Amyloidosis
USMLE Step 1Difficulty: easyLast updated:
A 63-year-old man is evaluated for 4 months of leg swelling and fatigue. Examination shows macroglossia and bilateral pitting edema. Urinalysis shows 4+ protein without hematuria; 24-hour urine protein is 6.2 g. Serum free light-chain testing shows a markedly increased lambda light-chain concentration. A renal biopsy shows glomeruli with deposits of pink, amorphous, acellular material on hematoxylin and eosin staining.
Which of the following additional findings would best confirm the nature of these deposits?
Answer and explanation
Correct answer: D. Apple-green birefringence under polarized light after Congo red staining
Nephrotic-range proteinuria, macroglossia, and a monoclonal lambda light chain suggest AL amyloidosis, and the biopsy shows amorphous eosinophilic deposits. Amyloid is made of insoluble fibrils that form congophilic beta-pleated sheets. According to the source, amyloid deposits stain pink with hematoxylin and eosin and can stain with PAS or Alcian blue. Their most characteristic feature is apple-green birefringence under polarized light microscopy after Congo red staining. Tissue diagnosis therefore relies on Congo red–stained sections examined with a polarizing microscope. The other options describe the hallmark lesions of diabetic nephropathy, membranous nephropathy, minimal change disease, and anti-GBM disease.
Each option explained
- A. Linear IgG deposition along the glomerular basement membraneIncorrect. Linear IgG along the GBM is the immunofluorescence pattern of anti-GBM (Goodpasture) disease.
- B. Nodular PAS-positive glomerulosclerosis (Kimmelstiel-Wilson nodules)Incorrect. Kimmelstiel-Wilson nodules are characteristic of diabetic nephropathy, not amyloid.
- C. Subepithelial 'spike-and-dome' deposits on silver stainIncorrect. Subepithelial spikes are typical of membranous nephropathy.
- D. Apple-green birefringence under polarized light after Congo red stainingCorrect. Congo red staining with apple-green birefringence under polarized light is the characteristic finding of amyloid.
- E. Diffuse podocyte foot-process effacement as the only abnormality on electron microscopyIncorrect. Isolated foot-process effacement with otherwise normal histology describes minimal change disease, which would not show amorphous deposits.
Key point
Amyloid is confirmed by Congo red staining showing apple-green birefringence under polarized light.
From the source
“Amyloid deposits stain pink with hematoxylin and eosin, contain carbohydrate constituents that stain with periodic acid-Schiff dye or with Alcian blue, but most characteristically have apple-green birefringence under polarized light microscopy after Congo red staining.”