LARGE-CELL CHANGE OF HEPATOCYTES IN CIRRHOSIS MAY REPRESENT A REACTION TO PROLONGED CHOLESTASIS

Large-cell change of hepatocytes (LCC), also called liver cell dysplas ia of large-cell type, is a set of cytologic changes comprising nuclea r and cytoplasmic enlargement, nuclear pleomorphism. and multinucleati on. This entity is encountered frequently on histologic or cytologic e xamination of specimens obtained from livers with a variety of chronic diseases and originally was thought to have a premalignant nature. Ac cumulating evidence, however, now suggests that LCC is merely a reacti ve change. Having often observed LCC in liver specimens with chronic b iliary tract disease, that is, in livers where cholestasis preceded he patocyte injury, we surmised that LCC may be a result of prolonged cho lestasis. To determine whether there was any association between LCC a nd cholestasis, we examined microscopically a series of 400 nodules fr om 40 consecutive adult cirrhotic livers, resected on transplantation, and graded LCC and cholestasis semiquantitatively. LCC was present di ffusely in cirrhotic nodules of 25 specimens (62.5%). Nine additional specimens (22.5%) had focal mild LCC. Usually, LCC and cholestasis occ urred together, in the same cirrhotic nodules and in the same areas of nodules. There was a statistically significant association between th e presence and grade of LCC and those of cholestasis (p < 0.0001; chi- square test). Within etiological categories of cirrhosis (chronic hepa titis; n = 28; alcoholic liver disease; n = 6: biliary disease: n = 6) , the significance was maintained. We conclude that, in cirrhosis of d ifferent etiologies, LCC may represent a reactive change that results from prolonged cytoplasmic cholestasis.