Case 4 -
Urothelial Carcinoma of the Prostate
John C. Cheville
Click on each slide thumbnail image for an enlarged view
A 65-year-old male presented to his urologist with hematuria. During the physical examination, a
nodule was palpated on the right side. His serum PSA was 3.8 ng/ml. A prostate needle biopsy was
performed followed by a radical cystoprostatectomy.
Case 4 - Figure 1 - Urothelial carcinoma in situ expands prostatic acini in the prostate needle biopsy specimen.
Case 4 - Figure 2 - Urothelial carcinoma in situ fills the prostatic acini. Cells have a urothelial appearance in contrast to high-grade prostatic intraepithelial neoplasia.
Case 4 - Figure 3 - Urothelial carcinoma with prostatic stromal invasion in the prostate needle biopsy specimen.
Case 4 - Figure 4 - Central luminal necrosis in urothelial carcinoma in situ of the prostate.
Case 4 - Figure 5 - Urothelial carcinoma in situ of the prostatic ducts in the radical cystoprostatectomy specimen.
Case 4 - Figure 6 - Prostatic stromal invasion with associated inflammation in the radical cystoprostatectomy specimen.
Urothelial Carcinoma of the Prostate
Urothelial carcinoma can involve the prostate through direct extension from a urinary bladder tumor or
it can arise from the urothelium of the prostatic urethra and proximal prostatic ducts. Urothelial
carcinoma arising in the bladder and invading into the prostate is staged according to the TNM
classification for urinary bladder cancer. These tumors are pT4 and are associated with a poor outcome.
Studies of urothelial carcinoma of the bladder have identified prostatic involvement in 12 to 55% of
In contrast, primary urothelial carcinoma of the prostate accounts for less than 5%
of prostatic carcinomas.  Urothelial carcinoma arising in the prostate has a separate TNM
staging classification based on the depth of invasion in the prostate.  Urothelial carcinoma
arising in the prostate is frequently associated with urothelial carcinoma in
situ (CIS) or a separate invasive urothelial carcinoma in the urinary bladder. The pathogenesis
of urothelial carcinoma of the prostate is debated, but primary mechanisms for its development include
mucosal extension of CIS from the urinary bladder into the prostatic urethra, implantation of neoplastic
cells from urinary bladder CIS or invasive tumor, or through a carcinogenic field effect.
Although the carcinogenic field affect hypothesis is accepted by many, none of these mechanisms are
mutually exclusive, and further molecular studies are required to determine the pathogenesis of
urothelial carcinoma involving the prostate.
The majority of patients with urothelial carcinoma of the prostate present with hematuria, and other
less common signs and symptoms include urinary obstruction, abnormal digital rectal examination, urinary
frequency, and hematospermia. Serum PSA is usually normal, but may be elevated.
diagnosis is made during cystoscopy that includes prostatic urethral and urinary bladder biopsies.
However, the primary diagnosis may rarely be made by prostate needle biopsy. Oliai et al identified 21
cases of urothelial carcinoma diagnosed on a prostate needle biopsy specimen, and 7 (41%) patients had no
prior or subsequent history of urothelial carcinoma outside the prostate.  Six (35%)
patients had concurrent urothelial carinoma of the bladder, 2 (12%) had prior urothelial carcinoma of the
bladder, and 2 (12%) subsequently developed urothelial carcinoma outside the prostate. Treatment
includes topical therapies, as well as cystoprostatectomy. In patients with CIS involving the prostatic
ducts and acini, BCG therapy may be ineffective as a result of the deep location of the CIS and the lack
of extended contact of the topical therapy to involved sites. Many urologists recommend urethrectomy
during radical cystoprostatectomy since urethral recurrence occurs in up to 20% of patients treated by
cystoprostatectomy without urethrectomy. 
