The Crucial Questions on Synovial Biopsy: When, Why, Who, What, Where, and How?

Abstract

In the majority of joint diseases, changes in the organization of the synovial architecture appear early. Synovial tissue analysis might provide useful information for the diagnosis, especially in atypical and rare joint disorders, and might have a value in case of undifferentiated inflammatory arthritis, by improving disease classification. After patient selection, it is crucial to address the dialogue between the clinician and the pathologist for adequately handling the sample, allowing identifying histological patterns depending on the clinical suspicion. Moreover, synovial tissue analysis gives insight into disease progression helping patient stratification, by working as an actionable and mechanistic biomarker. Finally, it contributes to an understanding of joint disease pathogenesis holding promise for identifying new synovial biomarkers and developing new therapeutic strategies. All of the indications mentioned above are not so far from being investigated in everyday clinical practice in tertiary referral hospitals, thanks to the great feasibility and safety of old and more recent techniques such as ultrasound-guided needle biopsy and needle arthroscopy. Thus, even in rheumatology clinical practice, pathobiology might be a key component in the management and treatment decision-making process. This review aims to examine some essential and crucial points regarding why, when, where, and how to perform a synovial biopsy in clinical practice and research settings and what information you might expect after a proper patient selection.

MRI Findings in Axial Psoriatic Spondylarthritis

“…Some studies [ 99 , 102 , 103 ] have shown that PsA has a similar synovial phenotype with AS and undifferentiated SpA, unlike RA; in addition, further studies have shown that PsA has a histological particularity involving the synovial vascularity pattern, but newer studies have observed no histological statistical significant differences between uSpA and PsA [ 101 , 103 ]. The synovial biopsy may be an additional tool in the diagnosis of atypical patients and may guide the treatment response follow-up, improve the treatment decision-making, and accelerate decisions in phase I–II clinical trials [ 104 ], although further studies are required.…”

Inside the Joint of Inflammatory Arthritis Patients: Handling and Processing of Synovial Tissue Biopsies for High Throughput Analysis

“…To date, patient' stratification and disease pathotype stratification, as well as response to therapy has been mainly obtained with histological analysis of the synovium. Although RA and PsA have many common clinical manifestations, we and others have demonstrated significant differences in the vascular pattern, immune-cell infiltrates and the invasive lining-layer at the site of inflammation (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), which may be associated with the distinct pattern of joint involvement and bone erosion observed between RA and PsA (12)(13)(14)(15)(16). Angiogenesis is dysregulated in both conditions, with the formation of elongated, torturous blood vessels, a distinct phenotype in the PsA joint (17).…”

“…Importantly, recent studies highlight that the burden associated with RA and PsA is underreported and is significantly higher than previously calculated while incidence rates are increasing globally ( 4 , 5 ). Current advances in clinical practice and the increasing use of ultrasonographic and arthroscopic technologies and patient partnerships have led to increased availability of synovial biopsies ( 6 , 7 ). This has fuelled recent advances in understanding the underlying immunological mechanisms involved in synovial inflammation and the development of targeted biologic therapies which have significantly improved outcomes for patients with IA.…”

Cell-Specific Gene Networks and Drivers in Rheumatoid Arthritis Synovial Tissues

“…Each sample contained the gene expression profile of 25,000 genes. As healthy biopsies are rare and difficult to obtain [27], we compared RA synovial biopsies to both OA and healthy samples We first used UMAP [28] to visualize the samples in two dimensions, and observed significant distributional differences between the gene expression profiles of RA biopsies and controls, the latter comprising OA and healthy samples (Figure 1A). A DEG analysis revealed that more than half of the genes (∼15k) were significantly differentially expressed (p < 0.05; Student's t-test with Benjamini-Hochberg correction [29]).…”