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)



Heavy Chain Deposition Disease (HCDD)



Light and Heavy chain deposition Disease (LHCDD)



Crioglobulinemia (tipo 1 e 2)



Monoclonal Immunotactoid Glomerulopathy



Tubular-interstitial involvement



Light chain Cast Nephropathy



Tubular epithelial cell dysfunction



Acute Tubular Necrosis

Electron Microscopy

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

Congo Red Congo Red

• Amyloid

Amyloid

Immunofluorescence for Light, Heavy Immunofluorescence for Light, Heavy and AA Protein and AA Protein

LC+ HC+ H&LC+ AA+ Amyloidosis Amyloidosis AL AL Amyloidosis Amyloidosis AH AH Amyloidosis Amyloidosis AHL AHL Amyloidosis Amyloidosis AA AA

Non Non-

• Amyloid

Amyloid

Immunofluorescence for Immunofluorescence for Immunoglobulins Immunoglobulins

• Collagenofibrotic

Collagenofibrotic Glomerulopathy Glomerulopathy

• Fibronectin

Fibronectin Glomerulopathy Glomerulopathy

• Chronic Sclerosis

Chronic Sclerosis

• Diabetes

Diabetes

• Fibrillar Glomerulonefritis

Fibrillar Glomerulonefritis

Randomly arranged microfibrils (diameter: 12-30 nm; usually around 20 nm) Polyclonal, subclass-restricted IgG in the deposits Mainly primary

• Immunotactoids

Immunotactoids

P Parallel arrays of microtubules (diameter: 10-90 nm; usually above 30 nm) Monoclonal IgG in the deposits Mainly secondary

• Cryoglobulinemia

Cryoglobulinemia

Curved microtubules (diameter: 25-35 nm)

• Light/heavy chains

Light/heavy chains deposition disease deposition disease

Dense granules Dense granules

Taken from Atlas of Non tumor Pathology Jennette JC, Silva FG, D’Agati V. (modified)

• 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

Immunotactoid Deposits