Focal nodular hypertensia
Executive Summary
Focal nodular hyperplasia (FNH) is a benign, non-cancerous liver lesion composed of a proliferation of hyperplastic hepatocytes organized around a central stellate scar. It is the second most commonly encountered benign liver lesion after hepatic hemangioma. FNH predominantly affects females, with up to 80% of cases occurring in this demographic, typically between the ages of 35 and 50. The pathogenesis is understood as a hyperplastic (regenerative) response to localized arterial hyperperfusion within the liver.
Clinically, FNH is most often asymptomatic and discovered as an incidental finding during abdominal imaging for other reasons. When symptoms do occur, they are typically nonspecific, with abdominal pain from mass effect being the most common complaint. Laboratory tests, including liver function and alpha-fetoprotein levels, are characteristically normal.
The diagnosis of FNH relies almost exclusively on its distinct features observed in contrast-enhanced, multiphase imaging, primarily magnetic resonance imaging (MRI) or computed tomography (CT). Key imaging hallmarks include homogeneous arterial hyper-enhancement, a central scar that often shows delayed enhancement, and specific behavior with hepatocyte-specific contrast agents, which typically obviates the need for a biopsy.
Management for the vast majority of patients with asymptomatic FNH is conservative observation without the need for routine surveillance imaging, given the lesion's extremely low risk of growth or complications. The prognosis is excellent, as FNH lesions are typically stable or may even regress over time. Complications such as bleeding are very rare, and malignant transformation has not been reported.
1.0 Overview and Definition
Focal nodular hyperplasia (FNH) is a benign tumor-like lesion of the liver characterized by a localized, well-demarcated proliferation of hyperplastic hepatocytes surrounding a central fibrous stellate scar. It is the second most common benign lesion found in the liver, exceeded only by hepatic hemangioma. Typically, FNH presents as a solitary lesion, although multiple lesions can be found in up to 20% of patients.
The underlying cause is considered a regenerative response of liver cells to an altered pattern of blood flow, specifically arterial hyperperfusion, which results in the characteristic scar tissue at the lesion's center.
2.0 Epidemiology and Pathogenesis
2.1 Prevalence
The estimated prevalence of FNH varies depending on the method of detection:
Autopsy Studies: Prevalence is estimated at 0.3 to 3 percent.
Clinical Series: Prevalence based on clinical findings is lower, at approximately 0.03 percent.
Imaging Studies: In large observational series of patients undergoing abdominal imaging, the prevalence was found to be between 0.2 and 1.6 percent.
2.2 Patient Demographics
Age: FNH can occur at any age but is most frequently diagnosed in patients between the ages of 35 and 50. It is uncommon in children, accounting for approximately 2 percent of pediatric liver tumors.
Sex: There is a strong female predominance, with FNH being found in females in up to 80 percent of cases.
2.3 Risk Factors
Despite the strong female predominance, available data suggests that female sex hormones, such as those in oral contraceptive pills, do not appear to be a risk factor for the initial development or subsequent growth of FNH.
2.4 Pathogenesis
FNH is not a true neoplasm but rather a hyperplastic regenerative response. The leading theory suggests that it develops due to altered oxygenated blood flow within the liver parenchyma. This may be caused by a congenital vascular malformation, an aberrant dystrophic artery, or an injury to a portal tract. The resulting arterial hyperperfusion stimulates a response from the hepatic stellate cells, leading to the formation of the characteristic central fibrous scar. FNH may also occur in association with other vascular diseases, such as hereditary hemorrhagic telangiectasia and hepatic hemangiomas.
3.0 Pathologic and Clinical Features
3.1 Pathologic Characteristics
Typical Form (Macroscopic): FNH is typically a firm, solitary lesion with a well-defined margin but without a true capsule. The size is usually less than 5 cm, though measurements up to 19 cm have been reported. A surgical specimen shows a mass lesion within a noncirrhotic liver, distinguished by the central stellate scar.
