Checkpoint Inhibition in the Treatment of Unresectable, Advanced Lymphoepithelioma-like Hepatocellular Carcinoma

Abstract

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 evidencebased 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.

High PD‐L1 level of advanced hepatic lymphoepithelioma‐like carcinoma response favorably to lenvatinib plus toripalimab

“…Subsequently, more optimal regimens have been brought forward. One patient with LEL‐HCC received oral sorafenib, 15 and another case with advanced LEL‐HCC was treated with nivolumab 16 . Despite a relatively low level of tumor PD‐L1 expression, the latter patient still had evidence of disease stability for 2 years 16 .…”

Human Papillomavirus-Associated Lymphoepithelioma-Like Carcinoma of the Anal Canal: A Case Report and Literature Review

“…Considering the rapid advancement and remarkable survival benefits for various tumor types, immunotherapy is now considered to be a promising cancer treatment, including for LELCs. It has been reported that a few unresectable, advanced LELCs originating from the liver and lung responded favorably to immune checkpoint inhibitors (38,39). The expression of PD-L1 and cytotoxic T cells expressing cell-surface CD8 has emerged as a potential predictive biomarker for immunotherapy response (40,41).…”

Programmed cell death ligand 1 expression in a case of poorly differentiated lymphocyte‐rich hepatocellular carcinoma

“… 6 We searched PubMed for articles from 1995 to 2021 using the keywords "lymphoepithelioma‐like hepatocellular carcinoma" or "hepatocellular carcinoma lymphocyte rich". As a result, there were 59 cases corresponding to poorly differentiated lymphocyte‐rich HCC (Table 2 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ). We examined a total of 60 cases including the current case.…”

“…Therefore, we decided to histopathologically assess the ICI treatment strategy for poorly differentiated lymphocyte‐rich HCC. So far, there is only one report for the use of ICIs in LEL‐HCC, 25 and there have been multiple reports of cases in which ICIs were effective for LELC in other organs. 28 , 29 In a study of 217 cases of HCC by Calderaro et al, the PD‐L1 positive rate (>1% of tumor cell‐positive cases were defined as PD‐L1 positive) of LEL‐HCC tumor cells was three of 13 cases, which was not different from the positive rate of 17% for all HCC.…”