Clinical History:
- A 66-year-old man had been complaining of back pain for the past 5 months, for which he had taken non-steroidal anti-inflammatory medications, but the dull pain persisted. On physical examination he has no abnormal findings. Radiographs of the spine and pelvis show lytic bone lesions at T11, T12, L2, and in the right posterior iliac crest. A radiograph of the skull shows multiple lytic lesions. His CBC shows Hgb 10.8 g/dL, Hct 32.2%, MCV 89 fL, platelet count 135,000/microliter, and WBC count 4890/microliter. A serum chemistry panel shows sodium 140 mmol/L, potassium 4.0 mmol/L, chloride 98 mmol/L, CO2 24 mmol/L, urea nitrogen 32 mg/dL, creatinine 2.9 mg/dL, glucose 79 mg/dL, calcium 11.6 mg/dL, phosphorus 2.2 mg/dL, AST 30 U/L, ALT 23 U/L, alkaline phosphatase 249 U/L, total bilirubin 0.9 mg/dL, albumin 3.5 g/dL, and total protein 9.6 g/dL. A urinalysis shows sp gr. 1.020, pH 6.5, and no glucose, protein, or blood. A posterior iliac crest bone marrow biopsy is performed.
- What is the predominant cell type present in the bone marrow?
The bone marrow is nearly replaced by plasma cells and is virtually 100% cellular, rather than the 40% cellularity expected at this site for the patient's age. The myeloid, erythroid, and megakaryocytic cell lines are difficult to find, explaining his pancytopenia. The lytic bone lesions explain his hypercalcemia.
- What other laboratory studies should be done in order to arrive at a
definitive diagnosis?
The high total serum protein with low normal albumin suggests increased globulins, which could be monocolonal. To confirm the diagnosis, you should order serum (shown below) and urine protein electrophoresis. These will show a monoclonal spike of abnormal gamma globulin secreted by the neoplastic plasma cells (in only rare cases will the plasma cells not secrete an identifiable globulin). The light chains are often excreted in the urine as Bence-Jones proteins, but the standard urine dipstick measures albumin and is insensitive to globulin, so a specific test for Bence-Jones proteins must be done on urine.
- What is your diagnosis in this case?
The diagnosis is multiple myeloma, which accounts for over
95% of cases in which a monoclonal gammopathy is present. The plasma cells can produce lytic bone lesions, such as those seen in the skull.
- What biotherapies are available?
The proteasome inhibitor bortezomib has been employed in treatment of multiple myeloma. Proteasomes are intracytoplasmic structures containing proteinase complexes that are involved in degradation of intracellular proteins, cell cycle regulation, and apoptosis. Inhibitors of proteasomes induce apoptosis. Malignant cells are more susceptible to proteasome inhibition than normal cells. In addition, proteasome inhibitors make malignant cells more susceptible to the apoptosis enhancing effects of chemotherapy and radiation therapy.
The drug thalidomide has anti-angiogenesis activity and can be used in combination with dexamethasone and/or chemotherapy agents in treating multiple myeloma.
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