Biomarkers of lymphoma in Sjogren's syndrome: what's the latest?

INTRODUCTION: Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease standing in the crossroads of autoimmunity and lymphomagenesis, characterized by chronic B-cell hyperactivity and ectopic lymphoid tissue neoformation, potentially driving lymphoid malignant transformation. Lymphoma development is considered the most serious complication of pSS. AREAS COVERED: 'Old-classical' biomarkers (clinical, serological, hematological, and histological) validated in the past are analyzed under the perspective of recently published research. Biomarkers that have emerged during the last decade are subdivided to 'old-new' and 'newly proposed-novel' ones, including biomarkers pathophysiologically related to B-cell differentiation, lymphoid organization, and immune responses, identified in serum and tissue, both at genetic and protein level. Upcoming new imaging biomarkers, promising for further patient stratification, are also analyzed. EXPERT OPINION: Salivary gland enlargement and cryoglobulinemia still remain the best validated 'classical-old' biomarkers for lymphoma development. Though new biomarkers still need to be validated, some can be used for the identification of high-risk patients long before lymphoma diagnosis, and some might be more relevant in distinct age subgroups, while others have an added value in the assessment of lymphoma remission or relapse. Future development of composite indices, integrating old and recently proposed biomarkers, could contribute to a more precise lymphoma prediction model.