Expanding the pathologic spectrum of immunoglobulin light chain proximal tubulopathy

Arch Pathol Lab Med. 2007 Sep;131(9):1368-72. doi: 10.1043/1543-2165(2007)131[1368:ETPSOI]2.0.CO;2.

Abstract

Context: In plasma cell dyscrasias, involvement of the distal tubules is frequent and well characterized. In contrast, proximal tubules have only rarely been reported to show diagnostic pathology such as intracytoplasmic crystals.

Objective: To look for additional morphologic features that might be helpful in the diagnosis of proximal tubulopathy associated with an underlying plasma cell dyscrasia.

Design: We examined patients presenting with nonspecific renal symptoms who were found to have light chain restriction limited to proximal tubular epithelium by immunofluorescence. We correlated these results with light microscopy, electron microscopy, and the clinical findings.

Results: By immunofluorescence, 5 patients had light chain restriction in proximal tubular epithelium. By light microscopy, only 1 patient had focal rhomboid crystals in the proximal tubular epithelium; all other biopsies failed to show any discernible pathology within the proximal tubules or elsewhere in the kidney. By electron microscopy, proximal tubules from 2 patients showed crystals with a latticelike structure, whereas the remaining 3 patients had only prominent phagolysosomes. However, by immunoelectron microscopy, the lysosomal content showed light chain restriction (in 2 cases studied). Post-kidney biopsy, all patients were diagnosed with multiple myeloma or plasma cell dyscrasia. One patient developed renal failure and had recurrence of crystals in the allograft.

Conclusions: Light chain proximal tubulopathy may be associated with the presence of crystals or with the presence of phagolysosomes with light chain restriction as the sole abnormality. Both kappa and lambda light chains may be involved. The prognosis is variable and the pathology may recur in transplants.

MeSH terms

  • Biopsy
  • Crystallization
  • Fanconi Syndrome / diagnosis
  • Fanconi Syndrome / metabolism*
  • Fanconi Syndrome / pathology*
  • Female
  • Gene Expression Regulation
  • Humans
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Light Chains / metabolism*
  • Immunoglobulin kappa-Chains / genetics
  • Immunoglobulin kappa-Chains / metabolism
  • Immunoglobulin lambda-Chains / genetics
  • Immunoglobulin lambda-Chains / metabolism
  • Kidney Tubules, Proximal / metabolism*
  • Kidney Tubules, Proximal / pathology*
  • Kidney Tubules, Proximal / ultrastructure
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Paraproteinemias / diagnosis
  • Paraproteinemias / metabolism
  • Paraproteinemias / pathology*
  • Phagosomes / ultrastructure
  • Renal Insufficiency / diagnosis
  • Renal Insufficiency / metabolism
  • Renal Insufficiency / pathology

Substances

  • Immunoglobulin Light Chains
  • Immunoglobulin kappa-Chains
  • Immunoglobulin lambda-Chains