In a series of 50 patients with primary urothelial carcinoma of the prostate (and
without a separate invasive bladder carcinoma) treated by cystoprostatectomy, cancer-specific survival
was associated with the depth of invasion into the prostate.  Patients with prostatic
stromal invasion had a significantly worse prognosis than patients with CIS involving prostatic ducts and
acini. The majority of these patients had associated urothelial carcinoma in situ of the bladder or
Urothelial Carcinoma of the Prostate:
Association with Urothelial Carcinoma
outside the Prostate in 50 Surgically Treated Patients 
| Feature ||No. of Patients (%)|
|Previous history of urothelial CIS of the bladder ||21 (42%)|
|Concurrent urothelial CIS of the bladder ||10 (20%)|
|Subsequent urothelial carcinoma of the upper tracts ||3 (6%)|
|Concurrent prostatic adenocarcinoma ||4 (8%)|
Urothelial Carcinoma of the Prostate:
Cancer-Specific Survival of 50 Patients Treated by Radical
|Tumor Extent|| No. of Patients (%) ||5-year Overall Survival ||5-Year Cancer-Specific Survival|
|Urothelial CIS ||19 (38%) ||62% ||100%|
|Prostatic Stromal Invasion ||21 (42%) ||35% ||45%|
|Extraprostatic Extension ||3 (6%) ||0% ||0%|
|LN metastasis ||7 (14%) ||30% ||30%|
|All cases ||50 ||40% ||52%|
Urothelial Carcinoma of the Prostate: Survival of Surgically Treated
CIS of Prostatic Urethra, Ducts and Acini versus Prostatic Stromal
| Study|| No. Pts with CIS ||No. Pts with Stromal Invasion ||5-Year SurvivalCIS ||5-Year SurvivalInvasive ||Bladder Tumor Stage|
|Esrig et al1 ||34 ||23 ||95% ||65% ||T0, Ta, Tis, T1|
| ||16 ||13 ||80% ||31% ||T2, T3a|
|Cheville et al12 ||19 ||21 ||100% ||45% ||T0, Tis|
|Schellhammer et al11 ||15 ||5 ||50% ||20% ||0, A, B|
|Pagano et al14 ||14 ||8 ||50% ||40% ||All stages|
The American Joint Committee on Cancer developed a TNM staging system for urothelial carcinoma of the
TNM Staging System (2003) for Urothelial Carcinoma of the
Prostate: T Stage
|T Stage ||Extent of Urothelial Carcinoma of the Prostate|
|Tis pu ||Urothelial Carcinoma in situ, involvement of prostatic urethra|
|Tis pd ||Urothelial Carcinoma in situ, involvement of subepithelial connective tissue|
|T1 ||Tumor invades into subepithelial connective tissue|
|T2 ||Tumor invades any of the following: prostatic stroma, periurethral muscle, corpus spongiosum|
|T3 ||Tumor invades any of the following: beyond prostatic capsule, bladder neck (extraprostatic extension), corpus spongiosum|
|T4 ||Tumor invades adjacent organs (invasion of the bladder)|
The differential diagnosis consists of high-grade prostatic intraepithelial neoplasia (PIN) and
prostatic ductal adenocarcinoma when urothelial CIS involves prostatic ducts and acini, and the
differential is expanded to high-grade prostatic adenocarcinoma when stromal invasion is present. Oliai
et al reported several important features in distinguishing high-grade PIN from urothelial CIS involving
prostatic ducts and acini.  Urothelial CIS expands and fills the prostatic ducts and acini,
and is frequently associated with comedonecrosis. The cells have a urothelial appearance and exhibit
significant cytologic atypia with nucleolar size variability, mitotic activity and apoptosis. In
contrast high-grade PIN does not obliterate the lumina of prostatic ducts and acini, and is infrequently
associated with central luminal necrosis. The cells of high-grade PIN had a columnar conformation, and
rarely show mitotic activity or the cytologic atypia of urothelial CIS. In contrast to urothelial CIS,
ductal prostatic adenocarcinoma forms cribriform or papillary structures lined by columnar epithelial
cells. The most difficulty arises in distinguishing high-grade prostatic adenocarcinoma from invasive
urothelial carcinoma. This can be a significant problem in needle biopsy specimens but is more
frequently encountered in transurethral resection specimens from the prostate. Invasive urothelial
carcinoma exhibits a greater degree of nuclear pleomorphism, usually lacks glandular differentiation, and
may have squamous features. Oliai recognized a greater degree of stromal inflammation associated with
invasion urothelial carcinoma. In many instances, immunohistochemical stains are useful in separating
urothelial carcinoma from prostatic adenocarcinoma. The following table provides the immunohistochemical
stains most commonly used to separate urothelial from prostatic carcinoma.
Genega et al identified mCEA and p53 staining in 41% and 33% of urothelial carcinomas compared to 12% and
3% in prostatic adenocarcinomas, respectively. 
Immunohistochemical Comparison of Urothelial Carcinoma from High-Grade Prostatic
| ||Leu 7 ||PSA ||PSAP ||CK7 ||HMWK|
|Urothelial Carcinoma ||17% ||0% ||0% ||83-100% ||65-89%|
|High-Grade Prostatic Adenocarcinoma ||94% ||94-100% ||94-100% ||12-33% ||6-11%|
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