A 60-year-old man with long-standing rheumatoid arthritis develops nephrotic syndrome. Renal biopsy shows amorphous eosinophilic material in the glomerular mesangium and vessel walls that is Congo red positive with apple-green birefringence under polarized light. Immunohistochemistry is positive for SAA protein. The amyloid type and classification per WHO 2022 amyloid nomenclature is:

• A AA amyloidosis (reactive/secondary amyloidosis); the amyloid fibril protein is serum amyloid A (SAA) cleaved to AA protein ✓
• B AL amyloidosis (primary amyloidosis); the amyloid fibril is formed from immunoglobulin light chain kappa or lambda
• C ATTR amyloidosis (transthyretin amyloidosis); the fibril protein is mutant transthyretin from hepatic synthesis
• D Abeta2M amyloidosis (dialysis-related amyloidosis); the fibril protein is beta-2 microglobulin retained in renal failure

Explanation

Secondary (AA) amyloidosis develops as a complication of chronic inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, familial Mediterranean fever, and chronic infections. The acute-phase reactant serum amyloid A (SAA) is produced in excess by the liver under IL-6 and IL-1 stimulation; partial proteolytic cleavage generates the AA fragment that misfolds and polymerizes into amyloid fibrils. Renal involvement (glomerular and vascular deposition) is the most common and clinically significant manifestation, presenting as nephrotic syndrome. IHC positivity with anti-SAA antibody confirms AA amyloidosis. AL amyloidosis is associated with plasma cell dyscrasias. ATTR amyloidosis causes cardiac and peripheral nerve involvement predominantly. Abeta2M occurs in long-term hemodialysis patients.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.