What are the characteristics of benign neoplasms?
- slow growth
- well differentiated
- not invasive
- no metastases
- generally not lethal but because of where they are located, can't get in there to change it (in heart)
what denotes benign mesenchymal neoplasm?
what suffix denotes malignant mesenchymal neoplasm?
What are the nomenclature exceptions?
•Lymphoma: Malignant tumor of lymphocytes
•Melanoma: Malignant tumor of melanocytes
•Glioma: Malignant tumor of glial cells
•Hepatoma: Malignant tumor of liver cells (hepatocellular carcinoma preferred name)
- •Teratoma: Benign tumor (usually) derived from germ cells with multiple
- cell types (ecto-, meso- and/or endoderm)
What makes a malignant tumors?
- altered growht kinetics
- 1. rapid growth from unregulated growth factor singaling which varies from tumor to tumor (even for the same type)
- 2. autonomous growth which is not dependent on external stimulus with unregulated growth factor signalling
what is the cytologic features of malignant tumors?
•Anaplasia: 1. Generally refers to nuclear atypia with enlarged nuclei, increased nuclear to cytoplasmic ratio, irregular nuclei and prominent nucleoli. 2. Variable degree (well vs. poorly differentiated)
•Hyperchromasia – Dark chromatin
•High mitotic rate
•Necrosis 1. Indicates high rate of growth. 2. Often secondary to lack of adequate blood supply
What is the behavioral features of malignant tumors?
•Stromal invasion. 1. Carcinomas grow through basement membrane 2. Malignancies elicit stromal desmoplasia 3. Malignancies not encapsulated like benign tumors
•Metastases 1. Defining feature of malignant tumors 2. Spread via blood or lymphatic vessels
- •Seeding 1. Chunks of tumor seed themselves on surfaces of open cavities2. Example: Ovarian
- cancer seeding peritoneum
What are the clinical characterization of neoplasia?
- tumor staging
- tumor grade
- systemic features
What is the tumor staging?
- determination of the size of tumor, extent of local spread, whether or not and to where metastases occur -> prognostic info to determine appropriate therapeutic options and pt counseling
- Is tumor confined to mucosa (carcinoma in situ) or has it invaded beyond basement membrane
- TNM system helps calculate the stage
Describe the TNM system.
- T = how big, extent
- N = lymnph node metastasis
- M = metastases to other organs
- Stage is determined by how bx is for specific tumor type with given TNM classification
- stage is best predictor for how far the disease is
What is tumor grade?
- it's a good indicator but not as good as stage. subjective measure
- helps predict aggressivenss of tumor
- Degree of differentiation – Poorly differentiated tumor more aggressive than well differentiated tumor
- Tumor proliferation rate – Immunostains for proliferation markers or assessment of mitotic rate can also help predict aggressiveness
What is the systemic features of clinical charac of neoplasia?
- Often underlie lethal effects of cancer
- •Mass (local) effects –
- Compression/obstruction; Hemorrhage; Infection
•Cachexia – Decreased appetite; Increased metabolism (TNFa, IL-1)
•Paraneoplastic syndromes – Distant effects not associated with metastases 1. Hormonal or other factor production by tumor cells 2. Characteristic associations: a. Lung cancer and finger clubbing b. Neuropathy and small cell cancer
What is the genetic basis of neoplastic disease?
- •Transformation: Non-lethal mutation gives a cell ability to proliferate and pass mutation on to progeny (clonal expansion)
- •Mutations affect cellularprocesses that contribute to the development of cancer 1. Uncontrolled proliferation 2. Abnormal DNA repair 3. Other (numerous)
- •Multistep theory of carcinogenesis: Accumulation of additional mutations allow for the development of malignant characteristics
what is the central gatekeeper/nexus in cell cycle progression?
- retinoblastoma (Rb) protein
- •Hypophosphorylated Rb blocks expression of pro-proliferation genes
•Hyperphosphorylated Rb allows expression of pro-proliferation genes
what are the classes of factors that can cause cellular transformation?
- •Growth factors and their downstream mediators for the family
- of proto-oncogenes: go from G1 to s phase
- •P53, TGF-beta and many other factors act as tumor suppressors
- •Apoptosis (programmed cell death) removes cells from the viable pool in appropriate situations and may also lead to transformation if factors that promote or inhibit this pathway are mutated producing altered activity
What is the epidemiologic trends in neoplasia?
- gender differences: differ for men vs. women in some types of cancer
- age: cancer increases with age for most types, but different types represent highest mortality in different age groups
What are the top 3 cancer killers in men? (in 2002)
- 1. lunch and bronchus cancer
- 2. prostate cancer
- 3. colon and rectum cancer
What are the top 3 cancer killers in women? (2002)
- 1. lung and bronchus cancer
- 2. breast cancer
- 3. colon and rectum cancer
Cancer mortality increases or decrease dramatically with age. Type of cancer that pppl get is to some extent _____-dependent.
What are the factors for mortality in neoplasm?
- type of malignancy
- environmental factors/ chemical carcinogenesis
Describe how geographic factors work.
- ex. increased incidenc of skin cancer in areas of high sun exposure
- ex. increased incidence of stoamch cancer in certain Asian populations that are likely related to diet
For male, what are the leading cancer for age <20, 20-39, 40-59, 60-79, and older than 80?
