[Early Detection of Systemic Amyloidosis through Routine Histological Examination in Risk Patients Undergoing Carpal...

Carpal tunnel syndrome (CTS) may represent an early manifestation of systemic amyloidosis. Musculoskeletal manifestations such as CTS, trigger finger, or Dupuytren's disease may precede cardiac or neurological symptoms by many years, thereby opening a potentially relevant diagnostic window.We conducted a retrospective-prospective analysis of all carpal tunnel release procedures performed at our center between 2013 and 2025. For the period from 2013 to 2023, demographic data and information on tissue excision and histological examination were collected. For 2024, an additional retrospective histological re-examination of available specimens was performed using Congo red staining and polarization microscopy. Beginning in May 2025, biopsies from trigger finger release and partial aponeurectomy for Dupuytren's disease were also prospectively examined. In addition, a narrative literature review on the clinical relevance of musculoskeletal manifestations in amyloidosis was conducted.Among 990 carpal tunnel releases, tissue samples were obtained in 32.4% (n=321), and 25.2% (n=81) were histologically examined. Amyloid deposits were detected in 18.8% (n=15) of the samples. The median age of amyloid-positive patients was 82 years; men were more frequently affected (73%; OR 4.6; p=0.001). Musculoskeletal red-flag conditions were strongly associated with amyloid detection (RR 6.0; p<0.001). Cardiac comorbidities were present in 37.5% of amyloid-positive patients, including two with confirmed cardiac amyloidosis. Five patients showed neither cardiac nor neurological symptoms. In biopsies obtained during trigger finger release (since May 2025), amyloid deposits were identified in 15.4%, while no deposits were found in partial aponeurectomies for Dupuytren's disease.Our results support the observation that amyloid deposits can be detected during hand surgery procedures. Targeted histopathological examination of synovial tissue samples obtained during carpal tunnel or A1 pulley release procedures may serve as a valuable tool for the early detection of systemic amyloidosis. Given the high number of undiagnosed cases and the prognostic relevance, the integration of a risk-adapted biopsy strategy into existing guidelines should be considered.