—  SPECIALTY CONFERENCE  —

Genitourinary Pathology

Case 4 - Urothelial Carcinoma of the Prostate

John C. Cheville
Mayo Medical School
Rochester, MN


Click on each slide thumbnail image for an enlarged view
Clinical History
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.

Diagnosis
Urothelial Carcinoma of the Prostate

Discussion
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 cases. [1, 2, 3, 4, 5, 6] In contrast, primary urothelial carcinoma of the prostate accounts for less than 5% of prostatic carcinomas. [7] Urothelial carcinoma arising in the prostate has a separate TNM staging classification based on the depth of invasion in the prostate. [8] 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. [9, 10, 11] 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. [12, 13] The 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. [13] 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. [12]

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. [12] 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 upper tracts.

Urothelial Carcinoma of the Prostate:
Association with Urothelial Carcinoma outside the Prostate in 50 Surgically Treated Patients [12]

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 Cystoprostatectomy [12]

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 Patients
CIS of Prostatic Urethra, Ducts and Acini versus Prostatic Stromal Invasion

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 prostate: [8]

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)

Differential Diagnosis:
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. [13] 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. [13, 15] In addition, Genega et al identified mCEA and p53 staining in 41% and 33% of urothelial carcinomas compared to 12% and 3% in prostatic adenocarcinomas, respectively. [16]

Immunohistochemical Comparison of Urothelial Carcinoma from High-Grade Prostatic Adenocarcinoma

  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%

References

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