Paraneoplastic Syndrome Flashcards
What are the top 3 canine tumours for paraneoplastic hypercalcemia?
- lymphoma
- anal sac apocrine gland adenocarcinoma
- multiple myeloma
What’s the most common tumour to induce GI ulceration?
MCT
What’s the top 3 feline tumour with paraneoplastic hypercalcemia?
- lymphoma
- SCC
- multiple myeloma
What’s the most common tumour to have paraneoplastic hyerestrogenemia?
sertoli cell tumour
What’s the most common tumour to have paraneoplastic acromegaly?
feline pituitary acroadenoma
What’s the most common tumour to have ectopic ACTH production?
Primary lung tumour
What are the 2 most common tumours to have paraneoplastic hyeprglobulinemia?
multiple myeloma & other meyloid related diseases
What are the 3 most common tumours to have paraneoplastic anemia?
- lymphoma
- leukemias
- hemangiosarcoma
What’s the most common tumour to have paraneoplastic erythrocytosis?
renal tumours
What’s the 2 most common tumours to have neutrophilic leuocytosis?
- lung tumours
- lymphoma
What’s the 3 most common tumours for paraneoplastic thrombocytopenia?
- lymphoma
- leukemia
- hemangiosarcoma
What’s the 3 most common tumours to have paraneoplastic DIC?
- hemangiosarcoma
- mammary carcinoma (esp inflammatory)
- pulmonary carcinoma
What’s the most common tumour with nodular dermatofibrosis?
reanl cystadenoma/ cystadenocarcinoma (dog)
What’s the most common tumour with paraneoplastic superficial necrolytic dermatitis?
glucagonoma (pancreatic, hepatic)
What’s the 2 common tumours for feline paraneoplastic alopecia?
- pancreatic carcinoma
- biliary carcinoma
What’s the most common feline tumour with paraneoplastic exfoliative dermatitis?
thymoma
What’s the 2 most common tumours for glomerulonephritis?
- primary erythrocytosis
- lymphocytic leukemia
What’s the most common tumour for paraneoplastic myasthenia gravis?
thymoma
What’s the 2 most common tumours for paraneoplastic hypertrophic osteopathy?
- pulmonary metastasis (esp osteosarcoma)
- primary lung tumour
What’s are the 3 common tumours with paraneoplastic peripheral neuropathy?
- insulinoma
- lung tumours
- mammary tumours
What are some (5) paraneoplastic syndromes associated with lung tumours?
- ectopic ACTH
- neutrophilic leukocytosis
- peripheral neuropathy
- DIC
- hypertrophic osteopathy
Which cytokines/ inflammatory mediator are involved in cancer cachexia?
- IL-1
- IL-6
- TNF-alpha
What’s the mechanism of action for gastric ulcer with mast cell tumours?
MCT –> hyperhistaminemia –> stimulates parietal cells in the stomach (H2 receptors) –> increases gastric secretion
Histamine can also have direct effect on the gastric mucosa –> increased vascular permeability, localized protein exudation, and increased mucosal blood flow
What % of dogs and cats have cancer when diagnosed with hypercalcemia?
60% dogs, 30% cats
What’s the most common clinical signs for cats with hypercalcemia of malignancy?
vomiting and anorexia (PU/PD less common, more so in dogs)
What are the most common reasons for hypercalcemia of malginancy?
- PTHrP
- bone destruction: IL-1, IL-6, TNF, RANKL, TGF-apha and beta, prostaglandins (esp PGE2)
What are the 3 most common tumours that have paraneoplastic hypoglycemia?
- insulinoma
- hepatic adenoma/ adenocarcinoma
- leiomyoma/ leiomyosarcoma (liver stomach, duodenum, jejunum)
What’s the most common cause for hypoglycemia in non-islet cell tumours?
production of IGF-2
What % of dogs with sertoli cell tumour will develop hyperestrogenemia?
25-50%
What are some signs of feminization?
