Dr Ian Roberts Oxford. Oxford Pathology Course 2010 for FRCPath Illustration-Cellular Pathology. Oxford Radcliffe NHS Trust

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1 Dr Ian Roberts Oxford Oxford Pathology Course 2010 for FRCPath

2 Plan of attack: Diagnostic approach to the renal biopsy Differential diagnosis of the clinical syndromes of renal disease Microscopy

3 Step 1: Provide a morphological label: where is the abnormality? what is the pattern of disease? Step 2: Refine the morphology to a diagnosis using: clinical information immunohistochemistry electron microscopy Step 3: Quantify activity and chronicity (grade and stage)

4 MICROSCOPIC DESCRIPTION: Glomeruli Tubules and Interstitium Vessels Immunohistochemistry Electron microscopy Conclusion These are cores of renal tissue containing up to 19 glomeruli in the plane of sections examined. Glomeruli 7/19 are globally sclerosed and the remaining show diffuse global thickening of capillary walls with membrane spikes and a reticulated appearance noted on silver stain. 1/19 glomeruli shows a segmental sclerosing lesion. Congo red stain does not reveal amyloid. Tubules and interstitium - there is focal mild chronic damage amounting to 10% of the cortex and interstitial foam cells are present. Vessels - interlobular arteries and arterioles are unremarkable. Immunofluorescence (8 glomeruli) - shows diffuse global granular staining with IgG (+++), IgM (++), C3 (trace), C1q (+), Kappa (+++) and Lambda (++). IgA is negative. Comment - The features are those of a membranous nephropathy with focal segmental sclerosis and mild chronic damage. SUMMARY: RENAL BIOPSY - MEMBRANOUS NEPHROPATHY

5 immune-mediated glomerulonephritis genetic basement membrane disorders lysosomal storage disorders non-immune deposits hyperlipidaemia amyloidosis deposition of light chains vascular diabetes mellitus thrombotic microangiopathy

6 What is the morphology? normal, sclerosis, proliferation, necrosis What is the distribution of the changes? focal or diffuse; segmental or global Proliferation: mesangial, endocapillary, extracapillary Sclerosis: mesangial, nodular, segmental, global Capillary walls: membrane spikes, reduplication Capillary lumen: collapse, inflammation, thrombosis

9 Proliferation - mesangial endocapillary extracapillary

10 Sclerosis - segmental global nodular

11 Capillary walls - normal membrane spikes reduplication

12 Capillary lumen - thrombi cryoglobulins inflammation

13 Lesson 1:Morphological pattern of disease is not the same as diagnosis One condition can result in varied morphologies and clinical presentations. One morphology can be the result of a variety of primary diseases. Target of injury, morphology and clinical presentation are linked. Provide a differential diagnosis based on clinical and morphological data, then refine it with IH & EM.

14 Normal by light microscopy Mesangial proliferative, focal or diffuse Focal segmental endocapillary proliferation/sclerosis Mesangiocapillary Membranous Necrotising/Crescentic Global sclerosis

15 Clinical Diagnosis IH proteinuria MCD MN neg cap IgG&C3 haematuria Normal IgAN TMN neg mes IgG&C3 neg EM loss of fps sub-epithelial deps normal mesangial deps thin bm

16 minimal change disease membranous nephritis IgA nephropathy lupus nephritis anti-gbm disease vasculitis podocyte injury no proliferation inflammation and/or mesangial proliferation necrosis, crescents proteinuria haematuria/nephritic acute renal failure renal fibrosis and chronic renal failure

17 Localises immune deposits: Antibodies directed to renal antigen Renal deposition of circulating immune complexes Antibodies binding trapped antigen/fc receptors Also: Non-specific trapping with increased capillary wall permeability Identifies non-immune deposits: eg amyloid A, light chains, fibrin, myoglobin

18 Immunoperoxidase staining in paraffin sections: Beware: false negative eg. anti-gbm disease false positive eg. staining of plasma proteins C3 IgG

19 Lesson 2: There is more information in the biopsy than the diagnosis Often the diagnosis is known before biopsy The biopsy can provide: Prognostic information An indication of what treatment should be given and the likely response Give a measure of activity and chronicity Quantitate the changes numbers count

20 Casts red cell, protein, crystals, calcification Epithelium necrosis, regeneration, vacuolation, re-absorbed material Inflammation neutrophilic, lymphocytic tubulitis, giant cells Atrophy Hyperplasia/neoplasia

21 Inflammation acute, chronic, granulomatous, eosinophils Deposits crystals, amyloid Fibrosis early, late pattern: striped Segmental subcapsular diffuse peritubular

27 Arterioles Wall: hyalinosis amyloid fibrinoid necrosis Lumen: thrombosis Arteries Wall: amyloid inflammation arteritis intimal proliferation, fibrosis, elastosis Lumen: thrombosis atheroemboli

Dr Ian Roberts Oxford. Oxford Pathology Course 2010 for FRCPath Illustration-Cellular Pathology. Oxford Radcliffe NHS Trust

Dr Ian Roberts Oxford. Oxford Pathology Course 2010 for FRCPath Illustration-Cellular Pathology. Oxford Radcliffe NHS Trust Dr Ian Roberts Oxford Oxford Pathology Course 2010 for FRCPath Present the basic diagnostic features of the commonest conditions causing proteinuria & haematuria Highlight diagnostic pitfalls Nephrotic