{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T09:57:28Z","timestamp":1760954248306},"reference-count":16,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2003,11,4]],"date-time":"2003-11-04T00:00:00Z","timestamp":1067904000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"the Associazione Italiana Ricerca sul Cancro"},{"name":"the Italian Ministero della Salute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2003,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To characterize Sj\u00f6gren's syndrome (SS)\u2013related 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed sequential parotid and lung biopsy specimens that were obtained from a single patient with SS at multiple time points over a 7\u2010year 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.11286","type":"journal-article","created":{"date-parts":[[2003,11,7]],"date-time":"2003-11-07T10:01:05Z","timestamp":1068199265000},"page":"3181-3186","source":"Crossref","is-referenced-by-count":37,"title":["Extrasalivary lymphoma development in Sj\u00f6gren's syndrome: Clonal evolution from parotid gland lymphoproliferation and role of local triggering"],"prefix":"10.1002","volume":"48","author":[{"given":"Daniela","family":"Gasparotto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"De Vita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valli","family":"De Re","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Marzotto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ginevra","family":"De Marchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathryn Ann","family":"Scott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annunziata","family":"Gloghini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianfranco","family":"Ferraccioli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Boiocchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,11,4]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-199609000-00008"},{"key":"e_1_2_5_3_2","first-page":"S94","article-title":"Lymphoid proliferations of the salivary glands","volume":"111","author":"Harris NL","year":"1999","journal-title":"Am J Clin Pathol"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/000348940010901217"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/bcmd.2001.0446"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-0172(96)80019-9"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10221"},{"key":"e_1_2_5_8_2","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1182\/blood.V91.6.1864","article-title":"Clonal salivary gland infiltrates associated with myoepithelial sialadenitis (Sj\u00f6gren's syndrome) begin as nonmalignant antigen\u2010driven selected expansion","volume":"91","author":"Bahler DW","year":"1998","journal-title":"Blood"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.12.3878"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200203)32:3<903::AID-IMMU903>3.0.CO;2-D"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780360814"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.61.6.554"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400217"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(94)90175-9"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200004)43:4<908::AID-ANR24>3.0.CO;2-K"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199307153290305"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1996.v110.pm8964425"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.11286","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.11286","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T01:23:20Z","timestamp":1696987400000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.11286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,11]]},"references-count":16,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2003,11]]}},"alternative-id":["10.1002\/art.11286"],"URL":"https:\/\/doi.org\/10.1002\/art.11286","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,11]]}}}