Myeloma Cast Nephropathy

Myeloma Cast Nephropathy

Anthony Chang, MD

Lynn D. Cornell, MD

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).



  • Myeloma cast nephropathy (MCN)


  • Light chain cast nephropathy

  • Bence Jones cast nephropathy

  • Myeloma kidney


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



  • Incidence

    • 30-50% among patients with multiple myeloma

  • Age

    • Typically > 40 years

  • Gender

    • Male > female


  • Acute renal failure & proteinuria

Laboratory Tests

  • Serum &/or urine protein electrophoresis

    • Immunoelectrophoresis

    • Immunofixation electrophoresis


  • Drugs

    • Treatment for underlying plasma cell dyscrasia, if present

      • Colchicine, thalidomide, bortezomib

  • Hematopoietic stem cell transplantation

  • Plasmapheresis


  • 5-year survival rate of 20-25%


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



  • 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


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


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


  • Concurrent amyloidosis and MCN rarely occur

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