ISRTPCON and CMEAIIMS

NEW DELHI12-14 Sept,2013

Dr Kiran KSenior Resident,

PDCC-Renal and Transplant PathologyDepartment of Histopathology

PGIMER,Chandigarh

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

General Physical examination-o PICKL- Negativeo Pedal and periorbital oedema-+o Normotensive (BP-110/80mmHg)

Systemic examination: NAD

Laboratory investigations-o SCreatinine -1.1mg/dLo 24hr urine protein -6.9g o Urine - 3+ protein with no active sedimentso Serologies:

• Negative for HCV, HBsAg, HIV, ANA• dsDNA, c-ANCA, p-ANCA• Rheumatoid factor and cryoglobulin

o LFT- WNLo CBC- No significant abnormality

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

H/E stain PAS stain

H/E stain PAS stain

Biopsy findings

Light microscopic examination Suggestive of Membranous Glomerulonephritis

IgG C3

KAPPA LAMBDA

IgG3 IgG4

IgG1 IgG2

Direct immunofluorescence staining

• Electron microscopy revealed subepithelial electron dense immune deposits.

Diagnosis

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

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

• Monoclonal immunoglobulin deposition disease associated with membranous features

Therapy

• Patient was treated with steroids

Follow up

• Symptomatic improvement with↓Proteinuria• Serum free light chain assay- Awaited

• 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

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

Clin Exp Nephrol (2012) 16:468–472

• Distinct entity or just a different morphological manifestation of the same disease?

• Therapy?

Acknowledgements

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

THANK YOU