Hepatocellular Adenoma: What We Know, What We Do Not Know, and Why It Matters

In the last 2 decades there has been significant progress in research and diagnosis of hepatocellular adenoma (HCA), resulting in the establishment of a molecular and immunohistological HCA classification. This review aims to fine-tune the current expertise in order to enhance the histopathological diagnostic possibilities, by refining issues that are already known, addressing diagnostic difficulties and identifying still unknown aspects of HCA. We will discuss novel methods to identify HCA subtypes, in particular the sonic hedgehog HCAs and the interpretation of glutamine synthetase patterns for the recognition of beta-catenin mutated HCAs. The major complications of HCAs, bleeding and malignant transformation, will be considered, including the dilemmas of atypical and borderline lesions. Paragraphs on HCAs in different clinical and geographical settings, e.g. pregnancy, cirrhosis and non-western countries are included. The natural history of the different HCA subtypes in relation with age, sex and risk factors is a feature still insufficiently investigated. This is also true for the risks of clinical bleeding and malignant transformation in association with HCA subtypes. As HCA is a relatively rare tumor, a multicenter and multidisciplinary approach across geographical boundaries will be the appropriate method to establish prospective programs to identify, classify and manage HCAs, focusing on several aspects, e.g. etiology, underlying liver disease, complications, regression and growth. Updating what we know, identifying and addressing features that we do not know matters to warrant optimal patient management.