Hepatocyte nuclear factor-1β expression in clear cell adenocarcinomas of the bladder and urethra: diagnostic utility and implications for histogenesis.

The histogenesis of clear cell adenocarcinoma of the bladder/urethra is uncertain. Hepatocyte nuclear factor-1β is a homeodomain protein that has been reported to be frequently overexpressed in ovarian clear cell adenocarcinoma in comparison with rare or no expression in other types of epithelial ovarian tumors. We assessed the expression of hepatocyte nuclear factor-1β in a series of 18 clear cell adenocarcinomas of the bladder and urethra and compared it with that of invasive high-grade transitional/urothelial carcinoma (n = 35); adenocarcinomas of the bladder, urethra, and paraurethral glands (n = 21); as well as nephrogenic adenomas of the bladder (n = 8). Staining intensity and extent were evaluated using a 4-tiered grading system (0-3). A case was considered positive for hepatocyte nuclear factor-1β if 10% or more of tumor cells showed at least weak nuclear staining or if any moderate or strong nuclear staining was observed. All 18 clear cell adenocarcinomas exhibited nuclear staining in at least 50% of tumor cells (16 strong, 1 moderate, and 1 weak with focal strong nuclear staining) in comparison with positive nuclear staining (moderate) in 1 of 21 bladder adenocarcinoma, 1 of 35 invasive high-grade transitional/urothelial carcinoma (weak to moderate staining), and 2 of 8 nephrogenic adenomas (1 weak and 1 moderate to strong staining). We concluded that hepatocyte nuclear factor-1β is a useful marker in differentiating clear cell adenocarcinomas of the bladder/urethra from invasive high-grade transitional/urothelial carcinoma and other types of bladder adenocarcinomas and to a lesser extent from nephrogenic adenomas. Hepatocyte nuclear factor-1β is of no diagnostic utility in discriminating primary bladder/urethral clear cell adenocarcinomas from metastatic clear cell adenocarcinomas of the female genital tract to the bladder/urethra. From a histogenesis standpoint, although the expression of hepatocyte nuclear factor-1β in both gynecologic and urologic tract clear cell adenocarcinomas may point to a Müllerian derivation/differentiation, this immunohistochemical evidence is insufficient to completely exclude an urothelial association.

Brimo F ，Herawi M ，Sharma R ，Netto GJ ，Epstein JI ，Illei PB ... -  《-》

Clear cell adenocarcinoma of the bladder and urethra: cases diffusely mimicking nephrogenic adenoma.

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.

Herawi M ，Drew PA ，Pan CC ，Epstein JI ... -  《-》

Clear cell adenocarcinoma and nephrogenic adenoma of the urethra and urinary bladder: a histopathologic and immunohistochemical comparison.

Gilcrease MZ ，Delgado R ，Vuitch F ，Albores-Saavedra J ... -  《HUMAN PATHOLOGY》

Histogenesis of clear cell adenocarcinoma in the urinary tract: evidence of urothelial origin.

Sung MT ，Zhang S ，MacLennan GT ，Lopez-Beltran A ，Montironi R ，Wang M ，Tan PH ，Cheng L ... -  《CLINICAL CANCER RESEARCH》

Immunohistochemical expression of prostatic antigens in adenocarcinoma and villous adenoma of the urinary bladder.

Lane Z ，Hansel DE ，Epstein JI 《-》