neoplasia

• 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)

suffix "-oma"

suffix "-sarcoma"

•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)

• 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

•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

•Increased cellularity


•Necrosis 1. Indicates high rate of growth. 2. Often secondary to lack of adequate blood supply

•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

• tumor staging
• tumor grade
• systemic features

• 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

• 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

• 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

• 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

• •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

• retinoblastoma (Rb) protein
• •Hypophosphorylated Rb blocks expression of pro-proliferation genes

•Hyperphosphorylated Rb allows expression of pro-proliferation genes

• •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

• 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

• 1. lunch and bronchus cancer
• 2. prostate cancer
• 3. colon and rectum cancer

• 1. lung and bronchus cancer
• 2. breast cancer
• 3. colon and rectum cancer

• increases
• age

• Gender
• Age
• type of malignancy
• geographic
• environmental factors/ chemical carcinogenesis
• heredity

• 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

• Overall: lung and bronchus
• <20: Leukemia
• 20-39: Leukemia
• 40-59: Lung and bronchus
• 60-79: lung and bronchus
• >80: Lung and bronchus

• Overall: lung and bronchus
• <20: Leukemia
• 20-39: Breast
• 40-59: Breast
• 60-79: Lung and bronchus
• >80: Lung and bronchus

initiators and promers.

• electrophilic agents that cause permanent, non-lethal DNA damage.
• are mutagens

• Direct - acting initiators: do not have to be metabolized before they are mutagenic.
• Indirect-acting agents: must be metabolized before they are mutagenic

tumor suppressor genes, apoptosis genes, and proto-oncogenes.

• 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

• 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

• 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

• 1. Autosomal dominant syndromes associated with altered control of cellular proliferation.
• 2. autosomal recessive syndromes associated with defective DNA repair.

• 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

• 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

• 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

a beign tumor of glands

For epithelial neoplasms

• an epithelial malignancy of glandular origin
• ex. colonic adenocarcinoma

for malignancies of mesenchymal tissues

a malignancy resembling embryonic cells

• 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

• 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

• 1. initial abnormalities allows for acquistion of additional mutations
• 2. aggregate effect of multiple mutations produces true malignant phenotype

G0/G1 to S phase transition.