Immunotactoid Glomerulopathy



Immunotactoid Glomerulopathy


Anthony Chang, MD










Jones methenamine silver reveals that the immune deposits along the glomerular capillaries are mostly negative for silver staining in this case of immunotactoid glomerulopathy. (Courtesy J. Kowalewska, MD.)






The characteristic microtubular pattern of deposits in immunotactoid glomerulopathy is evident even in this medium-power electron micrograph.


TERMINOLOGY


Abbreviations



  • Immunotactoid glomerulopathy (ITG)


Synonyms



  • Congo red negative organized glomerular immunoglobulin deposits


Definitions



  • Congo red negative microtubular deposits typically > 30 nm in diameter and arranged in parallel arrays


ETIOLOGY/PATHOGENESIS


Unknown Mechanism



  • Microtubular glomerular deposits usually represent monotypic immunoglobulins


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Rare


    • < 0.1% of adult native kidney biopsies


  • Age



    • 5th to 6th decade



      • Older than patients with fibrillary glomerulonephritis


  • Gender



    • Slight female predilection


  • Ethnicity



    • Caucasian predilection


Site



  • Typically limited to kidney


Presentation



  • Nephrotic syndrome


  • Hematuria


  • Hypocomplementemia


  • 67% of patients have an associated monoclonal gammopathy or hematologic malignancy


Laboratory Tests



  • Serum or urine protein electrophoresis


  • Immunofixation or immunoelectrophoresis


Treatment



  • Drugs



    • Chemotherapy for underlying lymphoproliferative disorder or plasma cell dyscrasia, if present


Prognosis



  • Data limited: Median time to end-stage renal disease is ˜ 2 years



    • Clinical course depends on underlying lymphoproliferative disorder, if present


    • Occasional response to chemotherapy



      • Repeat biopsies show loss of deposits in a minority


  • Recurrence after kidney transplantation (˜ 50%), more benign course


MICROSCOPIC PATHOLOGY


Histologic Features



  • Glomerulus



    • Varied patterns: Mesangioproliferative, membranoproliferative, nodular glomerular disease



      • Mesangial expansion by eosinophilic, PAS-positive material


      • GBM: Focal splitting and occasional “spikes”


      • Rare crescents (vs. fibrillary glomerulonephritis)


  • Tubular atrophy


  • Interstitial fibrosis


  • Extrarenal deposits rarely reported (e.g., peripheral nerve)



ANCILLARY TESTS


Immunofluorescence



  • Predominantly IgG, with rare cases showing IgA or IgM



    • IgG1 is most common subclass when monotypic deposits present


  • Kappa &/or lambda light chain



    • Most cases are monoclonal, but polyclonal staining can be observed


  • C3 usually positive, and C1q less frequently positive


Electron Microscopy



  • Transmission



    • Microtubular deposits with hollow core or electron-lucent tubular lumen organized in parallel arrays



      • Typically > 30 nm in diameter (range: 20-90 nm)


    • Subendothelial location in irregular, chunky pattern along capillary loops and mesangium


    • Subepithelial and intramembranous deposits may also be seen


DIFFERENTIAL DIAGNOSIS


Cryoglobulinemic Glomerulonephritis



  • Electron-dense deposits often with substructural organization


  • Serum positive for cryoglobulins


Fibrillary Glomerulopathy



  • Randomly arranged fibrils with average thickness of 20 nm without hollow core


  • Polyclonal IF staining; commonly IgG4


Fibronectin Glomerulopathy



  • Fibrillar deposits < 30 nm; IgG negative


  • Positive immunohistochemistry for fibronectin


Type III Collagen Glomerulopathy



  • Periodic banded collagen fibrils by EM and type III collagen by IHC

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