Answer: Invasive clear cell adenocarcinoma

Histology: none provided

Discussion: The tumor has a tubulopapillary and solid growth pattern. The tubulopapillary structures are lined by cuboidal-columnar cells that exhibit marked pleomorphism with large atypical “hobnail-shaped” cells also present. The soilid areas are composed of the same plarge pleomorphic ceels some of which have cytoplasmic vacuoles and form occasional pseudoglands. The tumor invades anterior parivesical soft tissue, muscularis propria of bladder neck and is seen in vascular channels in the outer layers of muscularis propria of the anterior bladder wall. Immunostains demonstrate that the tumor cells are PAX-8, racemase and HNF-1-beta positive and WT-1 negative. This staining pattern supports the diagnosis.

The histogenesis of clear cell adenocarcinoma (CCA) of the bladder-urethra is still unclear. The tumor was originally considered to be of mesonephric derivation and was labeled as ‘mesonephric adenocarcinoma’ and subsequently as CCA in the 2004 World Health Organization Classification of Tumors mainly due to the histological similarities with the homonymous tumors of the female genital tract. Since then, a Müllerian derivation has been favored for the following reasons:
1) the histological resemblance between gynecologic and genitourinary tract CCAs,
2) the marked female predominance of CCA of the bladder/urethra,
3) the association of CCA of the bladder with bladder endometriosis or Müllerian duct remnants/cysts in some cases, and
4) the expression of CA 125 (a marker that was originally thought to indicate Müllerian differentiation) by bladder/urethral CCA.

Others suggested that a large proportion of these tumors represent a distinctive form of glandular differentiation within the urothelial carcinoma spectrum. Supporting their argument is that male patients presenting with the disease have been increasingly noted, and that associated Müllerian-related structures were present much rarer than originally emphasized. Another clue to support a urothelial derivation is the fact that bladder CCAs can have minor admixed foci of conventional invasive high-grade urothelial carcinoma. The immunohistochemical profile of CCAs of the bladder/urethra is different from traditional urothelial carcinoma and even from other types of bladder/urethral adenocarcinomas: they are negative for p63, and positive PAX-8 and racemase similar to nephrogenic adenoma (NA). Though CCA and NA exhibit overlapping morphologic and immunophenotypic features most experts believe that the differing frequency, gender predisposition and clinical setting in which these two lesions occur, in addition to the extreme rarity of well documented cases showing transition from NA to CCA make the histogenic relationship between CCA and NA unlikely.

Reference(s):
– Young RH and Scully RE. Clear cell adenocarcinoma of the bladder and urethra. A report of three cases and review of the literature. Am.J.Surg.Pathol. 1985; 9:816-26.
– Oliva E, Amin MB, Jimenez R, Young RH. Clear cell carcinoma of the urinary bladder: a report and comparison of four tumors of mullerian origin and nine of probable urothelial origin with discussion of histogenesis and diagnostic problems. Am.J.Surg.Pathol. 2002; 26:190-7.
– Sun K, Huan Y, Unger PD. Clear cell adenocarcinoma of urinary bladder and urethra: another urinary tract lesion immunoreactive for P504S. Arch.Pathol.Lab.Med. 2008; 132:1417-22.
– Oliva E and Young RH. Clear cell adenocarcinoma of the urethra: a clinicopathologic analysis of 19 cases. Mod.Pathol. 1996; 9:513-20.