The prognostic value of routinely performed minor salivary gland assessments in primary Sjögren's syndrome

Risselada, Arne; Kruize, Aike A.; Goldschmeding, Roel; Lafeber, Floris P. J. G.; Bijlsma, J. W. J.; Roon, Joël A G van

doi:10.1136/annrheumdis-2013-204634

Cited by 131 publications

(94 citation statements)

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“…Moreover, it is particularly useful for those patients with glandular dysfunctions who do not show any autoantibody production [18]. Focus scoring is also essential for the prognosis of SS by providing information about different subsets of patients [19]. As a consequence, the diagnostic role of SG histopathology is widely accepted.…”

Section: Introductionmentioning

confidence: 99%

Adipose tissue is prominent in salivary glands of Sjögren’s syndrome patients and appears to influence the microenvironment in these organs

et al. 2016

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A minor salivary gland (SG) biopsy with focal lymphocytic sialadenitis and a focus score of ≥1 is today's widely accepted pathological finding confirming the SG component of Sjögren's syndrome (SS). Adipocytes can occupy a large percentage of the SG area although little is known about their significance in SS lesions. This study aimed to characterise adipose tissue infiltration in labial SG biopsies from 27 SS patients and 28 non-SS sicca controls. Biopsies were evaluated by one oral pathologist and assessed for focus score, acinar atrophy, fatty replacement and non-specific chronic inflammation. Moreover, to explore the SG microenvironment, immunohistochemical staining of paraffin-embedded SG tissue was performed using interleukin-6 (IL-6). The fatty replacement was evident in all SS patients possessing autoantibodies (Ro/SSA and/or La/SSB) as well as a positive SG biopsy (focus score ≥1). Additionally, 62% of SS patients having autoantibodies but a negative biopsy showed fatty infiltration (FI) while non-SS controls demonstrated fatty replacement in only 32% of the cases. Overall, the SS group (mean age 53.0 years) had a significantly higher incidence (p value 0.005) of FI than the non-SS controls (mean age 54.8 years). Interestingly, adipocytes were located in IL-6 rich areas, and IL-6 positive adipocytes were detected. As fat deposition seems to be more recurrent in SGs affected by SS, we propose the assessment of adipose tissue replacement as a helpful tool for diagnostic evaluation in SS. Detection of IL-6 positive adipocytes suggests their involvement in immune reactions. Still, functional studies are needed to investigate the SG microenvironment further.

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Section: Introductionmentioning

confidence: 99%

Adipose tissue is prominent in salivary glands of Sjögren’s syndrome patients and appears to influence the microenvironment in these organs

et al. 2016

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“…We would like to thank Dr Arnaud et al 1 for their comment on our article discussing the prognostic value of salivary gland assessments in primary Sjögren’s syndrome (pSS) 2…”

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confidence: 99%

Lymphocytic focus score as a prognostic tool

et al. 2015

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We would like to thank Dr Arnaud et al 1 for their comment on our article discussing the prognostic value of salivary gland assessments in primary Sjögren's syndrome ( pSS). 2 One of our findings was that having a lymphocytic focus score (LFS) ≥3 (number of foci/4 mm 2 ) at the time of diagnosis contributes significantly to the risk of lymphoma development during pSS disease course. We agree that the follow-up time after biopsy is important to take into account because differences observed could merely be a result of the time that patients have been followed. As displayed in our article, we therefore analysed the incidence rate of non-Hodgkin's lymphoma (NHL) per 1000 person-years and showed that the incidence rate was higher for patients with an LFS ≥3 than those with an LFS of either 1 or 2 (NHL incidence rate of 3.7 for LFS=1, 2.4 for LFS=2 and 12.8 for LFS ≥3, respectively, with a total of 1169 person-years at risk).As suggested, we have additionally performed Kaplan-Meier survival analysis and Cox's proportional hazard regression analysis. The Kaplan-Meier curve showed reduced survival for the patient group with an LFS ≥3 (Log-rank test: p=0.009). Using Cox's proportional hazard regression analysis, we observed that an LFS ≥3 was significantly associated with the development of NHL both in a univariate analysis (HR 6.2; 95% CI 1.3 to 29.3; p=0.021) and when adjusting for anti-SSA, anti-SSB, ≤40% immunoglobulin (Ig)A plasma cells and ≥25% IgM plasma cells in salivary gland specimens (HR 9.9; 95% CI 1.2 to 82.4; p=0.034).In addition, in the original manuscript, we had performed multivariable linear regression analysis to assess the association between LFS ≥3 and development of NHL. The results of multivariable logistic regression analysis, which is indeed more appropriate (variables in the equation: anti-SSA, anti-SSB, LFS ≥3, ≤40% IgA plasma cells and ≥25% IgM plasma cells in salivary gland specimens), are comparative to our previously reported findings and show independent and significant prediction for lymphoma development of LFS ≥3 (OR 14.72; 95% CI 1.6 to 136.4; p=0.018).Together, these results confirm our previous analyses that an LFS ≥3 might help to identify pSS patients with an increased risk for development of NHL.

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“…It is worth mentioning that, in recent years, also histological predictors of lymphoma have been identified. In this context, Risselada et al observed that high values of focus score, namely ≥3, are independent predictor of lymphoma development [56], while Theander et al reported that GC-like structures were more prevalent in patients who will later developed NHL versus those without subsequent NHL [57]. Taken that GC assessment is not included in routine histological assessment of MSGs at the time of pSS diagnosis, the focus score should be included among Bred flagst hat allow to identify a pSS patients at high risk of lymphoma.…”

Section: Rtx Treatment In Pss-associated B-cell Lymphomamentioning

confidence: 96%

Use of Rituximab in the Management of Sjögren’s Syndrome

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et al. 2015

Curr Treat Options in Rheum

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The prognostic value of routinely performed minor salivary gland assessments in primary Sjögren's syndrome

Abstract: Routine histopathological minor salivary gland assessment has important prognostic value. The LFS might help to identify patients with an increased risk for lymphoma.

Cited by 131 publications

References 13 publications

Adipose tissue is prominent in salivary glands of Sjögren’s syndrome patients and appears to influence the microenvironment in these organs

Adipose tissue is prominent in salivary glands of Sjögren’s syndrome patients and appears to influence the microenvironment in these organs

Lymphocytic focus score as a prognostic tool

Use of Rituximab in the Management of Sjögren’s Syndrome

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