Monoclonal gammopathy of renal significance is a term that was recently introduced by the International Kidney and Monoclonal Gammopathy Research Group in order to distinguish monoclonal gammopathies associated with severe renal complications due to deposition of monoclonal proteins in the kidney from benign monoclonal gammopathy of undetermined significance’, which cannot lead to end-organ damage

Monoclonal gammopathy of renal significance is a term that was recently introduced by the International Kidney and Monoclonal Gammopathy Research Group in order to distinguish monoclonal gammopathies associated with severe renal complications due to deposition of monoclonal proteins in the kidney from benign monoclonal gammopathy of undetermined significance’, which cannot lead to end-organ damage.1,2 We found that the ultrastructural findings can help distinguishing MPGN with masked monoclonal deposits from true C3 GN with monoclonal gammopathy. had findings on biopsy most consistent with C3 glomerulonephritis prior to performing paraffin immunofluorescence. Thus a high index of suspicion is necessary to avoid misdiagnosis in these cases, as many would have been mistakenly diagnosed as C3 glomerulopathy or unclassified MPGN if paraffin immunofluorescence was not performed. Keywords:C3 glomerulonephritis, masked deposits, membranoproliferative glomerulonephritis, monoclonal gammopathy, monoclonal gammopathy of renal significance, monoclonal gammopathy of undetermined significance Glomerular involvement is not uncommonly present in patients with paraproteinemia. The paraprotein-associated glomerulopathies are classified according to the findings on renal biopsy utilizing light, immunofluorescence (IF), and electron microscopy in combination with the clinical information. Glomerular disorders in this category include immunoglobulin (Ig)-related amyloidosis, immunotactoid GN, type 1 cryoglobulinemic GN, monoclonal Ig deposition disease, proliferative GN with monoclonal Ig deposits, and C3 glomerulopathy with monoclonal gammopathy.1These cases commonly fall into the category of monoclonal gammopathy of renal significance when the associated hematological process does not meet diagnostic criteria for overt multiple myeloma or B-cell lymphoma.2Even in the lack of a diagnostic hematological process, the monoclonal Ig can have serious renal consequences and treatment of the underlying clonal process is frequently warranted. 3 It has recently been reported that Ig proteins occasionally show false negative staining by routine IF.4,5These deposits can be unmasked’ by performing IF on the formalin-fixed paraffin-embedded tissue after protease digestion (paraffin IF). Applying this technique to cases that show a membranoproliferative glomerulonephritis (MPGN) pattern has enabled this case series detailing the first clinicopathological description of glomerulopathy with an MPGN pattern by light microscopy and masked monotypic Ig deposits by IF. All these patients had an associated underlying Rabbit Polyclonal to BTLA clonal hematological disorder and many of them would have been misdiagnosed as C3 glomerulopathy if paraffin IF was not performed and the masked Igs detected. == RESULTS == The Nephropath renal biopsy database was reviewed from 1 August 2013 to 1 VGX-1027 1 December 2014 for cases with an MPGN pattern by light microscopy that VGX-1027 showed masked’ monotypic Ig deposits on IF (little to no staining for Igs by routine IF and positive Ig staining on paraffin IF with light chain restriction;Figure 1). Nine cases were identified who fulfilled these criteria and were included in this series. During this same time period, there were also six cases of true C3 GN in adults aged >40 years (evidence of MPGN with C3-only staining who did not show Ig unmasking on paraffin IF). == Figure 1. == Light and immunofluorescence microscopic findings in a case of membranoproliferative glomerulonephritis with masked immunoglobulin VGX-1027 G (IgG) kappa deposits (patient 2).(a) Glomerulus with mesangial expansion, endocapillary hypercellularity, and extensive basement membrane duplication (Jones methenamine silver; original magnification 400). (b) Positive IgG staining within a glomerulus in the paraffin-embedded tissue after protease digestion (direct immunofluorescence). (c) Kappa was positive while (d) lambda was negative within glomeruli by paraffin immunofluorescence (direct immunofluorescence). (e) The C3 was the dominant stain in glomeruli by routine immunofluorescence (direct immunofluorescence). (f) Subendothelial electron dense deposits (arrow) were present by electron microscopy (original magnification 12,000). The renal biopsy database (from January 2000 to January 2015) of the division of Anatomic Pathology at Mayo Clinic was searched for patients with a known monoclonal gammopathy who had a kidney VGX-1027 biopsy showing C3-only or GN with negative glomerular staining for IgG, IgM, IgA, kappa, lambda and C3 by routine IF. Twenty-six cases were identified who fulfilled these criteria, of which 21 had residual paraffin tissue to undergo paraffin IF, including 11 cases of C3 GN, 6 dense deposit disease (DDD), and 4 unclassified MPGN/cryoglobulinemic GN cases. Paraffin IF identified 7 (33%) cases (4 of the 11 C3 GN cases and 3 of the 4 unclassified MPGN/cryoglobulinemic GN cases) with positive VGX-1027 staining for Igs (all.