Monoclonal Gammopathy: Test and Diagnosis

1st order laboratory parameters – obligatory laboratory tests.

  • Small blood count [plasmocytoma/multiple myeloma: normochromic anemia (anemia), leukopenia (decreased white blood cell count), and thrombocytopenia (decreased platelet count); final may be pancytopenia (synonym: tricytopenia: decrease in all three cell series in the blood; stem cell disease)]
  • Differential blood count
  • Inflammatory parameters – CRP (C-reactive protein) or ESR (erythrocyte sedimentation rate) [plasmacytoma/multiple myeloma: ↑↑↑]
  • Calcium [plasmocytoma/multiple myeloma: ↑]
  • Urine status (rapid test for: pH, leukocytes, nitrite, protein, blood), sediment, urine culture (pathogen detection and resistogram) if necessary.
  • Renal parameters – urea, creatinine, cystatin C or creatinine clearance if necessary [increase in renal retention parameters].
  • Total protein in blood serum
  • Serum electrophoresis / M-gradient
  • Immunofixation electrophoresis
  • Quantitative immunoglobulin determination (IgA, IgD, IgE, IgG, IgM).
  • Quantitative kappa-lambda light chain determination.
  • Uric acid

Laboratory parameters 2nd order – depending on the results of the history, physical examination and obligatory laboratory parameters – for differential diagnostic clarification.

  • Differentiation of proteins in the urine
  • Bence-Jones proteins in urine [detection in plasmacytoma/multiple myeloma].
  • Beta-2-microglobulin (β2-microglobulin) [high levels tend to be prognostically unfavorable]
  • LDH
  • Bone marrow aspiration with histological workup [proportion of more than 10% plasma cells is considered an unfavorable prognostic factor].

Diagnostic criteria for the differential diagnosis of symptomatic multiple myeloma (MM) from “smouldering (asymptomatic) MM” and monoclonal gammopathy of uncertain significance (MGUS):

MGUS* Smouldering MM Symptomatic MM (requiring treatment)
Monoclonal protein <30 g/l in serum ≥ 30 g/l in serum, small amounts (< 1 g/24h) possible in urine Present in serum and/or urine
and /or
Percentage of plasma monoclonal cells in the bone marrow. < 10 % ≥ 10 % > 10 % or plasmocytoma and
Organ damage according to CRAB criteria (see below). None none Organ damage present

* An MGUS (see below) progresses to a plasmacytoma in approximately 1% of cases.

Myeloma disease requires treatment if at least one of the CRAB criteria is met. The acronym CRAB stands for:

Further notes

  • Monoclonal gammopathy of uncertain significance (MGUS) – precancerous condition for lymphoproliferative disorders such as multiple myeloma or Waldenström’s disease; paraproteinemia with monoclonal IgM globulins without histologic infiltration of the bone marrow with plasma cells or lymphoma cells (i.e., there is no plasmacytoma/multiple myeloma or Waldenström’s disease); in the United States, monoclonal gammopathy of unclear significance (MGUS) is found in 3.2% of those over 50 years of age and 5.3% of those over 70 years of age; progresses to lymphoproliferative disease in 1.5% of cases per yearNote: MGUS may persist for more than 30 years before clinical disease develops; in these patients, an additional jag, the “M gradient,” can be seen in the gamma globulin region. This indicates the spread of cell clones in the bone marrow.