Lymphoepithelioma-Like Neoplasm of the Biliary Tract with 'Probable Low Malignant Potential'

Background Lymphoepithelioma-like carcinomas (LELCs) are uncommon epithelial cancers characteristically showing two distinct components consisting of malignant epithelial cells and prominent dense lymphoid infiltrate. Hepatic LELCs consist of two types, the lymphoepithelioma-like hepatocellular carcinoma and lymphoepithelioma-like cholangiocarcinoma (LEL-CCA), with the latter being strongly associated with Epstein Barr virus (EBV). Methods We present a series of three cases of intrahepatic biliary EBV-associated-LEL tumors in which the biliary epithelial component showed a distinctly benign appearance, instead of the usual malignant epithelial features of a typical CCA or EBV-associated LEL-CCA. Results In the lesions, the biliary epithelium showed interconnecting glands or cords of cells. All had a very low proliferation (Ki-67) index. Immunohistochemistry for IDH1 and TP53 done on two cases was negative and molecular tests for EGFR and KRAS gene mutations done on one were negative. Prognosis was very good in all three cases, with patients alive with no evidence of disease 24 to 62 months after surgery. Intriguingly, all three cases had co-infection of HBV and EBV. These cases are also discussed in the context of the 63 cases of LEL-CCA available in the literature, with a focus on epidemiology, clinicopathologic features and potential research interests. Conclusions Based on the distinct clinicopathologic features and unique survival benefits, we believe these tumors represent the benign end of the spectrum of EBV-associated lymphoepithelial biliary carcinomas. Whether these tumors require a revision of the current nomenclature to 'Lymphoepithelioma-like neoplasm of the biliary tract with probable low malignant potential' will require more detailed analysis with larger case series.