Fibrolamellar hepatocellular carcinoma

Fibrolamellar hepatocellular carcinoma (FLM) is a rare tumour that typically presents in young adults. It occurs in non-cirrhotic liver and is usually associated with normal serum alpha-fetoprotein. It is defined by a triad of morphological features: polygonal tumour cells with eosinophilic cytoplasm, prominent macronucleoli and lamellar fibrosis. A central scar can be present. The principal differential diagnosis is conventional hepatocellular carcinoma (HCC), especially the scirrhous variant. Acinar differentiation and focal mucin production are common and can be confused with adenocarcinoma. Focal neuroendocrine differentiation can occur and can be mistaken for neuroendocrine tumours. FLM also shows distinctive features at the molecular level; many of the commonly observed abnormalities in conventional HCC like p53 and β-catenin mutations are not observed in FLM. The extent of cytogenetic changes and CpG island methylation is low in FLM compared to conventional HCC. FLM is an aggressive neoplasm with 5-year survival of around 50%. Although the outcome in FLM has been considered more favourable compared to conventional HCC, this is likely to be related to absence of cirrhosis rather than unique morphological features of the tumour.