A case of condyloma acuminatum of the bladder concurrently diagnosed with urothelial carcinoma

Introduction Condyloma acuminatum usually occurs in the external genitalia and rarely in the bladder mucosa. Here, we report a case of condyloma acuminatum of the bladder that was detected concurrently with urothelial carcinoma. Case presentation A 42‐year‐old man was referred to our urology department with positive urine cytology for urothelial carcinoma. Cystoscopy revealed a broad‐base nonpapillary bladder tumor. The patient underwent a transurethral resection of the bladder tumor. Pathological examination revealed urothelial carcinoma, high‐grade pT1, and concurrent resection of condyloma acuminatum. DNA was extracted from the paraffin‐embedded transurethral resection of the bladder tumor tissue specimens. HPV11 was detected in condylomas by PCR and in situ hybridization, whereas HPV was not detected in urothelial carcinomas. Conclusion We report a rare case of condyloma acuminatum of the bladder that was concurrently diagnosed with urothelial carcinoma from the same site.


Introduction
Condyloma acuminatum is a HPV infection resulting in the formation of a wart, and it is relatively common among young adults.The annual incidence of condyloma acuminatum ranges from 160 in Spain to 289 in the United Kingdom cases per 100 000 individuals. 1 The most common sites affected by condyloma acuminatum are the perianal area, perineum, labia, penis, anal canal, and vagina, and it rarely occurs in the bladder.Herein, we report a case of bladder condyloma acuminatum concurrently diagnosed with bladder cancer from the same site.

Case
A 42-year-old male presented to a nearby clinic complaining of macroscopic hematuria and pain during urination.The patient was in good condition and had no urinary infection.Urine cytology was positive for urothelial carcinoma, and the patient was referred to our hospital.The patient had no history of HPV infection but he had multiple heterosexual partners.The physical and laboratory findings were within normal limits.The patient was immunocompetent and was free from HIV infection.Cystoscopy revealed a broad-base nonpapillary bladder tumor (Fig. 1a,b).There were no findings in the urethra.Computed tomography examination showed no apparent metastasis of the bladder tumor.
Transurethral resection of the bladder tumor was performed, and histopathologic examination revealed high-grade, pT1 urothelial carcinoma (Fig. 2a).The resected specimen concurrently involved the condyloma acuminatum of the bladder.There was also a poorly dysmorphic, stratified squamous epithelium and a papillary lesion covered with a proliferating squamous epithelium.Binucleated cells and koilocytosis were observed, which may correspond to condyloma acuminatum (Fig. 2b,c).We extracted from the paraffinembedded TUR-Bt tissue specimens.HPV11 was detected in condyloma using PCR and in situ hybridization, whereas HPV was not detected in urothelial carcinoma (Fig. 2d).
The patient underwent 7 weeks of intravesical instillation of BCG.The second TUR-Bt was performed 3 months after the first cycle of BCG therapy.We did not detect residual urothelial carcinoma or condyloma acuminatum.However, about 6 months later, cystoscopy revealed mucosal irregularities and redness, and urine cytology was positive for urothelial carcinoma.The patient underwent TUR-Bt and the pathological diagnosis was high-grade urothelial carcinoma in situ.No recurrence of condyloma acuminatum was observed.We recommended radical cystectomy for a BCG refractory case, but the patient wished to avoid radical cystectomy and preserve sexual function.Therefore, we performed a second BCG intravesical instillation therapy.The patient is currently under careful follow-up.

Discussion
Condyloma acuminatum is relatively common but rarely involves the urethra or bladder. 2 Condyloma acuminatum is attributed to HPV infection.HPV types 6 and 11 account for most condyloma acuminatum cases.
Given the route of HPV transmission, sexual contact results in an HPV infection affecting the external genitalia.Moreover, the infection invades the urothelial epithelium of the bladder through the urethra. 3The occurrence of condyloma acuminatum of the urinary tract has been reported in immunosuppressive conditions, such as renal transplant recipient. 4In this case, he had multiple heterosexual partners, which could be considered a risk factor, but there were no  sexually transmitted infections or urethritis.The route of infection was unknown; however, a subclinical HPV infection was suspected.
Condyloma acuminatum has malignant potential.HPV can infect the cervix, oropharynx, anus, penis, vagina, and vulva.Worldwide, high-risk HPV covers 10% of all cancers, with an estimated 570 000 women and 60 000 men with HPVrelated cancer yearly. 5][8][9][10][11][12][13] A previous meta-analysis showed a significantly high association between HPV infection and bladder cancer, with HPV-16 being the most prevalent genotype in bladder cancer. 14On the other hand, two recent meta-analyses have shown conflicting results, one showing that HPV infection is not associated with bladder cancer (OR: 2.077, 95% CI: 0.940-4.587), 6hile the other reported a significant association between HPV infection and bladder cancer (OR: 7.8406, 95% CI: 4.343-14.16). 15owever, condyloma acuminatum can develop into SCC.Samarska et al. summarized 38 patients with condyloma acuminatum of the bladder, 17 of whom had SCC concurrently with condyloma acuminatum or within a year of diagnosis. 16lthough low-risk HPV (HPV 6/11) is known to have little association with SCC at head and neck, gynecology tract, and anal cancers, the study showed an association of condyloma acuminatum and SCC with low-risk HPV and high-risk HPV. 16Condyloma acuminatum of the bladder is associated with SCC of the bladder, regardless of the HPV subtype.The high affinity of HPV to differentiating squamous epithelium and the ability to evade immune responses may explain the mechanism of cancer development in the bladder epithelium. 15 meta-analysis demonstrated that the association between HPV and bladder cancer risk was highest among Asians (OR 6.289; 95% CI 2.167-18.250).6 In addition to geographical factors, age is also a risk factor for HPV-related cancer.Among bladder cancer patients, HPV-positive patients were younger than HPV-negative patients, with mean ages of 60.2 and 70.3 years, respectively.17 In this case, the direct relationship between condyloma acuminatum and urothelial carcinoma is unclear; however, Asian ethnicity and young age are consistent risk factors.

Conclusion
We report a rare case of condyloma acuminatum of the bladder that was concurrently diagnosed with urothelial carcinoma at the same site.We detected HPV DNA in condyloma acuminatum samples, but HPV DNA was not in urothelial carcinoma samples.No consensus exists on the surveillance of condyloma acuminatum of the bladder.Therefore, close and careful observation is necessary.

Fig. 1
Fig. 1 (a) Cystoscopy of the broad-base nonpapillary bladder tumor.(b) Narrow band imaging of the bladder tumor.