Congo red stain

Congo red stain binds to the beta-pleated sheet structure common to all types of amyloid fibrils (regardless of the specific protein subtype - AL, AA, transthyretin, etc.). Under normal light, amyloid appears salmon-pink to red-orange. However, the diagnostic hallmark is examination under polarized light, which reveals apple-green birefringence due to the regular, repeating beta-pleated sheet configuration of amyloid fibrils.

Clinical applications include diagnosis of systemic amyloidosis (AL amyloidosis from plasma cell dyscrasias/multiple myeloma, AA amyloidosis from chronic inflammatory states, transthyretin amyloidosis), and localized amyloid deposits such as those found in Alzheimer disease (senile plaques), type 2 diabetes mellitus (islet amyloid polypeptide), and medullary thyroid carcinoma (calcitonin-derived amyloid).

Tissue biopsy sites commonly used include abdominal fat pad aspirate, rectal mucosa, kidney, heart, or other affected organs depending on clinical presentation. Once amyloid is confirmed via Congo red staining, further workup with immunohistochemistry, mass spectrometry, or genetic testing may be needed to identify the specific amyloid protein subtype, which guides treatment.

Amyloidosis can cause restrictive cardiomyopathy, nephrotic syndrome, hepatomegaly, macroglossia, peripheral neuropathy, and carpal tunnel syndrome depending on organ involvement. Recognizing the Congo red stain and its associated birefringence pattern is high-yield for boards, often tested with clinical vignettes describing these multi-organ manifestations.