Urethral cancer pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Vindhya BellamKonda, M.B.B.S [2] Aida Javanbakht, M.D.

Overview

Urethral cancer is a rare disease. The pathophysiology of urethral cancer depends on the histological subtypes.

Pathogenesis

Mucous cells in the urethra have the ability to turnover rapidly. It has been suggested that defect in DNA repair mechanism may cause urethral cancer.

Chronic inflammation and strictures: May happen after any surgery on urethra like urethroplasty [1].

Infection: sexually transmitted diseases like HPV type 16 [2].

External radiation therapy [3].

Urethral diverticula in female [4].

Other: Arsenic ingestion

Genetics

The exact gene and mutations that cause urethral cancer are unlnown.

Mutation in TERT promoter, PAX8, GATA3, p63, p40, p53 may play role in sarcomatoid urothelial carcinoma [5].

Fragile histidine triad (FHIT) gene may play a role in causing bladder urothelial carcinoma [6]

Gross Pathology

In end stage type they may appear as an exophytic mass.

Microscopic Pathology

The microscopic view of urethral cancer is depended on the location of teh cancer. The type of the cancer in the distal part of the urethra is usually squamous cell. [7]

  • SCC: keratinization, nuclear atypia. Positive with cytoplasmic beta-catenin stain.
  • Adenocarcinoma:  Columnar epithelium with hyperchromatic nuclei.
  • Clear Cell: clear or eosinophilic cytoplasm, vacuoles in the cytoplasm, hyperchromatic nuclei. Positive with  p53 and vimentin stain.

References

  1. Colapinto V, Evans DH (October 1977). "Primary carcinoma of the male urethra developing after urethroplasty for stricture". J. Urol. 118 (4): 581–4. PMID 916053. 
  2. Cupp MR, Malek RS, Goellner JR, Espy MJ, Smith TF (October 1996). "Detection of human papillomavirus DNA in primary squamous cell carcinoma of the male urethra". Urology. 48 (4): 551–5. PMID 8886059. doi:10.1016/S0090-4295(96)00246-4. 
  3. Mohan H, Bal A, Punia RP, Bawa AS (February 2003). "Squamous cell carcinoma of the prostate". Int. J. Urol. 10 (2): 114–6. PMID 12588611. 
  4. Ahmed K, Dasgupta R, Vats A, Nagpal K, Ashrafian H, Kaj B, Athanasiou T, Dasgupta P, Khan MS (June 2010). "Urethral diverticular carcinoma: an overview of current trends in diagnosis and management". Int Urol Nephrol. 42 (2): 331–41. PMID 19649767. doi:10.1007/s11255-009-9618-x. 
  5. Wang X, Lopez-Beltran A, Osunkoya AO, Wang M, Zhang S, Davidson DD, Emerson RE, Williamson SR, Tan PH, Kaimakliotis HZ, Baldridge LA, MacLennan GT, Montironi R, Cheng L (April 2017). "TERT promoter mutation status in sarcomatoid urothelial carcinomas of the upper urinary tract". Future Oncol. 13 (8): 705–714. PMID 28052688. doi:10.2217/fon-2016-0414. 
  6. Zhang CT, Lu R, Lin YL, Liu RL, Zhang ZH, Yang K, Dang RF, Zhang HT, Shen YG, Kong PZ, Ren HL, Li XL, Quan W, Xu Y (2012). "The significance of fragile histidine triad protein as a molecular prognostic marker of bladder urothelial carcinoma". J. Int. Med. Res. 40 (2): 507–16. PMID 22613411. doi:10.1177/147323001204000212. 
  7. Grivas PD, Davenport M, Montie JE, Kunju LP, Feng F, Weizer AZ (December 2012). "Urethral cancer". Hematol. Oncol. Clin. North Am. 26 (6): 1291–314. PMID 23116581. doi:10.1016/j.hoc.2012.08.006. 
  8. Cantiello F, Cicione A, Salonia A, Autorino R, Tucci L, Madeo I, Damiano R (May 2013). "Periurethral fibrosis secondary to prostatic inflammation causing lower urinary tract symptoms: a prospective cohort study". Urology. 81 (5): 1018–23. PMID 23608423. doi:10.1016/j.urology.2013.01.053. 

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