Rhabdomyosarcoma: present and future perspectives in diagnosis and treatment.

(RMS) is among the most common extracranial solid tumors occurring in children 1. It is the commonest form of soft tissue sarcoma in children and young adults and accounts for approximately 4%-5% of all childhood malignancy with an annual incidence of 5.3 per million children under the age of 15 2. The peak incidence is seen early in childhood with a median age at diagnosis of about 5 years. Males are reported to be more frequently affected than females. Because RMS is derived from primitive mesenchymal cells, it can be found virtually anywhere in the body, including those sites where striated muscles are not normally found. The most common primary sites are: genitourinary (24%), parameningeal (16%), extremities (19%), orbit (9%), other head and neck (10%), and miscellaneous other sites (22%) 3,4. ETIOLOGY Although the etiology is unknown, genetic factors may play an important role. An increase in both central nervous system anomalies and genitourinary abnormalities similar to those associated with Wilms' tumor is recognised. Other associations are with Gor-lin's syndrome, fetal alcohol syndrome, and neurofi-bromatosis 1 5. In 1969, Li et al reported an increased incidence of breast cancer in mother of children and young adults diagnosed with RMS 6. Further studies then identified the increased intrafamilial incidence of certain cancers as bone and soft tissue sarcomas, breast carcinoma, gliomas, leukaemia, and adreno-cortical carcinomas, predominantely occurring below the age of 45 7. This syndrome has a dominant inheritance pattern and is associated with a inactivation of p53 gene. P53 is a tumor suppressor gene that plays a critical role in mediating cell cycle arrest and apopto-sis in response to DNA damage 8. HISTOLOGY RMS is a small round, blue cell neoplasm and must be differentiated from neuroblastoma, Ewing's family of tumors, and lymphoma. The key for diagnosing RMS is the presence of malignant skeletal muscle differentiation. Immunohistochemical staining (e.g. myogenin, MyoD, muscle specific actin, myoglobin, and/or desmin) is commonly required for accurate diagnosis. Tumors are classified using the modified International Classification of RMS 9. This system identifies a favourable histological group comprising the embryonal histology tumors (which accounts for approximately 80% of all RMS), including the spindle cell and botryoid variants; and an unfavourable group comprising tumors with alveolar histology (15%-20% of RMS). In 1995 pathologists from the different Cooperative Groups agreed a new classification which identified prognostically significant and reproducible subtypes 10. Three main classes have been identified: a) …