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Bladder

Metaplasia

Nephrogenic metaplasia

 

Reviewers: Rugvedita Parakh, MD, Cedars-Sinai Medical Center (see Reviewers page)

Revised: 17 July 2010, last major update July 2010

Copyright: (c) 2002-2010, PathologyOutlines.com, Inc.

 

Definition

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● 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

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● Also called mesonephric adenoma / metaplasia, nephrogenic adenoma; also adenomatoid tumor (but a different entity), adenomatoid metaplasia

 

Epidemiology

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● Usually adults; rarely children (J Pediatr Urol 2006;2:323)

● 2/3 male

 

Sites

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● Affects bladder, urethra, ureter and renal pelvis in decreasing frequency

● More common at bladder neck and adjacent urethra

 

Etiology

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● 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

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● 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

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● 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 Reports 2008 May 18;2:164)

● 53 year old man with tumor after ibuprofen abuse for chronic arthritis (Urology 2004;64:1030)

 

Treatment

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● 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 (Macroscopy)

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● Polypoid, sessile or papillary, 20% are multiple

 

Micro description (Histopathology)

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● 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

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Papillary and cystic structures lined by cuboidal epithelium

 

 

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Various images

 

 

                                                               

Cuboidal (straight arrow) or teardrop-shaped (curved arrow) cells. Note the papillations arrowheads) on the luminal surface

 

 

                                                                               

Atypical nephrogenic metaplasia

Fig A: prominent nucleoli and intraluminal mucin

Fig B: intraluminal mucin secretion and clear cell

changes, mimicking signet ring cell adenocarcinoma

 

 

With focal development of an invasive adenocarcinoma

 

 

FIGURE 2 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author   FIGURE 3 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author   FIGURE 4 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

 

FIGURE 5 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author   FIGURE 6 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author   FIGURE 7 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author         
Lesion of ureter                                                                                  Site unspecified

 

Other images: #1;  #2;  #3;   #4;  #5

 

Virtual slides

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Urethral lesion

 

Cytology description

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● 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

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● 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

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● CK903, p63, CD10 (may be focally positive, Arch Pathol Lab Med 2008;132:1417, Mod Pathol 2006;19:356)

 

Electron microscopy images

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● Resembles proximal convoluted tubules (Hum Pathol 1981;12:907)

 

Molecular / cytogenetics description

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● Monosomy 9, trisomy 7 (Urology 1998;52:756)

 

Differential Diagnosis

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● 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 adenoma

 

 

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