Patterns of Proximal Tubulopathy in Monoclonal Light Chain-Associated Renal Damage Defined Ultrastructurally
Guillermo A Herrera, Elba A Turbat-Herrera. Nephrocor, Orlando
Background: Proximal tubulopathy (PT) has been recognized as a pattern of renal damage in a subset of patients with circulating monoclonal light chains and renal manifestations. The clinical presentation may be sudden (acute renal failure) or slowly progressive renal dysfunction. Recognition of this entity requires careful immunomorphologic correlation.
Design: 3300 renal biopsies from 2 institutions over a period of 5 years were analyzed to identify cases of PT in patients with monoclonal light chain-associated renal dysfunction. Only those cases where the PT and related manifestations were the main pathologic findings associated with the renal damage were selected.
Specimen were examined by light, immunofluorescence, and electron microscopy with an emphasis on ultrastructural findings. Immunogold labeling, using a well described post-embedding protocol, was used in selected cases to correlate the localization of the monotypical light chains in specific compartments within the proximal tubular cells to highlight the pathologic findings.
Results: A total of 42 cases were found for a 1.6% incidence of this entity in this renal biopsy series. In all cases the proximal tubular damage was associated with monoclonal deposition of either κ or λ light chains in proximal tubules and surrounding interstitial compartment.
There were 4 distinct patterns of proximal tubular injury: 1- Tubular damage with features of acute tubular necrosis (apical blebbing, desquamation, fragmentation, vacuolization, and lysosomal proliferation in proximal tubular cells) (n=15), 2- Monotypical light chain deposition on the basolateral side associated with interstitial inflammatory response (n=21), 3- Intracytoplasmic crystalline-like inclusions in proximal tubular cells (n=4), and 4- lysosomal accumulation with enlargement and atypical lysosomal forms ("lysosomal constipation" pattern) (n=2).
The most common patterns observed were 1 and 2. Pattern 3 was uncommon and only identified in 4 cases, while pattern 4 was the least common and only observed in 2 cases.
Conclusions: It is important to accurately identify the different patterns of PT in patients with monotypical light chain-associated renal damage. Ultrastructural evaluation together with immunofluorescence evaluation play crucial roles in confirming that the pathologic changes are indeed related to the pathologic circulating light chains. The findings by light microscopy may mimic a number of other unrelated pathologic processes. Ultrastructural labeling provides exquisite immuno-morphologic correlation in these cases and should be used in cases that require clarification.
Monday, March 19, 2012 11:45 AM
Platform Session: Section H, Monday Morning