Hepatobiliary System

Liver - Pigment

Narrative
Comment:
Both endogenous and exogenous pigment can occur in hepatocytes, but pigmentation occurs more often in Kupffer cells. Pigment may be prominent in portal areas. Identification of hepatic pigment typically requires multiple special stains. Different pigments frequently contain some iron and will thus have variable positivity with Prussian blue stain. In Figure 1, pigment is deposited in clusters of aggregated Kupffer cells, which was given a severity grade of 3+ (moderate). Figure 2 and Figure 3 show evidence of pigment deposition in Kupffer cells as well as in hepatocytes. The pigment deposition is primarily centrilobular and was given a severity grade of 3+ (moderate). In Figure 4, the pigment deposition is primarily within hepatocytes and has a panlobular distribution.
Recommendations:
Definitive pigment identification is often difficult in histologic sections, even with a battery of special stains. Therefore, a diagnosis of “pigment” is most appropriate. The pathology narrative should describe the morphologic features of the pigmentation, the lobular distribution, the cell type affected, and any accompanying histologic changes that might be associated with the pigment deposition. The pathologist may also speculate in the pathology narrative as to the type of pigment present. A severity grade should be assigned based on the relative amounts of pigment present.
References:

Cattley RC, Popp JA. 2002. Liver. In: Handbook of Toxicologic Pathology (Haschek WM, Rousseaux CG, Wallig MA, eds). Academic Press, San Diego, 2:187-225.

Eustis SL, Boorman GA, Harada T, Popp JA. 1990. Liver. In: Pathology of the Fischer Rat (Boorman GA, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds). Academic Press, San Diego, 71-94.

Evans JG, Lake BG. 1998. The digestive system II. Hepatobiliary system. In: Target Organ Pathology (Turton J, Hooson J, eds). Taylor and Francis, London, 61-98.

Greaves P. 2007. Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation, 3rd ed. Elsevier, Amsterdam.

Abstract: http://www.sciencedirect.com/science/book/9780444527714

Harada T, Enomoto A, Boorman GA, Maronpot RR. 1999. Liver and gallbladder. In: Pathology of the Mouse: Reference and Atlas (Maronpot RR, Boorman GA, Gaul BW, eds). Cache River Press, Vienna, IL, 119-183.

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

Hardisty JF, Brix AE. 2005. Comparative hepatic toxicity: Prechronic/chronic liver toxicity in rodents. Toxicol Pathol 33:35-40.

Full Text: http://tpx.sagepub.com/content/33/1/35.full.pdf

Haschek WM, Rousseaux CG, Wallig MA. 2010. Fundamentals of Toxicologic Pathology, 2nd ed. Academic Press, San Diego, 197-235.

National Toxicology Program. 1993. NTP TR-394. Toxicology and Carcinogenesis Studies of Acetaminophen (CAS No. 103-90-2) in F344 Rats and B6C3F1 Mice (Feed Studies). NTP, Research Triangle Park, NC.

Full Text: https://ntp.niehs.nih.gov/ntp/htdocs/lt_rpts/tr394.pdf

Thoolen B, Maronpot RR, Harada T, Nyska A, Rousseaux C, Nolte T, Malarkey D, Kaufmann W, Kutter K, Deschl U, Nakae D, Gregson R, Winlove M, Brix A, Singl B, Belpoggi F, Ward JM. 2010. Hepatobiliary lesion nomenclature and diagnostic criteria for lesions in rats and mice (INHAND). Toxicol Pathol 38:5S-81S.

Full Text: http://tpx.sagepub.com/content/38/7_suppl/5S.full
  • Image of pigment in the liver from a male B6C3F1 mouse in a subchronic study

    Pigment in hepatocytes in a male B6C3F1 mouse from a subchronic study.

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Pigment in hepatocytes in a male B6C3F1 mouse from a subchronic study.
Pigment in hepatocytes in a male B6C3F1 mouse from a subchronic study.
Pigment in hepatocytes in a male Harlan Sprague-Dawley rat from a chronic study.
Pigment in hepatocytes in a male Harlan Sprague-Dawley rat from a chronic study.
Pigment in hepatocytes in a male Harlan Sprague-Dawley rat from a chronic study.
Pigment in hepatocytes in a male Harlan Sprague-Dawley rat from a chronic study.
Pigment in hepatocytes in a female Wistar Han rat from a subchronic study.
Pigment in hepatocytes in a female Wistar Han rat from a subchronic study.

Author

Robert R. Maronpot, DVM, MS, MPH, DACVP, DABT, FIATP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Reviewers

John Cullen, VMD, PhD, DACVP, FIATP
Anatomic Pathology, Professor
North Carolina State University College of Veterinary Medicine
Raleigh, NC

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