Immunohistochemical markers for the differential diagnosis of nephrogenic adenomas

Nephrogenic adenoma (NA) is a rare benign lesion commonly occurring in the urinary bladder that poses challenges to devising a diagnosis. In this study, 21 cases of NAs were studied by performing immunohistochemistry for PAX8, p63, CK903, PSA, S100A1, BerEP4, and CEA on routine tissue sections. PAX8 showed diffuse moderate to strong (2 + and 3 +) nuclear staining in all of NAs (n = 6 and 15, respectively) and negative in the normal urothelium (n = 15). Nuclear staining for p63 was not seen in any case of NAs examined (n = 19) and was diffuse and strong (3 +) in the normal urothelium (n = 14). High-molecular-weight keratin CK903 showed weak (1 +) diffuse staining in all of the NAs examined (n = 19) and diffuse and moderate to strong positivity in the normal urothelium (n = 16). PSA staining was negative in both of the NAs (n = 21) and normal urothelium (n = 16). S100A1 showed strong (3 +) diffuse staining in 19 of 20 of the NAs examined (n = 19) and diffuse weak (1 +) (n = 14) to moderate (n = 3) staining in the normal urothelium. BerEP4 showed focal to diffuse, mild to moderate (1 + and 2 +) cytoplasmic staining in all of NAs (n = 2 and 19) and negative in the normal urothelium (n = 19). CEA staining was negative in both of the NAs (n = 21) and normal urothelium (n = 17). A panel composed of PAX8, p63, PSA, S100A1, and CEA appears to be sensitive and specific in differentiating NA from its mimics of urothelial and prostatic origins.