Hepatocellular adenomas (HCAs) are benign tumors developed in normal liver most frequently in women before menopause. HCAs lead to diagnostic pitfalls and several difficulties to assess the risk of malignant transformation in these young patients. Recent advances in basic knowledge have revealed a molecular classification related to risk factors, pathological features, and risk of transformation in hepatocellular carcinoma. Three major molecular pathways have been identified altered in specific HCA subgroups that are defined by either (1) inactivation of hepatocyte nuclear factor 1A (HNF1A) transcription factor, (2) activation of the WNT/β-catenin by CTNNB1 mutations, or (3) activation of the IL6/STAT3 pathway by somatic mutation of IL6ST, GNAS, or STAT3. Here, we will review the different molecular classes of HCA. 1. Introduction Hepatocellular tumors deriving from monoclonal proliferation of hepatocytes are classically divided in benign hepatocellular adenoma (HCA) and malignant hepatocellular carcinoma (HCC). HCAs are rare tumors most frequently-developed in women before menoaupose and after a long-term use of oral contraception [1]. Other risk factors such as glycogen storage diseases and androgen intake are also classically associated with HCA development. HCA could be complicated frequently by hemorrhage and more rarely by malignant transformation in HCC [2, 3]. For a long time, HCA was considered as a benign monoclonal proliferation of hepatocytes driven by oestrogen exposition [4, 5]. However, molecular classification has redrawn the physiopathological and clinical landscape of HCA [6]. This new classification linked specific risk factor, clinical history, and histological features to each molecular subgroup of HCA [6–9]. In addition, this genotype/phenotype classification has been validated by several groups worldwide demonstrating its robustness and its wide reproductibility in clinical practice [10–15]. In this paper we aimed to describe how genomic analyses enabled us to identify the different HCA molecular subgroups and their specific molecular defects. 2. Molecular Classification of Hepatocellular Adenomas 2.1. Adenomas Inactivated for HNF1A (H-HCA) In 2002, we identified HNF1A, as the first driver gene inactivated by mutation in hepatocellular adenomas [16]. HNF1A codes for the hepatocyte nuclear factor？？1？？A, a transcription factor involved in hepatocyte differentiation and metabolism control [17]. Previously, in 1996, Yamagata and collaborators had identified germline mutations of HNF1A as the causal alteration of the specific diabetes
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