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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 -
Histopathology Jan 2022Rhabdomyosarcomas comprise the single largest category of soft tissue sarcomas in children and adolescents in the United States, occurring in 4.5 million people aged... (Review)
Review
Rhabdomyosarcomas comprise the single largest category of soft tissue sarcomas in children and adolescents in the United States, occurring in 4.5 million people aged below 20 years. Based on the clinicopathological features and genetic abnormalities identified, rhabdomyosarcomas are classified into embryonal, alveolar, spindle cell/sclerosing and pleomorphic subtypes. Each subtype shows distinctive morphology and has characteristic genetic abnormalities. This review discusses the evolution of the classification of rhabdomyosarcoma to the present day, together with a discussion of key histomorphological and genetic features of each subtype and the diagnostic approach to these tumours.
Topics: Biomarkers, Tumor; Forkhead Box Protein O1; Humans; MyoD Protein; Rhabdomyosarcoma; Soft Tissue Neoplasms
PubMed: 34958505
DOI: 10.1111/his.14449 -
Nature Reviews. Disease Primers Jan 2019Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and represents a high-grade neoplasm of skeletal myoblast-like cells. Decades of clinical and... (Review)
Review
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and represents a high-grade neoplasm of skeletal myoblast-like cells. Decades of clinical and basic research have gradually improved our understanding of the pathophysiology of RMS and helped to optimize clinical care. The two major subtypes of RMS, originally characterized on the basis of light microscopic features, are driven by fundamentally different molecular mechanisms and pose distinct clinical challenges. Curative therapy depends on control of the primary tumour, which can arise at many distinct anatomical sites, as well as controlling disseminated disease that is known or assumed to be present in every case. Sophisticated risk stratification for children with RMS incorporates various clinical, pathological and molecular features, and that information is used to guide the application of multifaceted therapy. Such therapy has historically included cytotoxic chemotherapy as well as surgery, ionizing radiation or both. This Primer describes our current understanding of RMS epidemiology, disease susceptibility factors, disease mechanisms and elements of clinical care, including diagnostics, risk-based care of newly diagnosed and relapsed disease and the prevention and management of late effects in survivors. We also outline potential opportunities to further translate new biological insights into improved clinical outcomes.
Topics: Age Factors; Humans; Mass Screening; Quality of Life; Rhabdomyosarcoma; Rhabdomyosarcoma, Alveolar; Risk Factors
PubMed: 30617281
DOI: 10.1038/s41572-018-0051-2 -
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 -
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 -
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 -
JCO Precision Oncology Jan 2023Total cell-free DNA (cfDNA) and tumor-derived cfDNA (ctDNA) can be used to study tumor-derived genetic aberrations. We analyzed the diagnostic and prognostic potential...
PURPOSE
Total cell-free DNA (cfDNA) and tumor-derived cfDNA (ctDNA) can be used to study tumor-derived genetic aberrations. We analyzed the diagnostic and prognostic potential of cfDNA and ctDNA, obtained from pediatric patients with rhabdomyosarcoma.
METHODS
cfDNA was isolated from diagnostic plasma samples from 57 patients enrolled in the EpSSG RMS2005 study. To study the diagnostic potential, shallow whole genome sequencing (shWGS) and cell-free reduced representation bisulphite sequencing (cfRRBS) were performed in a subset of samples and all samples were tested using droplet digital polymerase chain reaction to detect methylated (M). Correlation with outcome was studied by combining cfDNA M detection with analysis of our rhabdomyosarcoma-specific RNA panel in paired cellular blood and bone marrow fractions and survival analysis in 56 patients.
RESULTS
At diagnosis, ctDNA was detected in 16 of 30 and 24 of 26 patients using shallow whole genome sequencing and cfRRBS, respectively. Furthermore, 21 of 25 samples were correctly classified as embryonal by cfRRBS. -M was detected in 21 of 57 patients. The presence of -M was significantly correlated with poor outcome (the 5-year event-free survival [EFS] rate was 46.2% for 21 -Mpositive patients, compared with 84.9% for 36 -Mnegative patients [ < .001]). -M positivity had the highest prognostic effect among patients with metastatic disease. Patients both negative for -M and the rhabdomyosarcoma-specific RNA panel (28 of 56 patients) had excellent outcome (5-year EFS 92.9%), while double-positive patients (11/56) had poor outcome (5-year EFS 13.6%, < .001).
