Clear cell adenocarcinoma of the urethra: a clinicopathologic analysis of 19 cases

Nineteen clear cell adenocarcinomas of the urethra, 18 from women and one from a man, are described. The patients ranged from 35 to 80 years of age (average, 58 yrs). The clinical presentation and gross findings were similar to those of urethral carcinomas, except that 12 tumors, all from women, arose within a urethral diverticulum. On microscopic examination, the neoplasms exhibited the classic triad of tubulocystic, papillary, and diffuse patterns that characterize this tumor. The tumors had the typical cytologic features of clear cell adenocarcinoma, including hobnail cells, flattened cells, and cells with abundant clear cytoplasm. Nuclear pleomorphism was typically at least moderate and was marked in almost half the specimens. Mitotic figures were easily found in almost all the specimens. These cytologic features should aid in distinction of this carcinoma from the benign nephrogenic adenoma, although one of our patients was initially misdiagnosed as having the latter. Immunostaining for prostate-specific antigen and prostatic acid phosphatase was performed on 13 tumors, and all were negative. Follow-up is available for 13 patients. Six of them had no evidence of recurrence up to 10 years postoperatively. Four patients died of disease from 5 months to 42 months postoperatively. Three additional patients have had recurrence but were alive up to 6.5 years after presentation. We conclude that urethral clear cell adenocarcinoma occurs in adults, and in women in the great majority of cases; has a particular association with a urethral diverticulum, which has been present in 56% of the patients; is indistinguishable from clear cell adenocarcinoma of the female genital tract but is not associated with endometriosis; probably does not arise by malignant transformation of nephrogenic adenoma; is usually readily distinguished from the latter because of greater cytologic atypicality and mitotic activity; and does not stain for prostate-specific antigen or prostatic acid phosphatase.