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
التفاصيل البيبلوغرافية
العنوان:
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 (VH/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/κ+,IgD−,CD5−,CD10−,Bcl-6−,CD23−,p53−,p21−,MDM2− phenotype and mutated VH1–69/D2–21/JH4α–VκA27/Jκ2 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 VH3–07/D3–22/JH3b–Vλ3L/Jλ2/3 and VH3–64/D3–03/JH2–VκA19/Jκ2 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 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) Ig VH/L mutations.
