Dissemination of a Sjogren's syndrome-associated extranoda marginal-zone B cell lymphoma -: Circulating lymphoma cells and invariant mutation pattern of nodal Ig heavy- and light-chain variable-region gene rearrangements
Dissemination of a Sjogren's syndrome-associated extranoda marginal-zone B cell lymphoma -: Circulating lymphoma cells and invariant mutation pattern of nodal Ig heavy- and light-chain variable-region gene rearrangements
复制标题
DOI：
10.1002/art.21558
复制
发表时间：
2006-01-01
影响因子：
--
通讯作者：
Dörner, T
中科院分区：
文献类型：
--
作者：
Hansen, A;Reiter, K;Dörner, T
Objective.粘膜相关淋巴组织（MALT）型结旁边缘区B细胞淋巴瘤（MZL）的发生和生长通常被认为是抗原驱动的过程。我们进行了这项研究，以分析淋巴瘤的进展和扩散以外的MALT型病变。对1例原发性干燥综合征（SS）患者的连续组织样本进行了组织学和IG重链和轻链可变区基因（V-H/L）分析，该患者有腺（腮腺）表现，随后淋巴结播散为低度MZL。该MZL表达CD 20+、CD 27+、sIgM/kappa+、IgD-、CD 5-、CD 10-、Bcl-6-、CD 23-、p53-、p21-、MDM 2-表型和突变的V（H）1-69/D2-21/J（H）4 α-V（kappa）A27/J（kappa）2 IG重排。值得注意的是，从腮腺循环淋巴瘤细胞发生在病人的血液中短暂的，通过单细胞聚合酶链反应检测。此外，还在腮腺和血液中检测到2个次要B细胞克隆（克隆2和3，分别具有V（H）3-O 7/D3-22/J（H）3b-V（lambda）3L/J（lambda）2/3和V（lambda）3-64/D3-03/J（H）2-V（kappa）A19/J（kappa）2重排），并且还在淋巴结中检测到其中1个（克隆2）。19例VH/L分析显示腺性淋巴瘤重排的持续（抗原驱动）突变，但其淋巴结对应物的突变模式不变。这些数据表明，在原发性SS相关结节性MZL中，淋巴瘤克隆和2个额外的腺B细胞克隆共扩增和瞬时（再）循环。淋巴结淋巴瘤亚克隆的组织学和分子特征反映了“滤泡定植”的过程，其最终在累积额外的（抗原驱动的）19个V-H/L突变后冻结突变机制。
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 Sjogren'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)4 alpha-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-O7/D3-22/J(H)3b-V(lambda)3L/J(lambda)2/3 and V(lambda)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 I of these (clone 2) was also detected in the lymph nodes. 19 VH/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) 19 V-H/L mutations.