TY - JOUR
T1 - Extrasalivary Lymphoma Development in Sjögren's Syndrome
T2 - Clonal Evolution From Parotid Gland Lymphoproliferation and Role of Local Triggering
AU - Gasparotto, Daniela
AU - De Vita, Salvatore
AU - De Re, Valli
AU - Marzotto, Alessandra
AU - De Marchi, Ginevra
AU - Scott, Cathryn Ann
AU - Gloghini, Annunziata
AU - Ferraccioli, Gianfranco
AU - Boiocchi, Mauro
PY - 2003/11
Y1 - 2003/11
N2 - Objective. To characterize Sjögren's syndrome (SS)-related B cell lymphoproliferation at the premalignant stage and during the evolution to B cell lymphoma, and to better understand the pathobiologic mechanisms associated with clonal expansion and the possible influence of different microenvironments on neoplastic transformation. Methods. We analyzed sequential parotid and lung biopsy specimens that were obtained from a single patient with SS at multiple time points over a 7-year period. Polymerase chain reaction DNA amplification, cloning, and sequencing of the immunoglobulin heavy chain variable region showed clonality, somatic mutations, intraclonal heterogeneity, and genealogic relationships of the B cell clones in the different biopsy specimens. Results. The evolution of a nonmalignant B cell clone that was present in the parotid gland and evolved into a B cell lymphoma was documented. During such a process, one subclone was selected that accumulated somatic mutations in a pattern consistent with the preservation of antigen receptor functionality, possibly attributable to continued hypermutation and selection. Intraclonal diversity indicated the presence of local triggers in both the parotid and lung microenvironments. Conclusion. Molecular followup of B cell lymphoproliferation in SS, from nonmalignant stage to overt B cell lymphoma, indicated a role for B cell receptor engagement in clonal survival. The outgrowth of one subclone, with malignant transformation in the lung, a target organ different from the initial site of the lymphoproliferative process (the parotid gland), indicates that resident stimuli in different microenvironments may locally sustain ongoing lymphoproliferation and B cell transformation.
AB - Objective. To characterize Sjögren's syndrome (SS)-related B cell lymphoproliferation at the premalignant stage and during the evolution to B cell lymphoma, and to better understand the pathobiologic mechanisms associated with clonal expansion and the possible influence of different microenvironments on neoplastic transformation. Methods. We analyzed sequential parotid and lung biopsy specimens that were obtained from a single patient with SS at multiple time points over a 7-year period. Polymerase chain reaction DNA amplification, cloning, and sequencing of the immunoglobulin heavy chain variable region showed clonality, somatic mutations, intraclonal heterogeneity, and genealogic relationships of the B cell clones in the different biopsy specimens. Results. The evolution of a nonmalignant B cell clone that was present in the parotid gland and evolved into a B cell lymphoma was documented. During such a process, one subclone was selected that accumulated somatic mutations in a pattern consistent with the preservation of antigen receptor functionality, possibly attributable to continued hypermutation and selection. Intraclonal diversity indicated the presence of local triggers in both the parotid and lung microenvironments. Conclusion. Molecular followup of B cell lymphoproliferation in SS, from nonmalignant stage to overt B cell lymphoma, indicated a role for B cell receptor engagement in clonal survival. The outgrowth of one subclone, with malignant transformation in the lung, a target organ different from the initial site of the lymphoproliferative process (the parotid gland), indicates that resident stimuli in different microenvironments may locally sustain ongoing lymphoproliferation and B cell transformation.
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U2 - 10.1002/art.11286
DO - 10.1002/art.11286
M3 - Article
C2 - 14613281
AN - SCOPUS:0242579568
VL - 48
SP - 3181
EP - 3186
JO - Arthritis care and research : the official journal of the Arthritis Health Professions Association
JF - Arthritis care and research : the official journal of the Arthritis Health Professions Association
SN - 0893-7524
IS - 11
ER -