Electron and immuno-electron microscopy of abdominal fat identifies and characterizes amyloid fibrils in suspected cardiac amyloidosis

We evaluated the role of electron microscopy and immuno-electron microscopy studies on abdominal fat fine-needle biopsy samples in diagnosis and characterization of cardiac amyloidosis. The series consists of 15 patients with echocardiographic evidence of "restrictive cardiomyopathy" suspected to be due to amyloidosis. Patients underwent: clinical examination, electrocardiography, 2-D and Doppler echocardiography, immunofixation of serum and urine for detection of monoclonal immunoglobulins, and abdominal fat biopsies that were investigated with polarized light (Congo red), electron and immuno-electron microscopy using specific antibodies to κ and λ light chains, apolipoprotein A1, serum amyloid A (SAA), and transthyretin (TTR). Ultrastructural study of abdominal fat samples identified amyloid deposits in 15/15 cases. Immuno-electron microscopy specifically stained amyloid fibrils with antibodies anti-λ (n = 8), -κ (n = 2), -apolipoprotein A1 (n = 2) and -TTR (n = 3). Immuno-electron microscopy revealed TTR immuno-labelling in 2 patients with accidental monoclonal components, and a λ reaction in 1 patient without monoclonal components. TTR and apolipoprotein A1 positive cases carried missense mutations in the corresponding genes. Our results demonstrate that amyloid deposits are present in the abdominal fat of patients suspected to have cardiac amyloidosis and that immuno-electron microscopy was able to characterize the amyloid protein in all cases.