A 71-year-old man is evaluated in the ER for a recent finding of high ESR in a routine blood test. He has history of hypertension, well controlled with metoprolol. His physical examination is completely normal. His laboratory workup reveals hemoglobin 12.6 gm/dL, leukocyte count 8500/mL, and platelet 265,000/mL. Total protein 6.2 g/dL, albumin 3.4 g/dL, BUN 16 mg/dL, creatinine 0.75 mg/dL, and calcium 9.2 mg/dL. Serum protein electrophoresis reveals a sharp, narrow spike, serum immunofixation reveals M-protein 1.2 gm/dL, bone marrow examination reveals less than 10% of monoclonal plasma cells. A skeletal survey is negative for any lytic lesions.
Multiple myeloma would best explain this patient's presentation. The onset of myeloma is often insidious. Pain caused by bone involvement, anemia, renal insufficiency, and bacterial pneumonia often follow. This patient presented with fatigue and bone pain, then developed bacterial pneumonia probably secondary to Streptococcus pneumoniae, an encapsulated organism for which antibody to the polysaccharide capsule is not adequately produced by the myeloma patient. There is also evidence for renal insufficiency. Hypercalcemia is frequently seen in patients with multiple myeloma and may be life-threatening. Definitive diagnosis of multiple myeloma is made by demonstrating greater than 30% plasma cells in the bone marrow. Seventy-five percent of patients with myeloma will have a monoclonal M spike on serum protein electrophoresis, but 25% will produce primarily Bence-Jones proteins, which, because of their small size, do not accumulate in the serum but are excreted in the urine. Urine protein electrophoresis will identify these patients. Approximately 1% of patients with myeloma will present with a non-secretory myeloma. Patients with non-secretory myeloma have no M-protein on serum/urine electrophoresis and immunofixation; the diagnosis can be made only with bone marrow biopsy. The bone scan in myeloma is usually negative. The radionuclide is taken up by osteoblasts, and myeloma is usually a purely osteolytic process. Renal biopsy might show monoclonal protein deposition in the kidney or intratubular casts but would not be the first diagnostic procedure. Rouleaux formation in peripheral smear is a characteristic finding of myeloma, although it is neither sensitive nor specific.Waldenstrom macroglobulinemia may cause hyper-viscosity syndrome with CNS manifestations including headache, blurring of vision, dizziness, nystagmus, ataxic gait, drowsiness, or even coma. Peripheral neuropathy, coagulopathy, lymphadenopathy, hepatosplenomegaly, and nonspecific constitutional symptoms are often present. An unusual gap between serum total protein and albumin indicates hyperglobulinemia, and a monoclonal IgM spike on serum protein electrophoresis helps establish an initial diagnosis. Bone marrow biopsy revealing more than 10% of lymphoid and plasmacytoid cells confirms the diagnosis. Unlike multiple myeloma, bony lesions are uncommon in Waldenstrom macroglobulinemia, whereas lymphadenopathy and organomegaly are uncommon in myeloma.Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder which is often suspected and detected incidentally from routine blood workup. The patients are asymptomatic with no end-organ damage such as renal failure, hypercalcemia, anemia, or lytic bone lesion. The serum electrophoresis reveals an M spike but the amount of M-protein on immunofixation is usually less than 3 gm/dL and bone marrow contains less than 10% of monoclonal plasma cells. Monitoring of patients is important since MGUS can progress to multiple myeloma over a period of time. It is recommended to get the first evaluation 6 months after initial diagnosis followed by annual or biannual checkup.
Multiple myeloma
Smoldering multiple myeloma
Monoclonal gammopathy of undetermined significance
Waldenstrom macroglobulinemia
Oncology