Description
Focal Nodular Hyperplasia (FNH) is a benign tumour-like hepatic lesion primarily occurring in the liver, characterised by the nodular proliferation of hepatic parenchyma, which typically centres around a fibrous scar. Despite its name, FNH is not a neoplasm but rather a hyperplastic response to a vascular abnormality within the liver tissue.
Pathogenesis
The pathogenesis of FNH is linked to a vascular malformation leading to a localised hyperperfusion. It is thought that this hyperperfusion, in turn, drives a hyperplastic response in the liver parenchyma surrounding the anomalous blood vessels, culminating in the formation of FNH.
Epidemiology, Risk Factors & Associations
- FNH predominantly affects women (female to male ratio is approximately 8:1).
- It is most common in the 20 to 50-year-old age group.
- The incidence of FNH in the general population is not well established. However, studies show that FNH is present in up to 0.6% of the population based on autopsy studies.
- While the majority of FNH cases are sporadic, associations with the use of oral contraceptives and hormone replacement therapy have been suggested.
- FNH is the 2nd most common benign tumour of the liver.
Clinical Features
The majority of FNH lesions are asymptomatic and are often detected incidentally. In cases where symptoms do occur, these can include:
- Nonspecific right upper quadrant abdominal discomfort
- Palpable mass
Complications
Complications of FNH are rare. Rarely, FNH lesions may rupture leading to intra-abdominal haemorrhage, although this is uncommon.
Subtypes
There are no formally recognised subtypes of FNH.
Pathological Features
Morphology
- Macroscopically, FNH lesions are well-demarcated, solitary nodules that are often subcapsular. They are typically tan or yellow in appearance and can be up to 20cm in diameter.
- A central scar is often visible. The central scar is not simply a fibrotic region; rather, it represents a complex network of fibrous septa that contain malformed vascular and biliary structures – hence the scar will enhance slowly.
Histopathology
Histologically, FNH is characterised by hepatocyte nodules separated by fibrous septa. The central scar typically contains large abnormal vessels. Bile duct proliferation is not typically seen.
Radiological Features
General Features
- Presents as a well-circumscribed solitary lesion, majority measuring <5 cm.
- The presence of a central scar is a key feature, although it may not be present in all cases.
- Homogeneously hyperenhancing mass on arterial phase that blends in imperceptibly on the portal venous-phase. Hyperintense enhancement on hepatobiliary phase of gadoxetate-enhanced MR.
- Central scar: Delayed enhancement of central scar.
- The near isointensity of the mass to the liver on both T1WI and T2WI is unusual for any mass other than a FNH
US
- FNH lesions typically appear as well-defined, hyperechoic or isoechoic lesions.
- Doppler US can show a spoke-wheel pattern of vasculature.
CT
- Non-Enhanced CT (NECT): Isodense or slightly hypodense to normal liver
- Contrast-Enhanced CT (CECT):
- Hepatic arterial-phase scan: Transient, intense, homogeneous enhancement ± large artery feeding central scar
- Portal venous-phase scan: Blends in imperceptibly with normal liver, large draining veins → hepatic veins
- Delayed scans: Mass approximately isodense to normal liver. The central scar becomes hyperdense due to fibrous tissue.
MRI
- T1: Isointense to slightly hypointense mass with hypointense central scar.
- T2: Slightly hyperintense to isointense mass with hyperintense central scar
- The near isointensity of the mass to the liver on both T1WI and T2WI is unusual for any mass other than a FNH
- Gd+:
- Arterial phase: Hyperintense homogeneous signal greater than background liver, central scar may not enhance.
- Portal venous: Isointense to liver.
- Delayed phase: Isointense mass with hyperintense scar
- Specific hepatobiliary MR contrast agents: Gadoxetate (Eovist or Primovist)
- Arterial phase: Bright, homogeneous enhancement of FNH
- Hepatobiliary phase (delayed, ~ 20 minutes): Prolonged enhancement of entire FNH
US
- Mass is mostly homogeneous and isoechoic to liver, occasionally hypoechoic or hyperechoic.
- Central scar is hypoechoic. On colour doppler, demonstrates spoke-wheel pattern (large central feeding artery with multiple small vessels radiating peripherally, large draining veins at tumour margins). May demonstrate high-velocity blood flow.
Angiography
- Arterial phase: Hypervascular mass with hypovascular scar. Enlargement of main feeding artery with centrifugal blood supply, same spoke-wheel pattern as on colour Doppler
- Venous phase: Large draining veins → hepatic veins
- Capillary phase: Intense “stain” (enhancement), no avascular zones
NM
- Technetium sulfur colloid (TcSC): Increased uptake in 60% (only FNH has both Kupffer cells and bile ductules) – almost pathognomonic.
- Tc-HIDA scan (hepatic iminodiacetic acid): Normal or increased uptake, prolonged enhancement (80%)
- Tc-99m-tagged RBC scan (not useful): Early isotope uptake and late defect.
Differential Diagnosis
- Hepatic Adenoma: A benign hepatic tumour often associated with oral contraceptive use and metabolic conditions such as glycogen storage diseases. However, unlike FNH, hepatic adenomas can have a significant risk of malignant transformation. They are typically hypervascular but lack a central scar. On MRI, they often appear hypointense on T1 and hyperintense on T2-weighted images. In contrast to FNH, hepatic adenomas usually show rapid washout of contrast on the portal venous phase and rarely retain gadoxetate on the delayed phase.
- Fibrolamellar Hepatocellular Carcinoma: A variant of hepatocellular carcinoma that typically affects young adults and is not associated with chronic liver disease. These tumours are typically large (>12 cm), heterogeneous masses. On imaging, they often present with a central scar, like FNH, but they can exhibit more “aggressive” features, such as lymphadenopathy, metastases, or vascular invasion. In contrast to FNH, the central scar is T2 hypointense and often does not enhance.
- Hepatic Cavernous Hemangioma: This is the most common benign hepatic tumour, which comprises a tangle of blood vessels.On imaging, they demonstrate characteristic peripheral nodular enhancement with centripetal fill-in on contrast-enhanced CT or MRI. Unlike FNH, the enhanced portions are isodense to blood vessels and the lesions do not typically show homogeneous enhancement or contain a central scar.
- Hypervascular Metastasis: These are secondary hepatic malignancies, which most commonly originate from primary tumours such as renal cell carcinoma, neuroendocrine tumours, melanoma, and thyroid carcinoma. Metastases are usually multiple and associated with a known primary tumour. On contrast-enhanced CT or MRI, they show rapid enhancement during the arterial phase with washout on portal venous or delayed phases, unlike FNH, which has more persistent enhancement. The presence of extrahepatic disease may also aid in differentiating these lesions from FNH.
Management
- Most FNH lesions require no treatment given their benign nature.
- Management typically involves observation with ultrasound or other imaging modality.
- In cases of uncertain diagnosis, a biopsy may be performed.
- Referral to a hepatologist or hepatobiliary surgeon may be necessary for symptomatic lesions or those with diagnostic uncertainty.