Extracellular, non-branching fibrils composed of misfolded proteins in a beta pleated sheet conformation, measuring 9-11 nm in diameter. Although many proteins can form these fibrils (as documented in humans), in animals the source is almost always Serum Amyloid A, an acute phase protein synthesized by the liver. Amyloid can be found in glomeruli, interstitium, and vessels. It appears peach to orange with Congo red stain and exhibits apple green birefringence when viewed with polarized light. Additional staining characteristics include: pink with HE, pale pink and waxy with PAS, and mottled blue to orange with MT. Amyloid does not take up silver with the JMS method.
Mural thickening with luminal narrowing of arterioles due to hyperplasia or hyaline.
Abnormal amounts of nitrogen-containing compounds (specifically creatinine) in the blood. Deviation of blood creatinine may lie within a laboratory’s designated normal reference interval but still be considered abnormal for a particular patient. Additional parameters of renal function (e.g. urine specific gravity, presence of proteinuria, etc.) should be assessed concurrently.
- Capillary loop remodeling: Loss of the normal smooth, thin contour of peripheral capillary walls due to spikes, holes, or double contours (tram tracks) with silver stain.
- Capillary loop thickening: The walls of peripheral capillary loops are expanded; best visualized by silver and PAS stains. Can be due to both immune complex mediated and nonimmune complex mediated processes.
- Hyaline (protein) casts: Tubular lumens filled by eosinophilic (HE) and PAS-positive glassy material.
- Cellular casts: Tubular lumens filled with aggregates of cells or cellular debris.
Multilayered accumulation of cells, often admixed with extracellular material, in Bowman’s space (i.e. “extracapillary hypercellularity”). Crescents are formed when glomerular capillary loops rupture or Bowman’s capsule basement membrane ruptures, allowing inflammatory cells to enter Bowman’s space. Over time crescents can modify from being predominantly cells with fibrin (so-called “cellular crescent”) to mostly fibrous matrix with fewer cells (“fibrous crescent”).
Cystic glomerular atrophy:
See glomerulocystic atrophy
Involving greater than 50% of glomeruli.
See glomerular basement membrane duplication
See glomerular basement membrane duplication
Increased cellularity internal to the glomerular basement membrane due to circulating leukocytes, endothelial cells, and/or interposed mesangial cells with resulting encroachment or obliteration of peripheral capillary lumens.
Glomeruli are small, contain few capillaries, and have prominent podocyte precursors lined up along the tuft surface.
Involving less than 50% of glomeruli.
Large finely vacuolated cells (cell unknown) with distinct cell borders that contain sudanophilic (lipid) material.
Involving the entire glomerular tuft.
Transmission electron microscopy reveals that this is a trilaminar membrane synthesized by predominantly by podocytes with some contribution by the endothelial cells. The layers are lamina rara interna (beneath the endothelium), lamina densa, and lamina rara externa (beneath the podocytes).
GBM Duplication: Thickened glomerular capillary wall with two separated layers of GBM matrix material i.e., ‘tram track’ appearance; best visualized with PAS and JMS.
GBM Holes: Small areas of lucency within the capillary walls; best visualized by silver stain (JMS).
GBM Spikes: Small irregular projections of GBM matrix on the outer aspect (abluminal) of the GBM. Best visualized by silver stain (JMS).
GBM Splitting: Lamellar appearance or basket-weave pattern of GBM with EM.
Glomerulocystic atrophy or glomerular cystic atrophy:
Cystic dilation of Bowman’s capsule with a compressed, atrophic glomerular tuft.
Accumulation of large foam cells in one or more lobules of a glomerular tuft. Foamy cells contain intracytoplasmic vacuoles that are sudanophilic (lipid material) but do not stain with routine methods (HE, PAS, MT and JMS). These cells are also autofluorescent on IF evaluation.
Glomerular thrombi :
Intracapillary acellular, fibrillar (non-glassy) material that stains orange to red on MT and pale pink on PAS.
Increased extracellular matrix leading to obliteration of capillary lumens and consolidation of part or most of the tuft. Sclerotic segments stain pale pink with HE, blue with MT, black (argyrophilic) with JMS, and pink with PAS.
- Hilar glomerulosclerosis: Increased extracellular matrix leading to obliteration of capillary lumens and consolidation near the vascular pole of the tuft.
