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Condyloma Acuminatum of the Bladder
Taz JOURNAL OF lh{OLGGY Copyright© 1976 by The \Villiarns & \.Vilkins Co.
Vol. 1:5, rv1ay ,,.Printed in U.S.A.
CONDYLOMA ACUMINATUM OF THE BLADDER SILAS PETTERSSON, GORAN HANSSON
AND
INGEMAR BLOHME
From the Departments of Urology, Pathology and Surgery, University of Goteborg, Goteborg, Sweden
ABSTRACT
Condyloma acuminatum in the bladder of 2 patients on immunosuppressive therapy after kidney transplantation is described. The successful treatment was transurethral electroresection and coagulation. We do not recommend radical operations in cases of condyloma acuminatum. Resected specimens should be examined pathologically to exclude papillary epithelial tumors. Condyloma acuminatum is a common disease, usually confined to the moist, cutaneous surfaces around the external genitalia and to the anal region; more rarely, it involves the urethra. 1 An exceedingly unusual manifestation of the disease is involvement in the bladder. 2 Our report concerns 2 patients with the unusual distribution of condyloma acuminatum in the bladder. Both patients were on immunosuppressive medication after kidney transplantation. CASE REPORTS
Case 1. A woman born in 1918 had analgesic nephropathy. After a short period on hemodialysis she was subjected to 2 cadaveric kidney transplantations in May and August 1970. However, both grafts were removed within 1 week owing to life-threatening arterial hemorrhage and acute rejection, respectively. A third and successful transplantation was performed in November. Convalescence was uneventful and the woman has had normal renal function without signs of allograft rejection. In addition to standard immunosuppressive treatment with prednisolone and azathioprine the patient was given antilymphocyte globulin during the first 10 days postoperatively. In May 1971 papillary, granular friable lesions were found at the inner aspects of the labia, in the vagina and perianally. The lesions were treated partly by sharp dissection and partly by electrocoagulation. Pathological examination of the excised material revealed tree-like growths with hyperplastic, stratified, squamous epithelium showing hyperkeratosis and parakeratosis. There was a distinct demarcation between the epithelium and the stroma, the latter containing a moderate number of lymphocytes and plasma cells. Pathological diagnosis was condyloma acuminatum. In December the papillary lesions recurred in the vulva and around the external urethra and the anus. In the central wall of the bladder, a few centimeters from the inner urethral orifice, urethroscopy revealed a low papillary tumor about 1 cm. in diameter. In the trigone, immediately inside the urethra, a more projecting and sessile lesion was found (fig. 1, A). Small papillary growths also were demonstrated in the urethra. A biopsy from 1 of the vesical lesions revealed condyloma acuminatum. The bladder lesions were excised by transurethral electroresection and the urethral lesions were carefully coagulated as were the vulvar and perianal growths. Microscopic examination of the vesical lesions showed a papillomatous pattern of condyloma acuminatum with squamous epithelium and inflammatory cells in the epithelium and stroma (fig. 1, B). A similar histologic picture was obtained at examination of a condyloma acuminatum from the vulva. At repeat followup visits recurrent lesions were coagulated in the urethra and vulva but recurrence was never seen in the bladder. To avoid scarring care was taken at coagulation in the urethra not to make the fulguration too deep. Not until
January 1974 was the patient free from recurrence and has remained so at repeat followup visits. There has been no sign of urethral stricture. Case 2. A woman born in 1932 had uremia owing to chronic pyelonephritis. In May 1967, before hemodialysis treatment became necessary, she received a kidney transplant from a brother. Necrosis of the ureter necessitated another operation; otherwise the postoperative period was uncomplicated. Renal function has been normal without signs of allograft rejection. The woman has been given standard immunosuppressive treatment with prednisolone and azathioprine. In November the patient complained of itching in the vulva and around the anus, where she also noted rapidly increasing growths. Examination in January 1968 revealed multiple