|Extramedullary Hematopoiesis (EMH) - Click on thumbnails to view larger images|
|Extramedullary hematopoiesis (EMH) can occur in the liver, especially when there is long-standing anemia. Typical morphological features consist of small aggregates of cells with intensely basophilic nuclei (erythroid) or small collections of immature and mature myelocytic cells (myelopoiesis) located in the sinusoids and, in severe cases, in portal areas.|
Extramedullary hematopoiesis characterized by small aggregates of immature erythroid cells.
|Multiple aggregates of neutrophilic band cells and erythroid precursor cells are present in the sinusoids with a large aggregate in a portal area.|
|Hepatocellular Hypertrophy/Cytomegaly - Click on thumbnails to view larger images|
Hepatocellular hypertrophy is frequently seen in the liver following exposure to agents that cause hepatic enzyme induction. The hypertrophy typically starts in the centrilobular area and extends to the mid-lobular and eventually periportal areas provided there is sufficient stimulus over time. In situations of prolonged exposure to some agents, the hypertrophic hepatocytes are seen to have enlarged polyploid nuclei. With some treatment regimens, hepatocytes may actually become cytomegalic. Cytomegalic hepatocytes typically have single polyploid and/or multiple nuclei.
|Generalized hepatocyte hypertrophy involving all portions of the hepatic lobule. Higher magnification shows a cytomegalic hepatocyte in the lower right. It has an enlarged nucleus with multiple nucleoli.|
|Hypertrophic and cytomegalic hepatocytes are present in the centrilobular and midlobular areas in these images from a mouse treated with chlordane for several months. Some cytomegalic hepatocytes have several nuclei.|
|Intrahepatocyte Erythrocytes and Pigment - Click on thumbnails to view larger images.|
The presence of erythrocytes within hepatocytes is seen on rare occasions. It is not known for sure why or how intact erythrocytes come to be located within individual hepatocytes. Perhaps it is by erythrophagocytosis, but that is only supposition. The affected hepatocytes often become very large and, presumably, ultimately die and become phagocytosized by Kupffer cells along with their contents. Exacerbation of this change by chronic treatment may occur. We have seen it in three of approximately 500 NTP two-year studies. The cause and significance of this change is not known.
|Several hepatocytes contain erythrocytes. The nucleus is of normal size while the cytoplasmic mass is markedly enlarged with margination of the cytoplasm. The nucleus in these cells is often localized at the cell margin.|
|In this example, the intrahepatocytic erythrocytes have become partially lysed.|
|In addition to an hepatocytes filled with erythrocytes, there is accumulation of pigment within Kupffer cells (macrophages).|
|Kupffer cells throughout the liver are filled with golden brown pigment which is believed to represent breakdown of hemoglobin.|
|Polyploidy - Click on thumbnails to view larger images.|
The normal mouse liver contains hepatocytes that are diploid, tetraploid, and octaploid with increase ploidy occurring as the animal ages. A tetraploid hepatocyte may have twice the complement of DNA either by having two diploid nuclei (binucleated hepatocyte) or a single nucleus which contains twice the diploid amount of DNA. A variety of treatment regimens cause alterations in ploidy with single hepatocytes sometimes having several diploid nuclei (multinucleated hepatocytes). The hepatocyte regeneration that follows partial hepatectomy is the result of proliferation of diploid cells. Polyploidy develops once the liver has completed regeneration.
|Extreme polyploidy consisting of cytomegalic hepatocytes with very large nuclei as well as cytomegalic hepatocytes with several diploid nuclei is seen in these images from a mouse treated with chlordane for 18 months.|
|Multinucleated Hepatocytes - Click on thumbnails to view larger images|
|Adult mouse liver with scattered multinucleated hepatocytes.|
|A mouse treated chronically with chlordane, showing enlarged hepatocytes with multiple nuclei.|
|Multinucleated hepatocytes in a B6C3F1 male mouse.|