Hepatobiliary System

Liver, Hepatocyte – Increased Mitosis

Narrative
Comment:
A high mitotic frequency can be seen during phases of early growth, during physiologic conditions such as pregnancy, or in rodents bearing tumors at other sites. While occasional mitoses can be seen in a normal liver, finding more than one or two mitoses per 10 high-power fields is not typical for adult rodents. In this example, the high frequency of mitosis (Figure 1, arrows) is a repair response following hepatocyte loss secondary to treatment with a hepatotoxicant.
Recommendations:
An increased frequency of mitosis is unusual; it should be documented whenever present and given a qualitative severity grade.
References:

Echave Llanos JM, Aloisso MD, Souto M, Balduzzi R, Surur JM. 1971. Circadian variations of DNA synthesis, mitotic activity, and cell size of hepatocyte population in young immature male mouse growing liver. Virchows Arch B Cell Pathol 8:309-317.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/4998660

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

Theologides A, Zaki GF. 1969. Mitotic index in the regenerating liver of tumor-bearing mice. Cancer Res 29:1913-1915.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/5358208

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 increased mitosis in the liver from a male F344/N rat in an acute study

    Increased mitosis (arrows) in a male F344/N rat from an acute repeated-dose study.

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Increased mitosis (arrows) in a male F344/N rat from an acute repeated-dose study.
Increased mitosis (arrows) in a male F344/N rat from an acute repeated-dose 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