Isolated Light Chain Proximal Tubulopathy without Crystal Formation – An Under-Recognized and Critically Important Entity.
Christopher P Larsen, Patrick D Walker. Nephropathology Associates, Little Rock, AR
Background: The renal diseases most frequently associated with myeloma include light chain deposition disease, cast nephropathy, and amyloidosis. Less frequently reported is light chain proximal tubulopathy (LCPT) characterized by kappa-restricted crystal deposits in the proximal tubule cytoplasm. These patients classically present with Fanconi syndrome in the setting of smoldering myeloma. LCPT without crystal deposition is only loosely related to the typical LCPT. Little is known about this entity as only 3 cases have previously been reported compared with over 50 cases of LCPT with crystals. We describe 10 cases of LCPT without intra-cytoplasmic crystals and detail the pathologic and clinical significance of this not so uncommon condition.
Design: A search was performed of the 10081 native kidney biopsies processed by our laboratory over the past 2 years for cases that had light chain restriction limited to the proximal tubule cytoplasm by immunofluorescence without evidence of other concurrent paraproteinemic renal diseases on biopsy. All cases were evaluated by light, immunofluorescence, and electron microscopy.
Results: 13 cases of isolated LCPT were found representing 4.0% of light chain-related diseases. 10/13 cases of LCPT did not have intracytoplasmic crystals and 9 of these 10 showed lambda restriction. In the cases with crystals, 2 were kappa subtype. Only 3/10 patients with LCPT without crystals had a diagnosis of a plasma cell dyscrasia at the time of renal biopsy. After the biopsy was reported, follow-up was available on 9/10 patients with 9/9 showing a plasma cell dyscrasia. 8/9 had multiple myeloma, only one of which was classified as smoldering myeloma. Six of the patients without crystals were tested for Fanconi'syndrome and none were positive.
Conclusions: LCPT without crystal formation is a diagnostic entity on renal biopsy that has several distinctions from the more commonly described LCPT with crystals. Whereas, over 90% of cases with crystals in the literature are of the kappa subtype, our series shows that 90% without crystals are of the lambda subtype. Additionally, PLCT without crystals is more likely to be associated with multiple myeloma than PLCT with crystals and less likely to be associated with a Fanconi syndrome. The fact that LCPT without crystals is so rarely described in the medical literature despite being more than 3 times as prevalent in our series leads us to believe that it is an under recognized entity. And given that it is often associated with previously unrecognized myeloma, it is a critically important diagnosis.
Category: Kidney (does not include tumors)
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 257, Wednesday Afternoon