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ESSENTIALS OF DIAGNOSIS
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Bone pain, often in the lower back Monoclonal paraprotein by serum and urine protein electrophoresis or immunoelectrophoresis Replacement of bone marrow by malignant plasma cells
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Treatment
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The treatment of Hodgkin s disease has evolved, with radiation therapy used as initial treatment only for patients with low-risk stage IA and IIA disease The addition of limited chemotherapy for some patients treated with radiation appears promising Most patients with Hodgkin s disease (including all with stage IIIB and IV disease) are best treated with combination chemotherapy using doxorubicin (Adriamycin), bleomycin, vincristine, and dacarbazine (ABVD) New shorter and more intensive regimens are being studied, but have not yet proved superior to ABVD
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Multiple myeloma is a malignancy of plasma cells characterized by replacement of the bone marrow, bone destruction, and paraprotein formation Myeloma causes clinical symptoms and signs through a variety of mechanisms Replacement of the bone marrow (and perhaps humoral suppression of myelopoiesis) leads initially to anemia and later to general bone marrow failure Malignant plasma cells can form tumors (plasmacytomas) that may cause spinal cord compression Bone involvement causes bone pain, osteoporosis, lytic lesions, pathologic fractures, and hypercalcemia The pathogenesis of osteoclast activation in myeloma appears to involve osteoprotegerin ligand, and the decoy receptor osteoprotegerin may be able to interfere with this pathway The paraproteins secreted by the malignant plasma cells may cause problems in their own right Very high paraprotein levels (either IgG or IgA) may cause hyperviscosity, though this is more often caused by IgM in Waldenstr m s
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Prognosis
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All patients with both localized and disseminated disease should be treated with curative intent The prognosis of patients with stage IA or IIA disease treated by radiotherapy is excellent, with 10-year survival rates in excess of 80% Patients with disseminated disease (IIIB, IV) have 5year survival rates of 50 60% Poorer results are seen in
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morphologically abnormal Many benign processes can result in plasmacytosis, but the presence of highly atypical plasma cells or effacement of normal bone marrow elements helps to distinguish myeloma Bone radiographs are important in establishing the diagnosis of myeloma Lytic lesions are most commonly seen in the axial skeleton: skull, spine, proximal long bones, and ribs At other times, only generalized osteoporosis is seen The radionuclide bone scan is not useful in detecting bone lesions in myeloma, as there is usually no osteoblastic component Positron emission tomography (PET) scans are being evaluated in the staging of myeloma, and may become routine Similarly, MRI scans may be helpful in demonstrating the extent of bone and bone marrow disease but are not currently standard practice The level of 2-microglobulin has strong prognostic significance in myeloma, with levels > 35 mg/L associated with poor survival Bone marrow cytogenetic characteristics have greater prognostic significance, with deletions of chromosome 13q and the translocation t(4,14) associated with a poor outcome Other laboratory features include hypercalcemia, renal failure, and an elevated erythrocyte sedimentation rate Some patients have proximal renal tubular acidosis, with phosphaturia, glycosuria, uricosuria, and aminoaciduria The urinalysis may reveal proteinuria, but the dipstick test (which detects primarily albumin) is unreliable for light chains Often there is a narrow anion gap when the paraprotein is cationic (70% of cases) The standard staging system for multiple myeloma, the Salmon-Durie system, has been based on the level of paraprotein, blood counts, bone radiographs, and serum calcium A new International Staging System based on serum albumin and 2 microglobulin has recently come into use
macroglobulinemia The light chain component of the immunoglobulin often leads to renal failure (often aggravated by hypercalcemia) Light chain components may be deposited in tissues as amyloid, worsening renal failure with albuminuria and causing a vast array of systemic symptoms Myeloma patients are prone to recurrent infections for a number of reasons, including neutropenia and the immunosuppressive effects of chemotherapy More often, there is a failure of antibody production in response to antigen challenge, and myeloma patients are especially prone to infections with encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae
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