Bladder cancer pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief:  Farima Kahe M.D. [3] Shanshan Cen, M.D. [4] Steven C. Campbell, M.D., Ph.D.

## Overview

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Genes involved in the pathogenesis of bladder cancer include HRAS, Rb1, PTEN/MMAC1, NAT2, and GSTM1. On gross pathology, flat lesions or papillary lesions are characteristic findings of non-invasive transitional cell carcinomas; a large infiltrative mass or a multifocal, flat to papillary lesion with delicate fronds are characteristic findings of invasive transitional cell carcinomas. On microscopic histopathological analysis, loss of cell polarity, nuclear crowding, and cytologic atypia are characteristic findings of flat lesion; fibrovascular stalks, umbrella cells, and eosinophilic cytoplasm are characteristic findings of papillary lesion; invasion beyond the basement membrane is the characteristic finding of invasive transitional cell carcinomas.

## Pathogenesis

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* Under normal conditions, the bladder, the lower part of the kidneys, the ureters, and the proximal urethra are lined with a specialized mucous membrane referred to as transitional epithelium (also called urothelium).[1]
* Most cancers that form in the bladder, the lower part of the kidneys, the ureters, and the proximal urethra are transitional cell carcinomas (also called urothelial carcinomas) that derive from transitional epithelium.
* Urothelial carcinomas may be non-invasive or invasive.
* Urothelial carcinomas with mixed epithelial features are invasive tumors that have different types of cells mixed with the cancer cells.

## Genetics

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* Genetic mutations involved in the pathogenesis of bladder cancer include:[2]

* HRAS mutation
* Rb1 mutation
* PTEN/MMAC1 mutation
* NAT2 slow acetylator phenotype
* GSTM1 null phenotype

## Gross Pathology

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* Non-invasive urothelial carcinoma[3][4]

* On gross pathology, flat lesions or papillary lesions are characteristic findings of non-invasive urothelial carcinoma.

* Invasive urothelial carcinoma[5]

* On gross pathology, a large infiltrative mass or a multifocal, flat to papillary lesion with delicate fronds are characteristic findings of invasive urothelial carcinoma.

## Microscopic Pathology

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* Non-invasive urothelial carcinoma[3][6][7]

* Flat lesions

* On microscopic histopathological analysis, loss of cell polarity, nuclear crowding, and cytologic atypia are characteristic findings.

* Papillary lesions

* On microscopic histopathological analysis, fibrovascular stalks, umbrella cells, and eosinophilic cytoplasm are characteristic findings.

* Invasive urothelial carcinoma

* On microscopic histopathological analysis, invasion beyond the basement membrane is the characteristic finding.[5]

Image showing muscle invasive urothelial carcinoma [1]

## References

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1. ↑ Bladder Cancer. Canadian Cancer Society 2015. http://www.cancer.ca/en/cancer-information/cancer-type/bladder/bladder-cancer/urothelial-carcinoma/?region=ab Accessed on October, 1 2015
2. ↑ National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq#link/_359_toc Accessed on October, 1 2015
3. ↑ 3.0 3.1 Cheng L, Cheville JC, Neumann RM, Bostwick DG (2000). "Flat intraepithelial lesions of the urinary bladder". Cancer. 88 (3): 625–31. PMID 10649257.CS1 maint: Multiple names: authors list (link)
4. ↑ Cheng L, Cheville JC, Neumann RM, Bostwick DG (1999). "Natural history of urothelial dysplasia of the bladder". Am J Surg Pathol. 23 (4): 443–7. PMID 10199474.CS1 maint: Multiple names: authors list (link)
5. ↑ 5.0 5.1 Pons F, Orsola A, Morote J, Bellmunt J (2011). "Variant forms of bladder cancer: basic considerations on treatment approaches". Curr Oncol Rep. 13 (3): 216–21. doi:10.1007/s11912-011-0161-4. PMID 21360040.CS1 maint: Multiple names: authors list (link)
6. ↑ McKenney JK, Amin MB, Young RH (2003). "Urothelial (transitional cell) papilloma of the urinary bladder: a clinicopathologic study of 26 cases". Mod Pathol. 16 (7): 623–9. doi:10.1097/01.MP.0000073973.74228.1E. PMID 12861056.CS1 maint: Multiple names: authors list (link)
7. ↑ Picozzi S, Casellato S, Bozzini G, Ratti D, Macchi A, Rubino B; et al. (2013). "Inverted papilloma of the bladder: a review and an analysis of the recent literature of 365 patients". Urol Oncol. 31 (8): 1584–90. doi:10.1016/j.urolonc.2012.03.009. PMID 22520573.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)

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