Low-Grade Pulmonary Mucosa-associated Lymphoid Tissue Lymphoma with or without Intraclonal Variation

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Abstract
We examined the immunoglobulin heavy chain variable (Ig VH) region genes of 11 low-grade pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas by a two-step polymerase chain reaction (PCR) and sequencing analysis. We observed frequent somatic mutations with the positive selective pressure of the rearranged Ig VH genes in all cases, indicative of postgerminal center cell origin. Eight cases demonstrated intraclonal variations (hypermutation with intraclonal variation type), but the other cases showed only one major clone without intraclonal heterogeneity (hypermutation without intraclonal variation type). The former might reflect the reentry of marginal zone B cells into a germinal center environment leading to further mutations. The latter might be no longer susceptible to hypermutation mechanisms and seemed to be stable. Four cases used Ig VH genes (hv3019b9, VH26, and VH4.21), which are frequently found in a variety of autoantibodies, such as cold agglutinins, rheumatoid factors, and anti-DNA antibodies.