Typical Form (Microscopic): The lesion consists of normal-appearing hepatocytes grouped into nodules, which are divided by fibrous septa radiating from the central scar. This scar contains a large artery that branches out into the septa. The fibrous septa also contain varying degrees of enlarged portal tracts with arteries, portal veins, and bile ductules. The presence of Kupffer cells helps to distinguish FNH from hepatocellular adenoma, which typically lacks these cells and bile ducts.
Atypical Forms: These forms lack one of the classic features but demonstrate a proliferation of bile ducts.
FNH without a central scar: This variant lacks the characteristic scar and lesions are often smaller than 3 cm.
FNH with steatosis: This is a recognized variant typically seen in patients who have underlying hepatic steatosis (fatty liver).
3.2 Clinical Presentation
The clinical presentation of FNH exists on a spectrum:
Asymptomatic Presentation: The majority of cases are asymptomatic, with the lesion being discovered incidentally on imaging or during surgery.
Symptomatic Presentation: When symptoms are present, the most commonly reported is abdominal pain, which is usually related to the mass effect of a larger lesion.
Physical Examination: The physical exam is typically normal. Infrequently, hepatomegaly or a palpable abdominal mass may be detected.
Laboratory Findings: Liver biochemical and function tests are usually normal in patients with FNH. The alpha-fetoprotein (AFP) level is also normal.
4.0 Diagnosis and Imaging
4.1 Diagnostic Approach
The diagnosis of FNH may be suspected in a patient without cirrhosis who is found to have a solid, hyperenhancing liver lesion on imaging. For suspected cases, the definitive diagnosis is typically made with cross-sectional, contrast-enhanced multiphase MRI or CT. A biopsy may be necessary to confirm the diagnosis if imaging features are not typical. For symptomatic patients who undergo surgical resection, the diagnosis is confirmed with histology.
4.2 Key Imaging Modalities and Findings
Contrast-enhanced imaging is central to diagnosing FNH. The key characteristics are summarized below.
5.0 Differential Diagnosis
When imaging features are not definitive, other liver lesions must be considered:
Hepatocellular adenoma (HCA): This is a critical differential diagnosis. Contrast-enhanced MRI with hepatocyte-specific contrast agents is highly effective in distinguishing between FNH and HCA, with reported sensitivity and specificity ranging from 91 to 100 percent and 87 to 100 percent, respectively.
Hepatocellular carcinoma (HCC): HCC typically occurs in patients with a history of cirrhosis and has a different imaging appearance (e.g., early washout of contrast) compared to FNH.
Fibrolamellar carcinoma: While more characteristic of FNH, a central scar may also be present in this rare variant of HCC.
6.0 Management and Prognosis
6.1 Management of Asymptomatic Patients
Observation: For asymptomatic lesions, routine surveillance imaging is not recommended due to the very low risk of lesion growth or complications.
Oral Contraceptives: It is not generally insisted that patients discontinue oral contraceptives or other estrogen-containing preparations. However, it is considered reasonable to obtain a follow-up imaging study in 6 to 12 months for female patients who continue taking these drugs.
Stability: A study of 34 asymptomatic FNH lesions monitored with ultrasound found that 97 percent either remained stable or regressed in size during a mean follow-up of 42 months.
6.2 Management of Symptomatic Patients
For the uncommon patient with persistent symptoms, such as abdominal pain attributed to FNH, procedural intervention may be required.
Surgical Resection: May be performed for persistent pain.
Less Invasive Approaches: Transarterial embolization and radiofrequency ablation have also been used.
6.3 Prognosis and Special Considerations
Prognosis: The prognosis for patients with FNH is generally excellent.
Complications: Complications like bleeding are very rarely reported.
Malignant Transformation: Malignant transformation of FNH has not been reported.
Pregnancy: Pregnancy is not contraindicated for asymptomatic patients with FNH who wish to conceive. Routine surveillance liver ultrasound is not performed during pregnancy.
