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Transitional Cell Carcinoma Involving the Prostate

Definition Transitional cell carcinoma (TCC) of the prostate is carcinoma of urothelial origin that involves prostatic tissue.

Etiology

Prostatic TCC may occur as a primary carcinoma of the prostatic urethra or duct; more commonly, it occurs secondary to bladder cancer.11 Well-established risk factors associated with carcinoma of the urothelium of the prostatic urethra or duct and the urinary bladder are cigarette smoking and any exposure to urothelium-specific carcinogens. Location

Primary prostatic TCC involves the entire prostatic urethra, particularly near the verumontanum, the large prostatic duct, and nearby acini. Secondary prostatic TCC mainly involves the bladder neck or posterior prostate tissue; it results from direct pagetoid spread of urothelial CIS or direct invasion of bladder urothelial carcinoma. Clinical Features and Imaging

Over 90% of cases of prostatic TCC are associated with bladder cancer. It is well established that prostatic stroma invasion, regardless of whether of primary or secondary involvement, is associated with poor prognosis. Currently, such disease is staged as pT4a bladder cancer. In contrast, prostatic involvement solely by CIS has no bearing on the staging of bladder cancer, but it may have implications for intravesical therapy.3,4,5,6,12,7 Gross Findings

Prostatic urethral involvement solely by CIS may not be evident grossly. Extensive prostatic duct and acini involvement may appear as areas of lumina necrosis and periductal fibrosis. In cases of prostatic stroma invasion, there are irregular areas of induration and fibrosis. Microscopic Findings

Primary prostatic papillary urothelial carcinoma is exceedingly rare. It is characterized by papillary growth lined by urothelial cells of multiple layers with mild to severe cytologic atypia. Endophytic growth pattern with involvement of superficial suburethral tissue and ductal spread may occur.

Urothelial CIS may involve the prostatic urethra, the prostatic duct, and acini. The vast majority of cases arise synchronously with bladder urothelial neoplasia or from pagetoid spread from the bladder neck. CIS is characterized by partial or complete replacement of urethra or duct by highly atypical urothelial cells with pleomorphic nuclei, coarse chromatin, and frequent mitoses or apoptosis. There may be large areas of well-defined nests of CIS as a result of extension of CIS into prostatic acini. Periductal fibrosis or fibrosis of the acini, as well as chronic inflammation, may be evident.

Invasion of urothelial carcinoma into prostatic stroma is characterized by irregular nests, clusters, or single atypical cells that infiltrate into dense prostatic tissue. Two well-recognized pathways of invasive carcinomas have been described: invasive carcinoma arising from prostatic urethra and duct, which is often associated with CIS within the prostatic duct or acini; and prostatic stroma invasion, in which bladder cancer penetrates from posterior periprostatic soft tissue or the bladder neck. Focal invasion of superficial lamina propria has also been reported to occur in association with prostatic urethra CIS. Immunohistochemistry

The immunoprofile of prostatic TCC is identical to that of bladder carcinoma. Tumors are positive for CK7 (90%), P63 (87%), thrombomodulin (79%), CK20 (61%), HMWCK 34βE12 (59%), CK5/6 (55%), and Uroplakin III (55%). Molecular/Genetics

The molecular and genetic features of prostatic TCC are similar to those of bladder TCC. Common cytogenetic abnormalities are chromosomal losses (2q, 5q, 8p, 9p, 9q, 11p, 18q) and gains (1q, 5p, 8q, 17q). Many oncogenes (Her2/neu, H-ras, EGFR, cyclin, and MDM2) and tumor suppressor genes (p53, RB, and PTEN) have been implicated in the tumorigenesis. Tumor Spread and Staging

TNM staging of TCC involving the prostate depends on the primary site.

Prostatic TCC secondary to bladder transitional cell carcinoma.

If prostatic stromal invasion is present, it is staged as pT4a bladder cancer, regardless of whether there is contiguous invasion of prostatic urethra, prostatic duct, or acini or direct, penetrating invasion of the bladder. If the prostate is only involved by CIS, the stage of bladder tumor depends on the depth of invasion into the bladder, independent of the amount and location of CIS.

Primary prostatic urethra urothelial carcinoma.

Tumor is staged according to the depth of invasion and the degree of involvement of the prostate: Ta, noninvasive papillary carcinoma; Tis, urethra CIS; T1, invasion of subepithelial connective tissue; T2, involvement of prostatic stroma; T3, invasion beyond the prostatic capsule or bladder neck; T4, invasion of adjacent organs. Prognosis and Predictive Factors

Studies have shown that the prognosis for patients with TCC involving the prostate is closely associated with the presence or absence of prostatic stromal invasion. The 5-year survival rate has ranged from 50-100% for patients with prostatic urothelial CIS alone and from 20-60% for patients with prostatic stromal invasion, independent of bladder tumor stage.3,4,5,6,12,7,8 Differentials

High-grade prostate adenocarcinoma Metastatic carcinoma Metastatic Tumors Prostate ductal adenocarcinoma