What is focal nodular hyperplasia of the liver?

What is Focal Nodular Hyperplasia of the Liver?

Focal nodular hyperplasia (FNH) is the second most common benign liver tumor after hemangioma, characterized by a hyperplastic response of normal liver tissue to a congenital vascular malformation, with a prevalence of 0.3% to 3% in the general population and predominantly affecting reproductive-aged women. 1, 2

Pathophysiology and Histologic Features

FNH represents a hyperplastic or regenerative response to hyperperfusion through anomalous arteries located centrally within the lesion. 1 The classic histologic hallmark is a central stellate scar containing a large artery with multiple vessel branches radiating through fibrous septae toward the periphery, creating the characteristic spoke-wheel vascular pattern. 1

The lesion consists of lobular proliferation of normally differentiated hepatocytes arranged around this central fibrous scar, distinguishing it from other benign liver tumors. 3

Epidemiology and Demographics

• Prevalence ranges from 0.3% to 3% in the general population 1, 2
• Female-to-male ratio is approximately 26:1, with predominance in reproductive-aged women 2
• Can occur in men and children, though less commonly 4
• May coexist with other vascular hepatic lesions (particularly hemangiomas) in up to 20% of cases 1, 2

Relationship with Hormones and Oral Contraceptives

The association between FNH and estrogen or oral contraceptive use is not well established. 1, 2 One case-control study found an association with prolonged oral contraceptive use, while another found no relationship between contraceptive use and lesion size or number. 1 Current guidelines do not consider oral contraceptive use causally related to FNH development or growth, and both oral contraceptive use and pregnancy are considered safe. 1, 2

Clinical Presentation and Natural History

• Usually asymptomatic and discovered incidentally on imaging performed for other indications 1, 3, 4
• Rarely grows or bleeds 4
• Has no malignant potential 3, 5
• Extremely low risk of spontaneous rupture, with only one case reported in the literature 1, 2
• When symptomatic, patients may present with upper abdominal pain, though other causes must be excluded first 5

Diagnostic Imaging Characteristics

Ultrasound Features

• Typically appears hyperechogenic on B-mode imaging 1
• Color-Doppler shows the pathognomonic spoke-wheel sign with a feeding vessel evident 1

Contrast-Enhanced Ultrasound (CEUS)

• Strong hyperperfusion from a large, tortuous feeding artery in the arterial phase 1, 2
• Centrifugal filling pattern (center to outward) producing spoke-wheel appearance 1, 6
• "Lightbulb" sign: lesion fills rapidly and appears more enhanced than surrounding liver 1
• Hyper- or isoechoic in late phase (unlike malignant lesions which show washout) 1

MRI Characteristics

• MRI with gadolinium contrast achieves 88-99% accuracy for FNH diagnosis 6
• Iso- or hyperintense on hepatobiliary phase with gadoxetate-enhanced MRI 6
• MRI is the definitive diagnostic test for distinguishing FNH from other lesions 6

Management Approach

Conservative observation is the standard of care for FNH, with no routine surveillance imaging needed. 2, 6 Key management principles include:

• No intervention required for typical-appearing FNH in asymptomatic patients 6, 3
• Pregnancy is not contraindicated, and vaginal delivery carries no increased risk 1, 2, 6
• No monitoring required during pregnancy, unlike hepatic adenomas which require trimester surveillance 1, 2
• Oral contraceptive use is safe and does not require discontinuation 1

Indications for Surgical Resection

Resection is rarely required but may be considered in specific circumstances:

• Diagnostic uncertainty when contrast-enhanced MRI cannot definitively exclude malignancy 3
• Symptomatic lesions with persistent upper abdominal pain after excluding other causes and observation period of 1-7 years 5
• Rapid growth in unusual cases 5

When performed, surgical resection has 14% morbidity and zero mortality, with immediate and lasting symptom control. 3, 5

Important Diagnostic Pitfalls

• Percutaneous biopsy should be avoided to prevent risk of tumor seeding and bleeding 3
• High-flow FNH can mimic hepatocellular carcinoma or hepatic adenoma if the nodular pattern and centripetal flow are not recognized 1, 6
• Late-phase washout can occur (especially in patients >35 years), potentially mimicking malignancy 1, 6
• FNH may be mistaken for hepatocellular carcinoma when the liver appears nodular 2
• Frequently found in hereditary hemorrhagic telangiectasia with 100-fold greater prevalence than general population 2

Key Distinction from Hepatic Adenoma

Unlike hepatic adenomas, FNH:

• Has no risk of malignant transformation 3
• Does not require pre-pregnancy intervention regardless of size 2
• Does not require surveillance during pregnancy 1, 2
• Has extremely low rupture risk 1, 2
• Shows centrifugal (center-to-periphery) filling on CEUS versus centripetal (periphery-to-center) in adenomas 1