33.1Introduction

Sjögren’s syndrome (SS) is a chronic, systemic, inflammatory rheumatic disease that demonstrates features of organ-specific and non-organ-specific autoimmunity [1]. SS can occur in a primary form (pSS) or in secondary form (sSS) in association with various other rheumatic diseases, primarily rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) [2]. In SLE, the term “associated disorder” or overlap syndrome may be more appropriate than “secondary” SS because of the similarities of pathogenic processes and clinical manifestations in the two diseases and the difficulties in differentiating reliably between them in a considerable number of patients [2].

This chapter outlines what is known about SS and cancer. We will summarize present knowledge on incidence and prevalence of cancer in SS, clinical risk factors and predictors, types and subtypes of malignancies, and prognosis. The focus will be on hematological malignancies, because lymphoma development is the major threat for patients with SS and one of the few factors that contribute to premature mortality in this disease [3]. Therapy of these cancers is dealt with in another chapter of this book (Chap. 37). With the exception of the most important classic papers, we focus this review on studies that have applied the American European Consensus Criteria (AECC) [4] for case definitions of pSS and sSS.

The association between autoimmune disease and malignancy risk, especially hematological malignancy, is not restricted to SS [5]. Heightened risks of cancer accompany states of chronic inflammation associated with autoimmunity in general and may be further increased by certain treatments [6]. Thus, we also review the results of recent important studies in SLE and RA in order to understand the risk of malignancy in SS in a fuller context. Patients with autoimmune disease constitute only a small part of patients with lymphoma.

33.2Methodological Considerations

Malignancy is a common phenomenon in human life. However, some types of malignancy (and in particular those that pertain to autoimmune diseases, e.g., hematological malignancies) are quite rare. Estimates of the prevalence of pSS have ranged widely, from as high as 0.3% [7] to as low as 0.05% [8]. Prevalence estimates for sSS and associated disorders are difficult to obtain because this condition has seldom been studied systematically. Thus, evaluations of the association between special types of malignancies and SS require studies within large, representative unselected patient cohorts with reliable case definition. Further, such studies require many years of follow-up time on individual patients, preferably decades, as well as registry data available for the relevant malignancies within the cohort and background population. Case reports and case series may give hints for additional rare associations. However, there is a strong risk of selection bias in such reports towards