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# Hepatocellular adenoma: the molecular subtypes and their risks

- Lesion

Hepatocellular adenoma is a benign liver tumour, mostly in young women on hormones; some types bleed or turn into cancer.

Updated Nov 12, 2026

## Key points

- Four main subtypes: HNF1A-inactivated, inflammatory, β-catenin-activated and sonic hedgehog.
- HNF1A-inactivated: fatty adenoma, loss of liver fatty acid-binding protein; germline HNF1A mutation also causes MODY3.
- Inflammatory: gp130/JAK-STAT activation; sinusoidal dilation, inflammation; serum amyloid A and CRP staining; linked to obesity and alcohol.
- β-catenin-activated: atypia, nuclear β-catenin, diffuse glutamine synthetase; highest risk of HCC; more in men.
- Sonic hedgehog: GLI1 fusions; prone to bleeding.
- Size of five centimetres or more and male sex raise the risk of bleeding and malignancy; adenomas may regress after stopping hormones.

## What it is

Hepatocellular adenoma is a benign neoplasm of hepatocytes that usually arises in a normal liver, classically in young women using oral contraceptives, and also with anabolic steroids, obesity and glycogen storage disease. It is now classified by molecular subtype, which predicts risk: inflammatory and HNF1A-inactivated types are most common, while β-catenin-activated adenomas carry the highest risk of hepatocellular carcinoma. Large adenomas can rupture and bleed into the abdomen.

## Structure

- Gross: well-demarcated pale or yellow-tan nodule, sometimes with hemorrhage, up to many centimetres, often under the capsule.
- Micro: sheets and cords of hepatocytes in plates one to two cells thick, isolated thick arteries, no portal tracts or bile ducts.

## Molecular subtypes of hepatocellular adenoma

| Subtype | Molecular change | Features and stains | Main risk |
| --- | --- | --- | --- |
| HNF1A-inactivated | Loss of HNF1A (somatic or germline) | Steatotic; loss of LFABP staining | Low malignancy risk |
| Inflammatory | Activating gp130 (IL6ST) or other JAK-STAT mutations | Sinusoidal dilation, inflammation, thick arteries; SAA and CRP positive | Bleeding; some also carry β-catenin mutation |
| β-catenin-activated | CTNNB1 (or other Wnt pathway) activation | Cell atypia; nuclear β-catenin, diffuse glutamine synthetase | Highest risk of HCC |
| Sonic hedgehog | GLI1 fusion genes | Often hemorrhagic | Bleeding |

## Markers

- LFABP
- Serum amyloid A
- C-reactive protein
- β-catenin (nuclear)
- Glutamine synthetase

## Clinical notes

- Pain or sudden intra-abdominal bleeding, especially in pregnancy; many are incidental.
- Resection is advised for β-catenin-activated tumours, lesions of five centimetres or more and adenomas in men.

## Memory aid

Four flavours of adenoma: Fatty (HNF1A), Fiery (inflammatory), Frightening (β-catenin, may become cancer) and Fragile (hedgehog, bleeds).

## Test yourself

Think of the answer, then tap the question to see it.

## Which subtype of hepatocellular adenoma has the highest risk of becoming carcinoma?

The β-catenin-activated subtype, which shows nuclear β-catenin and diffuse glutamine synthetase staining.

## Why does an adenoma lack portal tracts?

It is a neoplasm of hepatocytes alone, fed by isolated arteries, without normal portal tracts or bile ducts.

## Which hormone exposures are linked to hepatocellular adenoma?

Oral contraceptives in women and anabolic androgenic steroids.

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## Connections

## Related 5

- [Benign liver masses](https://durgical.com/en/general-pathology/benign-liver-masses/)
- [Hepatocellular carcinoma](https://durgical.com/en/general-pathology/hepatocellular-carcinoma/)
- [Drug- and toxin-induced liver injury](https://durgical.com/en/general-pathology/drug-and-toxin-induced-liver-injury/)
- [Benign vs malignant tumours: the comparison table](https://durgical.com/en/general-pathology/benign-vs-malignant-tumours-the-comparison-table/)
- [Immunohistochemistry: the principle and the markers to know](https://durgical.com/en/general-pathology/immunohistochemistry-the-principle-and-the-markers-to-know/)

## Related conditions 3

- [Benign liver lesions (haemangioma, focal nodular hyperplasia, adenoma)](https://durgical.com/en/conditions/benign-liver-lesions/)
- [Hepatocellular carcinoma](https://durgical.com/en/conditions/hepatocellular-carcinoma/)
- [Von Gierke disease (glycogen storage disease type I)](https://durgical.com/en/conditions/von-gierke-disease/)

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Primary Liver Cancer Treatment (PDQ®) - NCI](https://www.cancer.gov/types/liver/hp/adult-liver-treatment-pdq) (National Cancer Institute, 2026).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/hepatocellular-adenoma-the-molecular-subtypes-and-their-risks/