title: Large-cell change of hepatocytes in cirrhosis may represent a reaction to prolonged cholestasis.
abstract: Large-cell change of hepatocytes (LCC), also called liver cell dysplasia of large-cell type, is a set of cytologic changes comprising nuclear and cytoplasmic enlargement, nuclear pleomorphism, and multinucleation. This entity is encountered frequently on histologic or cytologic examination of specimens obtained from livers with a variety of chronic diseases and originally was thought to have a premalignant nature. Accumulating evidence, however, now suggests that LCC is merely a reactive change. Having often observed LCC in liver specimens with chronic biliary tract disease, that is, in livers where cholestasis preceded hepatocyte injury, we surmised that LCC may be a result of prolonged cholestasis. To determine whether there was any association between LCC and cholestasis, we examined microscopically a series of 400 nodules from 40 consecutive adult cirrhotic livers, resected on transplantation, and graded LCC and cholestasis semiquantitatively. LCC was present diffusely in cirrhotic nodules of 25 specimens (62.5%). Nine additional specimens (22.5%) had focal mild LCC. Usually, LCC and cholestasis occurred together, in the same cirrhotic nodules and in the same areas of nodules. There was a statistically significant association between the presence and grade of LCC and those of cholestasis (p < 0.0001; chi-square test). Within etiological categories of cirrhosis (chronic hepatitis; n = 28; alcoholic liver disease; n = 6; biliary disease: n = 6), the significance was maintained. We conclude that, in cirrhosis of different etiologies, LCC may represent a reactive change that results from prolonged cytoplasmic cholestasis.
authors.affiliation: Department of Pathology, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Natarajan
authors.forename: N D
authors.initials: ND
authors.lastname: Theise
authors.forename: S N
authors.initials: SN
authors.lastname: Thung
authors.forename: L
authors.initials: L
authors.lastname: Antonio
authors.forename: F
authors.initials: F
authors.lastname: Paronetto
authors.forename: P
authors.initials: P
authors.lastname: Hytiroglou
mesh_terms: D000328:Adult; D000368:Aged; D002779:Cholestasis / Q000150:complications* / Q000473:pathology; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000150:complications* / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged