Case 6 Helmut Hopfer, University Hospital Basel, Switzerland morphological features • • • • increased number of endocapillary leukocytes endothelial swelling dilatation of capillary loops occlusion or near occlusion of capillary lumina with cells usually a focal and segmental lesion! EM differential diagnosis transplant glomerulitis endocapillary glomerulonephritis (intravascular lymphoma) transplant glomerulitis: definition • recognizing a pattern: 1. 2. 3. 4. increased number of endocapillary leukocytes endothelial swelling dilatation of capillary loops occlusion or near occlusion of capillary lumina with cells • counting mononuclear cells (arbitrary cut-off) → no clear distinction between cell types by light microscopy! → immunohistochemistry, definition of cut-off by ROC CD5 Example: endocapillary immune-complex GN CD20 CD68 ERG counting cells will not tell you anything about the pathogenesis glomerular rejection: pathogenesis antibodies & complement ↓ endothelial cell damage lytic necrotic sublytic procoagulant proinflammatory proliferative / reparative 1. 1. 2. 3. discussion & conclusions antibodies & complement ↓ endothelial cell damage lytic sublytic proliferative / reparative proinflammatory procoagulant necrotic • Why are the leukocytes there? • What are the monocytes / macrophages doing there? • What are the lymphocytes doing there? → monocytes exert an early endocapillary reparative function on the endothelial cells case presentation Clinical history: 39 year old male. Renal transplantation (TR) in 2005 due to hypertension. Malcompliance with immunosuppresion → two episodes of interstitial cellular rejection. Diagnostic biopsy (BX) 40 months after TR, rise in creatinine and newly diagnosed proteinuria. Diagnosis: Transplant glomerulitis (by EM), severe diffuse interstitial cellular rejection, C4d negative. Focal IFTA (10-20%). Follow up: Dialysis dependence 7 months later. BX with mixed T cell- and antibody-mediated rejection, C4d positive.