Features of Gastric Carcinoma With Lymphoid Stroma Associated With Epstein-Barr Virus

Gastric carcinoma with lymphoid stroma (GCLS) is a distinct histologic subtype of gastric cancer that is characterized by undifferentiated carcinoma mixed with prominent lymphoid infiltration. More than 80% of GCLS cases are associated with Epstein-Barr virus (EBV) infection, but it is unclear if the virus affects disease progression. We investigated how EBV infection affects the clinical and pathologic features of GCLS, as well as patients' outcomes.

We performed a retrospective analysis of 274 patients (mean age, 56.8 y; 85.4% male) diagnosed with GCLS, based on pathology findings, from March 1998 through December 2012 at the Asan Medical Center in Seoul, South Korea. Their data were compared with those from 822 age- and sex-matched patients who underwent resection for gastric adenocarcinoma. EBV was detected in tumor samples by in situ hybridization.

Of the 274 patients with GCLS, 236 had EBV-positive tumors (86.1%) and 38 had EBV-negative tumors (13.9%). EBV-positive GCLS was more prevalent than EBV-negative GCLS in younger patients, tended to be located proximally, and was more frequently of an early stage macroscopic type. The 10-year, disease-specific rates of survival were 89.1% for patients with EBV-positive GCLS and 66.9% for patients with EBV-negative GCLS (P = .009). Patients with EBV-negative GCLS had clinical and pathologic features and survival times similar to those of patients with conventional adenocarcinoma. By multivariate analysis, longer survival time was associated with EBV-positive tumors (P = .007), younger patient age (P = .002), smaller tumor size (P = .046), lower stage (based on American Joint Committee on Cancer classification; P < .001), and lack of lymphovascular invasion (P = .012). The proportion of undifferentiated tumor cells was not associated significantly with patient survival time.

Clinical and pathologic features of GCLS differ based on EBV infection status. EBV-negative GCLS is similar to conventional adenocarcinoma, and patients have similar survival times. EBV status may be more important than the proportion of undifferentiated tumor cells in the diagnosis of GCLS and management of patients.