Hepatocellular (hepatic) adenoma

by Jason Wasserman MD PhD FRCPC
April 18, 2024

A hepatocellular (hepatic) adenoma is a rare, benign (noncancerous) liver tumour. These tumours are typically asymptomatic but can sometimes lead to complications, such as internal bleeding or even a risk of turning cancerous, especially if the adenoma is large.

What are the symptoms of a hepatocellular adenoma?

Although most hepatocellular adenomas do not cause symptoms, some patients may experience abdominal pain or discomfort, particularly on the upper right side of the abdomen. In some cases, a noticeable mass or a feeling of fullness in the abdomen might be present. The most severe symptom arises if the adenoma ruptures, causing sudden and intense pain which requires immediate medical attention.

What causes a hepatocellular adenoma?

The development of hepatocellular adenoma has been linked to the use of oral contraceptives or anabolic steroids, genetic predispositions, and metabolic syndrome. These conditions influence hormonal balances in the body, promoting abnormal liver tissue growth.

What are the histologic types of hepatocellular adenoma?

Hepatocellular adenomas are classified into several types based on their histological characteristics, which have implications for their clinical management:

• Hepatocyte nuclear factor 1 alpha (HNF1A)-inactivated hepatocellular adenoma: These adenomas lack HNF1A activity and often have a benign course with a very low risk of bleeding or malignancy.
• Inflammatory hepatocellular adenoma: Characterized by inflammatory infiltrates and often associated with obesity and alcohol use, these adenomas can be larger and carry a higher risk of bleeding.
• Beta-catenin-activated hepatocellular adenoma: These show mutations in the beta-catenin gene and are significant due to a higher risk of malignant transformation to a type of liver cancer called hepatocellular carcinoma.
• Unclassified hepatocellular adenoma: Adenomas that do not fit into the other categories.

Microscopic features

Hepatocellular adenoma is made up of hepatocytes, which are the main functional cells of the liver. These adenoma cells resemble normal hepatocytes but often exhibit certain differences in appearance and organization. For example, the hepatocytes in an adenoma are generally larger and have a more variable size and shape than normal hepatocytes. This variation can be subtle but is usually noticeable under microscopic examination. Most adenomas are round growths that are typically described as nodules in liver imaging studies.

Other microscopic features of a hepatocellular adenoma include:

• Plate thickness: One of the key differences is the architectural arrangement of the cells. In normal liver tissue, hepatocytes are arranged in plates that are one cell thick, separated by sinusoidal spaces. In adenomas, the cellular plates can be thicker (two to three cells thick), disrupting the normal lobular architecture of the liver.
• Cytologic atypia: Pathologists use the term atypia to describe cells that are abnormal in shape, size, or colour. The cells in a hepatocellular adenoma usually show only mild atypia. In contrast, hepatocellular carcinoma, a common type of liver cancer, shows more significant atypia.
• Lack of bile ducts: Bile ducts are generally absent within the lesion, differentiating adenomas from other types of liver nodules that might include bile duct structures.
• Unpaired arteries: The presence of arteries not accompanied by bile ducts or portal veins is abnormal and indicative of adenomas.

Immunohistochemistry

Immunohistochemistry (IHC) is a valuable diagnostic tool used in the evaluation, diagnosis and subtyping of hepatocellular adenoma. It not only aids in distinguishing these benign entities from hepatocellular carcinoma but also helps in predicting the clinical behaviour of the tumour, guiding the management strategies. For instance, identifying a beta-catenin-activated adenoma can lead to more vigilant monitoring due to its potential for malignant transformation.

Possible immunohistochemistry results for hepatocellular adenoma:

Hep Par 1

• Staining: Positive.
• Significance: Hep Par 1 is a reliable marker for hepatocellular origin and is usually positive in hepatocellular adenomas, indicating that the cells are derived from hepatocytes.

Glypican-3

• Staining: Usually negative.
• Significance: Glypican-3 is often used to distinguish between benign liver lesions (where it is typically negative) and malignant hepatocellular carcinoma (where it is positive).

Glutamine synthetase (GS)

• Staining: Varies by subtype.
• Significance: The staining pattern can help identify beta-catenin-activated adenomas. Diffuse or map-like staining indicates beta-catenin activation, which is associated with a higher risk of malignancy.

C-reactive protein (CRP)

• Staining: Positive in inflammatory adenomas.
• Significance: CRP positivity can indicate an inflammatory hepatocellular adenoma, which is linked to systemic inflammatory conditions and has distinct clinical management implications.

Liver fatty acid-binding protein (LFABP)

• Staining: Negative in HNF1A-inactivated adenomas.
• Significance: Loss of LFABP staining is characteristic of HNF1A-inactivated adenomas, which are usually benign with a very low risk of malignant transformation.

Serum amyloid A (SAA)

• Staining: Positive in inflammatory adenomas.
• Significance: Similar to CRP, positivity for SAA supports the diagnosis of an inflammatory subtype of hepatocellular adenoma.

Beta-catenin

• Staining: Abnormal (nuclear and/or diffuse cytoplasmic) in beta-catenin-activated adenomas.
• Significance: Nuclear or aberrant cytoplasmic beta-catenin staining suggests activation of the Wnt/beta-catenin pathway, which is associated with an increased risk of hepatocellular carcinoma.

Margins

In pathology, a margin is the edge of tissue removed during tumour surgery. The margin status in a pathology report is important as it indicates whether the entire tumour was removed or if some was left behind. This information helps determine the need for further treatment.

Pathologists typically assess margins following a surgical procedure, like an excision or resection, that removes the entire tumour. Margins aren’t usually evaluated after a biopsy, which removes only part of the tumour. The number of margins reported and their size—how much normal tissue is between the tumour and the cut edge—vary based on the tissue type and tumour location.

Pathologists examine margins to check if tumour cells are present at the tissue’s cut edge. A positive margin, where tumour cells are found, suggests that some cancer may remain in the body. In contrast, a negative margin, with no tumour cells at the edge, suggests the tumour was fully removed. Some reports also measure the distance between the nearest tumour cells and the margin, even if all margins are negative.

About this article

Doctors wrote this article to help you read and understand your pathology report. Contact us with any questions about this article or your pathology report. Read this article for a more general introduction to the parts of a typical pathology report.

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