Membranous Nephropathy

Primary/Secondary Membranous GN

• Histopathology: • Thickening of the peripheral capillary loops, with the presence

of basement membrane 'spikes' and 'craters' on silver- and PAS-stained sections

• Proximal tubules may contain prominent protein reabsorption granules

• The interstitium is usually delicate; foamy macrophages may be seen on rare occasions

• Pronounced glomerular sclerosis and/or interstitial fibrosis and tubular atrophy are poor predictors of outcome.

• Immunofluorescence: • There is fine granular deposition of IgG and C3 along the

peripheral capillary loops.

• Electron microscopy: • Visceral epithelial cells: Extensive effacement of visceral epithelial cell foot processes

overlying the subepithelial deposits; the foot processes are preserved in areas of loops without the deposits. Other degenerative changes of visceral epithelial cells can be seen as well, such as microvillous degeneration, vacuolization of the cytoplasm, increased number of lysosomes, and other cytoplasmic organelles.

• Electron-dense deposits are present in the subepithelial space and, depending on the stage of the disease, their appearance and distribution may vary: (1) Stage I: The deposits are small and sparse, sometimes sparing some capillary loops.(2) Stage II: The deposits are abundant, closely distributed, and separated from each other by basement membrane 'spikes'(projections of basement membrane between the individual deposits; visible by light microscopy on PAS and silver stains) (3) Stage III: The 'spike' projections of the basement membranes are embracing deposits, incorporating them into the glomerular basement membrane; the deposits vary in appearance from electron dense to electron lucent due to partial reabsorption. (4)Stage IV: Marked thickening of the wall with numerous intramembranous defects and lacunae due to extensive reabsorption of the deposits; only a few electron-dense deposits can be seen at this stage.

• Glomerular basement membranes: The glomerular basement membranes show attenuation or thickening and other irregularities in areas with subepithelial electron-dense deposits.

• Glomerular endothelial cells: Glomerular endothelial cells are usually unremarkable and do not contain tubuloreticular structures.

• Mesangium: The mesangium shows normal cell elements and an extracellular matrix without electron-dense deposits; a presence of deposits in the mesangium strongly suggests secondary forms of membranous nephropathy.

Lupus Nephritis Class V• Histopathology: • Light microscopic examination reveals membranous pattern of

glomerular injury, with thickened capillary loops and a presence of basement membrane 'spikes' on PAS- and silver-stained sections

• The mesangium shows various degrees of expansion and cellularity

• Subendothelial deposits, 'wire' loops, and microthrombi suggest a proliferative component (e.g., combined class III V lupus nephritis)

• Immunofluorescence: • There is 'full house' reactivity (reactivity for IgG, IgM, and IgA)

along the capillary loops and in the mesangium

• Electron microscopy: • Visceral epithelial cells: Extensive effacement of foot processes

overlying the subepithelial deposits and other degenerative changes of visceral epithelial cells, such as microvillous degeneration, vacuolization of the cytoplasm, increased number of lysosomes and other cytoplasmic organelles. The foot processes are spared in segments without deposits

• Glomerular basement membranes: Attenuation or thickening and other irregularities in areas with subepithelial electron-dense deposits

• Glomerular endothelial cells: May contain tubuloreticular structures. Small subendothelial deposits may be seen in some areas; large and widespread subendothelial deposition suggest a presence of proliferative types of lupus nephritis (class III or IV)

• Mesangium: Expanded by increase in cellular elements and extracellular matrix with scattered fine granular, electron-dense deposits