Abstract

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.

Highlights

  • Hepatocellular adenomas (HCA) are rare benign tumors most frequently observed in women on oral contraception [1, 2]

  • hepatocellular adenoma (HCA) was single in 22 patients (59.5%), whereas 3 patients (8.1%) had liver adenomatosis

  • Light has been recently shed on the genotype/phenotype correlation in hepatocellular adenoma (HCA) leading to the identification of four different subtypes: HNF1α-inactivated

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Summary

Introduction

Hepatocellular adenomas (HCA) are rare benign tumors most frequently observed in women on oral contraception [1, 2]. 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 HCA (IHCA) associated with the activation of inflammatory pathways, and showing expression of serum amyloid A (SAA) and C-reactive protein (CRP) by IHC. The third subgroup is related to activating mutation of the βcatenin pathway (b-HCA) and carries a higher risk of transformation in hepatocellular carcinoma (HCC). The b-HCA can be identified on IHC by a nuclear accumulation of βcatenin and by the presence of a strong cytoplasmic staining

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