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Head & Neck Apr 2024To summarize the clinical characteristics and prognosis of children with nasolabial fold rhabdomyosarcoma (RMS).
OBJECTIVES
To summarize the clinical characteristics and prognosis of children with nasolabial fold rhabdomyosarcoma (RMS).
METHODS
Retrospective review of children treated for nasolabial fold RMS from January 2014 to September 2019.
RESULTS
Of 21 patients with nasolabial fold RMS, 90.48% were alveolar subtype, in which PAX3/7-FOXO1 fusion positive accounted for 87.5%. Ten patients (47.62%) had nodals invasion. Almost all patients received comprehensive treatment (chemotherapy [100%], radiation therapy [100%], and surgery [95.24%]). The median follow-up time was 34.3 months. The 3-year overall survival (OS) and event-free survival (EFS) was 67.7% ± 14.1% and 42.1% ± 13.5%, respectively. Four patients had regional lymph node relapse (NR), all in the ipsilateral submandibular lymph node region.
CONCLUSION
Majority of the patients with RMS in the nasolabial fold area were alveolar subtype and had positive PAX3/7-FOXO1 gene fusion. In addition, the nasolabial fold RMS had a high probability of regional lymph node metastasis in the submandibular area. To maintain the facial aesthetics and functions, the surgical area for nasolabial fold RMS is often very conservative and restricted. This could be one of the contributors for the poor prognosis of nasolabial fold RMS beside its worse pathological subtype and gene fusion.
Topics: Child; Humans; Nasolabial Fold; Neoplasm Recurrence, Local; Rhabdomyosarcoma; Prognosis; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38214480
DOI: 10.1002/hed.27637 -
Orbital Rhabdomyosarcoma Masquerading as a Dermoid Cyst: A Case Report and Review of the Literature.Cureus Dec 2023The purpose of this report is to present a case of orbital rhabdomyosarcoma (RMS) masquerading as a dermoid cyst. A six-year-old boy with an unremarkable medical history...
The purpose of this report is to present a case of orbital rhabdomyosarcoma (RMS) masquerading as a dermoid cyst. A six-year-old boy with an unremarkable medical history presented in the outpatient department with a palpable mass in the superonasal region of the right orbit, which had rapidly grown in the past month. The most likely diagnosis was dermoid cyst and the patient was scheduled for surgical excision. A high index of suspicion was raised intraoperatively based on the appearance of the lesion due to the presence of a feeder vessel. The histopathology examination identified alveolar RMS. The patient was referred to a pediatric oncology department and commenced intravenous chemotherapy. RMS may masquerade as various conditions, including dermoid cysts and chalazion. A high index of suspicion should be raised in cases with rapidly growing lesions.
PubMed: 38205487
DOI: 10.7759/cureus.50332 -
EMBO Reports Feb 2024BRD4, a bromodomain and extraterminal (BET) protein, is deregulated in multiple cancers and has emerged as a promising drug target. However, the function of the two main...
BRD4, a bromodomain and extraterminal (BET) protein, is deregulated in multiple cancers and has emerged as a promising drug target. However, the function of the two main BRD4 isoforms (BRD4-L and BRD4-S) has not been analysed in parallel in most cancers. This complicates determining therapeutic efficacy of pan-BET inhibitors. In this study, using functional and transcriptomic analysis, we show that BRD-L and BRD4-S isoforms play distinct roles in fusion negative embryonal rhabdomyosarcoma. BRD4-L has an oncogenic role and inhibits myogenic differentiation, at least in part, by activating myostatin expression. Depletion of BRD4-L in vivo impairs tumour progression but does not impact metastasis. On the other hand, depletion of BRD4-S has no significant impact on tumour growth, but strikingly promotes metastasis in vivo. Interestingly, BRD4-S loss results in the enrichment of BRD4-L and RNA Polymerase II at integrin gene promoters resulting in their activation. In fusion positive alveolar rhabdomyosarcoma, BRD4-L is unrestricted in its oncogenic role, with no evident involvement of BRD4-S. Our work unveils isoform-specific functions of BRD4 in rhabdomyosarcoma.
Topics: Humans; Transcription Factors; Nuclear Proteins; Cell Cycle Proteins; Cell Line, Tumor; Protein Isoforms; Rhabdomyosarcoma; Bromodomain Containing Proteins
PubMed: 38191874
DOI: 10.1038/s44319-023-00033-1 -
Clinical Pediatrics Dec 2023Alveolar rhabdomyosarcoma (ARMS) is a rare but highly aggressive cancer predominantly affecting children and adolescents. This study explores prognostic factors for...
