CASE REPORTS
INTRAVESICAL CONDYLOMA ACUMINATUM WITH P R O G R E S S I O N TO V E R R U C O U S C A R C I N O M A ALEX G. BATTA, M.D. DONALD E. ENGEN, M.D. HERBERT M. REIMAN, M.D. R. K. WINKELMANN, M.D., PI~.D. From the Departments of Urology and Dermatology, and the Section of Surgical Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
-Condyloma acuminatum is a common form of venereal disease. Most patients with acuminata suffer from only the local cosmetic and irritative effects of the lesions. Few progression to aggressive, regionally distributed lesions that can be life-threatening. !forty-three-year-old white woman who had a seventeen-year history of scleroderma ~ical and intravesical condylomata acuminata. During two years of conservative with transurethral excision, electrocoagulation, and intravesical chemotherapy, the ~ssed to involve the entire bladder and resulted in obstructive renal insufficiency that erior exenteration and urinary diversion. The natural history of the disease is d the relevant literature is reviewed.
Lcuminatum is a common form of ase caused by human papilloma t 11) 1,2 that affects the mucocuta~s about the oral, perianal, and It is known to affect the urethra ,quently. Intravesical lesions have d to be rare. The verrucous ap:he disease bears a close similarity ae giant condyloma of Buschkerod, indeed, may be difficult to a an isolated pathologic specimen. of even simple condyloma may exasperating, but intravesieal le; not controlled at their onset can ~rapeutic enigma and may evena radical surgical procedure. Case Report tee-year-old white woman with a lr history of scleroderma was evalUated at our institution regarding management ~f persistent condylomata acuminata of the external genitalia and lower urinary tract.
The scleroderma, diagnosed when the patient was twenty-six years old, had been aggressive with widespread cutaneous and systemic manifestations, requiring corticosteroids, potassium aminobenzoate (Potaba), and multiple operations to relieve contractures and replace diseased articulations. At forty-one years of age, she began to have difficulty with persistent urinary tract infections. Subsequent urologic investigation had revealed multiple papillary lesions around the vaginal introitus, urethral meatus, trigone, and base of the bladder. Results of biopsies of the intravesical and extravesical lesions were consistent with condylomata acuminata. After a short trial of conservative therapy consisting of transurethral resection and electrocoagulation had proved unsuccessful, a radical surgical procedure had been recommended. At this point, the patient came to our institution for further investigation. The initial physical examination revealed the effects of severe scleroderma. The external
i
iRoLocy /
NOVEMBER 1990
/
VOLUME XXXVI, NUMBER 5
457
FIGURE1. Condylomata acuminata, characterized by benign squamous proliferation with numerous intraepithelial stromal papillae containing thinwalled vessels and connective tissue (hematoxylin and eosin; original magnification × 40). genitalia had condylomata acuminata involving the urethral meatus, left labia majora, and introitus. The serum ereatinine level was 0.8 rng/dL; an excretory urogram showed normal upper urinary tracts. After treatment of a urinary tract infection (group D streptococcus), cystoscopy showed eondylomatous lesions involving the trigone, base of the bladder, and half of the right and left lateral walls. Results of multiple bladder biopsies showed histologic changes consistent with the diagnosis of eondylomata aeuminata (Fig. 1). A program of regular eystoseopic examinations and high doses of vitamins A and E was begun. After six months, the cutaneous manifestations of the seleroderma had improved, but cystoscopy revealed continuance of the eondylomatous lesions throughout the bladder. Trials of intravesical chemotherapy eonsisting of thiotepa (60 mg in 60 mL of sterile water every other week for 2 months) followed by 5fluorouracil (1,000 mg in 20 mL of sterile water weekly for 3 months) elicited only a slight response. During this time, the serum ereatinine level remained stable. The patient returned for a follow-up examination at the conclusion of the intravesieal chemotherapy. The serum creatinine level had risen to 1.6 mg/dL. An excretory urogram showed bilateral pyeloealieetasis and ureterectasis down to the level of the ureterovesieal junction with a delayed nephrogram on the left (Fig. 2). Cystoseopy revealed that the bladder mueosa was completely replaced by the eondylomatous lesions. Multiple deep biopsy specimens from the bladder were consistent with
458
FIGURE 2. Excretory urogram showing bilate pyelocaliectasis and ureterectasis down io level ureteral vesical iunction with delayed nephrogr~ on left.