- Tip glomerulosclerosis: Increased extracellular matrix leading to obliteration of capillary lumens and consolidation near the urinary pole of the tuft.
- Glomerulosclerosis not at poles: Increased extracellular matrix leading to obliteration of capillary lumens and consolidation which is not at a polar location.
- Glomerulosclerosis location undetermined: Increased extracellular matrix leading to obliteration of capillary lumens and consolidation affecting an uncertain portion of the tuft.
See Glomerular basement membrane holes
Glassy eosinophilic (HE) and PAS-positive extracellular material (plasma proteins) that can be found adjacent to glomerular basement membranes, in the mesangium or in vessels.
Complexes of antigen and antibody that are seen as distinct red granular or nodular structures visible on light microscopy with Masson’s trichrome stain along the GBM (usually abluminal, but occasionally visible on the luminal surface). Electron microscopy is required to determine the location of immune complex deposits which are finely granular and electron dense:
- Subepithelial: deposits located between the podocyte and GBM.
- Subendothelial: deposits are located between the endothelium and the GBM.
- Mesangial: deposits are located within the mesangium.
- Paramesangial: deposits are located on the subepithelial surface of the GBM that overlies the mesangium.
- Intramembranous: deposits are within the GBM.
Broad term for abnormal nephrogenesis which may include histologic features such as fetal/immature glomeruli, glomerulocystic atrophy, paucity of glomeruli and/or tubules, atypical tubular epithelium, and/or presence of primitive ducts.
More than three nuclei in close apposition within the mesangial matrix.
Mesangial cell interpositioning:
Extension of cells (presumably mesangial cells) into the peripheral aspect of the capillary loops between the endothelium and GBM or between layers of GBM matrix. This term is used in the context of TEM, whereas “GBM duplication” is often used in the context of LM.
Disruption of mesangial matrix with subsequent dilatation of capillary lumens.
On transmission electron microscopy, these are collection of concentric layers of cell membrane within the cytoplasm of endothelial cells, podocytes, or mesangial cells.
Small glomerular remnants composed of residual matrix and few cells.
Epithelial cells that line the inner (urinary) surface of Bowman’s capsule and have a squamous morphology.
- Parietal cell hyperplasia: Increased numbers of epithelial cells lining Bowman’s capsule; cells are crowded and occasionally pile up.
- Parietal cell hypertrophy: Loss of the normal squamous morphology; often have more of a cuboidal appearance.
- Tubularization: Morphologic transformation of parietal epithelium into proximal tubular epithelial phenotype.
Epithelial cell that sits on the outside (abluminal) surface of the glomerular basement membrane.
- Podocyte foot process effacement: Flattening and spreading of foot processes over the surface of the GBM seen with EM.
- Podocyte hypertrophy: Visceral epithelial cells are enlarged, prominent and easily discernible.
- Podocyte hyperplasia: Visceral epithelial cells are increased in number and form clusters in Bowman’s space; rare lesion.
- Podocyte microvillous transformation: Formation of numerous podocyte cell membrane protuberances usually on the cell surface facing the urinary space.
- Podocyte protein droplets: Small round eosinophilic (HE) and PAS-positive (ie, proteinaceous) cytoplasmic globules in epithelial cells.
General term for protein in the urine. Renal proteinuria results from loss of selective glomerular filtration and/or impaired reabsorption of filtrate. Persistent renal proteinuria is typically an indication of some degree of renal dysfunction/injury.
Involving part of the glomerular tuft.
See glomerular basement membrane spikes
Adhesion between the glomerular tuft and Bowman’s capsule.
Tubule with thickened and/or wrinkled basement membrane and simplification or loss of tubular epithelium.
Tubular epithelial cell
- Vesiculation: Variably-sized clear vacuoles in tubular cell cytoplasm.
- Isometric vesiculation: Small equal-sized clear vacuoles in tubular cell cytoplasm.
- Protein droplets: Small round eosinophilic (HE) and PAS-positive (ie, proteinaceous) cytoplasmic globules in tubular epithelial cells.
- Pigment: coarse cytoplasmic granules of material having intrinsic color (eg, lipofuscin, bile, iron, copper).
Clusters of ~20 nm tubular/circular structures within the cytoplasm of endothelial or mesangial cells; uncommon in animals.
Folding of the GBM within capillary loops, often associated with areas of cellular interpositioning.