large papillomatous tumors around the anus and smaller growths in the vulva and vagina. The lesions were partly excised by sharp excision and partly fulgurated. Pathological diagnosis was condyloma acuminatum (fig. 2). In February recurrent lesions in the vulva and the perianal region were treated with podophyllin, sharp excision and electrocoagulation. Cystoscopy revealed 2 cm. papillary lesions in the trigone. These lesions showed the same characteristics as those of the vulva and were treated by transurethral electrocoagulation. During the following years the patient was treated with podophyllin and electrocoagulation for recurrent lesions in the vulva and the perianal region but no recurrence was demonstrated in the bladder. Since 1972 no recurrence has been observed. DISCUSSION
Condyloma acuminatum is a verrucose lesion of squamous epithelium caused a virus. 3 Intranuclear virus particles have been identified by the in sections of condyloma acuminatum specimens. ,-s Transmission has been inoculation of sterile filtrates of wart material. 7 • 8 proved Condyloma acuminatum is commonly found on the penis, labia and around the anus. There have been several reports of condyloma acuminatum involving the urethra in male and female patients. •- 11 Only 4 reports of condylorna acuminatum in the bladder have been found in the literature'· 2 • 12 and all were giant condylomas, that is so-called Buschke-Loewenstein tumors. 13 One major difference between simple and giant condylomas is that simple condylomas, as in our 2 cases, remain superficial sparing the underlying tissue, while giant condylomas consistently penetrate underlying tissue resembling squamous cell carcinoma. Histopathologically, the lesions in the bladders of our 2 cases consisted of papillary structures covered by squamous cell epithelium with hyperkeratosis and parakeratosis. The metaplasia of the bladder epithelium from its normal transitional cell type to the squamous cell type may have been the result of the virus infection in these cases. The growth and type of epithelium that build up these growths differentiate them from
Accepted for publication August 22, 1975. 535
536
PETTERSSON, HANSSON AND BLOHME
FIG. 1. Case 1, A, photograph taken through cystoscope of sessile papillomatous lesion from trigone. B, papillomatous pattern of condyloma acuminatum in bladder. Transitional cell epithelium of bladder is seen at bottom of photograph. Hematoxylin stain, reduced from x70.
FIG. 2. Case 2. Marked acanthosis as well as hyperkeratosis and parakeratosis of squamous epithelium is characteristic of condyloma acuminatum. A, hematoxylin stain, reduced from x70. B, hematoxylin stain, reduced from' x280.
the papillary epithelial tumors of the bladder. No histologic criteria of malignancy were found in these 2 cases. Both of our patients were on immunosuppressive treatment, which may well have contributed to the unusual spread of the disease. It is well known that the incidence of viral as well as fungal and protozoan infections is high among immunosuppressed patients and that some normally rather harmless infections in these patients sometimes take unusually serious and even fatal courses. 14- 16 Of our 2 patients, 1 also suffered common warts and the other contracted a herpes zoster infection some years later. The treatment of the bladder lesions of our 2 patients was transurethral electroresection and coagulation. Therapy was successful and no recurrences have been seen in the bladder. We believe that this treatment should be tried first and, therefore, do not share the opinion of Kleiman and Lancaster that condyloma acuminatum of the bladder should be considered malignant by position, indicating an early radical operation. 1 A pathological examination of the resected specimens should always be made to exclude papillary epithelial tumors of the bladder. The patients also should be examined repeatedly for several years. Recently, excellent results have been reported on the use of an autogenous vaccine. 3 This therapy should be kept in mind in resistant cases before a radical excision is performed. REFERENCES
1. Kleiman, H. and Lancaster, Y.: Condyloma acuminata of the
bladder. J. Urol., 88: 52, 1962. 2. Lewis, H. Y., Wolf, P. L. and Pierce, J.M.: Condyloma acuminatum of the bladder. J. Urol., 88: 248, 1962. 3. Powell, L. C., Jr.: Condyloma acuminatum. Clin. Obst. Gynec., 15: 948, 1972.