- bilateral symmetrical alopecia
- epidermal thinning
- cutaneous hyperpigmentation
- gynecomastia
- galactorrhea
- atrophy of the contralateral testes
- small prostate (or enlarged if there is squamous metaplasia)
- pendulous prepuce
- atrophy of the penis
- bone marrow toxicity (anaplastic anemia)
What are some signs of anaplastic anemia?
- anemia: weakness, lethargy, pale mucus membrane, tachycardia
- thrombocytopenia: petechia, ecchymoses, epistaxis, GI bleeding
- leukopenia: infection, sepsis
Canine cases of acromegaly is most commonly associated with which tumours?
over-production of growth hormone by progesterone-induced mammary ductal epithelium
What are the main features of acromegaly in the cat?
Growth hormone antagonizes insulin by reducing insulin receptors and interferring with post-receptor processing
1. broad facial features
2. prognathica inferior
3. diffuse thickening of oropharyngeal tissues
4. enlargement of liver, kidneys, adrenals, heart (HCM)
5. clubbing of paws/ extremities
6. degenerative arthropathy
What can be easily measured to determine if there is paraneoplastic acromegaly?
IGF-1, easier to measure than growth hormone. The effect GF is mostly mediated via IGF-1
What’s the cause of Cushing’s syndrome in dogs with primary lung tumour?
overexpression of proopiomelanocortin gene
What component of the plasma cell is commonly overexpressed in myeloid related disorders?
M- component
Which Ig is most commonly associated with hyper viscosity syndrome?
IgA
What are some signs of hyper viscosity syndrome?
- sludging of blood –> inability to deliver oxygen and nutrients effectively, coagulation abnormalities
- Ig coats the platelet cells, inhibit platelet aggregate formation,
- Neurological signs: stupour, ataxia, seizure
- Ocular signs: tortuous and enlarged retinal vessels, retinal hemorrhage, retinal detachment, acute blindness
- bleeding diathesis
- hypertrophic cardiomegaly (HCM)
- congestive heart failure (CHF)
Which cancers are most commonly associated with immune mediated hemolytic anemia?
Lymphoma and leukemia
Microangiopathic hemolytic anemia is most commonly seen in which cancer?
Hemangiosarcoma
This is due to endothelial cell injury and fibrin deposition
commonly seen in patients in DIC
leads to shearing and destruction of erythrocytes –> increased schistocytes in circulation
What’s the typical characterization of anemia in anima of inflammatory disease?
normocytic, normochromi, non-regenerative (mild to moderate)
What’s the role of IL-6 in anemia?
IL-6 –> increased hepcidin production, an acute phase protein.
Hepcidin –> increased internalization and degradation of ferroportin, which is responsible for export of iron from macrophages and hepatocytes, and duodenal enterocytes into the peripheral blood
ie. sequestration of iron –> hypoferremia –> decreased availability of iron for erythropoiesis
What’s the most common cause of paraneoplastic neutrophilic leukocytosis?
tumour production of granulocyte colony stimulating factor (G-CSF) and/or granulocyte-macrophage CSF (GM-CSF)
Which tumours are most commonly associated with immune-mediated thrombocytopenia?
- lymphoma
- multiple myeloma
- histiocytic sarcoma
What are some none immune mediated causes of thrombocytopenia in cancer patients?
- microagniopathy
- sequestration in the spleen (spleens stores 1/3 of platelet): cancers that lead to splenomegaly –> lymphoma, feline splenic MCT; hemangiosarcoma
IL-1, IL-6, and TNF-alpha are involved in which paraneoplastic syndromes?
- cancer cachexia: inducing anorexia, increasing energy metabolism, and accelerating loss of lean body mass
- hpercalcemia of malignancy
- anemia: IL-1, IL-6, and Il-10 – reduce the production of endogenous erythropoietin in the face of hypoxemia, and suppress the erythroid progenitor response to erythropoietin
- coagulopathy: directly activate certain clotting factors and downregulate protein C-thrombomodulin expression on endothelial cells
- Fever: due to effects on hypothalamus
What molecule released by mast cell tumours leads to bleeding? What’s the mechanism of action?
