Pathology of Transitional Cell Prostate Carcinoma

Transitional cell carcinoma (TCC) of the prostate is carcinoma of urothelial origin with a pathology that involves prostatic tissue. 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 prostatic tissue; it results from direct pagetoid spread of urothelial cancer in situ (CIS) or direct pathologic invasion of bladder urothelial carcinoma.

The reported incidence of prostatic TCC ranges from 21.8-36.7%, depending mainly on the manner of examination. ^{[1, 2, 3, 4, 5, 6, 7, 8]} Over 90% of cases are associated with bladder cancer.

Gross findings

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

Prostatic transitional cell carcinoma (TCC) may occur as a primary carcinoma of the prostatic urethra or duct, but more commonly, it arises secondary to bladder cancer. ^[9] 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.

The main factors that are predictive of the occurrence of prostatic TCC include the following ^{[2, 10, 11]} :

• Presence of either multifocal, papillary TCC of the bladder or carcinoma in situ of the bladder

• Location of tumor at the trigone or the bladder neck ^[12]

• Presence of advance-stage bladder cancer

In a study of 100 patients with TCC of the bladder, Tabibi et al found that the distance between the tumor and the bladder neck was predictive of whether the carcinoma would involve the prostate as well. ^[13]

Molecular/genetic characteristics

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.

In a review of 42 biopsies, Varinot and colleagues found HOXB13 expression was negative or weakly positive in individuals with carcinomas of urothelial origin, and positive in patients with prostatic carcinoma. They concluded that HOXB13 was a marker for prostatic origin of a carcinoma with good sensitivity (89 %) and very good specificity (100 %) and had the potential to be a diagnostic aide when poorly differentiated or neuroendocrine tumors were encountered. ^[14]

Primary prostatic papillary urothelium 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 cancer in situ (CIS) may involve the prostatic urethra, the prostatic duct, and the 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; these cells have pleomorphic nuclei, coarse chromatin, and frequent mitoses or apoptosis. There may be large areas of well-defined nests of CIS as a result of CIS's extension into prostatic acini. Periductal fibrosis or fibrosis of the acini, as well as chronic inflammation, may be evident. ^[15]

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: (1) invasive carcinoma arising from the prostatic urethra and duct, which is often associated with CIS within the prostatic duct or acini, and (2) 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 transitional cell carcinoma (TCC) is identical to that of bladder carcinoma. Tumors are positive for cytokeratin (CK) 7 (90%), p63 (87%), thrombomodulin (79%), CK20 (61%), high–molecular weight CK (HMWCK) 34βE12 (59%), CK5/6 (55%), and uroplakin III (55%).

TNM staging of transitional cell carcinoma (TCC) involving the prostate depends on the primary site.

Prostatic TCC secondary to bladder TCC

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

Primary prostatic urethra urothelial carcinoma

The tumor is staged according to the depth of invasion and the degree of involvement of the prostate, as follows:

• Ta - Noninvasive, papillary carcinoma

• Tis - Urethral CIS

• T1 - Invasion of subepithelial connective tissue

• T2 - Involvement of the prostatic stroma

• T3 - Invasion beyond the prostatic capsule or bladder neck

• T4 - Invasion of adjacent organs

It is well established that for patients with transitional cell carcinoma (TCC), prostatic stroma invasion, regardless of whether it represents primary or secondary involvement, is associated with poor prognosis. Currently, such disease is staged as pT4a bladder cancer.

In contrast, prostatic involvement solely by cancer in situ (CIS) has no bearing on the staging of bladder cancer, although it may have implications for intravesical therapy. ^{[3, 4, 5, 6, 7, 16]}

The 5-year survival rate has ranged from 50-100% for patients with prostatic urothelium CIS alone and from 20-60% for patients with prostatic stroma invasion, independent of bladder tumor stage. ^{[3, 4, 5, 6, 7, 8, 16]}