Crescentic IgM-κ Monoclonal Immunoglobulin Deposition Disease with Thrombotic Microangiopathy in Waldenström's Macroglobulinemia: A Rare and Aggressive Monoclonal Gammopathy of Renal Significance Presentation - A Case Report and Literature Review.

INTRODUCTION: Monoclonal immunoglobulin deposition disease (MIDD) is a rare monoclonal gammopathy of renal significance (MGRS) characterized by linear, non-organized deposition of immunoglobulin fragments along glomerular, tubular, and vascular basement membranes. While light and heavy chain MIDDs are more frequently reported, IgM-associated MIDD is exceedingly rare, with only a few cases documented.

CASE PRESENTATION: We report a 71-year-old man who presented with seronegative rapidly progressive glomerulonephritis (RPGN) and sub-nephrotic range proteinuria. Initial serologies were negative for autoimmune and infectious causes. A monoclonal workup revealed an IgM-κ paraprotein, prompting further evaluation. Kidney biopsy demonstrated diffuse crescentic glomerulonephritis (100%), linear IgM-κ deposits, and arterial thrombotic microangiopathy (TMA). Bone marrow studies confirmed lymphoplasmacytic lymphoma with an MYD88 c.794T>C (p.Leu265Pro) mutation, consistent with Waldenström's macroglobulinemia (WM).

CONCLUSION: This case represents the first reported instance of IgM-κ MIDD presenting with both crescentic GN and TMA in the setting of WM, defining a uniquely aggressive dual-injury kidney phenotype. It highlights the diagnostic challenge of seronegative RPGN, in which MIDD should be included in the differential diagnosis. The case underscores the importance of integrated histopathology and hematologic genomics in identifying rare MGRS entities, recognizing that severe kidney injury may evolve rapidly despite appropriate management.