Pathology of Urinary Bladder Urothelial Papilloma 

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Urothelial papilloma is a benign exophytic neoplasm composed of a delicate fibrovascular core covered by normal-appearing urothelium. ^{[1, 2]}

Urothelial papilloma has a low incidence; it represents 1-4% of bladder tumors. The male-to-female ratio is 1.9:1. Urothelial papilloma tends to occur in younger patients and may be seen in children. ^[1]

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]

The posterior or lateral walls close to the ureteric orifices and the urethra are the most common locations. ^{[1, 3, 4, 5, 6]}

Hematuria is the most common presenting symptom. 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]}

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

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

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]}

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. ^[7]

Papillomas are diploid and show frequent FGFR3 mutation (seen in 75% of cases). A recent study found FGFR3 mutations in urothelial papilloma; a comparable percentage of mutations was seen in cases of papillary urothelial neoplasm of low malignant potential 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. In contrast, the study reported that chromosomal abnormalities detected by UroVysion fluorescence in situ hybridization are sometimes present in patients above 19-20 years of age. The authors added that this finding supports the recently proposed hypothesis that an age of 19-20 years separates distinct molecular pathways of urothelial carcinogenesis. ^[8]

TNM stage Ta applies (noninvasive). Urothelial papilloma does not spread.

Urothelial papilloma is a benign tumor that may recur but does not progress. Rare cases of progression have been described in association with immunosuppressive therapy. ^[5]

Cheng L, Darson M, Cheville JC, et al. Urothelial papilloma of the bladder. Clinical and biologic implications. Cancer. 1999 Nov 15. 86(10):2098-101. [Medline].

Montironi R, Lopez-Beltran A, Scarpelli M, Mazzucchelli R, Cheng L. Morphological classification and definition of benign, preneoplastic and non-invasive neoplastic lesions of the urinary bladder. Histopathology. 2008 Dec. 53(6):621-33. [Medline].

Epstein JI, Amin MB, Reuter VR, Mostofi FK. The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am J Surg Pathol. 1998 Dec. 22(12):1435-48. [Medline].

van Rhijn BW, Montironi R, Zwarthoff EC, Jobsis AC, van der Kwast TH. Frequent FGFR3 mutations in urothelial papilloma. J Pathol. 2002 Oct. 198(2):245-51. [Medline].

McKenney JK, Amin MB, Young RH. Urothelial (transitional cell) papilloma of the urinary bladder: a clinicopathologic study of 26 cases. Mod Pathol. 2003 Jul. 16(7):623-9. [Medline].

Lopez-Beltran A, Montironi R. Non-invasive urothelial neoplasms: according to the most recent WHO classification. Eur Urol. 2004 Aug. 46(2):170-6. [Medline].

Harnden P, Mahmood N, Southgate J. Expression of cytokeratin 20 redefines urothelial papillomas of the bladder. Lancet. 1999 Mar 20. 353(9157):974-7. [Medline].

Williamson SR, Wang M, Montironi R, Eble JN, Lopez-Beltran A, Zhang S, et al. Molecular characteristics of urothelial neoplasms in children and young adults: a subset of tumors from young patients harbors chromosomal abnormalities but not FGFR3 or TP53 gene mutations. Mod Pathol. 2014 Nov. 27 (11):1540-8. [Medline].

Antonio Lopez-Beltran, MD, PhD Professor of Anatomic Pathology, Unit of Anatomic Pathology, Department of Surgery, Cordoba University School of Medicine, Spain

Disclosure: Nothing to disclose.

Liang Cheng, MD Professor of Pathology and Urology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine; Chief, Genitourinary Pathology Service, Indiana University Health

Liang Cheng, MD is a member of the following medical societies: American Association for Cancer Research, American Urological Association, College of American Pathologists, United States and Canadian Academy of Pathology, International Society of Urological Pathology, Arthur Purdy Stout Society

Disclosure: Nothing to disclose.

Pathology of Urinary Bladder Urothelial Papilloma 

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