A case of methotrexate-associated primary splenic lymphoma diagnosed by endoscopic biopsy of a small gastric lesion.

Methotrexate (MTX)-associated primary splenic lymphoma (PSL) is an extremely rare malignancy. A 74-year-old man with a history of rheumatoid arthritis treated with MTX was referred for evaluation of elevated serum lactate dehydrogenase (LDH) levels. He reported mild left flank pain without other systemic symptoms. Physical examination revealed splenomegaly without superficial lymphadenopathy. Laboratory tests showed an elevated LDH level and a markedly increased soluble interleukin-2 receptor level. Contrast-enhanced computed tomography demonstrated a large splenic mass occupying nearly the entire spleen, along with low-density hepatic nodules. Esophagogastroduodenoscopy revealed a small whitish elevated lesion in the gastric body, suggestive of subepithelial lesion. Histopathological examination of gastric biopsy showed diffuse infiltration of large atypical lymphoid cells. Immunohistochemistry demonstrated positivity for CD45 and CD20, negativity for CD3, CD10, and a high Ki-67 labeling index, consistent with diffuse large B-cell lymphoma (DLBCL). Based on these findings, the patient was diagnosed with MTX-associated primary splenic DLBCL. He was treated in a tertiary center and showed a favorable response to chemotherapy. This is a rare case of PSL associated with MTX therapy, and highlights secondary gastric involvement as a diagnostic pathway for suspected PSL without direct invasive intervention to the spleen.