Paraneoplastic Flashcards
Which cytokines are most commonly implicated in cancer associated anorexia?
IL-1 and IL-6
Interfere with normal balance of anorexigenic and orexigenic signals
Which cytokines play primary roles in cancer cachexia and how?
IL-1, IL-6, TNF-a
Induce anorexia, increase energy metabolism, accelerate loss of lean body mass through activation of NF-kB which activates the ubiquitin proteasome pathway
Are BCS and body weight prognostic factors in dogs and cats with cancer?
Low BW and low BCS = negative prognostic factors for survival across tumor types
What is the most common tumor type associated with PNS-associated GI ulceration?
MCTs through hyperhistaminemia
Describe the mechanism by which histamine results in GI bleeding?
Histamine binds to gastric parietal cell H2 receptors –> stimulate gastric acid secretion
Histamine direct effects on gastric mucosa –> increased vascular permeability, localized protein exudation, increased mucosal blood flow
What concentration of histamine in the plasma is predictive of clinical signs of GI ulceration?
Concentrations are NOT predictive
Which less common tumor may be responsible for PNS-associated GI ulceration?
Gastrinoma
What percentage of dogs with hypercalcemia have a cancer diagnosis? Cats?
Dogs - 60%
Cats - 30%
What is Zollinger-Ellison syndrome?
hypergastrinemia + non-beta cell neuroendocrine tumor in pancreas + GI ulceration
What are the most common causes of hypercalcemia of malignancy in cats?
Lymphoma, SCC, multiple myeloma
What are the most common causes of hypercalcemia of malignancy in dogs?
T-cell lymphoma (35-55%), AGASACA (25%)
How does PTHrP activate PTH receptors on osteoblasts and renal tubular cells?
70% sequence homology of the first 13 N-terminal amino acids with PTH
Clinical signs of hypercalcemia in cats?
anorexia and vomiting
What is PTHrP and where is it normally released?
Parathyroid hormone related protein
Fetal parathyroid glands, placenta, and mammary glands
What causes PU/PD in hypercalcemic patients?
Impaired action of ADH on tubular cells of the collecting duct
What is the most common cause of paraneoplastic hypoglycemia in dogs?
Insulinoma
Which non-islet cell tumors are most commonly associated with paraneoplastic hypoglycemia?
Primary liver tumors, smooth muscle tumors
What is the most common cause of PNS hypoglycemia in non-islet cell tumors?
Production of IGF-2
How are insulinomas most commonly diagnosed?
hypoglycemia + elevated serum insulin level
Which tumor is most commonly associated with hyperestrogenism in dogs? Cats?
Dogs - sertoli cell tumor
Cats - not reported
Clinical signs of hyperestrogenism?
Bilaterally symmetric alopecia, cutaneous hyperpigmentation, epidermal thinning, gynecomastia, galactorrhea, pendulous prepuce, penile atrophy, atrophy of the contralateral testicle, attraction to other males
What are some laboratory abnormalities you may see in patients with hyperestrogenism?
Myelotoxicosis
Transient increase in granulocytopoiesis and neutrophilic leukocytosis –> progressive bone marrow hypoplasia/aplasia –> aplastic anemia
What is the most common cause of acromegaly in cats?
Excessive GH secretion by a functional pituitary adenoma arising from somatotroph cells
What is the most common cause of acromegaly in dogs?
Progestin-induced GH secretion by mammary ductal epithelium
What causes insulin resistance in cats with acromegaly?
GH reduces insulin receptors and interferes with a wide range of post-receptor processes
What is the most practical way to confirm feline hypersomatotropism?
Measurement of serum IGF-1
Nodular dermatofibrosis is associated with what neoplasms?
bilateral renal cystadenocarcinomas or cystadenomas
Almost all cases of nodular dermatofibrosis are associated with what breed of dog?
German Shepherd Dog (autosomal dominant trait)
Mechanisms by which M components interfere with coagulation
Coating platelets, inhibiting platelet aggregation to damaged endothelial surfaces, and inhibition of platelet factor 3
What are Bence Jones proteins?
Antibody light chains excreted in the urine
Females affected with nodular dermatofibrosis almost always have what other neoplasm?
uterine leiomyomas
Two most common immunoglobulin types associated with HVS
IgM (pentamer) and IgA (dimer form)
Superficial necrolytic dermatitis is associated with what diseases?
(ie hepatocutaneous syndrome)
hepatic disease, glucagon secreting tumors in pancreas and liver
Percent occurrence of anemia in dogs and cats with lymphoma?
Dogs 30-43%
Cats 43-58%
Dermatologic findings in superficial necrolytic dermatitis
Erosions and ulcerations with alopecia, exudation, and crusts on feet, pressure points, flank, mucocutaneous jxn, and/or oral cavity
ALL ANIMALS HAVE: hyperkeratosis and fissuring of footpads
Cancer associated with feline paraneoplastic alopecia?
pancreatic carcinoma and biliary carcinoma
Mechanism of anemia of chronic disease / anemia of inflammatory disease
Inflammatory cytokines (TNF-a, IFN-g), IL-1, IL-6, IL-10 reduce production of erythropoietin in the face of hypoxemia and suppress the erythroid progenitor response to erythropoietin, and also iron sequestration via hepcidin production (IL-6 increases hepcidin production)
Extreme neutrophilic leukocytosis has been associated with what cancers? How does it happen?
Usually also with a concurrent monocytosis and eosinophilia, seen with
Dogs: pulmonary carcinoma, renal tumors, interstitial T-cell lymphoma, metastatic fibrosarcoma, adenomatous rectal polyps
Cats: Pulmonary SCC, dermal tubular adenocarcinoma
Tumor cells secrete granulocyte colony stimulating factor / granulocyte-macrophage colony stimulating factor
Most common type of phenotype of lymphoma associated with eosinophilia
T-cell
The spleen stores what percent of the body’s platelets?
33%
Distribution and characteristics of feline paraneoplastic alopecia
- ventrum and medial aspects of limbs
- hair is easily epilated and skin is shiny, inelastic, and thin but not fragile
- food pad involvement common
Heparin released by MCTs causes clotting dysfunction via what mechanism?
Acts as a cofactor for antithrombin III to inactivate clotting factors XII, XI, X, IX
Up to what percent of dogs with HSA have DIC at presentation
50%
Paraneoplastic thymoma associated exfoliative dermatitis….
exists. The end.
Myasthenia gravis is associated with what cancers?
Thymoma (most common)
Also, OSA, cholagiocarcinoma, oral sarcoma, nonepitheliotropic cutaneous lymphoma
Thrombocytosis may support cancer progression via what mechanism?
Fibrin deposition around neoplastic foci forms provisional extracellular matrix for angiogenesis and the formation of fibrin-platelet-tumor cell complexes increases adhesion to endothelium and enhances metastatic efficiency
What other cancers may have granules and be mistaken for MCTs?
granulated T-cell lymphoma, NK cell lymphoma, granular cell tumors
Hypertrophic osteopathy is caused by what cancer?
Lung tumors including metastatic lesions (most commonly OSA)
Non-neoplastic conditions associated with hypertrophic osteopathy?
infectious/inflammatory lung disease, heartworm, endocarditis, PDA, spirocerca lupi, congenital megaesophagus
Da Fuq is a Mott Cell?
Plasma cell that contain Russell Bodies, collections of immunoglobulin within the ER
5 types of round cell tumors?
Lymphoma, MCT, histiocytoma, plasmacytoma, TVT
cell of origin of cutaneous histiocytoma?
epidermal dendric/langerhans cells
