Multiple Myeloma: The Debilitating Disease that ‘Punches Out’ the Elderly

Dr. Christine I. Chen, MD, FRCPC
Princess Margaret Hospital,
University Health Network,
Toronto, ON

Introduction
Multiple myeloma arises from a malignancy of plasma cells in the bone marrow which typically produce an immunoglobulin, also referred to as a monoclonal protein (M-protein), that is detectable in the patient's blood and/or urine. Myeloma is not a common disease (incidence of 1400/year in Canada), typically affecting older individuals (median age 65 years). It is more common in blacks and slightly more prevalent in males. Since myeloma is a relatively slow-growing malignancy, many patients will have the disease for months or even years before a diagnosis is made and may continue to follow an indolent course. The pathogenesis of the disease is poorly understood.

Clinical Features
Characteristic clinical features of multiple myeloma are anemia, renal failure, bony lesions with pathologic fractures and associated pain, hypercalcemia, and recurrent infections (See Table 1). Many patients, however, will present with asymptomatic anemia or a monoclonal gammopathy, which is usually discovered during incidental lab testing.

TABLE 1 Clinical features of multiple myeloma
Skeletal	- "Punched out" lytic bone lesions (skull, long bones common) - Generalized osteoporosis - Pathologic fractures and bone pain
Renal	- Renal dysfunction due to light chain toxicity and/or deposition, hypercalcemia, amyloid deposition
Hematologic	- Cytopenias (anemia common) due to plasma cell infiltration of bone marrow, renal failure, anemia of chronic disease - Bleeding tendency--mostly due to interference of coagulation by M-protein or thrombocytopenia from marrow infiltration - Hyperviscosity syndrome--visual changes, headache, confusion, bleeding, coma, "sausage veins" on fundoscopy
Neurologic	- Cord compression from vertebral collapse and/or plasmacytoma - Mental changes (may be due to hyperviscosity, hypercalcemia) - Peripheral neuropathy due to M-protein, amyloidosis
Metabolic	- Hypercalcemia--confusion, polyuria, polydipsia,constipation, weakness, fatigue
Immunologic	- Predisposition to recurrent infections due to suppression and dysfunction of normal immunoglobulins or neutropenia from chemotherapy

Laboratory Features
The vast majority of patients with myeloma will have a serum M-protein that can be detected by serum protein electrophoresis, and/or M-protein in the urine with excreted light chains (Bence Jones protein) detectable by electrophoresis of a 24-hour urine collection. The most common immunoglobulin subtype is IgG (60%), followed by IgA (20%), light chains alone (10%), and less commonly IgD, IgE and IgM (less than 10%). In approximately 1% of patients, no M-protein can be detected in either serum or urine. Immunoelectrophoresis and immunofixation can be used to identify the heavy and light chain components of the M-protein. A bone marrow aspirate and biopsy will show an increase of plasma cells, which are often characterized by immature morphologic features. Other characteristic findings include a normocytic, normochromic anemia, rouleaux ("stacked coin" appearance) of red blood cells on peripheral film analysis, and an elevated sedimentation rate. The presence of one of these nonspecific findings that is not otherwise explained clinically should trigger an investigation for multiple myeloma.

Radiologic Findings
A skeletal survey, including plain x-rays of the skull, ribs, spine, pelvis, shoulders and long bones of the limbs, is used to identify osteopenia or the typical "punched-out" lesions of myeloma. As myeloma lesions are osteolytic in nature, a bone scan, which best detects osteoblastic lesions, is not generally useful.