Abstract Introduction/Objective Gastric carcinoma with lymphoid stroma (GCLS) is a distinct and rare histologic subtype of gastric adenocarcinoma that is characterized by undifferentiated carcinoma mixed with prominent lymphoid cell infiltration. Around 80% of GCLS cases are associated with Epstein-Barr virus (EBV) infection. Here we report a case of EBV-negative GCLS. Methods The patient was a 79-year-old female with a recent history of abdominal distention, weight loss, and gastrointestinal bleeding who presented for evaluation. Endoscopy found a 4.6 mm lobulated lesion at the incisura of the stomach with endosonographic evidence of invasion through the submucosa. Biopsy was consistent with intramucosal diffuse neoplasm, favoring adenocarcinoma. The decision was made to do subtotal gastrectomy. Results The patient underwent distal gastrectomy with Billroth 2 reconstruction. Gross examination of the stomach revealed a firm 1.4 cm nodule in the background of diffuse mucosal granularity in the adjacent stomach. Microscopically, the tumor invaded the submucosa without lymph nodes involvement. Staining showed the tumor diffusely positive for CAM5.2, focally and weakly positive for pancytokeratin and CK7, while negative for CK20. Mismatch repair (MMR) proteins staining demonstrated a loss of nuclear expression of MLH1 and PMS2. Her2/Neu FISH was non-amplified. The tumor was found to be EBV negative by EBER ISH while PD-L1 was expressed. The histopathological findings confirmed the final diagnosis of gastric carcinoma with lymphoid stroma (GCLS). Conclusion We report a case of GCLS that was EBV negative with non-amplified HER2, while MMR-deficient, and PD-L1 positive. These results suggest that this tumor subtype may be less responsive to targeted therapy, but show susceptibility to immune checkpoint inhibitors.
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