carefully review the “checklist” (Table 6.1) of the most commonly missed histologic findings in this setting (Figs. 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, and 6.7); and (4) correlate with clinical features, specifically searching for subtle changes related to clinically suspected condition and for features of diseases most commonly associated with a normal/near-normal pattern (Table 6.2). Chapter 7 discusses the “normal/near-normal” differential in more detail.
Table 6.1 Most common “easy-to-miss” findings in otherwise normal/nearly normal liver samples
(especially primary biliary cirrhosis) (Table 6.4). Fatty liver disease, especially in the setting of advanced fibrosis, can also show relatively dense portal infiltrate as a nonspecific finding, mimicking a superimposed chronic hepatitis. Cases with a pronounced plasma cell component are best classified as “plasma cell rich/autoimmune” pattern.
Figure 6.2 Ito (stellate) cell hyperplasia. Several Ito cells, characterized by multiple small clear cytoplasmic vacuoles indenting the nuclei, are present within spaces of Disse.
Figure 6.3 Hairy cell leukemia. A sinusoidal infiltrate by bland cells, mimicking Kupffer cell hyperplasia, is seen in this example of hairy cell leukemia.
Figure 6.4 Nodular regenerative hyperplasia (NRH). Subtle areas of hepatocyte regeneration alternating with slightly compressed/atrophic areas in this example of mild NRH.
Figure 6.5 Hepatitis B. An essentially normal H&E appearance of the liver in this patient with congenital hepatitis B.
Figure 6.6 Hepatitis B. A hepatitis B surface antigen immunostain in a diffuse membranous and focal cytoplasmic pattern in the same case of congenital hepatitis B illustrated in this igure.
be easily recognizable), often forming clusters, typically associated with brisk interface and lobular activity (Fig. 6.10). Cases showing typical histology most commonly represent autoimmune hepatitis, although clinical correlation is required to establish this diagnosis. Occasionally, this pattern in seen in viral hepatitis B and C (rarely in other infections), as well as in drug-induced liver injury (most notably nitrofurantoin, minocycline, halothane, statins, hydralazine, and methyldopa).4
Table 6.2 Diseases and conditions associated with clinical liver dysfunction and normal/nearly normal histology
Figure 6.8 Acute hepatitis pattern. Lobular injury and disarray with apoptotic hepatitis (acidophilic bodies) but no significant lobular inflammation in this example of hepatitis A.
Figure 6.9 Chronic hepatitis pattern. Marked portal inflammation with a lymphoid aggregate and germinal center as well as mild interface activity in this example of chronic viral hepatitis.
Table 6.3 Etiologies associated with the “acute hepatitis” pattern
Table 6.4 Diseases associated with the “chronic hepatitis” pattern
diseases such as lupus erythematosus, immune thrombocytopenic purpura, autoimmune hemolytic anemia, and various infections (CMV, HHV-6, HCV, HEV, EBV, and HIV).5, 6, 7, 8
Figure 6.11 Panacinar/panlobular hepatitis pattern. A moderate or severe hepatitis involving both portal tracts and hepatic lobules in a somewhat diffuse manner, as in this case of drug-induced liver injury.