Pathology of Transitional Cell Prostate Carcinoma

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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.

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 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]

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 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.

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.

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 -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]

Lerner SP, Shen S. Pathologic assessment and clinical significance of prostatic involvement by transitional cell carcinoma and prostate cancer. Urol Oncol. 2008 Sep-Oct. 26():481-. [Medline].

Wood DP Jr, Montie JE, Pontes JE, VanderBrug Medendorp S, Levin HS. Transitional cell carcinoma of the prostate in cystoprostatectomy specimens removed for bladder cancer. J Urol. 1989 Feb. 141(2):346-9. [Medline].

Esrig D, Freeman JA, Elmajian DA, et al. Transitional cell carcinoma involving the prostate with a proposed staging classification for stromal invasion. J Urol. 1996 Sep. 156(3):1071-6. [Medline].

Reese JH, Freiha FS, Gelb AB, Lum BL, Torti FM. Transitional cell carcinoma of the prostate in patients undergoing radical cystoprostatectomy. J Urol. 1992 Jan. 147(1):92-5. [Medline].

Revelo MP, Cookson MS, Chang SS, Shook MF, Smith JA Jr, Shappell SB. Incidence and location of prostate and urothelial carcinoma in prostates from cystoprostatectomies: implications for possible apical sparing surgery. J Urol. 2004 Feb. 171(2 Pt 1):646-51. [Medline].

Njinou Ngninkeu B, Lorge F, Moulin P, Jamart J, Van Cangh PJ. Transitional cell carcinoma involving the prostate: a clinicopathological retrospective study of 76 cases. J Urol. 2003 Jan. 169(1):149-52. [Medline].

Shen SS, Lerner SP, Muezzinoglu B, Truong LD, Amiel G, Wheeler TM. Prostatic involvement by transitional cell carcinoma in patients with bladder cancer and its prognostic significance. Hum Pathol. 2006 Jun. 37(6):726-34. [Medline].

Pettus JA, Al-Ahmadie H, Barocas DA, et al. Risk assessment of prostatic pathology in patients undergoing radical cystoprostatectomy. Eur Urol. 2008 Feb. 53(2):370-5. [Medline].

Melicow MM, Hollowell JW. Intra-urothelial cancer: carcinoma in situ, Bowen’s disease of the urinary system: discussion of thirty cases. J Urol. 1952 Oct. 68(4):763-. [Medline].

Prout GR Jr, Griffin PP, Daly JJ, Heney NM. Carcinoma in situ of the urinary bladder with and without associated vesical neoplasms. Cancer. 1983 Aug 1. 52(3):524-32. [Medline].

Herr HW, Donat SM. Prostatic tumor relapse in patients with superficial bladder tumors: 15-year outcome. J Urol. 1999 Jun. 161(6):1854-7. [Medline].

Arce J, Gaya JM, Huguet J, et al. Can we identify those patients who will benefit from prostate-sparing surgery? Predictive factors for invasive prostatic involvement by transitional cell carcinoma. Can J Urol. 2011 Feb. 18(1):5529-36. [Medline].

Tabibi A, Simforoosh N, Parvin M, et al. Predictive factors for prostatic involvement by transitional cell carcinoma of the bladder. Urol J. 2011 Winter. 8(1):43-7. [Medline].

Varinot J, Cussenot O, Roupret M, Conort P, Bitker MO, Chartier-Kastler E, et al. HOXB13 is a sensitive and specific marker of prostate cells, useful in distinguishing between carcinomas of prostatic and urothelial origin. Virchows Arch. 2013 Dec. 463(6):803-9. [Medline].

Aharony S, Baniel J, Yossepowitch O. Clinically unconfirmed positive urinary cytology: diagnostic implications and oncological outcomes. BJU Int. 2011 May 26. [Medline].

Cheville JC, Dundore PA, Bostwick DG, et al. Transitional cell carcinoma of the prostate: clinicopathologic study of 50 cases. Cancer. 1998 Feb 15. 82(4):703-7. [Medline].

Steven S Shen, , PhD Professor of Pathology and Laboratory Medicine, Houston Methodist Hospital and Weill Medical College of Cornell University; Associate Medical Director of Surgical Pathology, Houston Methodist Hospital

Steven S Shen, , PhD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, American Urological Association, College of American Pathologists, United States and Canadian Academy of Pathology, International Society of Urological Pathology

Disclosure: Nothing to disclose.

Liang Cheng, MD Professor of Pathology and Urology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine; Chief, Genitourinary Pathology Service, Indiana University Health

Liang Cheng, MD is a member of the following medical societies: American Association for Cancer Research, American Urological Association, College of American Pathologists, United States and Canadian Academy of Pathology, International Society of Urological Pathology, Arthur Purdy Stout Society

Disclosure: Nothing to disclose.

Pathology of Transitional Cell Prostate Carcinoma

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