Transitional Cell Carcinoma of the Ureter Associated with Cyclophosphamide Therapy for Benign Disease: A Case Report

Transitional Cell Carcinoma of the Ureter Associated with Cyclophosphamide Therapy for Benign Disease: A Case Report

{}022-5347 /82/1285-1023$02.00/0 Vol. 1281 :N D7ember Pr-frded in U.S. A. THE JOURNAL OF· UROLOGY Copy.fight© 198.2 by ThG 'NilliarrB & VVilldns Co...

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{}022-5347 /82/1285-1023$02.00/0 Vol. 1281 :N D7ember Pr-frded in U.S. A.

THE JOURNAL OF· UROLOGY

Copy.fight© 198.2 by ThG 'NilliarrB & VVilldns Co.

TRANSITIONAL CELL CARCINOrvIA OF THE URETER WITH CYCLOPHOSPHAMIDE THERAPY FOR BENIGN DISEASE: A CASE REPORT HOWARD t SCHIFF, MARTIN FINKEL AND HANS E. SCHAPIRA From the Departments of Urology and Medicine, lviount Sinai Hospital, New York, New York

ABSTRACT

Cyclophosphamide-induced uroepithelial tumors of the bladder and renal pelvis have been reported previously. We present the first case of transitional cell carcinoma of the ureter associated with cyclophosphamide therapy.

Excretory urography (!VP) revealed left hydroureteronephrosis with nonvisualization of the mid and distal left ureter (fig. 1, A). Retrog-rade pyelography disclosed marked irregularity of the mid and distal ureter (fig. 1, B). Urinary cytology showed malignant cells. Left nephroureterectomy was performed on February 13. Pathologic examination of the specimen revealed gTade IV, deeply infiltrating transitional cell carcinoma of the ureter. Areas of severe dysplasia and carcinoma in situ were present in the renal pelvis (figs. 2 and 3). The patient died on May 20 of metastatic transitional cell carcinoma.

Cyclophosphamide is an alkylating agent widely used in the treatment of malignant and benign disease. Among the well described urologic complications of this agent are hemorrhagic cystitis, vesical fibrosis and malignant neoplasms of the renal pelvis and bladder. Herein we report the first case of ureteral carcinoma associated with cyclophosphamide therapy. CASE REPORT

R. G., an 81-year-old woman with interstitial pneumonitis, had been treated with prednisone and cyclophosphamide from

Fm. 1. A, IVP at 60 minutes with left hydroureteronephrosis to Sl level. Middle and distal portions of u:rete:r are not visualized. B, left retrograde pyelogram shows marked irregularity of mid and distal ureteL

September 1978 until December 1979. At that time hemorrhagic cystitis developed and the cyclophosphamide was discontinued. She was treated with cyclophosphamide again from June 25 until July 18, 1980, when total gross painless hematuria developed. The total dose received was 230 gm. The hematuria subsided after treatment with sulfamethoxazole. In October gross hematuria recurred and the patient was treated with ampicillin for an Escherichia coli urinary infection. In February 1981 the patient was hospitalized for evaluation. Accepted for publication January 15, 1982.

DISCUSSION

Uroepithelial tumors associated with cyclophosphamide have been reported in the last 10 years. Worth was the first to describe transitional cell carcinoma in 2 patients who were treated with cydophosphamide for lymphoma. 1 Since then, 33 cases of bladder carcinoma and 2 cases of carcinoma of the renal pelvis have been reported by various authors. 1- 6 The exact pathogenesis of uroepithelial tumors associated with cyclophosphamide is unknown. Pearson and Soloway,2 Cox,3 and Fuchs and associates 5 discussed the possible etiologic mechanisms that might account for this complication. As men-

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SCHIFF, FINKEL AND SCHAPIRA

FIG. 2. Gross specimen of left nephroureterectomy shows lesions in mid and distal ureter (arrows).

tioned by Fuchs and associates there is little evidence that exists to link directly the occurrence of uroepithelial carcinoma to cyclophosphamide ingestion. 5 There appears to be emerging, however, a pattern of increasing numbers of urothelial tumors in patients treated with cyclophosphamide for benign and malignant disease. 1- 6 We have reported the first case of transitional cell carcinoma of the ureter associated with cyclophosphamide ingestion. It should not be surprising, however, that this lesion should appear as part of a spectrum of uroepithelial tumors associated with this chemotherapeutic agent. We agree with the editorial comment by Soloway following the article by Fuchs and associates that there is a need for a registry of these cases and a critical review of the use of cyclophosphamide in nonneoplastic conditions. 5 Our case illustrates well the entire spectrum of uroepithelial changes, progressing from simple dysplasia to carcinoma in situ and deeply invasive transitional cell carcinoma.

FIG. 3. A, superficial transitional cell carcinoma of ureter. B, transitional cell carcinoma of ureter infiltrating deeply into muscularis.

REFERENCES

1. Worth, P.H. L.: Cyclophosphamide and the bladder. Brit. Med. J., 3: 182, 1971. 2. Pearson, R. M. and Soloway, M. S.: Does cyclophosphamide induce bladder cancer? Urology, 11: 437, 1978. 3. Cox, P. J.: Cyclophosphamide cystitis and bladder cancer. A hypothesis. Eur. J. Cancer, 15: 1071, 1979. 4. Hicks, R. M.: Multistage carcinogenesis in the urinary bladder. Brit. Med. Bull., 36: 39, 1980. 5. Fuchs, E. F., Kay, R., Poole, R., Barry, J. M. and Pearse, H. D.: Uroepithelial carcinoma in association with cyclophosphamide ingestion. J. Urol., 126: 544, 1981. 6. Garvin, D. D. and Ball, T. P., Jr.: Bladder malignancy in patient receiving cyclophosphamide for benign disease. Urology, 18: 80, 1981.