Bladder, ureter & renal pelvis
Other nonneoplastic
Nephrogenic metaplasia

Topic Completed: 1 February 2013

Minor changes: 15 March 2021

Copyright: 2003-2021,, Inc.

PubMed Search: Nephrogenic metaplasia

Rugvedita Parakh, M.D.
Page views in 2020: 9,681
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Cite this page: Parakh R. Nephrogenic metaplasia. website. Accessed April 15th, 2021.
Definition / general
  • Metaplastic change with papillary or cystic structures composed of small hollow tubules similar to mesonephric tubules, usually lined by a single layer of bland cuboidal or hobnail cells, surrounding eosinophilic or basophilic secretions
  • Also called nephrogenic adenoma
  • Affects bladder, urethra, ureter and renal pelvis in decreasing frequency
  • More common at bladder neck and adjacent urethra
  • Increased incidence after organ transplantation and immunosuppression
  • In renal transplant recipients, derived from exfoliated and implanted renal tubular cells in the urinary tract (N Engl J Med 2002;347:653)
  • In other patients, appears to be metaplastic and not a neoplasm
  • Associated with inflammation (Urology 1976;8:283), bcg, calculi, chronic catheterization, exstrophy, interstitial cystitis, intravesical thiotepa, malakoplakia, Müllerian lesions, surgery (adults: prostatic lesions, children: congenital lesions); note that these conditions also cause cystitis glandularis and cystitis cystica
Clinical features
  • Irritative bladder symptoms, occasionally hematuria
  • Velvety appearance on cystoscopy; often mistaken for papillary urothelial carcinoma
  • Benign behavior; no malignant transformation even if significant cytologic atypia ( Cancer 2000;88:853 but see Hum Pathol 2006;37:117)
Case reports
  • Resection, but often recurs; requires longterm followup
  • Case report of 12 year old boy treated with sodium hyaluronate (J Pediatr Urol 2007;3:156)
  • May regress if underlying cause is removed
Gross description
  • Polypoid, sessile or papillary, 20% are multiple
Microscopic (histologic) description
  • Small hollow tubules similar to mesonephric tubules, usually lined by single layer of bland cuboidal or hobnail cells, surrounding eosinophilic or basophilic secretions (Mod Pathol 1995;8:722)
  • Cells have clear or eosinophilic cytoplasm, small nuclei, no prominent nucleoli
  • May have thickened basement membrane
  • Usually inflammatory infiltrate (plasma cells and lymphocytes) and stromal edema
  • Involves lamina propria but spares muscularis propria
  • Most cases also have a cystic pattern; occasionally are pseudoinfiltrative, may contain < 10% clear cells, may have small slender papillary structures on mucosal surface
  • Occasionally luminal blue mucin compresses the nuclei giving a signet ring-like appearance
  • Minimal atypia, minimal mitotic figures
  • No necrosis, no desmoplasia

  • Fibromyxoid subtype: compressed spindled cells within a fibromyxoid background with only rare tubular and cordlike structures, mimics mucinous carcinoma (Am J Surg Pathol 2007;31:1231)
  • Prostatic urethra: lesions closely resemble prostatic adenocarcinoma and are AMACR+
Microscopic (histologic) images

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Papillary and cystic structures lined by cuboidal epithelium

Papillary mucosal surface epithelium

Invasive adenocarcinoma

Tubulopapillary lesion

Small grouped ducts

Papillary lesion

Cytology description
  • Benign features and PAX2+ (Diagn Cytopathol 2008;36:47)
  • Small clusters and single scattered cells with central nuclei and vacuolated cytoplasm
  • Nuclei show evenly distributed chromatin with small nucleoli and regular nuclear membranes
  • Occasional small pseudopapillary clusters of cells with slightly irregular nuclear membranes and prominent nucleoli
  • Background of reactive urothelial cells and squamous cells (Diagn Cytopathol 2009;37:468)
Positive stains
Negative stains
Electron microscopy description
Molecular / cytogenetics description
Differential diagnosis
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