title: Correlation of histomorphological pattern of cardiac amyloid deposition with amyloid type: a histological and proteomic analysis of 108 cases.
abstract: OBJECTIVE
  Prognostication and treatment selection for cardiac amyloidosis requires accurate amyloid typing. The aim of this study was to investigate the utility of histomorphology for predicting type.
  
  
  RESULTS
  Autopsy cases with cardiac amyloidosis (1998-2010) were typed by the use of mass spectrometry-based proteomics. Deposition patterns were correlated with amyloid type. Among 108 decedents (mean age 75 years; 69% men), 107 had a single type, including transthyretin (ATTR) (60 cases), amyloid light chain (AL) (32 λ; 12 κ), amyloid A (AA) (two), and apolipoprotein AIV (AApoAIV) (one). Interstitial deposition was more extensive in AL amyloidosis cases than in ATTR cases [odds ratio (OR) 6.8, P = 0.0004]. Histomorphological patterns of interstitial deposition were mixed in 61% of AL amyloidosis cases and in 61% of ATTR cases, but diffuse pericellular deposits favoured AL amyloidosis (OR 10.7, P = 0.0001), nodular deposits favoured ATTR (OR 3.1, P = 0.0229), and discrete pericellular deposits tended to partially favour ATTR (OR 1.7, P = 0.1970). Arterial and venous deposits each favoured AL amyloidosis (OR ranging from 9.3 to 192.0, P-value ranging from 0.0022 to <0.0001), and were severe in AL amyloidosis. Endocardial deposits favoured AL amyloidosis (OR 46.3, P < 0.0001) and were also more severe in AL amyloidosis.
  
  
  CONCLUSIONS
  The extent and distribution of cardiac amyloidosis strongly correlate with amyloid type, suggesting fundamental differences in the pathobiology of deposition. The tendency for mixed patterns to occur limits the practicality and accuracy of using histopathology for amyloid typing.
authors.affiliation: Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA.|Department of Pathology, University of Arizona, Tucson, AZ, USA.
authors.forename: Brandon T
authors.initials: BT
authors.lastname: Larsen
authors.affiliation: Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA.|Division of Hematopathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Oana M
authors.initials: OM
authors.lastname: Mereuta
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Surendra
authors.initials: S
authors.lastname: Dasari
authors.affiliation: Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Ahmed U
authors.initials: AU
authors.lastname: Fayyaz
authors.affiliation: Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Theis
authors.affiliation: Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Vrana
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Grogan
authors.affiliation: Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA.|Division of Hematopathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.affiliation: Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA.|Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Edwards
authors.affiliation: Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kurtin
authors.affiliation: Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA.|Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Maleszewski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology; D001344:Autopsy; D002853:Chromatography, Liquid; D015331:Cohort Studies; D005260:Female; D006331:Heart Diseases / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008910:Minnesota; D040901:Proteomics; D053719:Tandem Mass Spectrometry
chemical_list: D000682:Amyloid
keywords: AL amyloid; ATTR amyloid; amyloid; amyloid typing; cardiac amyloidosis; histomorphology; mass spectrometry; proteomics