Categories: Hematology/Oncology

MGUS vs. Multiple Myeloma vs. Waldenstrom’s

Monoclonal gammopathy of undetermined significance (MGUS)

  • Asymptomatic premalignant state
  • Common in elderly population (~10% in patients >75 years old)
  • Paraprotein <30g/L (<3g/dL)
  • Plasma cells <10% on bone marrow
  • No CRAB syndromes (see below)
  • No other B-cell proliferation disorder
  • No treatment needed, but must be monitored as 1-1.5% will progress to Multiple Myeloma per year

Multiple Myeloma

  • Neoplastic proliferation of a single plasma cell lineage aka M-protein (Usually of the IgG or IgA type)
  • Incidence is increased after age 50
  • Paraprotein >30g/L (>3g/dL) [serum and/or urine]
  • Plasma cells >10% on bone marrow
  • HyperCalcemia: Due to bone destruction from lytic bone lesions
  • Renal Failure: Immunoglobulin precipitation in renal tubules leads to tubular casts of Bence Jones protein
  • Anemia: Normocytic normochromic. Also leukopenia, thrombocytopenia (look for rouleaux formation on peripheral smear—hyperglobulinemia causes the RBCs to stick together)
  • Bone pain: Due to osteolytic lesions and vertebral fractures 
  • Treated with bisphosphonates, steroids, chemotherapy (If below age 65 consider autologous hematopoietic stem-cell transplantation).

Waldenström’s macroglobulinemia

  • Malignant proliferation of plasmacytoid lymphocytes
  • IgM >50g/L (5 g/dL)
  • Bence Jones proteinuria in 10% of cases
  • Hyperviscosity syndrome (due to paraproteinemia of large sized IgM): visual changes due to retinopathy, headache, vertigo, mucosal bleeding, seizures and coma
  • Other Clinical features: constitutional symptoms, splenomegaly, anemia and lymphadenopathy
  • There is no definitive treatment (chemotherapy and plasmapheresis for hyperviscosity syndrome)


  1. Lichtman  MA. Chapter 108. Essential monoclonal gammopathy. In: Lichtman  MA, Kipps  TJ, Seligsohn  U, Kaushansky  K, Prchal  JT, eds. Williams Hematology. 8th ed. New York, NY: McGraw-Hill; 2010
  2. Clinical Genomics: Practical Applications in Adult Patient Care. Chapter  37: Multiple Myeloma and Other Plasma Cell Disorders. Esteban Braggio; Rafael Fonsec.
  3. The MD Anderson Manual of Medical Oncology, 3e. Chapter Chapter 11: Multiple Myeloma and Other Plasma Cell Dyscrasias. Hans C. Lee; Krina Patel; Piyanuch Kongtim; Simrit Parmar; Pei Lin; Muzaffar H. Qazilbash; Sheeba Thomas; Elisabet E. Manasanch
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Dr. C Humphreys

Internal Medicine

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