A 45-year-old man presents with nephrotic syndrome. Renal biopsy shows irregular spikes on silver stain along the outer aspect of the GBM, and granular IgG deposits on immunofluorescence in a subepithelial pattern. Anti-phospholipase A2 receptor (PLA2R) antibodies are elevated. What is the pathological diagnosis?
- A Primary membranous nephropathy ✓
- B Membranoproliferative glomerulonephritis type I
- C IgA nephropathy
- D Focal segmental glomerulosclerosis
Explanation
Primary membranous nephropathy is caused by autoantibodies against M-type phospholipase A2 receptor (PLA2R) on podocytes in approximately 70% of cases. These autoantibodies deposit in the subepithelial space, activating complement and injuring podocytes, leading to diffuse glomerular basement membrane thickening. On silver stain, GBM projections ('spikes') form between immune deposits. Serum anti-PLA2R antibodies are now used diagnostically and to monitor disease activity/treatment response. MPGN shows subendothelial deposits and tram-track pattern; FSGS shows segmental sclerosis without immune deposits.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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