Abstract
OBJECTIVE: Primary gastric lymphoma (PGL) is a rare form of lymphoma that arises within the gastric mucosa-associated lymphoid tissue (MALT), often linked to Helicobacter pylori (Hp) infection. The endoscopic features of PGL are heterogeneous, and understanding these characteristics could help distinguish between different lymphoma subtypes. This study aims to systematically assess the endoscopic features of PGL and explore the role of complement receptor type 2/B-cell lymphoma 6 protein (CD21/BCL6)-based grading of lymphoid follicular disruption in predicting the effectiveness of Hp eradication (HPE) treatment in gastric MALT lymphoma. METHODS: A retrospective study was conducted involving 100 patients diagnosed with PGL at Peking University Third Hospital between January 2010 and January 2025. Patients were divided into two groups based on histopathological findings: indolent and aggressive lymphoma. The clinical and endoscopic characteristics of these two groups were compared. Survival analysis, including overall survival (OS) and progression-free survival (PFS), was performed using Kaplan-Meier curves and Log-rank tests. A subgroup of 25 patients with gastric MALT lymphoma and known HPE outcomes was selected for further analysis. Diagnostic biopsies were immunohistochemically stained with CD21 and BCL6 and graded from G0 to G4 based on follicular disruption. Logistic regression analysis was used to identify factors associated with HPE failure. RESULTS: Among the 100 patients, the average age was 63.0 (55.8, 71.0) years, with 47 men and 53 women. Aggressive lymphoma showed a significantly higher incidence of B symptoms compared with indolent lymphoma (49.0% vs. 19.6%, P= 0.004). Endoscopically, aggressive lymphoma presented more frequently with ulcerative or mixed morphologies (P < 0.001) and exhibited higher rates of mucosal erosion, ulceration with white slough, lesion friability, bleeding tendency, gastric stenosis, and impaired peristalsis (P < 0.001 for all). Aggressive lymphoma also had significantly worse OS and PFS (OS: P=0.009; PFS: P=0.003). In the subgroup of 25 MALT lymphoma patients, those with ineffective HPE were more likely to be Hp-negative (P=0.049) and had a significantly higher degree of follicular disruption (P=0.015). Multivariable Logistic regression revealed that follicular disruption grading was independently associated with HPE failure (AOR=3.63, 95%CI: 1.14-11.58, P=0.021), while Hp infection status was not (P=0.240). CONCLUSION: PGL demonstrates considerable variability in its endoscopic presentation. Features, such as ulcerative/mixed morphology, friability, bleeding tendency, stenosis, and impaired peristalsis are indicative of more aggressive disease and correlate with poorer survival outcomes. The CD21/BCL6-based grading of lymphoid follicular disruption provides a valuable tool for identifying patients at high risk of HPE failure, supporting early intervention and risk stratification for gastric MALT lymphoma treatment.