Exam 3: Neoplasia Flashcards
What are the 7 steps of the metastasic cascade?
- Clonal expansion
- invaBM
- Intravasation
- Interaction with lymphoid cells
- Tumor cell embolus
- Adheres to BM
- Extravasation
- Angiogenesis
- Growth
Explain Tumor Angiogenesis
When a tumor outgrows its blood supply New vessels form from endothelial cells. The endothelial cells prduce GF which promotes tumor growth
What are the 3 pathways of tumor spreading?
- Transcoelomic (seeding)
- Hematogenous
- Lymphatic
Seeding of body cavities and surfaces
Transccoelomic spread
T/F. Hematogenoou spread usually involves invasion of veins rather than arteries
t
Sarcomas typically involve Which pathway of spread?
Hematogenous
Mesotheliomas and ovarian adenocarcinomas typically follow wich pathway of spread?
Transcoelomic (seeding)
Carcinomas typically follow which pathway of spread
Lymphatic
What is produced by the tumor to promote blood vessel growth
Vascular endothelial GF
In lymphatic spread, When metastasis is found in the _____ you know that the neoplasia is widely systemic
Regional Ln.
If a tumor is spreading via Hematogenous or lymphatic spread, then metastases often arrest where?
i the first capillary bed encountered
If you find bone metastasis what type of tumor are you likely dealing with?
Prostate or mammary
If you have a cat with pulmonary carcinoma, where is metastasis likely?
Digits
What is a tissue that is un-permissive to metastasis
Skeletal m.
Carbohydrates and proteins expressed on tumor cell surfaces
Tumor Antigens
What are the 3 types of Tumor Antigens?
- Cellular products encoded by mutated genes
- Antigens derived from oncogenic viruses
- Embryonic antigens in primitive cells
What is the importance of Tumor antigens
Can be exploited for Dx and therapeutics
Immune system is capable of recognizing self-antigens expressed on tumor cells and attacking these cells
Immunosurveillance
What are the 2 cell types of the innate immune response?
NK cells, Macrophages
What are the cells involved in cell mediated IR?
CD8 T cells
What are the cells involved in Humoral IR
T helper and B cells
___ Ligand stimulates apoptosis of binding T cells
Fas
What are the 3 mechanisms used to alter DNA
- Mutations
- Chromosomal alterations
- Epigenetic changes
What are mutations
change in nucleotide sequence
What are epigenetic changes?
Heritable change in gene expression resulting from something other than change in DNA sequence
What are the 2 sources of Altered DNA?
- Inherited
2. Acquired somatic mutation
How are germline mutations passed to the offspring?
ova or sperm
What are the 3 types of cancer that may be caused by germline mutations
- pediatric cancer
- Familial predispositions
- Individuals with more than 1 type of cancer
Bernese mountain dogs are susceptible to what type of cancer?
- Malignant histiocytosis
German shepherds are susceptible to what type of cancer?
Hemangiosarcoma
Boxers and lg. breed dogs are susceptible to what type of cancer?
Osteosarcoma
Occur in individual cells and their progeny, not passed in germline
Acquired somatic mutations
What are the 4 causes of DNA alteration?
- Spontaneous
- Chemical Carcinogens
- Ionizing radiation
- Oncogenic viruses
What are the two types of radiation
- ionizing
2. Ultraviolet
Examples of ionizing radiation
x-rays, gamma rays
type of radiation with enough energy to eject electrons from molecules
Ionizing
What is the result of ionizing radiation?
DNA strand breakage
What is the most damaging type of UV?
UVB
Type of radiation that forms pyrimidine dimers in DNA which overwhelms the nucleotide excision repair pathway
UV radiation
examples of chemical carcinogens
Bracken fern
Aflotoxin
Cigarette smoke
What is the MOA of chemical carcinogens?
metabolically transformed to become active, usually associated with other cancer predisposing mutations
What are the 3 mechanisms of Chemical carcinogens
- Genotoxic
- Cytotoxic
- Mitogenic
Mech. of Chemical carcinogens that inc. cell proliferation due to cell injury
Cytotoxic
Mech of chemical carcinogens that inc. cell proliferation w/o cell injury
Mitogenic
Mech of chemical carcinogens that directly damages DNA
Genotoxic
Oncogenic viruses frequently affect young/old animals?
young
What are the 3 ways oncogenic viruses interrupt host genes?
- oncogenes
- insertiona mutagenesis
- Immunosuppression
What are the other 2 causes of carcinogenesis
- Hormonal
2. Chronic inflammation
What are the 2 mech. of host damage?
- Direct effects
2. Paraneoplastic syndromes
Tumor necrosis is secondary to what 3 things?
inflammation in tumor
trauma of tumor
tumor out grows blood supply
What is cancer cachexia
many animals with cancer will show wt loss and debilitation
What are the cellular contributing factors to cancer cachexia
TNF IL-1 IL-6 IFN-gamma Prostaglanding PIF
T/F. you can fix cancer cachexia with nutrition supplementation
F
What is the obvious consequence of neoplasms of endocrine organs?
under-produce or over-produce hormones
Ex of Endocrinopathies
Hypercalcemia of malignancy
What is hypertrophic osteopathy
Occurs in dogs and cats
associated with space-occupying thoracic mass
How are cytologic Dx usually performed?
aspirate of mass
Why is cytologic Dx a better choice than histology?
- faster
- cheaper
- less invasive
T/F. Cytologic Dx cannot determine benign vs. malignant
F. can help
What do you do to confirm your cytologic Dx
Histopathology
Subset of mesencymal neoplasms that appear round on cytology
Round cell tumors
What are the what are the 5 diff. types of round cell tumors?
- Plasma Cell tumor
- Histiocytoma
- Mast cell tumor
- Lymphoma
- Transmissible venereal tumor
how do you perform a margin assessment?
delineate surgical margins with ink
What are the 2 pathologic findings when looking at margins
clean vs. dirty
based on presence or absence of tumor cells
T/F. clean margins guarantee complete excision
F
For histopathologic Dx, Biopsies are sampled from a tumor and stained with ___ for histopathologic eval.
HE
What are the 2 types of histopathologic dx?
- Incisional
2. Excision
What is Incisional histopathologic dx?
Dx may effect surgical or medical plan
What is excisional histopathologic Dx?
If the Dx will not affect surgical or medical plan
What are the 4 criteria of malignancy
- Degree of differentiation
- Invasion
- Mitotic rate
- Features of anaplasia (pleomorphism)
What special stain is used to stain mast cell tumors?
Granules stain with toluene blue
Assigned by the pathologist to designate how abnormal the neoplastic cells are
Histopathologic grading
What is the purpose of histopathologic grading?
To predict biologic behavior of neoplasm and inform treatment plan
Histopathologic grading scheme depends on tumor type and may use what 4 things?
- Degree of differentiation
- Miitotic rate
- Amt. of necrosis
- Invasiveness
T/F. Histopathologic grading is the same as staging
F
Uses dye-labelled abs. to detect various proteins expressed on neoplasm
Immunohistochemistry
When is immunohistochemistry used
to improve accuracy of dx in poorly differentiated neoplasms
What type of cancer cells produce vimentin
Sarcomas
What type of cancer cells produce Cytokeratin
Carcinomas
Originated from the expansion of a single transformed cell
Clonal
What type of cancer uses commonly uses clonality assays to detect?
lymphoma
Gives indication of etent of tumor growth and spread
Clinical staging
What 4 things are commonly used in clinical staging of tumors?
- size of primary tumor
- depth of invasion
- involvement of regional ln
- Extent of distant metastasis