FIGURE 3. Computed tomographic scan marked thickening of bladder wall with i mass arising from posterior margin. condylomata aeuminata. A preoperative c, puterized tomographie scan revealed maI thickening of the bladder wall with a lobul-" mass arising from its posterolateral margin. base of the bladder appeared to be extensi, involved. The disease also extended beyond bladder to involve the uterus and surround: soft tissue (Fig. 3). The findings were discussed with the pati, and an anterior exenteration with ileal conc
UROLOGY
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NOVEMBER 1990
/
VOLUME XXXVI,
Ecur~ 4. Bladder, opened anteriorly, shows vericous, condylomatous excrescences over entire minal sur]ace.
Lrinary diversion was performed. The bladder howed extensive involvement, with eondyloaatous lesions covering its entire surface (Fig. :), Grossly, the lesion penetrated into the deep auscle of the superior and posterior walls, with icute inflammation and abscess formation disecting posteriorly around both ureters, causing aarked stenosis with partial obstruction. Histologically, the squamous component iniltrated the muscularis as broad, pushing ilands of squamous cells without a central vasular and connective tissue core (Fig. 5A). Also, are foci of cellular atypia were among other, aore regular squamous cells deep in the invaive region (Fig. 5B). These findings led to the agnosis of verrucous carcinoma. The vagina nd cervix showed widespread, more superficial verrucous changes with no direct extension tom the bladder. i Follow-up examinations at six and twelve nonths showed the scleroderma to be stable, md no evidence of recurrent pelvic disease was Ound.
~
Comment Condylomata acuminata have been known medical science for many years and persist day as a common problem. Involvement of e urinary tract is considered rare. The first se of urethral involvement was reported in 191 by Coldenberg2 Kleiman and Lancaster 4 timated that 5 percent of all cases of condyloata acuminata involving the external genitawould result in involvement of the urinary act, but estimates as high as 23 percent are /
NOVEMBER 1990
/
found in the literature. 5 In their review, Kleiman and Lancaster* found that the disease was most commonly limited to the external urethral meatus or distal urethra, rarely involved the entire urethra, and never involved only the posterior urethra. In 1944 Culp and Kaplan ~ reported the successful treatment of condylomata acuminata with topically applied podophyllin; since that time, this agent, in addition to surgical excision and electrocoagulation, has remained a mainstay of medical management. Buschke in 1896 and later Buschke and L6wenstein in 1925, 7 described a more aggressive variety of "condyloma-like" lesion that affected the external genitalia. Variously, this neoplasm has been called giant c o n d y l o m a acuminatum, Buschke-L6wenstein tumor, or carcinoma-like condyloma. Histologically, its appearance was similar to the less aggressive condyloma aeuminatum; clinically, however, it was more virulent. It grew downward by pushing relentlessly against the basement membrane and penetrating the underlying tissue along a well-demarcated perimeter. No areas of stromal invasion or infiltration could be found, and metastasis was never noted. The cells themselves showed no evidence of anaplasia and typically were said to be "benignly hyperplastic." The lesions were unresponsive to topical therapy with podophyllin; because of their recurrent and aggressive nature, extensive surgical excision proved to be the best means of control. In 1948 Ackerman8 described a neoplasm that he called verrucous carcinoma. It is a distinct variant of epidermoid carcinoma known to affect the oral cavity and less frequently the larynx, nasal fossa, glans penis, scrotum, vulva, vagina, and perineum. He described four major characteristics, which are identical to those of the giant condyloma of Buschke and L6wenstein: an exophytic lesion with multiple filiform or warty superficial projections made up of w e l l - d i f f e r e n t i a t e d squamous epithelium throughout, whose cellular structure showed minimal evidence of anaplasia and whose aggressive growth was along a well-defined margin rather than by single-cell infiltration. The only histologic feature that distinguishes Ackerman's tumor from simple condyloma acuminatum is the absence of connective tissue stroma within the papillary fronds and focal nuclear atypia. Anaplastic degeneration or transformation has been reported to occur in both condyloma
