Cracking the Code: Molecular Analysis of Hepatic Adenomas

Introduction: Hepatocellular adenomas (HA) are benign monoclonal proliferations of hepatocytes that carry a potential for malignant transformation to hepatocellular carcinoma (HCC). HA demonstrate significant diversity at the molecular level resulting in distinct subtypes with variable risks of progression to HCC. Beta-catenin activated HCA result from a mutation in CTNNB1 and represent only 10% of all HA, but carry the highest risk of progression to HCC1,2. We describe a case of a young male who presented with a hepatic mass found to be HCC arising from a beta-catenin activated HA. Case Description/Methods: A 35-year-old man presented for evaluation of right-sided abdominal pain and jaundice. He had no relevant past medical or family history. Contrast-enhanced CT demonstrated a 16.7cmx16.6cmx13.6cm heterogenous mass in the right lobe of the liver. Multiphase MRI showed arterial enhancement around the periphery of the mass with lack of central enhancement and washout on delayed images concerning for fibrolamellar HCC (FlHCC). EUS-guided fine needle aspiration revealed scant liver parenchyma with thickened hepatic plates and loss of reticulin staining suggestive of HCC. Immunohistochemical (IHC) staining did not support FIHCC. Subsequent percutaneous biopsy revealed well differentiated adenocarcinoma with IHC diffusely positive for glutamine synthetase, beta-catenin, amyloid A, CK7, and CD34 suggestive of atypical HA. On molecular analysis, the mass possessed the beta-catenin activating CTNNB1 mutation with S33C (exon 3) variant. Overall, the combination of IHC and molecular analyses suggested a well differentiated adenocarcinoma arising in the background of beta-catenin activated HA. After multidisciplinary discussion, the patient started medical treatment with immunotherapy. Discussion: HA are rare neoplasms in men and usually occur in the setting of genetic mutations. FlHCC are rarer hepatic neoplasms that have a characteristic imaging finding, but require a liver biopsy for diagnosis. Though our patient had FlHCC on imaging, biopsy revealed instead adenocarcinoma arising from HA. Of the major subtypes of HA, beta-catenin activated HA carry the greatest risk of malignancy, particularly those with CTNNB1 exon 3 mutations as described in this case. In the right setting, HA should be biopsied for molecular classification to help define patients who are at higher risk for malignant transformation and consequently those who may benefit from early surgical resection (see Figure 1).Figure 1.: T2-weighted MRI of Well Differentiated Adenocarcinoma of the Liver.