Light has been shed on the genotype/phenotype correlation in hepatocellular adenoma (HCA) recognizing HNF1α-inactivated HCA (H-HCA), inflammatory HCA (IHCA), and β-catenin-activated HCA (b-HCA). We reviewed retrospectively our surgical HCA series to learn how to recognize the different subtypes histopathologically and how to interpret adequately their immunohistochemical staining. From January 1992 to January 2012, 37 patients underwent surgical resection for HCA in our institution. Nine had H-HCA (25%) characterized by steatosis and loss of L-FABP expression; 20 had IHCA (55.5%) showing CRP and/or SAA expression, sinusoidal dilatation, and variable inflammation; and 1 patient had both H-HCA and IHCA. In 5 patients (14%), b-HCA with GS and β-catenin nuclear positivity was diagnosed, two already with hepatocellular carcinoma. Two cases (5.5%) remained unclassified. One of the b-HCA showed also the H-HCA histological and immunohistochemical characteristics suggesting a subgroup of β-catenin-activated/HNF1α-inactivated HCA, another b-HCA exhibited the IHCA histological and immunohistochemical characteristics suggesting a subgroup of β-catenin-activated/inflammatory HCA. Interestingly, three patients had underlying vascular abnormalities. Using the recently published criteria enabled us to classify histopathologically our retrospective HCA surgical series with accurate recognition of b-HCA for which we confirm the higher risk of malignant transformation. We also underlined the association between HCA and vascular abnormalities. 1. Introduction Hepatocellular adenomas (HCA) are rare benign tumors most frequently observed in women on oral contraception [1, 2]. HCA can occur in men on anabolic steroids [3] or be associated with underlying metabolic diseases such as glycogen storage disease [4]. Some associations have also been described with congenital vascular abnormalities of the liver [5–8]. The existence of four different categories of HCA was recently recognized, and the clinical relevance of subtyping these liver lesions according to histological and immunohistochemical features and to molecular alterations was demonstrated [9–15]. HNF1α-inactivated HCA (H-HCA) are associated with HNF1α inhibiting mutations leading to the loss of expression of liver fatty acid binding protein (L-FABP) within the lesion as compared with the surrounding liver parenchyma by immunohistochemistry (IHC). These HCA are histologically associated with marked liver steatosis and do not show cytological abnormalities. The second group, the more frequent, is the inflammatory type of
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