OP0070 Non-malignant lymphoproliferation in sjoegren’s syndrome: proposed classification based on integrated clinico-phatologic and molecular studies and follow-up

Background Non-neoplastic B-cell lymphoproliferation (NNBLP) is a common feature in Sjoegre’s syndrome (SS) and predisposes to non-Hodgkin’s lymphoma (NHL). It is characterised by extranodal or nodal organ involvement or by the presence of an M-component in biologic fluids, in particular mixed monoclonal cryglobulinemia (MMC). Objectives To better address the issue of SS-NNLP of Mucosa-Associated Lymphoid Tissue (MALT), usually involving the major salivary glands, we investigated 13 consecutive patients with primary SS and persistent parotid swelling (12F, 1M; mean age 59.5 years). Methods Clinical and pathologic results were integrated with molecular analyses of B-cell clonal expansion in synchronous and metachronous biopsies (mean follow-up: 5.3 years). Results At baseline 6/13 patients presented a parotid MESA with lymphoproliferative lesion (Group 1) and 7/13 a MESA with fully benign lymphoid infiltrate (Group 2), according to strict pathologic criteria.1 Tissue B-cell clonal expansion was monoclonal in 5/6 cases in Group 1 and oligo-polyclonal in 6/7 cases in Group 2. B-cell NHL evolution was observed in 2/6 cases in Group 1 and in 0/7 in Group 2. Only the 2 cases evolved into NHL presented previous molecular evidence of ongoing expansion of the same clone or clonal dissemination in multiple biopsies. By contrast, the clinical and laboratory features were not relevant either for the diagnosis of NNLP vs NHL or to predict NHL evolution. MMC was detected in 2/13 cases, not evolved into NHL. Conclusion Pathologic features are crucial to distinguish between non-neoplastic and neoplastic extranodal LP in SS. Molecular analyses of B-cell clonal expansion appear relevant to identify a subset of patients with higher risk of NHL progression. When considering the whole spectrum of NNLP in SS and a practical diagnostic approch (“real” disease entities,1–3), the following classification is proposed: a) Fully benign lymphoproliferation: fully benign lymphoid infiltrates in MALT sites or reactive lymphoadenopathy in the lack of M-component; b) Lymphoproliferative disorder: lymphoproliferative lesions in MALT sites, nodal atypical lymphoproliferative disorder or persistent MMC or M-component in biologic fluids. A consensus on the classification of NNLP in SS will allow cooperative studies to clarify disease pathobiology and the risk of NHL evolution and to optimise follow-up and treatment. References De Vita, et al. Arthritis Rheum. 1997;40:318 Skopouli, et al. Semin Arthritis Rheum. 2000;29:296 De Vita, et al. Arthritis Rheum. 2000;43:94