Type III Collagen Glomerulopathy



Type III Collagen Glomerulopathy


Helen Liapis, MD

Joseph Gaut, MD, PhD





Key Facts


Terminology



  • Idiopathic glomerular disease defined by accumulation of mesangial and subendothelial type III collagen


Clinical Issues



  • Rare (< 0.1% of biopsies)


  • Presents with hematuria or proteinuria


  • Hemolytic uremic syndrome, children


  • Variable disease course


  • Increased serum and urine procollagen III peptide


Microscopic Pathology



  • Lobular glomeruli without inflammation


  • Thickened capillary walls


  • Mesangial and capillary wall expansion with eosinophilic, silver-positive material


  • Electron microscopy



    • Mesangial and subendothelial curvilinear fibrils


    • Fibers tend to be frayed and curved, ˜ 60 nm periodicity


  • Immunohistochemical staining for type III collagen positive in mesangium and GBM


Top Differential Diagnoses



  • Nail-patella syndrome


  • Hereditary multiple exostoses


  • Fibronectin glomerulopathy


  • Fibrillary glomerulopathy


Diagnostic Checklist



  • Diagnosis made by demonstration of collagen III in glomeruli







Type III collagen glomerulopathy has a varied glomerular pathology. In this particular case, the glomeruli are hypercellular with a lobular appearance. (Courtesy G. Herrera, MD.)






Immunohistochemical stain for collagen III shows deposits of collagen III in the GBM and mesangium in a case of type III collagen glomerulopathy. Normal glomeruli have no detectable collagen III.


TERMINOLOGY


Synonyms



  • Collagenofibrotic glomerulopathy


Definitions



  • Idiopathic glomerular disease defined by accumulation of mesangial and subendothelial type III collagen


  • Initially described by Arakawa and colleagues in 1979


ETIOLOGY/PATHOGENESIS


Proposed Etiologies



  • Probably systemic disease of collagen metabolism



    • Increased level of N-terminal procollagen type III in blood



      • Indicative of increased synthesis/catabolism


      • Deposit in glomeruli


      • Excreted in urine


  • Occasional cases in siblings suggest a genetic component, as yet unidentified


  • Some believe this is a primary disease of the glomerulus


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Rare (˜ 0.1% of biopsies)


  • Age



    • All ages


  • Gender



    • M:F = 1:1


  • Ethnicity



    • Majority of reported cases are Japanese


    • Cases also reported in USA, Europe, India, South America, China


Presentation



  • Microhematuria


  • Hypertension


  • Edema


  • Proteinuria, nephrotic range in 60%


  • Anemia



    • Adults typically have anemia of chronic disease


    • Children occasionally present with thrombotic microangiopathy


  • Hemolytic uremic syndrome, children


Laboratory Tests



  • 10-100x increase in serum and urine N-terminal procollagen type III peptide (PIIINP)


Treatment



  • Drugs



    • No specific treatment


    • Steroid therapy is reported to slow disease progression


Prognosis



  • Variable disease course, limited data



    • ˜ 35% of adults and ˜ 90% of children progress to end-stage renal failure


MICROSCOPIC PATHOLOGY


Histologic Features



  • Glomeruli



    • Lobular or mesangial hypercellularity, variable



      • Nodular pattern at times resembles diabetic glomerulopathy


    • Expansion of mesangium with eosinophilic, silver-positive material


    • Thickening of GBM



      • Occasional double contours


    • Closure of capillary loops


    • No inflammation


  • No specific changes in tubules, interstitium, or vessels


Tags:
Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Type III Collagen Glomerulopathy

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