VOLUME XXXVI, NUMBER 5
459
a e u m i n a t u m and giant condyloma of BuschkeL6wenstein. 9 In 1974 Kovi, Tillman, and Lee 9 cited the rarity of this occurrence. They believed that carcinomas developing from condylomata acuminata are basically different from those arising from giant condyloma and that g i a n t c o n d y l o m a or v e r r u c o u s c a r c i n o m a should be considered malignant from its inception whereas carcinomas arising from condylom a t a acuminata are believed to succeed the original disease. In 1966 Kraus and Perez-Mesa ~° studied 105 c a s e s of verrueous carcinoma, 12 of which in-
460
volved the external verrucous carcinom sions described by some forty years beJ verrucous carcinom lesions have been c( ties. In the study c l y m p h node metast stances in which it was secondary to m,' primary disease. D: found. Typically, tt 5 - f l u o r o u r a e i l prc
UROLOGY
/
NOVEMBER 199C
i~trolling the lesion. The only satisfactory rejLlts occurred with extensive surgical excision, ut recurrences were common and necessitated igilant follow-up. Intravesieal lesions characteristic of eondy~mata acuIninata or verrueous carcinoma or oth are relatively rare. A review of the literaire illustrates the confusion that exists in the ~,rminology used to refer to such lesions. Most ases can be classified in one of two (1) those associated with sehistosotion, and (9.) those in which no paraement can be detected. E1 Sebai et al. 11 described verrueous among patients in Cairo, Egypt, amented history of bilharzial cystitis. carcinoma accounted for 73.3 perbladder neoplasms. Of particular ine 9.2 patients with verrueous earAs m e n t i o n e d , all p a t i e n t s h a d bilharzial cystitis. Of the 22 patients eous carcinoma, 19 had no other aspes of bladder cancer, and the 3 reatients presented with focal changes ]er overwhelmingly occupied by orIdular infiltrating squamous earl this isolated population, verrueous eareinoma constituted 3.4 percent of 'tumors. In 1981 E1-Bolkainy et al.'2 a similar population consisting of ,rots from Egypt who were treated for of the bladder. Of this group, 33 had carcinoma, 32 of whom had schisto',in the bladder. ltment of choice in both studies was iysteetomy with urinary diversion. Both groups i~ investigators believed that chronic irritation Jf the bladder urothelium was an important ~ctor in the development of verrueous eari~oma. This conclusion was in agreement with ~at of other investigators. 1°,13 T h e other case reports in the literature had O evidence of schistosomal bladder involve~nt. To date, 16 patients with either intravesi~i condylomata acuminata or verrueous carinoma have been described. The first ease was !~cribed by Kleiman and Lancaster in 1962. 4 )fthe 16 patients, 10 were female and 6 were aale (Table I). Fourteen patients reported a ~Story of documented chronic urinary tract ineetions. In 12 patients, eondyloma aeumina:present as an external genital lesion discovery of intravesical involve~-ls.~l-~4 Superficial biopsy specimens bladder showed histologic charaeteris-
/
NOVEMBER 1990
/
