The Salivary Glands as the Key Site of Inflammation and Lymphoproliferation Leading to Lymphoma in Primary Sjögren’s Syndrome: Relevance for Dedicated Scoring, Biomarker Development and Lymphoma Prevention

Salvatore De Vita¹, Saviana Gandolfo ¹, Chiara Baldini ², Miriam Isola ³, Michael Voulgarelis ⁴, Andreas Goules ⁴, Ginevra De Marchi ⁵, Marco Binutti ¹, Sara Zandonella Callegher ⁵, Francesco Ferro ², Claudio Battistella ³, Loukas Chatzis ⁴ and Athanasios Tzioufas ⁴, ¹Rheumatology Clinic, Udine University Hospital, Department of Medical Area, University of Udine, Udine, Italy, Udine, Italy, ²Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, Pisa, Italy, ³Department of Medical Area, University of Udine, Udine, Italy, Udine, Italy, ⁴Department of Pathophysiology, Athens School of Medicine, National and Kapodistrian University of Athens, Athens, Greece, Athens, Greece, ⁵Rheumatology Clinic, Udine University Hospital, Udine, Italy, Udine, Italy

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: MALT lymphoma, Salivary gland, site and activity score, Sjogren's syndrome

Session Information

Date: Tuesday, November 12, 2019

Title: Sjögrenʼs Syndrome – Basic & Clinical Science Poster I

Session Type: Poster Session (Tuesday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Since the risk of B-cell non-Hodgkin’s lymphoma (NHL) evolution is increased in primary Sjögren’s syndrome (pSS), its prevention represents a relevant therapeutic end-point. A crucial preliminary step to this end is to determine the key site of inflammation and lymphoproliferation in pSS patients developing NHL.
We investigated the involvement of salivary gland (SG) mucosa-associated lymphoid tissue (MALT) in the development of NHL in pSS, based on: a) the history of major SG swelling (SGSW); b) the presence of geminal centres (GCs) in antedating salivary biopsies; and c) NHL localization itself, in particular salivary or lachrymal. The site of lymphoproliferation may be as relevant as the type of B-cells, given the role of microenvironment in B-cell expansion.

Methods: 165 cases pSS-related NHLs from the UPA Study Group (Udine, Pisa, Athens; 30, 27 and 108 cases respectively) were studied, with matched pSS controls with no lymphoma evolution. The history of SG and lachrymal swelling was evaluated in detail (both at pSS onset and in the follow-up before NHL development, episodical < or >2 months of duration, and chronic) together with the presence of GCs in SG biopsies well before NHL development, the different sites of NHL localization at its onset (salivary, lachrymal, gastric, lung, kidney, breast, skin, bone marrow, lymph nodes, spleen, others), and the NHL histotype.

Results: 165 pSS-related NHLs were studied (149 females: 90.3%; mean age: 56.3 years, range 25-82; mean time to NHL from pSS diagnosis: 5.8 years). Controls were 114, matched for sex, age and disease duration. By stepwise multivariate analyses, association with NHL was found for SGSW lasting > 2 months during follow-up (OR 16.41, 95%CI 5.97-45.08; p< 0.001) and SGSW at onset (OR 3.30, 95%CI 1.28-8.48; p< 0.013). In cases without SGSW at pSS onset, NHL evolution was higher only if SG swelling > 2 months occurred later (OR 114.29, 95%CI 14.05-929.80; p< 0.001). The SGs were then considered as the key site of inflammation and proliferation in pSS-related NHL if: 1) a history of SGSW (as above associated with NHL) was present, and/or 2) GCs were detectable in SG biopsy before NHL, and/or 3) NHL was indeed localized in the SG (n=105) or lachrymal glands (n=6) at its onset. 1 and/or 2 and/or 3 was detected in 85.4% of NHLs (140/165; 80,7% in Italy and 87.8% in Greece). Of note, this occurred more frequently than any lymphoma histotype (MALT NHL being, in any case, the largely most frequent histotype: 74.1%). No differences were noticed between the cohorts.

Conclusion: The SGs proved to be a key and early site of inflammation and lymphoproliferation in pSS-related lymphomagenesis, and the study of pSS-related NHL localization allowed a better understanding of the pathogenetic events implicated. NHL later develops in the SGs themselves or in other sites where MALT is accumulated, highlighting again the role of the local microenvironment. The SG MALT therefore represents a target to develop dedicated activity scoring and novel biomarker tools in pSS. Furthermore, a decrease in the amount and quality of SG MALT is a possible surrogate target for lymphoma prevention therapies in pSS, where long-term studies are poorly feasible.

Disclosure: S. De Vita, None; S. Gandolfo, None; C. Baldini, None; M. Isola, None; M. Voulgarelis, None; A. Goules, None; G. De Marchi, None; M. Binutti, None; S. Zandonella Callegher, None; F. Ferro, None; C. Battistella, None; L. Chatzis, None; A. Tzioufas, None.

To cite this abstract in AMA style:

De Vita S, Gandolfo S, Baldini C, Isola M, Voulgarelis M, Goules A, De Marchi G, Binutti M, Zandonella Callegher S, Ferro F, Battistella C, Chatzis L, Tzioufas A. The Salivary Glands as the Key Site of Inflammation and Lymphoproliferation Leading to Lymphoma in Primary Sjögren’s Syndrome: Relevance for Dedicated Scoring, Biomarker Development and Lymphoma Prevention [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/the-salivary-glands-as-the-key-site-of-inflammation-and-lymphoproliferation-leading-to-lymphoma-in-primary-sjogrens-syndrome-relevance-for-dedicated-scoring-biomarker-development-and-lympho/. Accessed .

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