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ONCOLOGY & CC > Metastasis and Paraneoplastic > Flashcards

Metastasis and Paraneoplastic Flashcards

1
Q

_______% of cancers have overt metastasis at diagnosis

A

30%

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1
Q

local tumors an often be dealth with successfully with

A

surgery and/or radiation therapy

few tumors are curable when they have spread beyond the lymph node

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2
Q

What cancers are highly metastatic

A

1) Hemangiosarcoma
2) Osteosarcoma
3) Malignant melanoma
4) Anal Sac ACA

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3
Q

_______ of tumors are cured with local therapy alone: clinicall signiciant metastasis never occurs

A

30-40%

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4
Q

90% of dogs diagnosed with osteosarcoma will have

A

a microscopic metastasis at the time of diagnosis

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5
Q

What are the 3 determinants of metastasis

A

1) Type of cancer
2) Histologic grade
3) Tumor size

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6
Q

Mast cell tumor histologic grade

A

Low-intermediate grade: 5% chance of metastasis

High-grade: 60% chance of metastasis

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7
Q

Soft tissue sarcoma histologic grade

A

Low-int grade: 10% chance of metastasis

High grade: 45% chance of met

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8
Q

Tumor Size grading

A

1: <2cm
2: 2-4cm
3: >4cm or already spread to node

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9
Q

How does cancer spread to different parts of the body

A

1) Direct extension
2) Lymphatics
3) Hematogenous

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10
Q

What is a classic cancer that spreads to different parts of the body using direct extension

A

Hemangiosarcoma
-ovary, lung, CNS (human)

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11
Q

What are classic cancers that spreads to different parts of the body through lymphatics

A

carcinomas
round cell tumors

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12
Q

What are classic tumors that spread via hematogenous

A

sarcomas
carcinomas

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13
Q

why is the lung/ liver often the first site that a cancer metastasizes to

A

theory: the closet one in which there are small blood vessel (lung is the first pass organ for many tumors, liver is first pass organ for colorectal and pancreas)

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14
Q

What is the first pass organ of the colon and pancreas, making it a good site for cancers of these organs to metastasize to

A

liver

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15
Q

seed and soil hypothesis

A

cells are dispered randomly but only grow in organs which provide the most correct factors necessary for growth of that particular tumor (fertile soil)
bone metastasis of prostate, breast, lung

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16
Q

In order for metastasis to occur, tumor cells need to detach from one another. How is this achieved

A

Cadherin downregulation

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17
Q

How do metastatic tumor cells move to new locations

A

1) Cytoskeletal proteins
2) C-met Receptor/ hepatocyte growth factor

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18
Q

How do metastatic tumor cells degrade extracellular matrix and basement membrane

A

1) Serine proteases (uPA)
2) Matrix metalloproteases
3) Cysteine proteases (cathepsins)

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19
Q

Once in the blood circulation, how do metastatic tumor cells survive in the blood

A

1) Survival in circulation
-Anchorage-independence to avoid anoikis
-Anti-apoptotic mechanisms
2) Avoid immune system- platelet cloak

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20
Q

cell death associated to loss of adhesion, occurs when metastatic cells enter the blood circulation

A

Anoikis

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21
Q

T/F: just because cells are in circulation does not mean they can successfully metastasize

A

True- if removing a tumor and you get some cells in the blood, they might not have the programming to survive in the blood and establish metastasize
-Tumor, surgery, biopsy, needle aspirates do not hasten metastasis
-Pleurovenous shunts- no difference in metastasis seen in individuals with and without

DO NOT worry about biopsies because you are worried about hasten metastasis

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22
Q

Once metastatic tumor cells are in capillary, what do they need to do

A

1) Survive after capillary arrest (shear stress, acute hypoxia, etc) - anti-apoptosis needed to survive during this capillary arrest

2) Bind to specific receptors on the target organ endothelium (sometimes) like ligands (very complicated to overcome)

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23
Q

What is needed for metastatic cells to undergo extravasation

A

induce endothelial apoptosis - similar mechanism to intravasation

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24
Q

What is the rate-limiting step in several models of metastasis

A

survival and proliferation in the new microenvironment
-need to be the right fertilizer of growth factors, matrix, support cells (fibroblasts, macrophages)
-again need to be able to avoid the immune system

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25
Q

the development of new blood vessels
important in tumorigenesis, wound healing, estrus cycle, inflammation

A

angiogenesis

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26
Q

When is angiogenesis seen

A

1) Tumorigenesis
2) Wound healing
3) Estrus cycle
4) Inflammation

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27
Q

What is the limit of diffusion for oxygen in tissues

A

200um - beyond this, cells become hypoxic

thus tumors should not be able to grow beyond 1mm (clinically meaningless) unless they have their own blood supply

