Cyclophosphamide Hemorrhagic Cystitis

Abstract

In addition to leucopenia, thrombocytopenia, nausea, vomiting, diarrhea and alopecia, hemorrhagic cystitis is a very serious complication of cyclophosphamide therapy. This complication was observed in 11 cases treated for advanced malignant disease in 1966-1969. the hematuria varied in severity from slight microscopic to profuse and life-threatening, and occurred with or without symptoms of cystitis. Early urinary culture has given no growth, but secondary infection has occurred. Cystoscopy revealed disseminated subepithelial bleeding in patients with mild to moderate hematuria. Large tumorlike masses were seen in the bladder in two patients with severe symptoms of cystitis and in others an edematous, swollen mucosa. Microscopic examination of the bladders showed many wide, thin-walled vessels beneath the epithelium. the mucous membrane was edematous, thickened or fibrotic. Necrosis, calcification and cystic epithelial nests were found. Cytologic examination of the urine showed epithelial atypia of varying severity. the cytologist and the clinician should be aware of the fact that pictures suggesting malignancy may appear during treatment with cyclophosphamide. the polymorphous, tumor-like granulation tissue sometimes seen on cystoscopy may be mistaken for metastases or primary bladder tumor both macroscopically and microscopically, particularly in very small biopsy specimens. the mechanisms responsible for the bladder damage and precautions to prevent this complication are discussed.