IntroductionPrimary mucosa-associated lymphoid tissue (MALT) lymphoma rarely arises at the gastroesophageal junction (GEJ). Subepithelial presentation is particularly uncommon and often misclassified as a mesenchymal tumor. Because GEJ subepithelial lesions are frequently presumed to represent GISTs or leiomyomas, lymphoid neoplasms may escape early consideration. We present a rare case of a GEJ subepithelial lesion originating from the muscularis mucosae, ultimately diagnosed as primary MALT lymphoma, emphasizing the diagnostic value of EUS-guided deep-tissue sampling.

Case DescriptionA 68-year-old man was evaluated for an incidentally identified GEJ subepithelial lesion. Endoscopy demonstrated a smooth, intact mucosal surface over a well-defined 23 × 10 mm mass. Endoscopic ultrasonography revealed a homogeneous, hypoechoic lesion confined to the muscularis mucosae, without perigastric lymph nodes. The differential diagnosis included gastrointestinal stromal tumor, leiomyoma, neuroendocrine tumor, and lymphoid neoplasia. EUS-guided tissue acquisition was performed using a 22-gauge fine-needle biopsy (FNB).

Histopathology revealed dense CD20(+)/CD3(–) B-cell infiltration, LCA(+), with absence of epithelial or neuroendocrine markers (Pankeratin–, Chromogranin A–, CD56–). Hematopathology demonstrated a monomorphic population of small B-cells expressing CD20 and bcl-2, negative for CD5, CD23, and Cyclin-D1, with a low proliferative index (Ki-67 ≈10%). These findings supported a diagnosis of primary MALT lymphoma. Staging CT identified no systemic disease, consistent with localized lymphoma.

DiscussionMALT lymphoma at the GEJ is exceptionally rare, and subepithelial morphology poses a diagnostic pitfall because EUS features may overlap with GIST or leiomyoma. High-resolution EUS is essential for characterizing the layer of origin, while FNB provides adequate deep-tissue samples crucial for immunophenotyping. The immunoprofile—CD20(+), bcl-2(+), Cyclin-D1(–), CD5(–), CD23(–)—allows differentiation from mantle cell and follicular lymphomas. Early diagnosis is clinically relevant, because localized disease carries an excellent prognosis and can be managed with organ-preserving therapeutic strategies.

ConclusionThis case illustrates a rare GEJ MALT lymphoma mimicking a mesenchymal subepithelial lesion. Accurate diagnosis required correlation of endoscopic appearance, EUS characterization, and targeted FNB with detailed immunohistochemistry. Lymphoid neoplasms, although rare, should be included in the differential diagnosis of GEJ subepithelial lesions, particularly those arising from the muscularis mucosae.