Focal nodular hyperplasia
Updates to Article Attributes
Focal nodular hyperplasia (FNH) is a benign tumour-like mass of the liver, second only to cavernous haemangiomas in frequency. It has characteristic radiographic features in multi-modality imaging, but some lesions may be atypical in appearance. FNH are usually treated conservatively.
Epidemiology
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.
Clinical presentation
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.
Associations
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
Pathology
The origin of FNH is thought to be due to a hyperplastic growth of normal hepatocytes with a malformed biliary draining system. It is also believed to be 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%
Typical FNH
Macroscopically, typical lesions demonstrate a tumour which is often quite large with well-circumscribed margins but poorly encapsulated. A prominent central scar is usually noted with radiating fibrous septae: <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 multinodular, composed of nearly normal hepatocytes 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.
Atypical FNH
An atypical FNH refers to a lesion which lacks the central scar and central artery and is thus harder to distinguish from other lesions on gross inspection and imaging 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.
Variants
Some authors also describe division of atypical FNH into several variants which include 8:
- telangiectatic variant
- mixed hyperplastic and adenomatous variant
- lesions with large cell hepatocellular atypia
Radiographic features
As FNH is usually treated conservatively, accurate imaging is essential in preventing unnecessary intervention.
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.
Ultrasound
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 (opposite to adenoma)
- unenhanced scar may be present
- arterial phase
CT
A multi-phase scan is ideal, commonly comprising 4:
- non-contrast
- 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 isoattenuatinghypo/isoattenuating to liver.
The fibrotic scar demonstrates enhancement on delayed scans in up to 80% of cases 4.
MRI
Liver MRI is both sensitive (70%) and specific (98%).
Signal characteristics
-
T1
- iso to moderately hypointense
- hypointense central scar
-
T2
- iso to somewhat hyperintense
- hyperintense central scar
-
contrast studies
-
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)
- 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 (c.f. adenomas which classically are 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)
Nuclear medicine
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.
Differential diagnosis
General imaging differential considerations include:
-
hepatic adenoma
- usually more heterogeneous due to haemorrhage, fat, or necrosis
- washout on the portal and delayed phases of contrasted studies
-
hepatocellular carcinoma (HCC)
- usually in a cirrhotic liver
- signs of vascular invasion
-
fibrolamellar HCC
- fibrous central scar with calcification
- has metastases in ~70%
- Tc-99m sulphur colloid scans are negative
-
hypervascular hepatic metastasis/metastases
- usually multiple
-
hepatic haemangioma
- peripheral and centripetal enhancement
- no central scar
Practical points
- 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); if the patient has risk factors (e.g. metabolic syndrome), consider both on a differential 15
-<a title="Hepatic haemangiomas" href="/articles/hepatic-haemangioma-3">hepatic haemangiomas</a> (most common) <sup>6</sup>- +<a href="/articles/hepatic-haemangioma-3">hepatic haemangiomas</a> (most common) <sup>6</sup>
-<li><a title="portal shunts" href="/articles/portal-shunts">portal shunts</a></li>- +<li><a href="/articles/portal-shunts">portal shunts</a></li>
-</ul><p>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 <sup>4</sup>.</p><p>FNH demonstrates bright arterial contrast enhancement except for the central scar which remains hypoattenuating <sup>4</sup>. Enlarged central arteries may be seen. </p><p>In the portal venous phase, the lesion becomes isoattenuating to liver.</p><p>The scar demonstrates enhancement on delayed scans in up to 80% of cases <sup>4</sup>.</p><h5>MRI</h5><p><a href="/articles/liver-mri-protocol">Liver MRI</a> is both sensitive (70%) and specific (98%).</p><h6>Signal characteristics</h6><ul>- +</ul><p>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 <sup>4</sup>.</p><p>FNH demonstrates bright arterial contrast enhancement except for the central scar which remains hypoattenuating <sup>4</sup>. Enlarged central arteries may be seen. </p><p>In the portal venous phase, the lesion becomes hypo/isoattenuating to liver.</p><p>The fibrotic scar demonstrates enhancement on delayed scans in up to 80% of cases <sup>4</sup>.</p><h5>MRI</h5><p><a href="/articles/liver-mri-protocol">Liver MRI</a> is both sensitive (70%) and specific (98%).</p><h6>Signal characteristics</h6><ul>
-<li>central scar retains contrast on delayed scans <sup>13</sup>- +<li>central fibrotic scar retains contrast on delayed scans <sup>13</sup>
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