Alveolar rhabdomyosarcoma (ARMS) is a rare but highly aggressive cancer predominantly affecting children and adolescents. This study explores prognostic factors for pediatric and adolescent ARMS, using the Surveillance, Epidemiology, and End Results (SEER) database. Leveraging SEER data (2000-2019), we analyzed 277 cases. Employing Kaplan-Meier survival analysis and Cox proportional hazards models, we identified significant prognostic factors. Gender distribution was nearly equal (56.0% boys, 44.0% girls), with the majority (70.8%) from the white ethnic group. Primary tumors were predominantly in extremities (37.2%). Distant metastases significantly increased mortality risk (hazard ratio [HR], 3.13; 95% CI: 2.14-4.58) and regional lymph node involvement raised mortality risk (HR, 1.36; 95% CI: 0.96-1.92). Chemotherapy-only treatment had higher mortality risk than chemoradiotherapy (HR, 1.16; 95% CI: 0.97-2.67). Conclusively, our study identifies distant metastases, regional lymph node involvement, and treatment modality as crucial predictors of overall survival in pediatric ARMS.
PubMed: 38153032
DOI: 10.1177/00099228231220236 -
Human Pathology May 2024Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents under the age of 20. The current World Health Organization (WHO) classification... (Review)
Review
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents under the age of 20. The current World Health Organization (WHO) classification for soft tissue and bone tumors recognizes 4 distinct subtypes of RMS based on clinicopathological and molecular genetic features: embryonal, alveolar, spindle cell/sclerosing and pleomorphic subtypes. However, with the increased use of molecular techniques, the classification of rhabdomyosarcoma has been evolving rapidly. New subtypes such as osseus RMS harboring TFCP2/NCOA2 fusions or RMS arising in inflammatory rhabdomyoblastic tumor have been emerging within the last decade, adding to the complexity of diagnosing skeletal muscle tumors. This review article provides an overview of classically recognized distinctive subtypes as well as new, evolving subtypes and discusses important morphologic, immunophenotypic and molecular genetic features of each subtype including recommendations for a diagnostic approach of malignant skeletal muscle neoplasms.
Topics: Humans; Rhabdomyosarcoma; Immunohistochemistry; Biomarkers, Tumor; Soft Tissue Neoplasms; Predictive Value of Tests; Molecular Diagnostic Techniques; Phenotype; Genetic Predisposition to Disease; Child
PubMed: 38135061
DOI: 10.1016/j.humpath.2023.12.004 -
Nature Communications Dec 2023Activation of oncogenic gene expression from long-range enhancers is initiated by the assembly of DNA-binding transcription factors (TF), leading to recruitment of...
Activation of oncogenic gene expression from long-range enhancers is initiated by the assembly of DNA-binding transcription factors (TF), leading to recruitment of co-activators such as CBP/p300 to modify the local genomic context and facilitate RNA-Polymerase 2 (Pol2) binding. Yet, most TF-to-coactivator recruitment relationships remain unmapped. Here, studying the oncogenic fusion TF PAX3-FOXO1 (P3F) from alveolar rhabdomyosarcoma (aRMS), we show that a single cysteine in the activation domain (AD) of P3F is important for a small alpha helical coil that recruits CBP/p300 to chromatin. P3F driven transcription requires both this single cysteine and CBP/p300. Mutants of the cysteine reduce aRMS cell proliferation and induce cellular differentiation. Furthermore, we discover a profound dependence on CBP/p300 for clustering of Pol2 loops that connect P3F to its target genes. In the absence of CBP/p300, Pol2 long range enhancer loops collapse, Pol2 accumulates in CpG islands and fails to exit the gene body. These results reveal a potential novel axis for therapeutic interference with P3F in aRMS and clarify the molecular relationship of P3F and CBP/p300 in sustaining active Pol2 clusters essential for oncogenic transcription.
Topics: Humans; RNA Polymerase II; Cysteine; Transcription Factors; PAX3 Transcription Factor; Rhabdomyosarcoma, Alveolar; RNA; Transcriptional Activation; Protein Binding; Forkhead Box Protein O1
PubMed: 38102136
DOI: 10.1038/s41467-023-43780-4 -
Cureus Nov 2023Head and neck rhabdomyosarcoma (HNRMS) is a rare type of soft tissue tumor that affects both adults and children with an overall incidence of 0.041 per 100,000 people....
