Page 763 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 33 Hematopoietic Tumors 741

(Waldenström’s) is often applied. Several cases of biclonal gam-
mopathy in dogs and cats have been reported, 761,767,770,771,789–795
and several cases of nonsecretory MM have been reported in
VetBooks.ir dogs. 762,796–798 Rarely, cryoglobulinemia occurs in dogs with MM
and IgM macroglobulinemia, and this has also been reported in a
cat with IgG myeloma. 764,799–801 Cryoglobulins are paraproteins
that are insoluble at temperatures below 37°C and require blood
collection and clotting to be performed at 37°C before serum sep-
aration. If whole blood is allowed to clot at temperatures below
this, the protein precipitates in the clot and is lost. Pure light-
chain M component is rare, but has been reported in both dogs
and cats. 762,802,803
The pathology associated with MM is a result of either high
levels of circulating M component, organ or bone infiltration with
neoplastic cells, or both. Associated pathologic conditions include
bone disease, bleeding diathesis, hyperviscosity syndrome (HVS),
renal disease, hypercalcemia, immunodeficiency (and subsequent
• Fig. 33.23 Bone marrow aspirate from a dog with multiple myeloma susceptibility to infections), cytopenias secondary to myelophthi-
showing an overabundance of large neoplastic plasma cells with charac- sis, and cardiac failure.
teristic paranuclear clear zone representing the Golgi apparatus (arrow). Bone lesions can be isolated, discrete osteolytic lesions (includ-
(Dif-quick stain, ×100 objective.)
ing pathologic fractures) (Fig. 33.25A), diffuse osteopenias, or both
(Fig. 33.26). Approximately one-quarter to two-thirds of dogs with
MM have radiographic evidence of bony lysis or diffuse osteopo-
rosis. 757,761,763,764 The incidence of radiographic skeletal lesions in
cats varies tremendously within reports from as few as 8% in some
case series to as high as 65% in others. 765,767,770,771,788 Those bones
engaged in active hematopoiesis are more commonly affected and
include the vertebrae, ribs, pelvis, skull, and the metaphyses of long
bones. Skeletal lesions are rare with IgM (Waldenström’s) macro-
globulinemia, in which malignant cells often infiltrate the spleen,
liver, and lymphoid tissue rather than bone. 764,804,805
Bleeding diathesis can result from one or a combination of
events. M components may interfere with coagulation by (1)
inhibiting platelet aggregation and the release of platelet factor-3;
(2) causing adsorption of minor clotting proteins; (3) generat-
Animal protein electrophoresis ing abnormal fibrin polymerization; and (4) producing a func-
tional decrease in calcium. 764,806,807 Approximately 10% to 30%
T.P.: 10.4 g/dL A/G 0.32 of dogs and up to one-quarter of cats have clinical evidence of
Fractions % Conc. Ref. Conc. hemorrhage. 757,761,767,770,771 In dogs, nearly half have abnormal
prothrombin (PT) and partial thromboplastin (PTT) times.
Albumin 24.4 2.54 L 2.60–4.00 Thrombocytopenia may also play a role if bone marrow infiltra-
Alpha 1 1.6 0.17 0.11–0.35 tion is significant (i.e., myelophthisis).
Alpha 2 3.0 0.31 L 0.92–1.66
Beta 1 8.7 0.90 H 0.22–0.61 HVS represents one of a constellation of clinicopathologic
Beta 2 7.8 0.81 H 0.08–0.50 abnormalities resulting from greatly increased serum viscosity.
Gamma 54.5 5.67 H 0.66–2.48 The magnitude of viscosity changes is related to the type, size,
• Fig. 33.24 Serum protein electrophoresis from a cat with multiple myeloma. shape, and concentration of the M component in the blood.
Stained cellulose acetate electrophoretic strip (upper right corner) with HVS is more common with IgM macroglobulinemia because of
accompanying densitogram. Note large M-component spike (representing the high molecular weight of this class of immunoglobulin. IgA-
an IgG monoclonal gammopathy) present in the gamma region. (Courtesy secreting myelomas (IgA is usually present as a dimer in the dog)
Dr. Frances Moore, Marshfield Laboratories, Marshfield, WI.) may undergo polymerization resulting in increased serum viscos-
ity. 757,764,808 IgG-associated HVS can also occur, albeit less fre-
(Fig. 33.24). The M component can be represented by any class quently. High serum viscosity occurs in approximately 20% to
of the entire immunoglobulin or only a portion of the molecule, 40% of dogs with MM and can result in bleeding diathesis, neu-
such as the light chain (Bence Jones protein) or heavy chain (heavy rologic signs (e.g., dementia, depression, seizure activity, coma),
chain disease) of the molecule. In the dog, the M component is ophthalmic abnormalities (e.g., dilated and tortuous retinal ves-
usually represented by either IgA or IgG immunoglobulin types sels, retinal hemorrhage [Fig. 33.27], retinal detachment), and
in nearly equal incidence, whereas the ratio of IgG to IgA in cats increased cardiac workload with the potential for subsequent
is approximately 5:1 in some reports and approximately 1:1 in development of cardiomyopathy. 757,761,764,804,805,808–811 In a ret-
others. 757,763–767,786,788 However, in two recent compilations of rospective compilation of 83 dogs with retinal hemorrhage, 5%
dogs with MM, including 27 dogs in which the immunoglobulin were due to MM. 812 These consequences of HVS are thought to
was typed, the vast majority (78%) were of the IgA type. 761,762 If be a result of sludging of blood in small vessels, ineffective deliv-
the M component is the IgM type, the term macroglobulinemia ery of oxygen and nutrients, and coagulation abnormalities. HVS