Detection yield of surrogate tissue biopsies across amyloidosis classes: a large-scale analysis of 4,027 patients

Congo red (CR) staining of surrogate tissues, such as the abdominal fat pad (FP) or bone marrow (BM), provides a minimally invasive approach to diagnosing systemic amyloidosis. This study evaluated the diagnostic yield of surrogate tissue biopsies across amyloidosis classes. We retrospectively analyzed 4,027 patients with systemic amyloidosis (1968–2023) who underwent CR staining of FP aspirates (<i>n</i> = 3,873) and/or BM core biopsies (<i>n</i> = 2,598). Detection rates were compared by amyloidosis class and biopsy site. AL amyloidosis had the highest CR positivity rates (FP: 73%; BM: 53%), whereas ATTRwt amyloidosis had the lowest (FP: 22%; BM: 26%). CR positivity in BM was not exclusive to AL amyloidosis; 74 CR-positive BM biopsies were in non-AL cases. Among 2,213 patients with AL amyloidosis who underwent both FP and BM sampling, combined testing increased detection to 85% (40% positive in both; 32% FP-only; 13% BM-only). Higher CR positivity grades in FP aspirates correlated with shorter survival in AL amyloidosis but not in other amyloidosis classes. The diagnostic yield of CR-stained surrogate tissue biopsies varies by amyloidosis class and biopsy site. In AL amyloidosis, combining FP and BM sampling enhances detection, and FP CR positivity grade offers prognostic insight.