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Table 1 Final set of items for both clinical practice and translational research

From: Standardisation of synovial biopsy analyses in rheumatic diseases: a consensus of the EULAR Synovitis and OMERACT Synovial Tissue Biopsy Groups

Clinical practice Translational research
1. Biopsy sampling
 - A minimum of four synovial biopsies needs to be retrieved in small joints.
 - Biopsies shall be retrieved in different areas of the joint, if possible.
 - If it is clinically relevant, bacteriological, fungal and mycobacteriological assessment should be performed.
 - Polymerase chain reaction analysis for RNA 16S should be performed if clinically relevant, especially if empiric antibiotic course has been started.
 - If it is clinically relevant, polymerase chain reaction analysis for Lyme and Whipple diseases should be performed.
2. Biopsy processing
 - The biopsies should spend 24 h in formalin 4%.
 - At least two biopsies should be formalin-fixed and paraffin-embedded.
3. Histological criteria
 - Synovial biopsy surface should be more than 2.5 mm2.
 - A lining layer should be seen.
 - Morphology of the synovial tissue should be preserved.
4. Staining and immunohistochemistry (IHC)
 - H&E staining should always be performed.
 - CD68 staining should be performed.
 - In particular clinically relevant cases, additional staining should be performed (CD3, CD20, CD138, CD31 or FVIII).
 - If performed, IHC results can be given using a semi-quantitative score.
5. Biopsies interpretation and pathologist’s report
 - A synovitis score should be performed, analysing: lining layer hyperplasia, inflammatory infiltrate and resident cell activation (Krenn, other).
 - Synovial pathotype should be described.
 - Presence or absence of lymphoid follicles within the membrane should be described.
 - Analysis can be semi-quantitative or quantitative depending on the question.
 - If a semi-quantitative or quantitative analysis is performed for multiple biopsies, an average score should be calculated and given for the analysis of inflammation and vascularisation.
 - The pathologist should mention the presence of granulomas
1. Biopsy sampling
 - A minimum of six synovial biopsies needs to be retrieved in large joints.
 - A minimum of four synovial biopsies needs to be retrieved in small joints
 - Biopsies shall be retrieved in different areas of the joint, if possible.
2. Biopsy processing
 - The biopsies should spend 24 h in formalin 4%*.
3. Histological criteria
 - Synovial biopsy surface should be more than 2.5 mm2.
 - A lining layer should be seen.
 - Morphology of the synovial tissue should be preserved.
4. Staining and IHC
 - H&E staining should always be performed.
 - CD68 staining should be performed.
 - CD3, CD19 or CD20 staining should be performed.
 - Additional CD 31 or FVIII, CD4, CD8, CD138 staining might be performed depending on the question.
5. Biopsies interpretation and Pathologist’s report
 - A synovitis score should be performed, analysing: lining layer hyperplasia, inflammatory infiltrate and resident cell activation (Krenn, other).
 - Lining layer hyperplasia should be scored.
 - Synovial pathotype should be described.
 - Presence or absence of lymphoid follicles within the membrane should be described.
 - Analysis can be semi-quantitative or quantitative depending on the question.
 - If a semi-quantitative or quantitative analysis is performed for a single biopsy: at least three areas of the biopsy should be assessed.
6. RNA analysis
 - Biopsies of one patient can be pooled for RNA extraction if needed.
  1. *This item refers to those biopsies where a decision has been made to process in formalin
  2. CD cluster of differentiation, FVIII factor VIII, H&E haematoxylin and eosin, IHC immunohistochemistry, RNA ribonucleic acid