Light Chain Proximal Tubulopathy: Expanding the Pathologic Spectrum with Deposition of Crystalline-Like Inclusions in Glomeruli and Interstitium in Addition to Proximal Tubules.
Shree G Sharma, Steve M Bonsib, Neriman Gokden. University of Arkansas for Medical Sciences, Little Rock; Louisiana State University Health Sciences Center, Shreveport
Background: Light chain proximal tubulopathy (LCPT) is a rare form of renal disease associated with plasma cell dyscrasias. There are less than 100 cases reported in literature. The affected patients may present with proteinuria, kidney failure, Fanconi syndrome, or osteomalacia. The extent of dysproteinemia varies from monoclonal gammopathy of undetermined significance to overt multiple myeloma (MM). It is characterized by the deposition of crystallized monoclonal light chains in the cytoplasm of proximal tubules (PT). By immunofluorescence (IF) these crystals are predominately staining with kappa, and ultrastructurally, crystals are located within lysosomes. Rare cases of LCPT without crystalline-like inclusions only showed prominent phagolysosomes by EM. Our case series expand the existing literature with the involvement of glomeruli and interstitial cells by crystalline-like inclusions.
Design: Retrospectively, the renal biopsy data base at 2 institutions was searched for last ten years for LCPT. 5 cases with LCPT were found. Clinical, light microscopic (LM), IF and EM findings were reviewed in each case.
Results: The patient ages ranged from 38 to 81 years (mean: 57; median: 54); 4 were male and 1 was female. 1 patient presented with Fanconi syndrome, 2 with proteinuria and 1 with renal failure. 4 patients were diagnosed with MM (IGG, kappa type); 1 patient had AL amyloidosis. LM showed abundant PAS negative, pale pink cytoplasmic inclusions in PT cells in all cases. In 1 case cytoplasmic inclusions were present in the podocytes, endothelial and parietal cells as well. IF revealed strong kappa staining of cytoplasmic inclusions in 4 cases. EM showed electron dense rectangular, rhomboid, or needle- shaped crystals in PT cells in 3 cases (60%), 1 of which had crystals in mesangial, endothelial, visceral epithelial and interstitial cells as well. One showed prominent endolysosomes and one had amyloid fibrils only.
Conclusions: In a small number of LCPT cases crystalline-like inclusions may be deposited in glomerular and interstitial cells. It is important to be aware of these findings and look for the specific crystalline inclusions by LM, IF and EM in podocytes, endothelial, mesangial, parietal and interstitial cells in addition to PT epithelial cells. The mechanism of accumulation of these crystals in non-proximal tubular epithelial cell types and the significance of this finding are not clear.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 277, Wednesday Morning