Discussion:

Nephrogenic adenoma of the urinary bladder (NAUB) is a rare lesion associated with nonspecific symptoms and could inadvertently be misdiagnosed. NAUB is a benign tubular and papillary lesion of the bladder, is more common in men and adults, and has been associated with chronic inflammation/irritation, previous bladder surgery, diverticula, renal transplantation, and intravesical BCG; recurrences and malignant transformations have been reported. Differential diagnoses include clear cell adenocarcinoma, endocervicosis (may resemble mucinous variant of nephrogenic adenoma), papillary urothelial carcinoma, prostatic adenocarcinoma of bladder, and nested variant of urothelial carcinoma; most NAUBs have both surface papillary and submucosal tubular components; both the papillae and tubules tend to be lined by a single layer of mitotically inactive bland cells which have pale to clear cytoplasm. Diagnosis may be established by using immunohistochemistry (positive staining with racemase; PAX2; keratins stain positive with fibromyxoid variant), electron microscopy, DNA analysis, and cytological studies. Endoscopic resection is the treatment but recurrences including sporadic malignant transformation have been reported.

Nephrogenic adenomas typically are not large invasive tumors although rare cases of NA may focally involve the superficial muscularis propria. They are typically positive with cytokeratin 7 (CK7), α-methylacyl-CoA racemase (AMACR) (P504S), PAX2, and epithelial membrane antigen and are usually negative with p63. PAX2, a key renal transcription factor, is commonly expressed in NA, which has been interpreted as evidence that NAs may be of renal tubular origin. Nephrogenic adenomas show patchy staining with high-molecular-weight cytokeratin (34βE12), although a subset of these (40%–45%) may be completely negative.