Neoplasia pt 2

Question 1

What are direct effects of neoplasia?

Answer 1

• replace normal tissue
• compression of neighbor tissue
• obstruction
• disrupt anatomical relationships
• vascular compression/infiltration = infarction = necrosis
• rupture
• erosion of vessels = rupture, hemorrhage

Question 2

Paraneoplastic effects

Answer 2

Tumors cause various systemic signs, indirect, from tumor cell products
- mostly seen in dogs

Question 3

Systemic

Answer 3

Anorexia, cachexia, fever

- weight loss despite a good appetite, driven by cytokines

Question 4

Endocrine

Answer 4

Hypercalcemia, hypoglycemia, hyperestrogenism, thyrotoxicosis

Question 5

Skeletal

Answer 5

Myelofibrosis, hypertrophic osteopathy (related to chest tumors)

Question 6

Vascular/hematopoietic

Answer 6

Leukocytosis, leukopenia, anemia, DIC

Question 7

Neurologic

Answer 7

Myasthenia gravis, peripheral neuropathy

Question 8

Cutaneous

Answer 8

Alopecia, nodular dermatofibrosis

Question 9

Paraneoplastic effects can facilitate ______

Answer 9

Early tumor detection

Question 10

Cachexia

Answer 10

Weight loss and debility associated with cancer

• muscle and fat are lost
• no compensatory decrease in basal metabolism (unlike starvation)
• added caloric intake does not alleviate
• TNF-alpha, IL1, IL6

Question 11

Endocrine

Answer 11

Functioning endocrine tumors

Question 12

Thyroid carcinomas

Answer 12

Hyperthyroidism

Question 13

Pancreas islet cell carcinomas

Answer 13

Insulinomas of beta cells

• hyperinsulinemia/hypoglycemia
• seizures, weakness, incoordination

Question 14

Ectopic hormone production

Answer 14

Production of hormone not normally found in tissue of origin

- insulin like hormone production, colonic leiomyoma = hypoglycemia

Question 15

Hypercalcemia

Answer 15

Parathyroid hormone-related peptide (PTHrP) = humoral hypercalcemia of malignancy

• adenocarcinoma of the apocrine glands of the anal sac (90% of cases)
• lymphoma (20% of cases)
• multiple myeloma (15% of cases)
• rare in cats

Question 16

PTHrP mimics the function of ______

Answer 16

PTH, including calcium release from bone, reabsorption from kidneys, and absorption from intestine
- hypercalcemia due to cancer metastasis to bone, or bone resorption, NOT paraneoplastic but is a direct effect of the tumor

Question 17

Hematopoietic/vascular

Answer 17

• eosinophilia, neutrophilia, basophilia, mast cells (rare) - cytokines
• anemia: chronic disease, blood loss, bone marrow invasion, hemolysis

Question 18

Thrombocytopenia

Answer 18

Immune mediate, hemangiosarcoma (DIC)

Question 19

Gastric mast cell tumors

Answer 19

Histamine release, ulcerations

Question 20

What are hallmarks of cancer?

Answer 20

• avoiding immune destruction
• evading growth suppressors
• enabling replicative immortality
• tumor promoting inflammation
• activating invasion and metastasis
• genomic instability
• inducing angeiogenesis
• resisting cell death
• deregulating cellular energetics
• sustaining proliferative signaling

Question 21

Heritable alterations

Answer 21

Progressive accumulation of genetic and epigenetic abnormalities

• lead to changes in cell growth, death, differentiation, DNA repair
• altered DNA sequences (mutations) passed onto progeny
• karyotype
• chromosome instability
• telomeres (protect cells from DNA damage)

Question 22

Molecular determinants

Answer 22

• driver mutations (oncogenes, tumor suppressor genes)

- multiple changes needed for neoplasia to occur

Question 23

Proto-oncogenes

Answer 23

Normal genes that regulate growth

Question 24

Mutation leads to ______

Answer 24

Overexpression

• is now an oncogene
• cells become less responsive to inhibitory signals

Question 25

Tumor suppressor genes

Answer 25

Genes that control cell cycle, apoptosis, DNA repair | - p53: regulates cell cycle arrest and apoptosis after DNA damage

Question 26

DNA damage ______ p53

Answer 26

Upregulates --> stops and slows down cell cycle

Question 27

p21 is _____

Answer 27

Upregulated = cycle arrest

Question 28

GADD45 directs _____

Answer 28

DNA repair

Question 29

BAX upregulation =

Answer 29

Apoptosis

Question 30

Carcinogenesis - chemicals

Answer 30

- direct: effective in causing damage in the form encountered - indirect: require metabolic activation in the body (cytochrome p450 enzymes in the liver) - ex: bracken fern in cattle

Question 31

Radiation is a complete ______

Answer 31

Carcinogen | - can initiate and promote

Question 32

Virus

Answer 32

Can be oncogenic - feline leukemia (leukemia/lymphoma) - bovine leukemia (leukemia/lymphoma) - feline immunodeficiency (lymphoma) - poxviruses

Question 33

Round cell tumors are a form of ______

Answer 33

Histocytoma - most common skin tumor of dogs (young) - rapid growth, button-like, ulcerated/alopecic - 1-2cm wide - spontaneous regression

Question 34

Round cell tumor histiopathology

Answer 34

Round to oval cells - oval nuclei, fine chromatin - abundant pale blue cytoplasm, few vacuoles - junctional activity/epitheliotropism

Question 35

Origin of round cell tumor

Answer 35

Langerhans dendritic origin

Question 36

Cutaneous lymphoma

Answer 36

Epitheliotropic (mycosis fungoides) and nonepitheliotropic | - B and T cell

Question 37

Lymphoma characteristics

Answer 37

- large cells - abundant cytoplasm - nucleoli visible

Question 38

Plasmacytoma

Answer 38

Benign, older dogs - head, feet - rarely functional - round cells, dense chromatin - 1-3 nuclei - abundant blue cytoplasm, prominent golgi zone

Question 39

Mast cell tumors

Answer 39

Nodules, well circumscribed or poorly defined/edematous - induce fibrosis of the skin - solitary or multiple - potentially malignant - older dogs - dermal (graded) - subcutaneous

Question 40

Mast cell are defined by _____

Answer 40

Metachromatic properties of the granules (eosinophils!)

Question 41

Transmissible venereal tumor of dogs

Answer 41

Direct physical spread/contact - cells in all tumors around the world have similar genetic and cytologic character, differ from the host (dog) - single tumor that disseminated to multiple hosts