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Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is a very rare neoplasm, with distinct epidemiologic, morphologic and clinical characteristics. Molecular mechanistic insight into the pathogenesis of this carcinoma suggests a pivotal role for the host immune system in the proliferation and progression of this tumor. However, while detailed genomic profiling of these hepatic tumors have revealed an intra-tumoral inflammatory mutational signature that may predispose to immune checkpoint inhibitor efficacy, no published report has described their use in this tumor type. Unfortunately, with near 100 cases of LEL-HCC reported in the literature to date and the majority of cases confined to localized and resectable disease, current evidence-based practices in the unresectable setting are lacking, with unknown benefit of chemotherapy or immunotherapy. We report on the case of a 68 year-old man with unresectable, advanced LEL-HCC who had evidence of disease stability after starting on the immune checkpoint inhibitor nivolumab. His disease response persisted off therapy for over a year and was potentially augmented by radiotherapy at the site of local progression. For this extremely rare tumor subtype, this case highlights the potential efficacy and safety of immune checkpoint blockade in LEL-HCC and reinforces the need for more robust, large-scale analysis of patients with these rare tumors to better evaluate treatment strategies and outcomes., Competing Interests: The authors have no conflict of interests related to this publication., (© 2021 Authors.)

Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is a rare distinct histopathological subtype of HCC, which is characterized histopathologically by the presence of abundant lymphocytes around the neoplastic cells, and less than 50 cases have been reported. In this report, we describe the first cytological case of LEL-HCC. A 58-year-old Japanese male had an elevated serum alpha-fetoprotein (AFP) level, and computed tomography scan demonstrated a tumorous lesion with contrast enhancement in the liver, thus, surgical resection was performed. The Papanicolaou smear of the liver tumor demonstrated small clusters and trabeculae of large-sized polygonal cells in a background of an abundance of small lymphocytes. These tumor cells had a rich granular cytoplasm and large centrally located round to oval nuclei containing conspicuous nucleoli. Immunocytochemical analyses revealed that these cells were positive for AFP, glypican-3, and Hep-Par1. Histopathological study demonstrated LEL-HCC. The cytological features of the present case represent both lymphoepithelioma-like carcinoma and conventional HCC. The prognosis of LEL-HCC may be favorable. Therefore, the diagnosis of this type of tumor is important, and a cytological examination can provide useful information for diagnosis of LEL-HCC., Competing Interests: None., (IJCEP Copyright © 2017.)