Miriam A Stats1, James R Stone2. 1. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 2. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: jrstone@partners.org.
Abstract
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 (99m)Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) and (99m)Tc-pyrophosphate ((99m)Tc-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× field, P=.008). In contrast, there were fewer macrophages in ATTR amyloidosis compared with AL amyloidosis (mean=2.5 vs. 11.7 per 200× 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.
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 (99m)Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) and (99m)Tc-pyrophosphate ((99m)Tc-PYP) are being used to selectively identify patients with ATTRamyloidosis rather than AL amyloidosis. The morphologic basis underlying the selectivity of these imaging modalities for ATTRamyloidosis 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 ATTRamyloidosis 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 ATTRamyloidosis (mean=16.8 vs. 6.5 per 200× field, P=.008). In contrast, there were fewer macrophages in ATTRamyloidosis compared with AL amyloidosis (mean=2.5 vs. 11.7 per 200× 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 ATTRamyloidosis and suggest that other pathologic entities containing microcalcifications might also result in positive scans with these imaging modalities.
Authors: Frederick L Ruberg; Martha Grogan; Mazen Hanna; Jeffery W Kelly; Mathew S Maurer Journal: J Am Coll Cardiol Date: 2019-06-11 Impact factor: 24.094
Authors: Riemer H J A Slart; Andor W J M Glaudemans; Walter Noordzij; Johan Bijzet; Bouke P C Hazenberg; Hans L A Nienhuis Journal: Eur J Nucl Med Mol Imaging Date: 2019-04-23 Impact factor: 9.236