hematology and oncology
Multiple Myeloma
Pathophysiology of Multiple Myeloma
The M-protein (monoclonal immunoglobulin 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 kappa (κ) or lambda (λ) light chains in the urine. In 15 to 20% of patients, plasma cells secrete only Bence Jones protein. IgM and IgD myeloma account for about 1% of cases each; IgD myeloma is more frequent among patients of Asian descent. IgE myeloma is exceedingly rare. Rarely, patients have no M-protein in blood and urine, although the currently used serum free light chain assay now demonstrates monoclonal light chains in many of these formerly so-called nonsecretory patients. Diffuse Osteoporosis or discrete osteolytic lesions are often present, with the most common sites being the pelvis, spine, ribs, femur, humerus, 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, leading to bone loss. The osteolytic lesions are usually multiple; occasionally, they are solitary intramedullary masses. Increased bone loss may also lead to In many patients, renal failure is present at diagnosis or develops during the course of the disorder. Renal failure has many causes, and most commonly, it results from deposition of light chains in the distal tubules ( Myeloma-Related Kidney Disease ) or hypercalcemia. Patients often develop anemia usually due to kidney disease or suppression of erythropoiesis by cancer cells but also may be due to other unrelated causes, including Iron Deficiency or Because of lack of normal antibodies and other immune dysfunction, some patients have increased susceptibility to bacterial infection. Viral infections, especially Herpes Zoster , occur as a result of treatment modalities such as proteasome inhibitors (eg, Amyloidosis occurs in 10% of myeloma patients, most often in patients with lambda-type M-proteins. Variant expressions of multiple myeloma occur (see table). 