Bladder & urothelial tract
Urothelial neoplasms - noninvasive
Urothelial papilloma
Author: Judy Sarungbam, M.D.
Editorial Board Member: Maria Tretiakova, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 25 August 2020
Last staff update: 25 August 2022
Copyright: 2003-2025, PathologyOutlines.com, Inc.
PubMed Search: Urothelial papilloma
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Sarungbam J. Urothelial papilloma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bladderpapilloma.html. Accessed January 1st, 2025.
Definition / general
- Papillary urothelial neoplasm characterized by delicate fibrovascular cores lined by urothelium of normal thickness and cytology
Essential features
- Rare papillary urothelial neoplasm with a benign clinical course: rare recurrence if completely excised
- Exophytic tumor composed of thin papillary fronds lined by prominent umbrella cells
- Should be distinguished from its morphologic mimics, including papillary urothelial neoplasm of low malignant potential (PUNLMP), urothelial carcinoma, polypoid cystitis and fibroepithelial polyp
Terminology
- Transitional cell papilloma
ICD coding
Epidemiology
- Rare urothelial neoplasm, comprises ~1% of all papillary bladder neoplasm
- Patients are generally younger than those with urothelial carcinoma
- Generally, < 50 years of age (Mod Pathol 2003;16:623)
- Can also be seen in children
- M:F - 1.9:1 (Cancer 1999;86:2098, Pathology 2014;46:37)
- Often presents as solitary lesion (Cancer 1999;86:2098)
- Usually presents de novo, also rarely seen in patients with other prior urothelial neoplasms (Mod Pathol 2003;16:623)
Sites
- Any site in the bladder, most commonly the posterior or lateral wall (Mod Pathol 2003;16:623)
Etiology
- Unknown at this time but often associated with KRAS / HRAS mutations
Clinical features
- Painless hematuria, gross or microscopic
Diagnosis
- Imaging: ultrasound (USG)
- Cystoscopy: papillary / elevated lesions, variable size, often unifocal (Mod Pathol 2003;16:623)
- Biopsy / transurethral resection of bladder tumor needed for diagnosis
Laboratory
- Urine cytology is negative for malignant cells
Radiology description
- Ultrasound: endovesical papillary lesion
Radiology images
Images hosted on other servers:
USG finding - solitary polypoid lesion
Lobulated soft-tissue mass
Prognostic factors
- Recurrences have been reported in 0 - 8.8% (Mod Pathol 2000;13:1315, Am J Surg Pathol 2004;28:1615, Mod Pathol 2003;16:623)
- Reported progression to higher grade lesion 0 - 8.8% but in fact extremely uncommon (Am J Surg Pathol 2004;28:1615, J Urol 2007;178:1201, Pathology 2014;46:37)
Case reports
- 9 year old boy with gross hematuria (BMJ Case Rep 2017;2017:219341)
Treatment
- Resection: transurethral resection of bladder tumor (TURBT)
Gross description
- Soft, pink, small isolated growth with delicate papillary structures, usually pedunculated
Microscopic (histologic) description
- Predominantly exophytic tumor
- Discrete papillary structures with central fibrovascular cores with hierarchical branching pattern but without fusion
- Papillae appear to float above urothelial surface due to transverse sectioning of branching papillae
- Papillae usually slender with scant stroma around fibrovascular cores
- May have large papillae with marked stromal edema or cystitis cystica-like invaginations
- Papillary structures are lined by urothelium of normal thickness and cytology; often with prominent umbrella cells layer
- Umbrella cells may show cytoplasmic vacuolization and degenerative type atypia
- There should be no marked cytologic atypia, increased thickness of the urothelium or increased mitotic / apoptotic figures
- Diffuse papillomatosis: rarely bladder mucosa covered / replaced by multiple papillomas (Virchows Arch 2002;441:109)
Microscopic (histologic) images
Contributed by Judy Sarungbam, M.D.
Discrete papillary structures
Slender fibrovascular core
Prominent umbrella cells
Edematous fibrovascular core
Positive stains
- CK20 is positive in the umbrella cell layer
Negative stains
- No p53 abnormality
Molecular / cytogenetics description
- Targeted next generation sequencing (NGS) and whole exome sequencing (WES) showed (J Pathol 2019;248:260)
- Activating mutations involving the MAPK / ERK pathway, in particular KRAS and HRAS genes, are common alterations
- KRAS mutations more frequent than HRAS
- Mutations in chromatin modifiers (often associated with urothelial carcinoma) are rare
- Low tumor mutational burden
- No APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like) mutational signature (identified in about 70% of muscle invasive urothelial carcinomas)
- Other earlier studies have shown
- FGFR3 mutations in 75% (J Pathol 2002;198:245)
- TERT promoter mutation in 46% (12/26) (Eur Urol 2017;71:497)
- However, these findings have not been replicated in the newer study using NGS and WES
Sample pathology report
- Urinary bladder, right lateral trigone, transurethral resection of bladder tumor:
- Urothelial papilloma
Differential diagnosis
- Papillary urothelial neoplasm of low malignant potential (PUNLMP):
- Complex papillary structures with branching and fusion
- Increased cellular proliferation, resulting in increased thickness of the urothelium
- No architectural abnormality (maintained polarity)
- No nuclear atypia
- Lacks prominent umbrella cell layer
- Noninvasive papillary urothelial carcinoma low grade:
- Complex papillary structures with branching and fusion
- Usually increased thickness of urothelium with architectural and cytologic atypia
- Papillary carcinoma without increased thickness shows marked cytologic and architectural abnormality
- Lacks prominent umbrella cell layer
- Polypoid / papillary cystitis:
- Usually has history of urothelial irritation, e.g. stones, radiation, stents etc. (Am J Surg Pathol 2008;32:758, J Urol 2013;189:1091)
- Best evaluated at low power microscopy
- Predominantly nonbranching broad base fronds with edematous / fibrotic stroma associated with inflammation
- Lining urothelium shows reactive atypia
- Lacks prominent umbrella cell layer
- Fibroepithelial polyp:
- More often seen in children, though they can be seen in adults
- Can be a polypoid mass or a papillary lesion
- Usually has broader stalks with dense fibrous tissue cores
- Lacks prominent umbrella cell layer
Board review style question #1
- What is the correct diagnosis seen in the images?
- Low grade papillary urothelial carcinoma
- Papillary urothelial neoplasia of low malignant potential (PUNLMP)
- Polypoid cystitis
- Urothelial papilloma
Board review style answer #1
D. Urothelial papilloma. Note the papillary architecture with thin fibrovascular cores, a normal appearing urothelial lining and prominent umbrella cell layer.
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Board review style question #2
- Which of the following is true regarding urothelial papilloma?
- Associated with high rate of recurrence and progression
- Lined by urothelium of normal thickness and cytology
- Seen in an older age group than urothelial carcinoma
- Umbrella cell atypia excludes the diagnosis
Board review style answer #2
B. Urothelial papilloma is an exophytic papillary neoplasm lined by urothelium of normal thickness and cytology. Urothelial papilloma is often seen in a younger age group than urothelial carcinoma and has no or a very low recurrence rate. A prominent umbrella cell layer is characteristic. The umbrella cells often show marked atypia and this should not be used to change the diagnosis from urothelial papilloma to urothelial carcinoma.
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