tics identical to those of the lesions involving the external genitalia. Three imrnunosuppressed renal transplant recipients had focal intravesical lesions less than 2 crn in diameter. 18.~1Eight patients with extensive bladder involvement were treated with eystectomy and urinary diversion. 4,14-1v,19'23 One patient with localized disease involving a bladder diverticulum was treated with partial eystectomy. 13 Four patients with limited bladder involvement (< 3 crn) responded to transurethral resection and electrocoagulation, 1s,2°,~2 and 1 patient with recurrenees had multiple transurethral resections to control disease. 21 The most recently described patient with intravesical condylomata acuminata, a thirty-three-year-old black man, underwent partial resection. After being lost to follow-up for two years, the patient returned with extensive intravesical disease with an apparent focus of undifferentiated carcinoma that proved to be metastatic and subsequently led to death from earcinomatosis.18 In all cases of extensive bladder involvement, local therapy was unsuccessful. In these cases, the pathologic diagnosis at the time of cysteetorny was either giant eondyloma or BuschkeL6wenstein tumor. According to the interpretation of Kraus and Perez-Mesa, 1° at least 10 of the 16 cases could be better described as verrueous carcinoma. Histologically, none of the lesions had evidence of anaplasia at the time of the original diagnosis and therefore could have been called "benignly hyperplastic" if it were not for their clinical presentation. Only 1 patient had evidence of anaplastie degeneration five years after the initial diagnosis. 25 Conservative therapy had been tried in every case, and the results were consistently poor. Podophyllin and other surface agents such as thiotepa and 5-fluorouracil proved to be of little benefit. All patients who underwent extensive surgical excision remained free of recurrent disease and enjoyed an excellent prognosis. In 1972 Powell ~6 described the use of an autogenous vaccine for 24 resistant eases of extravesieal c o n d y l o m a t a a e u m i n a t a and reported excellent results. The vaccine was ineffective in the only ease of verrueous carcinoma reported in his study. In 1 ease reported by Bissada, Cole, and Fried iv the injection of bacillus Calmette-Gu6rin directly into accessible lesions resulted in extensive sloughing of the warty lesions and no recurrences. Radiation therapy also has been tried, and the results have been mixed. The most extensive
VOLUME XXXVI, NUMBER 5
461
INTRAVESICAL CONDYLOMA ACUMINATUM WITH P R O G R E S S I O N TO V E R R U C O U S C A R C I N O M A ALEX G. BATTA, M.D. DONALD E. ENGEN, M.D. HERBERT M. REIMAN, M.D. R. K. WINKELMANN, M.D., PI~.D. From the Departments of Urology and Dermatology, and the Section of Surgical Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
-Condyloma acuminatum is a common form of venereal disease. Most patients with acuminata suffer from only the local cosmetic and irritative effects of the lesions. Few progression to aggressive, regionally distributed lesions that can be life-threatening. !forty-three-year-old white woman who had a seventeen-year history of scleroderma ~ical and intravesical condylomata acuminata. During two years of conservative with transurethral excision, electrocoagulation, and intravesical chemotherapy, the ~ssed to involve the entire bladder and resulted in obstructive renal insufficiency that erior exenteration and urinary diversion. The natural history of the disease is d the relevant literature is reviewed.
Lcuminatum is a common form of ase caused by human papilloma t 11) 1,2 that affects the mucocuta~s about the oral, perianal, and It is known to affect the urethra ,quently. Intravesical lesions have d to be rare. The verrucous ap:he disease bears a close similarity ae giant condyloma of Buschkerod, indeed, may be difficult to a an isolated pathologic specimen. of even simple condyloma may exasperating, but intravesieal le; not controlled at their onset can ~rapeutic enigma and may evena radical surgical procedure. Case Report tee-year-old white woman with a lr history of scleroderma was evalUated at our institution regarding management ~f persistent condylomata acuminata of the external genitalia and lower urinary tract.
