title: Varying levels of small microcalcifications and macrophages in ATTR and AL cardiac amyloidosis: implications for utilizing nuclear medicine studies to subtype amyloidosis.
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.
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Miriam A
authors.initials: MA
authors.lastname: Stats
authors.affiliation: 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.
authors.forename: James R
authors.initials: JR
authors.lastname: Stone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D028227:Amyloid Neuropathies, Familial / Q000000981:diagnostic imaging* / Q000473:pathology; D000686:Amyloidosis / Q000000981:diagnostic imaging* / Q000473:pathology; D002114:Calcinosis / Q000000981:diagnostic imaging* / Q000473:pathology; D009202:Cardiomyopathies / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism; D000075363:Immunoglobulin Light-chain Amyloidosis; D008264:Macrophages / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009683:Nuclear Medicine / Q000379:methods; D019275:Radiopharmaceuticals; D016698:Technetium Tc 99m Pyrophosphate
chemical_list: D007147:Immunoglobulin Light Chains; D019275:Radiopharmaceuticals; D016698:Technetium Tc 99m Pyrophosphate
keywords: Amyloid; Amyloidosis; Bone scan; Macrophage; Microcalcification; Nuclear medicine; Pyrophosphate scan