14. • The most frequent M protein produced by myeloma cells is IgG (60%),
followed by IgA (20% to 25%)
• rarely IgM, IgD, or IgE
• In the remaining 15% to 20% of cases, the plasma cells produce only κ or λ
light chains.
• Because of their low molecular weight, free light chains are excreted in the
urine, where they are termed Bence Jones proteins.
15. • Even more commonly, malignant plasma cells secrete both complete
immunoglobulins and free light chains and thus produce both
M proteins and Bence Jones proteins.
16. • Dysregulation of D cyclins is common in multiple myeloma.
• Proliferation of myeloma cells is supported by the cytokine interleukin
6 (IL-6)
• The characteristic bone resorption results from the secretion of
certain cytokines by myeloma cells.
• Patients with myeloma are immunosuppressed, because Myeloma
cells interfere with the function of normal plasma cells, leading to
defects in antibody production with high risk for bacterial infections.
17. Renal dysfunction is a common, serious problem in myeloma.
Results from several pathologic effects:-
• Obstructive proteinaceous casts(Bence Jones proteins ,complete
immunoglobulins, Tamm-Horsfall protein, and albumin).
• Light chain deposition in the glomeruli or the interstitium.
• Hypercalcemia, which may lead to dehydration and renal stones
• Frequent bouts of bacterial pyelonephritis
18.
19. • Multiple myeloma usually manifests with multifocal destructive
skeletal lesions, which most commonly involve the vertebral
column, ribs, skull, pelvis, femur, clavicle, and scapula.
• This destructive process often leads to pathologic fractures, most
frequently in the vertebral column or femur.
• The bone lesions usually appear as punched-out defects
20.
21. • Bone pain, due to pathologic fractures. Pathologic fractures of
vertebrae may lead to spinal cord impingement, an oncologic
emergency.
22. • Hypercalcemia stemming from bone resorption leads to neurologic
manifestations such as confusion and lethargy and contributes to
renal dysfunction.
23. • Anemia, due to marrow replacement by tumor cells as well as
suppression of hematopoiesis through uncertain mechanisms
24. • Recurrent infections with bacteria such as S. aureus, S.pneumoniae,
and E. coli, resulting from the marked suppression of normal humoral
immunity
25. • Renal insufficiency (in up to 50% of patients), resulting from the
deleterious effect of Bence Jones proteins on renal tubular cells, as
well as bacterial infections, hypercalcemia, and amyloidosis
• AL-type amyloidosis (5% to 10% of patients)
26. • Symptoms related to hyperviscosity may occur owing to excessive
production and aggregation of M proteins but this clinical
presentation is much more characteristic of lymphoplasmacytic
lymphoma.
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52. Urine free light chains (Bence Jones protein)
• These can be detected in the urine of some people with
multiple myeloma.
• The sample tested is usually a 24-hour urine (a
collection of all urine voided over a 24-hour period)
• because the total amount of free light chains in 24 hours
is related to the amount of tumor that is present.
• Either the kappa or lambda light chains (but not both in
the same person) may be measured to help diagnose
multiple myeloma and monitor the effectiveness of
treatment
53. Serum free light chains (SFLC)
• This test measures the amount of free light chains in the blood.
• Even in normal circumstances (and for unknown reasons), plasma
cells produce an excess of light chains compared to heavy chains, and
there is usually a small amount of light chains that do not become
incorporated into intact immunoglobulins.
• These remain as free light chains and are released into the
bloodstream.
• Most people with multiple myeloma produce increased amounts of
either kappa or lambda free light chains, which can be measured in
blood.
• Consequently, the ratio of kappa to lambda light chains is abnormal
and is a sensitive indicator for this disease.
• This test is used to monitor progression and/or treatment.
54.
55. Other laboratory tests
• Comprehensive metabolic panel (CMP), a group of tests used to evaluate
kidney and other organ function, electrolyte status, and to determine
calcium, albumin, and total protein levels
• Complete blood count (CBC), counts and evaluates white blood cells, red
blood cells, and platelets and determines the extent of anemia (measures
hemoglobin)
• Uric acid levels may be elevated as a complication of multiple myeloma.
• Beta-2 microglobulin, a protein on the cell surface of myeloma and other
cells; increased levels may indicate a poorer prognosis; this test may be
used to help stage the disease.
• Serum viscosity, a measure of how "thick" the fluid portion of the blood is;
when levels of the abnormal protein become very high, serum viscosity
may increase and cause symptoms.
Editor's Notes
Protein and immunofixation electrophoresis. These tests are used to help diagnose and monitor multiple myeloma. Protein electrophoresis separates the proteins in a blood or urine sample into several groups based on their electrical charge and size. In most people with multiple myeloma, large amounts of an abnormal immunoglobulin protein (M-protein) may show up as a large peak on the electrophoresis scan, also known as an M spike. The amount of normal immunoglobulins in the sample may be visibly decreased as well. Usually, both a blood and a urine sample will be tested to detect free light chains and intact immunoglobulins. Immunofixation electrophoresis is done to identify the specific type of protein that is being produced by the malignant plasma cells. The amount of protein produced may vary throughout the course of the disease, but the type will remain the same
Quantitative immunoglobulins. Each of these tests measures amounts of a different type of immunoglobulin, or antibody, in the blood. The multiple myeloma protein may be an IgG, IgA or, rarely, an IgD or IgE immunoglobulin. People with a monoclonal IgM immunoglobulin may have a related but different disease (Waldenstrom macroglobulinemia). Tests for IgG, IgA, and IgM may be ordered to help diagnose multiple myeloma and to monitor the course of the disease and its effect on the production of normal immunoglobulins. Note that the test does not differentiate abnormal immunoglobulin produced by myeloma cells and the non-tumor immunoglobulin of the same type produced by normal plasma cells.Serum immunoglobulin heavy chain/light chain. These tests can identify separately the different light chain types of each immunoglobulin class, including IgG-kappa, IgG-lambda, IgA-kappa, IgA-lambda, IgM-kappa, and IgM-lambda. The molecules are then measured in pairs (e.g., IgG-kappa / IgG-lambda) to calculate ratios of involved monoclonal immunoglobulin to background uninvolved immunoglobulin concentrations. The tests can be used to monitor people with multiple myeloma
Treatment
At this time, multiple myeloma is not considered curable, although current treatments may produce a complete remission (disappearance but not cure of the disease) in some people. The goals of treatment are to relieve pain and other symptoms, to decrease the amount of cancer present or eliminate it, to slow the progress of the disease, and/or to detect and minimize complications as they occur .
People who do not have significant symptoms are monitored but may not receive any treatment. Healthcare practitioners generally recommend that people with multiple myeloma stay as active as possible to help preserve the calcium in their bones and drink plenty of fluids to help with kidney function.
Complications such as infections, anemia, and bleeding should be promptly addressed with measures such as antibiotics and, when necessary, blood transfusions. Other supportive treatments may include injections of immunoglobulins to help fight infections and plasmapheresis to remove excess M protein from the blood. Plasmapheresis helps reduce the thickness (viscosity) of the blood. If treatment is indicated, a combination of the following may be used :
Bisphosphonates—drugs that slow the weakening of bones
Chemotherapy—drugs used to control or destroy cancerous plasma cells
Targeted therapy—drugs that target the specific cancer's cells, genes or proteins
Radiation therapy—may be used to treat areas of bone that has not responded to chemotherapy
Stem cell transplantation—this procedure involves killing cells within the bone marrow, including the myeloma cells, and then giving the patient healthy stem cells