Bladder, ureter & renal pelvis

Urothelial neoplasms - noninvasive

Inverted urothelial papilloma

Last author update: 1 December 2014
Last staff update: 25 April 2023 (update in progress)

Copyright: 2003-2023,, Inc.

PubMed Search: Inverted urothelial papilloma[title]

Monika Roychowdhury, M.D.
Page views in 2022: 12,945
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Cite this page: Roychowdhury M. Inverted urothelial papilloma. website. Accessed September 21st, 2023.
Definition / general
  • Rare benign tumor similar to counterparts at other sites
  • Also called brunnian adenoma
  • Rare; <1% of all urothelial neoplasms
  • Broad age range but most patients are in their sixth or seventh decade
  • More common in men than women (7.3:1 ratio)
  • Trigone, bladder neck and prostatic urethra are common sites
Clinical features
  • Presents with nonspecific hematuria or irritative voiding symptoms, rarely obstructive voiding symptoms
  • May be associated with urothelial carcinoma, rarely in the inverted urothelial papilloma itself
Case reports
  • Simple excision is curative
Gross description
  • Usually solitary, smooth, polypoid, sessile or pedunculated
  • Usually 3 cm or less but can be as large as 8 cm
  • Incidence of multiple lesions ranges from 1.3 to 4.4%
Microscopic (histologic) description
  • Smooth surface with minimal to absent exophytic component
  • Lesional circumscription with smooth base
  • No obvious infiltration and no/minimal cytologic atypia

Can be divided into 2 main subtypes:

1. Trabecular subtype – Classic type
  • Irregular, downward growing ramifying thin and orderly cords and sheets arising from the overlying urothelium
  • The cords have peripheral palisading of basaloid cells
  • The neoplastic cells within the cords and nests of urothelium often have a spindled appearance
  • The intervening stroma is variable in amount and can be fibrotic
  • Urothelial buds are frequently at various points along the undersurface of the urothelium
  • Overlying surface urothelium can be normal, attenuated or hyperplastic
  • Occasionally, punctuated by cystic spaces lined by flattened uorthelial cells and containing eosinophilic material
  • Rarely, foci of non-keratinizing squamous metaplsia or neuroendocrine differentiation present
  • Marked cytologic atypia and mitotic activity are absent
  • Can have mild cytologic atypia due to prominent nucleoli, atypical squamous features, degenerative appearing multinucleated giant cells or atypical large squamous cells with a pagetoid appearance (designated as inverted papilloma with atypia)
  • Cases with atypia have not been associated with urothelial carcinoma; recommended to classify them as “inverted papilloma with atypia” and not low grade urothelial carcinoma (Hum Pathol 2004;35:1499)

2. Glandular subtype – morphological overlap with cystitis glandularis
  • Nests of mature urothelium with either pseudoglandular spaces lined by urothelium or true glandular spaces containing mucus-secreting goblet cells
  • The luminal secretions stain with mucicarmine
Microscopic (histologic) images

Contributed by Daniel Athanazio, M.D., Ph.D. and Debra Zynger, M.D.
Inverted papilloma

Inverted papilloma

Inverted papilloma – anastomosing cords

Inverted papilloma - anastomosing cords

Thickened epithelium

Thickened epithelium

Epithelium / no atypia

Epithelium / no atypia

Inverted PUNLMP

Inverted papilloma

Inverted PUNLMP - no atypia

Inverted papilloma - no atypia

Surface with thin, flat urothelium

Anastomosing, basophilic cords

Oval nuclei

Molecular / cytogenetics description
  • Rare deletions at chromosome 9 and 17, rare FGFR3 mutations, low rate of LOH
Differential diagnosis
  • Urothelial carcinoma invading into Brunn’s nests: more atypia and mitotic activity, often papillary component
  • Exophytic papilloma
  • Papillary urothelial neoplasm of low malignant potential
Additional references
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