Multiple myeloma is a cancer of plasma cells that produce abnormal proteins called monoclonal proteins (M proteins). The most common M protein is IgG, followed by IgA. In some cases, only free light chains are produced. Free light chains can cause kidney damage and are detected in urine as Bence Jones proteins. Myeloma cells secrete cytokines like IL-6 that support their growth and cause bone damage. Patients experience symptoms like bone pain, fractures, anemia, and kidney problems. Diagnosis involves tests to detect M proteins in blood and urine and check for organ damage and immune suppression.

1. PRESENTED BY : Ali Faris

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

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

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.

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.

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.