Dissemination of a Sjögren's syndrome-associated extranodal marginal-zone B cell lymphoma: circulating lymphoma cells and invariant mutation pattern of nodal Ig heavy- and light-chain variable-region gene rearrangements.
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.


CONCLUSIONS
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.
Hansen
A
A
Dept. of Medicine and Outpatient Department, Charité Universitätsmedizin Berlin, Schumannstrasse 20/21, 10098 Berlin, Germany. ahansen@charite.de
Reiter
K
K
Pruss
A
A
Loddenkemper
C
C
Kaufmann
O
O
Jacobi
A M
AM
Scholze
J
J
Lipsky
P E
PE
Dörner
T
T
D005260:Female; D015321:Gene Rearrangement; D050439:Genes, Immunoglobulin Light Chain / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains; D016393:Lymphoma, B-Cell; D008875:Middle Aged; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology*
D007143:Immunoglobulin Heavy Chains