Inverted papilloma of the bladder: a review and an analysis of the recent literature of 365 patients

Objectives: Until the 1970s, inverted urothelial papilloma (IUP) of the bladder was generally regarded as a benign neoplasm. However, in the 1980s, several reported cases suggested the malignant potential of these papillomas, including cases with features indicative of malignancy, recurrent cases, and cases of IUP synchronous or metachronous with transitional cell carcinoma. The aim of this systematic review and analysis of the literature since 1990 to date is to contribute to unresolved issues regarding the biological behavior and prognosis of these neoplasms to establish some key points in the clinical and surgical management of IUP.

Materials and methods: Database searches yielded 109 references. Exclusion of irrelevant references left 10 references describing studies that fulfilled the predefined inclusion criteria.

Results: One problem regarding these neoplasms is the difficulty of obtaining a correct histopathologic diagnosis. The main differential diagnosis is endophytic urothelial neoplasia, including papillary urothelial neoplasia of low malignant potential or urothelial carcinoma of low or high grade, while other considerably rare differential diagnoses include nephrogenic adenoma, paraganglioma, carcinoid tumor, cystitis cystica, cystitis glandularis, and Brunn's cell nests. The size of the lesions ranged from 1 to 50 mm (mean 12.8 mm). Most cases occurred in the fifth and sixth decade of life. The mean age of affected patients was 59.3 years (range 20-88 years). Analysis of the literature revealed a strong male predominance with a male/female ratio of 5.8:1. The most commonly reported sites of IUP were the bladder neck region and trigone. Of 285 cases included in 8 studies, 12 cases (4.2%) were multiple. Out of the total of 348 patients, 6 patients (1.72%) had a previous history of transitional cell carcinoma of the urinary bladder, 5 patients (1.43%) had synchronous transitional cell carcinoma of the urinary bladder, and 4 patients (1.15%) had subsequent transitional cell carcinoma of the urinary tract. The time before recurrence was <45 months (range 5-45 months, mean 27.7 months) after surgery.

Conclusions: Inverted papilloma could be considered a risk factor for transitional cell carcinoma, and it is clinically prudent to exclude transitional cell cancer when it is diagnosed. Follow-up is needed if the histologic diagnosis is definitive or doubtful. We recommend 4-monthly flexible cystoscopy for the first year and then every 6 months for the subsequent 3 years. Routine surveillance of the upper urinary tract in cases of inverted papilloma of the lower part of the urinary tract is not deemed necessary.