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(American Journal of Pathology. 2003;162:105-113.)
© 2003 American Society for Investigative Pathology

Regular Articles

Primary Follicular Lymphoma of the Small Intestine

{alpha}4ß7 Expression and Immunoglobulin Configuration Suggest an Origin from Local Antigen-Experienced B Cells

Richard J. Bende*, Laura A. Smit*, Janneke G. Bossenbroek*, Wilhelmina M. Aarts*, Marcel Spaargaren*, Laurence de Leval{dagger}, Guy E. E. Boeckxstaens{ddagger}, Steven T. Pals* and Carel J. M. van Noesel*

From the Departments of Pathology*and Gastroenterology,{ddagger}Academic Medical Center, Amsterdam, The Netherlands; and the Department of Pathology,{dagger}Centre Hospitalier Universitaire Sart-Tilman, Liege, Belgium

Primary follicular lymphoma of the gastrointestinal tract (GI-FL) is a rare so far poorly studied entity. We analyzed four FL cases located in the small intestine and duodenum to gain insight in their pathogenesis and to find an explanation for their low tendency to disseminate outside the GI tract. GI-FLs resemble nodal FLs with respect to morphology and expression of typical GC markers such as CD10, CD38, and BCL-6. We established that the high levels of the anti-apoptosis protein BCL-2 in the tumor cells are in all cases due to a t(14;18) involving the immunoglobulin heavy chain and BCL-2 loci. Detailed immunoglobulin gene analyses on microdissected tissue samples further supported the GC-cell derivation: GI-FLs carry extensively mutated variable heavy-chain genes. The mutation patterns indicated that at some time point in development stringent antigen receptor-based selection processes must have occurred. Interestingly, three of four neoplasms expressed surface IgA, an immunoglobulin class typical of the mucosal immune system and seldom found in nodal FL. In contrast to nodal FLs, the GI-FLs expressed the {alpha}4ß7 integrin, an established mucosa-homing receptor also expressed by normal intestinal B and T lymphocytes and by low-grade mucosa-associated lymphoid tissue lymphomas. However, the chemokine receptor CXCR3, expressed on low-grade mucosa-associated lymphoid tissue lymphomas, was not detected on the GI-FLs or on nodal FLs. The combined data suggests that primary FL of the small intestine is a distinct entity that originates from local antigen-responsive B cells.




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