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Paraneoplastic syndromes Flashcards

1
Q

How many dog and cats with hypercalemia are diagnosed with cancer?

A

60% and 30%

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2
Q

Which neoplasia is the most common cause for hypercalcemia in dogs?

A

T-cell lymphoma (35-55%) followed by ASAC (25%)

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3
Q

Name 8 other neoplastic processes known to cause hypercalcemia?

A 
DOG:
Epithelial- 
Nasal
Thyroid
Thymoma
Pulmonary
Mammary
Hepatocellular
Adrenal
Renal 
Clitoral
ASAC

Round cell;
Lymphoma - T cell
Leukemia - chronic lymphocytic, acute lymphoblastic
Multiple myeloma

Mesenchymal:
Melanoma
Osteosarcoma
Achantomatous ameloblastoma

CAT:
Epithelial 
SCC
Thyroid
Pulmonary
Renal

ROUND CELL:
Acute leukemia
Lymphoma
MM

Mesenchymal:
OSA
FSA
Undifferentiated SA

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4
Q

What is the most common cause for hypercalcemia of malignancy in cats?

A

Lymphoma, SCC and multiple myeloma

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5
Q

Name 5 other neoplasia which have caused hypercalcemia in cats?

A 
Epithelial:
Pulmonary
Thyroid
Renal 
SCC

Mesenchymal
OSA
FSA

Rounds:
LSA
Acute leukemia

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6
Q

What are the main differentials to hypercalcemia?

A 
D- vitaminosis D
R - Renal disease
A - ddisons
G- granulomatous
O - Osteolysis
N - Neoplasia
S - spurious
H - hyperparathyroidism
I - idiopathic 
T- Total protein elevation
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7
Q

What is the MOA of bisphosphanates?

A

They inhibit the enzyme Farnesyl dephosphate synthase (FPPS) in the mevalonate pathway, inhibit formation of farnesyl-PP result in accumulation of cytotoxic intermediate substrates causing reduced osteoclast function and possible apoptosis.

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8
Q

Which AE have been associated with bisphosphanates?

A 
Osteonecrosis of the jaw (rare)
Human AE:
Nephrotoxicity
Electrolyte imbalances
acute phase reactions
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9
Q

What is the MAO of paraneoplastic fever?

A

Immune reaction to tumour antigens or tumour necrosis resulting in IL-1, IL-6 and TNF-alpha release- This will activate the arachidonic acid cascade which produce prostaglandin E2 which work on the hypothalamus

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10
Q

Which type of malignancy is most commonly found as the cause of paraneoplastic fever?

A

Haematological neoplasia

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11
Q

Which neoplastic process is most likely to be the cause of myastenia gravis?

A

Thymoma

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12
Q

Which other neoplastic diseases than thymoma may cause MG?

A

Oral sarcoma, non-epitheliotrophic lsa, cholangiocellular carcinoma, osteosarcoma

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13
Q

DDX paraneoplastic erythrocytosis

A
  • renal tumour (adenocarcinoma, LSA, FSA)
  • nasal fibrosarcoma
  • caecal leiomyosarcoma
  • spinal cord swannoma
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14
Q

DDX non-neoplastic causes erythropoietin

A

non-neoplastic renal disease
heart disease with right to left shunting
chronic respiratory disease

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15
Q

What is the suspected mechanisms of paraneoplastic erythrocytosis?

A

Increased production EPO by tumour cells
OR
Chronic reduced renal perfusion

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16
Q

By which mechanisms can paraneoplastic hypogycemia occur?

A 
Production of insulin
Production of IGF-1 or IGF-2
Hypermetabolism of glucose
production of substances stimulating insulin release
production stomatomedins
insulin binding by monoclonal immunoglobulin (plasma cell tumour)
insulin receptor proliferation
ectopic insulin production
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17
Q

Which tumours are associated with paraneoplastic hypoglycaemia

A 
Primary hepatic tumours (HCC, or adenoma)
Smooth muscle tumours - leiomyom and leiomyosarcoma. 
Case reports for:
HSA
LSA
LL
mammary carcinoma
melanoma
Plasmacell tumour
renal adenocarcinoma
salivary adenocarcinoma
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18
Q

HSA has been associated with the following PNS?

A

Anemia
DIC
Neutrophilic leukocytsosis
Hypoglycemia

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19
Q

How many dogs and diagnosed with LSA have anaemia?

A

30-60%

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20
Q

Which neoplastic process does most commonly cause paraneoplastic IMHA?

A

Lymphoma

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21
Q

What is microangiopathic hemolytic anaemia?

