Skip to main content
SpringerLink
Log in

Amyloid in endomyocardial biopsies

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Merlini G, Bellotti V (2003) Molecular mechanisms of amyloidosis. N Engl J Med 349(6):583–596

    Article  CAS  PubMed  Google Scholar 

  2. Picken MM (2007) New insights into systemic amyloidosis: the importance of diagnosis of specific type. Curr Opin Nephrol Hypertens 16(3):196–203

    Article  PubMed  Google Scholar 

  3. Hoyer C, Angermann CE, Knop S et al (2008) Cardiac amyloidosis. Med Klin (Munich) 103(3):153–160

    Article  Google Scholar 

  4. Röcken C, Sletten K (2003) Amyloid in surgical pathology. Virchows Arch 443(1):3–16

    Article  PubMed  Google Scholar 

  5. Eshaghian S, Kaul S, Shah PK (2007) Cardiac amyloidosis: new insights into diagnosis and management. Rev Cardiovasc Med 8(4):189–199

    PubMed  Google Scholar 

  6. 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):178–184

    PubMed  Google Scholar 

  7. Ikeda S (2004) Cardiac amyloidosis: heterogenous pathogenic backgrounds. Intern Med 43(12):1107–1114

    Article  PubMed  Google Scholar 

  8. Falk RH (2005) Diagnosis and management of the cardiac amyloidoses. Circulation 112(13):2047–2060

    Article  PubMed  Google Scholar 

  9. Shah KB, Inoue Y, Mehra MR (2006) Amyloidosis and the heart: a comprehensive review. Arch Intern Med 166(17):1805–1813

    Article  CAS  PubMed  Google Scholar 

  10. Smith TJ, Kyle RA, Lie JT (1984) Clinical significance of histopathologic patterns of cardiac amyloidosis. Mayo Clin Proc 59:547–555

    CAS  PubMed  Google Scholar 

  11. Rahman JE, Helou EF, Gelzer-Bell R et al (2004) Noninvasive diagnosis of biopsy-proven cardiac amyloidosis. J Am Coll Cardiol 43(3):410–415

    Article  PubMed  Google Scholar 

  12. 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):1022–1030

    Article  PubMed  Google Scholar 

  13. 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):257–262

    Article  PubMed  Google Scholar 

  14. Hv H, Mihatsch M, Lobeck H et al (2009) Prevalence and origin of amyloid in kidney biopsies. Am J Surg Pathol 33(8):1198–1205

    Article  Google Scholar 

  15. Gioeva Z, Kieninger B, Röcken C (2009) Amyloidosis in liver biopsies. Pathologe 30(3):240–245

    Article  CAS  PubMed  Google Scholar 

  16. Collins AB, Smith RN, Stone JR (2009) Classification of amyloid deposits in diagnostic cardiac specimens by immunofluorescence. Cardiovasc Pathol 18(4):205–216

    Article  CAS  PubMed  Google Scholar 

  17. 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 4:39–42

    Article  Google Scholar 

  18. Benson MD (1992) Hereditary amyloidosis and cardiomyopathy. Am J Med 93(1):1–2

    Article  CAS  PubMed  Google Scholar 

  19. Kebbel A, Röcken C (2006) Immunohistochemical classification of amyloid in surgical pathology revisited. Am J Surg Pathol 30(6):673–683

    Article  PubMed  Google Scholar 

  20. 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 433:19–27

    Article  CAS  PubMed  Google Scholar 

  21. 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):58–65

    Article  PubMed  Google Scholar 

  22. 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):224–232

    Article  PubMed  Google Scholar 

  23. 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):253–261

    Article  CAS  PubMed  Google Scholar 

  24. Baretton G, Linke RP, Löhrs U (1990) Systemische Amyloidosen. Immunhistochemische Typisierung an Autopsien mit Hilfe zahlreicher spezifischer Antikörper. Pathologe 11:71–79

    CAS  PubMed  Google Scholar 

  25. Chastonay P, Hurlimann J (1986) Characterization of different amyloids with immunological techniques. Path Res Pract 181:657–663

    CAS  PubMed  Google Scholar 

  26. Röcken C, Schwotzer E, Linke RP et al (1996) The classification of amyloid deposits in clinicopathological practice. Histopathology 29:325–335

    Article  PubMed  Google Scholar 

  27. 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] 408:649–664

    Article  Google Scholar 

  28. 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):4957–4959

    Article  CAS  PubMed  Google Scholar 

  29. Nilsson KP, Ikenberg K, Aslund A et al (2010) Structural typing of systemic amyloidoses by luminescent-conjugated polymer spectroscopy. Am J Pathol 176(2):563–574

    Article  CAS  PubMed  Google Scholar 

  30. 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):662–666

    Article  CAS  PubMed  Google Scholar 

  31. Rapezzi C, Riva L, Quarta CC et al (2008) Gender-related risk of myocardial involvement in systemic amyloidosis. Amyloid 15(1):40–48

    Article  CAS  PubMed  Google Scholar 

  32. 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):2440–2445

    Article  CAS  PubMed  Google Scholar 

  33. 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):196–204

    Article  PubMed  Google Scholar 

  34. Suhr OB, Svendsen IH, Andersson R et al (2003) Hereditary transthyretin amyloidosis from a Scandinavian perspective. J Intern Med 254(3):225–235

    Article  CAS  PubMed  Google Scholar 

  35. Jacobson DR, Pan T, Kyle RA et al (1997) Transthyretin ILE20, a new variant associated with late-onset cardiac amyloidosis. Hum Mutat 9:83–85

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Department of Pathology, Charité University Hospital, Berlin, Germany

    Barbara Kieninger, Magdalena Eriksson & Christoph Röcken

  2. Department of Molecular Pathology, Eberhard Karls University, Tübingen, Germany

    Reinhard Kandolf

  3. Department of Pathology, University of Heidelberg, Heidelberg, Germany

    Philipp A. Schnabel

  4. Medical Department V, Amyloidosis Clinic, Hematology, University of Heidelberg, Heidelberg, Germany

    Stefan Schönland & Ute Hegenbart

  5. Department of Cardiology, Angiology, and Respiratory Medicine, University of Heidelberg, Heidelberg, Germany

    Arnt V. Kristen

  6. Department of Clinical Chemistry—Grosshadern, Ludwig-Maximilians University, Munich, Germany

    Peter Lohse

  7. Department of Pathology, Christian-Albrechts-University, Arnold-Heller-Str. 3/14, 24105, Kiel, Germany

    Christoph Röcken

Authors
  1. Barbara Kieninger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Magdalena Eriksson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Reinhard Kandolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Philipp A. Schnabel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stefan Schönland
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Arnt V. Kristen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ute Hegenbart
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Peter Lohse
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Christoph Röcken
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christoph Röcken.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kieninger, B., Eriksson, M., Kandolf, R. et al. Amyloid in endomyocardial biopsies. Virchows Arch 456, 523–532 (2010). https://doi.org/10.1007/s00428-010-0909-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-010-0909-5

Keywords

Search

Navigation