Pathology of Urinary Bladder Urothelial Papilloma

Updated: Jun 07, 2019
  • Author: Antonio Lopez-Beltran, MD, PhD; Chief Editor: Liang Cheng, MD  more...
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Urothelial papilloma is an uncommon benign exophytic neoplasm composed of a delicate fibrovascular core covered by normal-appearing urothelium. [1, 2]  The posterior or lateral walls close to the ureteric orifices and the urethra are the most common locations. [1, 3, 4, 5, 6]  

Urothelial papilloma has a low incidence, representing 1%-4% of bladder tumors. The male-to-female ratio is 1.9:1. These neoplasms tend to occur in younger patients and may be seen in children. [1, 7]

The risk factors for urothelial papilloma are similar to those of other urothelial neoplasms. Cigarette smoking and occupational exposure to aromatic amines are the most important among them. [2]

These benign tumors may recur but generally do not progress. [8, 9] Rare cases of progression have been described in association with immunosuppressive therapy. [5]



Clinical Features and Imaging

Hematuria is the most common presenting symptom in pediatric and adult patients. [7, 10] Most papillomas are single and occur in younger patients (mean age, 46 years; range, 22-89 years). [1, 4] Urothelial papilloma may recur; however, it does not progress. Aggressive behavior has been reported in a patient with urothelial papilloma who was receiving immunosuppressive therapy secondary to renal transplantation. [5] Urothelial papilloma may arise as a de novo neoplasm, or it may occur as a secondary papilloma in patients with a history of bladder cancer. [1, 2]


Gross and Microscopic Findings

Gross findings

Urothelial papillomas are delicate and small; the endoscopic appearance is identical to that of low-grade papillary neoplasms. [6, 9]

Microscopic findings

Tumor, node, metastasis (TNM) stage Ta applies (noninvasive) to urothelial papilloma. These neoplasms do not spread.

Urothelial papilloma shows discrete papillary fronds with occasional branching but without fusion; these are covered by normal urothelium (see the image below). [1, 2]

Urothelial papilloma of the bladder. The lesion is Urothelial papilloma of the bladder. The lesion is composed of a delicate fibrovascular core covered by normal-appearing urothelium.

The superficial (umbrella) cells are often prominent and may display increased cytoplasm, vacuolization, and degenerative nuclear atypia. Mitoses are absent or rare; if present, they are located in the basal cell layer. The stroma may show edema and/or lymphoid inflammatory cells. Rarely, urothelial papilloma extensively involves the mucosa, a phenomenon referred to as diffuse papillomatosis. [1, 6]



Urothelial papilloma shows low proliferation and uncommon p53 nuclear accumulation. Cytokeratin 20 expression is limited to the superficial (umbrella) cells, as is usual in normal urothelium. [11]

In a study of the immunohistochemical expression of cytokeratin 20, p53, and Ki-67 in a group of 20 urothelial papilloma cases and 30 noninvasive papillary neoplasms of low malignant potential (PNLMP) of the urinary bladder, Alrashidy et al concluded that the intense positivity of suspicious cells for at least one of these markers would confirm the presence of malignant changes and favors the diagnosis of carcinoma. [12] Of the 30 carcinoma cases, 40% showed strong reactivity for the entire panel, 53% reacted positively for two markers, and 7% reacted to only one marker. Only small percentages of urothelial papillomas were positive, and only weakly. [12]



Urothelial papillomas are diploid and show frequent FGFR3 mutation (seen in 75% of cases). One study found a comparable percentage of FGFR3 mutations in cases of papillary urothelial neoplasm of low malignant potential (PUNLMP) and low-grade papillary urothelial carcinoma. [4]

Williamson et al reported results that support the idea that mutations of the FGFR3 and TP53 genes are rare or absent in urothelial neoplasms of young patients. [13] In contrast, the study reported that chromosomal abnormalities detected by UroVysion fluorescence in situ hybridization are sometimes present in patients older than 19-20 years. The authors added that this finding supports the proposed hypothesis that an age of 19-20 years separates distinct molecular pathways of urothelial carcinogenesis. [13]

More recently, investigators reported that TERT promoter mutations are driver mutations in most urothelial cancers, including urothelial papilloma and PUNLMP. [14]