A Rare Case of Light Chain Proximal Renal Tubulopathy with Lambda-Restricted Crystal Storing Histiocytosis

Crystal storing histiocytosis (CSH) is a rare morphologic manifestation of monoclonal gammopathy of renal significance (MGRS) in which monoclonal crystals of various geometric shapes collect within histiocytes and are deposited in various organs like kidneys, bone marrow, lungs, liver, stomach, spleen, skin and cornea. Usually kappa subtype of monoclonal crystals, in the renal interstitium or glomerular capillary walls have been described in the literature. We present a case of CSH with lambda monoclonal crystals involving the proximal renal tubules causing light chain tubulopathy in a patient with chronic kidney disease with sub-nephrotic range proteinuria.  

CASE PRESENTATION 

63-year-old Caucasian male with hypertension, history of pancreatitis about 6 years prior, Raynaud’s disease, hypertriglyceridemia who presented to nephrology outpatient clinic for evaluation of Chronic Kidney Disease (CKD). He did not have any foamy urine, gross hematuria, rashes or bony pain. Labs (Table 1): Baseline creatinine (Cr) was 0.8-0.9mg/dl, but Cr elevated to 1.6 mg/dl in 2018 and then increased upto 1.8-1.9 mg/dl at the time of presentation. Work up revealed microalbumin/creatinine ratio (UACR) of 100mg/gCr and sub-nephrotic range proteinuria with protein/Cr ratio (UPCR) of 1.8g/g, no microscopic hematuria, Kappa/lambda ratio of 0.03 with lambda predominance (kappa/lambda = 19.2/584.8). Serum protein electrophoresis (SPEP) was consistent with hypogammaglobulinemia with serum IgA level mildly low (53 mg/dl) while IgG and IgM levels were normal. Urine protein electrophoresis (UPEP) consistent with tubular proteinuria and monoclonal gammopathy, serum immunofixation (SIFE) with lambda free light chain (Bence Jones proteinemia), urine immunofixation (UIFE) with Lambda Bence Jones proteinuria. 24-hour urine protein was 1.9g. Kidney biopsy was pursued given suspicion of MGRS. Biopsy showed normocellular glomeruli. The proximal tubules showed focal histiocyte-like cells within the tubular epithelium and occasionally in the lumen. Congo Red stain was negative, suggesting no amyloidosis. Immunohistochemistry was positive for CD68, supporting a macrophage/histiocyte lineage. Immunofluorescence showed tubules with focal positive staining in cytoplasmic granules for lambda light chain 2+, but no staining for kappa, consistent with abnormally elevated free lambda light chain levels in the serum. Electron microscopy (EM) (Fig 1) showed histiocytic cells in the tubules had membrane-bound, lysosomal inclusions of fibrillary material, of about 10nm in size, focally arranged in vague bundles, similar to the “spicular” appearance often seen in amyloid glomerular deposits.  The patient was evaluated by oncology and bone marrow biopsy done which showed multiple myeloma with 12 % plasma cells. FDG-PET scan without any evidence of FDG avid disease. Patient has been initiated on Dara-CyBorD treatment (daratumumab, cyclophosphamide, bortezomib, and dexamethasone) with improving lambda light chain.

This case highlights the importance of considering light chain proximal tubulopathy with crystal storing histiocytosis in the evaluation of CKD along with proteinuria without significant albuminuria and that kidney biopsy with electron microscopy is crucial to diagnosis. The presence of crystal-storing histiocyte-like cells in the tubules is rare, and this condition is typically associated with kappa light chain monoclonality unlike our case with lambda light chain predominance. These cellular inclusions may consist of crystalline structures of various shapes. The type of fibrillary inclusions seen in this case is unusual and is similar to what has been described as amyloid-like deposits in the tubular cells associated with lambda light chain cast nephropathy, although in this case amyloidosis was ruled out with negative Congo red stain and patient had proximal tubulopathy rather than cast nephropathy.