Focal nodular hyperplasia (FNH) is a regenerative mass lesion of the liver and the second most common benign liver lesion (most common is cavernous haemangioma). Many FNHs have characteristic radiographic features in multimodality imaging, but some lesions may be atypical in appearance. FNHs are typically asymptomatic lesions usually requiring no treatment.
FNH is most frequently found in young to middle-aged adults, with a strong female predilection 3-4; ~15% (range 10-20%) occur in men 7. Although exogenous oestrogens do not cause FNH, they have been shown to increase the size of these masses 4. The isolated occurrence is the commonest but in up to 20% may be multiple and could occur with other lesions such as haemangiomas, etc.
These masses are either found incidentally on imaging or present due to mass effect, with right upper quadrant pain in 20% 5. Unlike hepatic adenomas, FNHs are only rarely complicated by spontaneous rupture and haemorrhage 1,4.
Association with other benign lesions is commonly seen (~25%) 8:
- hepatic haemangiomas (most common) 6
- hereditary haemorrhagic telangiectasia
- arteriovenous malformations (AVM)
- anomalous venous drainage
- hepatic adenoma (possible but not proven) 16
- congenital absence of portal vein/portal vein atresia
- Budd-Chiari syndrome
- portal shunts
- idiopathic portal hypertension
- portal or pulmonary hypertension 7
The origin of FNH is thought to be due to a hyperplastic growth of normal hepatocytes with a malformed biliary draining system, possibly in response to a pre-existent arteriovenous malformation 1,4. The arterial supply is derived from the hepatic artery whereas the venous drainage is into the hepatic veins. FNH does not contain portal venous supply 9.
FNH is divided into two types 4:
- typical: 80%
- atypical: 20%
Macroscopically, typical lesions demonstrate a mass which is often quite large with well-circumscribed margins but poorly encapsulated. A characteristic feature is a prominent central scar with radiating fibrous septae, but this is present in less than 50% of cases 7. A large central artery is usually present with spoke-wheel like centrifugal flow 3-4 (no portal veins).
Histologically the lesion is composed of abnormal nodular architecture, mal-formed vessels, and cholangiolar proliferation. Nearly normal hepatocytes are arranged in 1-2 cell-thick plates. Bile ductules are usually found at the interface between hepatocytes and fibrous regions 1-2. Kupffer cells are present 4,7.
There is essentially no malignant potential 1.
An atypical FNH refers to a lesion which lacks the central scar and central artery, thus harder to distinguish from other lesions on gross inspection and imaging, or abnormal nodular architecture but with abnormal cholangiolar proliferation 4 .
Atypical features also include pseudocapsule, lesion heterogeneity (more commonly seen in adenoma), non-enhancement of the central scar and intralesional fat 6.
Nodules can grow and disappear, and new nodules can appear even after resection 7.
Some authors also describe division of atypical FNH into several variants which include 8:
- telangiectatic variant: most common
- mixed hyperplastic and adenomatous variant
- lesions with large cell hepatocellular atypia
As FNH is usually treated conservatively, accurate imaging is essential in preventing unnecessary intervention. Moreover, in women of child-bearing age, hepatic adenoma is the chief differential diagnosis and biopsy of the latter can result in haemorrhage 1,17.
It should be noted that up to 20% of patients with an FNH will have multiple lesions 4 and a further 23% will have haemangiomas 4.
The echogenicity of both FNH and its scar is variable, and it may be difficult to detect on ultrasound. Some lesions are well marginated and easily seen whereas other are isoechoic with surrounding liver. Detectable lesions characteristically will demonstrate a central scar with the displacement of peripheral vasculature on colour Doppler examination. However, these findings are seen in only 20% of cases 4.
- contrast-enhanced ultrasound 14:
- arterial phase
- FNH will enhance relative to background liver
- prominent feeding vessel may be seen
- portal venous phase
- centrifugal filling (opposite to haemangioma and adenoma)
- sustained enhancement in the portal venous phase (as opposed to adenoma)
- unenhanced scar may be present
- arterial phase
A multi-phase scan is ideal, commonly comprising 4:
- arterial (25-35 second delay)
- portal venous (60-70 second delay)
- delayed (5-10 minute delay)
On the non-contrast series, the lesion is usually hypo- or isoattenuating but may appear hyperattenuating if the rest of the liver is fatty. A hypoattenuating central scar can be seen in up to 60% of lesions >3 cm in size 4.
