Diagnosis of Minimal Amyloid Deposits by Congo Red Fluorescence and Amyloid Type-Specific Immunohistochemistry: A Review
The diagnosis of amyloidosis on tissue sections containing minute amounts of amyloid poses the severe problem of making an incorrect diagnosis, due to the low sensitivity of the classical Congo red procedure. Increasing the sensitivity by using amyloid antibodies advanced the diagnosis by more than 2 years, according to a retrospective study. Even more sensitive is the application of Congo red fluorescence by means of which the missing of amyloid deposits rarely occurs. Nevertheless, diagnosis of amyloid is not trivial. To arrive at a flawless diagnosis, the awareness of the many pitfalls and if possible their remedies is mandatory, in particular those concerning sampling errors. The goal for the patient is to get the diagnosis of amyloid at the earliest clinical stages, concomitant with the clinician’s first suspicion, in order to get an early typing of amyloid and a suitable respective therapy before organ damage can occur, thus giving the chance of improving the course of the otherwise fatal disease. By using these expert methods, in tissue samples (evaluated as amyloid negative by the classical Congo red method or even by electron microscopy), amyloid could nevertheless be detected and thus diagnosis of amyloidosis could be made.
KeywordsAmyloidosis Preclinical amyloid Very early amyloid Quality of tissue Minute amyloid deposits Formalin-fixed paraffin sections Congo red Quality of staining Polarization microscopy Congo red fluorescence Light microscopy Electron microscopy Diagnosing amyloid Immunohistochemistry (IHC) of high quality Double staining Congo red and immunohistochemistry Triple illumination Pitfalls and remedies Sampling error Polarization shadow Quality of equipment Inconclusiveness of negative results Expert opinion Quality of evaluation and interpretation Expert evaluation
For technical assistance, I thank Mrs. A. Meinel; for secretarial help, Mrs. A. Feix, both Martinsried/Germany; and for artwork, I thank Ms. A.K.M. Linke, Essen/Germany.
- 2.Bennhold H. Eine spezifische Amyloidfärbung mit Kongorot. Münchn Med Wochenschr. 1922;69:1537–8.Google Scholar
- 7.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 11.1.CrossRefGoogle Scholar
- 9.Highman B. Improved method for demonstrating amyloid in paraffin sections. Arch Pathol. 1964;41:559–62.Google Scholar
- 13.Bandmann M, Linke RP. The diagnosis of amyloidosis may be hindered by the sampling error, and how to prevent it. In: Skinner M, Berk JL, Conners LH, Sheldon DC, editors. XIth International symposium on amyloidosis. Boca Raton, FL: CRC Press; 2007. p. 347–9.Google Scholar