由于其罕见性，关于胸腺EB病毒相关的低分化非角化鳞状细胞癌（PDNKSCC），也称淋巴上皮癌（LEC），的知识非常有限。本多中心研究招募了85名胸腺PDNKSCC患者。对所有85例进行了DNA原位杂交实验以评估EB病毒状态。使用免疫组织化学和下一代测序比较了EB病毒相关和EB病毒无关的PDNKSCC在临床病理和分子特征方面的差异。还使用这些方法分析了肿瘤浸润淋巴细胞（TIL）的情况。根据EB病毒状态，85个案例被分为27个EB病毒相关的PDNKSCC（31.8％）和58个EB病毒无关的PDNKSCC（68.2％），根据组织学特征被分类为35个淋巴上皮瘤型（LP）（41.2％）和50个纤维化型（DP）（58.8％）。与EB病毒无关的PDNKSCC相比，EB病毒相关的PDNKSCC表现出以年轻患者为主导，并更常见LP亚型。此外，LP型病例分为两组：第一组（EB病毒相关，20/85）和第二组（EB病毒无关，15/85）；DP型病例分为第三组（EB病毒无关，43/85）和第四组（EB病毒相关，7/85）。这四个组与患者的OS和PFS有显著关联。与EB病毒无关的PDNKSCC相比，EB病毒相关的PDNKSCC具有显着更高的PD-L1 + 肿瘤细胞（TC）和PD-L1 + 和CD8 + 免疫细胞（IC）。肿瘤微环境免疫类型（TMIT）I（PDL1-Tumor + / CD8-High）在EB病毒相关的PDNKSCC中更常见，特别是在第一组（LP和EB病毒相关）中，超过90％的病例属于TMIT I。分子分析表明，与EB病毒无关的病例相比，EB病毒相关的PDNKSCC具有显着更高的肿瘤突变负荷和体细胞突变频率。EB病毒相关的PDNKSCC，尤其是第一组，可作为免疫治疗的候选者，并且EB病毒阳性可能为靶向治疗的选择提供指示，因为它们具有较高的肿瘤突变负荷。 版权所有 © 2023. Elsevier B.V. 发布

Knowledge regarding thymic EBV-related poorly differentiated nonkeratinizing squamous cell carcinoma (PDNKSCC), also known as lymphoepithelial carcinoma (LEC), is extremely limited due to its rarity.This multi-institutional study enrolled 85 patients with thymic PDNKSCC. DNA in situ hybridization was performed to evaluate the EBV status of all 85 cases. Immunohistochemistry and next generation sequencing were performed to compare the differences in the clinicopathological and molecular features between EBV-related and EBV-unrelated PDNKSCC. Tumor-infiltrating lymphocytes (TILs) were also analyzed by these methods.The 85 cases were classified into 27 EBV-related PDNKSCCs (31.8 %) and 58 EBV-unrelated PDNKSCCs (68.2 %) according to the EBV status, and 35 Lymphoepithelioma pattern (LP) (41.2 %) and 50 desmoplastic pattern (DP) (58.8 %) according to the histological characteristics. Compared to the EBV-unrelated PDNKSCC, EBV-related PDNKSCC showed a younger patient predominance and more commonly displayed a LP subtype. Additionally, LP-type cases were divided into two groups: Group 1 (EBV-related, 20/85) and Group 2 (EBV-unrelated, 15/85); the DP-type cases were divided into Group 3 (EBV-unrelated, 43/85) and Group 4 (EBV-related, 7/85). The four Groups showed a significant association with patients' OS and PFS. EBV-related PDNKSCC had significantly higher PD-L1 + tumor cells (TCs) and PD-L1 + and CD8 + immune cells (ICs) than EBV-unrelated PDNKSCC. The tumor microenvironment immune type (TMIT) I (PDL1-Tumor+/CD8-High) was more common in EBV-related PDNKSCC, especially in Group 1(LP and EBV related) with more than 90 % cases belonged to TMIT I. Molecular analysis demonstrated that EBV-related PDNKSCC had a significantly higher tumour mutational burden and frequency of somatic mutations than EBV-unrelated cases.EBV-related PDNKSCC, especially the Group 1, could be a candidate for immunotherapy and EBV positivity may provide an indication for the selection of targeted therapy due to their high tumour mutational burden.Copyright © 2023. Published by Elsevier B.V.