IMMUNOCYTOCHEMICAL ANALYSIS OF FLEXOR TENOSYNOVIUM FROM PATIENTS WITH CARPAL TUNNEL SYNDROME

Participants: M. McDermott, M. R. Moalli, P. J. L. Jebson, D. S. Louis, R. Taylor, M. L. Greenfield

Keywords: CTS, upper extremity

Introduction

Carpal tunnel release has become one of the most frequently performed operations on adults in the United States with over 200,000 surgical procedures performed per year.1 Despite the common occurrence of carpal tunnel syndrome (CTS), the pathophysiology of the underlying process is not completely understood. The tenosynovium is frequently found to be thickened at the time of surgery, but the increased tissue mass is not due to an inflammatory response. The cellular processes that regulate the formation of this hypertrophied tissue are not well characterized. The purpose of this study was to evaluate the flexor tenosynovium for biologic factors that have been demonstrated to be involved in the repair of other musculoskeletal soft tissues. Characterization of this tissue may provide information on the etiopathogenesis of carpal tunnel syndrome, as well as new direction for the design of therapeutic strategies for the treatment of this prevalent disorder.

Materials and Methods

Flexor tenosynovium was biopsied (with Institutional Review Board approval) from 28 patients with CTS and 6 patients without CTS. Specimens were prepared for paraffin embedding and 5 m sections were evaluated by routine hematoxylin and eosin for histologic characterization. Sections were also stained with saffranin O/fast green for the detection of proteoglycans. Finally, immunocytochemical analysis was performed using antibodies for Types I and II collagen, and TGF-b .

Results

CTS synovial tissue was characterized by fibrous metaplasia with varying degrees of angiogenesis, and vascular hypertrophy with intimal thickening and thrombosis. There was no evidence of inflammatory cells. Non-CTS specimens contained loose irregular, non-fibrous, connective tissue, sparse small vessels and diffuse spindle shaped fibroblasts. Immunolocalization of TGF-b was positive in 16/17 CTS specimens. Type II collagen was present in 7/7 CTS specimens, while proteoglycans were never detected. Type I collagen immunostaining was localized within a few small blood vessels in 1/7 CTS specimens.

Discussion

Significant differences were found in histologic appearance between normal tenosynovium and tenosynovium from patients with CTS. We have demonstrated that the histologic changes in CTS patients corresponded to changes in the amount of tenosynovial immunoreactivity for TGF-ß and Type II collagen. There were no apparent changes in Type I collagen or proteoglycans between the two groups. In vitro studies have shown that intermittently loaded connective tissue cells are sensitive to changes in cellular shape and hydrostatic pressure. The literature also demonstrates that stretching cells enhances the production of fibrous and cartilaginous matrices. Based on the results of this study it is interesting to speculate that TGF-b may play an important role in the development of the hypertrophied CTS tissue. Interestingly, Type II collagen may represent an adaptive response to increased mechanical stresses. Elucidation of the mechanisms regulating TGF-b generation and Type II collagen production may lead to less invasive treatments of CTS.

References

¹Lavine, DW: JBJS, 75-A, 1585-15.