Histogenesis of Clear Cell Adenocarcinoma in the Urinary Tract: Evidence of Urothelial Origin

Abstract

Purpose: Clear cell adenocarcinoma in the urinary tract is a rare entity with an appearance resembling its counterpart in the female genital tract. Although several theories have been proposed about its origin, its exact histogenesis has remained uncertain. Experimental Design: We integrated molecular genetic evaluation by fluorescence in situ hybridization and X-chromosome inactivation with conventional morphologic and immunohistochemical analyses in 12 patients with clear cell adenocarcinomas in the urinary tract. Results: Concurrent urothelial carcinoma or urothelial carcinoma in situ was present in six cases (50%) and foci of cystitis glandularis were observed in four cases (33%). Neither intestinal metaplasia nor Mu« llerian component was identified in any case. Cytoplasmic expression of a-methylacyl-CoA racemase was demonstrable in 10 of 12 tumors (83%). Moderate to diffuse immunostaining for cytokeratin 7 was identified in all 12 tumors (100%), whereas only 3 of 12 (25%) tumors showed positive immunostaining for cytokeratin 20. Focal uroplakin III staining was seen in 6 of 12 tumors (50%). In five cases (42%), focal to moderate CD10 immunoreactivity was observed. Immunostains for OCT4 and CDX2 were completely negative in all tumors. In UroVysion fluorescence in situ hybridization assays, all tumors displayed chromosomal alterations similar to those commonly found in urothelial carcinoma. Identical patterns of nonrandom X-chromosome inactivation in concurrent clear cell adenocarcinoma and urothelial neoplasia were identified in two informative female cases. Conclusions: Our findings support an urothelial origin for most clear cell adenocarcinomas of the urinary tract, despite their morphologic resemblance to certain Mu« llerian-derived tumors of the female genital tract.Clear cell adenocarcinoma in the urinary tract is an extremely rare neoplasm predominantly occurring in adult females and morphologically identical to tumors of the same name that arise in female genital organs. Its precise histogenesis has remained controversial. It has been postulated to be of mesonephric origin (1), Mü llerian origin (2 -4), or urothelial origin (5, 6). The histogenetic connection between clear cell adenocarcinoma and adenocarcinoma of non-Mü llerian type has been addressed by some investigators (6), and others have suggested that it results from malignant transformation of nephrogenic adenoma (7,8). Previous investigations of its histogenesis have involved morphologic or immunohistochemical analyses of single cases or small series of cases. In our current study, we evaluated a large series of cases of clear cell adenocarcinoma of the urinary tract by molecular genetic appraisal with fluorescence in situ hybridization (FISH) and integrated these findings with conventional morphologic and immunohistochemical analyses in an effort to elucidate the histogenesis of this rare and enigmatic neoplasm. Materials and MethodsCases diagnosed as clear cell adenocarcinoma in the urinary tract were retrieved from the surgical...

Vesiculectomía con prostatectomía parcial laparoscópica en el tratamiento del adenocarcinoma primario de vesícula seminal con transformación carcinomatosa del conducto eyaculador

“…La forma en la que este tipo de lesiones infrecuentes y de mal pronóstico suele diagnosticarse es debido a que producen hematuria y síntomas obstructivos al flujo urinario o incluso retención urinaria 15 . Su perfil inmunohistoquímico habitual es racemasa, CK7 y CK20 positivo, CA125 variable y p63 negativo 16 . Desde un punto de vista histogenético, el adenocarcinoma de célula clara del tracto urinario tiene un origen urotelial, aunque existe cierta similitud con algunos tumores müllerianos, bien femeninos, bien más raramente masculinos 16 .…”

“…Su perfil inmunohistoquímico habitual es racemasa, CK7 y CK20 positivo, CA125 variable y p63 negativo 16 . Desde un punto de vista histogenético, el adenocarcinoma de célula clara del tracto urinario tiene un origen urotelial, aunque existe cierta similitud con algunos tumores müllerianos, bien femeninos, bien más raramente masculinos 16 . Conceptualmente la neoplasia que hemos tratado en este joven al final de la tercera década de su vida es un adenocarcinoma primario de vesícula seminal, de célula clara con crecimiento túbulo papilar.…”

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

“…The histogenesis of CCA of the lower urinary tract is controversial [2,9,[15][16][17]. Although a mesonephric (wolffian) origin of CCA has largely been abandoned, a müllerian (paramesonephric) origin has been suggested by most authors, partially because of their reported association with endometriosis in some women as well as their expression of CA125 [9,18,19].…”

“…Although a mesonephric (wolffian) origin of CCA has largely been abandoned, a müllerian (paramesonephric) origin has been suggested by most authors, partially because of their reported association with endometriosis in some women as well as their expression of CA125 [9,18,19]. However, a recent study using molecular techniques found evidence to support an urothelial origin for most clear cell adenocarcinomas of the urinary tract [15]. In the current study, only 1 case of classic CCA was seen concurrently with endometriosis of the bladder, compared to none in the NA-like CCA group.…”

Invasive micropapillary urothelial carcinoma of the bladder

“…This is based on the reported immunoreactivity to CA125 in about 30% of invasive micropapillary carcinoma cases, a marker that has also been found in urothelial carcinomas displaying clear-cell glandular differentiation [21,22]. However, CA125 may also be present in urothelial carcinoma unrelated to glandular differentiation [21,22].…”