CLINICAL SIGNS
Clinical signs associated with multiple myeloma, which are often nonspecific and insidious in onset, include lethargy, weakness,
and anorexia. Polyuria and polydipsia can occur secondary to hypercalcemia or myeloma-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.1,4,5 Retinal abnormalities occur frequently secondary to serum hyperviscosity and include retinal hemorrhage or venous dilatation
with tortuous vessels.1,27 Central nervous system deficits, including dementia with midbrain or brainstem deficits, and seizures may also be present
secondary to hyperviscosity syndrome or severe hypercalcemia.1,5,7 The median duration of clinical signs before presentation is 30 days in dogs.1
DIAGNOSIS
Table 1. Diagnostic Criteria for Multiple Myeloma*
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Diagnosing multiple myeloma is adapted from human medicine and requires confirming at least two of the criteria listed in
Table 1. Recent studies suggest that these criteria should be re-evaluated in cats. In a study of 16 cats with multiple myeloma,
noncutaneous extramedullary tumors (internal organ involvement) (see the next article in this issue: "Extramedullary and solitary osseous plasmacytomas in dogs and cats") were detected in all seven cats in which this was assessed. Affected sites included the spleen, liver, and lymph nodes.4 In this report, it was suggested that visceral organ infiltration be included in the diagnostic criteria for cats. Also
in a recent review of 24 cats with myeloma-related disorders, plasma cell neoplasia of an abdominal organ (primarily the liver
or spleen) accounted for 50% of cats at initial presentation. More than 40% of cats with internal organ involvement had bone
marrow infiltration by neoplastic cells.7 In people, extramedullary involvement is rare (about 5% of cases) at initial presentation for myeloma-related disorders.
Further studies suggest a primary extramedullary origin for neoplastic transformation in cats with multiple myeloma vs. primary
intramedullary neoplastic transformation as accepted in the human myeloma model.6
Staging
Table 2. Approximate Frequency of Clinicopathologic and Imaging Abnormalities in Patients with Multiple Myeloma*
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Recommended primary staging tests include a CBC, serum chemistry profile, and urinalysis, although advanced diagnostic modalities
may be required (Table 2). Nonregenerative anemia is the most common finding on a CBC, reported in 55% to 68% of cases.1,4,5 Key findings on a serum chemistry profile include azotemia and hypercalcemia; other common abnormalities include hypoalbuminemia
with hyperglobulinemia and hypocholesterolemia. Urine bacterial culture is also recommended since these animals may be immunologically
compromised and prone to urinary tract 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 beta or gamma globulin region or, less commonly, a biclonal gammopathy.4,7,15 Test urine samples for light chain proteinuria by using either the Bence Jones heat precipitation method or immunoelectrophoresis.
Evaulation by using a urine dipstick is not an adequate screening test for light chain proteinuria because dipsticks primarily
detect albuminurina.4 Bence Jones proteins in the urine without a corresponding monoclonal gammopathy on serum electrophoresis is diagnostic for
pure light chain disease.3
To evaluate for hyperviscosity syndrome, serum viscosity, relative to water, can be assessed with laboratory viscometers (e.g. Wells-Brookfield Cone/Plate Viscometer/Rheometer—Can-Am Instruments).4
Abdominal imaging (radiography or ultrasonography) is useful to evaluate commonly affected organs such as the liver and spleen.
In cats with multiple myeloma, 85% of abdominal organs with an imaging abnormality had cytologically confirmed plasma cell
infiltration within that tissue.7 Limb and spinal radiographs can help detect bone lesions.
Multiple myeloma is usually definitively diagnosed with cytologic examination of a bone marrow aspirate; plasma cells are
unevenly distributed among normal marrow elements.4 Optimal samples may be obtained by performing a bone marrow aspirate from the site of lytic lesions; however, multiple aspirates
or a core biopsy may be necessary for definitive diagnosis.
Differential diagnoses
Other conditions can induce monoclonal gammopathies in companion animals, including monoclonal gammopathy of undetermined
significance (MGUS), chronic infection (e.g. feline infectious peritonitis, ehrlichiosis, leishmaniasis, pyoderma), and other lymphoreticular neoplasms (e.g. B cell lymphoma, acute and chronic lymphocytic leukemia).28-30
MGUS has been reported in a cat in which paraproteinemia was detected several years before multiple myeloma was diagnosed.
MGUS was diagnosed based on a lack of evidence for multiple myeloma, including the absence of abnormal physical findings or
clinical signs and the lack of marrow plasmacytosis, radiographic changes, or light chain proteinuria.4 MGUS is considered a pre-myeloma condition in people; about 25% of people with MGUS ultimately develop multiple myeloma
or related diseases.31
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