Diffuse Proliferative GN

Renal pathology tutorial for nephrologists

1. Diffuse Proliferative GN

2. •Diffuse proliferative pattern of glomerular
injury consists of endocapillary or
extracapillary (crescents) proliferative changes
that occur in segmental or global fashion and
involve more than 50% of all glomeruli.
•The process is most commonly seen in various
immune complex-mediated processes, such as
lupus nephritis (class IV), post-infectious
(post-streptococcal) GN, or IgA nephropathy.

3. PIGN
•Histopathology:
•Acute proliferative glomerulonephritis with numerous neutrophils and
endocapillary hypercellularity in all or most glomeruli
•Cellular crescents are frequently seen in isolated glomeruli; true crescentic form
(involvement of 50% or more of glomeruli with crescents) is very unusual.
•Fibrinoid necrosis and thrombosis are uncommon.
•The tubulointerstitium may be unremarkable or show active inflammation with
or without edema.
•Immunofluorescence:
• In acute phase, there is strong coarse granular C3 reactivity, with usually less
intense immunoglobulin (most commonly IgG) deposition. Lack of significant
immunoglobulin reactivity may be seen in many cases. Three patterns of
immunofluorescence reactivity have been described: starry sky (discrete random
granules), garland (confluent subepithelial granular and band-like deposits), and
mesangial pattern (usually during resolving phase).

4. •Electron microscopy:
•Visceral epithelial cells: Different degrees of injury and
degenerative changes; the effacement of foot processes is usually
focal, but sometimes extensive
•Glomerular basement membranes: May show irregularities in
thickness. Subepithelial “hump”-like deposits are characteristic of
postinfectious GN; they may be sometimes large and confluent.
“Spike” formation is not characteristic of this entity. Sometimes
large subendothelial deposits and an intraluminal increase in
inflammatory cells may be seen as well
•Glomerular endothelial cells: May show non-specific signs of injury
and reactive changes; tubuloreticular structures are not seen
•Mesangium: Increase in cellularity and extracellular matrix, with
sometimes large and confluent fine granular electron-dense
deposits

7. Lupus Nephritis Class IV
•Histopathology:
•Light microscopic examination reveals segmental or global endocapillary
proliferative changes. The mesangium is variably expanded and
hypercellular
•The peripheral capillary loops are irregular in thickness, sometimes
showing 'wire loops' and intraluminal 'microthrombi' (hyaline thrombi)
•Leukocyte infiltration, focal necrosis, hematoxilin bodies, and cellular
crescents can all be seen
•In some cases, membranoproliferative pattern of injury may be
dominant in glomeruli (class IV)
•The tubulointerstitium may show active interstitial nephritis
•Immunofluorescence:
• There is 'full house' reactivity (reactivity for IgG, IgM, and IgA), with
granular deposits in the mesangium.

8. •Electron microscopy:
•Visceral epithelial cells: Show different degrees of injury and
degenerative changes, with focal, but sometimes extensive,
effacement of foot processes. Subepithelial deposits can be seen in
many cases
•Glomerular basement membranes: May be irregular in thickness,
with the presence of intramembranous, subepithelial, and/or
subendothelial deposits. Subendothelial deposits can be rather
large and may demonstrate substructural organization
('fingerprint'-like pattern)
•Glomerular endothelial cells: May contain tubuloreticular
structures
•Mesangium: Expanded by increase in cellular elements and
extracellular matrix, with sometimes large and confluent fine
granular, electron-dense deposits

11. •Histopathology:
•Light microscopic examination reveals mesangial hypercellularity and
expansion of mesangial matrix, with segmental or global endocapillary
proliferation and/or crescent formation
•If the number of involved glomeruli is below 50 percent, it is designated
as focal proliferative pattern; if there are 50 percent or more glomeruli
involved, the process is designated as diffuse proliferative IgA
glomerulonephritis
•The tubulointerstitium may be unremarkable or show active
inflammation or patchy fibrosis
•Immunofluorescence:
• There is dominant reactivity for IgA in the mesangium; C3 may be
equally or less reactive. There is usually stronger reactivity for lambda
than for kappa light chains in the mesangial deposits

12. •Electron microscopy:
•Visceral epithelial cells: Show different degrees of injury and
degenerative changes; the effacement of foot processes is usually
focal but sometimes extensive. Subepithelial and/or subendothelial
deposits can also be present
•Glomerular basement membranes: May be thin; there is a higher
incidence of thin glomerular basement membrane disease in IgA
nephropathy than in any other glomerular disease {6}
•Glomerular endothelial cells: May show non-specific signs of
injury; tubuloreticular structures are not seen
•Mesangium: Shows increase in cellularity and extracellular matrix,
with fine granular electron-dense deposits that are sometimes large
and confluent