Abstract | OBJECTIVE: Both the genesis and outgrowth of extranodal marginal-zone B cell lymphomas (MZLs) of the mucosa-associated lymphoid tissue (MALT) type are generally thought to represent antigen-driven processes. We undertook this study to analyze lymphoma progression and dissemination outside of the MALT-type lesions. METHODS: Histopathologic and Ig heavy- and light-chain variable-region gene (V(H/L)) analyses were performed in sequential tissue samples from a patient with primary Sjögren's syndrome (SS) with glandular (parotid) manifestations and subsequent nodal dissemination of a low-grade MZL. RESULTS: This MZL expressed a CD20+,CD27+,sIgM/kappa+, IgD-,CD5-,CD10-,Bcl-6-,CD23-,p53-,p21-,MDM2- phenotype and mutated V(H)1-69/D2-21/J(H)4alpha-V(kappa)A27/J(kappa)2 Ig rearrangements. Notably, circulating lymphoma cells from the parotid glands occurred transiently in the patient's blood, as detected by single-cell polymerase chain reaction. In addition, 2 minor B cell clones (clones 2 and 3, with V(H)3-07/D3-22/J(H)3b-V(lambda)3L/J(lambda)2/3 and V(H)3-64/D3-03/J(H)2-V(kappa)A19/J(kappa)2 rearrangements, respectively) were also detected in the parotid glands and blood, and 1 of these (clone 2) was also detected in the lymph nodes. Ig V(H/L) analyses revealed ongoing ( antigen-driven) mutations of the glandular lymphoma rearrangements, but an invariant mutation pattern of their nodal counterparts. CONCLUSION: These data indicate coexpansion and transient (re)circulation of the lymphoma clone and 2 additional glandular B cell clones in a primary SS-associated extranodal MZL. Combined histologic and molecular features of the nodal lymphoma subclone reflect a process of "follicular colonization" that eventually froze the mutation machinery after accumulation of additional ( antigen-driven) Ig V(H/L) mutations.
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Authors | A Hansen, K Reiter, A Pruss, C Loddenkemper, O Kaufmann, A M Jacobi, J Scholze, P E Lipsky, T Dörner |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 54
Issue 1
Pg. 127-37
(Jan 2006)
ISSN: 0004-3591 [Print] United States |
PMID | 16385504
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Immunoglobulin Heavy Chains
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Topics |
- Female
- Gene Rearrangement
- Genes, Immunoglobulin Light Chain
(genetics)
- Humans
- Immunoglobulin Heavy Chains
- Lymphoma, B-Cell
- Middle Aged
- Sjogren's Syndrome
(genetics, immunology)
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