Value and Limits of Routine Histology Alone or Combined with Glutamine Synthetase Immunostaining in the Diagnosis of Hepatocellular Adenoma Subtypes on Surgical Specimens
Immunohistochemistry is a valid method to classify hepatocellular adenoma (HCA). The aim was to test the performance of routine histology combined to glutamine synthetase (GS) staining to identify the 2 major HCA subtypes: HNF1α inactivated (H-HCA) and inflammatory HCA (IHCA). 114 surgical cases, previously classified by immunohistochemistry, were analysed. Group A comprised 45 H-HCAs, 44 IHCAs, and 9 β-catenin-activated IHCAs (b-IHCA), and group B, 16 b-HCA and unclassified HCA (UHCA). Steatosis was the hallmark of H-HCA. IHCA and b-IHCA were mainly characterized by inflammation, thick arteries, and sinusoidal dilatation; b-IHCA could not be differentiated from IHCA by routine histology. Group B was identified by default. A control set (91 cases) was analyzed using routine and GS stainings (without knowing immunohistochemical results). Among the 45 H-HCAs and 27 IHCAs, 40 and 24 were correctly classified, respectively. Among the 10 b-IHCAs, 4 were identified as such using additional GS. Eight of the 9 HCAs that were neither H-HCA nor IHCA were correctly classified. Conclusion. Routine histology allows to diagnose >85% of the 2 major HCA subtypes. GS is essential to identify b-HCA. This study demonstrates that a “palliative” diagnostic approach can be proposed, when the panel of specific antibodies is not available. 1. Introduction Hepatocellular adenomas (HCAs) are rare benign tumors. Molecular data have brought new insight in the characterization of this disease. They allow the distinction of focal nodular hyperplasia (FNH) from HCA and the identification of 2 major HCA subtypes which represent more than 80% of all HCAs, namely, HNF1A-mutated HCA (H-HCA, 35–40%) [1], and inflammatory HCA (IHCA, 50–55%) [2]; 10% of IHCAs being also β-catenin mutated (b-IHCA). The remaining HCAs are the β-catenin-mutated HCA (b-HCA, 10%) [3] and the unclassified HCA (UHCA, which account for less than 10%). The immunohistochemical (IHC) classification of HCA subtypes was derived from the above-mentioned molecular characterization and showed a good correlation with the molecular data [2]. Using specific IHC markers, such as liver fatty acid-binding protein (LFAPB), C reactive protein (CRP) or serum amyloid A (SAA), glutamine synthetase (GS), and β-catenin, it is possible to identify all HCA subgroups with good confidence. Among these markers, GS is of major importance to identify patients at high risk of malignant transformation. Indeed, abnormal GS staining [4] is a strong argument to suggest β-catenin activation. Unfortunately, the rarity of these tumors in routine
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