Skip to main content
Top
Published in: Virchows Archiv 5/2010

01-05-2010 | Original Article

Amyloid in endomyocardial biopsies

Authors: Barbara Kieninger, Magdalena Eriksson, Reinhard Kandolf, Philipp A. Schnabel, Stefan Schönland, Arnt V. Kristen, Ute Hegenbart, Peter Lohse, Christoph Röcken

Published in: Virchows Archiv | Issue 5/2010

Login to get access

Abstract

The prognosis of cardiac amyloidosis depends on the nature and origin of the amyloid protein deposited. However, little is known about the prevalence and origin of amyloid in heart muscle biopsies. We therefore examined retrospectively the distribution and origin of amyloid in a consecutive series of endomyocardial biopsies. Endomyocardial biopsies with verified presence of amyloid from 101 patients were included. Amyloid was classified immunohistochemically in each of them. Our collective comprised 63 men and 38 women, with a mean age of 66 years (range 37–85 years). Cardiac amyloidosis was the most common of the AL (54 patients) or ATTR type (42 patients). In five individuals, amyloid remained unclassified. AL amyloidosis was subdivided into ALλ (45 patients) and ALκ amyloid (nine patients). AA amyloid was not found in any individual. The amount of amyloid was higher in AL than in ATTR amyloidosis. Genomic DNA was extracted and examined by DNA sequencing in 19 patients with ATTR amyloidosis. Five (26%) individuals carried TTR mutations (p.Val20Ile, p.Val30Met (twice), p.Asp39Val and p.Glu54Asp) and were classified as suffering from hereditary ATTR amyloidosis. Amyloid in endomyocardial biopsies is most commonly of immunoglobulin light chain origin, followed by non-hereditary and hereditary-type ATTR amyloid.
Literature
1.
2.
go back to reference Picken MM (2007) New insights into systemic amyloidosis: the importance of diagnosis of specific type. Curr Opin Nephrol Hypertens 16(3):196–203CrossRefPubMed Picken MM (2007) New insights into systemic amyloidosis: the importance of diagnosis of specific type. Curr Opin Nephrol Hypertens 16(3):196–203CrossRefPubMed
3.
go back to reference Hoyer C, Angermann CE, Knop S et al (2008) Cardiac amyloidosis. Med Klin (Munich) 103(3):153–160CrossRef Hoyer C, Angermann CE, Knop S et al (2008) Cardiac amyloidosis. Med Klin (Munich) 103(3):153–160CrossRef
5.
go back to reference Eshaghian S, Kaul S, Shah PK (2007) Cardiac amyloidosis: new insights into diagnosis and management. Rev Cardiovasc Med 8(4):189–199PubMed Eshaghian S, Kaul S, Shah PK (2007) Cardiac amyloidosis: new insights into diagnosis and management. Rev Cardiovasc Med 8(4):189–199PubMed
6.
go back to reference Hassan W, Al-Sergani H, Mourad W et al (2005) Amyloid heart disease. New frontiers and insights in pathophysiology, diagnosis, and management. Tex Heart Inst J 32(2):178–184PubMed Hassan W, Al-Sergani H, Mourad W et al (2005) Amyloid heart disease. New frontiers and insights in pathophysiology, diagnosis, and management. Tex Heart Inst J 32(2):178–184PubMed
7.
go back to reference Ikeda S (2004) Cardiac amyloidosis: heterogenous pathogenic backgrounds. Intern Med 43(12):1107–1114CrossRefPubMed Ikeda S (2004) Cardiac amyloidosis: heterogenous pathogenic backgrounds. Intern Med 43(12):1107–1114CrossRefPubMed
8.
go back to reference Falk RH (2005) Diagnosis and management of the cardiac amyloidoses. Circulation 112(13):2047–2060CrossRefPubMed Falk RH (2005) Diagnosis and management of the cardiac amyloidoses. Circulation 112(13):2047–2060CrossRefPubMed
9.
go back to reference Shah KB, Inoue Y, Mehra MR (2006) Amyloidosis and the heart: a comprehensive review. Arch Intern Med 166(17):1805–1813CrossRefPubMed Shah KB, Inoue Y, Mehra MR (2006) Amyloidosis and the heart: a comprehensive review. Arch Intern Med 166(17):1805–1813CrossRefPubMed
10.
go back to reference Smith TJ, Kyle RA, Lie JT (1984) Clinical significance of histopathologic patterns of cardiac amyloidosis. Mayo Clin Proc 59:547–555PubMed Smith TJ, Kyle RA, Lie JT (1984) Clinical significance of histopathologic patterns of cardiac amyloidosis. Mayo Clin Proc 59:547–555PubMed
11.
go back to reference Rahman JE, Helou EF, Gelzer-Bell R et al (2004) Noninvasive diagnosis of biopsy-proven cardiac amyloidosis. J Am Coll Cardiol 43(3):410–415CrossRefPubMed Rahman JE, Helou EF, Gelzer-Bell R et al (2004) Noninvasive diagnosis of biopsy-proven cardiac amyloidosis. J Am Coll Cardiol 43(3):410–415CrossRefPubMed
12.
