Review Question - QID 104642

The patient in this vignette has an elevated M protein, which cannot distinguish between multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). Multiple myeloma does not cause altered thyroid function.

Multiple myeloma (MM) is cancer of monoclonal plasma cells, which produces large amounts of IgG (55%) or IgA (25%). MM is the most common primary tumor arising within bone in the elderly. If there are increased gamma globulins on serum electrophoresis, but no symptoms of multiple myeloma are present (including bone lesions, reduced renal function, and anemia), this condition is called monoclonal gammopathy of undetermined significance (MGUS). Of note, there is often a decreased humoral immunity in patients with MM as plasma cells become unable to generate neutralizing antibodies.

O'Connell et al. review the use of serum protein electrophoresis (SPEP) in diagnosis of serum protein disorders. Mechanistically, electrophoresis separates proteins based on their physical properties, including charge and size. A homogeneous peak in a focal region of the gamma-globulin zone indicates a monoclonal gammopathy, which may including MM, Waldenstrom's macroglobulinemia, or MGUS. This is in contrast to polyclonal gammopathies (more than one peak on SPEP), which may be caused by any reactive or inflammatory process.

Dispenzieri et al. discuss smoldering multiple myeloma (SMM), an intermediate condition between MGUS and active MM in which some symptoms are present but the patient does not have the classic MM presentation. The majority of studies involving MM treatment given to patients with SMM showed no improved overall survival with therapy as compared to observation. This study concludes that in cases with extreme bone marrow plasmacytosis, extremely abnormal serum immunoglobulin free light chain ratio, and multiple bone lesions detected only by modern imaging, these patients should be treated as having MM.

Illustration A shows an example SPEP seen with MM and MGUS. Note the circled peak in gamma globulins.

Incorrect Answers:
Answer 1: Skull radiograph may reveal lytic bone lesions which are seen in MM but not MGUS.
Answer 2: Bone marrow biopsy may reveal plasma cell cytosis which is seen in MM but not MGUS.
Answer 3: Serum creatinine may reveal signs of renal injury which is seen in MM but not MGUS.
Answer 4: Serum calcium may reveal signs of hypercalcemia which is seen in MM but not MGUS.