Algorithmic Approach to the  Interpretation of Renal Biopsy
Basic stains required for LM <ul><li>H&E </li></ul><ul><li>Glomerular: exudative lesions  </li></ul><ul><li>Tubular: tubul...
Routine antibody panel for IF <ul><li>IgG  immune complex disease, Anti-GBM disease </li></ul><ul><li>IgA IgA nephropathy,...
Descriptive terms and patterns of glomerular injury <ul><li>Related to distribution </li></ul><ul><li>Focal Involving less...
Descriptive terms and patterns of glomerular injury <ul><li>Related to Structure </li></ul><ul><li>Obsolescence  Total los...
Descriptive terms and patterns of glomerular injury <ul><li>Related to Structure </li></ul><ul><li>Hyalinosis Accumulation...
Descriptive terms and patterns of glomerular injury <ul><li>Related to Cell proliferation </li></ul><ul><li>Mesangial hype...
Descriptive terms and patterns of glomerular injury <ul><li>Related to Deposits  </li></ul><ul><li>Intramembranous Within ...
Descriptive terms and patterns of tubulointerstitial and vascular injury <ul><li>Tubules </li></ul><ul><li>Tubulitis Lymph...
Descriptive terms and patterns of tubulointerstitial and vascular injury <ul><li>Tubules </li></ul><ul><li>Hyaline droplet...
Descriptive terms and patterns of tubulointerstitial and vascular injury <ul><li>Interstitium </li></ul><ul><li>Edema Incr...
Descriptive terms and patterns of tubulointerstitial and vascular injury <ul><li>Vessels </li></ul><ul><li>Intimal thicken...
 
 
 
 
 
 
 
 
 
 
 
 
Components of Native Kidney Biopsy Pathology Report <ul><li>Light microscopy </li></ul><ul><li>Presence and relative propo...
Components of Native Kidney Biopsy Pathology Report <ul><li>Immunofluorescence microscopy </li></ul><ul><li>Total number o...
Components of Native Kidney Biopsy Pathology Report <ul><li>Electron microscopy </li></ul><ul><li>Total number of glomerul...
Components of Native Kidney Biopsy Pathology Report <ul><li>Diagnosis </li></ul><ul><li>Including morphologic pattern plus...
Components of Renal Transplant Biopsy Pathology Report <ul><li>Light microscopy </li></ul><ul><li>Glomeruli: glomerulitis,...
Components of Renal Transplant Biopsy Pathology Report <ul><li>Immunofluorescence microscopy </li></ul><ul><li>C4d stainin...
Components of Renal Transplant Biopsy Pathology Report <ul><li>Electron microscopy </li></ul><ul><li>Glomerular abnormalit...
Components of Renal Transplant Biopsy Pathology Report <ul><li>Diagnosis </li></ul><ul><li>Including a particular patholon...
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Algorithmic approach to the renal biopsy fellow

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Algorithmic approach to the renal biopsy fellow

