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Journal of Oral and Maxillofacial... 2016Rhabdomyosarcoma (RMS), a malignant neoplasm of skeletal muscle origin, is the most common soft tissue sarcoma seen in childhood and adolescence. The most frequent site...
Rhabdomyosarcoma (RMS), a malignant neoplasm of skeletal muscle origin, is the most common soft tissue sarcoma seen in childhood and adolescence. The most frequent site is the head and neck accounting for 40% of all cases and other involved sites are genitourinary tract, retroperitoneum, and to a lesser extent, the extremities. RMS is relatively uncommon in the oral cavity and the involvement of the jaws is extremely rare. Here, we report a case of 50-year-old female with oral RMS involving maxillary alveolar region with clinical, radiological, histopathological and immunohistochemical findings.
PubMed: 27194887
DOI: 10.4103/0973-029X.180987 -
Frontiers in Oncology 2024Alveolar Rhabdomyosarcoma is a profoundly malignant soft-tissue sarcoma that predominantly affects children and adolescents. However, the medical field lacks consensus...
Case report: A left forearm mass with eccentric intramedullary ulnar destruction diagnosed as alveolar rhabdomyosarcoma and treated by wide resection and free vascularized fibular graft.
BACKGROUND
Alveolar Rhabdomyosarcoma is a profoundly malignant soft-tissue sarcoma that predominantly affects children and adolescents. However, the medical field lacks consensus regarding the optimal surgical approach to be undertaken in cases where this tumor causes local bone destruction in the upper limb.
CASE DESCRIPTION
A 17-year-old male presented a mass in his left forearm and CT and MRI indicated that the mass had penetrated the ulnar cortex and infiltrating the medulla, resulting in the formation of an eccentric trans-ventricular tumor focus. The sizable tumor affected the volar muscles of the forearm as well as the ulnar bone marrow, exerting pressure on the ulnar artery and vein. It was confirmed by needle biopsy that the mass is alveolar rhabdomyosarcoma. Following two courses of neoadjuvant chemotherapy, the tumor was widely excised en bloc. Autologous fibula with a vascular pedicle was utilized for reconstruction during the procedure. In the postoperative follow-up, no local recurrence of the tumor was observed. Furthermore, the patient retained satisfactory wrist flexion and pronation function in the left forearm.
CONCLUSIONS
Alveolar rhabdomyosarcoma is an uncommon and highly aggressive form of soft tissue sarcoma. Scientific management necessitates a multidisciplinary approach, combining chemotherapy with surgery. In cases where the tumor invaded into compartment of the bone, careful consideration should be given to the boundaries of tumor resection, the extent of osteotomy, and the approach to musculoskeletal reconstruction when designing the surgical plan. Through reporting our own case and thoroughly reviewing previous clinical experiences, we aim to provide valuable insights for the treatment of this particular disease.
PubMed: 38800397
DOI: 10.3389/fonc.2024.1395233 -
BMJ Case Reports Jul 2021This is the case of a parameningeal alveolar rhabdomyosarcoma (ARMS) in a 13-year-old boy who presented with painless loss of vision in the right eye, but very few other...
This is the case of a parameningeal alveolar rhabdomyosarcoma (ARMS) in a 13-year-old boy who presented with painless loss of vision in the right eye, but very few other physical signs. The ARMS diagnosis was confirmed with imaging and molecular characterisation of the tumour. Despite tolerating the initial chemotherapy and radiotherapy regimens, there was leptomeningeal recurrence and the patient unfortunately passed away. Parameningeal ARMS occurs in an area of the body, which leads to a wide variety of possible presenting symptoms, creating a long list of differentials that can delay treatment. This tumour subtype has a poor prognosis, and due to the location of the tumour around vital structures in the head, treatment toxicities must be taken into account. This highlights the necessity for having a strong index of suspicion for this tumour in atypical presentations in children, and the necessity for prompt treatment to prevent leptomeningeal disease from occurring.
Topics: Adolescent; Child; Family; Head and Neck Neoplasms; Humans; Male; Meningeal Neoplasms; Neoplasm Recurrence, Local; Rhabdomyosarcoma; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma, Embryonal
PubMed: 34266827
DOI: 10.1136/bcr-2021-243267 -
Scientific Reports Feb 2017Rhabdomyosarcoma is the most common soft tissue sarcoma in children and young adults. Rhabdomyosarcomas are skeletal muscle-like tumours that typically arise in muscle...
