Pathology and Natural Behavior

Multiple myeloma (MM) is a B-cell malignancy characterized by the infiltration and proliferation of a clonal population of plasma cells in the bone marrow. MM is uncommon in animals, accounting for fewer than 8% of all canine hematopoietic tumors. No breed or sex predilections are seen, and older dogs are affected most commonly, with a mean age at onset of 8 to 9 years. MM is less common in cats than in dogs; the median age at presentation in cats is 12 to 14 years and there is a possible male predisposition. The cause of MM is largely unknown. Unlike in other hematopoietic diseases, there is no evidence that infection with feline immunodeficiency virus or feline leukemia virus is related to MM development in cats.

Myeloma cells produce large quantities of an identical immunoglobulin protein, called the paraprotein or monoclonal (M) protein, which often can be identified as a monoclonal spike on a serum or urine protein electrophoretogram. The paraprotein may represent a complete immunoglobulin or a portion of the immunoglobulin (light or heavy chain). Immunoglobulin G (IgG) and IgA gammopathies are the most common, whereas IgM gammopathy (macroglobulinemia) is rare. Although IgG and IgA gammopathies are equally common in dogs, in cats the proportions are reported to be 80% IgG gammopathies and 20% IgA gammopathies. Biclonal gammopathies occasionally are reported in veterinary patients. Production of pure light chains (κ or λ type), referred to as light-chain myeloma or Bence Jones myeloma, has been reported rarely in cats and dogs.

The pathologic conditions associated with MM are related to the effects of the circulating paraprotein as well as organ or bone marrow dysfunction caused by neoplastic infiltration. High serum paraprotein concentrations may result in hyperviscosity syndrome (HVS), manifesting in neurologic signs, retinopathy, and cardiomyopathy. Other pathologic conditions include osteolysis, hemorrhagic diathesis, cytopenias, hypercalcemia, renal disease, and increased susceptibility to bacterial infection.

Clinical Signs

Clinical signs associated with MM often are nonspecific and insidious in onset and include lethargy, weakness, and anorexia. Polyuria and polydipsia can occur secondary to hypercalcemia or MM-related renal disease. Lameness, paresis or paralysis, and pain occur secondary to osteolysis or spinal cord compression. Bleeding diatheses, including epistaxis, gingival bleeding, intraocular hemorrhage, and, less frequently, melena or hematuria, are common. Retinal abnormalities occur frequently secondary to HVS and include hemorrhage or tortuous, dilated vessels. Central nervous system deficits, including dementia and seizures, also may be present secondary to HVS, bleeding diathesis, or severe hypercalcemia. In dogs the median duration of clinical signs before presentation is 30 days.

Diagnosis

Diagnostic criteria for MM are adapted from those in human medicine. Establishing a diagnosis requires confirming the presence of at least two of the disease manifestations listed in Box 86-1. Recent studies suggest that these criteria should be reevaluated in cats because visceral organ infiltration (primarily of the liver or spleen) is common in cats at initial presentation (Mellor et al, 2006; Patel et al, 2005).

Initial diagnostic tests should include a complete blood count (CBC), serum chemistry panel, and urinalysis. Nonregenerative anemia is the most common CBC finding, reported in 55% to 68% of cases. Serum chemistry testing commonly reveals azotemia and hypercalcemia as well as hyperglobulinemia with secondary hypoalbuminemia and hypocholesterolemia. Urine culture is recommended since patients often have dilute urine and are immunologically compromised, and thus are prone to infection.

Serum and urine samples can be submitted for parallel protein electrophoresis. Serum protein electrophoresis generally reveals a monoclonal gammopathy with a peak in the β- or γ-globulin region or, less commonly, a biclonal gammopathy. Immunofixation electrophoresis or capillary zone electrophoresis may be used to detect M proteins in patients with normal protein and globulin concentrations and equivocal serum protein electrophoresis findings (Seelig et al, 2010). Urine electrophoresis can detect light-chain proteinuria that will not be detected with a urine dipstick. Bence Jones protein in the urine without a corresponding monoclonal gammopathy on serum electrophoresis is diagnostic for pure light-chain disease.

Abdominal imaging is useful to evaluate commonly affected organs such as the liver and spleen. In cats with MM, 85% of abdominal organs showing an abnormality on imaging had cytologically confirmed plasma cell infiltration (Mellor et al, 2006). Limb and spinal radiographs can help detect bone lesions. Importantly, bone lysis is rare in patients with macroglobulinemia, whereas hepatosplenomegaly and lymphadenopathy are common.

MM usually is diagnosed definitively by cytologic examination of a bone marrow aspirate; plasma cells are distributed unevenly among normal marrow elements. Optimal samples may be obtained by performing bone aspiration at the site of lytic lesions; however, multiple bone marrow aspirates or a core biopsy may be necessary for definitive diagnosis, especially when no lytic lesions are seen.

Treatment

When patients with MM are treated, not only the underlying cancer but also the secondary conditions associated with the disease must be treated.