Although
clear cell adenocarcinoma have been described focally mimicking nephrogenic
adenoma, we have identified a subset of
clear cell adenocarcinoma that diffusely resembles nephrogenic
adenoma (nephrogenic
adenoma-like
clear cell adenocarcinoma). Twelve classic
clear cell adenocarcinomas of the bladder and urethra and 7 nephrogenic
adenoma-like
clear cell adenocarcinomas were compared to 10 nephrogenic
adenomas. Classic
clear cell adenocarcinomas and nephrogenic
adenoma-like
clear cell adenocarcinomas comprised 4 men and 15 women. The following features were seen in classic
clear cell adenocarcinomas: nephrogenic
adenoma-like
clear cell adenocarcinomas: predominantly solid pattern (7/12:0/7), marked nuclear pleomorphism (7/12:1/7), prominent nucleoli (5/12:1/7), clear cytoplasm in 50% or greater of
tumor (7/12:0/7), and
necrosis (8/12:3/7), although the
necrosis in nephrogenic
adenoma-like
clear cell adenocarcinomas was often focal and intraluminal. Both patterns of
clear cell adenocarcinomas showed prominent hobnail features, although more pronounced in nephrogenic
adenoma-like
clear cell adenocarcinomas. Muscularis propria invasion was seen in 5 of 9 classic
clear cell adenocarcinomas and 6 of 6 nephrogenic
adenoma-like
clear cell adenocarcinomas, where evaluable. Classic
clear cell adenocarcinoma was associated with urothelial
carcinoma (n = 2) and
endometriosis (n = 1). The Ki-67 rate in
clear cell adenocarcinomas ranged from 10% to 80% compared with 0% to 5% in nephrogenic
adenoma. The following
antibodies were not helpful in distinguishing nephrogenic
adenoma-like
clear cell adenocarcinoma from nephrogenic
adenoma: CD10,
estrogen receptor, p63, high-molecular-weight
cytokeratin, and alpha-methylacyl
coenzyme-A racemase. PAX2 expression was more frequent in nephrogenic
adenoma (89%) compared to both patterns of
clear cell adenocarcinoma (29%-32%). The key features discriminating between nephrogenic
adenoma-like
clear cell adenocarcinoma and nephrogenic
adenoma include occasional clear cells, more prominent pleomorphism especially hyperchromatic enlarged nuclei, and extensive muscular invasion. Presence of mitoses and a high rate of Ki-67 expression in lesions resembling nephrogenic
adenoma require clinical correlation, close follow-up, and repeat biopsy with more extensive sampling.