A 32-year-old woman presents with nephrotic syndrome (proteinuria 8 g/day, serum albumin 2.1 g/dL, edema). Kidney biopsy shows diffuse thickening of the glomerular basement membrane with a characteristic 'spike-and-dome' appearance on electron microscopy. Which of the following is NOT a typical feature of membranous nephropathy?

Explanation

## Membranous Nephropathy: Pathological Features **Key Point:** Membranous nephropathy is characterized by **subepithelial** (not subendothelial) immune complex deposition, creating the pathognomonic 'spike-and-dome' appearance. ### Electron Microscopy Findings The hallmark of membranous nephropathy is: - **Subepithelial** electron-dense deposits (in the space between the visceral epithelial cell and the GBM) - GBM projections that extend around these deposits, creating 'spikes' and 'domes' - Progressive GBM thickening **Warning:** Subepithelial 'humps' (dome-shaped deposits) are characteristic of **post-infectious glomerulonephritis** (PIGN), NOT membranous nephropathy. This is a classic exam trap. ### Immunofluorescence Pattern - **Granular** IgG and C3 deposits along the **capillary wall** (not mesangium) - Pattern is **continuous and diffuse** along the GBM ### Serological Markers - **Anti-PLA2R** (phospholipase A2 receptor) antibodies: positive in 70–80% of primary membranous nephropathy - Anti-THSD7A in a small subset - Absence of anti-ANCA, anti-GBM, or ANA (helps exclude secondary causes) ### Differential: Membranous vs. Post-Infectious GN | Feature | Membranous | Post-Infectious GN | |---------|-----------|-------------------| | **EM deposits** | Subepithelial (spikes-and-domes) | Subendothelial + humps | | **IF pattern** | Granular, capillary wall | Granular, capillary + mesangium | | **Clinical** | Nephrotic (insidious) | Nephritic (acute post-strep) | | **Prognosis** | 30–40% progress to ESRD | Usually resolves | **High-Yield:** The question stem describes 'spike-and-dome' appearance — this is membranous nephropathy. The presence of 'subepithelial humps' is the distractor and is actually the hallmark of post-infectious GN, not membranous nephropathy. ## Why Option 0 is Correct Subepithelial 'humps' (dome-shaped subepithelial deposits) are the characteristic EM finding of **post-infectious (post-streptococcal) glomerulonephritis**, not membranous nephropathy. Membranous nephropathy has **subepithelial deposits with GBM spikes**, but NOT the large rounded 'humps' seen in PIGN. [cite:Robbins 10e Ch 20]