The scleroderma, diagnosed when the patient was twenty-six years old, had been aggressive with widespread cutaneous and systemic manifestations, requiring corticosteroids, potassium aminobenzoate (Potaba), and multiple operations to relieve contractures and replace diseased articulations. At forty-one years of age, she began to have difficulty with persistent urinary tract infections. Subsequent urologic investigation had revealed multiple papillary lesions around the vaginal introitus, urethral meatus, trigone, and base of the bladder. Results of biopsies of the intravesical and extravesical lesions were consistent with condylomata acuminata. After a short trial of conservative therapy consisting of transurethral resection and electrocoagulation had proved unsuccessful, a radical surgical procedure had been recommended. At this point, the patient came to our institution for further investigation. The initial physical examination revealed the effects of severe scleroderma. The external
i
iRoLocy /
NOVEMBER 1990
/
VOLUME XXXVI, NUMBER 5
457
FIGURE1. Condylomata acuminata, characterized by benign squamous proliferation with numerous intraepithelial stromal papillae containing thinwalled vessels and connective tissue (hematoxylin and eosin; original magnification × 40). genitalia had condylomata acuminata involving the urethral meatus, left labia majora, and introitus. The serum ereatinine level was 0.8 rng/dL; an excretory urogram showed normal upper urinary tracts. After treatment of a urinary tract infection (group D streptococcus), cystoscopy showed eondylomatous lesions involving the trigone, base of the bladder, and half of the right and left lateral walls. Results of multiple bladder biopsies showed histologic changes consistent with the diagnosis of eondylomata aeuminata (Fig. 1). A program of regular eystoseopic examinations and high doses of vitamins A and E was begun. After six months, the cutaneous manifestations of the seleroderma had improved, but cystoscopy revealed continuance of the eondylomatous lesions throughout the bladder. Trials of intravesical chemotherapy eonsisting of thiotepa (60 mg in 60 mL of sterile water every other week for 2 months) followed by 5fluorouracil (1,000 mg in 20 mL of sterile water weekly for 3 months) elicited only a slight response. During this time, the serum ereatinine level remained stable. The patient returned for a follow-up examination at the conclusion of the intravesieal chemotherapy. The serum creatinine level had risen to 1.6 mg/dL. An excretory urogram showed bilateral pyeloealieetasis and ureterectasis down to the level of the ureterovesieal junction with a delayed nephrogram on the left (Fig. 2). Cystoseopy revealed that the bladder mueosa was completely replaced by the eondylomatous lesions. Multiple deep biopsy specimens from the bladder were consistent with
458
FIGURE 2. Excretory urogram showing bilate pyelocaliectasis and ureterectasis down io level ureteral vesical iunction with delayed nephrogr~ on left.
FIGURE 3. Computed tomographic scan marked thickening of bladder wall with i mass arising from posterior margin. condylomata aeuminata. A preoperative c, puterized tomographie scan revealed maI thickening of the bladder wall with a lobul-" mass arising from its posterolateral margin. base of the bladder appeared to be extensi, involved. The disease also extended beyond bladder to involve the uterus and surround: soft tissue (Fig. 3). The findings were discussed with the pati, and an anterior exenteration with ileal conc
UROLOGY
/
NOVEMBER 1990
/
VOLUME XXXVI,
Ecur~ 4. Bladder, opened anteriorly, shows vericous, condylomatous excrescences over entire minal sur]ace.
Lrinary diversion was performed. The bladder howed extensive involvement, with eondyloaatous lesions covering its entire surface (Fig. :), Grossly, the lesion penetrated into the deep auscle of the superior and posterior walls, with icute inflammation and abscess formation disecting posteriorly around both ureters, causing aarked stenosis with partial obstruction. Histologically, the squamous component iniltrated the muscularis as broad, pushing ilands of squamous cells without a central vasular and connective tissue core (Fig. 5A). Also, are foci of cellular atypia were among other, aore regular squamous cells deep in the invaive region (Fig. 5B). These findings led to the agnosis of verrucous carcinoma. The vagina nd cervix showed widespread, more superficial verrucous changes with no direct extension tom the bladder. i Follow-up examinations at six and twelve nonths showed the scleroderma to be stable, md no evidence of recurrent pelvic disease was Ound.
