CUTANEOUS LEUKOCYTOCLASTIC VASCULITIS AND MEMBRANOPROLIFERATIVE - PowerPoint PPT Presentation

CLINICAL-PATHOLOGICAL CONFERENCE CUTANEOUS LEUKOCYTOCLASTIC VASCULITIS AND MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS WITH MONOCLONAL IGM GAMMOPATHY . Anna Maria Asunis Divisione di Anatomia Patologica AO Brotzu, Cagliari (CA), IT

Capillary loops: Irregulararly tickened in some tracts, with mesangial proliferation and large fibrinoid deposits (PAS – 20x)

Large fibrinoid deposits subendothelial. Some hyaline thrombi (PAS 40x)

Large fibrinoid deposits with intracapillary thrombi. Some double contours patterns (AFOG – 40x)

Irregular subendothelial fibrinoid deposits with numerous polymorphonuclear leukocytes and monocytes (AFOG – 40x)

Mild fibrosis in the mesangium and in some capillary loops

Extensive hyaline casts, fragmented and surrounded by multinucleated cells

Immunofluorescence  Renal specimen including 15 glomeruli.  IgM (+++) in capillary thrombi, irrugular and segmental in subendothelial zone in 5 glomeruli and in tubular casts.  C3 (++) located as IgM in the tuft.  Kappa Chains (++) as IgM in the tuft and in tubular casts.  Lambda Chains (++) in tubular casts.  IgG, IgA, C4, C1q, Fbg, and Thioflavine-T antisera were negative

LM and IF diagnosis  Atypical Membraneproliferative Glomerulonephritis with endocapillary thrombi and some aspects of Cast Nephropathy Glomerular/Vascolar patterns of Plasmacell dyscrasias  Amiloidosi AL  Amiloidosi AH  Light Chain Deposition Disease (LCDD)  Electron Heavy Chain Deposition Disease (HCDD)  Light and Heavy chain deposition Disease (LHCDD)  Crioglobulinemia (tipo 1 e 2)  Microscopy Monoclonal Immunotactoid Glomerulopathy  Tubular-interstitial involvement  Light chain Cast Nephropathy  Tubular epithelial cell dysfunction  Acute Tubular Necrosis 

Thrombus in a glomerular capillary corresponding to a hyaline thrombus by light microscopy. 5500x UrPb

A higher magnification shows deposits composed of slightly curved stacks of microtubular structures with parallel alignment (diameter: 25-30 nm). 87500x UrPb

Diagnostic Algoritm Organized Glomerular Electron- - Organized Glomerular Electron dense Deposits dense Deposits Non- - Non Amyloid Amyloid - - Congo Red Congo Red Amyloid Amyloid � Collagenofibrotic � Collagenofibrotic Immunofluorescence for Light, Heavy Immunofluorescence for Light, Heavy Glomerulopathy Glomerulopathy Immunofluorescence for - Immunofluorescence for - and AA Protein and AA Protein Immunoglobulins Immunoglobulins � Fibronectin � Fibronectin Glomerulopathy Glomerulopathy LC+ HC+ H&LC+ AA+ � Chronic Sclerosis � Chronic Sclerosis � Fibrillar Glomerulonefritis � Cryoglobulinemia � � Fibrillar Glomerulonefritis Cryoglobulinemia Amyloidosis Amyloidosis Amyloidosis Amyloidosis Amyloidosis Amyloidosis Curved microtubules Amyloidosis Amyloidosis Randomly arranged microfibrils (diameter: 12-30 nm; usually (diameter: 25-35 nm ) AL AL AH AH AHL AHL � Diabetes � AA AA Diabetes around 20 nm) Polyclonal, subclass-restricted IgG in the deposits Mainly primary � Light/heavy chains � Light/heavy chains � Immunotactoids � Immunotactoids deposition disease deposition disease Parallel arrays of microtubules P Dense granules Dense granules (diameter: 10-90 nm; usually above 30 nm) Monoclonal IgG in the deposits Taken from Atlas of Non tumor Pathology Jennette JC, Silva FG, Mainly secondary D’Agati V. (modified)

Immunotactoid Deposits Prof. T. Faraggiana – Università La Sapienza, Rome (IT): Electrondense subendothelial deposits composed mostly by fibrils of 30 nm , appearing also in endocapillary thrombi, pattern that matches with an Immunotactoid Glomerulopathy