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January 21, 2019

Diagnose This (January 21, 2019)

A limited sample showed this lesion and negative staining on paraffin-retrieved IF tissue.

What is your diagnosis?

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The photomicrograph shows a glomerulus with a segmental necrotizing lesion on silver stain. Typically, in the setting of negative or pauci-immune staining on IF these findings would be compatible with ANCA-mediated disease. Paraffin-retrieved IF is a very useful salvage technique and can also show previously masked deposits in some entities. However, as with all tests, it has pitfalls. One of the most dramatic is that the majority of Anti-GBM antibody disease patients will show false negative staining for linear IgG on paraffin-retrieved, pronase digested IF (see reference, and quote). Due to this, differentiation between ANCA-mediated disease and Anti-GBM antibody disease cannot be established on paraffin-retrieved IF alone and correlation with serologies should be advocated.

Reference: Nasr SH, D’Agati VD, et al. Immunofluorescence on pronase-digested paraffin sections: A valuable salvage technique for renal biopsies. Kidney International (2006) 70, 2148–2151.

Reference Quote: “The strong linear staining of GBM’s for IgG diagnostic of anti-GBM disease could not be demonstrated by IF-P in this study or by the immunoperoxidase technique on formalin fixed tissue in the study by Molne et al.5 Thus, IF-P and the immunoperoxidase technique on formalin-fixed tissue appear to be too insensitive for the diagnosis of anti-GBM disease.”