A 62-year-old man with a 10-year history of rheumatoid arthritis presents with nephrotic syndrome (proteinuria 8 g/day, serum albumin 2.1 g/dL). Renal biopsy shows deposits that stain positive with Congo red and display the characteristic finding marked **D** in the diagram under polarized light microscopy. Which of the following is the most likely type of amyloidosis in this patient?

Explanation

## Why AA amyloidosis secondary to chronic inflammatory disease is right The patient has a long-standing chronic inflammatory condition (rheumatoid arthritis) and now presents with nephrotic syndrome. AA amyloidosis arises from serum amyloid A protein, an acute-phase reactant produced during chronic inflammation. The Congo red stain with apple-green birefringence under polarized light (marked **D**) is the pathognomonic histopathologic finding for ALL forms of amyloid, regardless of precursor protein type. AA amyloidosis predominantly affects the kidneys, causing nephrotic syndrome, and is the most common form of systemic amyloidosis in developing countries and in patients with chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and chronic infections like tuberculosis. The clinical context of long-standing RA with nephrotic syndrome makes AA amyloidosis the diagnosis. ## Why each distractor is wrong - **AL amyloidosis (light chain) secondary to monoclonal gammopathy**: While AL amyloidosis is the most common form in developed countries and can cause nephrotic syndrome, it is typically associated with multiple myeloma or MGUS, not rheumatoid arthritis. There is no mention of monoclonal protein, lytic bone lesions, or hypercalcemia. AL amyloidosis also characteristically causes restrictive cardiomyopathy and macroglossia, which are not mentioned here. - **Aβ amyloidosis associated with Alzheimer disease**: Aβ amyloidosis is associated with Alzheimer disease and cerebral amyloid angiopathy, not systemic disease. It does not cause nephrotic syndrome or present with renal involvement in this clinical context. - **AH amyloidosis associated with hereditary transthyretin mutation**: Hereditary transthyretin (TTR) amyloidosis causes familial amyloid polyneuropathy or familial amyloid cardiomyopathy. There is no family history mentioned, and the clinical presentation is inconsistent with hereditary TTR amyloidosis. **High-Yield:** Congo red stain with apple-green birefringence under polarized light is the diagnostic hallmark of ALL amyloid types; AA amyloidosis is the classic complication of chronic inflammation (RA, IBD, TB) and presents with nephrotic syndrome. [cite: Robbins 10e Ch 6; Harrison 21e Ch 108]