Rhabdomyosarcoma (RMS) is a malignant tumor with skeletal muscle differentiation. Four subtypes are currently recognized: embryonal, alveolar, pleomorphic, and spindle cell/sclerosing. The embryonal and the spindle cell/sclerosing subtypes are by far the most common in the urogenital tract.
RMS is the most common pediatric soft tissue sarcoma, and approximately 10–15% of all RMSs originate in the bladder and prostate, making the genitourinary tract the second most common primary site.
RMS is a tumor of childhood and adolescence. Only rare cases have been reported in adults.
Urinary bladder RMS shows a slight male predominance.
Embryonal RMS occurs in the soft tissue of the paratesticular region, bladder, and prostate. Spindle cell RMS involves the paratesticular region, while alveolar and pleomorphic RMS are exceedingly rare in the urogenital tract.
RMS is treated with a multimodal approach. The local control may be achieved with surgical resection and/or radiotherapy. Chemotherapy protocols are employed in the neoadjuvant setting or after incomplete tumor resection, as well as in patients with systemic disease.
Patients with localized disease have an excellent survival (75–85% at 5 years). Patients with non-embryonal histologies and patients with metastatic disease at presentation have significant lower survival rates.
In the bladder the most frequently involved site is the trigone. The botryoid variant of embryonal RMS appears as a polypoid gelatinous multinodular lesion that protrudes in the lumen. Spindle cell RMS appears as a solid, firm, fibrous lesion, while other RMS types mainly consist of a poorly circumscribed, fleshy, pale tan mass with areas of necrosis and hemorrhage that infiltrate neighboring structures.
Embryonal rhabdomyosarcoma is characterized by a mixture of undifferentiated round cells with a well-differentiated population of rhabdomyoblasts exhibiting an intensely eosinophilic cytoplasm, within a myxoid stroma (Fig. 1). Cross striations are sometimes present. Botryoid RMS arising in the urinary bladder shows a cellular layer of round primitive cells under the intact epithelium, which is designated cambium layer. The deeper portions of the tumor appear as paucicellular, loose, edematous, or myxoid.
The spindle cell subtype displays a fascicular proliferation of elongated cells with bright eosinophilic cytoplasm and cross striations, with focal to extensive stromal sclerosis (Fig. 2). In the alveolar subtype, neoplastic cells grow in distinct nests separated by fibrous septa. They tend to be discohesive in the central part of the nest and aggregate at the periphery. Multinucleated giant cells may be seen. The pleomorphic subtype presents as a solid growth of highly pleomorphic cells with abundant eosinophilic cytoplasm.
The most useful immunohistochemical markers for skeletal muscle differentiation are desmin, myogenin (Myf4), and MyoD1, which are sensitive and specific.
The majority of alveolar rhabdomyosarcomas present a PAX3-FOXO1 or PAX7-FOXO1 gene fusion. A subset of spindle cell RMS presents MYOD1 mutations, often associated with a coexistent PIK3CA mutation.
References and Further Reading
- Fletcher, C. D., Bridge, J. A., Hogendoorn, P. C. W., & Mertens, F. (Eds.). (2013). WHO classification of tumours of soft tissue and bone. Lyon: IARC Press.Google Scholar
- Rodeberg, D. A., Anderson, J. R., Arndt, C. A., Ferrer, F. A., Raney, R. B., Jenney, M. E., Brecht, I. B., Koscielniak, E., Carli, M., Bisogno, G., Oberlin, O., Rey, A., Ullrich, F., Stevens, M. C., & Meyer, W. H. (2011). Comparison of outcomes based on treatment algorithms for rhabdomyosarcoma of the bladder/prostate: Combined results from the Children’s Oncology Group, German Cooperative Soft Tissue Sarcoma Study, Italian Cooperative Group, and International Society of Pediatric Oncology Malignant Mesenchymal Tumors Committee. International Journal of Cancer, 128, 1232–1239.CrossRefGoogle Scholar
- Seitz, G., Dantonello, T. M., Int-Veen, C., Blumenstock, G., Godzinski, J., Klingebiel, T., Schuck, A., Leuschner, I., Koscielniak, E., Fuchs, J., & CWS-96 Study Group. (2011). Treatment efficiency, outcome and surgical treatment problems in patients suffering from localized embryonal bladder/prostate rhabdomyosarcoma: A report from the cooperative soft tissue sarcoma trial CWS-96. Pediatric Blood & Cancer, 56, 718–724.CrossRefGoogle Scholar