~
Comment Condylomata acuminata have been known medical science for many years and persist day as a common problem. Involvement of e urinary tract is considered rare. The first se of urethral involvement was reported in 191 by Coldenberg2 Kleiman and Lancaster 4 timated that 5 percent of all cases of condyloata acuminata involving the external genitawould result in involvement of the urinary act, but estimates as high as 23 percent are /
NOVEMBER 1990
/
found in the literature. 5 In their review, Kleiman and Lancaster* found that the disease was most commonly limited to the external urethral meatus or distal urethra, rarely involved the entire urethra, and never involved only the posterior urethra. In 1944 Culp and Kaplan ~ reported the successful treatment of condylomata acuminata with topically applied podophyllin; since that time, this agent, in addition to surgical excision and electrocoagulation, has remained a mainstay of medical management. Buschke in 1896 and later Buschke and L6wenstein in 1925, 7 described a more aggressive variety of "condyloma-like" lesion that affected the external genitalia. Variously, this neoplasm has been called giant c o n d y l o m a acuminatum, Buschke-L6wenstein tumor, or carcinoma-like condyloma. Histologically, its appearance was similar to the less aggressive condyloma aeuminatum; clinically, however, it was more virulent. It grew downward by pushing relentlessly against the basement membrane and penetrating the underlying tissue along a well-demarcated perimeter. No areas of stromal invasion or infiltration could be found, and metastasis was never noted. The cells themselves showed no evidence of anaplasia and typically were said to be "benignly hyperplastic." The lesions were unresponsive to topical therapy with podophyllin; because of their recurrent and aggressive nature, extensive surgical excision proved to be the best means of control. In 1948 Ackerman8 described a neoplasm that he called verrucous carcinoma. It is a distinct variant of epidermoid carcinoma known to affect the oral cavity and less frequently the larynx, nasal fossa, glans penis, scrotum, vulva, vagina, and perineum. He described four major characteristics, which are identical to those of the giant condyloma of Buschke and L6wenstein: an exophytic lesion with multiple filiform or warty superficial projections made up of w e l l - d i f f e r e n t i a t e d squamous epithelium throughout, whose cellular structure showed minimal evidence of anaplasia and whose aggressive growth was along a well-defined margin rather than by single-cell infiltration. The only histologic feature that distinguishes Ackerman's tumor from simple condyloma acuminatum is the absence of connective tissue stroma within the papillary fronds and focal nuclear atypia. Anaplastic degeneration or transformation has been reported to occur in both condyloma
VOLUME XXXVI, NUMBER 5
459
a e u m i n a t u m and giant condyloma of BuschkeL6wenstein. 9 In 1974 Kovi, Tillman, and Lee 9 cited the rarity of this occurrence. They believed that carcinomas developing from condylomata acuminata are basically different from those arising from giant condyloma and that g i a n t c o n d y l o m a or v e r r u c o u s c a r c i n o m a should be considered malignant from its inception whereas carcinomas arising from condylom a t a acuminata are believed to succeed the original disease. In 1966 Kraus and Perez-Mesa ~° studied 105 c a s e s of verrueous carcinoma, 12 of which in-
460
volved the external verrucous carcinom sions described by some forty years beJ verrucous carcinom lesions have been c( ties. In the study c l y m p h node metast stances in which it was secondary to m,' primary disease. D: found. Typically, tt 5 - f l u o r o u r a e i l prc
UROLOGY
/
NOVEMBER 199C
