Carcinosarcoma of the urinary bladder following cyclophosphamide therapy: evidence for monoclonal origin and chromosome 9p allelic loss.

We report a case involving a 45-year-old man with a 12-year history of Wegener granulomatosis, who developed a carcinosarcoma of the urinary bladder after long-term cyclophosphamide therapy. Cyclophosphamide is well recognized as an etiologic agent for urothelial carcinoma of the urinary bladder. However, only 5 cases of carcinosarcoma of the urinary bladder following cyclophosphamide therapy have been reported. We used loss of heterozygosity studies and microsatellite markers to define the molecular basis of this rare neoplasm. These studies revealed evidence supporting a monoclonal origin for the 2 components of this tumor. We also demonstrated allelic loss of chromosome 9p. This loss associated with carcinosarcoma of the urinary bladder is in agreement with previous studies, suggesting a possible role for the tumor suppressor gene p16 in the pathogenesis of this tumor.