Solid Tumour Section

FLC shows immunohistochemical features of both hepatocytic and biliary differentiation and is most likely derived from a bipotential cell. A recent study examining 26 cases of FLC and 62 cases of classical HCC by immunohistochemistry showed that both tumor types stained uniformly positively with HepPar1 and most showed a canalicular staining pattern for pCEA confirming hepatocytic differentiation. In addition, 39% of hepatocellular carcinoma cases and 59% of fibrolamellar carcinoma cases were positive for glypican-3 and both tumor types were positive for albumin by in situ hybridization. All 22 FLC cases tested showed positive staining for cytokeratin 7 and epithelial membrane antigen, whereas less than onethird of HCC cases were positive for these markers associated with biliary differentiation. Further, 36% of FLC cases showed staining for other markers of biliary differentiation such as B72.3, cytokeratin 19, EpCAM, or mCEA (Ward et al., 2010). Immunopositivity for cytokeratin 19 and EpCAM are associated with a subset of hepatocellular carcinomas with worse prognosis and indicates a progenitor cell phenotype. A higher proportion of hepatoblastomas and pediatric hepatocellular carcinomas are positive for CK19 and EpCAM than adult HCC. As FLC also arises in a younger age group, there may be pathogenic similarities between these tumors and immunopositivity for these markers may indicate a progenitor phenotype. Zenali et al. studied the "stemness" of FLC and found that FLC was positive for the stem cell markers CD133 and CD44 and also showed reduced cell cycle progression (Zenali et al., 2010). Cases of combined (mixed) FLC with HCC or cholangiocarcinoma have also been reported (Malouf et al., 2012; Tanaka et al., 2005).