Hepatic Adenomas in Patients 60 and Older Are Enriched for HNF1A Inactivation and Malignant Transformation

Am J Surg Pathol. 2022 Jun 1;46(6):786-792. doi: 10.1097/PAS.0000000000001892. Epub 2022 Apr 6.


Hepatic adenomas occur most commonly in women between the ages of 20 and 40 years, but rarely they occur in older aged persons, including those 60 years of age or older. This group of adenomas, however, has not been systemically examined. Twenty-six hepatic adenomas in persons 60 years of age or older were studied, along with a control group of 50 hepatic adenomas in persons aged 30 to 39. Hepatic adenomas in persons 60 or more years of age were found in 21 women and 5 men, while the control group had 44 women and 6 men. Subtyping the adenomas in persons 60 years or older showed the following results: 18 HNF1A-inactivated adenomas (69%), 4 inflammatory adenomas (15%), and 4 unclassified adenomas (15%). In contrast, the control group showed a significantly different pattern (P=0.003), with a greater percentage of inflammatory adenomas (28, 56%), fewer HNF1A-inactivated adenomas (8, 16%), and more unclassified adenomas (14, 28%). Atypia and malignant transformation within the hepatic adenomas was studied next. Of the hepatic adenomas in persons age 60 or greater, 3 (12%) showed atypical histologic features, and 6 (23%) had a malignant transformation. In contrast, for hepatic adenomas in the control group, only 4 (8%) adenomas showed atypical histologic features, and 3 (6%) had undergone malignant transformation. In addition, the hepatic adenomas that were atypical or showed early malignant transformation were less likely to have beta-catenin activation in patients over 60 (2/9 cases) compared with those between 30 and 39 years (5/7 cases). Myxoid change and heavy lipofuscin deposition were also more common in adenomas in older aged persons. In conclusion, hepatic adenomas in persons 60 years of age or older are enriched for HNF1A-inactivated adenomas and have a higher frequency of malignant transformation. Malignant transformation, however, is less likely to develop through activation of the beta-catenin pathway.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoma, Liver Cell* / genetics
  • Adenoma, Liver Cell* / pathology
  • Adult
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • Female
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Humans
  • Lipofuscin
  • Liver Neoplasms* / pathology
  • Male
  • Middle Aged
  • beta Catenin / genetics


  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Lipofuscin
  • beta Catenin