A

Non-immune mediated destruction of RBCs secondary to microangiopahty, tumor cell erythrophagocytosis, oxidative damage to erythrocytes.

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22
Q

Which tumours are most commonly associated with paraneoplastic anaemia?

A

Lymphoma, leukemia, HSA, HS, disseminated MCT

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23
Q

Which other clinicopathological abnormalities can be seen with dogs with hemophagocytic HS?

A

Thrombocytopenia, regenerative anaemia, negative direct agglutination, hypoalbuminemia, hypocholesterolemia

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24
Q

Erythrocytosis have been documented in which neoplastic processes?

A 
HS
Plasma cell tumour
Lymphoma
acute megacaryopblastic leukemia
Cats with LSA and MCT
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25
What is the most common pathogenesis of anaemia in pets with cancer?
Anaemia of inflammatory disease: Mild to moderate, non regenerative, normocytic normochromic anaemia TNF-alpha INF-gamma IL1, IL-6, Il-19 reduce EPO production and suppress erythroid progenitor response IL-6 increase hepcidine production in the liver, causing internalisation and degradation of ferroportin, reducing available iron and decreased availability of iron for erythropoiesis.
26
Which factors are responsible for inducing cachexia?
IL-1, IL-6, TNF-alpha, myostatin, NF-kappa beta activating ubiquitin proteasome pathway, GH and IGF-1 Result in anorexia, energy metabolism and loss of lean body mass
27
Which tumours may cause GI ulceration?
1. MCT | 2. Gastrinoma
28
What is the effect of hypehistaminemia?
1. Increased HCl secretion 2. Increased vascular permeability of gastric mucosa 3. localised protein exudation 4. increased mucosal blood flow
29
What is Zollinger Ellison-syndrome?
Hypergastrinemia, GI ulceration and a no-neta cell neuroendocrine tumour in the pancrease
30
What is the most common cause of paraneoplastic hypoglycaemia?
Insulinoma - due to production of insulin
31
What is the most common cause for paraneoplastic hypoglycemia in non-islet cell tumour?
Production of IGF-2
32
Which 5 tumours have been reported to cause hypoglycemia?
``` Primary liver tumour Leiomyom Leiomyosarcoma HSA LSA Lymphocytic leukemia MC Melanoma Plasma cell tumour Renal carcinoma Salivary gland adenocarcinoma ```
33
By which mehcanisms can tumours potentially cause hypoglycemia?
1. insulin 2. IGF-1 or IGF-2 3. Glucose metabolism 3. Proliferation of insulin receptors 4. Ectopic insulin production 5. Produce substances stimulating insulin release 6. Produce hepatic glucose inhibitor 7. Insulin binding to monoconal AB - plasma cell tumour
34
which tumours may cause hyperestrogenism
1, Sertoli | less likely - seminoma, leydig cell or ovarian granulosa cell tumour
35
What are the clinical signs associated with hyperestrogenism
Bilateral symmetric alopecia, hyperpigmentation, epidermal thinning, gynecomastia, galactorrhea, pendulous prepuce penile atrophy, atrophy contralateral testicel, attraction other males BONEMARROW TOXICOSIS
36
What are the findings associated with hyperestrogenims on a CBC?
Initial granulocytosis- normally neutrophilic, followed by progressive bone marrow hypo-plasia leading to aplastic anaemia
37
What is the mechanism behind canine acromegaly?
Progesin-induced GH secretion from a mammary ductal epithelium - has been reported in 2 mammary tumours
38
What is the MAO for acromegaly in cats?
Hypersomatrophism due to a pituitary adenoma
39
What is the result of prolonged exposure to excessive amounts of GH?
Reduced insulin sensitivity and DM Overgrowth of connective tissue, bone and viscera - broad facia features, diffuse thickening oropharyngeal tissue, organomegaly, HCM, clubbing of the paws
40
How do we diagnose acromegaly?
Measure IGF-1
41
What is the cause of ectopic ACTH production documented in people with small cell carcinoma of the lungs?
The tumour express proopiomelanocortin gene
42
How can M components interfere with coagulation?
1. coat the platelets 2. inhibit platelet aggregation to damages surface 3. inhibit release platelet factor 3
43
How does BJ proteins cause renal damage?
They can form tubular casts which result in interstitial nephritis and possible renal failure
44
What are the possible neoplastic causes for hyperviscosity syndrome?
