Evaluation of Skin Biopsy Techniques for the Diagnosis of Systemic Amyloidosis

Systemic amyloidosis is a multisystem disorder that requires histological confirmation of amyloid deposition in at least one organ for a definitive diagnosis. While biopsies of organs such as the myocardium provide high diagnostic accuracy, they are highly invasive and technically demanding. Thus, skin biopsies are frequently performed as a less invasive alternative. However, when skin biopsies fail to detect amyloid depositions, more invasive procedures-such as gastrointestinal or myocardial biopsies-are often required. Despite the clinical importance of improving diagnostic yield, few studies have systematically evaluated optimal skin biopsy techniques. Then, we conducted a retrospective observational study of 100 patients who underwent skin biopsies for suspected systemic amyloidosis at Kobe University Hospital between April 2014 and November 2024. In this study, two skin biopsy methods were analyzed: Punch biopsies from multiple random sites (1-5 sites) using Dermapunch ("punch (multiple-punch) biopsy"), and spindle-shaped biopsy of long axis approximately 10 mm or more ("incision (spindle-shaped) biopsy"). As a result, among 69 cases diagnosed as systemic amyloidosis based on amyloid detection in any organ, including the skin, 13 of 28 punch biopsies (46.4%) were positive, and 21 of 41 incision biopsies (51.2%) were positive. The difference in sensitivity was not statistically significant (p = 0.81), but incision biopsies showed a numerically higher sensitivity. Furthermore, fatty tissue was the most common amyloid deposition site, with a mean depth of 5.1 mm. In two cases, depositions were found at a depth of approximately 12 mm. In this study, no significant difference was observed in the diagnostic yield between the two biopsy methods. However, because amyloid depositions may occur deep within subcutaneous fat and incision biopsy enables deliberate and consistent sampling of this layer, it potentially improves diagnostic accuracy. We, therefore, recommend incision biopsy as the preferred method for diagnosing systemic amyloidosis.