Hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) are benign hypervascular liver lesions that predominantly occur in young and middle-aged women. Differentiation of these two tumours using radiological imaging modalities may be difficult because of radiological features shared by both tumours [¹]. The frequency with which the diagnosis is in question after routine radiological examination is unclear. Recently it has been reported that MRI with a hepatospecific contrast agent distinguishes HCA from FNH with a sensitivity and specificity of 96.9% and 100%, respectively. However, the diagnosis of most of these lesions was based solely on imaging results without histological confirmation [²]. Differentiation is crucial to decide on appropriate management because of the different therapeutic consequences. FNH is a strictly benign liver lesion and complications are very rare. Conservative treatment is therefore justified, in the absence of mechanical symptoms. On the other hand, HCA carries a risk of spontaneous bleeding [³] and malignant transformation, especially when the lesion is larger than 5 cm [⁴]. Therefore, resection of a HCA larger than 5 cm is usually advocated.

When radiological analysis remains inconclusive, a liver biopsy is required to establish the diagnosis. This is an invasive procedure with associated risks. Therefore, there is a need for accurate noninvasive diagnostic imaging techniques. In previous studies, the use of the ⁹⁹Tc sulphur-colloid scan was found not to be helpful in diagnosis because many lesions showed atypical uptake of the tracer [⁵]. In our experience, the use of ⁹⁹Tc mebrofenin is not accurate enough, probably due to inferior resolution of SPECT or biliary excretion on hepatobiliary scintigraphy masking smaller centrally located lesions. Bumsel and et al. recently suggested that PET/CT using the tracer ¹⁸F-fluoromethylcholine (¹⁸F-FCH) may be able to differentiate between FNH and HCA [⁶]. In this pilot study, we prospectively assessed the use of PET/CT with ¹⁸F-FCH with semiquantitative uptake measurements in patients in whom the diagnosis FNH or HCA was considered.

This study shows that PET/CT with ¹⁸F-FCH can differentiate FNH from HCA. All HCAs showed an SUV ratio ≤1.12 and all FNH showed an SUV ratio ≥1.22. The 100% sensitivity and specificity based on visual interpretation are in accordance with the findings of Bumsel et al. [⁶]. They found an intense and early uptake of FCH by all FNH and no uptake by adenoma or telangiectatic FNH. The latter lesion has, however, recently been reclassified as HCA [⁷]. The results of both studies are promising, but must be considered carefully because of the small sample size. In our ongoing study we will further assess the accuracy of PET/CT with ¹⁸F-FCH in more patients.

The question arises as to the phenomenon that underlies the difference in choline uptake. Choline is used in the synthesis of phosphatidylcholine and sphingomyelin, two phospholipids that are structural components of all human cell membranes. Malignant tumour cells are known to show rapid cell duplication and therefore have a higher uptake of choline as a substrate for the cell membranes. However, HCA and especially FNH are slowly proliferating liver tumours making this duplication theory unlikely. Another theory is a difference in perfusion, since choline uptake is flow-dependent [⁸]. On hepatobiliary scintigraphy, FNH shows increased flow, in contrast to HCA. On contrast-enhanced ultrasonography, both FNH and HCA show rapid filling of the lesion, but an HCA also shows rapid wash-out of the contrast material [⁹]. Finally, there could be a difference in the metabolism of very low-density lipoproteins (VLDL) in the tumours. The membrane of VLDL particles mainly consists of phospholipids. Although less plausible, it could be that FNH has an increased synthesis of VLDL particles.

A drawback of the use of PET/CT using noncontrast-enhanced low-dose CT is that the tumours might be difficult to localize. In such cases image fusion with a contrast-enhanced CT or MRI scan is needed to locate the lesions.

Based on the findings of this study, we can conclude that PET/CT with ¹⁸F-fluorocholine is able to differentiate HCA from FNH with high sensitivity and specificity. Study of a larger patient series is, however, needed to confirm these results.

The authors wish to acknowledge the support of Dr. A.D. Windhorst and the Radionuclide Center at the Free University of Amsterdam for synthesis of FCH.

Financial support None.

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