i~trolling the lesion. The only satisfactory rejLlts occurred with extensive surgical excision, ut recurrences were common and necessitated igilant follow-up. Intravesieal lesions characteristic of eondy~mata acuIninata or verrueous carcinoma or oth are relatively rare. A review of the literaire illustrates the confusion that exists in the ~,rminology used to refer to such lesions. Most ases can be classified in one of two (1) those associated with sehistosotion, and (9.) those in which no paraement can be detected. E1 Sebai et al. 11 described verrueous among patients in Cairo, Egypt, amented history of bilharzial cystitis. carcinoma accounted for 73.3 perbladder neoplasms. Of particular ine 9.2 patients with verrueous earAs m e n t i o n e d , all p a t i e n t s h a d bilharzial cystitis. Of the 22 patients eous carcinoma, 19 had no other aspes of bladder cancer, and the 3 reatients presented with focal changes ]er overwhelmingly occupied by orIdular infiltrating squamous earl this isolated population, verrueous eareinoma constituted 3.4 percent of 'tumors. In 1981 E1-Bolkainy et al.'2 a similar population consisting of ,rots from Egypt who were treated for of the bladder. Of this group, 33 had carcinoma, 32 of whom had schisto',in the bladder. ltment of choice in both studies was iysteetomy with urinary diversion. Both groups i~ investigators believed that chronic irritation Jf the bladder urothelium was an important ~ctor in the development of verrueous eari~oma. This conclusion was in agreement with ~at of other investigators. 1°,13 T h e other case reports in the literature had O evidence of schistosomal bladder involve~nt. To date, 16 patients with either intravesi~i condylomata acuminata or verrueous carinoma have been described. The first ease was !~cribed by Kleiman and Lancaster in 1962. 4 )fthe 16 patients, 10 were female and 6 were aale (Table I). Fourteen patients reported a ~Story of documented chronic urinary tract ineetions. In 12 patients, eondyloma aeumina:present as an external genital lesion discovery of intravesical involve~-ls.~l-~4 Superficial biopsy specimens bladder showed histologic charaeteris-
/
NOVEMBER 1990
/
tics identical to those of the lesions involving the external genitalia. Three imrnunosuppressed renal transplant recipients had focal intravesical lesions less than 2 crn in diameter. 18.~1Eight patients with extensive bladder involvement were treated with eystectomy and urinary diversion. 4,14-1v,19'23 One patient with localized disease involving a bladder diverticulum was treated with partial eystectomy. 13 Four patients with limited bladder involvement (< 3 crn) responded to transurethral resection and electrocoagulation, 1s,2°,~2 and 1 patient with recurrenees had multiple transurethral resections to control disease. 21 The most recently described patient with intravesical condylomata acuminata, a thirty-three-year-old black man, underwent partial resection. After being lost to follow-up for two years, the patient returned with extensive intravesical disease with an apparent focus of undifferentiated carcinoma that proved to be metastatic and subsequently led to death from earcinomatosis.18 In all cases of extensive bladder involvement, local therapy was unsuccessful. In these cases, the pathologic diagnosis at the time of cysteetorny was either giant eondyloma or BuschkeL6wenstein tumor. According to the interpretation of Kraus and Perez-Mesa, 1° at least 10 of the 16 cases could be better described as verrueous carcinoma. Histologically, none of the lesions had evidence of anaplasia at the time of the original diagnosis and therefore could have been called "benignly hyperplastic" if it were not for their clinical presentation. Only 1 patient had evidence of anaplastie degeneration five years after the initial diagnosis. 25 Conservative therapy had been tried in every case, and the results were consistently poor. Podophyllin and other surface agents such as thiotepa and 5-fluorouracil proved to be of little benefit. All patients who underwent extensive surgical excision remained free of recurrent disease and enjoyed an excellent prognosis. In 1972 Powell ~6 described the use of an autogenous vaccine for 24 resistant eases of extravesieal c o n d y l o m a t a a e u m i n a t a and reported excellent results. The vaccine was ineffective in the only ease of verrueous carcinoma reported in his study. In 1 ease reported by Bissada, Cole, and Fried iv the injection of bacillus Calmette-Gu6rin directly into accessible lesions resulted in extensive sloughing of the warty lesions and no recurrences. Radiation therapy also has been tried, and the results have been mixed. The most extensive
VOLUME XXXVI, NUMBER 5
461
