Imaging of Hepatic Focal Nodular Hyperplasia: Pictorial Review and Diagnostic Strategy

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Focal nodular hyperplasia (FNH) is the second most common benign solid liver lesion after hemangioma, occurring more frequently in young women. The prime differential diagnoses include hepatocellular adenoma, hepatocellular carcinoma, and hypervascular metastasis. As the management of FNH is typically conservative, imaging plays a key role in diagnostic pathway, and misdiagnosis may have a major clinical effect. In this article, we describe the ultrasound, computed tomography, and magnetic resonance imaging features of FNH, underlining the importance of typical radiological features that allow a specific noninvasive diagnosis. We present a large spectrum of a typical imaging findings that FNH may present and discuss the up-to-date diagnostic strategy.

Introduction

Focal nodular hyperplasia (FNH) is the second most common benign solid liver lesion after hemangioma, with a reported prevalence of 0.9% in the adult population and most lesions occurring in young patients.1 The male-to-female ratio of 1:8, and the characteristics of FNH regarding patient sex have been debated. Some authors have reported that FNHs developing in men were smaller and more often atypical,2 though a recent study has showed no difference in age of occurrence, size, and imaging features.3

Histologically, FNHs are characterized by the presence of normally functioning hepatocytes with malformed biliary ducts (cholangiolar proliferation), which lead to a slower biliary excretion.4 They have been variously considered as neoplasms, hamartomas, or as a reaction to focal injury.5 It is now clear that FNHs are polyclonal lesions that should be distinguished from true neoplasms.6 The presence of focal vascular malformation has been suggested as a possible underlying pathogenetic mechanism. According to that hypothesis, FNHs emerged as a response to a local greater blood flow when compared with the adjacent liver parenchyma.5

FNH is often an incidental finding at imaging in asymptomatic patients, and distinction between FNHs and other hypervascular focal liver lesions such as hepatocellular adenoma, hepatocellular carcinoma (HCC), and hypervascular metastases is critical to ensure proper management.7, 8, 9 Indeed, FNH is not associated with any malignant potential.5, 10, 11 Therefore, most confirmed FNHs are managed conservatively.11, 12, 13 Surgical approach is considered for rare symptomatic lesions and when the diagnosis of hepatocellular adenoma or carcinoma cannot be ruled out. As these lesions are discovered fortuitously in young patients, noninvasive characterization by imaging techniques should be privileged. Several imaging criteria have been associated with FNH, their association allowing for a highly specific diagnosis. Yet, all these criteria have to be scrupulously searched for, as a misdiagnosis of FNH may affect patient management and outcome.

In this article, we aim to underline ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) findings of FNH, stressing the importance of typical radiological features that lead to a specific noninvasive diagnosis. We present a large spectrum of atypical imaging findings that FNH may present and discuss the up-to-date diagnostic strategy.

Section snippets

Gray-Scale US

FNH shows variable nonspecific patterns of appearance on gray-scale US.14 FNHs are usually well delineated, and more than 60% of FNHs appear hypoechoic when compared with the surrounding liver parenchyma; however, isoechoic or slightly hyperechoic appearance is not uncommon.14 US appearance also depends on the surrounding liver, and hypoechoic FNHs are more frequently encountered in the setting of a steatotic and hyperechoic liver parenchyma.14 In case of isoechoic FNH the lesion may be

Multiphasic CT and MRI: Typical Appearance With Extracellular Contrast Agents

The diagnosis of FNH is based on a combination of features, none of them being specific to FNH, taken separately. There are 5 major criteria to assess a proper diagnosis and they are as follows:

  • (a)

    Attenuation or signal intensity similar to that of the surrounding liver.

  • (b)

    Homogeneity.

  • (c)

    Strong enhancement at arterial phase without washout.

  • (d)

    Presence of a central scar.

  • (e)

    Absence of capsule (± lobulated aspect).

All these signs must be unequivocally present to allow confident diagnosis (Figure 4, Figure 5),

Value of Diffusion-Weighted Imaging

Most FNHs show mild signal hyperintensity on higher b-value diffusion-weighted images, with a significantly lower mean apparent diffusion coefficient when compared with the surrounding parenchyma, explaining that diffusion-weighted imaging is not useful for the differentiation between FNH and other focal liver lesions, including malignancy.35 This is mostly because of the presence of fibrotic septa.36 Yet, diffusion restriction is minimal as an apparent diffusion coefficient ratio (lesion or

Value of Hepatobiliary MR Contrast Agent Injection

Hepatobiliary contrast agents are gadolinium-based contrast media that are selectively uptaken by functional hepatocytes. There are 2 available agents such as gadoxetic acid (or gadoxetate disodium or Gd-EOB-DTPA—Primovist or Eovist, Bayer Schering, Berlin, Germany) and gadobenate dimeglumine (Gd-BOPTA - Multihance; Bracco Imaging, Milan, Italy) that have different pharmacokinetics and pharmacodynamics proprieties. After the acquisition of classical vascular phases, in which FNH MR appearance

Size Variation

Size variation is not uncommon in FNH. Approximately 20%-30% of the lesions are reported to show significant size variation.56, 57 Most of these variations are represented by tumoral size decreasing (up to 90%), whereas size increasing (Fig. 8) is more rare. These changes in tumor size seem not to be related to hormonal factors.56 Moreover, FNHs can undergo self-regression, especially in elderly subjects, which is probably why most lesions are encountered in younger female subjects.58

Pedunculated Lesions

FNH may

Association With Other Benign Lesions

FNH has been reported to be associated with other focal liver lesions. Prevalence of hemangioma or hepatocellular adenoma (Fig. 16) is higher in patients with FNH when compared with the general population.69, 70 These benign lesions may share common pathogenic factors, including focal disturbance of the hepatic blood supply that somehow facilitates their development. Radiologists should be aware of these associations because the presence of multiple hypervascular liver masses with variable

Modern Diagnostic Strategy

Figure 17 details a proposition for diagnostic strategy of FNH according to the principles of the recent EASL Clinical Practice Guidelines on the management of benign liver tumors.71

It can be summarized in the following 6 points:

  • 1.

    A lesion suggestive of FNH on gray-scale or Doppler US requires performing another examination. CEUS and MRI are the best options.

  • 2.

    Diagnosis of FNH can be made when all typical imaging features are present on contrast-enhanced imaging, if the patient has no chronic liver

Conclusion

FNH of the liver is a relatively frequent benign hepatic tumor, encountered typically in young female patients. FNH can be easily diagnosed on imaging only if all typical radiological findings are present. Nevertheless, radiologists must be aware of the large spectrum of atypical findings that the lesion may present to pursue a correct diagnostic pathway and avoid misdiagnosis.

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