Targeted tenosynovial biopsy during carpal tunnel release for detection of transthyretin amyloid deposits.

INTRODUCTION: Carpal tunnel syndrome is increasingly recognized as an early musculoskeletal manifestation of transthyretin amyloidosis. Tenosynovial biopsy during carpal tunnel release may detect transthyretin amyloid deposits, but the yield of a targeted strategy remains uncertain. METHODS: We conducted a single-centre comparative before-after study of 347 patients undergoing carpal tunnel release with tenosynovial biopsy. The non-targeted cohort was recruited between October 2021 and July 2023 and the targeted cohort between October 2023 and May 2026. Targeting was based on predefined clinical red flags. Histopathological assessment used Congo red staining with confirmation of transthyretin by immunohistochemistry. The primary outcome was histopathological positivity for transthyretin amyloid deposits. Two multivariable models assessed the targeting strategy and individual clinical factors. RESULTS: Overall, 82 of 347 biopsies were positive. Targeted biopsy was associated with a higher positivity rate than non-targeted biopsy, at 37% compared with 18%. Male sex and treated trigger finger were associated with increased positivity. Diabetes was associated with lower synovial transthyretin positivity, at 12% compared with 26%, and remained inversely associated after adjustment. CONCLUSION: Targeted tenosynovial biopsy during carpal tunnel release was associated with higher detection of transthyretin amyloid deposits than non-targeted biopsy. However, because the study compared two successive periods using a historical control group, the observed difference cannot be attributed to the targeting strategy alone. Diabetes was associated with lower synovial transthyretin positivity, suggesting that biopsy yield may differ between clinical subgroups. LEVEL OF EVIDENCE: IV.