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Extended report
Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the development of malignant lymphoma in primary Sjögren's syndrome
  1. Elke Theander1,
  2. Lilian Vasaitis2,
  3. Eva Baecklund2,
  4. Gunnel Nordmark2,
  5. Gunnar Warfvinge3,
  6. Rolf Liedholm4,
  7. Karl Brokstad5,
  8. Roland Jonsson5,6,
  9. Malin V Jonsson5,7
  1. 1Department of Rheumatology, Skåne University Hospital Malmö, Lund University, Lund, Sweden
  2. 2Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden
  3. 3Department of Oral Pathology, Malmö University, Malmö, Sweden
  4. 4Department of Oral and Maxillofacial Surgery, Skåne University Hospital Malmö, Sweden
  5. 5Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway
  6. 6Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
  7. 7Institute of Medicine – Section for Rheumatology, University of Bergen, Bergen, Norway
  1. Correspondence to Professor Roland Jonsson, Broegelmann Research Laboratory, The Gade Institute, University of Bergen, N-5021 Bergen, Norway; roland.jonsson{at}gades.uib.no

Abstract

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 χ2 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.

This paper is freely available online under the BMJ Journals unlocked scheme, see http://ard.bmj.com/info/unlocked.dtl

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Footnotes

  • See editorial, p 1351

  • Funding This study was supported by the Swedish Rheumatism Association (ET), the Strategic Research Program at Helse Bergen, the Western Norway Regional Health Authority and the Broegelmann Foundation (RJ, MVJ, KB), Anna-Greta Crafoord Foundation (ET), a postdoctoral grant from Astrid Karlsson Foundation (GN), Malmö University Hospital Cancer Research Foundation (ET).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the local ethics committees at the universities of Lund, Uppsala and Bergen.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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