You are here

Plain English summary of Hepatocellular Carcinoma, Fibrolamellar Variant: Diagnostic Pathologic Criteria and Molecular Pathology Update. A Primer.

Published in Diagnostics, December 2015 Free Article 

The article provides a literature overview of fibrolamellar hepatocellular carcinoma (FL-HCC) with particular focus on the pathologic markers used for diagnosis, including findings on gross anatomy, microscopy, and immunohistochemistry. The author highlights that the cancer is remarkable for being predominantly found in children and young adults who have no evidence of liver disease. The disease can be confused with focal nodular hyperplasia (FNH) and sclerosing variant of hepatocellular carcinoma (SV-HCC). The author reviews the defining features of FL-HCC on heamtoxylin and eosin staining including the thick fibrous bands, large polygonal cells with prominent nucleoli, pale bodies. On immunohistochemistry the tumor is distinguished by staining for CK-7, CD68. The author runs through outher immunohistochemical findings of the tumor and contrasts it to SV-HCC. The paper evaluates signalling pathways typically mutated in HCC versus FL-HCC, pointing out that FL-HCC shows upregulation in mTORC1 (mechanistic target of rapamycin complex 1) signaling and FGFR1 (fibroblast growth factor receptor 1) signaling. The author cites literature describing three classes of FL-HCC (proliferative class, inflammatory class, unannotated class) which are assigned based on geneset enrichment analysis (GSEA) and nearest template prediction and immunohistochemistry. Lastly, the author reviews what is known of genetic mutations in FL-HCC highlighting the finding of a chimeric protein composed of DNAJB1-PRKACA (a fusion protein from a chaperone protein DNAJ and the catalytic subunit of protein kinase A). The author speculates that the chimeric protein contributes to tumor pathogenesis and recommends it be used as a diagnostic marker due to its sensitivity and specificity for FL-HCC. The author further recommends that future efforts be made in understanding the mitochondrial genome in FL-HCC due to the abundance of mitochondria found in the disease.