-
Journal of Dental Research Apr 2012Rhabdomyosarcoma (RMS) is a morphologically and clinically heterogeneous group of malignant tumors that resemble developing skeletal muscle and is the most common... (Review)
Review
Rhabdomyosarcoma (RMS) is a morphologically and clinically heterogeneous group of malignant tumors that resemble developing skeletal muscle and is the most common soft-tissue sarcoma in children and adolescents. The most prominent sites involve head and neck structures (~40%), genito-urinary track (~25%), and extremities (~20%). Embryonal (ERMS) and alveolar (ARMS) are the two major RMS subtypes that are distinct in their morphology and genetic make-up. The prognosis for this cancer depends strongly on tumor size, location, staging, and child's age. In general, ERMS has a more favorable outcome, whereas the mortality rate remains high in patients with ARMS, because of its aggressive and metastatic nature. Over the past two decades, researchers have made concerted efforts to delineate genetic and epigenetic changes associated with RMS pathogenesis. These molecular signatures have presented golden opportunities to design targeted therapies for treating this aggressive cancer. This article highlights recent advances in understanding the molecular pathogenesis of RMS, and addresses promising research areas for further exploration.
Topics: Adolescent; Cell Differentiation; Cell Lineage; Cell Proliferation; Child; Humans; Molecular Targeted Therapy; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma, Embryonal
PubMed: 21917598
DOI: 10.1177/0022034511421490 -
Gene Aug 2018The PAX3 gene encodes a member of the PAX family of transcription factors that is characterized by a highly conserved paired box motif. The PAX3 protein is a... (Review)
Review
The PAX3 gene encodes a member of the PAX family of transcription factors that is characterized by a highly conserved paired box motif. The PAX3 protein is a transcription factor consisting of an N-terminal DNA binding domain (containing a paired box and homeodomain) and a C-terminal transcriptional activation domain. This protein is expressed during development of skeletal muscle, central nervous system and neural crest derivatives, and regulates expression of target genes that impact on proliferation, survival, differentiation and motility in these lineages. Germline mutations of the murine Pax3 and human PAX3 genes cause deficiencies in these developmental lineages and result in the Splotch phenotype and Waardenburg syndrome, respectively. Somatic genetic rearrangements that juxtapose the PAX3 DNA binding domain to the transcriptional activation domain of other transcription factors deregulate PAX3 function and contribute to the pathogenesis of the soft tissue cancers alveolar rhabdomyosarcoma and biphenotypic sinonasal sarcoma. The wild-type PAX3 protein is also expressed in other cancers related to developmental lineages that normally express this protein and exerts phenotypic effects related to its normal developmental role.
Topics: Animals; Gene Expression; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; Humans; Mutation; PAX3 Transcription Factor; Sarcoma; Waardenburg Syndrome
PubMed: 29730428
DOI: 10.1016/j.gene.2018.04.087 -
Frontiers in Medicine 2022Rhabdomyosarcoma (RMS) is the most frequent soft sarcoma in children and adolescents. Alveolar rhabdomyosarcoma (ARMS) is a relatively rare subtype that is characterized...
BACKGROUND
Rhabdomyosarcoma (RMS) is the most frequent soft sarcoma in children and adolescents. Alveolar rhabdomyosarcoma (ARMS) is a relatively rare subtype that is characterized by aggressive behavior and an unsatisfactory prognosis. An ARMS can arise anywhere but most commonly occurs at extremity sites with a very small fraction in the retroperitoneum. The utility of 2-Deoxy-2-[fluorine-18]-fluoro-D-glucose (F-FDG) positron emission tomography combined with computed tomography (PET/CT) remains to be established in ARMS.
CASE REPORT
A 3-year-old female child was accidentally found with a large left upper abdominal mass for a day. CT examination indicated a huge soft tissue mass in the left retroperitoneum extending superiorly to the level of the left hilus renalis and inferiorly to the left acetabulum in the pelvic cavity, with intrusion into the lumbar foramens. F-FDG PET/CT found a mass in the left retroperitoneum from the level of T12 to the left acetabulum, with the maximum standardized uptake value (SUV) of about 7.0, and a CT value of about 39 HU, invading the left L3-5 intervertebral foramina and protruding into the spinal canal, with unclear boundary with the spinal cord. Retroperitoneal tumor resection and the repair operation of vascular exploration were performed. An ARMS was confirmed by postoperative biopsy, immunohistochemical staining, and genetic detection with the rupture of the fork head in rhabdomyosarcoma (FKHR). The patient received chemotherapy and was in a good condition with no recurrence and obvious complications.
