Classification of amyloidosis: misdiagnosing by way of incomplete immunohistochemistry and how to prevent it

SummaryClassification of every individual case of amyloid disease is necessary in order to recognize its origin and its possible pathogenesis for therapeutic consideration. Classification of the amyloids can be performed in different ways. One method primarily exploits serum proteins-but these are risk factors only, and therefore render only ancillary information. In principle, one cannot establish the diagnosis alone through their use. Another approach analyzes the origin of the deposited amyloids, either by extracting the amyloid proteins followed by immunochemical or chemical analysis, or by using immunohistochemistry. Based on chemical analysis of prototypes of amyloid fibril proteins, we have developed a profile of antibodies over the years that specifically identify amyloid in tissue sections. These antibodies have been used for years as a routine service for clinicians and pathologists in immunohistochemically classifying amyloid found in formalin-fixed tissue sections. The typing is always controlled by established amyloid classes. In several cases, we have been asked for a second opinion on a diagnosed amyloid class. Our own immunohistochemical data were then compared with those submitted. These submitted immunohistochemical results represented misdiagnoses of amyloid classes in most patients, since the technique performed was usually incomplete. It is the purpose of this report to analyze such cases and to document some of the typical mistakes. Here, we show how to avoid common pitfalls and how one can arrive at a correct diagnosis using immunohistochemistry appropriately.