Nodular lymphoid hyperplasia of the stomach in a patient with multiple submucosal tumors
A 38-year-old man was referred to our hospital for multiple gastric submucosal lesions after an annual medical checkup. The patient did not have a history of congenital or acquired immunodeficiency or symptoms of abdominal pain, weight loss, or fever. He was immunocompetent, as shown by a complete blood count with differential and the absence of serum viral markers, such as anti-human immunodeficiency virus (HIV) antibodies. Esophagogastroduodenoscopy revealed multiple protruding lesions covered with normal mucosa on the body and antrum of the stomach (). The lesions appeared as well-demarcated oval masses that varied in size from several millimeters to 1 cm. In addition, they were hypoechoic and originated in the submucosal layer without invasion into the deeper layers, as shown by endoscopic ultrasonography (). The Campylobacter-like organism (CLO) test was negative. No pathologic lesions were found by colonoscopy. Computed tomography also did not reveal any abnormal thickening of the gastric wall or regional lymphadenopathy. Three mass lesions were resected by endoscopic submucosal dissection and endoscopic mucosal resection.\nThe resected polyps revealed several well-defined submucosal nodules of dense lymphoid infiltrates mimicking ectopic lymph nodes (). These infiltrates had a diffuse and nodular architecture with primary and secondary lymphoid follicles (). A few lymphoid follicles also had a prominent mantle zone and small germinal center (). The lymphoid cells in the diffuse areas and primary follicles were composed predominantly of small cells, although there were a few multinucleated giant cells, which were considered to be Warthin-Finkeldey-type cells (). The infiltrate between the follicles was composed mainly of medium-sized lymphoid cells with abundant clear cytoplasm and indented or round nuclei with small nucleoli, admixed with a small number of plasma cells. In addition, a few large cells with vesicular nuclei and one or two prominent nucleoli were identified (). The gastric mucosa revealed multifocal lymphoid aggregates and some of the epithelial cells were infiltrated by small lymphocytes mimicking lymphoepithelial lesions ().\nImmunohistochemistry tests showed that the lymphoid infiltrates, including the medium-sized cells, in the interfollicular areas expressed CD2, CD3, CD4, CD5, CD8, and CD43, but the small cells in the lymphoid follicles and the large cells in the interfollicular areas did not express these markers (). However, the latter cell types expressed the CD20 antigen (). CD10 and bcl-6-positive B lymphoid cells were confined to small germinal centers (), but were negative for bcl-2. In addition, staining with CD21 and CD23 showed a normal reactive pattern in lymphoid follicles () and expanded follicular dendritic cell networks. CD30-positive large cells were rare. The plasma cells were polyclonal, as shown by kappa and lambda light chain immunohistochemistry.\nResults of in situ hybridization for Epstein-Barr virus-encoded RNA were negative. In addition, no evidence of a chromosomal translocation was found by using interphase fluorescence in situ hybridization analysis of paraffin sections using the API2/MALT1 dual-color, dual-fusion translocation probe, which revealed two orange and two green signals. However, polymerase chain reaction analysis of the immunoglobulin heavy chain and T-cell receptor gene rearrangements using the standard Biomed-2 PCR protocol, demonstrated a polyclonal pattern on Gene Scanning. The patient was followed for 1 year and the polypoid lesions remained unchanged without any additional treatment.