Myeloma Cast Nephropathy



Myeloma Cast Nephropathy


Anthony Chang, MD

Lynn D. Cornell, MD





Key Facts


Terminology



  • Synonyms



    • Light chain cast nephropathy


    • Myeloma kidney


  • Accumulation of monoclonal light chains may form casts (both cytotoxic and obstructive) in distal nephron segments


Clinical Issues



  • Acute renal failure


  • 30-50% incidence among patients with multiple myeloma


  • 5-year survival rate of 20-25%


Microscopic Pathology



  • Tubular casts



    • Usually involve distal nephron segments (distal tubules and collecting ducts)


    • Sharp-edged or fractured appearance


    • Giant cell reaction to intratubular casts


    • Prominent intratubular aggregates of neutrophils can be present


Ancillary Tests



  • Immunofluorescence or immunohistochemistry



    • Kappa is more common than lambda with ratio ranging from 2:1 to 4:1


Top Differential Diagnoses



  • Rhabdomyolysis-associated acute tubular injury


  • mTOR inhibitor toxicity


  • Monoclonal immunoglobulin deposition disease


  • Acute tubular injury







H&E demonstrates a tubular cast that appears broken into 2 fragments image (or a fractured appearance). Scattered interstitial inflammatory cells image with plasma cells are present.






Lambda light chain immunofluorescence microscopy strongly stains tubular casts image in a patient with myeloma cast nephropathy. No kappa light chain staining was present (not shown).


TERMINOLOGY


Abbreviations



  • Myeloma cast nephropathy (MCN)


Synonyms



  • Light chain cast nephropathy


  • Bence Jones cast nephropathy


  • Myeloma kidney


ETIOLOGY/PATHOGENESIS


Plasma Cell Dyscrasia



  • Monoclonal light chain overproduction



    • Light chains (Bence Jones proteins) freely filtered by glomeruli


    • Not all monoclonal light chains are nephrotoxic


    • Accumulation of Tamm-Horsfall protein and monoclonal light chains in distal nephron segments may lead to both obstruction and direct cytotoxicity


    • Precipitating factors for cast formation include



      • Dehydration


      • Diuretics


      • Hypercalcemia


      • Nonsteroidal anti-inflammatory drugs


      • Contrast media


      • Infections


CLINICAL ISSUES


Epidemiology



  • Incidence



    • 30-50% among patients with multiple myeloma


  • Age



    • Typically > 40 years


  • Gender



    • Male > female


Presentation



  • Acute renal failure & proteinuria


Laboratory Tests



  • Serum &/or urine protein electrophoresis



    • Immunoelectrophoresis


    • Immunofixation electrophoresis


Treatment



  • Drugs



    • Treatment for underlying plasma cell dyscrasia, if present



      • Colchicine, thalidomide, bortezomib


  • Hematopoietic stem cell transplantation


  • Plasmapheresis


Prognosis



  • 5-year survival rate of 20-25%


MICROSCOPIC PATHOLOGY


Histologic Features



  • Tubular casts



    • Usually involve distal nephron segments (distal tubules and collecting ducts)


    • PAS negative (vs. Tamm-Horsfall protein [THP])


    • Trichrome stains red (vs. blue THP)


    • Sharp-edged or fractured appearance


    • Lined by flattened to reactive tubular epithelial cells


    • Giant cell reaction to intratubular casts may be present


    • Prominent intratubular aggregates of neutrophils can be present


    • Rare crystal appearance may be present


  • Interstitial inflammation


  • Interstitial neoplastic plasma cell infiltrates may be present



    • Monoclonal staining by in situ hybridization or immunohistochemistry



ANCILLARY TESTS


Immunofluorescence



  • Kappa is more common than lambda with ratio ranging from 2:1 to 4:1



    • Can be performed on paraffin tissue sections with good results


Electron Microscopy



  • Transmission



    • Monoclonal light chain tubular casts demonstrate a spectrum of substructural organization



      • Nonspecific appearance to crystalline, granular, or even fibrillar substructure


    • Immunogold labeling may be more sensitive than immunofluorescence or immunohistochemistry to demonstrate monoclonality in some cases


Immunohistochemistry



  • κ and λ can be tested on paraffin tissue sections if tubular casts are not present in specimen submitted for immunofluorescence microscopy


DIFFERENTIAL DIAGNOSIS


Rhabdomyolysis-associated Acute Tubular Injury



  • Tubular casts are pigmented with granular consistency


  • Absence of monoclonal immunolocalization


mTOR Inhibitor Toxicity



  • Reported in kidney transplant patients with delayed graft function after using an immunosuppressive regimen containing rapamycin


  • Tubular casts with fractured appearance



    • Multinucleated giant cell reaction can be present


    • Casts may consist of myoglobin


Monoclonal Immunoglobulin Deposition Disease



  • Often occurs concurrently with MCN


Amyloidosis



  • Concurrent amyloidosis and MCN rarely occur


Acute Tubular Injury

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Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Myeloma Cast Nephropathy

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