Hepatic adenoma

Hepatic adenomas, also referred to as hepatocellular adenomas, are benign, generally hormone-induced, liver tumours. The tumours are usually solitary, have a predilection for haemorrhage, and must be differentiated from other focal liver lesions.

Epidemiology

The incidence of hepatic adenomas is unknown, with studies showing migration from the classically described female predominance related to the use of oral contraceptives to an increased prevalence in men, particularly recognising that obesity and metabolic syndrome are emerging risk factors for adenomas ¹⁸. 

Hepatic adenoma is traditionally considered the most frequent hepatic tumour in young women on the oral contraceptive pill.

They are found in certain situations, including ³:

• oral contraceptive use (especially the first generation pills which have a high concentration of oestrogens)
• anabolic steroids: typically young men
• glycogen storage diseases:
  • type I (von Gierke disease)
  • type III (Cori or Forbes disease)
• obesity
• metabolic syndrome ¹⁸
• diabetes mellitus ¹⁹

Clinical presentation

The lesions usually remain asymptomatic until they spontaneously rupture, resulting in abdominal pain. Occasionally rapid bleeding into the peritoneal cavity can lead to massive exsanguination and death.

Pathology

Hepatic adenomas are usually solitary (70-80% of cases ¹⁰) and large at the time of diagnosis (5-15 cm) ^3,13. They are most frequently seen at a subcapsular location in the right lobe of the liver and are often round, well-defined pseudo-encapsulated masses. Occasional dystrophic calcification may be present. 

When multiple, usually >10 adenomas ⁹, the term hepatic adenomatosis is used. Multiple lesions are frequently observed in patients with type I glycogen storage disease.

Macroscopic appearance

The lesion is well-circumscribed, often subcapsular with yellow colouration on account of frequently abundant fat and lack of bile. Haemorrhagic change is frequent. The tumour may be surrounded by a fibrous pseudocapsule ¹⁵.

Histology

Histologically, hepatic adenomas are characterised by proliferation of pleomorphic hepatocytes without normal lobular architecture. These cells frequently have abundant glycogen (thus the link with von Gierke disease) ⁵. They are traditionally described as being devoid of bile ducts and Kupffer cells, although this has been shown not to be the case, with a diminished number of Kupffer cells found in many cases ^1,3-4. This has an important implication forTc-99m sulfur colloid scans (see below).

Molecular classifications

According to the original 2006 Bordeaux classification, there are four subtypes of hepatic adenomas ¹⁷:

1. inflammatory hepatic adenoma
   • ​​most common subtype
   • highest bleed rate
2. HNF-1 alpha mutated hepatic adenoma
   • ​​second most common subtype
   • often multiple
3. beta catenin-mutated hepatic adenoma
   • ​​least common subtype
   • higher risk in men on anabolic steroids and patients with glycogen storage disease, familial adenomatous polyposis 
4. unclassified hepatocellularhepatic adenoma

Radiographic features

Ultrasound

A hepatic adenoma usually presents as a solitary, well-demarcated, heterogeneous mass. Echogenicity is variable ³:

• hypoechoic: 20-40%
• hyperechoic: up to 30%, often due to fat ^3,8

A hypoechoic halo of focal fatty sparing is also frequently seen.

• colour Doppler: may show perilesional sinusoids
• contrast-enhanced ultrasound ¹⁶
  • arterial phase
    • hypervascular (similar to focal nodular hyperplasia [FNH], although adenomas usually enhance to a lesser degree)
  • portal venous and delayed phases
    • centripetal filling (opposite of FNH, which shows centrifugal filling)

CT

The attenuation of these tumours is variable, depending on ⁸:

• fresh haemorrhage: may be hyperattenuating
• fat content may render the mass hypoattenuating

In general, they are well-marginated and isoattenuating to the liver. On contrast administration, they demonstrate transient, relatively homogeneous enhancement, returning to near isodensity on portal venous and delayed phase images ^8,10.

If the rest of the liver shows diffuse fatty infiltration, they will appear hyperattenuating.

Calcification may be seen in areas of old haemorrhage (5-10% of cases ¹⁰).

MRI

In non-haemorrhagic adenomas, they typically appear as:

• T1
  • variable and can range from being hyper-, iso-, to hypointense
    • hyperintense: 35-77% cases ⁸
• T2
  • mildly hyperintense: 47-74% ^2,8
• in/out-of-phase
  • the presence of fat typically leads to signal drop out on out-of-phase imaging
• contrast studies
  • T1 C+ (Gad)
    • on the dynamic postcontrast sequence, adenomas show early arterial enhancement and become nearly isointense about liver on delayed images ¹⁰
    • some reports suggest that the enhancement becomes isointense to the rest of the liver by 1 minute ⁶
  • T1 C+ (hepatocyte-specific): adenomas usually appear hypointense on hepatobiliary phase (20 mins after injection) due to reduced uptake of Gd-EOB-DTPA/Eovist ¹⁴ (cf. FNH which appears iso- to hyperintense)

If haemorrhagic, blood and its products may cause significant heterogeneity in signal on all sequences.

Nuclear medicine

Although classically described as a focal photopenic lesion with a surrounding rim of increased uptake on Tc-99m sulfur colloid scans, uptake may be seen in up to 23% of cases ¹. This is accounted for by the presence of Kupffer cells in many adenomas, though they may be reduced in number.

Usually has increased activity on a HIDA scan, but does not take up gallium on a gallium scan.

Treatment and prognosis

Complications

• spontaneous rupture
• rare: hepatic adenomas can degenerate into hepatocellular carcinomas (HCC) ⁸, particularly in men

In general, and if feasible, adenomas are resected, both to eliminate the risk of spontaneous rupture and to conclusively confirm the diagnosis ⁷. In cases where the lesion is small, not subcapsular, and has a typical appearance, some would choose to observe (with imaging and alpha-fetoprotein levels) and cease oral contraceptives. In such instances, the adenoma may regress. In inoperable cases, hepatic arterial embolisation may have a role ⁷. 

Differential diagnosis

General imaging differential considerations include:

• hepatocellular carcinoma (HCC)
  • washout tends to render the lesion hypointense to the liver
  • rim enhancement of the pseudocapsule may persist on the delayed scan
  • different demographics
  • may be difficult to distinguish from an adenoma if well-differentiated ⁷
• fibrolamellar hepatocellular carcinoma
  • radiating/central scar
  • calcification more common ⁸
  • lymph node enlargement common
• focal nodular hyperplasia (FNH)
  • T2:bright central scar that has late enhancement
  • retains hepatocyte-specific contrast material (e.g. Eovist [gadoxetate]) on delayed phase MRI
• hepatic metastases (hypervascular) 
  • usually hypointense on T1 and moderately hyperintense on T2
  • fat and haemorrhage are less common
• hepatic haemangioma