Multiple myeloma

Multiple myeloma (also known simply as myeloma or plasma cell myeloma, or as Kahler's disease after Otto Kahler) is a presently incurable hematological malignancy of plasma cells, the cells of the immune system that produce antibodies. Although it initially develops in the bone marrow, it spreads to the peripheral blood, lymph nodes and other organs. Its prognosis despite therapy is generally poor, and treatment may involve chemotherapy and bone marrow transplant.

Diagnosis

Investigations

The existence of unexplained anemia, a high erythrocyte sedimentation rate (ESR) and a high serum protein (especially raised globulin) may suggest further testing. A doctor will then order protein electrophoresis of the blood and urine, on which a paraprotein (monoclonal protein, or M protein) band can be noticed. Quantitative nephelometric measurements of the paraprotein are necessary to determine the severity of the disease. The paraprotein is a deviant immunoglobulin produced by the tumor clone. Very rarely, the myeloma is nonsecretory (not producing immunoglobulins).

Related Topics:
Anemia - Erythrocyte sedimentation rate - Protein - Globulin - Doctor - Protein electrophoresis - Paraprotein - Immunoglobulin

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

In theory, myeloma can produce all classes of immunoglobulin, but IgD, IgM and IgE myeloma are very rare compared to IgG and IgA. In addition, light and heavy chains (the building blocks of antibodies) may be secreted in isolation: κ- or λ-light chains or any of the five types of heavy chains (α-, γ-, δ-, ε- or μ-heavy chains).

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Additional findings are: a raised calcium (when myeloma cells are breaking down bone, releasing calcium into the bloodstream) and decreased renal function (due to amyloid of the kidney).

Related Topics:
Calcium - Renal function - Amyloid - Kidney

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Workup

Once a paraprotein has been detected, or biopsy of a lesion suggests the presence of myeloma, a skeletal survey is performed. This is a series of X-rays of the skull, axial skeleton and proximal long bones. Myeloma deposits appear as "lytic lesions" (with local disappearance of normal bone due to resorption), and on the skull X-ray as "punched-out lesions". Routine biochemical markers of elevated bone turnover (e.g. alkaline phosphatase) are not typically elevated.

Related Topics:
Biopsy - Skeletal survey - X-ray - Alkaline phosphatase

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

A bone marrow biopsy is required for a complete diagnosis, on which plasma cells are detected. Immunohistochemistry (staining particular cell types using antibodies against surface proteins) can confirm the plasma cell character of uncertain cells; myeloma cells are CD56 positive and CD19 negative{{mn|IMWG|2}}. Cytogenetics is generally not performed in myeloma, although particular aberrations have been reported (see below).

Related Topics:
Bone marrow biopsy - Immunohistochemistry - CD56 - Cytogenetics

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Criteria

New international critera{{mn|IMWG|2}}, agreed in 2003, require the following:

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

• Plasma cells >10% on bone marrow biopsy or (in any quantity) in a biopsy from other tissues (plasmacytoma)
• A monoclonal protein in either serum (of >30 g/L) or urine
• Evidence of end-organ damage (related organ or tissue impairment, ROTI):
• Hypercalcemia
• Renal insufficiency
• Anemia
• Bone lesions
• Frequent severe infections (>2 a year)
• Amyloidosis of other organs
• Hyperviscosity syndrome

Some myelomas do not secrete any paraprotein. These are termed "non-secretory myeloma", and paraproteins are thus not available for blood or urine testing. Progression in these cases is monitored through bone marrow biopsy. It is rare compared to the secretory forms.

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Related conditions are solitary plasmacytoma (a single tumor of plasma cells, typically treated with irradiation), plasma cell dyscrasia (where only the antibodies produce symptoms, e.g. amyloidosis) and monoclonal gammopathy of undetermined significance (MGUS). Most cases of myeloma probably start as MGUS.

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Staging

International Staging System (ISS):

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

• Stage I: β₂-microglobulin (β2M) < 3.5 mg/L, albumin >= 3.5 g/dL
• Stage II: β2M < 3.5 and albumin < 3.5; or β2M between 3.5 and 5.5
• Stage III: β2M > 5.5