CONCLUSION
Analyzing ctDNA at diagnosis using various techniques is feasible in pediatric rhabdomyosarcoma and has potential for clinical use. Measuring M in plasma at initial diagnosis correlated significantly with outcome, particularly when combined with paired analysis of blood and bone marrow using a rhabdomyosarcoma-specific RNA panel.
Topics: Humans; Child; Cell-Free Nucleic Acids; Prognosis; Rhabdomyosarcoma; RNA; Biomarkers
PubMed: 36652664
DOI: 10.1200/PO.22.00113 -
Science Advances Feb 2023Rhabdomyosarcoma (RMS) is a group of pediatric cancers with features of developing skeletal muscle. The cellular hierarchy and mechanisms leading to developmental arrest...
Rhabdomyosarcoma (RMS) is a group of pediatric cancers with features of developing skeletal muscle. The cellular hierarchy and mechanisms leading to developmental arrest remain elusive. Here, we combined single-cell RNA sequencing, mass cytometry, and high-content imaging to resolve intratumoral heterogeneity of patient-derived primary RMS cultures. We show that the aggressive alveolar RMS (aRMS) subtype contains plastic muscle stem-like cells and cycling progenitors that drive tumor growth, and a subpopulation of differentiated cells that lost its proliferative potential and correlates with better outcomes. While chemotherapy eliminates cycling progenitors, it enriches aRMS for muscle stem-like cells. We screened for drugs hijacking aRMS toward clinically favorable subpopulations and identified a combination of RAF and MEK inhibitors that potently induces myogenic differentiation and inhibits tumor growth. Overall, our work provides insights into the developmental states underlying aRMS aggressiveness, chemoresistance, and progression and identifies the RAS pathway as a promising therapeutic target.
Topics: Child; Humans; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma; Muscle, Skeletal; Cell Differentiation; Antineoplastic Agents; Cell Line, Tumor
PubMed: 36753540
DOI: 10.1126/sciadv.ade9238 -
Archives of Pathology & Laboratory... Aug 2022Rhabdomyosarcoma, the most common soft tissue sarcoma of children, is currently classified into the following 4 subtypes: embryonal rhabdomyosarcoma, alveolar... (Review)
Review
CONTEXT.—
Rhabdomyosarcoma, the most common soft tissue sarcoma of children, is currently classified into the following 4 subtypes: embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, spindle cell/sclerosing rhabdomyosarcoma, and pleomorphic rhabdomyosarcoma, based on recent molecular genetic knowledge and morphologic features.
OBJECTIVE.—
To highlight the most recent advances of molecular genetic alterations, and to familiarize pathologists with most recent genotype and phenotype correlation in rhabdomyosarcoma.
DATA SOURCES.—
Data were derived from the World Health Organization Classification of Soft Tissue and Bone Tumors, fifth edition, recently published literature (PubMed), and clinical practice experience.
CONCLUSIONS.—
Current classification has been significantly impacted by genotype and phenotype correlation, especially with PAX-FOXO1 fusion-positive rhabdomyosarcoma versus fusion-negative rhabdomyosarcoma, and with the emergence of 3 distinct new subtypes of spindle cell/sclerosing rhabdomyosarcoma. Although all rhabdomyosarcomas were considered a single diagnostic entity in the past, they are now considered to be a group of histologically similar but biologically diverse entities because their clinical behavior and underlying molecular alterations dramatically differ. This review outlines recent molecular genetic developments, corresponding morphologic features, and current challenges faced by pathologists in daily practice.
Topics: Humans; Mutation; Rhabdomyosarcoma; Rhabdomyosarcoma, Embryonal; Soft Tissue Neoplasms; World Health Organization
PubMed: 35051261
DOI: 10.5858/arpa.2021-0183-RA