Varying levels of small microcalcifications and macrophages in ATTR and AL cardiac amyloidosis: implications for utilizing nuclear medicine studies to subtype amyloidosis

Background: Recently, there has been much interest in using nuclear medicine studies to noninvasively identify and subtype cardiac amyloidosis. In particular, modified bone scans using Tc-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (Tc-99m-DPD) and Tc-99m-pyrophosphate (Tc-99m-PYP) are being used to selectively identify patients with ATTR amyloidosis rather than AL amyloidosis. The morphologic basis underlying the selectivity of these imaging modalities for ATTR amyloidosis has been unclear. Methods: To determine if variations in microcalcifications and/or macrophages within ATTR and AL amyloidosis might be responsible for the selectivity for these imaging modalities, 8 endomyocardial biopsies of ATTR amyloidosis and 7 endomyocardial biopsies of AL amyloidosis were stained with von Kossa calcium stains and with immunohistochemistry for the macrophage marker CD68. Results: Compared with AL amyloidosis, there was a greater density of small microcalcifications in cases of ATTR amyloidosis (mean = 16.8 vs. 6.5 per 200 x field, P = .008). In contrast, there were fewer macrophages in ATTR amyloidosis compared with AL amyloidosis (mean = 2.5 vs. 11.7 per 200 x field, P = .0004). The density of microcalcifications within each group was not related to patient age, echocardiographic features of cardiac function, or serum levels of calcium and creatinine. Conclusions: These data suggest that microcalcifications but not macrophages likely underlie the selectivity of modified bone scans for ATTR amyloidosis and suggest that other pathologic entities containing microcalcifications might also result in positive scans with these imaging modalities. (C) 2016 Elsevier Inc. All rights reserved.