Pathologic effects

The pathologic conditions associated with multiple myeloma are related to the effects of the circulating paraprotein as well as organ or bone marrow dysfunction due to neoplastic infiltration. High serum paraprotein concentrations may result in hyperviscosity syndrome. Other conditions include osteolysis, hemorrhagic diathesis, cytopenias, hypercalcemia, renal disease, and increased susceptibility to bacterial infection.

Hyperviscosity syndrome. Hyperviscosity syndrome is an increase in the viscosity of the blood secondary to the high concentrations of circulating paraprotein, clinically manifesting in neurologic signs, retinopathy, and cardiomyopathy.⁷ IgA and IgM are most often associated with hyperviscosity syndrome because of their structure and size (IgA dimers and IgM pentamers). Cardiomegaly and cardiac disease may result secondary to increased cardiac workload and myocardial hypoxia caused by hyperviscosity. In a study of cats with multiple myeloma, two-thirds of the cats had cardiomegaly on thoracic radiographs, and nearly half had a heart murmur.⁴

Figure 2. A lateral thoracic spinal radiograph of a dog with multiple myeloma. This patient has multiple osteolytic lesions in the dorsal spinous processes, as demonstrated by the white arrow. (Radiograph courtesy of Dr. Laura Garrett.)

Figure 3. A lateral stifle radiograph of a dog with multiple myeloma. A lytic punched-out bone lesion (white arrow) is present in the proximal tibia. (Radiograph courtesy of Dr. Laura Garrett.)

Bone lesion detection improves with focused imaging on specific regions or bones vs. routine survey abdominal and thoracic radiographs.⁵ In people, conventional radiography remains the gold standard imaging technique. Computed tomography and magnetic resonance imaging may also be useful; however, nuclear scintigraphy is generally not recommended since myeloma patients have inadequate skeletal uptake of technetium-99 secondary to osteoblast dysfunction.^17,20

Hemorrhagic diathesis. Patients with multiple myeloma can manifest unique hemostatic disorders that predispose them to hemorrhage. Mechanisms include paraprotein-induced thrombocytopathy, in which protein coating of platelets leads to platelet dysfunction, and paraprotein interference with clotting factors.^1,4,21 Other potential causes of bleeding include abnormalities in the formation and polymerization of fibrin, tissue fragility associated with amyloidosis, hypervolemia secondary to hyperviscosity syndrome, and thrombocytopenia.²¹ About one-third of dogs and cats with multiple myeloma have clinical signs of bleeding, most commonly epistaxis, intraocular hemorrhage, and gingival bleeding. These patients may have prolonged prothrombin and partial thromboplastin times, and about 50% of cats and 30% of dogs are thrombocytopenic.^1,4,5

Cytopenias. Patients with multiple myeloma can develop anemia from a variety of causes including chronic disease, hemorrhage due to coagulopathy, myelophthisis, and red blood cell destruction. Normocytic, normochromic, nonregenerative anemia is one of the most common findings on a complete blood count (CBC); two-thirds of dogs and cats are affected.^1,4,5,7 Erythrophagocytic multiple myeloma has been reported in a cat, dogs, and people, so it may be a source of anemia as well.^22-24 Pancytopenia may be seen in patients with marked bone marrow infiltration with neoplastic cells.

Hypercalcemia. Hypercalcemia in cases of multiple myeloma can result from osteoclastic bone resorption, hypercalcemia of malignancy, or hyperglobulinemia. Bone stores of calcium can be released by osteoclasts secondary to cytokine secretion by myeloma cells (e.g. lymphotoxin, tumor necrosis factor alpha, interleukins 1, 3, and 6).¹⁸ Myeloma cells can also secrete parathyroid hormone-related peptide, resulting in paraneoplastic hypercalcemia of malignancy.² Hyperglobulinemia results in calcium binding by the paraprotein, increasing the total calcium concentration while the ionized calcium concentration remains normal. Ionized calcium measurement is, therefore, needed to confirm true hypercalcemia in patients with multiple myeloma.²²

Renal disease. Renal disease occurs in about one-third of dogs and cats with multiple myeloma. Renal insufficiency is most commonly associated with excessive light chain production or hypercalcemia. First, excessive light chain production overwhelms the catabolic capacity of the renal tubular cells, and the free light chains complex with proteins to form tubular casts, leading to renal tubular obstruction. Endocytosis of light chains by tubular cells also induces cytokine release and inflammation, resulting in further renal damage.²⁵ Second, hypercalcemia can lead to prerenal azotemia secondary to antidiuretic hormone inhibition and eventual renal mineralization.²⁶ Other potential causes of renal disease include amyloidosis, pyelonephritis, and decreased renal perfusion secondary to hyperviscosity syndrome.

Bacterial infection. Increased susceptibility to bacterial infection is common in patients with multiple myeloma, and infections can be life-threatening if not addressed. Immunodeficiency can be secondary to myelophthisis (which results in leukopenia), decreased production of functional immunoglobulin, and compromised B cell function.⁴