go back to reference Vogelsberg H, Mahrholdt H, Deluigi CC et al (2008) Cardiovascular magnetic resonance in clinically suspected cardiac amyloidosis: noninvasive imaging compared to endomyocardial biopsy. J Am Coll Cardiol 51(10):1022–1030CrossRefPubMed Vogelsberg H, Mahrholdt H, Deluigi CC et al (2008) Cardiovascular magnetic resonance in clinically suspected cardiac amyloidosis: noninvasive imaging compared to endomyocardial biopsy. J Am Coll Cardiol 51(10):1022–1030CrossRefPubMed
13.
go back to reference Sack FU, Kristen A, Goldschmidt H et al (2008) Treatment options for severe cardiac amyloidosis: heart transplantation combined with chemotherapy and stem cell transplantation for patients with AL-amyloidosis and heart and liver transplantation for patients with ATTR-amyloidosis. Eur J Cardiothorac Surg 33(2):257–262CrossRefPubMed Sack FU, Kristen A, Goldschmidt H et al (2008) Treatment options for severe cardiac amyloidosis: heart transplantation combined with chemotherapy and stem cell transplantation for patients with AL-amyloidosis and heart and liver transplantation for patients with ATTR-amyloidosis. Eur J Cardiothorac Surg 33(2):257–262CrossRefPubMed
14.
go back to reference Hv H, Mihatsch M, Lobeck H et al (2009) Prevalence and origin of amyloid in kidney biopsies. Am J Surg Pathol 33(8):1198–1205CrossRef Hv H, Mihatsch M, Lobeck H et al (2009) Prevalence and origin of amyloid in kidney biopsies. Am J Surg Pathol 33(8):1198–1205CrossRef
15.
16.
go back to reference Collins AB, Smith RN, Stone JR (2009) Classification of amyloid deposits in diagnostic cardiac specimens by immunofluorescence. Cardiovasc Pathol 18(4):205–216CrossRefPubMed Collins AB, Smith RN, Stone JR (2009) Classification of amyloid deposits in diagnostic cardiac specimens by immunofluorescence. Cardiovasc Pathol 18(4):205–216CrossRefPubMed
17.
go back to reference Crotty TB, Li CY, Edwards WD et al (1995) Amyloidosis and endomyocardial biopsy: correlation of extent and pattern of deposition with amyloid immunophenotype in 100 cases. Cardiovasc Pathol 4:39–42CrossRef Crotty TB, Li CY, Edwards WD et al (1995) Amyloidosis and endomyocardial biopsy: correlation of extent and pattern of deposition with amyloid immunophenotype in 100 cases. Cardiovasc Pathol 4:39–42CrossRef
19.
go back to reference Kebbel A, Röcken C (2006) Immunohistochemical classification of amyloid in surgical pathology revisited. Am J Surg Pathol 30(6):673–683CrossRefPubMed Kebbel A, Röcken C (2006) Immunohistochemical classification of amyloid in surgical pathology revisited. Am J Surg Pathol 30(6):673–683CrossRefPubMed
20.
go back to reference Strege RJ, Saeger W, Linke RP (1998) Diagnosis and immunohistochemical classification of systemic amyloidoses. Report of 43 cases in an unselected autopsy series. Virchows Arch 433:19–27CrossRefPubMed Strege RJ, Saeger W, Linke RP (1998) Diagnosis and immunohistochemical classification of systemic amyloidoses. Report of 43 cases in an unselected autopsy series. Virchows Arch 433:19–27CrossRefPubMed
21.
go back to reference Eriksson M, Büttner J, Todorov T et al (2009) Prevalence of germline mutations in the TTR gene in a consecutive series of surgical pathology specimens with ATTR amyloid. Am J Surg Pathol 33(1):58–65CrossRefPubMed Eriksson M, Büttner J, Todorov T et al (2009) Prevalence of germline mutations in the TTR gene in a consecutive series of surgical pathology specimens with ATTR amyloid. Am J Surg Pathol 33(1):58–65CrossRefPubMed
22.
go back to reference Bergstrom J, Gustavsson A, Hellman U et al (2005) Amyloid deposits in transthyretin-derived amyloidosis: cleaved transthyretin is associated with distinct amyloid morphology. J Pathol 206(2):224–232CrossRefPubMed Bergstrom J, Gustavsson A, Hellman U et al (2005) Amyloid deposits in transthyretin-derived amyloidosis: cleaved transthyretin is associated with distinct amyloid morphology. J Pathol 206(2):224–232CrossRefPubMed
23.
go back to reference Ihse E, Ybo A, Suhr O et al (2008) Amyloid fibril composition is related to the phenotype of hereditary transthyretin V30M amyloidosis. J Pathol 216(2):253–261CrossRefPubMed Ihse E, Ybo A, Suhr O et al (2008) Amyloid fibril composition is related to the phenotype of hereditary transthyretin V30M amyloidosis. J Pathol 216(2):253–261CrossRefPubMed
24.
go back to reference Baretton G, Linke RP, Löhrs U (1990) Systemische Amyloidosen. Immunhistochemische Typisierung an Autopsien mit Hilfe zahlreicher spezifischer Antikörper. Pathologe 11:71–79PubMed Baretton G, Linke RP, Löhrs U (1990) Systemische Amyloidosen. Immunhistochemische Typisierung an Autopsien mit Hilfe zahlreicher spezifischer Antikörper. Pathologe 11:71–79PubMed
