Case 3 -

MPGN Pattern with Prominent Pseudothrombi and IgM Kappa Restriction, Consistent with Waldenstrom's Lois J. Arend, Johns Hopkins Hospital, Baltimore, MD

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Clinical History History of Present Illness: 73-year-old white male was healthy until 2006 when he was diagnosed with rhinosinusitis. Since then, he has had recurrent sinus infections treated on multiple occasions with antibiotics and a regimen of steroids. He also has a history of BPH. In mid August 2010 he complained of severe sore throat and was hospitalized and treated with antibiotics. He was not informed of any kidney abnormalities. After discharge, the patient started developing lower extremity edema and shortness of breath, along with weight gain. The patient was started on diuretics at that time with significant improvement. Ten days after the patient was started on diuretics, he was admitted to an outside hospital for shortness of breath. On admission, he was febrile and diagnosed with pneumonia and left-sided pleural effusion. He was also found to have leukocytosis and significant weight gain. He was noted to have a creatinine of 2.39 mg/dL that improved to 1.7 mg/dL upon discharge, and after having been given steroids. The patient was started on broad-spectrum antibiotics initially that were switched to Zosyn afterwards. His leukocytosis improved on antibiotics. During his stay, the patient was found to have mild hematuria. After discharge the patient's creatinine improved to as low as 1.3 mg/dL. Repeat labs on follow-up one month later showed a creatinine of 3.4 mg/dL with an estimated GFR of 17. Review of Systems: He denies any shortness of breath. He has had difficulty controlling his blood pressure, systolic ranging in the 150s to 160s. His edema has improved significantly on the diuretic. Otherwise, his review of systems is negative. Medications: Bumetanide, Carvedilol, Famotidine, Levaquin, Terazosin, Avodart Physical Exam: BP 156/80 sitting, pulse 65; 167/82 standing, pulse 65 RR 16; temperature 36.5; weight 85.9 kg Lower extremities 2+ edema bilaterally. Other Labs: Negative for anti-GBM, ANCA, MPO, PR3, ASO, rheumatoid factor, ANA, and hepatitis C3 58, C4 6, both low. Proteinuria by ratio 576 mg/24 hr Ultrasound: 12.2-cm right and 13.1-cm left, no hydronephrosis Case 3 - Figure 1 H&E. Glomeruli contain massive eosinophilic, glassy intracapillary material (pseudothrombi) and focal subendothelial collections of the same material. Case 3 - Figure 2 H&E. The mesangial regions have a segmental increase in cellularity. Case 3 - Figure 3 PAS. The material is strongly PAS- positive. Some double contour formation is seen. Case 3 - Figure 4 Jones methenamine silver. The material is silver negative. Some double contour formation is seen. No spikes are present. Case 3 - Figure 5 Jones methenamine silver. Case 3 - Figure 6 H&E. The interstitium contains a focally intense inflammatory infiltrate containing lymphocytes, plasma cells, and focally numerous eosinophils. Case 3 - Figure 7 IHC, CD3. Scattered T-lymphocytes are present. Case 3 - Figure 8 IHC, CD20. Large numbers of B-lymphocytes are present. Case 3 - Figure 9 IF, IgM. There is 3-4+ granular and globular staining for IgM along capillary walls, within the mesangium, and in capillary lumens (pseudothrombi). Case 3 - Figure 10 IF, IgG. There is trace staining for IgG. Case 3 - Figure 11 IF, Kappa. There is 3-4+ granular and globular staining for kappa along capillary walls, within the mesangium, and in capillary lumens (pseudothrombi). Case 3 - Figure 12 IF, Lambda. There is trace staining for lambda. Case 3 - Figure 13 EM, 3800x. Electron dense deposits are present in the subendothelial region. There is foot process effacement. The glomerular basement membrane is duplicated. Case 3 - Figure 14 EM, 3000x. This capillary loop has a very large subendothelial deposit protruding into the lumen Case 3 - Figure 15 EM, 3000x. The lumen contains a large thrombus of electron dense material. Introduction: Follow-up information: Serum viscosity was normal. UPEP: spike in the Gamma region, 0.65 mg/dl, 10.0 mg/24h. Pattern consistent with glomerular proteinuria. Pattern consistent with monoclonal gammopathy. Immunofixation: One band of restricted electrophoretic mobility is present in the IgM lane with a corresponding band in the kappa lane. Kappa and lambda free light chains: 57.5 mg/L and 10.3 mg/L, ratio 5.58 (normals - kappa:3.3-19.4, lambda:5.7- 26.3, ratio: 0.26-1.65). Bone marrow flow: 8% phenotypically abnormal cells estimated to be present. The specimen contains a mixture of cell types. The pattern indicates involvement by a B cell lymphoproliferative disorder. Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: Kidney biopsy: Two cores of renal cortex and medulla contained 21 glomeruli, three obsolescent. H&E stain showed glomeruli with large eosinophilic, glassy intracapillary material and focal subendothelial collections of the same material. The material is strongly PAS-positive and silver negative. The mesangial regions have a segmental increase in cellularity. Some capillary walls show duplication of the basement membrane on the PAS and silver stains. No spikes are present. No crescents are seen. The interstitium contains a focally intense inflammatory infiltrate containing lymphocytes, plasma cells, and focally numerous eosinophils. There is moderate tubular atrophy and interstitial fibrosis. The arteries have moderate to severe intimal fibrotic thickening. Differential Diagnoses: Cryoglobulinemia Waldenstrom's macroglobulinemia MPGN Lupus nephritis Acute interstitial nephritis versus neoplastic infiltrate Nephrosclerosis, moderate Final Diagnosis: MPGN Pattern with Prominent Pseudothrombi and IgM Kappa Restriction, Consistent with Waldenstrom's Conclusion(s): Waldenstrom's Macroglobulinemia. References: Adamia, S, Pilarski PM, Belch AR, Pilarski LM. Genetics of Waldenstrom’s macroglobulinemia. 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