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.


TERMINOLOGY


Synonyms



  • Fibrillary glomerulonephritis (FGN)


  • Nonamyloidotic fibrillary glomerulopathy


  • Congo red negative amyloidosis-like glomerulopathy


Definitions



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


ETIOLOGY/PATHOGENESIS


Unknown



  • 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%)


CLINICAL ISSUES


Epidemiology



  • Incidence



    • < 1% of native kidney biopsies


  • Age



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


  • Gender



    • Slight female predilection


  • Ethnicity



    • Caucasian predilection (> 90%)


Presentation



  • Proteinuria (100%)



    • Nephrotic (38%)


  • Hematuria (52%)


  • Hypertension (70%)


  • Renal insufficiency


Laboratory Tests



  • Normocomplementemic (97%)


Treatment



  • Drugs



    • None effective, corticosteroids if acute inflammation


Prognosis



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



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


  • Recurrence rate of 35-50% in kidney allografts


MICROSCOPIC PATHOLOGY


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



ANCILLARY TESTS


Immunofluorescence



  • 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


DIFFERENTIAL DIAGNOSIS


Amyloidosis



  • 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


DIAGNOSTIC CHECKLIST


Pathologic Interpretation Pearls



  • Pathologic predictor of poor outcome



    • Global glomerulosclerosis



SELECTED REFERENCES

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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