CONCLUSION
Retroperitoneal ARMS is rare and indicates a poor outcome with the potential to involve vital organs and intrude into the spinal canal. Accurate diagnosis and staging using PET/CT would contribute to better risk stratifications and appropriate treatment individually.
PubMed: 36405590
DOI: 10.3389/fmed.2022.1019964 -
Sarcoma 2022Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma for which subsets of patients have longstanding unmet clinical needs. For example, children with...
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma for which subsets of patients have longstanding unmet clinical needs. For example, children with alveolar rhabdomyosarcoma and metastases at diagnosis will experience only 8% disease-free 5-year survival for nonlocalized unresectable recurrent disease. Hence, development of novel therapeutic strategies is urgently needed to improve outcomes. The Plexin-Semaphorin pathway is largely unexplored for sarcoma research. However, emerging interest in the Plexin-Semaphorin signaling axis in pediatric sarcomas has led to phase I cooperative group dose-finding clinical trials, now completed (NCT03320330). In this study, we specifically investigated the protein expression of transmembrane receptor Plexin-B2 and its cognate SEMA4C ligands in clinical RMS tumors and cell models. By RNA interferences, we assessed the role of Plexin-B2 in cell growth and cell migration ability in selected alveolar and embryonal RMS cell model systems. Our results affirmed expression of Plexin-B2 across human samples, while also dissecting expression of the different protein subunits of Plexin-B2 along with the assessment of preferred Semaphorin ligands of Plexin-B2. Plexin-B2 knockdown had positive or negative effects on cell growth, which varied by cell model system. Migration assayed after Plexin-B2 knockdown revealed selective cell line specific migration inhibition, which was independent of Plexin-B2 expression level. Overall, these findings are suggestive of context-specific and possibly patient-specific (stochastic) role of Plexin-B2 and SEMA4 ligands in RMS.
PubMed: 35570846
DOI: 10.1155/2022/9646909 -
Epidemiology, Incidence, and Survival of Rhabdomyosarcoma Subtypes: SEER and ICES Database Analysis.Journal of Orthopaedic Research :... Oct 2019Rhabdomyosarcoma is the most common soft-tissue sarcoma in children and adolescents and accounts for 3% of all pediatric tumors. Subtypes include alveolar, spindle cell,...
Rhabdomyosarcoma is the most common soft-tissue sarcoma in children and adolescents and accounts for 3% of all pediatric tumors. Subtypes include alveolar, spindle cell, embryonal, mixed-type, pleomorphic, and rhabdomyosarcoma with ganglionic differentiation. The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was queried for patients diagnosed with any type of rhabdomyosarcoma between 1973 and 2014. Patient demographics, tumor characteristics, and incidence were studied with χ analysis. Survival was modeled with Kaplan-Meier survival curves and Cox proportional hazards models were used to assess the effect of age and gender on survival. Pleomorphic subtype had higher grade and larger sized tumors compared to other subtypes (p < 0.05). Pleomorphic and alveolar rhabdomyosarcoma had the worst overall survival with a 26.6% and 28.9% 5-year survival, respectively. Embryonal rhabdomyosarcoma had the highest 5-year survival rate (73.9%). Tumor size was negatively correlated with survival months, indicating patients with larger tumors had shorter survival times (p < 0.05). Presence of higher-grade tumors and metastatic disease at presentation were negatively correlated with survival months (p < 0.05). No significant differences in the survival were found between gender or race between all of the subtypes (p > 0.05). This study highlights key differences in the demographic and survival rates of the different types of rhabdomyosarcoma that can be used for more tailored patient counseling. We also demonstrate that large, population-level databases provide sufficient data that can be used in the analysis of rare tumors. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2226-2230, 2019.
