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Пульмонология, гематология (англ,рус)

 

 

Short theoretic material

 

Multiple Myeloma(Myelomatosis; Plasma Cell Myeloma)

Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include bone pain, renal insufficiency, hypercalcemia, anemia, and recurrent infections. Diagnosis requires demonstration of M-protein (sometimes present in urine and not serum) and either lytic bone lesions, light-chain proteinuria, or excessive marrow plasma cells. A bone marrow biopsy is usually needed. Specific treatment includes conventional chemotherapy with the addition of bortezomib, lenalidomide, thalidomide, corticosteroids, and high-dose melphalan followed by autologous peripheral blood stem cell transplantation.

The incidence of multiple myeloma is 2 to 4/100,000. Male:female ratio is 1.6:1, and the median age is about 65 yr. Prevalence in blacks is twice that in whites. Etiology is unknown, although chromosomal and genetic factors, radiation, and chemicals have been suggested.

Pathophysiology

The M-protein produced by the malignant plasma cells is IgG in about 55% of myeloma patients and IgA in about 20%; of patients producing either IgG or IgA, 40% also have Bence Jones proteinuria, which is free monoclonal κ or λ light chains in the urine. In 15 to 20% of patients, plasma cells secrete only Bence Jones protein. IgD myeloma accounts for about 1% of cases.

Diffuse osteoporosis or discrete osteolytic lesions develop, usually in the pelvis, spine, ribs, and skull. Lesions are caused by bone replacement by expanding plasmacytomas or by cytokines that are secreted by malignant plasma cells that activate osteoclasts and suppress osteoblasts. The osteolytic lesions are usually multiple; occasionally, they are solitary intramedullary masses. Enhanced bone loss may also lead to hypercalcemia. Extraosseous solitary plasmacytomas are unusual but may occur in any tissue, especially in the upper respiratory tract.

Renal failure (myeloma kidney) occurs in many patients at diagnosis or during the course of the disorder due to many causes, most commonly from deposition of light chains in the distal tubules and hypercalcemia. Patients also often develop anemia usually from kidney disease or suppression of erythropoiesis by cancer cells.

Susceptibility to bacterial infection may occur in some patients. Viral infections, especially herpetic infections, are increasingly occurring as a result of newer treatment modalities. Secondary amyloidosis (see Amyloidosis: Secondary amyloidosis (AA)) occurs in 10% of myeloma patients, most often in patients with Bence Jones proteinuria of λ-type.

Variant expressions of multiple myeloma occur: Plasma Cell Disorders: Variant Expressions of Multiple Myeloma ).

Symptoms and Signs

Persistent bone pain (especially in the back or thorax), renal failure, and recurring bacterial infections are the most common problems on presentation, but many patients are identified when routine laboratory tests show an elevated total protein level in the blood or show proteinuria. Pathologic fractures are common, and vertebral collapse may lead to spinal cord compression and paraplegia. Symptoms of anemia predominate or may be the sole reason for evaluation in some patients, and a few patients have manifestations of hyperviscosity syndrome (see Plasma Cell Disorders: Symptoms and Signs). Peripheral neuropathy, carpal tunnel syndrome, abnormal bleeding, and symptoms of hypercalcemia (eg, polydipsia) are common. Patients may also present with renal failure. Lymphadenopathy and hepatosplenomegaly are unusual.

Diagnosis

• CBC with platelets, peripheral blood smear, ESR, chemistry panel (BUN, creatinine, Ca, uric acid, LDH)

• Serum and urine protein electrophoresis, followed by immunofixation

• X-rays (skeletal survey)

• Bone marrow examination

Multiple myeloma is suspected in patients > 40 yr with persistent unexplained bone pain, particularly at night or at rest, other typical symptoms, or unexplained laboratory abnormalities, such as elevated blood protein or urinary protein, hypercalcemia, renal insufficiency, or anemia. Laboratory evaluation includes routine blood tests, protein electrophoresis, x-rays, and bone marrow examination.

Routine blood tests include CBC, ESR, and chemistry panel. Anemia is present in 80% of patients, usually normocytic-normochromic anemia with formation of rouleau, which are clusters of 3 to 12 RBCs that occur in stacks. WBC and platelet counts are usually normal. ESR usually is > 100 mm/h; BUN, serum creatinine, LDH, and serum uric acid are frequently elevated. Anion gap is sometimes low. Hypercalcemia is present at diagnosis in about 10% of patients.

Protein electrophoresis is done on a serum sample and on a urine sample concentrated from a 24-h collection to quantify the amount of urinary M-protein. Serum electrophoresis identifies M-protein in about 80 to 90% of patients. The remaining 10 to 20% are usually patients with only free monoclonal light chains (Bence Jones protein) or IgD. They almost always have M-protein detected by urine protein electrophoresis. Immunofixation electrophoresis can identify the immunoglobulin class of the M-protein and can often detect light-chain protein if the serum immunoelectrophoresis is falsely negative; immunofixation electrophoresis is done even if the serum test is negative if multiple myeloma is strongly suspected. Light-chain analysis with delineation of κ and λ ratios helps confirm the diagnosis. Light-chain analysis can also be used to follow efficacy of therapy and provide prognostic data. Serum level of β2-microglobulin is measured if diagnosis is confirmed or very likely; it frequently is elevated, and albumin may be decreased. A new international staging system uses the levels of serum albumin and β2-microglobulin to indicate severity of disease and subsequent prognosis.

X-rays include a skeletal survey. Punched-out lytic lesions or diffuse osteoporosis is present in 80% of cases. Radionuclide bone scans usually are not helpful. MRI can provide more detail and is obtained if specific sites of pain or neurologic symptoms are present.

Bone marrow aspiration and biopsy are done and reveal sheets or clusters of plasma cells; myeloma is diagnosed when > 10% of the cells are of this type. However, marrow involvement is patchy; therefore, some samples from patients with myeloma may show < 10% plasma cells. Still, the number of marrow plasma cells is rarely normal. Plasma cell morphology does not correlate with the class of immunoglobulin synthesized. Chromosomal studies on bone marrow may reveal specific karyotypic abnormalities in plasma cells associated with differences in survival.

 

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