- Overall: lung and bronchus
- <20: Leukemia
- 20-39: Leukemia
- 40-59: Lung and bronchus
- 60-79: lung and bronchus
- >80: Lung and bronchus
For female, what are the leading cancer for age <20, 20-39, 40-59, 60-79, and older than 80?
- Overall: lung and bronchus
- <20: Leukemia
- 20-39: Breast
- 40-59: Breast
- 60-79: Lung and bronchus
- >80: Lung and bronchus
What are the 2 broad categories of chemicals?
initiators and promers.
What does chemical initiators do?
- electrophilic agents that cause permanent, non-lethal DNA damage.
- are mutagens
What are the 2 subgroups of initiators?
- Direct - acting initiators: do not have to be metabolized before they are mutagenic.
- Indirect-acting agents: must be metabolized before they are mutagenic
The mutations caused by initiators presumably involve what?
tumor suppressor genes, apoptosis genes, and proto-oncogenes.
What are promoters?
- Promoters do not cause DNA damage, and their effect is reversible.
- Function - provide growth stimulus so that clonal expansion occurs
- provides the opportunity for more mutations to occur so that the fully malignant phenotype may be realized
Do promoters work by itself? If not, with what and how?
- No, most requires both promoters and initiators
- initiators must be applied before the promoter and the promoter must be applied at certain times after the initiator
Besides, promoters and initiators, what are other important cancer-causing agents?
- a. ionizing radiation and UV rays (UVB particularly)
- b. Viruses associated with human malignancy.
- 1. human papillomavirus
- 2. epstein-barr virus
- 3. hepatitis B and Hepatitis C virus
- 4. human T-cell leukemia virus
How are predisposition to cancer inherited?
- 1. Autosomal dominant syndromes associated with altered control of cellular proliferation.
- 2. autosomal recessive syndromes associated with defective DNA repair.
Inherited cancers are characterized by what 2 things?
- 1. higher incidence of tuor type in affected individuals as compared to the general population.
- 2. development of cancer at an earlier age than that associated with the sporadic incidnece of the tumor.
- a decrease in the size of a tissue/organ due either to a decrease in cell size or cell number.
- often reversible
- ex. decrease in skeletal muscle mass due to disuse.
- an increase in the size of a tissue/organ due to an increas in cell size
- ex. increase in the size of the left ventricle of the heart due to hypertension
- an increas in the size of a tissue due to increas in cell #
- ex. increas in the number of glands ad stroma in the prostates of older men
- abnormality of cellular differntiation in which one type of matures ell type is replaced by anotehr type
- ex. reaplacement of respiratory epithelium by squamous epithelium in the lungs of cigarette smokers
- abnormalities of cellular differntiation that may be pre-neoplastic
- characteristics: abnormal morphology including disordered maturation and cytologic aypia
- these cells have acuired some, but not all of the mutations required for autonomous growth
- abnormalities of cels that indicate malignancy.
- abnormalities - more severe manifestations of changes seen in dysplastic cells such as increased nuclear to cytoplasmic ratio, and nucelear hyperchromatism
- may also assume gian forms, possess bizarre mitotic figures, and suffer such a loss in organization ability that the benign counterpart of the cell cannot be ascertained
- more anaplastic the cells of a particular malignancy are, the more poorly differentiated the malignancy is
- use interchangeably with neolasm
- swelling of any type
- abnormal mass of cells that exhibits uncontrolled proliferation and persists after cessation of the stimulus producing it
- most are irreversible
- some show some degree of growth autonomy
Define germline mutation.
- mutations that are transmitted to progeny by either the parental or maternal genetic aterial at fertilization
- every cell in progeny will carry the mutated gene
Define somatic mutation.
- acquired mutation generally resulting from some type of environmental exposure
- muation occurs in a single cell w/in an organism that can then become a precursor of cancer
- ex. oncogene mutation producing clone of cells w/ increased proliferative capacity
What is adenoma?
a beign tumor of glands
When do you use the word carcinoma?
For epithelial neoplasms
what is adenocarcinoma?
- an epithelial malignancy of glandular origin
- ex. colonic adenocarcinoma
When you do use the word sarcoma?
for malignancies of mesenchymal tissues
What is blastoma?
a malignancy resembling embryonic cells
Describe the transformation theory as genetic basis of neoplastic disease.
- initated by non-lethal damage to genome, not repaired, and get passed on
- genetic damage can come about through the action of several different agents
- agents - radiation, chemicals, viruses
- genetic abnormalities that predispose to malignancy may be inherited
Describe the non-lethal genetic mutations theory of the genetic basis of neoplastic disease.
- non-lethal genetic mutations affect a variety of processes that contribute to neoplasia
- mutations (germline or somatic) affect important cellular processes such as control of proliferation...
- uncontrolled proliferation
- abnormal DNA repair
- tumor progression - additional abnormalities are acquired thus leading to establishment of malignant clone of cells from precursor dysplastic lesions
Describe the multistep theory of carcinogenesis.
- 1. initial abnormalities allows for acquistion of additional mutations
- 2. aggregate effect of multiple mutations produces true malignant phenotype
Retinoblastoma proteins controls what step in the cell cycle?
G0/G1 to S phase transition.