Topics: Adult; Female; Humans; Incidence; Male; Retrospective Studies; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma, Embryonal; SEER Program; United States
PubMed: 31161653
DOI: 10.1002/jor.24387 -
Head and Neck Pathology Sep 2017Head and neck rhabdomyosarcoma occurs frequently in children and adolescents, and has been well studied in that population. In contrast, it is rare in adults and is not...
Head and neck rhabdomyosarcoma occurs frequently in children and adolescents, and has been well studied in that population. In contrast, it is rare in adults and is not as well characterized clinically and pathologically. Seven cases of adult rhabdomyosarcoma occurring in head and neck were retrieved from the archives of Department of Pathology and Division of Oral Pathology at University of Washington. Radiologic findings and clinical history, as well as pathologic findings from hematoxylin and eosin slides and immunohistochemistry for myogenic markers were reviewed. A total of seven cases of rhabdomyosarcoma (two embryonal, three alveolar and two pleomorphic subtype) were reviewed. Patient ages ranged from 18 to 57 years (median 21 years). Classic and unique histologic features for each subtype, including post-treatment morphologic changes, were identified. Clinical follow-up information was available for 4 patients. 3 of 4 patients experienced recurrence, including two with distant metastasis. One patient died of disease progression 41 months after presentation. Head and neck rhabdomyosarcoma in adults can manifest both classic and unique histologic features for each subtype. In addition, recurrence and distant metastasis were observed, suggesting aggressive clinical behavior regardless of subtype.
Topics: Adolescent; Adult; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Rhabdomyosarcoma; Young Adult
PubMed: 27896667
DOI: 10.1007/s12105-016-0771-0 -
Oncoimmunology 2022Rhabdomyosarcoma (RMS) is an aggressive pediatric soft tissue sarcoma characterized by a very poor prognosis when relapses occur after front-line therapy. Therefore, a...
Rhabdomyosarcoma (RMS) is an aggressive pediatric soft tissue sarcoma characterized by a very poor prognosis when relapses occur after front-line therapy. Therefore, a major challenge for patients' management remains the identification of markers associated with refractory and progressive disease. In this context, cancer autoantibodies are natural markers of disease onset and progression, useful to unveil novel therapeutic targets. Herein, we matched autoantibody profiling of alveolar RMS (ARMS) patients with genes under regulatory control of PAX3-FOXO1 transcription factor and revealed fibroblast growth factor 8 (FGF8) as a novel ARMS tumor antigen of diagnostic, prognostic, and therapeutic potential. We demonstrated that high levels of FGF8 autoantibodies distinguished ARMS patients from healthy subjects and represented an independent prognostic factor of better event-free survival. FGF8 was overexpressed in ARMS tumors compared to other types of pediatric soft tissue sarcomas, acting as a positive regulator of cell signaling. Indeed, FGF8 was capable of stimulating ARMS cells migration and expression of pro-angiogenic and metastasis-related factors, throughout MAPK signaling activation. Of note, FGF8 was found to increase in recurrent tumors, independently of PAX3-FOXO1 expression dynamics. Risk of recurrence correlated positively with FGF8 expression levels at diagnosis and reduced FGF8 autoantibodies titer, almost as if to suggest a failure of the immune response to control tumor growth in recurring patients. This study provides evidence about the crucial role of FGF8 in ARMS and the protective function of natural autoantibodies, giving new insights into ARMS biology and laying the foundations for the development of new therapeutic strategies.
