What is the pathophysiology of hepatocellular adenoma (HCA)?

Updated: Feb 21, 2018
  • Author: Bradford A Whitmer, DO; Chief Editor: BS Anand, MD  more...
  • Print

Hepatic adenomas consist of sheets of hepatocytes without bile ducts or portal areas. Kupffer cells, if present, are reduced in number and are nonfunctional. Hepatic adenomas are tan in color, smooth, well circumscribed, fleshy in appearance, and vary from 1 to 30 cm in size. They have large blood vessels on the surface, and the lesions may outgrow their arterial blood supply, causing necrosis within the lesions. A fibrous capsule may be present or absent; if absent, this may predispose to intrahepatic or extrahepatic hemorrhage. Most adenomas present as solitary lesions in the right lobe of the liver; however, tumors do occur in both the right lobe and the left lobe, and up to 20% of cases have multiple lesions.

The pathogenesis is thought to be related to a generalized vascular ectasia that develops due to exposure of the vasculature of the liver to oral contraceptives and related synthetic steroids. Estrogen may exert an influence via estrogen receptors in the cytoplasm or nucleus of hepatocytes. However, this remains controversial as adenomas can occur in males and children without predisposing risk factors, and these receptors have not been identified even with the use of monoclonal antibodies. [17] Rebouissou et al [18] and Bioulac-Sage et al [13, 19] also reported that hepatic adenomas are monoclonal tumors and probably develop from an interaction between gene defects and environmental changes such as OCPs and steatosis. HCAs are now believed to result from specific genetic mutations involving transcription factor 1 gene (TCF1), interleukin 6 signal transducer gene (IL6ST), and β catenin-1 gene (CTNNB1). [20]

Adenomas have also been associated with diabetes mellitus and GSD, leading to speculation as to whether imbalances between insulin and glucagon also play a role. Patients with GSD are more likely to present with multiple lesions. Lesions associated with GSD often appear in younger patients (early third decade of life) and have a male-to-female ratio of 2:1. In this group, the abnormal amounts of stored glycogen may have some effect, perhaps by oncogene stimulation.

Insulin and glucagon appear to play a larger role, because GSD-related adenomas have been reported to seemingly disappear with dietary manipulation. A germline mutation of the hepatocyte nuclear factor (HNFα) was described by Reznik et al in 2 families that had both diabetes mellitus and liver adenomatosis. [21] Tumor cell analysis showed biallelic inactivation of HNFα. Micro/small HNF1α-inactivated hepatocellular adenoma have also been found incidentally in pathological liver resected specimens. [22]

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!