Stanford School of Medicine

Surgical Pathology Criteria

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Inverted Papilloma


  • Benign urothelial neoplasm with an inverted, pseudoinvasive pattern

Diagnostic Criteria

  • Distinguishing inverted from everted/exophytic can be tricky in fragmented specimens
    • If inverted, the stroma is around the outside of the epithelial nest and there is no central fibrovascular core (as seen in exophytic papillary processes)
  • Regular anastomosing trabeculae of urothelium within submucosa
    • Periphery including deep aspect circumscribed, but may not be assessible in fragmented specimens
      • No muscularis propria invasion
    • Trabeculae are randomly oriented with respect to surface
    • Peripheral cells in trabeculae are palisaded
      • Central cells appear abruptly to spindle and flow perpendicularly to palisaded cells
      • Nonkeratinizing squamous differentiation may be present
    • Cystic spaces lacking secretory differentiation may be present
  • Covered by a surface of flat normal urothelium
    • At most, a minimal exophytic component
    • May require careful examination in a fragmented specimen
    • Process usually shows multiple contacts/take-offs from the surface
  • Predominantly cytologically bland
    • Occasional cases show foci of mild to moderate cytologic atypia with nucleoli, hypercellularity, squamous metaplasia and multinucleated cells
      • Has been termed "inverted papilloma with atypia"
      • Mitotic figures rare
      • No adverse behavior has been reported for such cases
    • High grade cytologic features are not permitted
  • Stroma generally loose and not reactive
  • A glandular variant has been described (Kunze)
  • Rare variant with foamy or clear cytoplasm has been described (Broussard)

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 10/20/12, 8/22/13

Supplemental studies


  • CK20, p53 and Ki67 negative
  • p16 positive in 40% but in situ hybridization negative for HPV (Alexandr)

Differential Diagnosis

  • Florid von Brunn nests and cystitis cystica/glandularis
  • Nested variant urothelial carcinoma
  • Inverted urothelial carcinoma

Inverted Papilloma Florid von Brunn Nests, Cystitis Cystica/Glandularis
Regular pattern of anastomosing cords and trabeculae Round nests, may show fusion
Peripheral palisading and central streaming Lacks biphasic palisading/streaming pattern
Criteria above apply to both solid and cystic processes
An older description of inverted papilloma composed of cystic nests (Kunze) may not be separable from florid von Brunn nests

Nested Variant Urothelial Carcinoma Inverted Papilloma
Overall invasive pattern, not circumscribed Circumscribed (if sample permits assessment)
May involve muscularis propria Does not involve muscularis propria
Varying sizes and shapes of nests Uniform trabeculae and cords
Disorder of cells in nests Orderly peripheral palisading and central streaming

Urothelial Carcinoma with Inverted Growth Pattern Inverted Papilloma
Usually has a surface papillary component Surface everted papillary component absent or minimal
Cytologic features and disorder of carcinoma, appropriate to grade Bland, uniform, orderly cells
Mitotic figures present, appropriate to grade No mitotic figures
These may represent a spectrum, with an intermediate PUNLUMP with inverted pattern

Grading / Staging


  • Not applicable


  • Not applicable


  • Frequent concurrent or prior urothelial carcinoma
    • Considered by some to be a risk factor for development of carcinoma
    • If no prior history of urothelial neoplasia, recurrence is very rare and progression is not reported
  • Most cases in men (7:1 M:F)
  • May appear sessile or pedunculated on cystoscopy with smooth surface
  • Most common in bladder but may occur anywhere in urinary tract

Classification / Lists

Flat Lesions of the Urinary Bladder

Papillary Lesions of the Urinary Bladder

Subtypes of High Grade Urothelial Carcinoma

Inverted Lesions of the Urinary Bladder

Glandular Lesions of the Urinary Bladder


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  • Broussard JN, Tan PH, Epstein JI. Atypia in inverted urothelial papillomas: pathology and prognostic significance. Hum Pathol. 2004 Dec;35(12):1499-504.
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