58-year-old woman with a past medical history of GERD presented with indigestion and bloating. Vital signs, physical exam, and routine labs were unremarkable. She underwent an EGD which revealed a 15-mm frond-like lesion in the second portion of the duodenum along the lateral wall. Biopsy was obtained and pathology showed a lymphoid infiltrate with prominent germinal centers concerning for a lymphoproliferative disorder. However the specimen was inadequate. She therefore underwent an EGD/EUS which revealed a 15-mm sessile polypoid lesion in the same location. The lesion was noted to be limited to the mucosa with normal appearance of all the other duodenal wall layers. No abnormal appearing lymph nodes were seen surrounding the examined portion of the duodenum. The lesion was resected by endoscopic mucosal resection (EMR). Pathology showed frequent intramucosal follicular aggregates of lymphocytes. Immunostains showed the follicles to be positive for pan B-cell antigens CD20 and CD79a. Numerous associated T cells were positive for CD3 and CD5. Cyclin D1 was negative and CD10 was positive consistent with follicular center cells and follicles were positive for BCL-2 consistent with neoplastic follicles. Diagnosis was consistent with indolent grade 1-2 follicular lymphoma stage IE. A body CT scan showed heterogenous attenuation pattern within the vertebral bodies. No lymphadenopathy or splenomegaly were present. She is scheduled to undergo a spine MRI with plans for a bone marrow biopsy if bone marrow replacement is detected. Primary GI FL accounts for only 1-3% of the GI lymphomas. It predominantly affects middle-aged females. The duodenum accounts for the majority of small intestinal FL. Endoscopic findings include isolated follicles, single or multiple polyps, plaques and nodularity of mucosa. Histopathologic features include predominant involvement of lamina propria and to a lesser extent, submucosa. Isolated mucosal involvement such as in our case is extremely rare. EUS can assess the size and depth of the lesion as well as detect locoregional spread. Endoscopic biopsies may not always provide adequate diagnostic material. In such situations, EMR could be considered to enhance the diagnostic yield as well as to diagnose the infiltrative type of lymphoma. We hereby report a rare presentation of primary GI FL that exclusively involved the mucosal layer, using a combination of advanced endoscopic techniques.Figure: EGD showing polypoid lesion within the duodenum.Figure: EUS showing no lesion within the deeper duodenum layer.