Skip to main content
SpringerLink
Log in

Differential Diagnosis of Amyloid in Surgical Pathology: Organized Deposits and Other Materials in the Differential Diagnosis of Amyloidosis

  • Chapter
Amyloid and Related Disorders

Part of the book series: Current Clinical Pathology ((CCPATH))

Abstract

The accurate diagnosis of amyloidosis is essential. Delay in diagnosis results in significant adverse consequences. Likewise, making the wrong diagnosis results in unwarranted therapy with marked adverse effects.

Understanding the appropriate use of stains to confirm or exclude a diagnosis of amyloidosis is crucial for the surgical pathologist. In some instances, the material that suggests amyloid may be in very small amounts deposited in various organs, and this may pose significant diagnostic challenges.

While electron microscopy is the gold standard to confirm the presence of amyloid, it is seldom that the tissue available for evaluation to surgical pathologists (excluding kidney) is properly fixed for ultrastructural evaluation. Stains then become the main diagnostic technique available. There are important considerations when these stains are used for diagnosis or confirmation of amyloid deposits. This chapter addresses differential diagnosis with emphasis on a practical algorithmic approach.

It also discusses entities in the differential diagnosis and how to distinguish these. The challenge to diagnose amyloid is increased when non-renal tissue is the specimen under consideration, as the routine diagnostic biopsy is generally fixed in formalin and embedded in paraffin. While electron microscopic examination of tissue retrieved from a paraffin block may be sufficient for a definitive diagnosis of amyloidosis, it is preferable to properly fix tissue for ultrastructural evaluation to preserve diagnostic features. Immunofluorescence, immunohistochemistry, and mass spectroscopy can be used to determine the type of amyloid, and these techniques play important roles in a variety of circumstances.

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

Access this chapter

Log in via an institution
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. Rokitansky MH. Virchow and, Heschl on the problem of amyloidosis [German]. Zentrablatt fur Allgeneine Pathologie and Pathologische Anatomie (Jena). 1968;111:103–7.

    Google Scholar 

  2. Aterman K. A historical note on the iodine-sulphuric acid reaction of amyloid. Histochemistry. 1976;49:131–43.

    Article  CAS  PubMed  Google Scholar 

  3. Ruske W. August Kekule and the development of the theory of chemical structure [German]. Naturwissenschaften. 1965;52:485–9.

    Article  CAS  PubMed  Google Scholar 

  4. Kallee E. The 110th birthday of Hans Hermann Bennhold [German]. Dtsch Med Wochenschr. 1993;118:1336–8.

    CAS  PubMed  Google Scholar 

  5. Elghetany MT, Saleen A, Barr K. The Congo red stain revisited. Ann Clin Lab Sci. 1989;19:190–5.

    CAS  PubMed  Google Scholar 

  6. Reznik M. Paul Divry: the discovery of cerebral amyloidosis [French]. Acta Neurol Belg. 1989;89:168–78.

    CAS  PubMed  Google Scholar 

  7. Puchtler H, Waldrop FS, McPolan SN. A review of light, polarization and fluorescence microscopic methods for amyloid. Appl Pathol. 1985;3:5–17.

    CAS  PubMed  Google Scholar 

  8. Hobbs JR, Morgan AD. Fluorescence microscopy with thioflavin-T in the diagnosis of amyloid. J Pathol Bacteriol. 1963;86:437–42.

    Article  CAS  PubMed  Google Scholar 

  9. Rosenmann E, Eliakim M. Nephrotic syndrome associated with amyloid-like glomerular deposits. Nephron. 1977;18:301–8.

    Article  CAS  PubMed  Google Scholar 

  10. Duffy JL, Khurana E, Susin M, Gomez-Leon G. Fibrillary renal deposits and nephritis. Am J Pathol. 1983;113:279–90.

    PubMed Central  CAS  PubMed  Google Scholar 

  11. Olesnicky L, Doty SB, Bertani T, Pirani CL. Tubular microfibrils in the glomeruli of membranous nephropathy. Arch Pathol Lab Med. 1984;108:902–5.

    CAS  PubMed  Google Scholar 

  12. Herrera GA, Turbat-Herrera EA. Renal diseases with organized deposits: an algorithmic approach to classification and diagnosis. Arch Pathol Lab Med. 2010;134:512–31.

