Fibrillary Glomerulopathy

Fibrillary Glomerulopathy

Anthony Chang, MD

Periodic acid-Schiff shows diffuse expansion of mesangial areas image by eosinophilic material with normal glomerular basement membranes in a young female with FGN.

Jones methenamine silver reveals increased mesangial hypercellularity image and focal duplication of the glomerular basement membrane image.



  • Fibrillary glomerulonephritis (FGN)

  • Nonamyloidotic fibrillary glomerulopathy

  • Congo red negative amyloidosis-like glomerulopathy


  • Glomerular disease characterized by nonamyloid, nonperiodic fibrillar deposits of immunoglobulin, 10-30 nm in diameter



  • Fibrils contain IgG, usually IgG4 ± IgG1, with both light chains (polyclonal)

    • Occasional cases monotypic light chains (10-20%)

    • Most cases idiopathic

  • Associations

    • Malignancy (23%)

    • Dysproteinemia (17%)

    • Autoimmune disease (15%), including systemic lupus erythematosus

    • Infection, including hepatitis C virus (3%)



  • Incidence

    • < 1% of native kidney biopsies

  • Age

    • Average: ˜ 50 years; range: 19-81 years

  • Gender

    • Slight female predilection

  • Ethnicity

    • Caucasian predilection (> 90%)


  • Proteinuria (100%)

    • Nephrotic (38%)

  • Hematuria (52%)

  • Hypertension (70%)

  • Renal insufficiency

Laboratory Tests

  • Normocomplementemic (97%)


  • Drugs

    • None effective, corticosteroids if acute inflammation


  • 40-50% progress to ESRD in 2-4 years

    • Occasional complete (5%) or partial (8%) remission

  • Recurrence rate of 35-50% in kidney allografts


Histologic Features

  • Glomeruli

    • Diffuse mesangial expansion by eosinophilic material

    • Mesangial sclerosis &/or hypercellularity pattern

      • Can manifest as nodular glomerulosclerosis

      • Segmental &/or global glomerular scarring

    • Membranoproliferative pattern

      • Focal GBM duplication

    • Marked subepithelial deposits may mimic membranous GN

    • Cellular crescents in ˜ 25% of cases

      • Usually < 20% of glomeruli

    • Congo red stain negative

    • PAS and Jones silver stain negative (or weak)

  • Tubules and interstitium

    • Interstitial fibrosis and tubular atrophy common

    • Interstitial inflammation may be prominent when tubular basement membrane deposits present



  • Prominent IgG deposits in mesangium and along GBM

    • Often IgG4 (90%) with (80%) or without (10%) IgG1; rarely IgG1 alone (10%)

      • IgG4 heavy chains spontaneously reassociate, impairing detection of monotypic light chains

    • Kappa = lambda in most cases

      • 10-20% monotypic light chains (70% lambda)

    • May mimic anti-GBM disease or MGN

  • C3 almost always strongly positive (92%), often lesser C1q (60%)

  • May have IgM (47%) or IgA (28%) but at a lesser intensity than IgG

  • TBM deposits of IgG in a subset

Electron Microscopy

  • Randomly arranged fibrils deposited in mesangial areas and along GBM

    • Fibrils without hollow core or organized substructure

      • Average diameter: 18-20 nm; range: 10-30 nm

      • Resemble amyloid fibrils but usually larger diameter

    • Fibrils composed of immunoglobulins by immunogold labeling

  • TBM has fibrillar deposits in subset of cases



  • Congo red positive with apple-green birefringence under polarized light; 8-12 nm thick fibrils

Immunotactoid Glomerulopathy

  • Microtubular substructure of deposits larger (30-50 nm thick fibrils)

  • Often associated with underlying plasma cell dyscrasia

  • Usually (˜ 80%) monotypic

Cryoglobulinemic Glomerulonephritis

  • Serum cryoglobulins present

  • Membranoproliferative pattern of injury with “pseudothrombi” on light microscopy

  • Strong IgM, not IgG4 dominant

Fibronectin Glomerulopathy

  • Mesangial and subendothelial deposition of PAS(+) material

  • Negative immunofluorescence staining


Pathologic Interpretation Pearls

  • Pathologic predictor of poor outcome

    • Global glomerulosclerosis


1. Nasr SH et al: Fibrillary glomerulonephritis: a report of 66 cases from a single institution. Clin J Am Soc Nephrol. Epub ahead of print, 2011

2. Alpers CE et al: Fibrillary glomerulonephritis and immunotactoid glomerulopathy. J Am Soc Nephrol. 19(1):34-7, 2008

3. Rosenstock JL et al: Fibrillary and immunotactoid glomerulonephritis: Distinct entities with different clinical and pathologic features. Kidney Int. 63(4):1450-61, 2003

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Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Fibrillary Glomerulopathy

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