Renal Digest
Electron microscopy
Clinical differential diagnosis
Pathologic differential diagnosis
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    Fibrillary glomerulonephritis
     Key features:
Clinical: Variable presentation, but patients often have nephrotic-range proteinuria; the disease is invariably progressive
Light microscopy: Diverse histologic patterns, most commonly membranoproliferative or mesangioproliferative; Congo red stain is negative
Immunofluorescence: Polyclonal IgG reactivity
Electron microscopy: Randomly arranged, non-branching fibrils, 12-30 nm in diameter

Fibrillary glomerulopathy is characterized by progressive clinical course, variable histologic patterns (most commonly membranoproliferative or mesangioproliferative), with extracellular deposition of Congo red negative material, ultrastructurally consisting of non-branching, randomly arranged microfibrils 12-30 nm in diameter, usually with polyclonal IgG4 immunofluorescence reactivity.

Fibrillary glomerulopathy

Differential diagnosis:
Immunoglobulin A (IgA) nephropathy, mesangioproliferative type
Lupus nephritis, mesangioproliferative type (class II)
Membranoproliferative glomerulonephritis (MPGN), idiopathic, type I
Monoclonal immunoglobulin deposition disease (MIDD)
Immunotactoid glomerulopathy

Unclear etiology; fibrillary GN is only rarely associated with B-cell neoplasias while the link is stronger in cases of immunotactoid glomerulopathy {1}

Occurs more commonly in older patients (very rare in children) and Caucasians
There is usually nephrotic range proteinuria; other presenting symptoms vary, including nephrotic syndrome, acute renal failure, rapidly progressive nephritis, chronic renal insufficiency
Outcome may be dependent on histologic pattern of injury {2}. The disease is associated with significant risk of ESKD {3}
Outcome may be dependent on histologic pattern of injury {2}

Commonly, there is mesangial expansion with increased mononuclear inflammatory cells and matrix and peripheral capillary loop thickening (MPGN-like pattern of injury); sometimes, the predominant pattern is mesangioproliferative (if the deposition is not involving capillary loops) or even less commonly, membranous, diffuse proliferative, or sclerosing patterns may be seen {2}
Proliferative changes, such as increased endocapillary proliferation or crescent formation, are uncommon but occur
Congo red stain is negative
Silver stain may reveal “moth eaten” appearance (non-reactive deposits admixed with reactive matrix)


      There is polyclonal deposition of IgG (most often IgG1 or IgG4) and C3 in the mesangium and along the peripheral capillary loops; in less than 10% of cases, the reactivity will be of monoclonal IgG; in very rare cases there will be no immunoglobulin reactivity.
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Electron microscopy:  
Visceral epithelial cells: Focal, sometimes marked effacement of visceral epithelial cell foot processes
Glomerular basement membranes: Usually marked thickening of the membranes with extensive fibrillary deposits; the deposition extends to subepithelial, subendothelial, and paramesangial spaces. The fibrils are non-branching, randomly oriented, 12-30 nm in diameter
Glomerular endothelial cells: Show loss of fenestrations and other non-specific changes; they do not contain tubuloreticular structures
Mesangium: Usually expanded by matrix and organized fibrillary deposits

Clinical differential diagnosis:  
Diseases that present with nephrotic syndrome: Membranous nephropathy, amyloidosis, idiopathic focal and segmental glomerulosclerosis
Diseases with acute renal failure and rapidly progressive nephritis: Crescentic glomerulonephritides

Pathologic differential diagnosis:  
Immune complex-mediated glomerulonephritides with MPGN-pattern of injury; these include idiopathic MPGN, autoimmune diseases (lupus class IV, MCTD, RA, SS, etc.) and chronic infections (hepatitis B and C, hepatitis C-related cryoglobulinemia, endocarditis, shunt infections, parasitic infections)
Chronic thrombotic angiopathies
Diabetic glomerulosclerosis
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Fibrillary glomerulopathy, with marked mesangial expansion and mildly increased cellularity. Some of the loops are thickened; H&E, 200x
Fibrillary glomerulopathy; marked mesangial expansion and thickening of some loops; H&E, 400x
Fibrillary glomerulopathy superimposed to advanced diabetic glomerulosclerosis; fibrillary deposits are seen in very expanded mesangium; EM, 25,000
Fibrillary glomerulopathy, EM, 20,000x
Low power electronmicrograph of fibrillary glomerulopathy; the deposits are present in the mesangium, while capillary loops are spared, EM, 2,000x
Mesangial deposits in fibrillary glomerulopathy, EM, 4,000x
Intramembranous and subepithelial fibrillary deposits in fibrillary glomerulopathy; EM, 4,000x
High power view of fibrillary GN; EM, 44,000x
Fibrillary glomerulopathy, with deposits made of non-branching, randomly arranged fibrils; EM, 50,000x
Capillary loop involvement in fibrillary glomerulopathy; EM, 6000x
Capillary loop involvement in fibrillary glomerulopathy; EM, 8,000x
Fibrillary glomerulopathy, with mesangial expansion and thickening of some loops. There is prominence of glomerular epithelial cells in some parts of the tuft; JMS stain, 200x
Cellular crescent in fibrillary glomerulonephritis; JMS stain, 200x
Fibrillary glomerulopathy; trichrome, 200x
Fibrillary glomerulonephritis, low power view; mesangial expansion, increased cellularity, and a cellular crescent in a single glomerulus; PAS, 100x
Fibrillary glomerulonephritis; there is a cellular crescent and segmental hypercellularity due to inflammatory infiltrate; PAS, 200x
Marked mesangial expansion and mild mesangial hypercellularity in fibrillary glomerulopathy; PAS, 400x
Thickened capillary loops and prominent mesangium in fibrillary glomerulopathy; JMS, 400x
Fibrillary glomerulopathy; PAS, 200x
Thickened capillary loops, expanded mesangium, and mesangial hypercellularity in fibrillary glomerulopathy; PAS, 400x
Fibrillary glomeruopathy; PAS, 400x
Negative Congo red stain in fibrillary glomerulopathy; Congo red, 400x
Fibrillary glomerulopathy; JMS, 100x
Fibrillary glomerulopathy, low magnification; PAS, 100x
Mesangial reactivity for IgG in fibrillary GN; IF, 200x
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References :
1. Bridoux F, Hugue V, Coldefy O, Goujon JM, Bauwens M, Sechet A, Preud´HommeJL, Touchard G. Fibrillary glomerulonephritis and immunotactoid (microtubular) glomerulopathyare associated with distinct immunologic features.Kidney Int. 2002 Nov;62(5):1764-75.  PUBMED  
2. Rosenstock JL, Markowitz GS, Valeri AM, Sacchi G, Appel GB, D´Agati VD. Fibrillary and immunotactoid glomerulonephritis: Distinct entities withdifferent clinical and pathologic features.Kidney Int. 2003 Apr;63(4):1450-61.  PUBMED