Temporal association of diffuse large B-cell lymphoma with PD-1 inhibitor therapy in a patient with gastric adenocarcinoma: a case report

Background: Immune checkpoint inhibitors (ICIs) have demonstrated substantial clinical benefit across a wide range of malignancies. With their expanding use, uncommon immune-related events, including hematologic abnormalities and lymphoid proliferations, are increasingly recognized. However, a causal relationship between ICI exposure and lymphoma development remains unproven. Case description: We report a 70-year-old woman with moderately to poorly differentiated gastric adenocarcinoma who was diagnosed with diffuse large B-cell lymphoma (DLBCL) during postoperative treatment with FOLFOX chemotherapy combined with the PD-1 inhibitor sintilimab. During therapy, the patient developed recurrent pleural and pericardial effusions. Early pleural fluid cytology revealed atypical lymphoid cells with occasional Epstein-Barr virus-encoded RNA (EBER) positivity, but immunophenotypic and clonality assessments were not performed, precluding a definitive lymphoma diagnosis at that time. Subsequent cytological, immunophenotypic, and molecular studies confirmed Ann Arbor stage IV DLBCL, predominantly presenting as malignant effusions. The patient achieved remission with R-CHOP therapy but later experienced relapsed and refractory disease. Conclusion: This case illustrates a temporal association between PD-1 inhibitor-based therapy and the diagnosis of DLBCL. Given the lack of baseline systemic staging, overlapping PET/CT findings, early diagnostic uncertainty in effusion cytology, and potential contributions from chemotherapy-induced immune perturbation and EBV-associated processes, a direct causal relationship cannot be established. This report underscores the importance of comprehensive baseline evaluation and cautious interpretation of atypical lymphoid findings during immunotherapy.