Dr Ian Roberts Oxford Oxford Pathology Course 2010 for FRCPath
Plan of attack: Diagnostic approach to the renal biopsy Differential diagnosis of the clinical syndromes of renal disease Microscopy
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)
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
immune-mediated glomerulonephritis genetic basement membrane disorders lysosomal storage disorders non-immune deposits hyperlipidaemia amyloidosis deposition of light chains vascular diabetes mellitus thrombotic microangiopathy
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
Proliferation - mesangial endocapillary extracapillary
Sclerosis - segmental global nodular
Capillary walls - normal membrane spikes reduplication
Capillary lumen - thrombi cryoglobulins inflammation
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.
Normal by light microscopy Mesangial proliferative, focal or diffuse Focal segmental endocapillary proliferation/sclerosis Mesangiocapillary Membranous Necrotising/Crescentic Global sclerosis
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
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
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
Immunoperoxidase staining in paraffin sections: Beware: false negative eg. anti-gbm disease false positive eg. staining of plasma proteins C3 IgG
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
Casts red cell, protein, crystals, calcification Epithelium necrosis, regeneration, vacuolation, re-absorbed material Inflammation neutrophilic, lymphocytic tubulitis, giant cells Atrophy Hyperplasia/neoplasia
Inflammation acute, chronic, granulomatous, eosinophils Deposits crystals, amyloid Fibrosis early, late pattern: striped Segmental subcapsular diffuse peritubular
Arterioles Wall: hyalinosis amyloid fibrinoid necrosis Lumen: thrombosis Arteries Wall: amyloid inflammation arteritis intimal proliferation, fibrosis, elastosis Lumen: thrombosis atheroemboli