.Increased globulins- ie myeloma related disorders PV Paraneoplastic erythrocytosis- TVT, caecal leiomyosarcoma, renal tumour, nasal fibrosarcoma, spinal cord schwannoma
45
Which Ig is most likely to cause hyperviscosity+
IgM or IgA
46
What are the clinical signs associated with hyperviscosity syndrome?
Neurological: seizure, abnormal mentation, ataxia Ocular: Retinal bleeding, tortuous vessels, retinal detachment Bleeding diathesis Cardiomyopathy
47
What would be a treatment option for severe hyperviscosity syndrome?
Plasmapheresis | Phlebotomy and IV-fluids if due to erythrocytosis
48
What are possible ddx for agglutination?
- IMHA | - EDTA-agglutination - spurious
49
What is the possible causes of Rouleaux formation?
- Hyperglobulinemia - fibrinogen og immunoglobulin
50
How does anaemia of inflammatory disease cause anemia?
It is caused by increase in inflammatory cytokines - TNF-alpha, IFN-gamma, IL1, IL6, IL-10 reduce the production of EPPO in the face of hypoxemia and suppress the erythroid progenitor response. and IL-6 produce more hepcidin, which degrade ferroportine reducing availability of iron . decreased iron for erythropoiesis.
51
Paraneoplastic neutrophilic leukocytosis has been documented with :
Dog: Renal tumours, pulmonary carcinoma, interstitial t-cell lymphoma, fibrosarcoma, rectal polyos Cat: Pulmonary carcinoma, dermal adeocarcinoma
52
What is the suspected cause for neutrophilic leukocytosis?
Tumor production of G-CSF
53
What are possible causes of paraneoplastic eosinophilia?
IL-5 production -
54
What is the cause of paraneoplastic eosinophilia?
IL-5
55
Which tumours have been documented to cause hypereosinopilia?
MCT, T-cell lymphoma most common, others include FSA, MC, leiomyosarcoma in dogs Oral SCC and TCC in cats
56
How many dogs with neoplasia present with thrombocytopenia?
10-35%
57
T/F The cause of paraneoplastic thrombocytopenia is not identified in up to 60% of cases
T
58
Which neoplastic disease most commonly cause immune mediated thrombocytopenia?
1. lymphoma 2. MM 3. HS Other: Mammary carcinoma Nasal adenocarcinoma MCT HSA FSA
59
Which tumours can cause thrombocytopenia by increased splenic sequestration?
LSA Feline MCT Hemangioma HSA
60
Which canine tumour most commonly cause hypogoaulability by causing clotting factor dysfunction? AND what is the mechanism?
MCT - cofactor for antithrombin 3 - inactivate clotting facto 12, 11, 10 and 9
61
What is most common in cancer patients - hyper or hypo coagulability?
Hyper
62
Which tumours most commonly cause DIC?
HSA Mammary carcinoma - inflammatory especially Pulmonary adenocarcinoma
63
What are the mechanisms of DIC in neoplasia?
1. Abnormal vasculature cause rearrangement of the haemodynamics triggering coagulation 2. Hyperviscosity reduced efficacy of the PLT and slugging of blood 3. Inflammation cause cross-talk with coags- tissue factor complex with factor 7a and activate the extrinsic pathway - main source of thrombin in neoplasia 4. Cytokines TNF-alpha, IL-1 and IL6 can activate the extrinsic clotting cascade, and down regulate C-thrombomodulin
64
Which tumours are commonly found in dogs with nodular fibrosis in addition to the renal cyst adenomas and carcinomas?
Uterine leyomyoma
65
Superficial necrolytic dermatitis is seen with which tumour?
Glucagonma in Pancras or liver
66
Give ddx for a dog presenting with hyperkeratosis man fissuring uf the foot pads and ulceration and crusting of mucocutaneous junctions
Paraneoplastic superficial necrolytic dermatitis - glucagonoma in liver or pancreas
67
What is the MAO causing hypoaminoacidemia
Elevated glucagon sustain glyconeogenesis and amino acid catabolism . causing low AA resulting in epidermal protein depletion and keratinocyte necrolysis
68
Which tumours have been known to cause paraneoplastic alopecia in cats?
Pancreatic carcinoma | Biliary carcinoma
69
What is the difference between feline paraneoplastic alopecia and feline thymoma associated exofoliative dermatitis?
Alopecia is at the venture and medial aspect of limb, skin is shiny and thin Exofoliative dermatitis affect the head and pinna, and progress, cause scaling and mild erythema
70
What is the most common PNP glomerular disorder
Membranous nephropathy caused by immuncomplex formation
71
T/F HS can cause hypercalcemia
True

Paraneoplastic syndromes (1 decks)

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