Renal Ultrastructural PathologyRenal Ultrastructural PathologyLecture 2 Me - MiLecture 2 Me - Mi

Bart E Wagner Bart E Wagner BSc CSc FIBMS Dip Ult PathBSc CSc FIBMS Dip Ult Path

Chief Biomedical ScientistChief Biomedical ScientistElectron Microscopy SectionElectron Microscopy SectionHistopathology DepartmentHistopathology DepartmentNorthern General HospitalNorthern General Hospital

SheffieldSheffieldSouth YorkshireSouth Yorkshire

UKUKS5 7AUS5 7AU

bart.wagner@sth.nhs.ukTel+44(0)114-27 14154Tel+44(0)114-27 14154

Basic Renal EM workshop

Southampton

September 30th 2011

Histopathology DepartmentNorthern General Hospital

Renal ultrastructural pathologyRenal ultrastructural pathologyLecture 2 - TopicsLecture 2 - Topics

1.1. Mesangio Capillary Glomerulo Nephritis MCGN type IMesangio Capillary Glomerulo Nephritis MCGN type I

2.2. Mesangio Capillary Glomerulo Nephritis MCGN type II Mesangio Capillary Glomerulo Nephritis MCGN type II (linear dense deposit disease)(linear dense deposit disease)

3.3. Membranous Glomerulo NephritisMembranous Glomerulo Nephritis

4.4. Minimal Change nephropathyMinimal Change nephropathy

Mesangiocapillaryglomerulonephritis Mesangiocapillaryglomerulonephritis MCGN type 1MCGN type 1

or or Membranoproliferativeglomerulonephritis Membranoproliferativeglomerulonephritis

MPGN type 1MPGN type 1

Mesangiocapillaryglomerulonephritis MCGN Mesangiocapillaryglomerulonephritis MCGN type 1type 1

Membranoproliferativeglomerulonephritis Membranoproliferativeglomerulonephritis MPGN type 1 & 2MPGN type 1 & 2

Immunofluorescence: C3 mainlyImmunofluorescence: C3 mainly

Can be occasionally confused with subacute postinfectious GNCan be occasionally confused with subacute postinfectious GN

Accentuation of lobular architecture

Accentuation of lobular architecture

Mesangial interposition

Mesangial deposits Deposits are ‘moth eaten’

Mesangial interposition in response to subendothelial deposits

Hypercellular nodular glomerular sclerosis

Hypercellular glomerulus

Mesangial interpositionMonocyte interacting with endothelium

Mesangial matrix expansion – numerous depositsMesangial interposition

MCGN / MPGN type 2MCGN / MPGN type 2oror

Linear dense deposit diseaseLinear dense deposit diseaseoror

Dense deposit diseaseDense deposit disease

Nodular glomerular sclerosis

Interrupted linear dense deposits

Mesangial deposits

Linear dense depositMesangial interposition (between deposit and endothelial cell)

LDDD or MCGN type II

Dense deposit around tubular basement membrane Interstitial foam cell

Subendothelial expansion but no deposit or interposition

Membranous Membranous GlomerulonephritisGlomerulonephritis

Membranous Membranous GlomerulonephritisGlomerulonephritis

Stage 1: Small subepithelial deposits – no spikes on silver stainStage 1: Small subepithelial deposits – no spikes on silver stain

Stage 2: New basement membrane around lateral border of Stage 2: New basement membrane around lateral border of deposits – spikes present on silver staindeposits – spikes present on silver stain

Stage 3: Occasional lysed deposit, occasional new basement Stage 3: Occasional lysed deposit, occasional new basement membrane between deposit and podocytemembrane between deposit and podocyte

Stage 4: Occasionally find mesangial cell undergoing interposition, Stage 4: Occasionally find mesangial cell undergoing interposition, glomerulosclerosis – silver stain chain ropeglomerulosclerosis – silver stain chain rope

Membranous GNMembranous GN

Can find different stages on different loopsCan find different stages on different loops

Therefore stage is usually bracketedTherefore stage is usually bracketed

Stage 1 membranous

Appears similar to minimal change at low magnification

Tiny subepithelial deposits

Stage 1 membranous

Moderate numbers of small subepithelial deposits (IgG C3)

Stage 1 membranous

Occasional small epithelial deposits

Stage 1 membranous

Stage 1 membranous

Mesangial cell lysosomes

Unstained section Intralysosomal aurosomes / colloidal gold

Stage 1 membranous

Stage 2 membranous

Stage 2 membranous

Numerous medium sized subepithelial deposits

Stage 2 membranous

New basement membrane between subepithelial deposits – forming spikes

Aggregates of filamentous actin in podocyte

Deposit lysis

Stage 3 membranous

Stage 4/chronic membranous

Stage 4 membranous

Lysis of depositsDeposits undergoing incorporation Fresh deposit

Minimal Change NephropathyMinimal Change Nephropathy

Minimal Change NephropathyMinimal Change Nephropathy

Histologically normal glomeruli in context of nephrotic syndromeHistologically normal glomeruli in context of nephrotic syndrome

Trace IgM on IFTrace IgM on IF

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CaveatCaveat

Not a good correlation between level of proteinuria and extent of foot Not a good correlation between level of proteinuria and extent of foot process effacement within a single glomerulus due to variability of process effacement within a single glomerulus due to variability of degree of pathology between glomeruli.degree of pathology between glomeruli.

Proteinuria reflects mean of foot process effacement.Proteinuria reflects mean of foot process effacement.

Normal-looking glomerulus

Normal foot processes occasionally

Foot processes effaced

Foot process effacement

Tiny mesangial deposits (IgM)