Rhabdomyosarcoma is the most common soft tissue sarcoma in children and young adults. Rhabdomyosarcomas are skeletal muscle-like tumours that typically arise in muscle beds, and express key myogenic regulatory factors. However, their developmental program remains blocked in the proliferative phase with cells unable to exit the cell cycle to fuse into myotubes. Recently, we uncovered a key role for the RNA-binding protein Staufen1 during myogenic differentiation through the regulation of c-myc translation. Given the known implication of c-myc in rhabdomyosarcoma, we hypothesized in the current work that Staufen1 controls rhabdomyosarcoma tumorigenesis. Here, we report for the first time the novel role of Staufen1 in cancer, specifically in rhabdomyosarcoma. We demonstrate that Staufen1 is markedly upregulated in human rhabdomyosarcoma tumours and cell lines as compared to normal skeletal muscle. Moreover, we show that Staufen1 promotes the tumorigenesis of embryonal and alveolar rhabdomyosarcoma subtypes both in cell culture and in animal models. Finally, our data demonstrate that Staufen1 has differential roles in embryonal versus alveolar rhabdomyosarcoma through the control of proliferative and apoptotic pathways, respectively. Together, these results provide the first evidence for Staufen1's direct implication in cancer biology. Accordingly, Staufen1 thus represents a novel target for the development of future therapeutic strategies for rhabdomyosarcoma.
Topics: Animals; Apoptosis; Carcinogenesis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cytoskeletal Proteins; Female; Gene Knockdown Techniques; HEK293 Cells; Humans; Mice, SCID; Neoplasm Invasiveness; Proto-Oncogene Proteins c-myc; RNA-Binding Proteins; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma, Embryonal; Xenograft Model Antitumor Assays
PubMed: 28211476
DOI: 10.1038/srep42342 -
Oncotarget May 2017Rhabdomyosarcoma (RMS), which represents the most frequent soft tissue sarcoma in pediatric populations, is classified into two major subtypes: embryonal RMS (ERMS) and...
Rhabdomyosarcoma (RMS), which represents the most frequent soft tissue sarcoma in pediatric populations, is classified into two major subtypes: embryonal RMS (ERMS) and alveolar RMS (ARMS). ARMS subtype, which shows greater aggressiveness and proneness to metastasis with respect to ERMS, are characterized, in about 75% of cases, by specific chromosomal translocations that involve PAX and FOXO1 genes. Many findings have demonstrated that PAX/FOXO1-positive ARMS have a worse prognosis than PAX/FOXO1-negative ones and that distinct molecular features characterize RMS with different gene fusion statuses. DNA methylation, which presently represents a challenging research area, is involved in the modulation of gene expression.We performed a genome-wide DNA methylation analysis using reduced-representation bisulfite sequencing (RRBS) in RMS samples and we found that fusion-positive alveolar and embryonal subgroups have different DNA methylation signatures and that ARMS fusion-positive subtypes are characterized by overall hypomethylation levels. While NELL1 was found to be hypomethylated and transcriptionally enhanced in RMS alveolar subtypes, high NELL1 expression levels, which proved to be correlated with negative RMS prognostic factors such as fusion status and histology (P < 0.0001), were found to discriminate between RMS patients with different outcomes (P < 0.05).In conclusion, our results demonstrated that different DNA methylation patterns distinguish between different RMS subgroups and they suggest that epigenetic signatures could be useful for risk stratification of patients.
Topics: Calcium-Binding Proteins; Cell Line, Tumor; Child; Child, Preschool; DNA Methylation; Epigenesis, Genetic; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Nerve Tissue Proteins; Oncogene Proteins, Fusion; Prognosis; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma, Embryonal; Translocation, Genetic; Up-Regulation
PubMed: 28380437
DOI: 10.18632/oncotarget.16526 -
Pediatric Blood & Cancer Mar 2021Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and...
BACKGROUND
Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and European cooperative groups. In order to define a better therapeutic strategy, we analyzed two studies conducted between 2005 and 2016 by the European paediatric Soft tissue sarcoma Study Group (EpSSG) and Children's Oncology Group (COG).
METHODS
We retrospectively identified patients with ARMS N1 enrolled in either EpSSG RMS2005 or in COG ARST0531. Chemotherapy in RMS2005 comprised ifosfamide + vincristine + dactinomycin + doxorubicin (IVADo), IVA and maintenance (vinorelbine, cyclophosphamide); in ARST0531, it consisted of either vincristine + dactinomycin + cyclophosphamide (VAC) or VAC alternating with vincristine + irinotecan (VI). Local treatment was similar in both protocols.
