Are the Pathologic Features of Enthesopathy, Tendinopathy, and Labral and Articular Disc Disease Related to Mucoid Degeneration? A Systematic Review
Authors: Bruni David F. , Pierson S. Ryan , Sarwar Faiza , Ring David , Ramtin Sina 
Published: December 2022

Abstract

Background
Tendinopathy, enthesopathy, labral degeneration, and pathologic conditions of the articular disc (knee meniscus and ulnocarpal) are sometimes described in terms of inflammation or damage, while the histopathologic findings are often consistent with mucoid degeneration. A systematic review of the histopathology of these structures at diverse locations might reconceptualize these diseases as expected aspects of human aging. The potential benefits of this evolution might include healthier patient and clinician mindsets as well as a reduced likelihood of overdiagnosis and overtreatment resulting from greater awareness of base rates of pathology.

Question/purpose
In this systematic review of studies of surgical specimens, we asked: Are there are any differences in the histopathologic findings of structural soft tissue conditions (mucoid degeneration, inflammation, and vascularity) by anatomic site (foot, elbow, or knee) or structure (tendon body, muscle or tendon origin or insertion [enthesis], labrum, or articular disc)?

Methods
Studies between 1980 and 2021 investigating the histopathologic findings of specimens from surgery for trigger digit, de Quervain tendinopathy, plantar fasciitis, lateral and medial elbow enthesopathy, rotator cuff tendinopathy, posterior tibial tendinopathy, patellar tendinopathy, Achilles tendinopathy, or disease of the hip labrum, ulnocarpal articular disc, or knee meniscus were searched for in the PubMed, EMBASE, and CINAHL databases. Inclusion criteria were the prespecified anatomic location or structure being analyzed histologically and any findings described with respect to inflammation, vascularity, or mucoid degeneration. Studies were excluded if they were nonhuman studies or review articles. Search terms included “anatomy,” “pathology,” and “histopathology.” These terms were coupled with anatomic structures or disorders and included “trigger finger,” “de Quervain,” “fasciitis, plantar,” “tennis elbow,” “rotator cuff tendinopathy,” “elbow tendinopathy,” “patellar tendonitis,” “posterior tibial tendon,” and “triangular fibrocartilage.” This resulted in 3196 studies. After applying the inclusion criteria, 559 articles were then assessed for eligibility according to our exclusion criteria, with 52 eventually included. We recorded whether the study identified the following histopathologic findings: inflammatory cells or molecular markers, greater than expected vascularity (categorized as quantitative count, with or without controls; molecular markers; or qualitative judgments), and features of mucoid degeneration (disorganized collagen, increased extracellular matrix, or chondroid metaplasia). In the absence of methods for systematically evaluating the pathophysiology of structural (collagenous) soft tissue structures and rating histopathologic study quality, all studies that interpreted histopathology results were included. The original authors’ judgment regarding the presence or absence of inflammation, greater than expected vascularity, and elements of mucoid degeneration was recorded along with the type of data used to reach that conclusion.

Results
Regarding differences in the histopathology of surgical specimens of structural soft tissue conditions by anatomic site, there were no differences in inflammation or mucoid degeneration, and the knee meniscus was less often described as having greater than normal vascularity. There were no differences by anatomic structure. Overall, 20% (10 of 51) of the studies that investigated for inflammation reported it (nine inflammatory cells and one inflammatory marker). Eighty-three percent (43 of 52) interpreted increased vascularity: 40% (17 of 43) using quantitative methods (14 with controls and three without) and 60% (26 of 43) using imprecise criteria. Additionally, 100% (all 52 studies) identified at least one element of mucoid degeneration: 69% (36 of 52) reported an increased extracellular matrix, 71% (37 of 52) reported disorganized collagen, and 33% (17 of 52) reported chondroid metaplasia.

Conclusion
Our systematic review of the histopathology of diseases of soft tissue structures (enthesopathy, tendinopathy, and labral and articular disc) identified consistent mucoid degeneration, minimal inflammation, and imprecise assessment of relative vascularity; these findings were consistent across anatomic sites and structures, supporting a reconceptualization of these diseases as related to aging (senescence or degeneration) rather than injury or activity.

Clinical Relevance
This reconceptualization supports accommodative mindsets known to be associated with greater comfort and capability. In addition, awareness of the notable base rates of structural soft tissue changes as people age might reduce overdiagnosis and overtreatment of incidental, benign, or inconsequential signal changes and pathophysiology.