  1. 1. Algorithmic Approach to the Interpretation of Renal Biopsy
  2. 2. Basic stains required for LM <ul><li>H&E </li></ul><ul><li>Glomerular: exudative lesions </li></ul><ul><li>Tubular: tubular epithelial damage </li></ul><ul><li>Interstitial: edema, inflammation </li></ul><ul><li>Vascular: inflammation </li></ul><ul><li>Methanamine-silver (Jones stain) </li></ul><ul><li>Glomerular: GBM spikes, double contours, breaks in GBM/Bowman’s capsule </li></ul><ul><li>Tubular: tubulitis </li></ul><ul><li>Interstitial: Fibrosis </li></ul><ul><li>Vascular: internal elastic lamina </li></ul><ul><li>PAS </li></ul><ul><li>Glomerular: GBM thickening, capillary wall collapse, Bowman’s capsule, hyalinosis, sclerosis, mesangial cellularity and matrix increase, mesangiolysis, endo/extracapillary proliferation </li></ul><ul><li>Tubular: tubular protein droplets, TBM thickening, tubulitis </li></ul><ul><li>Vascular: hyaline arteriolosclerosis </li></ul><ul><li>Masson trichrome </li></ul><ul><li>Glomerular: immune deposits, thrombi, fibrin, platelets </li></ul><ul><li>Tubular: tubular atrophy </li></ul><ul><li>Interstitial: fibrosis </li></ul><ul><li>Vascular: thrombi </li></ul>
  3. 3. Routine antibody panel for IF <ul><li>IgG immune complex disease, Anti-GBM disease </li></ul><ul><li>IgA IgA nephropathy, HSP, Liver disease, SLE </li></ul><ul><li>IgM Waldenstrom’s macroglobulinemia, mixed cryoglobulinemia </li></ul><ul><li>C1q C1q nephropathy, SLE </li></ul><ul><li>C3 Dense deposit disease, C3 mesangial GN, resolving PIGN </li></ul><ul><li>Fibrinogen Necrotizing lesion, thrombotic microangiopathy, crescents </li></ul><ul><li>Kappa & Lambda Monoclonal Ig deposition disease, amyloidosis </li></ul><ul><li>C4d (transplant) Humoral rejection </li></ul>
  4. 4. Descriptive terms and patterns of glomerular injury <ul><li>Related to distribution </li></ul><ul><li>Focal Involving less than 50% of glomeruli by LM </li></ul><ul><li>Diffuse Involving 50% or more of glomeruli by LM </li></ul><ul><li>Segmental Involving a portion of the glomerular tuft </li></ul><ul><li>Global Involving the entire glomerular tuft </li></ul>
  5. 5. Descriptive terms and patterns of glomerular injury <ul><li>Related to Structure </li></ul><ul><li>Obsolescence Total loss of normal glomerular architecture due to replacement by </li></ul><ul><li>sclerosis </li></ul><ul><li>Sclerosis Increased collagenous extracellular matrix expanding the mesangium, </li></ul><ul><li>occluding capillary lumina or forming adhesions to Bowman’s capsule </li></ul><ul><li>Fibrinoid necrosis Disruption of structure, with degeneration of local cells, extracellular matrix </li></ul><ul><li>and the basement membrane, often associated with fibrin deposition </li></ul><ul><li>Lobular Hypersegmentation of the normal lobular architecture of the normal </li></ul><ul><li>glomerular capillary tuft due to intracapillary hypercellularity or significant </li></ul><ul><li>mesangial expansions </li></ul><ul><li>Mesangiolysis Dissolution or attenuation of mesangial matrix and degeneration of </li></ul><ul><li>mesangial cells, often associated with glomerular capillary aneurysms </li></ul><ul><li>Mesangial interposition Extension of mesangial cells in the peripheral glomerular capillary </li></ul><ul><li>walls in the space located between endothelial cells and GMB </li></ul><ul><li>(subendothelial zone) </li></ul>
  6. 6. Descriptive terms and patterns of glomerular injury <ul><li>Related to Structure </li></ul><ul><li>Hyalinosis Accumulation of glassy, refractile acellular material/plasmatic insudation </li></ul><ul><li>(PAS positive, methenamine-silver negative) which contains serum </li></ul><ul><li>proteins, other glycoproteins and lipids </li></ul><ul><li>Glomerular capillary collapse Retraction of glomerular tuft with closure of capillary lumina and </li></ul><ul><li>wrinkling and thickening of glomerular capillary walls </li></ul><ul><li>Glomerular capillary aneurysm Capillary lumen balloons out and appears ectatic due to </li></ul><ul><li>degeneration of mesangial cells and matrix (mesangiolysis) </li></ul><ul><li>Wire-loops Thickened glomerular capillary walls with a rigid appearance (wire-loop-like) </li></ul><ul><li>due to the presence of large and confluent subendothelial immune deposits </li></ul><ul><li>Tram-tracking/GBM reduplication Double contoured appearance of glomerular capillary walls </li></ul><ul><li> on PAS/silver stains due to the presence of deposits and </li></ul><ul><li>mesangial interposition between the endothelium and the </li></ul><ul><li>original GBM with creation of a new inner (subendothelial </li></ul><ul><li>side) basement-membrane-like material </li></ul>