25.
go back to reference Chastonay P, Hurlimann J (1986) Characterization of different amyloids with immunological techniques. Path Res Pract 181:657–663PubMed Chastonay P, Hurlimann J (1986) Characterization of different amyloids with immunological techniques. Path Res Pract 181:657–663PubMed
26.
go back to reference Röcken C, Schwotzer E, Linke RP et al (1996) The classification of amyloid deposits in clinicopathological practice. Histopathology 29:325–335CrossRefPubMed Röcken C, Schwotzer E, Linke RP et al (1996) The classification of amyloid deposits in clinicopathological practice. Histopathology 29:325–335CrossRefPubMed
27.
go back to reference van de Kaa CA, Hol PR, Huber J et al (1986) Diagnosis of the type of amyloid in paraffin wax embedded tissue sections using antisera against human and animal amyloid proteins. Virchows Archiv [A] 408:649–664CrossRef van de Kaa CA, Hol PR, Huber J et al (1986) Diagnosis of the type of amyloid in paraffin wax embedded tissue sections using antisera against human and animal amyloid proteins. Virchows Archiv [A] 408:649–664CrossRef
28.
go back to reference Vrana JA, Gamez JD, Madden BJ et al (2009) Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood 114(24):4957–4959CrossRefPubMed Vrana JA, Gamez JD, Madden BJ et al (2009) Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood 114(24):4957–4959CrossRefPubMed
29.
go back to reference Nilsson KP, Ikenberg K, Aslund A et al (2010) Structural typing of systemic amyloidoses by luminescent-conjugated polymer spectroscopy. Am J Pathol 176(2):563–574CrossRefPubMed Nilsson KP, Ikenberg K, Aslund A et al (2010) Structural typing of systemic amyloidoses by luminescent-conjugated polymer spectroscopy. Am J Pathol 176(2):563–574CrossRefPubMed
30.
go back to reference Pellikka PA, Holmes DR Jr, Edwards WD et al (1988) Endomyocardial biopsy in 30 patients with primary amyloidosis and suspected cardiac involvement. Arch Intern Med 148(3):662–666CrossRefPubMed Pellikka PA, Holmes DR Jr, Edwards WD et al (1988) Endomyocardial biopsy in 30 patients with primary amyloidosis and suspected cardiac involvement. Arch Intern Med 148(3):662–666CrossRefPubMed
31.
go back to reference Rapezzi C, Riva L, Quarta CC et al (2008) Gender-related risk of myocardial involvement in systemic amyloidosis. Amyloid 15(1):40–48CrossRefPubMed Rapezzi C, Riva L, Quarta CC et al (2008) Gender-related risk of myocardial involvement in systemic amyloidosis. Amyloid 15(1):40–48CrossRefPubMed
32.
go back to reference Palladini G, Campana C, Klersy C et al (2003) Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis. Circulation 107(19):2440–2445CrossRefPubMed Palladini G, Campana C, Klersy C et al (2003) Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis. Circulation 107(19):2440–2445CrossRefPubMed
33.
go back to reference Hosch W, Kristen AV, Libicher M et al (2008) Late enhancement in cardiac amyloidosis: correlation of MRI enhancement pattern with histopathological findings. Amyloid 15(3):196–204CrossRefPubMed Hosch W, Kristen AV, Libicher M et al (2008) Late enhancement in cardiac amyloidosis: correlation of MRI enhancement pattern with histopathological findings. Amyloid 15(3):196–204CrossRefPubMed
34.
go back to reference Suhr OB, Svendsen IH, Andersson R et al (2003) Hereditary transthyretin amyloidosis from a Scandinavian perspective. J Intern Med 254(3):225–235CrossRefPubMed Suhr OB, Svendsen IH, Andersson R et al (2003) Hereditary transthyretin amyloidosis from a Scandinavian perspective. J Intern Med 254(3):225–235CrossRefPubMed
35.
go back to reference Jacobson DR, Pan T, Kyle RA et al (1997) Transthyretin ILE20, a new variant associated with late-onset cardiac amyloidosis. Hum Mutat 9:83–85CrossRefPubMed Jacobson DR, Pan T, Kyle RA et al (1997) Transthyretin ILE20, a new variant associated with late-onset cardiac amyloidosis. Hum Mutat 9:83–85CrossRefPubMed
Metadata
Title
Amyloid in endomyocardial biopsies
Authors
Barbara Kieninger
Magdalena Eriksson
Reinhard Kandolf
Philipp A. Schnabel
Stefan Schönland
Arnt V. Kristen
Ute Hegenbart
Peter Lohse
Christoph Röcken
Publication date
01-05-2010
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 5/2010
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-010-0909-5

Other articles of this Issue 5/2010

Virchows Archiv 5/2010 Go to the issue