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28
Q

Due to hypoxia, tumors cannot grow beyond _______ unless they have their own blood supply

A

1mm

29
Q

What are the 3 mechanisms of angiogenesis

A

1) Classical/Sprouting angiogenesis: ingrowth of endothelial cells from existing vessels due to signals from the tumor
2) Vasculogenesis: outgrowth and recruitment of circulating endothelial precursors from blood
3) Vasculogenic Mimicry, mosaicism - tumors make other tubes lined with extracellular matrix that mimic vessels to deliver blood to them

30
Q

ingrowth of endothelial cells from existing vessels due to signals from the tumor or other tissues

A

Classical/Sprouting Angiogenesis

31
Q

outgrowth and recruitment of circulating endothelial precursors from blood

A

vasculogenesis

32
Q

tumors make other tubes lined with extracellular matrix that mimic vessels to deliver blood to them

A

Vasculogenic mimicry, mosaicism

33
Q

Angiogenic balance

A

+ factors: VEGF, bFGF, IL-8, Ang-1,2

vs

  • factors: Tsp-1,2. Endostatin, Angiostatin
34
Q

What factors increase + factors for pro-angiongenesis

A

Hypoxia
Oncogenes
Loss of TS Genes
Aberrant Signal Transduction

35
Q

What do angiogenic growth factors do

A

1) Attract endothelial cells via chemotaxis
2) Stimulate endothelial proliferation
3) Stimulate endothelial cell invasion and migration
4) Promote endothelial cell survival

36
Q

Why do we care about angiogenesis

A

Potentiall great target for therapy
1) Getting rid of single capillary might destroy hundreds/thousands of tumo cells
2) Endothelial cells are genetically stable and should be much less able to mutate and acquire resistance

37
Q

What 4 ways can we inhibit angiogenesis by tumor cells *

A

1) Block angiogenic growth factors: Antibodies and small molecules (ex: Palladia)
2) Give angiogenesis inhibitors (Angiostatin and endostatin)
3) Target cytotoxic drugs to growing endothelial cells
4) Metronomic chemotherapy- small amounts of drugs given over time- rapdily dividing cells is sensitive for these (doesnt impact normal cells as much

38
Q

antiangiogenic and antiproliferative therapy specifically developed for Patnaik grade II or III, recurrent, cutaneous mast cell tumors with or without regional lymph node involvement in dogs

A

Palladia®
(toceranib phosphate)

39
Q

Angiostatin and endostatin are examples of

A

angiogenesis inhibitors
-but need to be on continuous infusion pumps

40
Q

What should you consider when giving drugs that inhibit tumor angiogenesis

A

1) Dont give to animals that are trying to get pregnant?
2) dont give to animals that will be getting surgery

inhibit endothelial cells from dividing which are one of the slowest dividing cells in the body

normal vasculature that doesnt need to heal is probably good

41
Q

Examples of transmissible tumors

A

1) Transmissible V enerea Tumor (dogs)
2) Transmissible Facial Tumor Disease (Tazmanian Devil)
3) Syrian Hamster Cheek Pouch Tumor
4) Leukemia in Clams

42
Q

cancer-associated alterations in bodily structure and/or function that are not directly related to the physical effects of the primary or metastatic tumor

A

Paraneoplastic syndromes (PNSs)

43
Q

What causes paraneoplastic syndromes

A

tumor production of molecules (hormones, cytokines, peptides) that are released into the circulation, tumor depletion of normal small molecules or host responses to the tumor (immune mediated)

44
Q

What are the GI manifestations of cancer

A

1) Anorexia and Cachexia
2) GI ulceration- commonly MCTs via hyperhistaminemia

45
Q

What are the endocrinologic manifestations of cancer

A

1) Hypercalcemia - via PTHrP from lymphoma,anal sac apocrine gland adenocarcinoma, MM, thymoma, etc.

2) Hypoglycemia- insulinoma

3) Hyperestrogenism- Sertoli cell tumor

4) Hypersomatropism- Acromegaly via functional pituitaty adenoma of somatotroph cells

5) Ectopic Adrenocorticotropic Hormone Syndrome - ACTH

46
Q

What are the hematologic manifestations of cancer

A

1) Hyperglobulinemia and Bence Jones Proteinura - MM

2) Hyperviscosity Syndrome - MM, polycythemia vera, paraneoplastic erythrocytosis

3) Anemia- leukemias and HSA

4) Erythrocytosis - increased erythropoietin (renal tumors)

