title: Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the development of malignant lymphoma in primary Sjögren's syndrome.
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 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.
authors.affiliation: Department of Rheumatology, Skåne University Hospital Malmö, Lund University, Lund, Sweden.
authors.forename: Elke
authors.initials: E
authors.lastname: Theander
authors.forename: Lilian
authors.initials: L
authors.lastname: Vasaitis
authors.forename: Eva
authors.initials: E
authors.lastname: Baecklund
authors.forename: Gunnel
authors.initials: G
authors.lastname: Nordmark
authors.forename: Gunnar
authors.initials: G
authors.lastname: Warfvinge
authors.forename: Rolf
authors.initials: R
authors.lastname: Liedholm
authors.forename: Karl
authors.initials: K
authors.lastname: Brokstad
authors.forename: Roland
authors.initials: R
authors.lastname: Jonsson
authors.forename: Malin V
authors.initials: MV
authors.lastname: Jonsson
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D004812:Epidemiologic Methods; D005260:Female; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D008046:Lip / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012470:Salivary Glands, Minor / Q000473:pathology*; D012793:Sialadenitis / Q000150:complications / Q000453:epidemiology / Q000473:pathology; D012859:Sjogren's Syndrome / Q000150:complications / Q000453:epidemiology / Q000473:pathology*; D013548:Sweden / Q000453:epidemiology