Page 123 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

102 PART I The Biology and Pathogenesis of Cancer

cardiomyopathy, clubbing of the paws and distal extremities, Hyperviscosity Syndrome
and degenerative arthropathy. 71–73 Many effects of GH are Hyperviscosity syndrome refers to a constellation of clinical signs
mediated by IGF-1, and because GH assays are not readily
VetBooks.ir available, measurement of serum IGF-1 remains the most prac- caused by an increase in blood viscosity. It can occur in patients
73
with MRD (see Hyperglobulinemia, earlier), polycythemia vera (see
tical way to confirm feline hypersomatotropism. The reader is
directed to Chapter 26 for a more detailed discussion regarding Chapter 33, Section C), or paraneoplastic erythrocytosis (see Erythro-
feline acromegaly. cytosis, later). 79,88–91 In patients with MRD, hyperviscosity syndrome
occurs most frequently in patients with IgM macroglobulinemia
Ectopic Adrenocorticotropic Hormone because IgM typically forms a high molecular weight pentamer. 79,91
When it occurs in patients with multiple myeloma, the M-compo-
Syndrome nent is more commonly IgA than IgG, as the former exists as a dimer
The ectopic production of adrenocorticotropic hormone and occasionally will polymerize, and the latter is a monomer. 79
(ACTH) or ACTH-like substances is a common PNS in The clinical signs of hyperviscosity syndrome result from sludg-
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humans. About 3% to 5% of people with small cell lung can- ing of blood in small vessels, ineffective delivery of oxygen and
cer develop hyperadrenocorticism. This PNS also is reported in nutrients, and coagulation abnormalities. Reported neurologic
people with other carcinomas, including pancreatic carcinoma, signs include stuporous mentation, ataxia, and seizures. 79,88,89
thymic carcinoma, and carcinoids. This PNS results from expres- Ocular abnormalities include enlarged and tortuous retinal vessels,
sion of the proopiomelanocortin gene, which contains not only retinal hemorrhages, and retinal detachment, often resulting in
ACTH, but also melanocyte-stimulating hormone, lipotropin, acute-onset blindness. 79,88,92 Bleeding diathesis, hypertrophic car-
1
endorphins, and enkephalins. As a result, patients present with diomyopathy, and congestive heart failure can also occur. 79,83,88,93
clinical signs typical of hyperadrenocorticism (Cushing’s dis- In severe cases of hyperviscosity syndrome, emergency treat-
ease), but occasionally will also have other clinical signs such as ment is warranted. Plasmapheresis is indicated when hyper-
hyperpigmentation. The diagnosis is made based on documen- viscosity is caused by serum proteins. 93,94 Phlebotomy and
tation of increased urine cortisol, a dexamethasone suppression intravenous fluids are indicated when hyperviscosity is caused by
90
test where serum cortisol is consistently suppressed, and elevated erythrocytosis.
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plasma levels of ACTH or ACTH precursors. This PNS is very
rare in veterinary oncology, with single case reports in dogs with Anemia
a primary lung tumor, a metastatic neuroendocrine tumor aris-
ing in the pancreas, and a hepatic carcinoid. 76–78 When clinical The true prevalence of anemia in veterinary cancer patients is
signs cannot be controlled with surgery, trilostane is an effective unknown, but it is likely one of the most common PNS observed.
77
alternative. Anemia is reported in 30% to 43% of dogs and 43% to 58% of
cats with lymphoma, and it is a negative prognostic factor in both
Hematologic Manifestations of Cancer species. 83,95–97 It also is commonly reported in dogs and cats with
leukemias and HSA, and dogs with disseminated MCT and histio-
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Hyperglobulinemia and Bence Jones Proteinuria cytic sarcoma (HS). The pathogenic mechanisms common to all
anemias—blood loss, increased red blood cell (RBC) destruction
Hyperglobulinemia, or more specifically monoclonal gammopa- (hemolysis), and decreased RBC production—can each play a role
thy or paraproteinemia, is seen most commonly with multiple in cancer-related anemia, and multiple mechanisms can simulta-
myeloma, but also has been reported with all other myeloma- neously contribute to the anemia observed in a given patient.
related disorders (MRD) including solitary plasma cell tumor Anemia secondary to hemorrhage classically is regenerative,
of bone, extramedullary plasmacytoma (cutaneous and noncu- although it can take 2 to 3 days after the onset of bleeding for retic-
taneous), IgM (Waldenstrӧm’s) macroglobulinemia, plasma cell ulocytosis to be present, and is accompanied by hypoproteinemia.
98
leukemia, Ig-secreting lymphoma, and Ig-secreting chronic lym- Acute, severe hemorrhage is most commonly associated with splenic
phocytic leukemia. 79–82 MRD tumor cells typically produce an HSA, but it also can occur in dogs with other benign and malignant
overabundance of a single type or component of immunoglobu- splenic tumors, adrenal medullary and cortical carcinomas, hepa-
lin, which is referred to as the M component. On serum electro- tocellular carcinoma, and thyroid carcinoma. 98–101 Chronic, low-
phoresis, a narrow-based spike typically is identified in the gamma grade hemorrhage can occur with tumors involving the GI tract,
region (i.e., monoclonal gammopathy), although on rare occasion nasal cavity, urinary bladder, and with tumors causing paraneoplas-
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it can extend into the beta region. Biclonal spikes also have been tic GI ulceration (see earlier). With chronic external hemorrhage
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reported in both dogs and cats. 80,84,85 M components can inter- iron deficiency can result, characterized by microcytosis, hypochro-
fere with coagulation primarily by coating platelets, inhibiting masia, low serum iron, and low saturation of transferrin. 102
platelet aggregation to damaged endothelial surfaces and release of Hemolytic anemias can be immune mediated or non–immune
platelet factor 3. 79,83 M components also can lead to hyperviscos- mediated. Immune-mediated hemolytic anemia (IMHA) is
ity syndrome (see later). characterized by severe anemia that is usually but not always
Intact Ig molecules usually are released by plasma cells, but adequately regenerative, along with spherocytes, autoagglutina-
occasionally there is an imbalance in heavy and light chain produc- tion, and/or a positive direct agglutination test (Coombs test). 103
tion. If there is an excess of free light chain, they will be excreted Hemoglobinemia and/or hyperbilirubinemia are also commonly
in the urine—Bence Jones proteinuria. Bence Jones proteinuria seen. IMHA is most commonly idiopathic in dogs and second-
is diagnosed on urine electrophoresis; it is not detected on rou- ary to feline leukemia virus (FeLV) infection in cats, but it can
tine urine dipstick. 86,87 Bence Jones proteins can cause light-chain be secondary to neoplasia in both species. 83,103 Lymphoma and
renal tubular casts, leading to interstitial nephritis and possibly leukemias are the cancers most frequently associated with IMHA
renal failure. 79,83 in both small animals and humans. 83,103