Prognostic markers of lymphoma development in primary Sjögren syndrome

Abstract

Sjögren syndrome is a systemic autoimmune disease that principally affects women between the fourth and sixth decades of life who present with sicca symptomatology caused by dryness of the main mucosal surfaces. The clinical spectrum of Sjögren syndrome extends from dryness to systemic involvement. Since 1978, Sjögren syndrome has been closely associated with an enhanced risk of lymphoma, one of the most severe complications a patient may develop. Primary Sjögren syndrome patients have a 10–44-fold greater risk of lymphoma than healthy individuals, higher than that reported for systemic lupus erythematosus and rheumatoid arthritis. The close link between lymphoma and Sjögren syndrome is clearly exemplified by the very specific type of lymphoma arising in Sjögren syndrome patients, mainly low-grade B-cell lymphomas (predominantly a marginal zone histological type) with primary extranodal involvement of the major salivary glands (overwhelmingly parotid), with a primordial role of cryoglobulinemic-related markers (both clinical and immunological). The most recent studies support a higher number of risk factors detected in an individual leads to a higher lymphoma risk. A close follow-up of high-risk groups with longitudinal assessments of all known risk factors, including cryoglobulin-related markers and EULAR Sjögren's syndrome disease activity index measurement in particular, is mandatory.

Immune response in LPD during methotrexate administration (MTX-LPD) in rheumatoid arthritis patients

“…100 Among Japanese RA patients, the comorbidity rate of secondary Sjögren syndrome was reported to be approximately 10%. 101 Although primary Sjögren syndrome patients are estimated to have a 10-44-fold higher risk of lymphoma, especially B cell lymphoma, than healthy individuals, 102 one large epidemiological study reported that secondary Sjögren syndrome yielded an even higher risk than the primary form. 103 On the other hand, several studies have reported a higher risk for patients with primary Sjögren syndrome.…”

“…104,105 As increased BAFF levels were reported to be associated with the risk of non-Hodgkin lymphoma in primary Sjögren syndrome, 106 the environment of chronic B cell stimulation may be associated with the risk of lymphoma development in Sjögren syndrome. 102 As the LPD developing in Sjögren syndrome is commonly low-grade B cell lymphoma, especially B-cell marginal zone lymphoma and mucosa-associated lymphoid tissue (MALT) lymphoma, which are not common in MTX-LPD, the environment of chronic B cell stimulation in concomitant Sjögren syndrome does not directly influence the pathogenesis of MTX-LPD, but it may indirectly influence MTX-LPD in RA patients.…”

“…Although the association between other autoimmune diseases, such as systemic lupus erythematosus (SLE) and lymphoma, has been reported, 102 their comorbidity rate in RA is low compared with that of Sjögren syndrome.…”

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

“…As of today, there are no certain biomarkers of developing lymphoma in the course of pSS. In the recent years, there have been attempts to develop models which would increase the sensitivity of early lymphoma diagnosis in the population of pSS patients [16,17]. Some symptoms such as palpable purpura, salivary gland enlargement, low C4, leukopenia, positive cryoglobulins, monoclonal gammopathy, disease duration and positive RF are considered risk factors [18].…”

Lymphoma of the Sublingual Gland: Clinical, Morphological, Histopathological, and Genetic Characterization

“…These are distributed with 79% in the parotid glands, 18% in the submandibular glands, 2% in the minor salivary glands, and 1% in the sublingual glands (4). In the parotid gland, the most frequent types of lymphomas are extranodal marginal zone lymphoma (EMZL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL) (5), with EMZL being especially predominant in patients with Sjögren's syndrome (6). The detection of certain chromosomal translocations by fluorescence in situ hybridization (FISH) is used as a diagnostic tool and especially in EMZL genetic rearrangements vary in frequency according to the primary anatomical site of disease establishing a link between genetics and homing of malignant lymphocytes (7).…”