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Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the development of malignant lymphoma in primary Sjogren's syndrome
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.ORCID iD: 0000-0001-6715-3704
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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2011 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 70, no 8, 1363-1368 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE:

The development of non-Hodgkin's lymphoma (NHL) confers a high risk of mortality in primary Sjögren's syndrome (pSS) patients, but the sensitivity and specificity of proposed lymphoma predictors are insufficient for practical use. The performance of lymphoid organisation in the form of germinal centre (GC)-like lesions was evaluated in labial salivary gland biopsies taken at pSS diagnosis as a potential lymphoma-predicting biomarker.

METHODS:

Labial salivary gland tissue biopsies available from two Swedish pSS research cohorts (n=175) were re-evaluated by light microscopy in a blind study in order to identify GC-like structures as a sign of ectopic lymphoid tissue formation and organisation. A linkage study was performed with the Swedish Cancer Registry for lymphoma identification. The risk of developing NHL in GC-positive patients in comparison with GC-negative patients was evaluated using Kaplan-Meier statistics and log-rank test. Associations between GC-like structures and clinical and/or laboratory disease markers were also determined using χ(2) or Fisher's exact tests.

RESULTS:

At diagnosis, 25% of pSS patients had GC-like structures in their salivary glands. Seven of the 175 patients studied (14% GC+ and 0.8% GC-) developed NHL during 1855 patient-years at risk, with a median onset of 7 years following the initial diagnostic salivary gland biopsy. Six of the seven patients had GC-like structures at diagnosis; the remaining patient was GC negative at the time of diagnosis (p=0.001).

CONCLUSIONS:

The detection of GC-like structures by light microscopy in pSS diagnostic salivary biopsies is proposed as a highly predictive and easy-to-obtain marker for NHL development. This allows for risk stratification of patients and the possibility to initiate preventive B-cell-directed therapy.

Place, publisher, year, edition, pages
2011. Vol. 70, no 8, 1363-1368 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-156261DOI: 10.1136/ard.2010.144782ISI: 000292188100004OAI: oai:DiVA.org:uu-156261DiVA: diva2:431240
Available from: 2011-07-18 Created: 2011-07-18 Last updated: 2017-12-08
In thesis
1. Lymphoma studies in patients with Sjögren's syndrome
Open this publication in new window or tab >>Lymphoma studies in patients with Sjögren's syndrome
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patients with primary Sjögren’s syndrome (pSS) are at increased risk of developing malignant lymphoma. The studies in this thesis aim at broadening our understanding of the association between these two conditions.

Germinal centre (GC)-like structures were found in minor salivary gland biopsies taken at the time of pSS diagnosis in 25% of 175 studied patients. Lymphoma development was observed in 86% of the GC-positive pSS patients and 14% of the GC-negative patients. GC-like structures in salivary gland biopsies at pSS diagnosis might identify pSS patients at high risk for later lymphoma development.

We used the National Patient Register and the Cancer Register to identify pSS patients with lymphoid malignancy for the following studies. The lymphoma tissues were reviewed and classified according to the WHO classification.

In a study of 79 patients with available lymphoma tissues, we identified histopathological and clinical features compatible with IgG4-related disease (IgG4-RD) in one patient (1.3%). Histological features of IgG4-RD in lymphoma tissue in patients with an initial pSS diagnosis seem to be rare but, if present, may indicate underlying IgG4-RD.

We identified and compared pSS patients with (n=18/17%) and without (n=87) pre-existing lymphoma at pSS diagnosis and found similar pSS characteristics in both groups. Mucosa-associated lymphoid tissue (MALT) lymphoma in salivary glands was more common in patients with pre-existing lymphoma. The findings support the removal of pre-existing lymphoma as a general exclusion criterion for a pSS diagnosis in classification criteria. Further, the findings suggest an investigation for pSS in patients presenting with MALT lymphoma in salivary glands.

We compared the distribution of lymphoma subtypes with a general population reference. Both diffuse large B-cell lymphoma (DLBCL) (32%) and marginal zone lymphoma (MZL) (31%) were common, but only MZL (MALT lymphomas) occurred at an increased relative frequency compared to the general population.

Men constituted 15% of 105 pSS patients with lymphoma. Men had a shorter time between the pSS and lymphoma diagnoses and more often had lymphoma in the salivary glands compared with women. Increased awareness of signs of lymphoma in salivary glands already during the first years after pSS diagnosis is justified in men with pSS.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 94 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1331
Keyword
Sjögren's syndrome, primary Sjögren's syndrome, lymphoma, IgG4-related disease
National Category
Rheumatology and Autoimmunity
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-320220 (URN)978-91-554-9912-9 (ISBN)
Public defence
2017-06-07, Enghoffsalen, Ingång 50 bv, Akademiska sjukhuset, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2017-05-17 Created: 2017-04-18 Last updated: 2017-06-07

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Vasaitis, LilianBaecklund, Eva

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