  7. 7. Descriptive terms and patterns of glomerular injury <ul><li>Related to Cell proliferation </li></ul><ul><li>Mesangial hypercellularity Presence of 3 or more mesangial and/or inflammatory cells per </li></ul><ul><li>mesangial area away from the vascular pole in a section that is </li></ul><ul><li>2-3 micron in thickness (WHO definition) </li></ul><ul><li>Endocapillary hypercellularity Increased cellularity within the confines of GMB composed of </li></ul><ul><li>endothelial cells, mesangial cells and /or inflammatory cells, </li></ul><ul><li>resulting in luminal narrowing or occlusion </li></ul><ul><li>Intracapillary hypercellularity Hypercellularity present in both mesangium and endocapillaries </li></ul><ul><li>Crescent The build-up of more than 2 layers of cells within Bowman’s </li></ul><ul><li>space caused by the proliferation of parietal cells, podocytes and </li></ul><ul><li> inflammatory cells, often with fibrin and collagen deposition. </li></ul><ul><li>Adhesion/synechia Localized narrow bridges of connective tissue between </li></ul><ul><li>glomerular tufts and Bowman’s capsule </li></ul><ul><li>Membranoproliferative Glomerular capillary wall thickening due to mesangial </li></ul><ul><li>interposition and duplication of GMB </li></ul>
  8. 8. Descriptive terms and patterns of glomerular injury <ul><li>Related to Deposits </li></ul><ul><li>Intramembranous Within the GBM </li></ul><ul><li>Mesangial Within the mesangial matrix </li></ul><ul><li>Subendothelial Between the GBM and the endothelium </li></ul><ul><li>Subepithelial/epimembranous Between the GBM and podocytes </li></ul><ul><li>Humps Subepithelial electron-dense immune-type deposits with </li></ul><ul><li>a cigar-or dome-like appearance </li></ul>
  9. 9. Descriptive terms and patterns of tubulointerstitial and vascular injury <ul><li>Tubules </li></ul><ul><li>Tubulitis Lymphocytes or other inflammatory cells infiltrating tubular epithelium </li></ul><ul><li>Tubular atrophy Tubular involution/obsolescence due to ischemia, obstruction, toxic or </li></ul><ul><li>inflammatory injury with different LM appearances including classic </li></ul><ul><li>atrophy, endocrine and thyroidization changes </li></ul><ul><li>Tubular casts Various coagulated proteins and other elements in tubular lumens usually </li></ul><ul><li>but not exclusively seen in distal nephron </li></ul><ul><li>Hydropic degeneration/ Fine regular cytoplasmic vacuolization of the proximal tubules </li></ul><ul><li>Osmotic nephrosis </li></ul>
  10. 10. Descriptive terms and patterns of tubulointerstitial and vascular injury <ul><li>Tubules </li></ul><ul><li>Hyaline droplet PAS/silver-positive protein reabsorption droplets because of increased </li></ul><ul><li>protein loss by glomeruli </li></ul><ul><li>Fatty change Finely vacuolated cytoplasm with clear vacuoles in the cytoplasm of tubular </li></ul><ul><li>epithelium in which the lipid has been dissolved out during preparation of </li></ul><ul><li>paraffin sections </li></ul><ul><li>Hypokalemic change Large irregular sized coarse clear vacuoles in the cytoplasm of tubular epithelial cells, especially the distal tubular cells </li></ul><ul><li>Intranuclear inclusions Seen in nuclei with various morphology depending on etiology, often </li></ul><ul><li>associated with viral infections (CMV, BK polyomavirus and adenovirus), </li></ul><ul><li>can be observed in tubular epithelial cell regeneration and lead </li></ul><ul><li>nephropathy </li></ul>
  11. 11. Descriptive terms and patterns of tubulointerstitial and vascular injury <ul><li>Interstitium </li></ul><ul><li>Edema Increased extracellular fluid in the interstitium resulting in increased spacing </li></ul><ul><li>between tubules </li></ul><ul><li>Interstitial foam cells Macrophages with cytoplasm lipid-containing vacuoles </li></ul><ul><li>Inflammation Infiltration of lymphocytes, plasma cells, and often eosinophils and </li></ul><ul><li>neutrophils with associated tubular injury </li></ul><ul><li>Fibrosis Interstitial expansion by collagen </li></ul><ul><li>Granuloma Collection of epithelioid histiocytes with/with out surrounding multinucleated </li></ul><ul><li>giant cells and lymphocytes </li></ul>
