A 60-year-old man with IgG kappa multiple myeloma develops macroglossia, periorbital purpura (racoon eyes), and restrictive cardiomyopathy. Congo red staining of the endomyocardial biopsy shows apple-green birefringence under polarized light. Mass spectrometry-based proteomic analysis of the amyloid deposits would be most informative for which reason?
- A To quantify the degree of cardiac amyloid burden and predict prognosis
- B To identify somatic mutations in the amyloid fibrils requiring targeted therapy
- C To distinguish AL from ATTR amyloidosis — both can occur in elderly patients and differ in treatment ✓
- D To differentiate amyloid from pseudo-amyloid deposits such as LECT2 amyloidosis
Explanation
The clinical presentation (myeloma + macroglossia + periorbital purpura + cardiomyopathy) strongly suggests AL amyloidosis from immunoglobulin light chains. However, in elderly patients ATTR (transthyretin) amyloidosis must be excluded because: wild-type ATTR cardiac amyloidosis has similar cardiac presentation, treatment differs dramatically (tafamidis for ATTR vs. chemotherapy/stem cell transplant for AL), and both can coexist. Mass spectrometry-based proteomics is the gold standard for typing amyloid fibrils, identifying not just the precursor protein (kappa/lambda light chain vs. TTR) but also specific variants. IHC can be inconclusive; laser capture microdissection + mass spectrometry has 98%+ accuracy.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.