Congo red

Congo red is a diazo dye that binds to the beta-pleated sheet structure common to all forms of amyloid protein (e.g., AL, AA, transthyretin, beta-2 microglobulin). On routine light microscopy, amyloid appears as an amorphous, eosinophilic, extracellular substance. When stained with Congo red and viewed under polarized light, amyloid deposits display apple-green birefringence due to the regular, repeating beta-pleated sheet conformation of the fibrils. This finding is used diagnostically in conditions such as AL amyloidosis (light chain, associated with plasma cell dyscrasias/multiple myeloma), AA amyloidosis (serum amyloid A, secondary to chronic inflammatory diseases like rheumatoid arthritis or chronic infections), familial transthyretin amyloidosis, and senile systemic amyloidosis. Clinically, amyloidosis can affect multiple organs, leading to nephrotic syndrome (kidney), restrictive cardiomyopathy (heart), hepatomegaly (liver), macroglossia, carpal tunnel syndrome, and peripheral neuropathy. Biopsy sites commonly used for diagnosis include abdominal fat pad aspirate, rectal mucosa, or the affected organ itself (e.g., renal biopsy). Congo red staining remains the gold standard confirmatory test for amyloid, often followed by immunohistochemistry or mass spectrometry to determine the specific amyloid protein subtype for targeted treatment.