    PubMed  Google Scholar 

  13. Brouet JC, Clauvel JP, Danon F, et al. Biologic and clinical significance of cryoglobulins: a report of 86 cases. Am J Med. 1974;57:775–8.

    Article  CAS  PubMed  Google Scholar 

  14. Herrera GA, Gu X. Lesions associated with plasma cell dyscrasias in renal biopsies: a 10 year retrospective study (abstract). Lab Invest. 2006;86:A262.

    Article  Google Scholar 

  15. Koike H, Misu K, Sugiura M, et al. Pathology of early-vs late-onset TTR Met30 familial amyloid polyneuropathy. Neurology. 2004;63:129–38.

    Article  CAS  PubMed  Google Scholar 

  16. Carson FL, Kingsley WB. Non-amyloid green birefringence following Congo red staining. Arch Pathol Lab Med. 1980;104:333–5.

    CAS  PubMed  Google Scholar 

  17. Korbet SM, Schwartz MM, Lewis EJ. The fibrillary glomerulopathies. Am J Kidney Dis. 1994;23:751–65.

    Article  CAS  PubMed  Google Scholar 

  18. Iskandar SS, Herrera GA. Glomerulopathies with organized deposits. Semin Diagn Pathol. 2002;19:116–32.

    PubMed  Google Scholar 

  19. Howell D, Gu X, Herrera GA. Organized deposits and look-alikes. Ultrastruct Pathol. 2003;27:295–312.

    Article  PubMed  Google Scholar 

  20. Herrera GA, Lott RL. Silver stains in diagnostic renal pathology. J Histotechnol. 1996;19:219–23.

    Article  CAS  Google Scholar 

  21. Alpers CE, Rennke HG, Hopper J, et al. Fibrillary glomerulonephritis: an entity with unusual immunofluorescence features. Kidney Int. 1987;31:781–9.

    Article  CAS  PubMed  Google Scholar 

  22. Iskandar SS, Falk RJ, Jennette C. Clinical and pathologic features of fibrillary glomerulonephritis. Kidney Int. 1992;42:1401–7.

    Article  CAS  PubMed  Google Scholar 

  23. D’Agati V, Sacchi G, Truong L, et al. Fibrillary glomerulopathy: defining the disease spectrum (abstract). J Am Soc Nephrol. 1991;2:591.

    Google Scholar 

  24. Nasr SH, Valeri AM, Cornell LD, et al. Fibrillary glomerulonephritis: a report of 66 cases from a single institution. Clin J Am Soc Nephrol. 2011;6:775–84.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Yang GCH, Nieto R, Stachura I, Gallo GR. Ultrastructural immunohistochemical localization of polyclonal IgG, C3, and amyloid P component on the Congo red-negative amyloid-like fibrils of fibrillary glomerulopathy. Am J Pathol. 1992;141:409–19.

    PubMed Central  CAS  PubMed  Google Scholar 

  26. Nasr SH, Valeri AM, Cornell LD, et al. Fibrillary glomerulonephritis: a report of 66 cases from a single institution. Clin J Am Soc Nephrol. 2011;6:775–84.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Sohar E, Ravid M, Ben-Shaul Y, Reshef T, Gafni J. Diabetic fibrillosis. Am J Med. 1970;49:64–9.

    Article  CAS  PubMed  Google Scholar 

  28. Gonul II, Gough J, Jim K, Benediktsson H. Glomerular mesangial fibrillary deposits in a patient with diabetes mellitus. Int Urol Nephrol. 2006;38:767–72.

    Article  PubMed  Google Scholar 

  29. Sanders PW, Herrera GA, Kirk KA, Old CW, Galla JH. The spectrum of glomerular and tubulointerstitial renal lesions associated with monotypical immunoglobulin light chain deposition. Lab Invest. 1991;64:527–37.

    CAS  PubMed  Google Scholar 

  30. Müller-Höcker J, Weiss M, Sitter T, et al. Fibrillary glomerulonephritis mimicking membranous nephropathy—A diagnostic pitfall. Pathol Res Pract. 2009;205:265–71.

    Article  PubMed  Google Scholar 

  31. Rosenmann E, Brisson M-L, Bercovitch DD, Rosenberg A. Atypical membranous glomerulonephritis with fibrillary subepithelial deposits in a patient with malignant lymphoma. Nephron. 1988;48:226–30.