4. Stoppelli, I.: Ultrastructural considerations on the presence of virus-like particles in condyloma acuminatum. Attualita Ostet. Ginec., 11: 431, 1965. 5. Dunn, A. E. and Ogilvie, M. M.: Intranuclear virus particles in human genital wart tissue: observations on the ultrastructure of the epidermal layer. J. Ultrastruct. Res., 22: 282, 1968. 6. Oriel, J. D. and Almeida, J. D.: Demonstration of virus particles in human genital warts. Brit. J. Vener. Dis., 46: 37, 1970. 7. Biberstein, H.: Immunization therapy of warts. Arch. Dermat. Syph., 50: 12, 1944. 8. Blank, H., Buerk, M. S. and Weidman, F.: Nature of the inclusion body of verruca vulgaris: a histochemical study of nucleotids. J. Invest. Dermat., 16: 19, 1951. 9. Gartman, E.: Intraurethral verruca acuminata in men. J. Urol., 75: 717, 1956. 10. Lindner, H.J. and Pasquier, C. M., Jr.: Condylomata acuminata of the urethra. J. Urol., 72: 875, 1954. 11. Dretler, S. P. and Klein, L. A.: The eradication of intraurethral condyloma acuminata with 5 per cent 5-fluorouracil cream. J. Urol., 113: 195, 1975. 12. Hotchkiss, R. S. and Rouse, A. J .: Papillomatosis of the bladder and ureters, preceded by condyloma acuminata of the vulva: a case report. J. Urol., 100: 723, 1968. 13. Loewenstein, L. W.: Carcinoma-like condylomata acuminata of the penis. Med. Clin. N. Amer., 23: 789, 1939. 14. Rifkind, D., Marchioro, T. L., Schneck, S. A. and Hill, R. B., Jr.: Systemic fungal infections complicating renal transplantation and immunosuppressive therapy: clinic, microbiologic, neurologic and pathologic features. Amer. J. Med., 43: 28, 1967. 15. Spencer, E. S. and Andersen, H.K.: Clinically evident, non-terminal infections with herpesviruses and the wart virus in immunosuppressed renal allograft recipients. Brit. Med. J ., 1: 251, 1970. 16. Simmons, R. L., Lopez, C., Balfour, H., Jr., Kalis, J., Rattazzi, L. C. and Najarian, J. S.: Cytomegalovirus: clinical virological correlations in renal transplant recipients. Ann. Surg., 180: 623, 1974.
Vol. 1:5, rv1ay ,,.Printed in U.S.A.
CONDYLOMA ACUMINATUM OF THE BLADDER SILAS PETTERSSON, GORAN HANSSON
AND
INGEMAR BLOHME
From the Departments of Urology, Pathology and Surgery, University of Goteborg, Goteborg, Sweden
ABSTRACT
Condyloma acuminatum in the bladder of 2 patients on immunosuppressive therapy after kidney transplantation is described. The successful treatment was transurethral electroresection and coagulation. We do not recommend radical operations in cases of condyloma acuminatum. Resected specimens should be examined pathologically to exclude papillary epithelial tumors. Condyloma acuminatum is a common disease, usually confined to the moist, cutaneous surfaces around the external genitalia and to the anal region; more rarely, it involves the urethra. 1 An exceedingly unusual manifestation of the disease is involvement in the bladder. 2 Our report concerns 2 patients with the unusual distribution of condyloma acuminatum in the bladder. Both patients were on immunosuppressive medication after kidney transplantation. CASE REPORTS
Case 1. A woman born in 1918 had analgesic nephropathy. After a short period on hemodialysis she was subjected to 2 cadaveric kidney transplantations in May and August 1970. However, both grafts were removed within 1 week owing to life-threatening arterial hemorrhage and acute rejection, respectively. A third and successful transplantation was performed in November. Convalescence was uneventful and the woman has had normal renal function without signs of allograft rejection. In addition to standard immunosuppressive treatment with prednisolone and azathioprine the patient was given antilymphocyte globulin during the first 10 days postoperatively. In May 1971 papillary, granular friable lesions were found at the inner aspects of the labia, in the vagina and perianally. The lesions were treated partly by sharp dissection and partly by electrocoagulation. Pathological examination of the excised material revealed tree-like growths with hyperplastic, stratified, squamous epithelium showing hyperkeratosis and parakeratosis. There was a distinct demarcation between the epithelium and the stroma, the latter containing a moderate number of lymphocytes and plasma cells. Pathological diagnosis was condyloma acuminatum. In December the papillary lesions recurred in the vulva and around the external urethra and the anus. In the central wall of the bladder, a few centimeters from the inner urethral orifice, urethroscopy revealed a low papillary tumor about 1 cm. in diameter. In the trigone, immediately inside the urethra, a more projecting and sessile lesion was found (fig. 1, A). Small papillary growths also were demonstrated in the urethra. A biopsy from 1 of the vesical lesions revealed condyloma acuminatum. The bladder lesions were excised by transurethral electroresection and the urethral lesions were carefully coagulated as were the vulvar and perianal growths. Microscopic examination of the vesical lesions showed a papillomatous pattern of condyloma acuminatum with squamous epithelium and inflammatory cells in the epithelium and stroma (fig. 1, B). A similar histologic picture was obtained at examination of a condyloma acuminatum from the vulva. At repeat followup visits recurrent lesions were coagulated in the urethra and vulva but recurrence was never seen in the bladder. To avoid scarring care was taken at coagulation in the urethra not to make the fulguration too deep. Not until
January 1974 was the patient free from recurrence and has remained so at repeat followup visits. There has been no sign of urethral stricture. Case 2. A woman born in 1932 had uremia owing to chronic pyelonephritis. In May 1967, before hemodialysis treatment became necessary, she received a kidney transplant from a brother. Necrosis of the ureter necessitated another operation; otherwise the postoperative period was uncomplicated. Renal function has been normal without signs of allograft rejection. The woman has been given standard immunosuppressive treatment with prednisolone and azathioprine. In November the patient complained of itching in the vulva and around the anus, where she also noted rapidly increasing growths. Examination in January 1968 revealed multiple large papillomatous tumors around the anus and smaller growths in the vulva and vagina. The lesions were partly excised by sharp excision and partly fulgurated. Pathological diagnosis was condyloma acuminatum (fig. 2). In February recurrent lesions in the vulva and the perianal region were treated with podophyllin, sharp excision and electrocoagulation. Cystoscopy revealed 2 cm. papillary lesions in the trigone. These lesions showed the same characteristics as those of the vulva and were treated by transurethral electrocoagulation. During the following years the patient was treated with podophyllin and electrocoagulation for recurrent lesions in the vulva and the perianal region but no recurrence was demonstrated in the bladder. Since 1972 no recurrence has been observed. DISCUSSION
Condyloma acuminatum is a verrucose lesion of squamous epithelium caused a virus. 3 Intranuclear virus particles have been identified by the in sections of condyloma acuminatum specimens. ,-s Transmission has been inoculation of sterile filtrates of wart material. 7 • 8 proved Condyloma acuminatum is commonly found on the penis, labia and around the anus. There have been several reports of condyloma acuminatum involving the urethra in male and female patients. •- 11 Only 4 reports of condylorna acuminatum in the bladder have been found in the literature'· 2 • 12 and all were giant condylomas, that is so-called Buschke-Loewenstein tumors. 13 One major difference between simple and giant condylomas is that simple condylomas, as in our 2 cases, remain superficial sparing the underlying tissue, while giant condylomas consistently penetrate underlying tissue resembling squamous cell carcinoma. Histopathologically, the lesions in the bladders of our 2 cases consisted of papillary structures covered by squamous cell epithelium with hyperkeratosis and parakeratosis. The metaplasia of the bladder epithelium from its normal transitional cell type to the squamous cell type may have been the result of the virus infection in these cases. The growth and type of epithelium that build up these growths differentiate them from
Accepted for publication August 22, 1975. 535
536
PETTERSSON, HANSSON AND BLOHME
FIG. 1. Case 1, A, photograph taken through cystoscope of sessile papillomatous lesion from trigone. B, papillomatous pattern of condyloma acuminatum in bladder. Transitional cell epithelium of bladder is seen at bottom of photograph. Hematoxylin stain, reduced from x70.
