Kidney Biopsy of the Month: Light Chain Proximal Tubulopathy with Crystals (LCPT)

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We continue the focus on Myeloma kidney, which started last month with Light Chain Cast Nephropathy. This month the emphasis is on Light Chain Proximal Tubulopathy with Crystals (LCPT)- a distinct entity.

Terminology

  • Chronic tubulointerstitial nephropathy caused by intracytoplasmic crystalline inclusions
  • Composed of monoclonal light chains present in proximal tubular epithelial cells

Pathogenesis

  • Abnormal monoclonal immunoglobulin light chains (usually kappa, Vk1)
  • Produced by clonal proliferation of plasma cells
  • Resistant to enzymatic breakdown

Clinical Issues

Incidence

Rare (~ 0.06% of renal biopsies) but may be overlooked

Fanconi syndrome (acquired)

  • Normoglycemic glycosuria
  • Aminoaciduria, uricosuria
  • Hyperphosphaturia with hypophosphatemia
  • Chronic renal failure, slowly progressive

Histology

  • Glomeruli: normal
  • Tubules: intracellular crystalline inclusions within proximal tubular epithelial cells
  • Acute and chronic tubular injury
  • May show other manifestations of monoclonal protein deposition
    – Crystal-storing histiocytosis with monoclonal light chains
    – Myeloma cast nephropathy
    – Light chain deposition disease (in GBM and TBM)
Figure 1: Tubular epithelial cells with a variable swollen appearance with PAS cytoplasmic crystalline-like material. Intracytoplasmic crystalline material that stained for monotypic light chain can be seen in the proximal tubules
Figure 2: Trichrome Intracytoplasmic crystals.

Figure 3: Kappa-light chain restricted atypical plasma cell infiltrate (in situ hybridization)

Immunofluorescence (IF)

  • Intracellular monotypic staining for κ or λ light chain
  • IF can often be negative in crystalline monogammopathy, and staining of formalin-fixed paraffin-embedded (FFPE) tissue using IHC or pronase IF is recommended to demonstrate monotypic light chain
Figure 4: Large aggregates of crystals revealed positive staining for kappa light chain (circled). Immunofluorescence showed bright linear staining of the tubular basement membranes for kappa light chain without staining for lambda light chain. There is a concurrent light chain deposition disease in this case.
Figure 5: Negative lambda staining in proximal tubular crystals.

Electron Microscopy

Electron-dense crystalline structures within cytoplasm of proximal tubular epithelial cells

Figure 6: Finely granular electron-dense deposits demonstrated in the tubular basement membranes. Crystals of various sizes and shapes within the tubular epithelium
Figure 7: Crystals of various sizes and shapes within the tubular epithelium

Serologic Testing

  • Monoclonal protein in serum, usually IgG kappa
  • Bence Jones proteinuria, usually kappa light chain

Treatment

Treatment of underlying plasma cell dyscrasia or lymphoma

Tiffany Shao, MD FRCPC FCAP
University of Calgary, Canada

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