Fever, Cough, Back Pain and Fatigue

Robert A. Kyle, MD, and Michael Tomasson, MD

Dr. Kyle: Mayo Clinic College of Medicine
Dr. Tomasson: Washington University School of Medicine, St. Louis, MO

Copyright of the American Society of Hematology, 2006. ISSN: 1931-6860.

This case was reviewed and updated in March 2011 by Dr. Shirley Parker Levine and members of the Teaching Cases Subcommittee.

IV. PATHOPHYSIOLOGY

Patient Summary:
This patient presented with pneumococcal pneumonia, and on admission was found to be anemic with renal insufficiency. Evaluation of her renal disease disclosed increased urine kappa light chains with a small amount of free kappa light chain in her serum. Her serum calcium and skeletal survey were normal and negative, respectively. Bone marrow exam revealed 20% plasma cells, and no congo red staining was found.

Plasma cell proliferative disorders are a spectrum of disorders characterized by the growth and/or survival of a population of clonal plasma cells. At the benign end of the spectrum, if the plasma cell clone does not expand, the disorder is monoclonal gammopathy of undetermined significance (MGUS). MGUS patients will progress to malignant disease, usually multiple myeloma, at a rate of 1% per year. The vast majority of MGUS patients never progress to overt malignancy because of competing causes of death (e.g., cardiovascular, cerebrovascular or non-plasma cell malignancy). If the clonal plasma cell population expands over time, as is typically associated with lytic bone lesions, the disease is multiple myeloma.

Criteria for the diagnosis of multiple myeloma are: bone marrow containing monoclonal plasma cells and M-protein in serum and/or in urine, and evidence of end-organ damage. (A mnemonic for end-organ damage, which is the hallmark of multiple myeloma, is CRAB, for hypercalcemia, renal insufficiency, anemia and lytic bone lesions.)

Some patients have the criteria for a diagnosis of multiple myeloma, but they have not had a progressive course. These patients are considered to have "smoldering multiple myeloma." Both of the following criteria must be met:

  1. Serum monoclonal protein (IgG or IgA greater or equal to 3 g/dl and/or clonal bone marrow plasma cells greater than or equal to 10%).
  2. Absence of end-organ damage such as lytic bone lesions, anemia, hypercalcemia, or renal failure that can be attributed to a plasma cell proliferative disorder.

A distinct clinical entity is solitary plasmacytoma – a focal mass of malignant plasma cells that occurs in isolation anywhere in the body, without involvement of the bone marrow or end-organ damage. A patient with a solitary plasmacytoma is at risk for progressing to multiple myeloma, but may be cured with radiotherapy alone.

Primary amyloidosis is characterized by a relatively small plasma cell clone that secretes light chain protein that forms insoluble, congo-red-staining fibrils in tissues, leading to multi-organ dysfunction. Light chain deposition disease is similar, except that deposits of light chains are not fibrillar but granular, and they do not stain with congo red.

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