Expression of Alpha-Methylacyl-Coenzyme A Racemase in Nephrogenic Adenoma

Abstract

Nephrogenic adenoma is a benign lesion composed of small glandular structures that develops along the urothelium with uncertain pathogenesis. Some investigators believe that nephrogenic adenoma develops by a metaplastic process in response to injury to the urothelium, while others believe that it arises from detached renal tubules. Nephrogenic adenoma may be present in the prostatic urethra and morphologically mimic prostatic adenocarcinoma. Alpha-methylacyl-coenzyme A racemase (AMACR), a recently identified prostate cancer marker, is typically negative in normal urothelium and prostatic glands, and positive in distal convoluted renal tubules in addition to prostatic adenocarcinomas. Therefore, evaluation of AMACR expression in nephrogenic adenoma will have significance in the pathologic diagnosis and in understanding pathogenesis of this lesion. We studied 38 nephrogenic adenomas by clinical, histologic, and immunohistochemical analyses for AMACR (P504S) and high molecular weight cytokeratin (34betaE12). Twenty-two of 38 nephrogenic adenomas (58%) demonstrated strong cytoplasmic positivity for AMACR, ranging from patchy, focal to diffuse staining. In addition, 16 of 26 (62%) nephrogenic adenomas were negative for 34betaE12. To our knowledge, this is one of the first report of a completely benign lesion, which can be found in the prostate, showing strong AMACR immunoreactivity. Our findings suggest using caution when interpreting positive AMACR immunostaining in prostatic specimens. These findings could be explained by possible renal tubular origin or renal differentiation, at least in a subset, of nephrogenic adenomas.

Primary Adenocarcinoma of the Urinary Bladder: Differential Diagnosis and Clinical Relevance

“…Two common features found in nephrogenic adenomas but not in adenocarcinoma are (1) thick basement membranes and (2) granulation tissue-like background with prominent stromal edema and inflammatory cell infiltrate. 42 Large amount of mucin, mitoses, and necrosis are uncommon in nephrogenic adenomas. The diagnosis of nephrogenic adenoma should be primarily based on hematoxylin-eosin staining, because of its variable immunoprofile, which can be similar to that of adenocarcinoma.…”

“…42 There are many different patterns such as tubular (Figure 7, C), papillary, capillary, or signet ring-like. Most often the pattern is mixed.…”

Benign Diseases of the Bladder

“…Positive immunohistochemical staining with AMACR and PAX-2 (markers of renal tubular epithelium) and absence of uroplakin immunostaining (present within normal urothelium) lend credence to this position. 23,24 Gross Appearance Nephrogenic adenoma may present grossly as an exophytic papillary or polypoid mass, mimicking carcinoma. Alternately, the lesion may appear flat.…”

Flat pattern of nephrogenic adenoma: previously unrecognized pattern unveiled using PAX2 and PAX8 immunohistochemistry

“…[4][5][6][7][8] Several studies have shown that PAX2 and PAX8 are expressed in nearly 100% of nephrogenic adenomas [9][10][11][12] and are helpful markers when the diagnosis of nephrogenic adenoma is difficult. In this study, we corroborated the frequent expression of PAX2 (93%) and PAX8 (100%) in our series of nephrogenic adenomas and identified a flat pattern associated with other traditional nephrogenic adenoma patterns that extended along the adjacent urothelium.…”

“…2,3 By immunohistochemistry, nephrogenic adenomas are positive for the renal tubule markers cytokeratin 7 (CK7), CD10, alpha-methylacyl-coenzyme A racemase (AMACR), PAX2 and PAX8, but negative for bladder urothelium or prostate antigens. [4][5][6][7][8] The transcription factors PAX2 and PAX8 (paired box genes) are crucial proteins during the embryonic and fetal development of several organs, particularly intermediate mesoderm and Mü llerian-derived tissues, and are expressed in nearly 100% of nephrogenic adenomas in some series. [9][10][11][12] Tong et al 13 have shown that urothelial cells from the upper genitourinary tract are PAX8 positive, whereas urinary bladder urothelium lacks PAX8 expression.…”