    Article  CAS  PubMed  Google Scholar 

  32. Hvala A, Ferluga D, Vizjak A, et al. Fibrillary non-congophilic renal and extrarenal deposits: a report on 10 cases. Ultrastruct Pathol. 2003;27:341–7.

    Article  PubMed  Google Scholar 

  33. Masson RG, Rennke HG, Gotlieb MN. Pulmonary hemorrhage in a patient with fibrillary glomerulonephritis. N Eng J Med. 1992;326:36–9.

    Article  CAS  Google Scholar 

  34. Rovin BH, Bou-Khalil P, Sedmak D. Pulmonary renal syndrome in a patient with fibrillary glomerulonephritis. Am J Kidney Dis. 1993;22:713–6.

    Article  CAS  PubMed  Google Scholar 

  35. Calls GJ, Torras A, Ricart MJ, et al. Fibrillary glomerulonephritis and pulmonary hemorrhage in a patient with renal transplantation. Clin Nephrol. 1995;43:180–3.

    Google Scholar 

  36. Strom EH, Hurwitz N, Mayr AC, et al. Immunotactoidlike glomerulopathy with fibrillary deposits in liver and bone marrow gammopathy. Am J Nephrol. 1996;16(52):3–8.

    Google Scholar 

  37. Satoskar A, Calomeni E, Nadasdy G, et al. Fibrillary glomerulonephritis with splenic involvement: a detailed autopsy study. Ultrastruct Pathol. 2008;32:113–21.

    Article  PubMed  Google Scholar 

  38. Korbet SM, Schwartz MM, Lewis EJ. Immunotactoid glomerulopathy (Fibrillary glomerulonephritis). Clin J Am Soc Nephrol. 2006;1:1351–56.

    Article  PubMed  Google Scholar 

  39. Schwartz MM, Korbet SM, Lewis EJ. Immunotactoid glomerulopathy. J Am Soc Nephrol. 2002;13:1390–7.

    Article  PubMed  Google Scholar 

  40. Alpers C, Kowalewska J. Fibrillary glomerulonephritis and immunotactoid glomerulopathy. J Am Soc Nephrol. 2008;19:34–7.

    Article  PubMed  Google Scholar 

  41. Alpers C. Fibrillary glomerulonephritis and immunotactoid glomerulopathy: two entities, not one. Am J Kidney Dis. 1993;22:448–51.

    Article  CAS  PubMed  Google Scholar 

  42. Fogo A, Qureshi N, Horn RG. Morphologic and clinical features of fibrillary glomerulonephritis versus immunotactoid glomerulopathy. Am J Kidney Dis. 1993;22:367–77.

    Article  CAS  PubMed  Google Scholar 

  43. Rosenstock JL, Markowitz GS, Valeri AM, et al. Fibrillary and immunotactoid glomerulonephritis: distinct entities with different clinical and pathologic features. Kidney Int. 2003;63:1450–61.

    Article  PubMed  Google Scholar 

  44. Bridoux F, Hugue V, Coldefy O, et al. Fibrillary glomerulonephritis and immunotactoid (microtubular) glomerulopathy are associated with distinct immunologic features. Kidney Int. 2002;62:1764–75.

    Article  CAS  PubMed  Google Scholar 

  45. Rostagno A, Kumar VR, Chuba J, et al. Fibrillary glomerulonephritis related to serum fibrillar immunoglobulin-fibronectin complexes. Am J Kidney Dis. 1996;28:676–84.

    Article  CAS  PubMed  Google Scholar 

  46. Isaac J, Herrera GA, Shihab FS. De-novo fibrillary glomerulopathy in the renal allograft of a patient with systemic lupus erythematosus. Nephron. 2001;87:365–8.

    Article  CAS  PubMed  Google Scholar 

  47. Sundaram S, Mainali R, Norfolk ER, et al. Fibrillary glomerulopathy secondary to light chain deposition disease in a patient with monoclonal gammopathy. Ann Clin Lab Sci. 2007;37:370–4.

    PubMed  Google Scholar 

  48. Sethi S, Theis JD, Vrana JA, et al. Laser microdissection and proteomic analysis of amyloidosis, cryoglobulinemic GN, fibrillary GN and immunotactoid glomerulopathy. Clin J Am Soc Nephrol. 2013;8:915–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Sethi S, Vrana J, Theis JD, Dogan A. Mass spectrometry based proteomics in the diagnosis of kidney disease. Curr Opin Nephrol Hypertens. 2013;22:273–80.

