ARMS tends to form more often in the extremities, trunk, and peritoneum. It is also typically more aggressive than ERMS. Pleomorphic
Pleomorphic rhabdomyosarcoma (undifferentiated) rhabdomyosarcoma), also known as anaplastic rhabdomyosarcoma, is defined by the presence of pleomorphic cells with large, lobate hyperchromatic nuclei and multipolar mitotic figures. These tumors display high heterogeneity and extremely poor differentiation. The pleomorphic cells may be diffuse or localized, with the diffuse variation correlating to a worse prognosis. It occurs most often in adults, rarely in children, and is often discovered in the extremities. Due to the lack of discernible separation among cancers of this type, clinicians will often label undiagnosed sarcomas with little to no discernible features as anaplastic RMS. It is the most aggressive type of RMS, and will often require intensive treatment. Spindle cell/sclerosing
Spindle cell/sclerosing rhabdomyosarcoma is an added subtype listed in the 2020 WHO classification of soft tissue sarcomas.This subtype is very similar to that of leiomyosarcoma (cancer of the smooth muscle tissue), and it has a fascicular, spindled, and leiomyomatous growth pattern with notable rhabdomyoblastic differentiation . It occurs most commonly in the paratesticular region, and the prognosis for this particular form of RMS is excellent with a reported five-year survival rate of 95%. The sclerosing aspect of this subtype has a hyaline sclerosis and pseudovascular development.Multiple classification systems have been proposed for guiding management and treatment, and the most recent and widely used classification system is the "International Classification of Rhabdomyosarcoma" or ICR.
The fourth IRSG study found that 23% of patients were diagnosed in time for a complete resection of their cancer, and 15% had resection with only minimal remnants of the diseased cells. Risk factors
Rhabdomyosarcoma is difficult to diagnose. Risk factors that increase the likelihood of this cancer include inherited disorders such as Li-Fraumeni syndrome, Neurofibromatosis type 1, Beckwith-Wiedemann syndrome, Costello syndrome, Noonan syndrome, and DICER1 syndrome. Genetic
There are multiple genetic lesions associated with rhabdomyosarcoma, but there has been little consistent data demonstrating an association between specific genetic abnormalities and outcome. However, alveolar and embryonal types of RMS can be distinguished cytogenetically, and identification of specific genetic lesions can allow for accurate classification of the ARMS subtype when the histopathological findings are equivocal or unclear. This is valuable for clinical practice as the alveolar type presents a higher risk to the patient and will often require more aggressive treatment than the embryonal type. Thus, ARMS is also referred to as Fusion Positive rhabdomyosarcoma (FP-RMS). Up to 90% of alveolar RMS cases present with a translocations of t(2;13)(q35, q14) or, less commonly, t(1;13)(p36, q15). Both involve the translocation of a DNA binding domain of either PAX3 or PAX7, a member of the Paired Box family of transcription factors, to a transactivation site on FOXO1 (previously known as FKHR), a member of the forkhead/HNF-3 transcription factor family. The t(2;13) translocation results in a fusion of the PAX3 gene with FOXO1, while the t(1;13) translocation involves the fusion of PAX7 with FOXO1.