Table 5.

Summary of the main pathological findings in MGRS

Glomerular diseasesLMIF/IHCEM
 AmyloidosisCongo red+ mesangial expansion/nodulesAL: LC restriction (mostly λ)Unbranched randomly distributed fibrils (8-12 nm diameter)
Hairbrush projections from glomerular basement membranesAH: 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 expansionMesangial and capillary loop IgG, C3, κ and λ depositsUnbranched, randomly distributed 15-20 nm diameter fibrils
Positivity for DNAJB9 on IHC
 ITGMembranous-like or MPGN-like changesCoarse mesangial IgG (monoclonal in 60% of cases), C3 and occasional IgM depositsMicrotubules (20-60 nm diameter)
Congo red, silver mesangial expansion
 Type I cryoglobulinemic GNMPGN patternMonoclonal immunoglobulin (most frequently κ) of the same type as found in circulation, C3, C4 depositsPaired microtubules (25-40 nm diameter)
Endocapillary proliferative pattern/exudation
PAS+ capillary pseudothrombi common
 MIDDMesangial proliferation and Congo red, silver+ mesangial matrix expansion/nodulesLCDD: mesangial and/or glomerular basement membrane monoclonal LC depositsPowdery 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)
 PGNMIDEndocapillary proliferative GN/MPGNMonoclonal immunoglobulin or, more rarely, monoclonal LC depositsNonorganized mesangial, subendothelial, and subepithelial electron-dense deposits
 Membranous GN with monoclonal immunoglobulinMembranous changes (spikes, lucencies)Monoclonal immunoglobulin depositsNonorganized subepithelial electron-dense deposits
 C3G associated with monoclonal gammopathyEndocapillary proliferative GN/MPGNGranular, C3-dominant depositsNonorganized mesangial, subendothelial, and subepithelial electron-dense deposits
Dense osmiophilic transformation of basement membranes if DDD
 TMAGlomerular and/or arterial TMAPauci-immune pattern; occasional C3 trappingAcute: subendothelial flocculent material
Chronic: new subendothelial basement membrane and/or subendothelial widening
Tubulointerstitial diseases
 LCPTProximal tubular vacuolation/fragmentationLC inclusions within tubular epitheliumIntralysosomal or free rhomboid-shaped crystals in proximal tubules
Intracytoplasmic inclusions, often crystalloid
 Miscellaneous
 CSHAccumulated crystals within macrophages/histiocytes within glomerular or peritubular capillaries and in the mesangiumLC crystalloid inclusions within macrophages/histiocytesRhomboid 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