    Article  CAS  PubMed  Google Scholar 

  50. Dispenzieri A, Gorevic PD. Cryoglobulinemia. Hematol Oncol Clin North Am. 1999;13:1315–49.

    Article  CAS  PubMed  Google Scholar 

  51. Porush JG, Grishman E, Alter AA, et al. Paraproteinemia and cryoglobulinemia associated with atypical glomerulonephritis and the nephrotic syndrome. Am J Med. 1969;47:957–64.

    Article  CAS  PubMed  Google Scholar 

  52. Karras A, Noel L-H, Droz D, et al. Renal involvement in monoclonal (type I) cryoglobulinemia: two cases associated with IgG3κ cryoglobulin. Am J Kidney Dis. 2002;40:1091–6.

    Article  PubMed  Google Scholar 

  53. D’Amico G. Renal involvement in human hepatitis C infection: cryoglobulinemic glomerulonephritis. Kidney Int. 1998;54:650–71.

    Article  PubMed  Google Scholar 

  54. Golde D, Epstein W. Mixed cryoglobulins and glomerulonephritis. Ann Intern Med. 1956;69:1221–7.

    Article  Google Scholar 

  55. Markowitz GS, Cheng J-T, Colvin RB, Trbbin WM, D’Agati VD. Hepatitis C infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy. J Am Soc Nephrol. 1998;9:2244–52.

    CAS  PubMed  Google Scholar 

  56. Ojemakinde K, Turbat-Herrera EA, Zeng X, Gu, X, Herrera GA: The many faces of cryoglobulinemic nephropathy: a clinico-apthologic study with emphasis on the value of electron microscopy. Ultrastruct Pathol 2014;38:367–76.

    Google Scholar 

  57. Pais B, Panadés MJ, Ramos J, Montoliu J. Glomerular involvement in type I monoclonal cryoglobulinaemia. Nephrol Dial Transplant. 1995;10:130–2.

    CAS  PubMed  Google Scholar 

  58. Verroust P, Mery JP, Morel-Maroger L, et al. Glomerular lesions in monoclonal gammopathies and mixed essential cryoglobulinemias IgG-IgM. Adv Nephrol Necker Hosp. 1871;1:161–94.

    Google Scholar 

  59. Feiner H, Gallo G. Ultrastructure in glomerulonephritis associated with cryoglobulinemia. Am J Pathol. 1977;88:145–55.

    PubMed Central  CAS  PubMed  Google Scholar 

  60. Ogihara T, Saruta T, Saito I, Abe S, Ozawa Y, Kato E, Sakaguchi H. Finger print deposits of the kidney in pure monoclonal IgG kappa cryoglobulinemia. Clin Nephrol. 1979;12:186–90.

    CAS  PubMed  Google Scholar 

  61. Cordonnier D, Martin H, Groslambert P, Micouin C. Mixed IgG-IgM cryoglobulinemia with glomerulonephritis. Am J Med. 1975;59:867–72.

    Article  CAS  PubMed  Google Scholar 

  62. Nasr SH, Fidler ME, Cornell LD, et al. Immunotactoid glomerulopathy: clinicopathologic and proteomic study. Nephrol Dial Transplant. 2012;27:4137–46.

    Article  CAS  PubMed  Google Scholar 

  63. Schifferli JA, Merot Y, Cruchaud A, Chatenat F. Immunotactoid glomerulopathy with leukocytoclastic skin vasculitis and hypocomplementemia: a case report. Clin Nephrol. 1987;27:151–5.

    CAS  PubMed  Google Scholar 

  64. Orfila C, Meeus F, Bernadet P, et al. Immunotactoid glomerulopathy and cutaneous vasculitis. Am J Nephrol. 1991;11:67–72.

    Article  CAS  PubMed  Google Scholar 

  65. Garibaldi DC, Gottsch J, de la Cruz Z, Haas M, Green R. Immunotactoid keratopathy: a clinicopathologic case review and review of reports of corneal involvement in paraproteinemias. Surv Ophthalmol. 2005;1:61–80.

