A hepatic adenoma (HA), also known as a hepatocellular adenoma, is a relatively rare, non-cancerous growth originating from the liver’s main cells, the hepatocytes. This benign tumor does not spread to other organs, but its presence requires medical attention due to the possibility of serious complications. While most adenomas are found incidentally, they carry a risk of internal bleeding and, less commonly, transformation into liver cancer.
Defining Hepatic Adenoma and Molecular Subtypes
Histologically, a hepatic adenoma is characterized by a proliferation of hepatocytes that lack the normal architecture of the liver, specifically missing the organized arrangement of central veins and portal tracts. The tumor cells are often well-differentiated, closely resembling normal liver cells, but they are supplied by abnormal, thin-walled blood vessels. These growths vary significantly in size, sometimes ranging from less than one centimeter to over 15 centimeters at diagnosis.
Hepatic adenomas are classified into several molecular subtypes based on underlying genetic mutations. This classification is important because each subtype is associated with a different level of risk for complications. Primary groups include HNF1A-inactivated, \(\beta\)-catenin activated, and inflammatory adenomas, with a small percentage remaining unclassified.
The HNF1A-inactivated subtype is often associated with the presence of fat within the tumor cells and carries the lowest risk of malignant transformation. Inflammatory hepatic adenomas (I-HCA) are the most common subtype and are frequently linked to systemic inflammation and conditions like obesity. The \(\beta\)-catenin activated adenomas are of particular concern due to their significantly higher potential for progression to hepatocellular carcinoma (HCC), or liver cancer.
Primary Causes and Risk Factors
The development of hepatic adenoma is strongly linked to hormonal influences, with the majority of cases occurring in young women who use oral contraceptive pills (OCPs). Estrogen is believed to promote tumor growth, and studies indicate that the risk increases with both the duration of OCP use and the concentration of estrogen in the medication. The decline in HA incidence in recent decades is partly attributed to the lower estrogen doses used in newer oral contraceptives.
Hormonal exposure in men is also a clear risk factor, particularly the use of anabolic steroids for body building or medical conditions. These exogenous androgens can induce HA formation, and adenomas in male patients are often associated with the higher-risk \(\beta\)-catenin-activated subtype. Discontinuing the causative hormonal medication is typically the first step in management for all patients, as it can often lead to tumor regression or stabilization.
Beyond hormonal factors, specific metabolic and genetic conditions increase susceptibility to HA formation. Patients with Glycogen Storage Diseases, particularly types I and III, have a recognized predisposition to developing multiple adenomas. The rising prevalence of metabolic syndrome, obesity, and non-alcoholic steatohepatitis are also recognized as emerging risk factors for inflammatory-type adenomas.
Diagnosis and Surveillance Methods
Hepatic adenomas are frequently discovered incidentally during imaging procedures performed for unrelated reasons, as they often do not cause noticeable symptoms unless they grow large or bleed. When symptoms occur, they typically involve mild upper right abdominal discomfort or a feeling of fullness. A sudden onset of severe abdominal pain should prompt immediate medical attention, as it may signal a life-threatening rupture and internal hemorrhage.
Non-invasive imaging is the primary method for diagnosis and differentiation of HA from other liver masses, such as focal nodular hyperplasia or hepatocellular carcinoma. Dynamic magnetic resonance imaging (MRI) with hepatocyte-specific contrast agents is considered the preferred imaging modality for characterizing these lesions. MRI can often provide clues about the molecular subtype, for example, by detecting fat content characteristic of the lower-risk HNF1A-inactivated adenomas.
A liver biopsy may be necessary when the diagnosis remains uncertain or if there is a suspicion of malignant transformation. Biopsy allows for immunohistochemical and molecular analysis to definitively confirm the subtype, which is an important step in determining the appropriate long-term management plan. Surveillance, involving repeat imaging every six months to one year, is implemented for managed or small lesions to monitor for any changes in size or appearance.
Treatment and Management Decisions
The management of a hepatic adenoma is highly individualized, depending primarily on the tumor’s size, the patient’s gender, and the identified molecular subtype. For women with an adenoma smaller than 5 centimeters that is not causing symptoms, the standard approach is conservative management. This strategy involves the immediate cessation of all exogenous hormones, such as oral contraceptives, and lifestyle modifications like weight loss.
The decision to pursue active intervention, typically surgical resection, is driven by the risk of two major complications: rupture with acute hemorrhage and malignant transformation. Tumors larger than 5 centimeters have a significantly increased risk of rupture, which can lead to severe, life-threatening internal bleeding. Surgical removal is generally recommended for these larger lesions to prevent this complication.
The molecular subtype also strongly influences the decision for surgery, regardless of size. Any adenoma confirmed or highly suspected to be the \(\beta\)-catenin activated subtype is typically recommended for surgical resection due to its high risk of becoming cancerous. Furthermore, all male patients with a hepatic adenoma are generally advised to undergo surgical removal because they have a higher baseline risk of malignant change compared to women. For patients who cannot undergo surgery, alternative treatments like radiofrequency ablation or transarterial embolization may be considered for smaller or bleeding lesions.