Skip to main content

The Role of Immuno-Electron Microscopy in Amyloid Typing: The Experience of the Pavia Referral Center

  • Chapter
Amyloid and Related Disorders

Abstract

The diagnosis of amyloidosis requires that amyloid deposits are demonstrated in patient’s tissues. Congo red staining is still the most commonly used method to detect amyloid deposits. Nevertheless, the results of Congo red stain may be ambiguous, especially if it is performed in centers with limited expertise in its execution and/or interpretation. Furthermore, Congo red stain does not provide any information concerning the nature of amyloidogenic protein. The characterization of amyloid proteins by light microscopic immunohistochemistry in paraffin-embedded samples frequently yields nonspecific results. On the basis of our experience at the Amyloid Center and Pathology Unit of IRCCS Policlinico San Matteo/University of Pavia, the ultrastructural examination of abdominal fat aspirate and other tissue biopsies is capable of confirming or ruling out a diagnosis of amyloidosis and can detect even very small deposits of amyloid fibrils. Moreover, immuno-electron microscopy can correctly characterize the amyloidogenic protein in all the commonest forms of amyloidosis, i.e., AL, AA, ATTR, A(beta)2M, and AApoAI.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Picken MM. Amyloidosis—where are we now and where are we heading? Arch Pathol Lab Med. 2010;134:545–51.

    PubMed  Google Scholar 

  2. Casanova S, Donini U, Zucchelli P, Mazzucco G, Monga G, Linke RP. Immunohistochemical distinction between amyloidosis and fibrillar glomerulopathy. Am J Clin Pathol. 1992;97:787–95.

    CAS  PubMed  Google Scholar 

  3. Arbustini E, Morbini P, Verga L, Concardi M, Porcu E, Pilotto A, Zorzoli I, Garini P, Anesi E, Merlini G. Light and electron microscopy immunohistochemical characterization of amyloid deposits. Amyloid: Int J Exp Clin Invest. 1997;4:157–70.

    Article  CAS  Google Scholar 

  4. Sipe JD, Benson MD, Buxbaum JN, Ikeda S, Merlini G, Saraiva M, Westermark P. Amyloid fibril protein nomenclature committee of the International Society of Amyloidosis. Amyloid. 2010;17:101–4.

    Article  CAS  PubMed  Google Scholar 

  5. Bandini S, Bergesio F, Conti P, Mancini G, Cerretini C, Cirami C, Rosati A, Caselli GM, Arbustini E, Merlini G, Ficarra G, Salvadori M. Nodular macroglossia with combined light chain and beta-2 microglobulin deposition in a long-term dialysis patient. J Nephrol. 2001;14:128–31.

    CAS  PubMed  Google Scholar 

  6. Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2002;349:583–96.

    Article  Google Scholar 

  7. Arbustini E, Verga L, Concardi M, Palladini G, Obici L, Merlini G. Electron and immuno-electron microscopy of abdominal fat identifies and characterizes amyloid fibrils in suspected cardiac amyloidosis. Amyloid. 2002;9:108–14.

    CAS  PubMed  Google Scholar 

  8. Lachmann HJ, Booth DR, Booth SE, Bybee A, Gilbertson JA, Gillmore JD, Pepys MB, Hawkins PN. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med. 2002;346:1786–91.

    Article  CAS  PubMed  Google Scholar 

  9. Palladini G, Obici L, Merlini G. Hereditary amyloidosis. N Engl J Med. 2002;347:1206.

    Article  PubMed  Google Scholar 

  10. Satoskar AA, Burdge K, Cowden DJ, Nadasdy GM, Hebert LA, Nadasdy T. Typing of amyloidosis in renal biopsies: diagnostic pitfalls. Arch Pathol Lab Med. 2007;131:917–22.

    PubMed  Google Scholar 

  11. Solomon A, Murphy CL, Westermark P. Unreliability of immunohistochemistry for typing amyloid deposits. Arch Pathol Lab Med. 2008;132:14.

    PubMed  Google Scholar 

  12. Palladini G, Verga L, Corona S, Obici L, Morbini P, Lavatelli F, Donadei S, Sarais G, Roggeri L, Foli A, Russo P, Zenone Bragotti L, Paulli M, Magrini U, Merlini G. Diagnostic performance of immuno-electron microscopy of abdominal fat in systemic amyloidoses. Amyloid. 2010;17:59–60.

    Google Scholar 

  13. Foli A, Palladini G, Caporali R, Verga L, Morbini P, Obici L, Russo P, Sarais G, Donadei S, Montecucco C, Merlini G. Role of minor salivary gland biopsy in the diagnosis of systemic amyloidosis: results of a prospective study in 62 patients. Amyloid. 2011;18(S1):80–2.

    Article  PubMed  Google Scholar 

  14. Karnovsky MJ. A formaldehyde-glutaraldehyde fixative of high osmolarity for use in electron microscopy. J Cell Biol. 1965;27:137A.

    Google Scholar 

  15. Reynolds ES. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963;17:208–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Roth J, Bendayan M, Orci L. Ultrastructural localization of intracellular antigens by the use of protein A-gold complex. J Histochem Cytochem. 1978;26:1074–81.

    Article  CAS  PubMed  Google Scholar 

  17. Perkins EM, McCaffery JM. Conventional and immunoelectron microscopy of mitochondria. Methods Mol Biol. 2007;372:467–83.

    Article  CAS  PubMed  Google Scholar 

  18. Cowan AJ, Skinner M, Berk JL, Sloan JM, O’hara C, Seldin DC, Sanchorawala V. Macroglossia—not always AL amyloidosis. Amyloid. 2011;18:83–6.

    Article  PubMed  Google Scholar 

  19. Rapezzi C, Quarta CC, Guidalotti PL, Pettinato C, Fanti S, Leone O, Ferlini A, Longhi S, Lorenzini M, Reggiani LB, Gagliardi C, Gallo P, Villani C, Salvi F. Role of (99m)Tc-DPD scintigraphy in diagnosis and prognosis of hereditary transthyretin-related cardiac amyloidosis. JACC Cardiovasc Imaging. 2011;4(6):659–70.

    Article  PubMed  Google Scholar 

  20. Quarta CC, Obici L, Guidalotti PL, Pieroni M, Longhi S, Perlini S, Verga L, Merlini G, Rapezzi C. High 99mTc-DPD myocardial uptake in a patient with apolipoprotein AI-related amyloidotic cardiomyopathy. Amyloid. 2013;20(1):48–51.

    Article  PubMed  Google Scholar 

  21. Briani C, Cavallaro T, Ferrari S, Taioli F, Calamelli S, Verga L, Adami F, Fabrizi GM. Sporadic transthyretin amyloidosis with a novel TTR gene mutation misdiagnosed as primary amyloidosis. J Neurol. 2012;259(10):2226–8.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Laura Verga DVM, PhD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Verga, L. et al. (2015). The Role of Immuno-Electron Microscopy in Amyloid Typing: The Experience of the Pavia Referral Center. In: Picken, M., Herrera, G., Dogan, A. (eds) Amyloid and Related Disorders. Current Clinical Pathology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-19294-9_22

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-19294-9_22

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-19293-2

  • Online ISBN: 978-3-319-19294-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics