| Embryonic origin | mesoderm |
| Epidemiology | the most common pediatric soft tissue sarcoma (5 to 8% of all malignancies in childhood): annual incidence is 4/106; E-RMS accounts for 75% of all RMS, and is observed in young children (3-12 yrs); A-RMS is found in the remaining 25 %, and is observed in older children and young adults (6-21 yrs) |
| Clinics | E-RMS occurs predominantly in the head and neck region, the genito-urinary tract, and the retroperitoneum;
A-RMS occurs predominantly in the extremities and the trunk;
RMS often present as a tumour mass, or may be discovered from symptomsaccording |
| Pathology | in E-RMS, tumor cells are round or spindle-shaped and may exhibit various degrees of muscular differentiation; they are often dispersed in an abundant myxoid stroma; the botryoid type, observed in tumors developped in mucosa-lined organs (vagina, bladder), exhibits a polypoid grape-like pattern. in A-RMS, tumor cells are round and more dense than in E-RMS and, typically, they are arranged according a pattern reminiscent of lung alveoli. |
| Prognosis | dependent on the extent of disease at time of diagnosis, and on the type of RMS; patients with A-RMS have a poorer survival than those with E-RMS |
Cytogenetics
Morphological | E-RMS do not show recurrent structural chromosome rearrangement; the majority of the tumors are hyperdiploid, with an increased copy number for chromosomes 2, 7, 8, 12, and 13, in particular; comparative genomic hybridization (CGH) confirms these findings, showing gains of a variety of whole chromosomes, 2, 13, 12, 8, and 7 (in 50-60% of the cases), 17, 18, and 19 (40%), and the loss of chromosomes 16 and 10 (in 30-40%), and 15 and 14 (20%); polymorphism studies shows that E-RMS is associated with the loss of heterozygosity at 11p13. A-RMS is characterized by two pathognomonic translocations:
- t(2;13)(q35;q14) and
- t(1;13)(p36;q14), found in 80 and 15% of the cases respectively,
leading to the formation of gene fusions, namely
- PAX3 - FKHR, in the t(2;13), and
- PAX7 - FKHR in the t(1;13), generating fusion transcripts;
double-minute chromosomes have been reported in some RMS, and CGH has showed a high frequency of genomic amplifications; the amplicons are located in 12q13-15 (50% of the cases), 2p24 (36%), 13q14, 13q32, and 1q36 (14%), 1q21 and 8q13-q21 (7%);
the 12q13-15 amplicon could involve genes:
- CHOP,
- MDM2, and
- SAS;
- MYCN gene is amplified in cases with the amplicon at 2p24, but unlike in neuroblastoma, no correlation with prognosis seems to exist in RMS; cases with the fusion PAX7-FKHR often show an amplification of the fusion gene (and more frequently than cases with the PAX3-FKHR gene do). |
| Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. |
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