Waldenström's Macroglobulinemia and Cryoglobulinemic Glomerulonephritis: An Unusual Case of Monoclonal Gammopathy of Renal Significance

Abstract

Cryoglobulins are immunoglobulins that precipitate at temperatures below 37 °C and dissolve upon reheating. They can induce small-vessel vasculitis with renal involvement. Cryoglobulinemic glomerulonephritis is a rare manifestation that occurs in patients with monoclonal gammopathy, specifically Waldenström's macroglobulinemia. We present the case of a 52-year-old patient with a history of cutaneous vasculitis and hypothyroidism, who presented with generalized edema, moderate anemia, hypercholesterolemia, nephrotic range proteinuria of 12.69 g/day, microhematuria, arterial hypertension, and hypocomplementemia via the classical pathway, without acute kidney injury and with negative serological studies and positive cryoglobulins in the second determination. Serum and urine protein electrophoresis and immunofixation studies showed a monoclonal band of IgM and kappa light chain. Renal biopsy was consistent with cryoglobulinemic glomerulonephritis. In the context of dysproteinemia and cryoglobulinemic glomerulonephritis, bone-marrow aspiration and biopsy were performed, leading to the diagnosis of Waldenström's macroglobulinemia. Monoclonal gammopathies have been described in association with type I cryoglobulinemias. This described association is uncommon, which is why we present this case, along with a review of the literature.

Keywords: Waldenström’s macroglobulinemia; cryoglobulinemia glomerulonephritis; monoclonal gammopathy of renal significance.

Figure 1

(A). Light microscopy showing a glomerulus with intracapillary pseudotrombi (indicatedby arrows) positive for PAS staining (PAS Stain ×400). (B). Pseudotrombi with negative Trichrome staining (Masson’s Trichrome Stain ×400).

Figure 2

Immunofluorescence Staining. (A). IgM: Positive 2+ in loops, mesangium, and thrombi in 12/12 glomeruli. (B). C3: Positive 1+ in loops and in thrombi in 7/12 glomeruli. (C). C1q: Positive 1+ in loops and in thrombi in 7/12 glomeruli. (D). Fibrinogen: positive +/− in loops in 3/12 glomeruli. (E). Kappa: positive 2+ in loops and thrombi in 12/12 glomeruli.

Figure 3

Electron Microscopy. (A). Presence of pseudothrombus in the capillary lumen of a glomerulus. (B). Subendothelial deposits are evident in electron microscopy. The black arrow points to podocyte processes, the white arrow indicates the glomerular basement membrane, and the white asterisk marks a subendothelial deposit. (C). Subendothelial deposits in electron microscopy. (D). Subendothelial deposit measuring 942 nm at 43,000× magnification.