Glomerular histiocytosis characterized by intracapillary foam cells engulfing monotypic immunoglobulin light chains without crystallization: Two case reports

Nephrotoxic monoclonal light chains (LCs) in monoclonal gammopathy (MG) often cause kidney lesions. Although a few case reports have described glomerular histiocytosis in which infiltrating histiocytes engulfed noncrystalline monotypic immunoglobulin LCs in the setting of MG, this condition has not been considered a variant of MG-associated kidney lesions. We present two Japanese patients with MG who developed progressive proteinuria, hematuria, and kidney dysfunction with associated hematological conditions. Kidney biopsy revealed membranoproliferative glomerulonephritis characterized by glomerular CD68 + macrophage infiltration that contained noncrystalline monotypic LCs. Paraffin immunofluorescence revealed monotypic LCs that were masked during frozen immunofluorescence in one of the patients. One patient also exhibited peripheral IgG1λ deposition, which was suggestive of superimposition of proliferative glomerulonephritis with monoclonal immunoglobulin deposits, and monotypic LC deposition in the tubular epithelial cell cytoplasm, which was suggestive of noncrystalline LC proximal tubulopathy. The other patient also exhibited a few subepithelial deposits of fibril-like microstructures. Proteinuria and kidney dysfunction improved after initiation of LC-targeted therapy in one patient; however, the other patient presented with progressive kidney dysfunction without therapy. In conclusion, glomerular histiocytosis with noncrystalline monotypic LCs could be a variant of MG-associated kidney lesions, although it might also be called a noncrystalline variant of crystal-storing histiocytosis or a histiocyte-rich variant of MG-associated glomerulonephritis. The accumulation of similar cases is necessary to elucidate the overall picture, clinical and pathological characteristics, and prognosis.