Kidney biopsy of a patient with nephrotic syndrome shows focal segmental glomerulosclerosis (FSGS). Electron microscopy reveals diffuse podocyte foot process effacement. IHC with anti-phospholipase A2 receptor (PLA2R) antibody stains the glomerular capillary walls strongly positive. How does this finding alter the diagnosis?
- A It confirms PLA2R-associated FSGS, a distinct entity requiring immunosuppression targeting PLA2R autoantibodies
- B PLA2R staining in FSGS indicates secondary FSGS due to malignancy
- C It changes the diagnosis to primary membranous nephropathy — PLA2R is the dominant target antigen in ~75% of primary MN, not FSGS ✓
- D It suggests collapsing variant FSGS associated with PLA2R gene polymorphisms
Explanation
Strong granular PLA2R staining along glomerular capillary walls is pathognomonic of primary (idiopathic) membranous nephropathy (MN), not FSGS. PLA2R is the major autoantigen in ~75% of primary MN; circulating anti-PLA2R IgG4 antibodies bind podocyte PLA2R, form subepithelial immune complexes that activate complement and disrupt the filtration barrier. If this staining pattern is present, the diagnosis of FSGS should be reconsidered — the FSGS pattern may be a secondary finding in advanced MN with podocyte depletion. Clinically, serum anti-PLA2R antibodies are used to monitor disease activity and guide treatment.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.