Eosinophilic Biliary Cystic Neoplasm of the Liver: A Case Report of an Unrecognized Subtype of Intrahepatic Biliary Neoplasm.

We report a multicystic intrahepatic neoplasm in a 54-year-old Japanese woman, representing a previously unrecognized subtype. Grossly, the lesion was a well-demarcated multicystic tumor with focal papillary projections. Histologically, the cysts were lined by columnar to cuboidal neoplastic cells with brush border-like luminal microvilli, abundant granular eosinophilic cytoplasm, and small round nuclei. The cystic lumina contained colloid-like secretion, and bile-filled glands were occasionally observed. The septa were composed of thin hepatocellular parenchyma. Immunohistochemically, the tumor cells were positive for CD10, CK7, CK19, EpCAM, and SPINK1 and negative for HepPar1, MUC1, MUC2, MUC5AC, and MUC6. Whole-exome sequencing identified a pathogenic somatic KRAS p.G12V variant. RNA sequencing detected no PRKACA/B fusions. Single-cell spatial transcriptomics demonstrated that tumor cells clustered most closely with septal and medium-sized interlobular bile ducts. Gene set activity analysis showed significant suppression of gene sets downregulated by KRAS activation and upregulation of KRAS dependency signature gene sets in tumor cells. These findings distinguish this lesion from established entities of intrahepatic biliary cystic neoplasms, including intraductal papillary neoplasm, intraductal tubulopapillary neoplasm, intraductal oncocytic papillary neoplasm, and mucinous cystic neoplasm. We propose the designation "eosinophilic biliary cystic neoplasm of the liver" for this distinct intrahepatic biliary neoplasm.