Background. Gastric carcinoma with lymphoid stroma (GCLS) has been reported to have a more favorable prognosis than ordinary gastric carcinoma, however, the precise mechanism of the pathogenesis for GCLS remains unclear.

Methods. The authors analyzed 99 GCLS in 94 patients for Epstein‐Barr virus (EBV) sequences using polymerase chain reaction (PCR) and in situ hybridization (ISH); these were compared with 42 ordinary gastric carcinomas.

Results. Two series of PCR showed 81 (82%) and 46 (47%) of the 99 GCLS to have EBV sequences, which were significantly higher compared with ordinary gastric carcinoma (50% and 9.5%, respectively). With ISH using thymine‐thymine dimerized oligonucleotide probes corresponding to EBV‐encoded small RNA 1 (EBER1), 82 (83%) of 99 GCLS showed clear, intense hybridization signals localized over the nuclei of the tumor cells, in contrast to only 4 (9.5%) of 42 ordinary carcinomas (P < 0.001). A comparative morphologic analysis of EBER1‐positive and negative GCLS revealed that typical features of GCLS, such as mild cellular pleomorphism, rare mitoses, a marked degree of lymphoid stroma, and mild fibrosis, together with a lymphoid infiltration within the cancer cell nests were significantly more frequent in EBER1‐positive GCLS.

Conclusions. More than 80% of GCLS were associated with EBV. The presence of EBV association in GCLS was characterized by the above morphologic features.