Distribution characteristics of tumor infiltrating lymphocytes in EBV-associated lymphoepithelioma-like carcinoma and their clinical significance

Abstract

Objective: To investigate the association between the distribution of tumor infiltrating lymphocytes (TIL) in EBV associated lymphoepitheliomatoid carcinoma (LELC) and the pathological subtypes of LELC, as well as the clinical significance of TIL distribution. Methods: The LELC patients with sufficient tumor tissues, complete clinical data and positive EBER, who visited Zhejiang Cancer Hospital, Hangzhou, China from January 2006 to October 2018, were selected. Various immunohistochemical markers (CD20, CD138, CD4, CD8, CD56 and FOXP3) were examined for TIL typing. Two pathologists reviewed the hematoxylin and eosin (HE) staining sections and interpreted the immunohistochemical results. Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC's pathological characteristics. Survival analyses were conducted to study the prognostic values of TIL subgrouping. Results: A total of 102 patients with EBV related LELC were included. 46 of them were classic LELC (c-LELC) with rich interstitial TIL, and 56 were non-classic LELC (n-LELC) with relatively fewer interstitial TIL. The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL, with B lymphocytes as the dominant subgroup. The number of TIL in n-LELC was fewer than that in c-LELC, with T lymphocytes as the dominant subgroup. There was no significant difference in the distribution of plasma cells between the two groups. Survival analysis showed that the total number of TIL, and the infiltrations of CD20+B cells, CD4+T cells, and FOXP3+Treg cells were associated with better overall survivals (P=0.004, 0.003, 0.008 and 0.025, respectively) and disease-free survivals (P=0.011, 0.003, 0.038 and 0.041, respectively) in patients with LELC. Conclusions: The morphologic subtypes of EBV-related LELC have different tumor immune characteristics. The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC. Interestingly, B lymphocytes are the dominant TIL in c-LELC, while T lymphocytes are the dominant TIL in n-LELC. The infiltration of TIL, CD20+B cells, CD4+T cells and FOXP3+Treg cells in LELC may suggest a better prognosis.