Clinical picture, outcome and predictive factors of lymphoma in Sjӧgren syndrome ★

• Parotid gland enlargement, purpura and lymphadenopathy are the most consistent clinical risk factors for NHL development.
• Low serum C4 complement levels and MMC constitute important laboratory predictors.
• High LFS and GCs presence mark excess risk for malignant proliferation.
• Serum BAFF and Flt3 ligand levels represent promising biologic markers.
• At the time of lymphoma diagnosis pSS patients present increased disease activity and low IPI score and SS disease activity at lymphoma diagnosis are suggestive of a favorable prognosis.

The intrinsic and complex nature of primary Sjӧgren's syndrome (pSS) makes it difficult to identify risk factors that can predict the development and outcome of non-Hodgkin's lymphoma (NHL), yet patients at high risk for such complication seem to bear certain clinic-serological characteristics that render them a unique profile. In the last decade, research focusing on B-cell hyperactivity as the hallmark of pSS-related lymphoproliferation has shed light on certain biological and molecular factors that participate in disease evolution and lymphoma development, thus indicating possible predictors of lymphoma development and outcome. In this review, we explore all the available data concerning the clinical picture, risk prognostication and outcome of pSS-associated NHLs.