsorTium to evaluate the specific genetic abnormalities and generate and integrate molecular and clinical data related to patients with RMS across different trial settings. We review relevant data and present a consensus view on what molecular features should be assessed. In particular, we recommend the assessment of the MYOD1-LR122R mutation for risk escalation, as it has been associated with poor outcomes in spindle/sclerosing RMS and rare RMS with classic embryonal histopathology. The prospective analyses of rare fusion genes beyond PAX3/7-FOXO1 will generate new data linked to outcomes and assessment of TP53 mutations and CDK4 amplification may confirm their prognostic value. Pathogenic/likely pathogenic germline variants in TP53 and other cancer predisposition genes should also be assessed. DNA/RNA profiling of tumours at diagnosis/relapse and serial analyses of plasma samples is recommended where possible to validate potential molecular biomarkers, identify new biomarkers and assess how liquid biopsy analyses can have the greatest benefit. Together with the development of new molecularly-derived therapeutic strategies that we review, a synchronised international approach is expected to enhance progress towards improved treatment assignment, management and outcomes for patients with RMS.
Topics: Adolescent; Child; Consensus; Humans; Molecular Diagnostic Techniques; Neoplasm Recurrence, Local; Prospective Studies; Rhabdomyosarcoma; Rhabdomyosarcoma, Embryonal; Risk Assessment; Soft Tissue Neoplasms
PubMed: 35839732
DOI: 10.1016/j.ejca.2022.05.036 -
Case Reports in Obstetrics and... 2022Nonpuerperal uterine inversion is a rare clinical condition that involves prolapse of the uterine fundus into the uterine cavity and vaginal vault and possibly passed...
Nonpuerperal uterine inversion is a rare clinical condition that involves prolapse of the uterine fundus into the uterine cavity and vaginal vault and possibly passed the introitus. The majority of these cases commonly involve benign tumors such as leiomyoma. However, another common cause of nonpuerperal uterine inversion is due to malignancies such as sarcomas. Rhabdomyosarcoma is a rare and aggressive malignancy of soft tissue cells that are common in children and rare in adults. One subtype called embryonal rhabdomyosarcoma is exceptionally rare. Therefore, report of embryonal rhabdomyosarcoma-induced uterine inversion is an exceedingly scarce and rarely documented clinical condition. In this case report, we present a rare case of a nulliparous 27-year-old female who presented with embryonal rhabdomyosarcoma-induced uterine inversion.
PubMed: 35915828
DOI: 10.1155/2022/1361803 -
Nature Cancer Aug 2022Rhabdomyosarcoma (RMS) is a common childhood cancer that shares features with developing skeletal muscle. Yet, the conservation of cellular hierarchy with human muscle...
Rhabdomyosarcoma (RMS) is a common childhood cancer that shares features with developing skeletal muscle. Yet, the conservation of cellular hierarchy with human muscle development and the identification of molecularly defined tumor-propagating cells has not been reported. Using single-cell RNA-sequencing, DNA-barcode cell fate mapping and functional stem cell assays, we uncovered shared tumor cell hierarchies in RMS and human muscle development. We also identified common developmental stages at which tumor cells become arrested. Fusion-negative RMS cells resemble early myogenic cells found in embryonic and fetal development, while fusion-positive RMS cells express a highly specific gene program found in muscle cells transiting from embryonic to fetal development at 7-7.75 weeks of age. Fusion-positive RMS cells also have neural pathway-enriched states, suggesting less-rigid adherence to muscle-lineage hierarchies. Finally, we identified a molecularly defined tumor-propagating subpopulation in fusion-negative RMS that shares remarkable similarity to bi-potent, muscle mesenchyme progenitors that can make both muscle and osteogenic cells.
Topics: Child; Humans; Muscle, Skeletal; Rhabdomyosarcoma; Rhabdomyosarcoma, Embryonal; Single-Cell Analysis; Stem Cells
PubMed: 35982179
DOI: 10.1038/s43018-022-00414-w -
Nature Communications May 2023Paediatric rhabdomyosarcoma (RMS) is a soft tissue malignancy of mesenchymal origin that is thought to arise as a consequence of derailed myogenic differentiation....
Paediatric rhabdomyosarcoma (RMS) is a soft tissue malignancy of mesenchymal origin that is thought to arise as a consequence of derailed myogenic differentiation. Despite intensive treatment regimens, the prognosis for high-risk patients remains dismal. The cellular differentiation states underlying RMS and how these relate to patient outcomes remain largely elusive. Here, we use single-cell mRNA sequencing to generate a transcriptomic atlas of RMS. Analysis of the RMS tumour niche reveals evidence of an immunosuppressive microenvironment. We also identify a putative interaction between NECTIN3 and TIGIT, specific to the more aggressive fusion-positive (FP) RMS subtype, as a potential cause of tumour-induced T-cell dysfunction. In malignant RMS cells, we define transcriptional programs reflective of normal myogenic differentiation and show that these cellular differentiation states are predictive of patient outcomes in both FP RMS and the less aggressive fusion-negative subtype. Our study reveals the potential of therapies targeting the immune microenvironment of RMS and suggests that assessing tumour differentiation states may enable a more refined risk stratification.
Topics: Child; Humans; Transcriptome; Cell Proliferation; Rhabdomyosarcoma; Rhabdomyosarcoma, Embryonal; Gene Expression Profiling; Cell Line, Tumor; Tumor Microenvironment
PubMed: 37244912
DOI: 10.1038/s41467-023-38886-8