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Bladder
Metaplasia
Nephrogenic metaplasia
Reviewer: Rugvedita Parakh, M.D. (see Reviewers page)
Revised: 9 February 2013, last major update July 2010
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.
Definition
=========================================================================
● 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 mesonephric adenoma / metaplasia, nephrogenic adenoma; also adenomatoid tumor (but a different entity), adenomatoid metaplasia
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, Mullerian 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 long term follow-up
● 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
Micro 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+
Micro images
=========================================================================
Papillary and cystic structures lined by cuboidal epithelium
|
|
|
Tiny tubules and apparent compressed single nucleus mimic appearance of signet-ring cells |
 Cuboidal (straight arrow) or teardrop-shaped (curved arrow) cells; note the papillations (arrowheads) on the luminal surface |
(a) Typical tubules with a single lining of cells, (b) A mixed pattern of small tubules and cysts |
|
Tubules containing colloid-like material |
Tubules surrounded by conspicuous hyaline material |
Pseudoinfiltrative pattern |
 Focal development of an invasive adenocarcinoma |
Tubulopapillary lesion lined by a low columnar epithelium |
Small grouped ducts lined by a low columnar epithelium |
|
Papillary lesion lined by a bland low columnar epithelium |
 Atypical nephrogenic metaplasia |
|
 Various stains |
Virtual slides
=========================================================================
Several transurethral resection fragments of 59 year old man with nodular hyperplasia of the prostate
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
=========================================================================
● AE1/ AE3 (pancytokeratin), CAM5.2, CK7, CK20, EMA
● CA-125, PAX8 and PAX2 (89-100%,
Am J Surg Pathol 2008;32:1380)
● PSA or PAP (weak, 33%), variable P504S
(Am J Surg Pathol 2004;28:701)
● Luminal mucin is PAS+, mucicarmine+
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
End of Bladder > Metaplasia > Nephrogenic metaplasia
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