RESULTS
The analysis of the clinical characteristics of 239 patients showed some differences between study groups: in RMS2005, advanced Intergroup Rhabdomyosarcoma Study Group (IRS) and large tumors predominated. There were no differences in outcomes between the two groups: 5-year event-free survival (EFS), 49% (95% confidence interval [CI]: 39-59) and 44% (95% CI: 30-58), and overall survival (OS), 51% (95% CI: 41-61) and 53.6% (95% CI: 40-68) in RMS2005 and ARST0531, respectively. In RMS2005, EFS of patients with FOXO1-positive tumors was significantly inferior to those with FOXO1-negative (49.3% vs 73%, P = .034). In contrast, in ARST0531, EFS of patients with FOXO1-positive tumors was 45% compared with 43.8% for those with FOXO1-negative.
CONCLUSIONS
The outcome of patients with ARMS N1 was similar in both protocols. However, patients with FOXO1 fusion-negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that different strategies of chemotherapy may have an impact in the outcome of this subgroup of patients.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Lymph Nodes; Male; Prognosis; Retrospective Studies; Rhabdomyosarcoma, Alveolar; Survival Rate
PubMed: 33245207
DOI: 10.1002/pbc.28832 -
The Journal of International Medical... Mar 2020Rhabdomyosarcoma (RMS) is a common soft tissue tumor in children, but it is rare in adults. Alveolar rhabdomyosarcoma (ARMS) is a subtype of RMS and is extremely rare in... (Review)
Review
Rhabdomyosarcoma (RMS) is a common soft tissue tumor in children, but it is rare in adults. Alveolar rhabdomyosarcoma (ARMS) is a subtype of RMS and is extremely rare in adults, especially concerning the genital tract. We report a case of a 20-year-old woman who was admitted to and treated in our hospital for an RMS of the vulva. The patient presented with local recurrence and bone metastasis during chemotherapy after surgery and died within 1 year of diagnosis. Based on a literature review, the prognosis of ARMS in adults is poor. The treatment strategy for ARMS is not well established yet. The lungs and bone are two common sites of metastasis of ARMS.
Topics: Adult; Fatal Outcome; Female; Humans; Rhabdomyosarcoma, Alveolar; Vulva; Young Adult
PubMed: 32223663
DOI: 10.1177/0300060520905438 -
Cells Jul 2021Rhabdomyosarcoma (RMS), is the most frequent soft tissue tumor in children that originates from disturbances in differentiation process. Mechanisms leading to the...
Rhabdomyosarcoma (RMS), is the most frequent soft tissue tumor in children that originates from disturbances in differentiation process. Mechanisms leading to the development of RMS are still poorly understood. Therefore, by analysis of two RMS RH30 cell line subclones, one subclone PAX7 negative, while the second one PAX7 positive, and comparison with other RMS cell lines we aimed at identifying new mechanisms crucial for RMS progression. RH30 subclones were characterized by the same STR profile, but different morphology, rate of proliferation, migration activity and chemotactic abilities in vitro, as well as differences in tumor morphology and growth in vivo. Our analysis indicated a different level of expression of adhesion molecules (e.g., from VLA and ICAM families), myogenic microRNAs, such as miR-206 and transcription factors, such as MYOD, MYOG, SIX1, and ID. Silencing of PAX7 transcription factor with siRNA confirmed the crucial role of PAX7 transcription factor in proliferation, differentiation and migration of RMS cells. To conclude, our results suggest that tumor cell lines with the same STR profile can produce subclones that differ in many features and indicate crucial roles of PAX7 and ID proteins in the development of RMS.
Topics: Animals; Cell Adhesion Molecules; Cell Differentiation; Cell Line, Tumor; Cell Movement; Cell Proliferation; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Inhibitor of Differentiation Proteins; Mice, Inbred NOD; Mice, SCID; MicroRNAs; Neoplasm Invasiveness; PAX7 Transcription Factor; Rhabdomyosarcoma, Alveolar; Signal Transduction; Tumor Burden; Mice
PubMed: 34440639
DOI: 10.3390/cells10081870 -
Disease Models & Mechanisms Sep 2017Alveolar rhabdomyosarcoma (aRMS) is a pediatric soft tissue cancer commonly associated with a chromosomal translocation that leads to the expression of a Pax3:Foxo1 or...
