FIGURE 7.

Histological analysis of the liver of older CerS2 null mice. A, low magnification of a section through the right median lobe of a 12- month-old CerS2 null mouse liver. The lobe is markedly enlarged, and its capsular outline is convex due to replacement of the normal parenchyma by coalescing nodules. All are nodules of regenerative hepatocellular hyperplasia. B, high magnification showing the typical appearance of hepatocytes within nodules of regenerative hyperplasia. The hepatocytes are not organized into cords, and their size is variable, and large cells abound. The arrowhead indicates a focus of spindle cell proliferation, probably oval cell hyperplasia. An apoptotic cell is identified by an arrow. C, high magnification showing hepatocytes with round intracytoplasmic structures consistent with Mallory bodies (arrowhead). A portal triad showing mild oval cell hyperplasia located in the nodule is identified by an arrow. D, high magnification of florid oval cell hyperplasia. E, hepatocellular carcinoma. The field is occupied by two thick trabeculae composed of neoplastic hepatocytes. The inset shows subgross magnification of a similar tumor. F, hepatocellular carcinoma. This tumor is less well differentiated than the one shown in E. The neoplastic hepatocytes have a high nuclear/cytoplasmic ratio, and mitotic figures are common (arrowheads). The inset shows differentiation into glandular (adenoid) structures in a hepatocellular carcinoma from another mouse. G, low magnification of a liver with cystic degeneration/spongiosis hepatitis. The lesion consists of multiple variably sized cavities. The boxed area is shown in H. H, in the lower half there are several cavities (asterisks) lined by hepatocytes. In the surrounding parenchyma, there is marked bile duct and oval cell hyperplasia (arrows). The inset shows cystic degeneration from another mouse exhibiting accumulation of proteinaceous material within the cavity. I, high magnification of two small cysts of spongiosis hepatitis with walls composed of hepatocytes (arrowheads). Free-floating cells and a small amount of eosinophilic fluid are present in the cavities.