Synovial Tissue Biopsy Collection by Rheumatologists: Ready for Clinical Implementation?

Abstract

Synovial tissue from arthritis patients is increasingly used for both basic pathophysiological and clinical translational research. This development has been spurred by the development of biotechnological techniques for analysis of complex tissues and the validation of ultrasound guided biopsies for easier tissue sampling. This increasing use of synovial tissue raises questions on standardization of methodologies for tissue processing and cellular & molecular analyses. Furthermore, it raises the question if synovial tissue biopsy analysis may be more widely implemented in clinical practice, what are the methodological hurdles for implementation and what are the lessons that can be learned from previous experience. This will be the focus of this review.

Arthroscopic Guided Synovial Biopsies

“…In addition to this challenge, international guidelines standardizing AGSB as performed by rheumatologists, are scarce ( 22 ). As noted by Smits et al, it is certain that ongoing performance of the procedure is important in maintaining skills, which can be appraised by examining biopsy yield and quality, as well as safety record, but it is not known how many supervised procedures are required to attain competency, and how frequently procedures should be performed to maintain this competency, and these factors might be operator dependent ( 23 ).…”

Ultrasound-Guided Synovial Biopsy: A Review

“…Synovial biopsies are conducted for clinical reasons or research purposes (6,7). In the clinical setting, formal indication for synovial biopsy occurs in cases of monoarthritis for which all other auxiliary diagnostic tests, including synovial fluid examination, are insufficient for diagnosis.…”

“…Compared with arthroscopic biopsy, USGSB is less invasive and can be conducted in both large and small joints (6). Arthroscopic biopsy allows direct visualization of synovial membranes but is more costly, is performed in only a few specialized centers, requires two operators and a dedicated environment (an operating theater or equivalent), and is not viable for small joints (1,2,13,14).…”

“…Other authors have recommended six as the minimum number of samples to collect for immunohistochemistry, to reduce T cell variability; however, the minimum number of samples for other cell types is less wellestablished. For macrophages, it depends on the goals pursued by the research (6). Other measures of synovial tissue quality include the number or percentage of synovial fragments and gradable synovial fragments, the total area of gradable synovial tissue, the area of gradable tissue by biopsy sample, and the RNA integrity number (RIN) (2); RIN ranges from 1 to 10, where samples from synovial tissue with values > 3 are considered adequate for subsequent transcriptomic analysis (2), molecular analysis, gene expression profiling, or gene sequencing methods (e.g., next-generation sequencing) (5).…”

“…Published data show that USGSB facilitates the collection of synovial samples of sufficient quality in 82-96% of biopsies, compared with 48-85% of blind needle biopsies (4-6, 32, 37, [50][51][52]. Results are also influenced by operator expertise, joint size and type, and synovitis grade, as determined by grayscale ultrasound (6). In our department, of a series of 64 NB performed in all kinds of joints, synovial bursae, and tendon sheaths, 81% were done within clinical practice to investigate a possible infection, or to help to clarify a diagnosis, and 19% in the context of research activities (37).…”