Neoplasia- Dr Llanes Flashcards
Neoplasia
the process of tumor formation
Neoplasm
“New Growth” - occurs when genetic changes allow cells to “ignore” growth mediators and expand indefinitely.
Oncology
Study of tumors
2 components of a neoplasm
- Parenchyma
2. Stroma
Pre-neoplastic changes
- hyperplasia
- metaplasia
- dysplasia
Meaning of the suffix “oma”
benign
Meaning of suffix “sarcoma”
malignant
Mesnchymal tumor origin
mesoderm
Epithelial tumor origins
- endoderm
- ectoderm
Benign epithelial tumors
- papilloma
- polyp
Malignant epithelial tumor
-carcinoma
Tumor that comes form multiple cells types
Mixed tumor
Teratoma
a tumor that is derived from all embryonic cell layers and arises from totipotent germ cells
4 factors that differentiate benign vs. malignant tumors
- Differentiation/anaplasia
- Growth rate
- Local invasion
- Presence/absence of metastasis
This refers to the extent that parenchymal tumor cells resemble normal parenchymal cells in morphology and function.
Differentiation/anaplasia
T/F Benign tumors are not very well-differentiated.
False. They are well-differentiated
Malignant tumors that are undifferentiated are considered________.
anaplastic
T/F Neoplasms can only be malignant if they are not well-differentiated.
False. Malignant tumors (neoplasms) can be either well or undifferentiated.
Anaplasia is characterized by what 4 things?
- pleomorphism
- abnormal nuclear morphology
- high mitotic rate
- loss of polarity
Anaplasia is sometimes understood as a reversal of differentiation to a more primitive level. What is a more appropriate way to look at anaplasia?
anaplastic cells arising from less differentiated cells such as totipotent cells
What are the 2 main mechanisms that regulate tissue growth?
- Rate of cell proliferation
2. rate of apoptosis
What is the key reason the local invasion of tumor cells is an indicator of malignancy?
it refers to the degree of damage to surrounding tissues caused by a neoplasm
Metastases
neoplastic areas that are not continuous with the primary tumor
Do benign tumors undergo metastasis?
No, metastasis is an indicator of malignancy
What are 3 pathways by which malignant tumors spread?
- Transcolemic
- Lymphatic
- Hematogenous
What process causes the breakdown of the basement membrane and the extracellular matrix during the spread of tumors?
Metastatic cascade
When is hetergeneity generated in tumor cells and what does it result in?
- during tumor growth
- subclones and successful subclones
High proliferative rate, immune response evasion, development of independent blood supply, independence from exogenous growth factors, and the ability to spread to distant sites are all characteristics of what cells?
Successful subclones
Gastric carcinomas arising from the esophageal region of the gastric mucosa are common in what species?
Equine
Mucous secreting neoplastic epithelial cells are histologically characterized by what?
Bluish, foamy cytoplasm
What 3 things add up to give us the phenotype of a particular cancer?
- DNA mutations
- Epigenetic changes
- Chromosomal alterations
Epigenetic changes
heritable changes in gene expression not due to change in DNA sequence.
Common epigenetic changes
- DNA methylation
- histone modification
T/F Tumors are polyclonal.
False. Tumors arise from a single precursor cells that has been damaged (Monoclonal)
4 main classes of normal regulatory genes that play a significant role in carcinogenesis when damaged.
- growth-promoting proto-oncogenes
- growth inhibiting suppressor genes
- apoptosis regulating genes
- DNA repair genes
Why is it that cancer is a relatively rare occurrence despite the abundance of environmental carcinogens?
Because of the ability of normal cells to repair damaged DNA.
Which tumor suppressor gene can be called the “Guardian of the Genome”?
p53 gene
3 effects of p53 activation and DNA binding
- CDK inhibition (p21)
- DNA repair (GADD45)
- Apoptosis (BAX)
8 changes in cell physiology that determine malignant phenotype of cancer.
- self-sufficiency in growth signals
- insensitivity to growth inhibitory signals
- evasion of apoptosis
- defects in DNA repair
- limitless replicative potential
- sustained angiogenesis
- ability to invade and metastasize
- ability to escape from immunity and rejection
What is the strongest argument for the presence of immune survillience of tumors?
The increased incidence of cancer in immuno-suppressed individuals.
What cells are the major immune defense against tumors?
CD8+ cytotoxic T lymphocytes
_________ and ________ cells also play a role in immune surveillance of tumor cells.
natural killer cells and macrophages
Macrophages are strongly activated by _______ released by NK cells and T-cells.
IFN-gamma
3 mechanisms of tumor evasion of immune system
- variant of tumor cell without antigen
- deficiency of MHC Class I
- Immunosuppressive protein production
Macro-environmental (extrinsic) etiologies
- UV light
- Ionizing radiation
- chemicals
- oncoviruses
Micro-environmental (intrinsic) etiologies
- inherited genes
- byproducts of metabolism
T/F Benign tumors doe not cause morbidity or mortality.
False. Any tumor can cause disease or death.
Paraneoplastic syndromes
Indirect effects of tumor cells products other the those caused directly by the tumor and its spread.
What is the loss of body fat and lean tissue along with weakness, anorexia and anemia?
Cancer cachexia
Factors involved with pathogenesis of cancer cachexia
- TNF
- IL-1
- IL-6
- IFN-gamma
- Prostaglandins
- PIF
Examples of paraneoplastic syndromes in domestic animals
- Cachexia
- Hypercalcemia of malignancy
- Hypoglycemia
- Thrombotic disease
- Peripheral neuropathy
- Nodular dermatofibrosis
- Hypertrophic osteoarthropathy
What paraneoplastic syndrome is most commonly observed and what species is it primarily found in?
Hypercalcemia of malignancy, canine
Hypercalcemia of malignancy is cause by the production by neoplastic cells of a protein that is related to which organ?
Parathyroid
T/F hypercalcemia caused by osteolysis by skeletal metastases is not a paraneoplastic syndrome.
True
T/F hypercalcemia caused by osteolysis by skeletal metastases is not a paraneoplastic syndrome.
True
Clinical signs of Hypercalcemia
- Muscle weakness
- cardiac arrhythmia
- anorexia
- vomiting
- renal failure
- Pu/Pd (remember this from Physio)
Hyperparathyroidism, renal failure, hypoadrenocorticism, and hypervitaminosis D are all considered what in relation to neoplasia?
Causes that should be considered and ruled out.
What species and breed of said species is nodular dermatofibrosis most commonly associated with.
Canine, German Shepherd
T/F Dogs with nodular dermatofibrosis develop multiple benign cutaneous lesions that are almost always associated with underlying bilateral renal disease.
True
Advantages of immunohistochemistry in diagnosis
- Categorization of undifferentiated malignant tumors
- categorization of leukemias and lymphomas
- determination of metastisis
- determination of prognosis
range of cancer grading scale
1-4
TNM system for staging a tumor
T- size of primary neoplasm (T0-T4)
N- extent of lymphatic spread (N0-N3)
M- presence of hematogenous metastses (M0-M2)
T/F Clinically grading is more useful than staging.
False. Staging is more useful.
