Programmed death-ligand 1 is upregulated in intrahepatic lymphoepithelioma-like cholangiocarcinoma

Intrahepatic lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare variant of cholangiocarcinoma. Here, we report the largest single series of LELCC cases yet studied (n = 13). We retrospectively analyzed the clinical data of the 13 patients and measured the expression of programmed death-ligand 1 (PD-L1) in tumors using immunohistochemical staining. We also analyzed 15 cases of conventional intrahepatic cholangiocarcinoma (IHCC) for comparison. We found that eight patients with LELCC were infected with Epstein-Barr Virus (EBV), and EBV infection correlated with poor prognosis in LELCC. Four patients among the five (80.0%) without EBV had a history of chronic viral hepatitis B. None of the 15 cases of conventional cholangiocarcinoma were positive for EBV. PD-L1 was expressed in both the tumor cells and tumor-infiltrating immune cells in LELCC patients at higher levels than in IHCC patients (P < 0.05). These observations suggest that EBV infection may promote the development of LELCC, and that PD-L1 may be a potential therapeutic target for treatment of EBV-associated LELCC.