Summary of the main pathological findings in MGRS
| Glomerular diseases . | LM . | IF/IHC . | EM . |
|---|---|---|---|
| Amyloidosis | Congo red+ mesangial expansion/nodules | AL: LC restriction (mostly λ) | Unbranched randomly distributed fibrils (8-12 nm diameter) |
| Hairbrush projections from glomerular basement membranes | AH: HC deposits (g1 or g4, or a) | ||
| Congo red+ deposits in interstitium and vessel walls (occasional) | AHL: LC and HC deposits | ||
| FG* | Congo red−, silver− mesangial expansion | Mesangial and capillary loop IgG, C3, κ and λ deposits | Unbranched, randomly distributed 15-20 nm diameter fibrils |
| Positivity for DNAJB9 on IHC | |||
| ITG | Membranous-like or MPGN-like changes | Coarse mesangial IgG (monoclonal in 60% of cases), C3 and occasional IgM deposits | Microtubules (20-60 nm diameter) |
| Congo red−, silver− mesangial expansion | |||
| Type I cryoglobulinemic GN | MPGN pattern | Monoclonal immunoglobulin (most frequently κ) of the same type as found in circulation, C3, C4 deposits | Paired microtubules (25-40 nm diameter) |
| Endocapillary proliferative pattern/exudation | |||
| PAS+ capillary pseudothrombi common | |||
| MIDD | Mesangial proliferation and Congo red−, silver+ mesangial matrix expansion/nodules | LCDD: mesangial and/or glomerular basement membrane monoclonal LC deposits | Powdery electron-dense deposits along inner aspect of glomerular basement membranes, mesangium, and outer aspect of tubular basement membranes |
| HCDD: κ and λ negative, staining for 1 of the immunoglobulins (most commonly IgG or IgM) | |||
| PGNMID | Endocapillary proliferative GN/MPGN | Monoclonal immunoglobulin or, more rarely, monoclonal LC deposits | Nonorganized mesangial, subendothelial, and subepithelial electron-dense deposits |
| Membranous GN with monoclonal immunoglobulin | Membranous changes (spikes, lucencies) | Monoclonal immunoglobulin deposits | Nonorganized subepithelial electron-dense deposits |
| C3G associated with monoclonal gammopathy | Endocapillary proliferative GN/MPGN | Granular, C3-dominant deposits | Nonorganized mesangial, subendothelial, and subepithelial electron-dense deposits |
| Dense osmiophilic transformation of basement membranes if DDD | |||
| TMA | Glomerular and/or arterial TMA | Pauci-immune pattern; occasional C3 trapping | Acute: subendothelial flocculent material |
| Chronic: new subendothelial basement membrane and/or subendothelial widening | |||
| Tubulointerstitial diseases | |||
| LCPT | Proximal tubular vacuolation/fragmentation | LC inclusions within tubular epithelium | Intralysosomal or free rhomboid-shaped crystals in proximal tubules |
| Intracytoplasmic inclusions, often crystalloid | |||
| Miscellaneous | |||
| CSH | Accumulated crystals within macrophages/histiocytes within glomerular or peritubular capillaries and in the mesangium | LC crystalloid inclusions within macrophages/histiocytes | Rhomboid and needle-shaped crystalloid inclusions and vacuoles within macrophages/histiocytes. |
| Glomerular diseases . | LM . | IF/IHC . | EM . |
|---|---|---|---|
| Amyloidosis | Congo red+ mesangial expansion/nodules | AL: LC restriction (mostly λ) | Unbranched randomly distributed fibrils (8-12 nm diameter) |
| Hairbrush projections from glomerular basement membranes | AH: HC deposits (g1 or g4, or a) | ||
| Congo red+ deposits in interstitium and vessel walls (occasional) | AHL: LC and HC deposits | ||
| FG* | Congo red−, silver− mesangial expansion | Mesangial and capillary loop IgG, C3, κ and λ deposits | Unbranched, randomly distributed 15-20 nm diameter fibrils |
| Positivity for DNAJB9 on IHC | |||
| ITG | Membranous-like or MPGN-like changes | Coarse mesangial IgG (monoclonal in 60% of cases), C3 and occasional IgM deposits | Microtubules (20-60 nm diameter) |
| Congo red−, silver− mesangial expansion | |||
| Type I cryoglobulinemic GN | MPGN pattern | Monoclonal immunoglobulin (most frequently κ) of the same type as found in circulation, C3, C4 deposits | Paired microtubules (25-40 nm diameter) |
| Endocapillary proliferative pattern/exudation | |||
| PAS+ capillary pseudothrombi common | |||
| MIDD | Mesangial proliferation and Congo red−, silver+ mesangial matrix expansion/nodules | LCDD: mesangial and/or glomerular basement membrane monoclonal LC deposits | Powdery electron-dense deposits along inner aspect of glomerular basement membranes, mesangium, and outer aspect of tubular basement membranes |
| HCDD: κ and λ negative, staining for 1 of the immunoglobulins (most commonly IgG or IgM) | |||
| PGNMID | Endocapillary proliferative GN/MPGN | Monoclonal immunoglobulin or, more rarely, monoclonal LC deposits | Nonorganized mesangial, subendothelial, and subepithelial electron-dense deposits |
| Membranous GN with monoclonal immunoglobulin | Membranous changes (spikes, lucencies) | Monoclonal immunoglobulin deposits | Nonorganized subepithelial electron-dense deposits |
| C3G associated with monoclonal gammopathy | Endocapillary proliferative GN/MPGN | Granular, C3-dominant deposits | Nonorganized mesangial, subendothelial, and subepithelial electron-dense deposits |
| Dense osmiophilic transformation of basement membranes if DDD | |||
| TMA | Glomerular and/or arterial TMA | Pauci-immune pattern; occasional C3 trapping | Acute: subendothelial flocculent material |
| Chronic: new subendothelial basement membrane and/or subendothelial widening | |||
| Tubulointerstitial diseases | |||
| LCPT | Proximal tubular vacuolation/fragmentation | LC inclusions within tubular epithelium | Intralysosomal or free rhomboid-shaped crystals in proximal tubules |
| Intracytoplasmic inclusions, often crystalloid | |||
| Miscellaneous | |||
| CSH | Accumulated crystals within macrophages/histiocytes within glomerular or peritubular capillaries and in the mesangium | LC crystalloid inclusions within macrophages/histiocytes | Rhomboid and needle-shaped crystalloid inclusions and vacuoles within macrophages/histiocytes. |
HC, heavy chain; LC, light chain.
Occasional cases of FG could show congophilia (congophilic FG). These cases could be reliably distinguished from amyloid deposits by DNAJB9 immunostain or mass spectroscopy.72