Benign Hepatocellular Tumors

Focal Nodular Hyperplasia

A plethora of terms has been used in the past to designate this tumor, including hepatic pseudotumor , hamartoma , solitary hyperplastic nodule , lobar or focal cirrhosis , benign hepatoma, and even adenoma ; these terms have now been abandoned in favor of focal nodular hyperplasia , or FNH. The definition of FNH requires the presence of several key features: multiple, spherical aggregates of benign hepatocytes held together in a fibrous meshwork that radiates outward from a prominent scar containing aberrant variably sized vessels with eccentrically thickened walls, as well as a ductular reaction and inflammatory infiltrate at the interface between the fibrous bands and hepatocytic nodules. The presence of unusual features or absence of some key ones makes the pathologic diagnosis more difficult.

The term subtle FNH indicates an early, not well-developed lesion that lacks, at least partially, the major key features. Telangiectatic FNH is now an obsolete term because this lesion has been shown to be an HCA (see later). FNH-like lesion is a term used for nodules with some morphologic characteristics of FNH that arise in the context of cirrhosis, vascular disorders, or in the vicinity of other tumors. The term multiple FNH syndrome is used to indicate the association of multiple FNH with other pathologic manifestations in the liver and outside the liver; this poorly characterized entity awaits reevaluation apropos the genotype-phenotype classification of HCA described later. The same is true for progressive FNH and mixed tumors.

Additional information about FNH is presented in Table 32.1 .

Hepatocellular Adenoma

The term hepatocellular adenoma , or HCA, is favored over others such as benign hepatoma, liver cell adenoma, and liver adenoma, which are sometimes used to designate this tumor. HCA is a benign tumor of hepatocytes characterized by arterial vascularization that occurs in a liver that may be steatotic in some instances but is otherwise normal. The tumor is usually solitary but may be multifocal and varies in size from 0.5 to 15 cm in diameter. It is not encapsulated and composed of cells that resemble normal hepatocytes and may be steatotic. HCA is characterized by the absence of mitosis, portal tracts, and bile ducts; however, biliary cells and ductules may be present in some cases. The lesions display varying degrees of steatosis, sinusoidal dilatation, and inflammation; the strong correlation of these morphologic phenotypes with recently characterized molecular changes in HCA has led to the identification of distinct subgroups of HCA and the formulation of a genotype-phenotype classification.

The definition of the term adenomatosis requires the presence of at least 10 HCAs and is based on the number of nodules detected by imaging studies; the latter may, however, miss small (micro) adenomas. The term is however often used inappropriately. Mixed adenoma-focal nodular hyperplasia , a confusing term, indicates a collision tumor between FNH and HCA.

Additional information about HCA can be found in Table 32.2 .

Focal Nodular Hyperplasia

Distinction between FNH and other hypervascular liver lesions such as HCA, HCC, and hypervascular metastases is critical for appropriate management. Asymptomatic FNH requires no specific treatment whereas other hypervascular lesions need specific treatment and/or close follow up. In its “classic form” FNH can be easily diagnosed with cross-sectional contrast-enhanced imaging. Characteristic imaging features of FNH include lesional homogeneity, significant enhancement on the arterial phase with lack of washout during the portal venous and delayed phases, peripheral lobulation, and the presence of a central scar. Based on these criteria, cross-sectional contrast-enhanced imaging has a sensitivity and a specificity of 70% and 100%, respectively, for the diagnosis of FNH.

Ultrasonography and Contrast-Enhanced Ultrasound

The majority of FNH lesions are discovered during an ultrasound examination undertaken for abdominal pain. FNH is typically isoechogenic or slightly hypoechogenic to the surrounding liver parenchyma. The presence of a central arterial pedicle with low resistance index on a Doppler study greatly assists its diagnosis.

Contrast-enhanced ultrasound (CEUS) shows a characteristic pattern of hypervascularity in the arterial phase, centrifugal filling, and the presence of stellate arteries producing a ‘‘spoke wheel’’ sign. Sustained portal venous phase enhancement is seen in the delayed phase. However, CEUS may not show centrifugal filling and the stellate arteries in very large lesions ( Fig. 32.1 ).

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) has higher sensitivity and specificity for diagnosis of FNH than ultrasonography or computed tomography. The lesion is typically isointense or slightly hypointense on T1-weighted images and slightly hyperintense or isointense on T2-weighted images obtained by MRI; the central scar is typically hypointense on T1-weighted images and hyperintense on T2-weighted images. During the arterial phase of gadolinium-enhanced imaging, FNH demonstrates intense homogeneous enhancement except for the central scar. During the portal and delayed phase, FNH returns to isointensity or occasionally remains slightly hyperintense to the surrounding liver parenchyma, whereas the central scar shows delayed enhancement because of slow diffusion of contrast through the myxoid stroma (see Fig. 32.1 ).

However, sensitivity for diagnosis decreases if one of these imaging features is missing, for example, in the absence of central scar ( Fig. 32.2 ), or in the presence of additional findings such as fat deposition or sinusoidal distention ( Fig 32.3 ). In these cases, the use of CEUS and/or liver-specific MRI contrast agents is paramount for differentiating FNH from other lesions such as HCA (see the section later on differential diagnosis ).

Hepatocellular Adenoma

Diagnosis of HCA is often more difficult because imaging features encompass a variety of appearances. Imaging findings include fatty, necrotic, and hemorrhagic components, but a homogeneous hypervascular appearance may also be seen.