A case of endocapillary proliferative glomerulonephritis with macrophages phagocytosing monoclonal immunoglobulin lambda light chain

Abstract

Multiple myeloma (MM) is a plasma-cell neoplasm that can cause renal disorders. Renal lesions in MM can present with a very rare pathological manifestation involving a specific monoclonal immunoglobulin (Ig). We report the case of a 33-year-old woman who had edema, fatigue, elevated serum creatinine levels, hypoalbuminemia, and hypercholesterolemia. She had persistent hematuria and proteinuria lasting 3 years. Serum protein electrophoresis showed an M-spike, and serum immunofixation demonstrated the presence of monoclonal IgG λ. She had proteinuria in the nephrotic range, and a monoclonal λ fragment was present on urine immunofixation. Renal biopsy showed proliferative glomerulonephritis with λ light chain and C3c deposition and inflammatory cell infiltration with CD68. Macrophage lysosomes contained λ light chains, suggesting their partial phagocytosis. She was diagnosed with symptomatic MM and was treated with bortezomib and dexamethasone and an autologous peripheral stem cell transplant conditioned with intravenous melphalan. She achieved a partial response with decreased serum monoclonal protein and improved renal function. This case may be categorized as a monoclonal gammopathy-associated proliferative glomerulonephritis. The biopsy finding of partially phagocytosed Ig λ light chains by macrophages is very rare; this pathological condition is similar to crystal-storing histiocytosis.

Successful treatment with bortezomib and dexamethasone for proliferative glomerulonephritis with monoclonal IgG deposits in multiple myeloma: a case report

“…In that case, the types of immunoglobulin in the myeloma cells and kidneys were not identical, suggesting that the PGNMID was not related to MM. Recently, Watanabe et al have shown that a patient with PGNMID complicated with MM was treated with BD therapy and achieved a partial response with decreased serum monoclonal protein and improved renal function [8]. Although they did not examine renal histology after treatment, immunofluorescence with IgG subclasses and electron microscopic analysis of a glomerulus, the response for the BD therapy was consistent with our case that the patient reduced proteinuria and elevated serum albumin level after the first BD course.…”

“…However, PGNMID is rarely associated with a hematological malignancy [2]. Including our case, only six cases of PGNMID with multiple myeloma (MM) have been reported [2, 6–8]. In four previous cases, the pathogenic relationship between PGNMID and MM was unclear because a detailed description was not provided [2, 6, 7].…”

“…In four previous cases, the pathogenic relationship between PGNMID and MM was unclear because a detailed description was not provided [2, 6, 7]. The other case with PGNMID complicated with MM was treated with bortezomib and dexamethasone (BD) therapy and her renal function improved after initiating treatment for MM, though they did not examine second renal biopsy after treatment [8]. …”

An Unusual Case of Lysosomal Paraprotein Accumulation in Glomerular Endothelial Cells

“…LCDD and amyloidosis result from the deposition of monoclonal LCs, and LC proximal tubulopathy is caused by direct tubular damage due to monoclonal LCs and characterized by crystals or by an increased number of swollen lysosomes containing monoclonal LCs in proximal tubular cells. The presence of many enlarged lysosomes containing monoclonal LCs is documented most frequently in proximal tubular cells 1,2 and was reported in macrophages infiltrating the glomeruli in 1 patient with PCD 3 ; however, such lysosomes are rarely observed in glomerular intrinsic cells. We herein report the case of a patient with multiple myeloma (MM) who developed a rare renal manifestation.…”

Monoclonal Immunoglobulin Deposition Disease and Related Diseases

“…In light chain myeloma cast nephropathy (B, HE stain, 600×), large, acellular, hyaline casts show a cleavage plane or "fracture", and the cast is surrounded by large multinucleated giant cells. In cases with paraproteinemia, the glomeruli show endocapillary hypercellularity with infiltration of mononuclear cells (C, Masson's trichrome stain, 600×), which are CD68+ macrophages40 . In electron microscopy (D, 10,000×), phagolysosomes and crystals are noted in infiltrating macrophages, indicating crystal-storing histiocytosis in the glomeruli.…”