Case 1 -

Proliferative GN with Monoclonal IgG3κ Deposits Vivette D'Agati, M.D. Columbia University New York, NY

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Click here to view (or print) handout in single page format. (1.94 MB) Note: Any slides will be printed in color. Click here to view (or print) black and white handout. (1.63 MB) Note: Text will be in single page format and any slides will be in 6-per-page format. Clinical History The patient is a 74 year-old Caucasian female with longstanding hypothyroidism and depression and a 3-year history of hypertension. In March, 2003 she underwent a workup for chronic headaches, which led to discovery of a cerebellar mass and successful surgical resection of a cerebellar hemangioblastoma. In February, 2006 she developed asymptomatic microhematuria, and urologic work up (including cystoscopy and renal ultrasound) was negative. In July, 2006 she was noted on routine urinalysis to have 3+ proteinuria, 0-3 rbc/hpf, and 6-10 wbc/hpf. In December, 2006 she developed edema and was referred to a nephrologist for investigation of nephrotic syndrome. Medications at that time included Avalide, Zoloft, Singulair, Allegra, Toprol and Synthroid. On nephrologic work-up in January, 2007 the patient was found to have BP 138/80 and 2+ lower extremity edema. The patient denied history of diabetes, fever, rash, arthralgias, or gross hematuria. Laboratory studies included serum creatinine 1.3 mg/dL, BUN 43 mg/dL, 24 hour urine protein 5.119 grams, serum albumin 3.3 g/dL, Hct 31.4%, WBC 7.2K, platelets 340K, and normal serum electrolytes (Na, K, Cl, CO2, Ca). Urinalysis revealed 3+ protein and microhematuria, without rbc casts. Serologies included negative ANA, ANCA, hepatitis B surface Ag, HCV, HIV and rheumatoid factor. Serum complements (C3 and C4) were within the normal range. Serum protein electrophoresis revealed reduced albumin 3.0 (normal 3.6-4.7 g/dL) and reduced gamma globulins 0.4 (normal 0.6-1.6 g/dL). Kidney size by ultrasound was 10.4 and 10.3 cm. A renal biopsy was performed in January, 2007. Case 1 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 1 - Slide 2 Click to view with ImageScope Click to view with a Web-Based Viewer Case 1 - Slide 3 Click to view with ImageScope Click to view with a Web-Based Viewer   Case 1 - Figure 1 (PAS). Low power view shows uniform enlargement and hyperlobulation of glomeruli. Case 1 - Figure 2 (H&E). Glomerular capillary lumina are globally narrowed by mesangial and endocapillary proliferation including infiltrating monocytes and neutrophils. Case 1 - Figure 3 (PAS). Some of the expanded mesangial areas display nodular mesangial sclerosis. Many glomerular basement membranes appear duplicated, producing a membranoproliferative pattern. Case 1 - Figure 4 (Jones methenamine silver). There are widespread double contours of the glomerular basement membranes. Some mesangial nodules contain non-argyrophilic deposits. Case 1 - Figure 5 (Immunofluorescence micrograph stained for IgG). There is global granular to semilinear staining of glomerular basement membranes for IgG. Fewer punctate granular deposits are also present in the mesangium. No staining is observed in Bowman's capsule or the tubular basement membranes. Case 1 - Figure 6 (Immunofluorescence micrograph stained for IgG). High power shows the confluent granular texture of the IgG deposits in a predominantly subendothelial distribution. Case 1 - Figure 7 (Immunofluorescence micrograph stained for C3). There is intense staining for C3 in a similar distribution to IgG above. Case 1 - Figure 8 (Immunofluorescence micrograph stained for kappa). Strong global granular to semilinear staining for kappa light chain outlines the glomerular capillary walls, with fewer deposits in the mesangium. There is no staining of Bowman's capsule or tubular basement membranes. Case 1 - Figure 9 (Immunofluorescence micrograph stained for lambda). The stain for lambda light chain is completely negative in glomeruli, as well as tubules. Case 1 - Figure 10 (Electron micrograph). On low power, granular electron dense deposits can be identified in the sclerotic mesangial nodules and subendothelial regions (x 2000). Case 1 - Figure 11 (Electron micrograph). Glomerular capillary lumina are narrowed by circumferential mesangial interposition and duplication of glomerular basement membrane in association with granular mesangial and subendothelial electron dense deposits (x 4000). Case 1 - Figure 12 (Electron micrograph). On higher power examination, some of the subendothelial deposits exhibit a variegated texture, but without evidence of organized substructure (x 6000).