Immunohistological assessment of the synovial tissue in small joints in rheumatoid arthritis: validation of a minimally invasive ultrasound-guided synovial biopsy procedure

Abstract

The aim of the present study was to perform an immunohistological assessment of the synovial tissue from involved small joints in rheumatoid arthritis (RA) and to explore the reliability of a mini-invasive ultrasound (US)-guided technique of small joint synovial biopsy for the histopathological assessment. Synovial tissue collected during arthrotomic surgery of small joints in nine patients served as the gold standard for the validation of the histological assessment. Small hand-joint synovial biopsies from an additional nine patients with erosive RA were obtained by a mini-invasive US-guided procedure, performed percutaneously by the portal and rigid forceps technique. Using digital image analysis, the area fractions of synovial macrophages (CD68 cells), T cells (CD3 cells) and B cells (CD20 cells) were measured in all high-power fields of every sample at different cutting levels. The representative sample was defined as the minimal number of high-power fields whose mean area fraction would reflect the overall mean area fraction within a percentage mean difference of 10%. For each patient, a range of three to five large samples for surgical biopsies and a range of 8-12 samples for USguided biopsies were collected and analysed. In arthrotomic samples, the analysis of a randomly selected tissue area of 2.5 mm 2 was representative of the overall value for CD68, CD3 and CD20 cells. US-guided samples allowed histological evaluation in 100% of cases, with a mean valid area of 18.56 mm 2 (range 7.29-38.28 mm 2 ). The analysis of a cumulative area of 2.5 mm 2 from eight randomly selected sections (from different samples or from different cutting levels) allowed to reduce the percentage mean difference to less than 10% for CD68, CD3 and CD20 cells. In conclusion, US-guided synovial biopsy represents a reliable tool for the assessment of the histopathological features of RA patients with a mini-invasive approach.

Success Rate and Utility of Ultrasound-guided Synovial Biopsies in Clinical Practice

“…The success rates in retrieving synovial tissue described by other authors vary from 89% to 100% (23,25,(27)(28)(29). Although, the rate of success in our cohort was slightly lower, for which there are several potential reasons.…”

“…To our knowledge, five other studies, reporting their experience of US guided synovial biopsies, have been published to date. Two reported their experience using the first technique (27,28), one of them a technique using semi-automatic guillotine-type needle without co-axial needle (23) and two of them using the second technique outlined above (24,25).…”

Synovial Tissue Heterogeneity and Peripheral Blood Biomarkers

“…These procedures also can be safely performed in small joints, such as in the metacarpophalangeals [17,18], although tissue quantity (and occasional quality) in the latter case may limit more extensive analyses. Nonetheless and very positively, small-bore arthroscopy promises to yield adequate sampling even in quiescent joints [19], thus extending synovial tissue accessibility to preclinical [20•] and remission phases.…”

Use of Ultrasound‐Guided Small Joint Biopsy to Evaluate the Histopathologic Response to Rheumatoid Arthritis Therapy: Recommendations for Application to Clinical Trials

“…Synovial biopsy of small joints using ultrasound (US) guidance has been reported (8), and recently, a modification of this approach, using a Quick-Core biopsy needle (Cook Medical) under US guidance, was applied to small and large joint biopsy procedures in an early arthritis cohort (9). However, the performance of this technique in a clinical trial setting in RA patients undergoing serial biopsies of small joints following therapeutic intervention, when the degree of synovitis may be reduced dramatically, has not been established.…”