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Hepatic adenomas, also referred to as hepatocellular adenomas, are benign, generally hormone-induced, liver tumors. The tumors are usually solitary, have a predilection for hemorrhage, and must be differentiated from other focal liver lesions.
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 recognizing that obesity and metabolic syndrome are emerging risk factors for adenomas 18.
Hepatic adenoma is traditionally considered the most frequent hepatic tumor 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 estrogens)
- anabolic steroids: typically young men
- glycogen storage diseases:
- metabolic syndrome 18
- diabetes mellitus 19
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.
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.
The lesion is well-circumscribed, often subcapsular with yellow coloration on account of frequently abundant fat and lack of bile. Hemorrhagic change is frequent. The tumor may be surrounded by a fibrous pseudocapsule 15.
Histologically, hepatic adenomas are characterized 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 for
Tc-99m sulfur colloid scans (see below).
According to the original 2006 Bordeaux classification, there are four subtypes of hepatic adenomas 17:
inflammatory hepatic adenoma
- most common subtype
- highest bleed rate
HNF-1 alpha mutated hepatic adenoma
- second most common subtype
- often multiple
- beta catenin-mutated hepatic adenoma
- unclassified hepatic adenoma
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.
- color 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)
- arterial phase
The attenuation of these tumors is variable, depending on 8:
- fresh hemorrhage: 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 hemorrhage (5-10% of cases 10).
In non-hemorrhagic adenomas, they typically appear as:
- variable and can range from being hyper-, iso-, to hypointense
- hyperintense: 35-77% cases 8
- variable and can range from being hyper-, iso-, to hypointense
- mildly hyperintense: 47-74% 2,8
- the presence of fat typically leads to signal drop out on out-of-phase imaging
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)
- T1 C+ (Gad)
If hemorrhagic, blood and its products may cause significant heterogeneity in signal on all sequences.
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.
Treatment and prognosis
- 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 embolization may have a role 7.
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 hemorrhage are less common
- typical hemangioma: discontinuous peripheral nodular enhancement, with gradual centripetal fill-in
- flash-filling hemangioma: isodense/isointense to blood pool on all phases
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