Topics: Autoantibodies; Fibroblast Growth Factor 8; Humans; Immunity; Neoplasm Recurrence, Local; PAX3 Transcription Factor; Paired Box Transcription Factors; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma, Embryonal
PubMed: 35813575
DOI: 10.1080/2162402X.2022.2096349 -
Adolescent Health, Medicine and... 2014Rhabdomyosarcoma (RMS), a malignant tumor of mesenchymal origin, is the third most common extracranial malignant solid tumor in children and adolescents. However, in... (Review)
Review
Rhabdomyosarcoma (RMS), a malignant tumor of mesenchymal origin, is the third most common extracranial malignant solid tumor in children and adolescents. However, in adults, RMS represents <1% of all solid tumor malignancies. The embryonal and alveolar histologic variants are more commonly seen in pediatric patients, while the pleomorphic variant is rare in children and seen more often in adults. Advances in the research of the embryonal and alveolar variants have improved our understanding of certain genes and biologic pathways that are involved in RMS, but much less is known for the other variants. Multimodality therapy that includes surgery and chemotherapy with or without radiation therapy is the mainstay of treatment for RMS. Improvements in the risk stratification of the pediatric patients based on presurgical (primary tumor site, tumor size, regional lymph node involvement, presence of metastasis) and postsurgical parameters (completeness of resection or presence of residual disease or metastasis) has allowed for the treatment assignment of patients in different studies and therapeutic trials, leading to increases in 5-year survival from 25%-70% over the past 40 years. However, for adult patients, in great part due to rarity of the disease and the lack of consensus on optimal treatment, clinical outcome is still poor. Many factors have been implicated for the differing outcomes between pediatric RMS versus adult RMS, such as the lack of standardized treatment protocols for adult RMS patients and the increased prevalence of advanced presentations. Now that there are increased numbers of survivors, we can appreciate the sequelae from therapy in these patients, such as bone growth abnormalities, endocrinopathies, and infertility. Improvements in risk stratification have led to clinical trials using lower doses of chemotherapy or radiation therapy with the intention of decreasing the incidence of side effects without compromising survival outcome.
PubMed: 24966711
DOI: 10.2147/AHMT.S44582 -
Seminars in Cell & Developmental Biology Aug 2015PAX transcription factors are key players in the development of different tissues and organs. At the cellular level they are involved in regulating lineage commitment... (Review)
Review
PAX transcription factors are key players in the development of different tissues and organs. At the cellular level they are involved in regulating lineage commitment and differentiation. Interference with these tightly regulated functions of PAX proteins is associated with developmental abnormalities and tumorigenesis of several types of cancer. As a result of aberrant PAX protein activity, either by gain- or loss of function mechanisms, affected cells are kept in a proliferative state by blocking their terminal differentiation. PAX proteins with a gain-of-function role in cancer are active in the proliferative state of cells and have to be downregulated before they can complete the differentiation process. Such PAX proteins are usually activated in malignancies by chromosomal translocations generating fusions with strong transcriptional activators. PAX proteins with tumor suppressor activity are actively driving the differentiation process and are necessary for the exit from the proliferative state. In cancer, a diverse set of mutational mechanisms is involved in reducing their activity. Here, we discuss the characteristics of mutant PAX proteins in different types of cancer including alveolar rhabdomyosarcoma, biphenotypic sinonasal sarcoma, thyroid cancer and leukemia, with special focus on their role in interference with normal differentiation pathways of the cell lineage involved.
Topics: Animals; Humans; Mutation; Neoplasms; Paired Box Transcription Factors
PubMed: 26391565
DOI: 10.1016/j.semcdb.2015.09.011 -
Annals of Medicine and Surgery (2012) Sep 2022Omental alveolar rhabdomyosarcoma (ARMS) in adults is a rare tumor and is not a common presentation of abdominal pain. We aim to report the eighth case of omental ARMS...
INTRODUCTION AND IMPORTANCE
Omental alveolar rhabdomyosarcoma (ARMS) in adults is a rare tumor and is not a common presentation of abdominal pain. We aim to report the eighth case of omental ARMS and perform a review of all publications that pertains to this topic.
CASE PRESENTATION
we show a case of a Mediterranean 52 year old smoker male, complaining of unbearable dull pain in the right iliac fossa. He had no relevant medical history other than general abdominal pain in the past several months.
CLINICAL DISCUSSION
the chief complaint was abdominal pain mimicking appendicitis. Physical examination showed a palpable mass in that region. Ultrasound and CT scan revealed a mass arising from the omentum. At this point we excluded the diagnosis of appendicitis and a laparotomy with biopsies sampling had been performed. The microscopical examination led to the diagnosis of alveolar rhabdomyosarcoma (ARMS). Treatment involved multidisciplinary care but the patient died during chemotherapy.
CONCLUSION
Adult rhabdomyosarcomas (RMS) are rare tumors that can arise from any soft tissue including omentum and should be taken into consideration when dealing with primary tumors that originate from the omental area. The studies and our understanding for this neoplasm are still very limited and should be expanded widely.
PubMed: 36147128
DOI: 10.1016/j.amsu.2022.104464