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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