Objective:  To discuss the clinical and pathological features, diagnosis, differential diagnosis, and prognosis of intrahepatic lymphoepithelioma-like cholangiocarcinoma (LEL-ICC).

  Methods:  The clinical and pathological data of seven cases of LEL-ICC treated in Zhongshan Hospital, Xiamen University, from 2014 to 2019 were collected. Tumor cells were detected using immunohistochemistry and in situ hybridization, and the clinical and pathological morphological features and prognosis were analyzed. Finally, the differential diagnosis was obtained.

  Results:  This study included seven patients with LEL-ICC (four women and three men); the mean age was 60.7 (49-71) years. Only one patient had right upper-quadrant abdominal pain, while the remaining six patients underwent physical examination without obvious clinical symptoms. LEL-ICC occurred in both the left and right lobes of the liver, mostly unilaterally, with a maximum diameter of (13-45) mm. Grossly, LEL-ICC was usually circumscribed with a gray, homogeneous, firmly cut surface, without an envelope. Microscopically, the tumor tissue could grow infiltratively into the surrounding liver tissue, usually presenting as lamellar nests, streaks, or unicellular-like, with varying degrees of glandular differentiation. Tumor cells were large and cuboidal, with poorly defined cell boundaries in a syncytial pattern, abundant cytoplasm, homogeneous, pinkish or slightly eosinophilic, and vacuolated, rounded or oval nuclei, usually with a small nucleolus and few mitotic figures. The stroma was infiltrated with a large number of mature, polyclonal lymphocytes and plasma cells, and lymphoid follicle formation could be present. The surrounding liver tissue showed interstitial hepatitis changes. Tumor cells were positive for CK7, CK8/18, CK19 by immunohistochemistry, and could express CEA and CD10 but generally not express Hep-Par1, Arginase-1, AFP, Glypican-3, CDX-2, CK20, Vimentin, etc. The Ki-67 labelling index was usually 20%-30%. EBER was positive in most cases by in situ hybridization. Recurrence or metastasis was not observed with a mean follow-up of 45.9 months.

  Conclusions:  LEL-ICC occurs mostly in middle-aged and elderly individuals and is often clinically asymptomatic. Its pathological morphology is similar to that of nasopharyngeal lymphoepithelial carcinoma but with glandular differentiation. The final diagnosis mainly depends on histopathology, immunohistochemistry and in situ hybridization. The prognosis of LEL-ICC is better than that of classical intrahepatic cholangiocarcinoma(ICC) and should be differentiated from other histological types of ICC, metastatic lymphoepithelioma-like carcinoma, and lymphoepithelioma-like hepatocellular carcinoma.