Is gastric lymphoepithelioma-like carcinoma a special subtype of EBV-associated gastric carcinoma? New insight based on clinicopathological features and EBV genome polymorphisms

Gastric lymphoepithelioma-like carcinoma (LELC) is a rare entity that is closely associated with Epstein-Barr virus (EBV). However, the EBV latency pattern and genome polymorphisms in gastric LELC have not been systematically explored. The clinicopathological features, EBV latency pattern and genome polymorphisms of EBV-positive gastric LELC in Guangzhou, southern China were investigated and compared with those of ordinary EBV-associated gastric carcinoma (EBVaGC) in the same area. Ten (1.42 %) of 702 gastric carcinoma cases were identified as gastric LELC, in which eight (80 %) cases were EBV-positive. The clinicopathological characteristics and EBV latency pattern of EBV-positive gastric LELC were similar to those of ordinary EBVaGC. In EBV genotype analysis, type A strain, type F, I, mut-W1/I, XhoI- and del-LMP1 variants were predominant among EBV-positive gastric LELCs, accounting for eight (100 %), six (75 %), eight (100 %), seven (87.5 %), five (62.5 %) and six (75 %) cases, respectively, which are similar to those in ordinary EBVaGC. For EBNA1 polymorphisms, the V-leu and P-ala subtypes were predominant in EBV-positive gastric LELC, which is different from the predominant V-val subtype in ordinary EBVaGC. EBV-positive gastric LELC has a favorable prognosis when compared to ordinary EBVaGC (median survival time 43.0 vs. 18.0 months). Gastric LELC is strongly associated with EBV and EBV-positive gastric LELC should be regarded as a special subtype of EBVaGC. This, to our best knowledge, is the first time in the world that the EBV latency pattern and genome polymorphisms of EBV-positive gastric LELC are systematically revealed.