    Article  Google Scholar 

  66. Herrera GA, Ojemakinde K, Gu X, Iskandar S. Immunotactoid glomerulopathy and cryoglobulinemic nephropathy: two entities with many similarities. A unified conceptual approach. Ultrastruct Pathol. 2015.

    Google Scholar 

  67. Rostagno A, Vidal R, Kumar A, et al. Fibrillary glomerulonephritis related to serum fibrillar immunoglobulin fibronectin complexes. Am J Kidney Dis. 1996;28:675–84.

    Article  Google Scholar 

  68. Saltykov BB, Malkina LA. Vascular hyalinosis in diabetic microangiopathy. Ann Pathol. 1975;37:38–44.

    CAS  Google Scholar 

  69. Kubo M, Kiyohara Y, Kato I, et al. Risk factors for renal glomerular and vascular changes in an autopsy-based population survey: the Hisayama Study. Kidney Int. 2003;63:1508–15.

    Article  PubMed  Google Scholar 

  70. Denduchis B, Gonzalez N, Mancini RE. Concentration of hydroxyproline in testes of hypophysectomized patients before and after treatment with gonadotropins and testosterone. J Reprod Fertil. 1972;31:111–4.

    Article  CAS  PubMed  Google Scholar 

  71. Kronz JD, Neu AM, Nadasdy T. When noncongophilic glomerular fibrils do not represent fibrillary glomerulonephritis: nonspecific mesangial fibrils in sclerosing glomeruli. Clin Nephrol. 1998;50:218–23.

    CAS  PubMed  Google Scholar 

  72. Shirahama T, Cohen AS. Fine structure of the glomerulus in human and experimental amyloidosis. Am J Pathol. 1973;73:97–114.

    PubMed Central  CAS  PubMed  Google Scholar 

  73. Linke RP. Congo red staining of amyloid: improvements and practical guide for a more precise diagnosis of amyloid and the different amyloidoses. In: Uversky VN, Fink AL, editors. Protein misfolding, aggregation, and conformational diseases, Protein reviews (Atassi MZ, editor), vol. 4. New York, NY: Springer; 2006. p. 239–76. Chapter 11.

    Chapter  Google Scholar 

  74. Klastskin G. Non-specific green birefringence in Congo-red stained tissues. Am J Pathol. 1969;56:1–13.

    Google Scholar 

  75. Picken MM, Herrera GA. The burden of “sticky” amyloid. Arch Pathol Lab Med. 2007;131:850–1.

    PubMed  Google Scholar 

  76. 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;131:917–23.

    PubMed  Google Scholar 

  77. Herrera GA, Richard P, Turbat EA, et al. Ultrastructural immunolabeling in the diagnosis of light chain related renal disease. Pathol Immunopathol Res. 1986;5:170–87.

    Article  CAS  PubMed  Google Scholar 

  78. Murphy CL, Eulitz M, Hrncic R, et al. Chemical typing of amyloid protein contained in formalin-fixed paraffin-embedded biopsy specimens. Am J Clin Pathol. 2001;116:135–42.

    Article  CAS  PubMed  Google Scholar 

  79. Hvala A, Kobenter T, Fergula D. Fingerprint and other organized deposits in lupus nephritis. Wien Klin Wochenschr. 2000;112:711–5.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Louisiana State University Health Sciences Center, 1501 Kings Highway, 71103, Shreveport, LA, USA

    Guillermo A. Herrera MD

  2. Departments of Pathology and Medicine, Louisiana State University, Shreveport, LA, USA

    Elba A. Turbat-Herrera MD

Authors
  1. Guillermo A. Herrera MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elba A. Turbat-Herrera MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guillermo A. Herrera MD .

Editor information

Editors and Affiliations

  1. Department of Pathology, Loyola University Medical Center, Maywood, Illinois, USA

    Maria M. Picken

  2. Department of Pathology, LSU Health Shreveport, Shreveport, Louisiana, USA

    Guillermo A. Herrera

  3. Department of Pathology and Laboratory Medicine, Department of Pathology and Laboratory Medicine, New York, New York, USA

    Ahmet Dogan

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Herrera, G.A., Turbat-Herrera, E.A. (2015). Differential Diagnosis of Amyloid in Surgical Pathology: Organized Deposits and Other Materials in the Differential Diagnosis of Amyloidosis. 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_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-19294-9_9

  • 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

Search

Navigation