Focal Nodular Hyperplasia is a benign lesion incidentally seen in healthy middle-aged women with a history of oral contraceptive which demonstrates a hallmark central stellate scar.
Description
Focal nodular hyperplasia (FNH) is a benign liver lesion frequently discovered incidentally on imaging or at the time of abdominal surgery. It’s considered the second most common benign liver tumour in adults, predominantly in women, particularly those on oral contraceptives. It is characterised by a central stellate scar surrounded by nodules of hepatocytes.
Pathogenesis
FNH is believed to result from a hyperplastic response of hepatocytes to increased blood flow in a vascular malformation. It is not considered a true neoplasm, rather a nodular hyperplasia. The lesion lacks a complete portal triad and is usually composed of normal or slightly atypical hepatocytes.
Subtypes
Classic FNH, the most common variant, and nonclassic FNH, which includes telangiectatic, mixed hyperplastic and adenomatous, and atypical forms.
- Classic FNH: The most common variant (60-70% of all FNH). It characteristically demonstrates a central scar and radiating fibrous septa. The central scar often shows delayed enhancement on CT and MRI, which is a key imaging feature.
- Non-classic FNH:
- Telangiectatic FNH: Also known as FNH-like nodules (10% of all FNH). Histologically, it shows dilated sinusoids and minimal fibrous septa without a central scar. On imaging, it often appears as multiple confluent nodules and can be mistaken for hepatocellular carcinoma or adenoma due to the absence of a central scar.
- Mixed hyperplastic and adenomatous FNH: This rare variant, accounting for less than 5% of FNH cases, displays features of both FNH and hepatic adenoma. These lesions are often larger and have a propensity to hemorrhage, making the clinical presentation similar to hepatic adenoma.
- Atypical FNH: 20% of all FNH. Nodules exhibit atypical feature (absence of a central scar or septa, making them difficult to differentiate from adenoma or hepatocellular carcinoma on imaging. However, they tend to have a characteristic homogenous enhancement pattern on contrast-enhanced MRI.
Epidemiology, Risk Factors & Associations
- Most common in females (8:1 female to male ratio)
- Associated with oral contraceptive use – thought to have trophic effects
- Typically occurs in the 3rd to 5th decades of life
Clinical Features
- Most FNH lesions are asymptomatic
Complications
- Virtually no risk of malignant transformation
- Rare risk of haemorrhage
Pathological Features
Histopathology
Generally:
- Macroscopic: Typically well-circumscribed, solitary lesions, often with a characteristic central scar.
- Microscopic: FNH consists of normal hepatic parenchyma with malformed vessels, ductular proliferation, and often a central stellate scar.
By subtype:
- Classic FNH: Characteristically demonstrates a central scar and radiating fibrous septa.
- Telangiectatic FNH: Shows dilated sinusoids and minimal fibrous septa without a central scar.
- Mixed hyperplastic and adenomatous FNH: Often larger and have a propensity to haemorrhage, making the clinical presentation similar to hepatic adenoma.
- Atypical FNH: Nodules exhibit atypical features(absence of a central scar or septa).
Serology
- Typically normal liver function tests
Biochemistry
- No distinct biochemical markers
Radiological Features
General Features
- Characteristically demonstrates a solitary, well-circumscribed, round-to-oval lesion, often with a central scar.
- Usually subcapsular in location
- Most commonly found in the right lobe of the liver.
- Classic FNH: The central scar often shows delayed enhancement on CT and MRI, which is a key imaging feature.
- Telangiectatic FNH: Often appears as multiple confluent nodules and can be mistaken for hepatocellular carcinoma or adenoma due to the absence of a central scar.
- Mixed hyperplastic and adenomatous FNH: Lesions are often larger and have a propensity to haemorrhage.
- Atypical FNH: Tend to have a characteristic homogenous enhancement pattern on contrast-enhanced MRI.
CT
- Non-contrast: Typically hypo- or iso-dense to liver parenchyma
- C+ Arterial: Early intense enhancement of the lesion, including the central scar
- C+ Venous: Iso-intense to liver parenchyma, with the scar becoming hypo-intense
- C+ Delayed: Typically demonstrates delayed enhancement.
MRI
- T1: Lesion appears isointense or slightly hypointense compared to the surrounding liver parenchyma.
- T2: Lesion appears slightly hyperintense. Central scar may be hyperintense. May demonstrate hyperintense pseudocapsule (compression of adjacent liver parenchyma).
- DWI/ADC: No restricted diffusion.
- T1 C+ (gadolinium) Arterial phase: Lesion demonstrates intense and homogenous enhancement, often appearing hyperintense compared to surrounding liver parenchyma.
- T1 C+ Venous phase: Enhancement becomes isointense with the surrounding liver.
- T1 C+ Delayed phase: The central scar typically enhances in the delayed phase due to the presence of fibrous tissue.
- T1 Primovist Arterial phase: Similar to gadolinium, the lesion demonstrates intense and homogenous enhancement.
- T1 Primovist Venous phase: The enhancement becomes isointense with the surrounding liver.
- T1 Primovist Delayed phase (20 minutes): The lesion typically becomes isointense to liver parenchyma due to the uptake of contrast by hepatocytes. This can be a helpful differentiating feature from adenomas and hepatocellular carcinoma, which typically remain hypointense in this phase due to lack of hepatocellular function.
- In-Out-Phase: No signal drop-out, distinguishing it from hepatic adenoma
US
- B-mode: Hyperechoic or isoechoic to liver, with possible central scar
- Colour Doppler: Increased arterial flow and large draining veins
NM
- Tc-99m sulfur colloid scintigraphy: Normal uptake, consistent with functioning hepatocytes
Grading and Staging
Not applicable as FNH is a benign lesion.
Diagnosis
Mostly based on characteristic imaging findings. Biopsy is rarely required.
Differential Diagnosis
- Hepatic adenoma: Typically shows signal drop-out on in-out phase imaging, can be difficult to distinguish especially in the absence of a central scar
- Hepatocellular carcinoma: Usually in the context of cirrhosis or chronic liver disease, has a different enhancement pattern, often with a T2 hypointense fibrous capsule (vs. T2 hyperintense pseudocapsule).
- Fibrolamellar Hepatocellular Carcinoma: Main differential for lesion with central scar. The central scar however generally demonstrates T2 hypointensity.
- Metastasis: Usually multiple, with a different enhancement pattern
- Giant haemangiomas: Occassionally demonstrate a central scar.
Management
Observation is the primary management strategy. Surgical resection is reserved for symptomatic patients, those with diagnostic uncertainty, or if the lesion is rapidly enlarging.