New case of syncytial giant-cell variant of hepatocellular carcinoma in a pediatric patient withHNF1Bdeficiency: does it fit with the syndrome?

Hepatocyte nuclear factor 1B (HNF1B) is a member of the homeodomain-containing family of transcription factors located on 17q12.HNF1Bdeficiency is associated with a clinical syndrome (kidney and urogenital malformations, maturity-onset diabetes of the young, exocrine pancreatic insufficiency) and to an underdiagnosed liver involvement. Differently fromHNF1A, the correlation between hepatocellular carcinoma (HCC) and germlineHNF1Bdeficiency has been poorly evaluated.Here, we report a novel case of a syndromicHNF1B-deficient paediatric patient that developed HCC with unique histopathological features characterised by neoplastic syncytial giant cells, which was observed only in one additional case of paediatric cholestatic liver disease of unknown origin.Our case highlights the influence ofHNF1Bdeficiency in liver disease progression and its putative association with a rare yet specific HCC histotype. We hypothesised that HCC could be secondary to the repressive effect ofHNF1Bvariant on theHNF1Atranscriptional activity.