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

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, V_k1)
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