Alveolar rhabdomyosarcoma (aRMS) is a pediatric soft tissue cancer commonly associated with a chromosomal translocation that leads to the expression of a Pax3:Foxo1 or Pax7:Foxo1 fusion protein, the developmental underpinnings of which may give clues to its therapeutic approaches. In aRMS, the NFκB-YY1-miR-29 regulatory circuit is dysregulated, resulting in repression of and loss of the associated tumor suppressor activity. To further elucidate the role of NFκB in aRMS, we first tested 55 unique sarcoma cell lines and primary cell cultures in a large-scale chemical screen targeting diverse molecular pathways. We found that pharmacological inhibition of NFκB activity resulted in decreased cell proliferation of many of the aRMS tumor cultures. Surprisingly, mice that were orthotopically allografted with aRMS tumor cells exhibited no difference in tumor growth when administered an NFκB inhibitor, compared to control. Furthermore, inhibition of NFκB by genetically ablating its activating kinase inhibitor, , by conditional deletion in a mouse model harboring the chimeric oncogene failed to abrogate spontaneous tumor growth. Genetically engineered mice with conditionally deleted exhibited a paradoxical decrease in tumor latency compared with those with active NFκB. However, using a synthetic-lethal approach, primary cell cultures derived from tumors with inactivated NFκB showed sensitivity to the BCL-2 inhibitor navitoclax. When used in combination with an NFκB inhibitor, navitoclax was synergistic in decreasing the growth of both human and wild-type mouse aRMS cells, indicating that inactivation of NFκB alone may not be sufficient for reducing tumor growth, but, when combined with another targeted therapeutic, may be clinically beneficial.
Topics: Allografts; Animals; Cell Line, Tumor; Cell Proliferation; Dogs; Female; Gene Deletion; Genetic Complementation Test; Humans; I-kappa B Kinase; Mice, SCID; NF-kappa B; Peptides; Phenotype; Proto-Oncogene Proteins c-bcl-2; Rhabdomyosarcoma, Alveolar; Signal Transduction
PubMed: 28883017
DOI: 10.1242/dmm.030882 -
Frontiers in Pediatrics 2021The head and neck (HN) are the most frequent sites of pediatric rhabdomyosarcoma (RMS). Alveolar RMS (ARMS) represents ~20% of all RMS cases and frequently spread to...
INTRODUCTION
The head and neck (HN) are the most frequent sites of pediatric rhabdomyosarcoma (RMS). Alveolar RMS (ARMS) represents ~20% of all RMS cases and frequently spread to lymph nodes (LNs). The aim was to report locoregional control, event-free survival (EFS), and overall survival (OS), according to clinical and pathological features, LN staging, and treatment modalities.
METHODS
The study included all patients prospectively enrolled in EpSSG RMS 2005 study under 21 years of age with localized HN ARMS and diagnosed between 2005 and 2016 in France. Medical data including imaging, surgical report, and radiation therapy planes were analyzed.
RESULTS
Forty-eight patients (median age 6 years; range 4 months-21 years), corresponding to 30 parameningeal and 18 non-parameningeal ARMS, were included. There were 33 boys (69%). Tumor locations included the following: orbit ( = 7) among which four cases had bone erosion, paranasal sinuses and nasal cavity ( = 16), deep facial spaces ( = 10), nasolabial fold ( = 8), and other non-parameningeal HN sites ( = 7). A fusion transcript of PAX3-FOXO1 or PAX7-FOXO1 was expressed in 33 of the 45 cases (73%) with molecular analysis. At diagnosis, 10 patients had primary resection of the primary tumor (PRPT) (none with microscopic complete resection) and 9 had LN staging. After induction chemotherapy, 26 patients (54%) had secondary resection of the primary tumor (SRPT) and 13 patients (27%) had cervical LN dissection. A total of 43 patients (90%) were treated with radiation therapy.With a median follow-up of 7 years (range 2-13 years), 5-year OS and EFS were 78% (95% CI, 63-88%) and 66% (95% CI, 51-78%), respectively. We observed 16 events (10 deaths): 4 local, 4 regional, 1 local and regional, and 7 metastatic. In univariate analysis, OS was only superior for patients under 10 years of age ( = 0.002), while -negative ARMS, SRPT for parameningeal ARMS, and LN surgery were associated with significantly better EFS.
CONCLUSION
Our study confirms a better outcome for fusion-negative ARMS and ARMS in children under 10 years. Moreover, LN surgery and SRPT of parameningeal tumor may improve EFS of ARMS. Larger studies are needed to confirm our findings.
PubMed: 35186818
DOI: 10.3389/fped.2021.783754