  12. 12. Descriptive terms and patterns of tubulointerstitial and vascular injury <ul><li>Vessels </li></ul><ul><li>Intimal thickening Fibrous thickening of the intimal layer, usually in a concentric configuration </li></ul><ul><li>and associated with varying degrees of luminal stenosis </li></ul><ul><li>Hyaline sclerosis Accumulation of PAS-positive/silver-negative material in the intima and /or </li></ul><ul><li>media resulting in a characteristic “glassy” acellular refractile change in </li></ul><ul><li>small arteries and arterioles </li></ul><ul><li>Endothelialitis/endarteritis Infiltration of mononuclear cells under arterial and arteriolar </li></ul><ul><li>endothelium </li></ul><ul><li>Arteritis Necrosis, fibrinoid degeneration and inflammation of arteries with </li></ul><ul><li>leukocytoclasia and disruption of internal elastic lamina </li></ul><ul><li>Vasculitis Necrosis, fibrinoid degeneration and leukocytoclastic inflammation of </li></ul><ul><li>arteries, arterioles and veins </li></ul>
  13. 25. Components of Native Kidney Biopsy Pathology Report <ul><li>Light microscopy </li></ul><ul><li>Presence and relative proportion of renal capsule, cortex, medulla, pelvic urothelial lining and others (i.e., skeletal muscle, liver, intestine) </li></ul><ul><li>Total number of glomeruli and the number/percentage of globally sclerotic glomeruli if any </li></ul><ul><li>Description of diagnostic morphology lesions/changes/patterns in glomeruli, tubules, interstitium and vessels </li></ul><ul><li>Description of important or relevant negative findings </li></ul>
  14. 26. Components of Native Kidney Biopsy Pathology Report <ul><li>Immunofluorescence microscopy </li></ul><ul><li>Total number of glomeruli and the number of globally sclerotic glomeruli if present </li></ul><ul><li>Description of positive or negative results for each Ig and complement components in glomeruli </li></ul><ul><li>Description of the location, stain pattern and intensity of the deposits in glomeruli </li></ul><ul><li>Description of immunoreactants in tubulointerstitial compartment and vessels if present </li></ul>
  15. 27. Components of Native Kidney Biopsy Pathology Report <ul><li>Electron microscopy </li></ul><ul><li>Total number of glomeruli and the number of globally sclerotic glomeruli if present </li></ul><ul><li>Description of glomerular abnormalities/changes </li></ul><ul><li>Description of the location, number, size, appearance/substructure of electron dense deposits if present </li></ul><ul><li>Description of degree of foot process effacement </li></ul><ul><li>Description of relative changes in tubulointerstitial and vascular component </li></ul>
  16. 28. Components of Native Kidney Biopsy Pathology Report <ul><li>Diagnosis </li></ul><ul><li>Including morphologic pattern plus a particular pathogenic or clinicopathologic category of the disease </li></ul><ul><li>Comment </li></ul><ul><li>Clinicopathologic correlation </li></ul><ul><li>List of differential diagnoses if necessary </li></ul><ul><li>Pertinent histologic prognostic indicators </li></ul><ul><li>Activity/chronicity indices of lupus nephritis </li></ul>
  17. 29. Components of Renal Transplant Biopsy Pathology Report <ul><li>Light microscopy </li></ul><ul><li>Glomeruli: glomerulitis, fibrin thrombosis, double contours, and other glomerular lesions </li></ul><ul><li>Tubules: tubular injury, inflammation (tubulitis), nuclear atypia/inclusions </li></ul><ul><li>Interstitium: nature and degree of cellular infiltrate (i.e., edema, activated mononuclear cell, malignant cells, leukocytes in peritubular capillaries) </li></ul><ul><li>Vessels: endarteritis, myocyte necrosis, thrombi, nodular hyaline, intimal elastosis </li></ul>
  18. 30. Components of Renal Transplant Biopsy Pathology Report <ul><li>Immunofluorescence microscopy </li></ul><ul><li>C4d staining in peritubular capillaries </li></ul>
  19. 31. Components of Renal Transplant Biopsy Pathology Report <ul><li>Electron microscopy </li></ul><ul><li>Glomerular abnormalities </li></ul><ul><li>Viral particles </li></ul><ul><li>Peritubular capillary basement membrane multilayering </li></ul>
  20. 32. Components of Renal Transplant Biopsy Pathology Report <ul><li>Diagnosis </li></ul><ul><li>Including a particular patholonic or clinicopathologic category of the disease </li></ul><ul><li>(Banff Classification for Renal Transplant Pathology) </li></ul><ul><li>Comment </li></ul><ul><li>Clinicopathologic correlation </li></ul><ul><li>List of differential diagnoses if necessary </li></ul><ul><li>Pertinent histologic prognostic indicators </li></ul>

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