Heparin
it’s a cofactor to antithrombin III, which inactivates XII, XI, X, IX (intrinsic pathway)
What is the most common cause of DIC (disseminated intravascular coagulopathy)?
Cancer
Approximately 10% of dogs with cancer will have DIC, esp hemangiosarcoma, mammary carcinoma, and pulmonary adenocarcinoma
What are some causes of DIC in cancer patients?
- inherent vascular abnormalities (leaky vessels, tortuous, blood flow turbulence)
- expression of tissue factor on cancer cells and pro-inflammatory cells (monocytes and endothelial cells) –> activation of the extrinsic pathway
- TNF-alpha, IL-1, IL-6 –> also directly activate certain clotting factors and downregulate protein C-thrombomodulin expression on endothelial cells (leading to hypercoagulable state)
What’s a common signalment of paraneoplastic nodular dermatofibrosis?
- common in German Shepherd dogs
- most on limbs, can see in head and trunk in advanced cases
- none painful, none pruritic
- well differentiated dense collagen fibers
- genetic component: mutation in BHD gene on chromosome 5
- similar to Birt-Hogg-Dube syndrome in people
- affected females can also have concurrent uterine leiomyomas (no clinical significance)
- no effective therapy for underlying cancer (renal cystadenoma/ adenocarcinoma)
MST ~ 2.5y from appearance of the nodular dermatofibrosis (often seen years prior to c/s due to the cancer)
What’s the most common cause of superficial necrolytic dermatitis?
dogs with liver disease (hepatocutaneous syndrome)
What are the features of superficial necrolytic dermatitis?
- may be painful, pruritic
- erosion and ulceration, alopecia, exudation, crusts on feet, pressure point, flank, perineal area, muzzle, facial MCJ, oral cavity
- hyperkeratosis and fissure of foot pads on all affected
What’s a proposed pathophysiology for superficial necrolytic dermatitis?
over-production of glucagon –> increased amino acid catabolism –> hypoaminoacidemia –> epidermal protein depletion –> keratinocyte necrolysis
What’s the presenting features of feline paraneoplastic alopecia?
- none pruritic
- symmetrical, progressive, mostly on ventrum and limbs
- hair is easily epilated, skin is shiny, inelastic, thin, but not fragile
- affected pads can be painful
pancreatic and biliary carcinoma
What are the features of feline thymoma associated exfoliative dermatitis?
- starts off as none pruritic scaling & erythema on the head and ears, then progressive down the neck, trunk and limbs
- unknown mechanism, likely immune mediated
What’s the pathophysiology for myasthenia gravis?
- antibodies formed against nicotinic acetylcholine (Ach) receptors
- often but not always exercise induced weakness in the appendicular muscles
- definitive test = antibodies against Ach receptor in serum
- can also do endrophonium chloride challenge test
- itself is not a prognostic factor, but the consequences of megaesophagus can be
What are some paraneoplastic syndrome seen in cats with thymoma?
- exfoliative dermatitis
- pemphigus vulgaris
What are some paraneoplastic syndrome seen in dogs with thymoma?
- polyarthritis
- masticatory muscle myositis
- perianal fistula
- immune mediated thrombocytopenia
- hypothyroid
What are some none neoplastic differentials for hypertrophic osteopathy?
- infection/inflammatory lung disease
- heartworm
- bacterial endocarditits
- patent ductus arteriosus with R to L shunting , spirocera lupi esophageal granulomas, esophageal FB, congenital megaesophagus
What are some features of hypertrophic osteopathy?
- starts off with swelling/ edema of the distal limbs, and progresses proximally
- lameness, difficulty ambulating
- often painful or warm on palpation
- can see bilateral serous to mucopurulent ocular discharge and episcleral injection
- may be due to increased peripheral blood flow, proliferation of vascular connective tissue, and bone spicule formation
- neural reflex possible
