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prostatic urothelial carcinoma


Thursday 16 February 2012

Urothelial carcinoma of the prostate

Definition: Urothelial carcinoma involving the prostate.

Urothelial (also known as transitional cell) carcinoma in the prostate is usually associated with a primary urinary bladder or urethral urothelial carcinoma.

This association may be attributable to intraprostatic extension from the bladder or urethra, implantation from one of these sites, or multifocal disease as a result of a ‘field effect’ of urothelial carcinogenesis, where urothelium normally lining the intraprostatic ducts might be affected.

The argument has therefore been made that the terms primary and secondary should not be used for prostatic urothelial carcinoma.

Indeed, it is often difficult to know with certainty the primary site of origin, and so prostatic urethral and periurethral prostatic ductal sites are often lumped together.

Prostatic urothelial carcinomas diagnosed in the absence of a urinary bladder urothelial carcinoma are rare.

The mean incidence in nine series of 11 678 patients was 1.1% (range 0.2–3.5%) of all prostatic carcinomas.


The frequency of primary urothelial carcinoma ranges from 0.7-2.8% of prostatic tumours in adults.

Most patients are older with a similar age distribution to urothelial carcinoma of the bladder (range 45-90 years).

In patients with invasive bladder carcinoma, there is involvement of the prostate gland in up to 45% of cases. This is highest when there is
multifocality or carcinoma in situ associated with the invasive carcinoma.


Primary urothelial carcinomas presumably arise from the urothelial lining of the prostatic urethra and the proximal portions of prostatic ducts.

It has been postulated that this may arise through a hyperplasia to dysplasia sequence, possibly from reserve cells within the urothelium.

Secondary urothelial carcinoma of the prostate is usually accompanied by CIS of the prostatic urethra.

Involvement of the prostate appears to be by direct extension from the
overlying urethra, since in the majority of cases the more centrally located prostatic ducts are involved by urothelial neoplasia to a greater extent than the peripheral ducts and acini.

Less commonly, deeply invasive urothelial carcinoma from the bladder directly invades the prostate.


Primary urothelial carcinoma is usually located within the proximal prostatic ducts. Many cases are locally advanced at diagnosis and extensively replace the prostate gland.

Clinical features

Signs and symptoms

Primary urothelial carcinoma presents in a similar fashion to other prostatic masses including urinary obstruction and haematuria.

Digital rectal examination is abnormal in the majority but is infrequently the presenting sign.

There is limited data on PSA levels in patients with urothelial carcinoma of the prostate. In one series, 4 of 6 patients had elevated serum PSA (>4 ng/ml) in the absence of prostatic adenocarcinoma.

In some cases patients present with signs and symptoms related to metastases.

Methods of diagnosis

Most cases are diagnosed by transurethral resection or less often needle biopsy. In all suspected cases, the possibility of secondary involvement from a bladder primary must be excluded; the bladder tumour can be occult and random biopsies may be necessary
to exclude this possibility.

Biopsies of the prostatic urethra and suburethral prostate tissue are often recommended as a staging procedure to detect secondary urothelial cancer involving the prostate of patients undergoing conservative treatment for superficial bladder tumours.


No reliable gross features of prostatic transitional cell carcinoma have been reported.


Microscopically, prostatic urothelial carcinoma has a striking propensity for growth within prostatic ducts and acini. Rounded or elongated cylinders and plugs of solid tumour within ducts are characteristic profiles.

Comedo necrosis can also commonly be found, and may undergo dystrophic calcification.

Partial involvement of benign prostatic glands is typical. Pagetoid spread can also be found.

Intraductal papillary architecture is rarely detected. Spread of prostatic urothelial carcinoma within ducts and acini can be extensive, without stromal invasion.

Prostatic stromal invasion by urothelial carcinoma is typified by irregular solid nests and cords that extend beyond the rounded, smooth outer profile of the urothelial carcinoma in situ, with a fibroinflammatory stromal response.

Cytologically, urothelial carcinoma in the prostate has a high nuclear grade, with substantial nucleomegaly, nuclear pleomorphism, and nuclear hyperchromasia. The cytoplasm often has an eosinophlic ‘squamoid’ appearance.

The full range of histologic types and grades of urothelial neoplasia can be seen in primary and secondary urothelial neoplasms of the prostate.

A few examples of papillary urothelial neoplasms arising within prostatic ducts are described.

The vast majority, however, are high-grade and are associated with an in situ component. The in situ component has the characteristic histologic features of urothelial carcinoma in situ elsewhere with marked nuclear pleomorphism, frequent mitoses and apoptotic bodies.

A single cell pattern of pagetoid spread or burrowing of tumour cells between the basal cell and secretory cell layers of the prostate is characteristic.

With extensive tumour involvement, urothelial carcinoma fills and expands ducts and often develops central comedonecrosis.

Stromal invasion is associated with a prominent desmoplastic stromal response with tumour cells arranged in small irregular nests, cords and single cells.

Inflammation in the adjacent stroma frequently accompanies in situ disease but without desmoplasia.

With stromal invasive tumours, squamous or glandular differentiation can be seen.

Angiolymphatic invasion is often identified.

Incidental adenocarcinoma of the prostate is found in up to 40% of cystoprostatectomy specimens removed for urothelial carcinoma of the bladder and can accompany primary urothelial carcinoma.

In cases of direct invasion of the prostate from a poorly differentiated urothelial carcinoma of the bladder, a common problem is its distinction from a poorly differentiated prostatic adenocarcinoma.

Poorly differentiated urothelial carcinomas have greater pleomorphism and mitotic activity compared to poorly differentiated adenocarcinomas of the prostate.

Urothelial carcinomas tend to have hard glassy eosinophilic cytoplasm or more prominent squamous differentiation, in contrast to the foamy, pale cytoplasm of prostate adenocarcinoma.

Urothelial cancer tends to grow in nests, as opposed to cords of cells or focal cribriform glandular differentiation typical of prostatic adenocarcinoma.


The immunophenotypic profile of prostatic urothelial carcinomas is the same as for urothelial carcinomas elsewhere, and is useful in the differential diagnostic distinction from poorly differentiated prostatic adenocarcinoma.

They are negative for PSA and PSAP, and are frequently positive for CK7, CK20, high molecular weight CKs bound by 34βE12 (CK903), p63, and thrombomodulin.


Grading and pathological staging have been inconsistently performed.

The 2004 WHO low-grade and high-grade urothelial carcinoma designations should be used. A large majority of cases are high-grade.

Tumour spread and staging

For staging, the 2010 American Joint Committee on Cancer system for primary prostatic urothelial carcinoma should be used.

In situ carcinoma can spread along ducts and involve acini, or the tumour can spread along ejaculatory ducts and into seminal vesicles.

Subsequent spread is by invasion of prostatic stroma. Local spread beyond the confines of the prostate may occur. Metastases are to regional lymph nodes and bone. Bone metastases are osteolytic. These
tumours are staged as urethral tumours.

For tumours involving the prostatic ducts, there is a T1 category for invasion of subepithelial connective tissue distinct from invasion of prostatic stroma.

The prognostic importance of these categories has been confirmed in clinical studies.


The outcome for patients diagnosed with primary urothelial carcinoma of the prostate has been dismal in the past, with an average survival of 17–29 months.

In contrast, it is abundantly clear that the prognosis for men with pure urothelial carcinoma in situ in the prostate is excellent.