Bladder, ureter & renal pelvis
Other nonneoplastic
Nephrogenic metaplasia
Author: Rugvedita Parakh, M.D.
Topic Completed: 1 February 2013
Minor changes: 7 February 2020
Copyright: 2003-2020, PathologyOutlines.com, Inc.
PubMed Search: Nephrogenic metaplasia
Table of Contents
Definition / general | Terminology | Epidemiology | Sites | Etiology | Clinical features | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Differential diagnosisCite this page: Parakh R. Nephrogenic metaplasia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bladdernephroadenoma.html. Accessed August 7th, 2020.
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
Terminology
- Also called nephrogenic adenoma
Epidemiology
- Usually adults; rarely children (J Pediatr Urol 2006;2:323)
- 2/3 male
Sites
- Affects bladder, urethra, ureter and renal pelvis in decreasing frequency
- More common at bladder neck and adjacent urethra
Etiology
- 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
- 10 year old boy with prune belly syndrome and recurrent nephrogenic adenoma (Pediatr Surg Int 2008;24:605)
- 25 year old man with adenocarcinoma after nephrogenic adenoma (J Med Case Rep 2008;2:164)
- 53 year old man with tumor after ibuprofen abuse for chronic arthritis (Urology 2004;64:1030)
Treatment
- 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
Images hosted on other servers:
Papillary and cystic structures lined by cuboidal epithelium
Cells have hobnail appearance
Papillary mucosal surface epithelium
Invasive adenocarcinoma
Tubulopapillary lesion
Small grouped ducts
Papillary lesion
Various stains
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
- CK903, p63, CD10 (may be focally positive, Arch Pathol Lab Med 2008;132:1417, Mod Pathol 2006;19:356)
Electron microscopy description
- Resembles proximal convoluted tubules (Hum Pathol 1981;12:907)
Molecular / cytogenetics description
- Monosomy 9, trisomy 7 (Urology 1998;52:756)
Differential diagnosis
- Clear cell adenocarcinoma: usually women, lacks clinical features of nephrogenic adenoma; very large tumors, mostly clear cells, marked atypia, muscularis propria invasion; also high mitotic rate, necrosis, high Ki-67 percentage, usually PAX2 negative (although distinction is usually made on morphologic grounds), strong p53 staining (Hum Pathol 1998;29:1451, Am J Surg Pathol 1986;10:268, Hum Pathol 2010;41:594)
- Endocervicosis: may resemble mucinous variant of nephrogenic adenoma
- Papillary urothelial carcinoma: > 1 layer of urothelial type cells with atypia
- Prostatic adenocarcinoma of bladder: more atypia, strongly PSA+
- Urothelial carcinoma-nested variant: cystic degeneration of nests, not a single layer; also marked atypia