Head and neck rhabdomyosarcoma (HNRMS) is a rare type of soft tissue tumor that affects both adults and children with an overall incidence of 0.041 per 100,000 people. Adults make up approximately 31.2% of all HNRMS diagnoses and have an overall survival rate between 20% and 40%. We present a case of a 46-year-old male who initially presented with nasal congestion and vision changes. Maxillofacial computed tomography and magnetic resonance imaging of the brain showed involvement of the orbital apex, abutment of the planum sphenoidale, and extension to the foramen rotundum (FR). Nasal endoscopy with biopsy confirmed the diagnosis of T2aN0M0 parameningeal HNRMS. The patient underwent induction chemotherapy, followed by endoscopic resection, which resulted in negative intraoperative margins. Subsequently, he underwent adjuvant concurrent chemotherapy and proton beam radiation after positive microscopic positive margins were found on the optic nerve. The patient did not experience any significant complications, and he is currently without radiographic or clinical recurrence 18 months after the treatment. He was able to maintain his vision throughout the treatment. In adults, HNRMS is usually treated with chemoradiotherapy based on pediatric protocols, since there are limited data available for adult treatment protocols and outcomes. Although surgery has been associated with positive outcomes in adult patients, there are no previous reports of its use with either neoadjuvant or adjuvant treatment. This type of treatment protocol has never been described for adult HNRMS. We hope that our report can add more data to the growing body of literature on HNRMS treatment protocols.
PubMed: 38098924
DOI: 10.7759/cureus.48761 -
PAX3-FOXO1 dictates myogenic reprogramming and rhabdomyosarcoma identity in endothelial progenitors.Nature Communications Nov 2023Fusion-positive rhabdomyosarcoma (FP-RMS) driven by the expression of the PAX3-FOXO1 (P3F) fusion oncoprotein is an aggressive subtype of pediatric rhabdomyosarcoma....
Fusion-positive rhabdomyosarcoma (FP-RMS) driven by the expression of the PAX3-FOXO1 (P3F) fusion oncoprotein is an aggressive subtype of pediatric rhabdomyosarcoma. FP-RMS histologically resembles developing muscle yet occurs throughout the body in areas devoid of skeletal muscle highlighting that FP-RMS is not derived from an exclusively myogenic cell of origin. Here we demonstrate that P3F reprograms mouse and human endothelial progenitors to FP-RMS. We show that P3F expression in aP2-Cre expressing cells reprograms endothelial progenitors to functional myogenic stem cells capable of regenerating injured muscle fibers. Further, we describe a FP-RMS mouse model driven by P3F expression and Cdkn2a loss in endothelial cells. Additionally, we show that P3F expression in TP53-null human iPSCs blocks endothelial-directed differentiation and guides cells to become myogenic cells that form FP-RMS tumors in immunocompromised mice. Together these findings demonstrate that FP-RMS can originate from aberrant development of non-myogenic cells driven by P3F.
Topics: Animals; Child; Humans; Mice; Cell Line, Tumor; Endothelial Cells; Forkhead Box Protein O1; Gene Expression Regulation, Neoplastic; Muscle, Skeletal; Oncogene Proteins, Fusion; Paired Box Transcription Factors; PAX3 Transcription Factor; Rhabdomyosarcoma; Rhabdomyosarcoma, Alveolar
PubMed: 37968277
DOI: 10.1038/s41467-023-43044-1 -
Frontiers in Pediatrics 2023A full-term infant with an unremarkable prenatal course presented at birth with a large midline facial mass and smaller masses in the head and neck. In addition,...
A full-term infant with an unremarkable prenatal course presented at birth with a large midline facial mass and smaller masses in the head and neck. In addition, multiple diffuse flesh-colored nodules spread along all the upper and lower limbs. An extensive evaluation to cover a broad differential diagnosis of infectious, lymphatic/vascular, and oncologic etiology was undertaken. The initial suspicion was confirmed by biopsy of the skin lesion as congenital alveolar rhabdomyosarcoma (RMS). RMS is the most common soft tissue sarcoma that occurs in childhood. However, neonatal RMS is exceedingly rare. The infant's initial treatment included vincristine, dactinomycin, and cyclophosphamide in addition to salvage ifosfamide and etoposide, which were dose-adjusted for age. Herein, we present a case of an infant with RMS who showed initial improvement before relapsing and succumbing to her disease at 5 months of age. A review of the limited literature available on this rare condition and newer treatment regimens with improved mortality rates is performed.
PubMed: 37964815
DOI: 10.3389/fped.2023.1233334 -
Cancers Nov 2023Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults. It is a worldwide challenge in child health as treatment... (Review)
Review
Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults. It is a worldwide challenge in child health as treatment outcomes for metastatic and recurrent disease still pose a major concern for both basic and clinical scientists. The treatment strategies for rhabdomyosarcoma include multi-agent chemotherapies after surgical resection with or without ionization radiotherapy. In this comprehensive review, we first provide a detailed clinical understanding of rhabdomyosarcoma including its classification and subtypes, diagnosis, and treatment strategies. Later, we focus on chemotherapy strategies for this childhood sarcoma and discuss the impact of three mechanisms that are involved in the chemotherapy response including apoptosis, macro-autophagy, and the unfolded protein response. Finally, we discuss in vivo mouse and zebrafish models and in vitro three-dimensional bioengineering models of rhabdomyosarcoma to screen future therapeutic approaches and promote muscle regeneration.
PubMed: 37958442
DOI: 10.3390/cancers15215269