Long-term outcome of metachronous, multiple, early Epstein-Barr virus-associated gastric carcinoma: a case report

Background: Epstein-Barr virus is associated with various malignancies. Epstein-Barr virus-associated gastric carcinoma (EBVaGC) was reported in 1990. While gastric carcinoma with lymphoid stroma (GCLS) is a rare gastric cancer, 80% to 90% of these tumors are associated with Epstein-Barr virus infection.Case Description: The patient was a 67-year-old male in 2004, when he underwent laparoscopy-assisted distal gastrectomy with Billroth I reconstruction to treat early stage 0-IIc gastric cancer; the pathological diagnosis was moderately differentiated adenocarcinoma, pT1b, pN0, stage IA with a negative margin. In 2009, endoscopic submucosal dissection (ESD) was performed on reoccurring stage 0-IIc gastric cancer; pathology results identified well-differentiated adenocarcinoma, pT1b, Ly0, V0, pHM0, pVM0. Although further gastric resection was recommended, the patient declined the procedure and opted to receive only follow-up evaluation. During the follow-up period, upper gastrointestinal (GI) endoscopy revealed a protruding mass on the remaining gastric fundus; biopsy indicated a poorly differentiated adenocarcinoma. Approximately 15 years after the initial treatment, the patient underwent total resection of the remnant stomach and Roux-en-Y reconstruction. The histopathological diagnosis was gastric cancer, pT1b, N0, no lymphatic and venous invasion, stage IA with lymphoid stroma and lymphocyte infiltration associated with formation of lymphoid follicles. Immunohistochemistry with EBV-encoded RNA in situ hybridization (EBER-ISH) was positive, resulting in diagnosis of EBVaGC. Retrospective EBER-ISH performed on resected specimens from the 2 prior surgeries yielded similar results. Furthermore, immunohistochemistry using anti-programmed death ligand 1 (PD-L1) antibody demonstrated an increase in the combined positive score (CPS) over time.Conclusions: This report describes the rare case of a patient who experienced 3 occurrences of EBVaGC at different times and locations over 15 years and discusses the clinical relevance in the context of a literature review. It aims to increase awareness among clinicians and pathologists of the necessity of considering EBVaGC when deciding on the treatment strategy after reoccurrence of gastric cancer.