Predicting lymphoma development in patients with Sjögren’s syndrome

Abstract

Introduction: The issue of predicting lymphoma in primary Sjögren's syndrome (pSS) starts from its clinical and biologic essence, i.e., an autoimmune exocrinopathy with sicca syndrome, inflammation and lymphoproliferation of MALT (mucosa-associated lymphoid tissue) in exocrine glands. Areas covered: The two major predictors to be firstly focused are persistent salivary gland (SG) swelling and cryoglobulinemic vasculitis with related features as purpura and low C4, or the sole serum cryoglobulinemia repeatedly detected. They are pathogenetically linked and reflect a heavier MALT involvement by histopathology, with the expansion of peculiar rheumatoid factor (RF)-positive clones/ idiotypes. Other predictors include lymphadenopathy, splenomegaly, neutropenia, lymphopenia, serum beta2-microglobulin, monoclonal immunoglobulins, light chains, and RF. Composite indexes/scores may also predict lymphoma. Expert opinion: Prediction at baseline needs amelioration, and must be repeated in the follow-up. Careful clinical characterization, with harmonization and stratification of large cohorts, is a relevant preliminary step. Validated and new biomarkers are needed in biologic fluids and tissues. SG echography with automatic scoring could represent a future imaging biomarker, still lacking. Scoring MALT involvement in pSS, as an additional tool to evaluate disease activity and possibly to predict lymphoma, is welcomed. All these efforts are now ongoing within the HarmonicSS project and in other research initiatives in pSS.

Prevalence and clinical presentation of lymphoproliferative disorder in patients with primary Sjögren’s syndrome

“…MALT is the most commonly diagnosed type of lymphoma in pSS patients [13]. One of the possible locations of MALT are lungs [14,15]. In described group of patients from our Department the frequency of lymphoproliferative disorders was 2% (mostly common being MALT).…”

Primary Breast Extranodal Marginal Zone Lymphoma in Primary Sjögren Syndrome: Case Presentation and Relevant Literature

“…Based on the data available in the literature about PBL-SS association [40][41][42][43][44], and the current theories about lymphoma prevalence at immune-privileged sites [45], we can assume that the diagnosis of SS-related lymphoid proliferations, especially when occurring in the breast, currently is very challenging and would probably benefit from wider studies including SS patients with prolonged follow-up (>10 years). Therefore, we may suggest more attentive monitoring for lymphoma development in those SS patients who display higher risk factors (such as palpable purpura, low C4, mixed monoclonal cryoglobulinemia) and to incorporate breast surveillance in such patients.…”

Primary Breast Extranodal Marginal Zone Lymphoma in Primary Sjögren Syndrome: Case Presentation and Relevant Literature

“…On the bases of data available in the literature about PBL-SS association, [42,43] the single case clinical reports, [44][45][46] the current theories about lymphoma occurrence in immune-privileged sites (as recently reviewed by King et al in 2020) [47] and the several attempts to predict lymphoma in SS patients, we can assume that the early diagnosis of a SS-related lymphoid proliferation, especially in the breast, is at present very challenging, and will probably remain as such in the near future, due to the wide clinical-epidemiological and histopathological scenario. Close monitoring of SS patients, including clinical observation and serologic investigations (for palpable purpura, low C4, mixed monoclonal cryoglobulinemia) along with breast surveillance, should be strongly advised in such patients.…”