Standardisation of labial salivary gland histopathology in clinical trials in primary Sjögren's syndrome

Abstract

Labial salivary gland (LSG) biopsy is used in the classification of primary Sjögren's syndrome (PSS) and in patient stratification in clinical trials. It may also function as a biomarker. The acquisition of tissue and histological interpretation is variable and needs to be standardised for use in clinical trials. A modified European League Against Rheumatism consensus guideline development strategy was used. The steering committee of the ad hoc working group identified key outstanding points of variability in LSG acquisition and analysis. A 2-day workshop was held to develop consensus where possible and identify points where further discussion/data was needed. These points were reviewed by a subgroup of experts on PSS histopathology and then circulated via an online survey to 50 stakeholder experts consisting of rheumatologists, histopathologists and oral medicine specialists, to assess level of agreement (0–10 scale) and comments. Criteria for agreement were a mean score ≥6/10 and 75% of respondents scoring ≥6/10. Thirty-nine (78%) experts responded and 16 points met criteria for agreement. These points are focused on tissue requirements, identification of the characteristic focal lymphocytic sialadenitis, calculation of the focus score, identification of germinal centres, assessment of the area of leucocyte infiltration, reporting standards and use of prestudy samples for clinical trials. We provide standardised consensus guidance for the use of labial salivary gland histopathology in the classification of PSS and in clinical trials and identify areas where further research is required to achieve evidence-based consensus.

Germinal centres in diagnostic labial gland biopsies of patients with primary Sjögren’s syndrome are not predictive for parotid MALT lymphoma development

“…Besides FS, we also measured the extent of glandular inflammation as proposed 2. This was assessed using CD45 staining.…”

“…Histopathologically, this inflammatory process is characterised by a periductal lymphoid infiltrate in the glandular parenchyma 2. In roughly one quarter of the patients with pSS, germinal centres (GCs) can be found within these lymphoid infiltrates reflecting the B-cell hyperactivity that characterises the disease 3 4.…”

The challenge to interpret conflicting results and the need of a univocal definition for germinal centres in primary Sjögren’s syndrome

“…The protocol provided by the Sjögren’s International Clinical Collaborative Alliance is widely used7; however, it does not provide specific guidance regarding the GCs. On the contrary, in the recent standardisation of labial salivary gland histopathology in clinical trials in pSS, there was strong agreement that the presence of GC-like structures should be reported in routine practice 8. H&E is considered sufficient to allow accurate detection of fully formed GC by experienced pathologists, in particular in secondary lymphoid organs with a well-distinguished light and dark zone segregation.…”

Standardisation of labial salivary gland biopsies in Sjogren's syndrome: importance for the practicing rheumatologist

“…Fisher et al 1 present an expert consensus for ‘standardisation of LSG’ histopathology in clinical trials in primary SS in this issue.…”

“…The consensus for important points in the evaluation of LSB is summarised in table 1 in the article by Fisher et al 1. It presents some of the relevant points for the practicing rheumatologist.…”