Secondary Polycythemia in Male B6C3F1 Mice with Spontaneously Occurring Hepatocellular Carcinomas

Abstract

The purpose of this study was to investigate the cause of polycythemia occurring in control male B6C3F, mice with hepatocellular carcinomas from 2-yr carcinogenicity studies. Erythrocyte counts and plasma erythropoietin levels in these mice were significantly increased compared to those in nontumor-bearing mice. Hepatocellular carcinomas in the mice were well differentiated, and the neoplastic hepatocytes contained either or both of 2 types of intracytoplasmic inclusion bodies; one was relatively large and weakly eosinophilic (pale inclusion body), while the other was relatively small and strongly eosinophilic (globular inclusion body). The pale eosinophilic inclusions but not the globular ones were immunohistochemically positive for erythropoietin. Ultrastructurally, the erythropoietin-positive inclusions were characterized by granular materials in dilated cisternae of rough endoplasmic reticulum, suggesting increased protein synthesis. Erythropoietin-negative inclusions were dense bodies that were not surrounded by a delimiting membrane. These findings indicate that polycythemia in hepatocellular carcinoma-bearing mice occurs secondary to excess synthesis and secretion of erythropoietin by neoplastic hepatocytes.

A Hepatocellular Adenoma in a Diet-induced Obese Mouse

“…The eosinophilic cytoplasmic inclusions were also thought to support the diagnosis because such inclusions are characteristically found in murine hepatic neoplasms 2 – 5 . Also, the ultrastructure of the inclusions was the same as in previous reports 2 .…”

“…The eosinophilic cytoplasmic inclusions were also thought to support the diagnosis because such inclusions are characteristically found in murine hepatic neoplasms 2 – 5 . Also, the ultrastructure of the inclusions was the same as in previous reports 2 . 5 The fact that they were found in the rough endoplasmic reticulum was presumably the result of abnormal transportation of proteins and lipids 6 , 7 …”

Giant Mitochondria in Pancreatic Acinar Cells of Alloxan-Induced Diabetic Rats

“…Giant cytoplasmic eosinophilic granules have often been observed in various cells under some pathological conditions and age-related changes. They are formed when cytoplasmic organelles such as endoplasmic reticulum, mitochondria, lysosome, secretory granules, and cytoskeleton are altered or increased (Herdson et al 1964; Horinouchi et al 1997; Ito et al 1998; Kambara et al 2009; Ozaki et al 1994; Remmer and Merker 1963). Eosinophilic inclusions or granules have also been detected as viral inclusion bodies and nuclear invagination (Kim et al 2002; Weller and Stoddard 1952).…”