Will the pathomolecular classification of hepatocellular adenomas improve their clinical management?

Abstract

Hepatocellular adenomas (HCA) are rare benign tumors. Women taking oral contraceptives (OC) represent the most classical circumstance of HCA appearance. In recent years, clinical diagnosis of focal nodular hyperplasia (FNH) vs HCA has significantly improved due to the wide use of contrast agent ultrasonography and magnetic resonance imaging (MRI). However, there are circumstances where the differential diagnosis remains difficult and consequently require specimen resection. In addition, the diagnosis of benign hepatocellular nodules has greatly benefited from the contribution of molecular biology [1–3] allowing for the differential diagnosis between FNH and HCA and the identification of HCA subtypes. To date three major subtypes have been identified: HNF1A mutated HCA (H-HCA), b-catenin mutated HCA (b-HCA), and inflammatory HCA (IHCA). IHCA can be also b-catenin mutated (b-IHCA). Less than 10% of HCA remain unclassified. A phenotypic classification of those benign tumors using immunohistochemistry has been derived from the above-mentioned molecular characterization. Liver fatty acid binding protein (LFABP), serum amyloid A (SAA)/C reactive protein (CRP), glutamine synthase (GS), and b-catenin immunohistochemical analyses performed on surgical specimens discriminate FNH from HCA and identify the different HCA subtypes (Table 1) [4–8]. The advantages of immunohistochemistry-based approaches are (i) simplicity (can be performed on formalin fixed, paraffin-embedded tissue), (ii) reproducibility and (iii) easiness to analyze (in most cases). Briefly, the use of molecular markers and its pathological counterparts has allowed (i) to clearly separate FNH from HCA by introducing the previously called telangiectatic FNH [9] in the subgroup of IHCA, (ii) to identify different clinical, biological, radiological, and pathological HCA subtypes andmost importantly (iii) to identify HCA at risk to malignant transformation