Myeloma is a disease of older adults (median age 65 years). The most common presenting complaints are those related to anemia, bone pain, kidney disease, and infection. Bone pain is most common in the back, hips, or ribs or may present as a pathologic fracture, especially of the femoral neck or vertebrae. Patients may also come to medical attention because of spinal cord compression from a plasmacytoma or the hyperviscosity syndrome (mucosal bleeding, vertigo, nausea, visual disturbances, alterations in mental status, hypoxia). Many patients are diagnosed because of laboratory findings of elevated total protein, hypercalcemia, proteinuria, elevated sedimentation rate, or abnormalities on serum protein electrophoresis obtained for symptoms or in routine screening studies. A few patients come to medical attention because of organ dysfunction due to amyloidosis.
Examination may reveal pallor, bone tenderness, or soft tissue masses. Patients may have neurologic signs related to neuropathy or spinal cord compression. Fever occurs mainly with infection. Acute oliguric or nonoliguric kidney injury may be present due to hypercalcemia, hyperuricemia, light chain cast injury, or primary amyloidosis.
Anemia is nearly universal. Red blood cell morphology is normal, but rouleaux formation is common and may be marked (eFigure 13–35). The absence of rouleaux formation, however, excludes neither plasma cell myeloma nor the presence of a serum paraprotein. The neutrophil and platelet counts are usually normal at presentation. Only rarely will plasma cells be visible on peripheral blood smear (plasma cell leukemia).
Plasma cell myeloma. (Peripheral blood smear, 50 ×.) Rouleaux formation, commonly seen in patients with monoclonal gammopathies, including plasma cell myeloma. Negatively charged gamma globulins disrupt the normal electrostatic field around red blood cells, allowing them to move into closer than normal proximity to each other. (Used, with permission, from L Damon.)
The hallmark of myeloma is the finding of a paraprotein on serum or urine protein electrophoresis (PEP) or immunofixation electrophoresis (IFE). The majority of patients will have a monoclonal spike visible in the gamma- or beta-globulin region of the PEP. The semi-quantification of the paraprotein on the PEP is referred to as the M-protein, and IFE will reveal this to be a monoclonal immunoglobulin. Approximately 15% of patients will have no demonstrable paraprotein in the serum on PEP because their myeloma cells produce only light chains and not intact immunoglobulin (but often seen on serum IFE), and the light chains pass rapidly through the glomerulus into the urine. Urine PEP and IFE usually demonstrate the light chain paraprotein in this setting. The free light chain assay will sometimes demonstrate excess monoclonal light chains in serum and urine, and in a small proportion of patients, will be the only means to identify and quantify the paraprotein being produced. Overall, the paraprotein is IgG (60%), IgA (20%), or light chain only (15%) in plasma cell myeloma, with the remainder being rare cases of IgD, IgM, or biclonal gammopathy. In sporadic cases, no paraprotein is present (“nonsecretory myeloma”); these patients have particularly aggressive disease.
The bone marrow will be infiltrated by variable numbers of monoclonal plasma cells. The plasma cells may be morphologically abnormal often demonstrating multi-nucleation and vacuolization. The plasma cells will display marked skewing of the normal kappa-to-lambda light chain ratio, which will indicate their clonality. Many benign inflammatory processes can result in bone marrow plasmacytosis, but with the absence of clonality and morphologic atypia.
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, since there is little osteoblastic component. In the evaluation of patients with known or suspected plasma cell myeloma, MRI and PET/CT scans are more sensitive to detect bone disease than plain radiographs and are preferred.