S6286 Unmasking Primary Gastric Diffuse Large B-Cell Lymphoma (DLBCL)

Introduction: Primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is an aggressive and uncommon subtype of extranodal non-Hodgkin lymphoma (NHL), accounting for 5% of all gastric malignancies. It is most commonly seen in males aged 50–60 and often presents with nonspecific gastrointestinal symptoms. While Helicobacter pylori infection is implicated in the pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma, its association with PG-DLBCL is less clearly established. Case Description/Methods: We report the case of a 64-year-old Vietnamese man who presented with progressive dysphagia. Although esophagogastroduodenoscopy (EGD) was recommended, the patient was lost to follow-up. He later re-presented with hematemesis, epigastric pain, and weight loss. Multiple EGDs identified a large antral gastric ulcer that repeatedly tested negative for malignancy but was positive for H. pylori. Eventually, endoscopic ultrasound (EUS) with fine needle biopsy confirmed PG-DLBCL, staged as T3 N1. Notably, the patient was nonadherent to H. pylori eradication therapy, and his course was marked by delays in diagnosis due to social determinants of health, including housing instability. The patient is currently undergoing R-CHOP chemotherapy. His course was further complicated by gastric outlet obstruction secondary to the cancer, status post EUS-guided gastrojejunostomy with Axios stent placement. Discussion: This case underscores the diagnostic challenges associated with PG-DLBCL. The disease often mimics benign gastric pathology, leading to diagnostic delays. Repeat EGDs with biopsy and EUS are critical when clinical suspicion for malignancy remains high despite initial negative findings. Diagnosis of PG-DLBCL requires histologic confirmation of large atypical B-cells, supported by immunohistochemical markers such as CD20. Staging typically follows the Lugano classification and involves imaging modalities such as PET-CT. Standard treatment consists of R-CHOP chemotherapy, which is associated with favorable outcomes in limited-stage disease. Prognostic factors include the International Prognostic Index (IPI) score and response to initial therapy.