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/κ+,IgD−,CD5−,CD10−,Bcl‐6−,CD23−,p53−,p21−,MDM2− phenotype and mutated V H 1–69/D2–21/J H 4α–V κ A27/J κ 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 λ 3L/J λ 2/3 and V H 3–64/D3–03/J H 2–V κ A19/J κ 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.