Proximal Tubulopathy without Crystalline-Like Inclusions: An Important Yet Not Well Recognized Lesion in the Spectrum of Monoclonal Light Chain-Related Renal Diseases
GA Herrera, EA Turbat-Herrera. Nephrocor, Bostwick Laboratories, Tempe, AR
Background: Light chain-related renal lesions encompass a heterogeneous group of glomerular, interstitial, and vascular manifestations. Proximal tubular damage without crystalline-like inclusions is a poorly recognized member of the group. This lesion is characterized by various degrees of proximal tubular damage associated with a prominent lysosomal system containing enlarged lysosomes, some with atypical shapes. Clinical presentation includes acute renal failure, impairment of normal proximal tubular function, and / or slowly progressive renal insufficiency. Some patients carry a diagnosis of monoclonal gammopathy of unknown significance (MGUS) and are biopsied because of renal dysfunction, in an attempt to determine whether the renal dysfunction is related to the circulating monoclonal light chains.
Design: In an effort to obtain a better idea of the incidence and clinical importance of this lesion, the renal biopsy files of two institutions were carefully examined over a period of three years to identigy cases with this diagnosis. Light, immunofluorescence, and electron microscopy were carefully reviewed in each case.
Results: A total of 1200 renal biopsies were part of the study. lesions associated with nephropathic light chains were collected. Seven cases of proximal tubulopathy were found representing 14% of all monoclonal light chain-associated renal lesions identified. Electron microscopy was crucial in revealing findings suggestive or indicative of the diagnosis. Either immunofluorescence or ultrastructural labeling demonstrated that the lysosomes were packed with monotypical light chains in each case.
Conclusions: Proximal tubulopathy without crystalline-like inclusions is not an uncommon lesion but it remains significantly unrecognized. In patients with a diagnosis of MGUS, this finding indicates that the renal dysfunction is produced by the circulating light chains and that therapeutic intervention is indicated. Because the findings at the light microscopic level may be subtle and immunofluorescence may not be able to demonstrate monoclonal light chains in proximal tubules, ultrastructural evaluation is crucial in some cases. Ultrastructural immunolabeling for light chains to demonstrate monoclonality may be needed to solidify the diagnosis in some cases.
Category: Kidney (does not include tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 233, Wednesday Afternoon