5) Leukocytosis

6)
Thrombocytopenia- hematopoetic and vascular cancers

7) Coagulopathies / DIC

47
Q

Paraneoplastic myasthenia gravis is reported in dogs and cats with

A

thymoma - can also be seen in some other cancers too

48
Q

Hypertrophic osteopathy is an osteoproductive disroder of periosteum that affects the long bones and extremities and are commonly associated with

A

primary lung tumors or tumors that have metastasized to the lungs

49
Q

What causes paraneoplastic fever

A

innate immune response against tumor antigens or areas of tumor necrosis
Fever mediated primarily by TNF-a, IL-1, IL-6 on the hypothalmus

50
Q

Nodular dermatofibrosis is a PNS that is associated with

A

bilateral renal cystadenocarcinomas or cystadenomas

51
Q

Superficial necrolytic dermatitis is seen in animals that have

A

1) Hepatic disease (hepatocutaneous syndrome)
2) Glucagon secreting tumors (PNS)

52
Q

Paraneoplastic exfoliative dermatitis is reported in cats with

A

thymoma

53
Q

What may be the first sign of malignancy

A

paraneoplastic syndrome

54
Q

With Apocrine gland anal sac adenocarcinma that spread the the medial iliac LNs
-Difficult defecating
-Lethargy PU/PD
-Ionized calcium of 1.8

What parenoplastic syndrome is present

A

Hypercalcemia

55
Q

Sevo has hypercalcemia os 2.1 mmol/L (1.25-1.45)
Is this mild, moderate, or severe/marked

A

Severe- calcium is very tightly regulated and shouldnt be much over the reference

56
Q

How do you treat hypercalcemia of malignancy

A

1) Remove the underlying cause via surgery, chemo, or radiation
2) IV fluids to correct existing dehydration
3) Once rehydrated, furosemide to enhance calcium elimination
4) zonedronate potentially later

57
Q

Zoledronate

A

a drug that can be used to eliminate hypercalcemia

58
Q

What are the differentials for hypercalcemia

A

HARD IOS
1) Hyperparathyroudism
2) addisons
3) Renal
4) D (vit) toxicity
5) Idiopathic (cats)
6) Osteolytic
7) Neoplastic
8) Spurious

Also HOGS IN YARD
G= granulomatous
Y= young

59
Q

What are the most common tumors associated with hypercalcemia of malignancy in dogs

A

Most
1) Apocrine gland anal sac adenocarcinoma *
2) Lymphoma *
3) Multiple Myeloma *
4) Thymoma

60
Q

T/F: cancer is the most common cause of hypercalcemia in cats

A

False- cats dont get it as much as dogs

most common cause in cats is idiopathic, then renal, then cancer

61
Q

What cancers typically cause hypercalcemia in cats

A

1) Lymphoma
2) Squamous Cell Carcinoma

62
Q

What should you do when you see a patient has hypercalcemia for further diagnostics

A

1) Recheck rectal examination for small nodules in anal sacs

2) Thoracic radiographs - mediastinal mass,

3) Abdominal ultrasound

4) Malignancy panel - PTH/ PTHrp/ iCa++

63
Q

What are possible differentials for mediastinal masses

A

1) Lymphoma (t-cell)
2) Thymoma- ectopic thyroid carcinoma, branchial cyst, metastatic neoplasia

64
Q

What should you do to work up a mediastinal mass

A

ultrasound guided FNA of mass to see if lymphoma or thymoma- very different treatment procedures

65
Q

Why is it important to monitor iCa++ throughout treatment of cancer (ie lymphoma)

A

increased calcium was a marker for disease reucurrence

66
Q

Hyperglobulinemia is a paraneoplastic syndrome associated with which two cancers

A

1) Multiple Myeloma - plasma cells
2) Lymphoma- some B cell types can produce immunoglobulins

67
Q

What should you do for a dog with significant periosteal reactions on the distal forelimbs (radius, ulna, metacarpals, phalanges). What should you do?

A

Thoracic Radiographs- likely caused by chest lesions

68
Q

Cancerous causes of hypertrophic osteopathy

A

-Primary lung tumur
-Metastatic cancer to tumor
-Rhabdomyosarcoma of bladder (rare)
-esophageal sarcoma (rare)

69
Q

What are the non-neoplastic causes of Hypertrophic osteopathy

A

1) Difilaria immitis infection
2) Patent ductus arteriosus w R to L shunting
3) Spirocerca lupia esophageal granulomas
4) Esophageal foreign body
5) Bacterial endocarditis

70
Q

How do patients with hypertropic osteopathy typically present

A

swelling and/or edema of the distal limbs and lameness or difficulty ambulating

limbs are often painful on palpation and/or warm to touch

71
Q
A

ONCOLOGY & CC (6 decks)

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