Hepatic adenomas in males: Is molecular characterization helpful in guiding its management?

BACKGROUND AND AIMS: Hepatocellular adenomas (HCAs) in males are very rare. We performed detailed clinicopathologic, immunohistochemical and molecular characterization of HCAs in males, to understand their pathogenesis and malignant potential.

METHODS

Seven cases of HCA in males formed our study cohort. The histologic slides, clinical and follow-up information were reviewed and immunohistochemical stains were performed. DNA was extracted and targeted sequencing was performed using Ion Torrent chemistry. Filtered variants were annotated to identify pathogenic mutations.

RESULTS

Six (86 %) patients were morbidly obese. All showed at least focal cytologic atypia. Three lesions were markedly steatotic and 2 were hemorrhagic. One lesion showed focal reticulin loss, diffuse glutamine synthetase (GS) positivity and beta-catenin (β-catenin) nuclear staining, suggestive of atypical hepatocellular neoplasm. Three (42.8 %) cases were inflammatory-type, showing diffuse serum amyloid-associated protein/C-reactive protein. One other inflammatory-type HCA showed peripheral accentuation with GS and another non-inflammatory HCA showed patchy staining with GS; both revealed CTNBB1 mutations but no β-catenin nuclear staining. None showed TP53, TERT promotor mutations, or significant copy number alterations.

CONCLUSION

A significant proportion of HCAs in males occurred in obese patients and were inflammatory-type. While some are beta-catenin mutated and need to be resected, a subset of HCAs in males appears to be low-risk by molecular features and may be treated conservatively.