Large-cell change of hepatocytes in cirrhosis may represent a reaction to prolonged cholestasis

Suneetha Natarajan, Neil D. Theise, Swan N. Thung, Lilian Antonio, Fiorenzo Paronetto, Prodromos Hytiroglou

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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.

Original languageEnglish
Pages (from-to)312-318
Number of pages7
JournalAmerican Journal of Surgical Pathology
Issue number3
StatePublished - Mar 1997


  • Carcinoma
  • Cholestasis
  • Cirrhosis
  • Dysplasia
  • Hepatocellular carcinoma
  • Hepatoma
  • Large-cell change
  • Liver
  • Precancerous
  • Premalignant
  • Reactive


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