Review Clinical picture, outcome and predictive factors of lymphoma in Sjӧgren syndrome ☆ , ☆☆ ,★ Aristea Papageorgiou, Michael Voulgarelis, Athanasios G. Tzioufas ⁎ Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece abstract article info Article history: Received 5 March 2015 Accepted 16 March 2015 Available online 22 March 2015 Keywords: Lymphoma Sjӧgren's syndrome Predictors Prognosis Outcome 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 ex- plore all the available data concerning the clinical picture, risk prognostication and outcome of pSS-associated NHLs. © 2015 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 641 1.1. Clinical picture of pSS-related NHLs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 642 1.2. Predicting NHL development in SS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 642 1.2.1. Clinical predictors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 642 1.2.2. Hematological and serological predictors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 644 1.2.3. Histological predictors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 645 1.2.4. Molecular and immunophenotypical predictors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 646 2. Outcome of pSS-associated NHL patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 646 3. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 647 Take-home messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 647 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 647 1. Introduction Primary Sjӧgren's syndrome (pSS) is generally considered to be a chronic benign autoimmune disorder characterized by lymphocytic infiltration of the exocrine glands, predominantly the salivary and lacri- mal glands, which leads to their gradual destruction and consequent oral and ocular dryness [1]. While several studies related to survival have demonstrated a minimal increase in mortality risk compared to the general population, supporting the benign nature of the disease, others have also documented that approximately one in three patients will unarguably develop severe systemic manifestations, either as a re- sult of organ lymphocytic infiltration or immune complex-mediated disease [2–8]. Among those manifestations that severely complicate the disease and result in an increased risk of death, non-Hodgkin's lymphoma (NHL) is the most deleterious [2–5,7,8]. Given that B-cell hyperactivity is the hallmark of pSS, it has long been documented that malignant lymphoproliferation is not an unex- pected event. The first report to record an increased risk of lymphoma development in the setting of pSS was published in the late 70s by Autoimmunity Reviews 14 (2015) 641–649 ☆ Competing interests: The authors declare no competing interests. ☆☆ Review criteria: We searched for original articles published between 1968 and 2015 focusing on Sjögren's syndrome associated non-Hodgkin's lymphoma clinical picture, pre- dictive factors and outcome. The search terms we used were Sjögren's syndrome, lympho- ma, and predictive factors. All papers identified were English-language, full text papers. ★ Author contributions: A. Papageorgiou researched the data for the article, provided a substantial contribution to the discussion of content and wrote the article. M. Voulgarelis and A.G Tzioufas reviewed and edited the manuscript before submission. ⁎ Corresponding author at: Department of Pathophysiology, Medical School, University of Athens, M. Asias 75, Athens 11527, Greece. E-mail address: agtzi@med.uoa.gr (A.G. Tzioufas). http://dx.doi.org/10.1016/j.autrev.2015.03.004 1568-9972/© 2015 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev