The Role of Tissue Biopsy: Identification of the Amyloid Precursor and Beyond

Tissue biopsy study has significantly contributed to the diagnosis and to the knowledge of cardiac amyloidosis in the last decades. A multistep tissue analysis approach, using different techniques, from routine histology to histochemistry, immunohistochemistry, and more recently proteomic analyses, has allowed for the characterization of amyloidosis also in challenging or unknown cases of amyloidosis. The most common amyloidogenic proteins of cardiac amyloidosis are the immunoglobulin light chains and the transthyretin (TTR) protein, causing light chains (AL) and TTR (ATTR) cardiac amyloidosis, respectively. The presence of amyloid fibrils can be shown by Congo red staining on formalin-fixed and paraffin-embedded histological sections, under a polarized light microscope. The different prognosis and treatment of the AL and ATTR cardiac amyloidosis require in many cases the characterization of the amyloidogenic protein by immunohistochemistry and/or proteomic analyses. So far, tissue biopsy represents the gold standard for diagnosis and characterization of cardiac amyloidosis, although a non-biopsy diagnosis of ATTR can be achieved in patients with significant 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) scintigraphy uptake and concordant echocardiography or magnetic resonance features, in the absence of monoclonal gammopathy. The investigations on tissue biopsy are also providing new insights on the pathogenetic mechanisms of cardiac amyloidosis, and in the next future, they could offer new clues for the treatment of such a complex and heterogeneous disease.