Encyclopedia of Pathology

Living Edition
| Editors: J.H.J.M. van Krieken

Rhabdomyosarcoma

  • Alessandro FranchiEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-28845-1_4931-1

Synonyms

Definition

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.

Clinical Features

  • Incidence

    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.

  • Age

    RMS is a tumor of childhood and adolescence. Only rare cases have been reported in adults.

  • Sex

    Urinary bladder RMS shows a slight male predominance.

  • Site

    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.

  • Treatment

    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.

  • Outcome

    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.

Macroscopy

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.

Microscopy

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.

Immunophenotype

The most useful immunohistochemical markers for skeletal muscle differentiation are desmin, myogenin (Myf4), and MyoD1, which are sensitive and specific.

Molecular Features

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.

Differential Diagnosis

Other tumors with myogenic differentiation, including inflammatory myofibroblastic tumor and smooth muscle tumors, can be easily ruled out based on the histologic and immunohistochemical findings. The distinction between solid or translocation negative alveolar RMS and embryonal RMS may be difficult. The tumor population in embryonal RMS is more heterogeneous, with the presence of round and spindle elements, while neoplastic cells of alveolar RMS are larger and show a more diffuse immunostaining for myogenin. Desmoplastic small round cell tumor (DSRCT) shows partial overlapping histologic and immunophenotypic features (desmin positivity) with embryonal and alveolar RMS. However, RMS is positive for myogenin, which is not detected in DSRCT. In the rare cases occurring in adult patients, sarcomatoid carcinoma with heterologous rhabdomyoblastic differentiation must be entered in the differential diagnosis.
Fig. 1

Embryonal rhabdomyosarcoma of the urinary bladder, formed by undifferentiated round and spindle cells with scattered rhabdomyoblasts

Fig. 2

Paratesticular spindle cell rhabdomyosarcoma, with intersecting fascicles of elongated neoplastic cells

References and Further Reading

  1. Ferrari, A., Bisogno, G., Casanova, M., Meazza, C., Piva, L., Cecchetto, G., Zanetti, I., Pilz, T., Mattke, A., Treuner, J., & Carli, M. (2002). Paratesticular rhabdomyosarcoma: Report from the Italian and German Cooperative Group. Journal of Clinical Oncology, 20, 449–455.CrossRefGoogle Scholar
  2. 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
  3. 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
  4. Rodríguez, D., Barrisford, G. W., Sanchez, A., Preston, M. A., Kreydin, E. I., & Olumi, A. F. (2014). Primary spermatic cord tumors: Disease characteristics, prognostic factors, and treatment outcomes. Urologic Oncology, 32, 52.e19–52.e25.CrossRefGoogle Scholar
  5. 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
  6. Tavora, F., Kryvenko, O. N., & Epstein, J. I. (2013). Mesenchymal tumours of the bladder and prostate: An update. Pathology, 45, 104–115.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Translational Research and of New Technologies in Medicine and SurgeryUniversity of PisaPisaItaly