HNF1A-inactived Hepatocellular Adenomas in Fibropolycystic Kidney and Liver Disease Are Associated With Germline HNF1B Variant.

HNF1A-inactivated hepatocellular adenomas are rarely described in patients with hepatorenal fibrocystic disease, and their genetic relationship remains unexplored. This study reports a series of HNF1A-inactivated hepatocellular adenomas with molecular sequencing analysis in patients with fibrocystic kidney and/or liver disease. Cases were retrospectively identified from the pathology archives of 3 institutions. Clinical history was collected from chart review, and hematoxylin-and-eosin-stained slides along with relevant immunohistochemistry were reviewed for liver specimens. Next-generation sequencing was performed on paired lesional hepatocellular adenoma and nonneoplastic tissue. The study group comprised 8 patients (median age, 25 years; male:female, 1:7). Six patients had evidence of congenital hepatic fibrosis, 1 had polycystic liver disease with multiple cysts and bile duct hamartomas, and 1 had an uninvolved background liver but with polycystic kidney disease. Histologic examination revealed that all hepatocellular adenomas showed circumscribed, well-differentiated hepatocellular proliferation with unpaired arterioles and loss of liver fatty acid-binding protein staining via immunohistochemistry. Three patients were found to have novel HNF1B germline variants (c.1430A>C). Our data reveal a new syndromic association for HNF1A-inactivated hepatocellular adenomas. We hypothesize that aberrant interactions between HNF1A and HNF1B may contribute to the pathogenesis of hepatocellular adenomas in these patients. Further studies are necessary to discover additional germline variants that may result in a similar phenotype.