Intestinal dissemination of gastric mucosa-associated lymphoid tissue lymphoma

Abstract

Despite increasing identification of concurrent gastric and intestinal lymphomas of mucosa-associated lymphoid tissue (MALT), the clonal relationship between the two tumors and their sequential development are poorly understood. It is also unknown whether the development of these concurrent tumors is closely associated with direct antigen stimulation, which is thought to play an important role in the clonal expansion of low-grade MALT lymphomas. To investigate these, we have studied six cases of concurrent gastric and intestinal MALT lymphomas by polymerase chain reaction (PCR) amplification, cloning, and sequencing of the rearranged Ig gene, a strategy that has been widely used for analysis of clonality and antigen-driven properties of B-cell malignancies. In each case, an identical or nearly identical complementarity determining region (CDR) 3 sequence was observed between the dominant clones of concurrent gastric and intestinal MALT lymphomas. In four of six cases examined, sufficient Ig variable region sequence information was obtained to permit analysis of somatic mutations. The mutation patterns in one case suggest that the intestinal lesion is secondary to the gastric tumor, and the mutation patterns in two cases indicate that the gastric and intestinal lesions are derived from different tumour subclones, which emerge after expansion of a common early tumor clone. Furthermore, three of four cases showed ongoing Ig mutations among different PCR clones at each site. These results show that concurrent gastric and intestinal MALT lymphomas are derived from the same clone and suggest that the intestinal lesions result from dissemination of gastric tumours. Antigen stimulation may play a role in tumor evolution, particularly at an early stage.