FIG. 2. Case 2. Marked acanthosis as well as hyperkeratosis and parakeratosis of squamous epithelium is characteristic of condyloma acuminatum. A, hematoxylin stain, reduced from x70. B, hematoxylin stain, reduced from' x280.
the papillary epithelial tumors of the bladder. No histologic criteria of malignancy were found in these 2 cases. Both of our patients were on immunosuppressive treatment, which may well have contributed to the unusual spread of the disease. It is well known that the incidence of viral as well as fungal and protozoan infections is high among immunosuppressed patients and that some normally rather harmless infections in these patients sometimes take unusually serious and even fatal courses. 14- 16 Of our 2 patients, 1 also suffered common warts and the other contracted a herpes zoster infection some years later. The treatment of the bladder lesions of our 2 patients was transurethral electroresection and coagulation. Therapy was successful and no recurrences have been seen in the bladder. We believe that this treatment should be tried first and, therefore, do not share the opinion of Kleiman and Lancaster that condyloma acuminatum of the bladder should be considered malignant by position, indicating an early radical operation. 1 A pathological examination of the resected specimens should always be made to exclude papillary epithelial tumors of the bladder. The patients also should be examined repeatedly for several years. Recently, excellent results have been reported on the use of an autogenous vaccine. 3 This therapy should be kept in mind in resistant cases before a radical excision is performed. REFERENCES
1. Kleiman, H. and Lancaster, Y.: Condyloma acuminata of the
bladder. J. Urol., 88: 52, 1962. 2. Lewis, H. Y., Wolf, P. L. and Pierce, J.M.: Condyloma acuminatum of the bladder. J. Urol., 88: 248, 1962. 3. Powell, L. C., Jr.: Condyloma acuminatum. Clin. Obst. Gynec., 15: 948, 1972.
4. Stoppelli, I.: Ultrastructural considerations on the presence of virus-like particles in condyloma acuminatum. Attualita Ostet. Ginec., 11: 431, 1965. 5. Dunn, A. E. and Ogilvie, M. M.: Intranuclear virus particles in human genital wart tissue: observations on the ultrastructure of the epidermal layer. J. Ultrastruct. Res., 22: 282, 1968. 6. Oriel, J. D. and Almeida, J. D.: Demonstration of virus particles in human genital warts. Brit. J. Vener. Dis., 46: 37, 1970. 7. Biberstein, H.: Immunization therapy of warts. Arch. Dermat. Syph., 50: 12, 1944. 8. Blank, H., Buerk, M. S. and Weidman, F.: Nature of the inclusion body of verruca vulgaris: a histochemical study of nucleotids. J. Invest. Dermat., 16: 19, 1951. 9. Gartman, E.: Intraurethral verruca acuminata in men. J. Urol., 75: 717, 1956. 10. Lindner, H.J. and Pasquier, C. M., Jr.: Condylomata acuminata of the urethra. J. Urol., 72: 875, 1954. 11. Dretler, S. P. and Klein, L. A.: The eradication of intraurethral condyloma acuminata with 5 per cent 5-fluorouracil cream. J. Urol., 113: 195, 1975. 12. Hotchkiss, R. S. and Rouse, A. J .: Papillomatosis of the bladder and ureters, preceded by condyloma acuminata of the vulva: a case report. J. Urol., 100: 723, 1968. 13. Loewenstein, L. W.: Carcinoma-like condylomata acuminata of the penis. Med. Clin. N. Amer., 23: 789, 1939. 14. Rifkind, D., Marchioro, T. L., Schneck, S. A. and Hill, R. B., Jr.: Systemic fungal infections complicating renal transplantation and immunosuppressive therapy: clinic, microbiologic, neurologic and pathologic features. Amer. J. Med., 43: 28, 1967. 15. Spencer, E. S. and Andersen, H.K.: Clinically evident, non-terminal infections with herpesviruses and the wart virus in immunosuppressed renal allograft recipients. Brit. Med. J ., 1: 251, 1970. 16. Simmons, R. L., Lopez, C., Balfour, H., Jr., Kalis, J., Rattazzi, L. C. and Najarian, J. S.: Cytomegalovirus: clinical virological correlations in renal transplant recipients. Ann. Surg., 180: 623, 1974.