Report of a Case of Unusual Morphology of Cyclophosphamide-Induced Lateral Bladder Wall Cancer Arising in a Patient With Remote Treatment for Childhood Acute Lymphoblastic Leukemia

Primary glandular bladder neoplasms have typically been reported in the trigone region or dome of the bladder from urachal remnants or in bladder exstrophy or diverticula. Cyclophosphamide-induced bladder carcinomas are rare neoplasms in which, to our knowledge, glandular differentiation has not been described. We report a case of high-grade urothelial carcinoma with focal papillary and unusual glandular differentiation arising from the lateral bladder wall in a 36-year-old man, a nonsmoker, who received chemotherapy, including cyclophosphamide, from 7 to 12 years of age for acute lymphoblastic leukemia. He had no bladder exstrophy, urinary cancer, intravesical mitomycin therapy, or evidence of leukemic disease for the past 24 years. During workupfor flank pain and hematuria, a ureteral stone and left bladder wall lesion were identified. Microscopic examination of a transurethrally resected lesion demonstrated low-grade and focal highgrade urothelial carcinoma with papillary and glandular differentiation. Subepithelial but not detrusor invasion was present. His symptoms resolved, but cells “suspicious” for malignancy were subsequently seen on urine cytology. Imaging studies delineated left bladder wall thickening and minute renal lesions. Repeated cystoscopy revealed a 6-cm, flat lesion occupying 25% of the bladder in the region of prior scar. Again, low- and high-grade urothelial carcinoma with glandular and papillary features was noted microscopically, with subepthelial tissue invasion. Glandular differentiation may have prognostic significance, with studies suggesting a possible increased occurrence with invasion, as in our case. Although cyclophosphamide side effects include urothelial carcinoma, glandular morphology has been rarely noted. The lateral wall tumor location, unusual for glandular differentiation, may be due to carcinoma arising from cystitis glandularis, which, however, is not seen in either of our patient's resections. Glandular tumor morphology in cyclophosphamide-induced urothelial carcinoma is an infrequently described lesion awaiting further elucidation of its prognostic significance.