AJKD Atlas of Renal Pathology: Light ChainDeposition Disease
Agnes B. Fogo, MD,1 Mark A. Lusco, MD,1Behzad Najafian, MD,2 and Charles E. Alpers, MD2
Clinicaland Pathologic Features
Light chain deposition disease (LCDD) isthe most common of the non-AL amyloid monoclonal immunoglobulin depositiondiseases (MIDD), which also include subtypes with both light and heavy chainsor only heavy chain component. The specific type of MIDD is diagnosed byimmunofluorescence or immunohistochemistry. Patients with LCDD are middle-agedor older adults, and men are affected more often than women. The kidney is themajor organ involved, often with nephrotic range proteinuria. Patients lesscommonly have dominant tubular basement membrane, with lesser glomerulardeposits and little or no proteinuria. Patients may also show signs related tothe underlying plasma cell dyscrasia, such as anemia. Other organs may beinvolved, such as the liver or heart, but these extrarenal deposits do notusually cause clinical signs. Some patients have concomitant light chain castnephropathy caused by the monoclonal protein, with resulting acute kidneyinjury. Patients who are eligible for treatment of the underlying plasma celldyscrasia/multiple myeloma have hematologic response in about half of cases,with corresponding stabilization or even improvement of end-organ function.Most untreated patients develop end-stage renal disease. Patients who undergokidney transplantation despite persistent monoclonal protein develop recurrentdisease in the transplant.
Light microscopy: Advanced LCDD showsnodular sclerosis, with very similar appearance to diabetic nephropathy bylight microscopy. Early LCDD shows only mild mesangial expansion. Congo Redstain is negative.
Immunofluorescence microscopy: Monoclonallight chain staining, most commonly k light chain, in mesangium and alongglomerular and tubular basement membranes.
Electron microscopy: Mesangial and innerglomerular and outer tubular basement membrane deposits of extracellularpunctate, powdery, ground-pepper–like deposits, with extensive foot processeffacement. In some early cases, deposits may only be detected byimmunofluorescence.
Etiology/Pathogenesis
LCDD is due to deposition of a monoclonallight chain in mesangial areas and along glomerular and tubular basementmembranes. The monoclonal protein is due to underlying plasma cell dyscrasia.About half of patients have multiple myeloma by bone marrow examination.Patients with LCDD without diagnostic multiple myeloma were previously said tohave monoclonal gammopathy of undetermined significance, now called monoclonalgammopathy of renal significance.
DifferentialDiagnosis
LCDD may be distinguished from other causesof nodular sclerosis and mesangial expansion by specific light chain stainingin glomeruli and tubular basement membranes, negative Congo Red stain, andpunctate amorphous, ground-pepper–like appearance of deposits on electronmicroscopy. Fibrillary glomerulonephritis is Congo Red negative, and has polyclonalimmunoglobulin G and proliferative appearance; diabetic nephropathy shows nodeposits; and other MIDD show light and heavy chain staining or only heavychain staining. Other causes of a membranoproliferative glomerulonephritispattern show disease-specific immunofluorescence and electron microscopicappearances.
KeyDiagnostic Features
-Mesangial expansion or nodular sclerosis
-Monoclonal light chain staining inmesangium and along glomerular and basement membranes with linear appearance,most often k light chain
-Punctate amorphous ground-pepper–likedeposits on electron microscopy
Figure1. Light chain deposition disease can have anodular glomerulosclerosis appearance, which bears a striking resemblance todiabetic nephropathy (Masson trichrome stain). Reproduced with permission fromAJKD 32(6):e1.
Figure2. Light chain deposition disease which has k lightchain– restricted glomerular mesangial and capillary loop, and tubular basementmembrane staining (immunofluorescence microscopy, k light chain). Reproducedwith permission from AJKD 32(6):e1.
Figure3. Light chain deposition disease has granular,amorphous deposits on the endothelial aspect of the glomerular basementmembrane (electron microscopy). Reproduced with permission from AJKD 32(6):e1.
Figure4. Light chain deposition disease has granular,amorphous deposits on the endothelial aspect of the glomerular basementmembrane (electron microscopy). Reproduced with permission from AJKD 32(6):e1.
Figure5. Light chain deposition disease has granular,amorphous deposits on the outer aspect of the tubular basement membrane(electron microscopy). Reproduced with permission from AJKD 32(6):e1. - Atlasof Renal Pathology II e48 Am J Kidney Dis. ;66(6):e47-e48
