Alpha-Methylacyl-CoA racemase (AMACR, P504S) has recently been shown to be a useful marker for the diagnosis of prostatic adenocarcinoma and a potential aid in its distinction from its many mimics, one of which is the benign lesion, nephrogenic adenoma (NA). The goal of this study was to assess the expression of AMACR in NA by immunohistochemistry, as well as other potentially useful markers, high-molecular-weight cytokeratin clone 34betaE12, p63, and prostate-specific antigen (PSA). AMACR was expressed in 4/4 NAs involving the prostatic urethra and underlying stroma, and in 3/16 NAs involving the bladder. The prostatic cases showed circumferential granular cytoplasmic AMACR expression of at least moderate intensity, in >75% of tubules in 3 cases and in <10% of tubules in the remaining case. The AMACR-positive cases in the bladder typically showed focal weak noncircumferential staining of the tubules and stronger staining of the cells lining the papillae. 34betaE12 staining was observed in 1/4 prostatic NAs and 4/16 bladder NAs, typically in a cytoplasmic pattern in a minority of cells. p63 and PSA were negative in all cases. Our data indicate that NA of the prostatic urethra commonly expresses AMACR and lacks basal cell-specific markers, making it not only a potential morphologic mimic of prostatic adenocarcinoma but also a significant immunohistochemical mimic as well. Awareness of NA as a significant pitfall in the diagnosis of prostatic adenocarcinoma and careful examination of hematoxylin and eosin-stained sections remains the key to the correct diagnosis, which can be supported by a negative PSA stain.

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