Fat aspiration for amyloidosis screening of 2830 patients from 2013 to 2020: compelling sensitivity for AL and better sensitivity in females for all major subtypes

INTRODUCTION: Subcutaneous fat aspiration is a minimally-invasive screening tool for systemic amyloidosis (SA) with high variability in reported sensitivities. METHODS: Sensitivity and specificity were studied for consecutive Congo red-stained fat aspirates for amyloidosis screening performed between 2013 and 2020. For sensitivity analysis patients with symptomatic SA proven by either histopathology or scintigraphy and for specificity analysis patients with clinically certain exclusion of SA were chosen. Deposits were classified as substantial when >10% of analyzed tissue stained positive. RESULTS: 1320/2830 probes were positive of which 617 were graded as substantial.Overall sensitivity was 70.0% (1190/1701) according to gold-standard and specificity was 99.4% (613/617). Additionally, in 110/114 patients with clinically certain SA and in 16/398 probes from patients with nonspecific findings amyloid was detected. For subtypes, sensitivities were: systemic light-chain (AL) 90.1% (922/1023), transthyretin wild-type (ATTRwt) 18.8% (69/368), AA 72.3% (107/148) and transthyretin variant (ATTRv) amyloidosis 71% (63/89). Sensitivity overall and in AL, ATTRwt, AA and ATTRv was higher in females. Substantial deposits were more common in females overall and in AL. SUMMARY: Fat aspiration for symptomatic SA yielded excellent specificity. Sensitivity was very good in AL and fair in ATTRv and AA amyloidosis. Sensitivity was higher in females than in males.