FNH demonstrates bright arterial contrast enhancement except for the central scar which remains hypoattenuating 4. Enlarged central arteries may be seen.
In the portal venous phase, the lesion becomes hypo/isoattenuating to liver.
The fibrotic scar demonstrates enhancement on delayed scans in up to 80% of cases 4.
Liver MRI is both sensitive (70%) and specific (98%).
- iso to moderately hypointense
- hypointense central scar
- iso to somewhat hyperintense
- hyperintense central scar
T1 C+ (Gd)
- intense early arterial phase enhancement, similar to CT
- central fibrotic scar retains contrast on delayed scans 13
- isointense to liver on portal venous phase 10-12
T1 C+ (Eovist/Primovist)
- early arterial enhancement
- enhancement persists into delayed phases 11 to a greater degree than the background liver due to the presence of normal hepatocytes and abnormal bile ductules
- fades toward background liver intensity on the delayed hepatobiliary phase, with a small amount of enhancement remaining (cf. adenomas, which are classically hypointense relative to liver on hepatobiliary phase)
T2* C+ (reticuloendothelial agent: SPIO)
- hypointense mass as a result of susceptibility signal loss due to uptake by Kupffer cells
- T1 C+ (Gd)
The presence of Kupffer cells in FNH allows these lesions to take up technetium (Tc) 99m sulphur colloid. P\A positive scans are seen in 80% of lesions and are helpful in distinguishing them from hepatic adenomas, HCC and hepatic metastases which, usually but not always, do not contain Kupffer cells 4.
Treatment and prognosis
FNH is benign, with no malignant potential and a minuscule risk of complication (rupture, haemorrhage) and thus are usually treated conservatively 1.
General imaging differential considerations include:
- hepatic adenoma: usually more heterogeneous CT portal and delayed phases contrast washout; no gadoxetate retention on delayed phase MR
- hepatocellular carcinoma (HCC): usually in cirrhosis; vascular invasion
- fibrolamellar HCC: larger >12 cm mass with T2 hypointense fibrous central scar with calcification; 70% has metastases; biliary, vascular, and nodal invasion; negative Tc-99m sulfur colloid scans
- hypervascular hepatic metastases: usually multiple; CT portal and delayed phases hypodense (washout); older patients with known primary tumor
- hepatic haemangioma: peripheral and centripetal enhancement; blood vessels isodense; no central scar; only small ones with rapid enhancement simulate focal nodular hyperplasia (FNH)
- be wary of calling a hypervascular lesion in a cirrhotic liver an FNH, unless definitively able to prove it is not HCC.
- FNH typically has no capsule; if a hypervascular liver mass has a capsule, put HCC above FNH on the differential.
- there is likely overlap in appearance between FNH and inflammatory hepatic adenoma when using gadoxetic acid (Eovist/Primovist); if the patient has risk factors (e.g. metabolic syndrome), consider both on a differential 15.
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- depositional disorders
- infection and inflammation
- liver abscess
- hepatic hydatid infection
- liver and intrahepatic bile duct tumours
- benign epithelial tumours
- hepatocellular hyperplasia
- hepatocellular adenoma
- hepatic/biliary cysts
- benign nonepithelial tumours
- primary malignant epithelial tumours
- primary malignant nonepithelial tumours
- haematopoietic and lymphoid tumours
- secondary tumours
- adrenal rest tumours
- hepatic carcinosarcoma
- hepatic fibroma
- hepatic Kaposi sarcoma
- hepatic lipoma
- hepatic mesenchymal hamartoma
- hepatic myxoma
- hepatic rhabdoid tumour
- hepatic solitary fibrous tumour
- hepatic teratoma
- hepatic yolk sac tumour
- inflammatory myofibroblastic tumour (inflammatory pseudotumor)
- nodular regenerative hyperplasia
- pancreatic rest tumours
- primary hepatic carcinoid
- benign epithelial tumours
- extrahepatic bile duct tumours
- liver and intrahepatic bile duct tumours
- portal venous gas
- portal hypertension
- portal vein thrombosis
- arterioportal shunts
- hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)
- Budd-Chiari syndrome
- passive hepatic congestion
- hepatic veno-occlusive disease
- hepatic infarction
- peliosis hepatis
- hepatic venous malformations (haemangiomas)
Ultrasound - liver
- ultrasound (introduction)
- liver ultrasound
- hepatic vasculature
- hepatic trauma on ultrasound
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