Hepatic Lesions Caused by Large Granular Lymphocyte Leukemia in Fischer 344 Rats: Similar Morphologic Features and Morphogenesis to Those of Nodular Regenerative Hyperplasia (NRH) in the Human Liver

Toxicol Pathol. 2015 Aug;43(6):852-64. doi: 10.1177/0192623315578719. Epub 2015 Apr 22.

Abstract

To characterize the hepatic lesions in Fischer 344 (F344) rats afflicted with large granular lymphocyte (LGL) leukemia, the livers of rats with LGL leukemia at various stages were examined histopathologically and immunohistochemically. The morphologic features in the livers of rats afflicted with LGL leukemia were diffuse, uniform-sized, granular, or micronodular lesions consisting of hepatocytes showing centrilobular atrophy and perilobular hypertrophy (CAPH) without fibrosis. With progression in the stage of the LGL leukemia, the severity of the CAPH of hepatocytes increased resulting in fatty change and/or single-cell necrosis, along with compensatory hyperplasia of the hepatocytes, finally resulting in lesions similar to those seen in nodular regenerative hyperplasia (NRH) in the human liver. The CAPH of hepatocytes was a nonspecific tissue adaptation against ischemia or hypoxemia and/or imbalance in blood supply due to disturbance in the portal circulation and hemolytic anemia induced by the leukemia cells. In addition, direct and/or indirect hepatocellular injuries by leukemia cells were considered to be necessary for the formation of human NRH-like lesions. Morphogenetic investigation of the livers of rats afflicted with LGL leukemia may be helpful to clarify the pathogenesis of NRH in the human liver.

Keywords: F344 rat; LGL leukemia; hyperplasia; liver.

MeSH terms

  • Animals
  • Atrophy
  • Hepatocytes / pathology
  • Hepatomegaly / pathology
  • Humans
  • Hyperplasia / pathology
  • Immunohistochemistry
  • Leukemia, Large Granular Lymphocytic / complications
  • Leukemia, Large Granular Lymphocytic / pathology*
  • Liver / pathology
  • Liver Diseases / etiology
  • Liver Diseases / pathology*
  • Mitosis
  • Portal Vein / pathology
  • Rats
  • Rats, Inbred F344
  • Spleen / pathology