Urinary System

Urinary Bladder, Urothelium - Hyperplasia

Narrative
Comment:
Urothelial hyperplasia, defined as an increased number of epithelial cells, is commonly observed with inflammation, with the presence of calculi, or as a response to chemical administration. In general, hyperplasia can either be simple, nodular, or papillary (Figure 1image opens in a pop-up window, Figure 2image opens in a pop-up window, Figure 3image opens in a pop-up window, and Figure 4image opens in a pop-up window), which may not be important to diagnose for occasional and spontaneous cases. Most cases of hyperplasia are focal to diffuse. Hyperplastic cells may be normal in appearance or pleomorphic, or (rarely) may have atypia. Mitotic figures are variable. Metaplastic foci of squamous, glandular, or mixtures of cell metaplasia may be noted. Urothelial hyperplasia may be reversible but may also progress to neoplasia. Hyperplasia is less commonly observed in the mouse. Minimal hyperplasia is difficult to diagnose because of the variability of the bladder appearance during fixation.
Recommendations:
Usually a guideline of an increase above the normal 3- to 4-cell-thick urothelium constitutes hyperplasia. However, sectioning also poses a difficulty in determining minimal or borderline hyperplasias because of folding of the bladder lining in nondistended states. Care should be taken to not confuse tangential sectioning as hyperplasia. Hyperplasia should be diagnosed and given a severity grade. Hyperplastic modifiers such as “simple,” “nodular,” or “papillary” associated with chemical exposure should be discussed in the narrative report.
References:

Cohen SM. 1989. Toxic and nontoxic changes induced in the urothelium by xenobiotics. Toxicol Appl Pharmacol 101:484-498.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/2603162

Cohen SM. 2002. Comparative pathology of proliferative lesions of the urinary bladder. Toxicol Pathol 30:663-671.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/12512866

Cohen SM, Cano M, Anderson T, Garland EM. 1996. Extensive handling of rats leads to mild urinary bladder hyperplasia. Toxicol Pathol 24:251-257.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/8992616

Gaillard ET. 1999. Ureter, urinary bladder and urethra. In: Pathology of the Mouse: Reference and Atlas (Maronpot RR, Boorman GA Gaul BW, eds). Cache River Press, Vienna, IL, 235-258.

Abstract: http://www.cacheriverpress.com/books/pathmouse.htm

Greaves P. 2007. Histopathology of Preclinical Studies, 3rd ed. Elsevier, Amsterdam, 591-592.

Abstract: http://www.sciencedirect.com/science/book/9780444538567

Jokinen MP. 1990. Urinary bladder, ureter, and urethra. In: Pathology of the Fischer Rat: Reference and Atlas (Boorman GA, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds). Academic Press, San Diego, 109-126.

Abstract: http://www.ncbi.nlm.nih.gov/nlmcatalog/9002563

Kunze E. 1998. Hyperplasia, urinary bladder, rat. In: Monographs on Pathology of Laboratory Animals: Urinary System, 2nd ed (Jones TC, Hard GC, Mohr U, eds). Springer, Berlin, 331-368.

Abstract: http://www.ilsi.org/publications/urinarysystem.pdf

Shinohara Y, Frith CH. 1981. Comparison of experimental and spontaneous bladder urothelial hyperplasias occurring in BALB/c mice. Invest Urol 18:233-238.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/7451083
  • Image of hyperplasia in the urinary bladder from a male F344/N rat in a chronic study

    Urothelial hyperplasia (simple) from a male F344/N rat in a chronic study.

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Urothelial hyperplasia (simple) from a male F344/N rat in a chronic study.
Urothelial hyperplasia (simple) with minimal inflammatory infiltration of epithelium and submucosa, from a female Harlan Sprague-Dawley rat in a chronic study.
Urothelial hyperplasia (nodular) from a male F344/N rat in a chronic study.
Urothelial hyperplasia with little to no inflammation, from a male TG/RASH2/CB6F1 mouse.

Authors

John Curtis Seely, DVM, DACVP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Abraham Nyska,  DVM, Diplomate ECVP, Fellow IATP
Expert in Toxicologic Pathology
Visiting Full Professor of Pathology
Sackler School of Medicine, Tel Aviv University
Timrat Israel

Reviewers

Samuel M Cohen, PHD, MD
Professor
Havlik-Wall Professor of Oncology
Director of Pathology Residency Program
Nebraska Medical Center
Omaha, NE

David E. Malarkey DVM, PhD, DACVP, FIATP
Head, National Toxicology Program Pathology Group
Cellular and Molecular Pathology Branch
Division of the National Toxicology Program
National Institute of Environmental Health Sciences
Research Triangle Park, NC