1. ISRTPCON and CME AIIMS NEW DELHI 12-14 Sept,2013 Dr Kiran K Senior Resident, PDCC-Renal and Transplant Pathology Department of Histopathology PGIMER, Chandigarh

2.  Clinical history: o A 40 year old male with no previous comorbidities presented with complaints of facial puffiness and oedema of lower extremeties of 7 months duration. o Found to have proteinuria and was referred to Nephrologist

3.  General Physical examination- o PICKL- Negative o Pedal and periorbital oedema-+ o Normotensive (BP-110/80mmHg)  Systemic examination: NAD

4.  Laboratory investigations- o SCreatinine -1.1mg/dL o 24hr urine protein -6.9g o Urine - 3+ protein with no active sediments o Serologies: Negative for HCV, HBsAg, HIV, ANA dsDNA, c-ANCA, p-ANCA Rheumatoid factor and cryoglobulin o LFT- WNL o CBC- No significant abnormality

5. Clinical diagnosis A syndromic diagnosis of nephrotic syndrome was considered and an ultrasound guided percutaneous kidney biopsy was performed. Clinical possibilities- – Membranous glomerulonephritis – Focal segmental glomerulosclerosis

6. H/E stainPAS stain

7. H/E stainPAS stain

9. Biopsy findings Light microscopic examination Suggestive of Membranous Glomerulonephritis

10. IgG C3

11. KAPPALAMBDA

12. IgG3IgG4 IgG1 IgG2

13. Direct immunofluorescence staining 8 glomeruli Granular positivity (3+)along capillary loops IgG C3 Kappa IgA,IgM,C1q, PLAR 2- Negative  IgG Subtyping –IgG3 + Monoclonal IgG3-kappa deposition and C3 along the glomerular capillary loops

16. Electron microscopy revealed subepithelial electron dense immune deposits.

17. Diagnosis Monoclonal immunoglobulin deposition disease with membranous nephropathy – LM: Diffusely thickened GBM – DIF: IgG3,Kappa, C3 deposits – EM: Subepithelial Immune complex type deposits

18. Post biopsy work-up SPEP, UPEP, BJP- Negative Serum free light chain assay- ↑κ : λ ratio (5.2:1) Bone Marrow: 2% of plasma cells Serum Ca- WNL Radiology: No lytic lesions

19. Monoclonal immunoglobulin deposition disease associated with membranous features

20. Therapy Patient was treated with steroids

21. Follow up Symptomatic improvement with↓Proteinuria Serum free light chain assay- Awaited

22. Till date 13 cases of MIDD with membranous morphology have been described in the English literature. This is the fourteenth such case worldwide Only three (21%) of the 14 patients with available data had a monoclonal protein in serum or urine Three cases had overt B-cell neoplasms

25. Definition The modified criteria for proliferative GN with monoclonal IgG deposits: 1.The presence of glomerular monoclonal IgG deposits restricted to a single IgG subclass and a single light chain isotype, associated with membranous features without proliferative patterns 2.The presence of granular (‘immunecomplex type’) deposits by electron microscopy 3.The absence of clinical and laboratory evidence of cryoglobulinaemia

26. Clin Exp Nephrol (2012) 16:468–472

29. Distinct entity or just a different morphological manifestation of the same disease? Therapy?

30. Acknowledgements Prof Kusum Joshi Dr Ritambhra Nada Dr Raja Ramchandran Dr CS Rayat Dept. of Nephrology

31. THANK YOU