Define neoplasia.
Uncontrolled cell proliferation - even with the removal of the stimulus.
The basis for neoplastic growth is an alteration in the cell’s _________.
genome
What are the two categories of neoplasms?
Benign, malignant
What are the two components of a neoplasm?
- The transformed neoplastic parenchymal cells.
2. The supporting stroma (non-transformed).
What suffix is used to denote a benign tumor?
-oma
Name five examples of benign tumors of mesenchymal origin.
- Lipoma
- Fibroma
- Chondroma
- Angioma
- Leiomyoma
Name four examples of benign tumors of epithelial origin.
- Adenoma
- Papilloma
- Polyp
- Cystadenoma
An adenoma is _____-like or _____-derived.
gland-like or gland-derived
What characterizes a papilloma?
Finger-like projections
What is the definition of a polyp?
Mass projecting from the mucosa into the lumen
What suffix is used to denote a malignant tumor of mesenchymal origin?
-sarcoma (solid) or leukemia/lymphoma (blood mesenchyme)
What suffix is used to denote a malignant tumor of epithelial origin?
-carcinoma
What is an adenocarcinoma?
Malignant tumor of epithelial origin that has glandular patterns
How do mixed tumors form?
Through divergent differentiation from one germ cell layer to form tumor(s) with more than one parenchymal cell type.
What is pleomorphism?
Heterogenous histologic characteristics
What is a teratoma?
Mixed tumors that derive from germ cells - can be made up of more than one germ cell layer.
Is an invasive meningioma malignant or benign?
Malignant
The “foot in the brain” is an example of what?
Teratoma - germ cells growing in the wrong place
What is a choristoma?
Non-neoplastic masses of histologically normal cells found in abnormal locations
What is a hamartoma?
Non-neoplastic masses of disorganized tissue found in the correct location.
What are the four criteria used to distinguish benign vs. malignant neoplasms?
- Malignant change (differentiation characteristics)
- Growth rate
- Local invasion
- Metastasis
The extent to which a transformed parenchymal cell in a tumor resembles comparable normal cells in morphology and function is called __________.
differentiation
Are well-differentiated tumor cells more likely to retain functional capabilities of normal cells?
Yeah
What does anaplastic mean?
Un-differentiated - no morphological features shared with normal counterparts
What is hyperchromasia and what can cause it?
Dark staining nuclei. Caused by increased DNA content and/or chromosomal abnormalities
What is dysplasia?
Disorderly (loss of uniformity and architecture) but non-neoplastic growth, usually in epithelia
What is the term used to describe dysplasia that spans the entire thickness of the epithelium? What is at risk from happening in this case?
Called a carcinoma in situ aka preinvasive neoplasm. At risk of breaking through the basal lamina –> metastasis.
Does dysplasia always progress to cancer?
Nope
Is dysplasia reversible?
Sometimes, if it doesn’t involve the entire thickness of the epithelium
What is mass effect?
When a benign tumor causes pathological defects by pushing on surrounding tissues
Fast-growing tumors are often easier to treat with chemo drugs because they: ______________
have high turnover rates
What is growth fraction?
Percentage of proliferating cells vs. resting cells
What is the smallest clinically detectable mass? How many cell doublings does this require?
1 gram. Requires 30 doublings to make 10^9 cells.
What is the maximal tumor size compatible with life?
1 kg
At what stage (late or early) is a tumor in by the time it is detected clinically?
late
Describe the anatomical differences between benign and malignant tumors.
Benign tumors are well-circumscribed and can be encapsulated. Malignant tumors are poorly circumscribed and do not develop capsules.
What is the most reliable feature that distinguishes malignant from benign tumors?
local invasiveness
What is the most common cause of cancer death?
Metastasis
What are the three methods of metastatic spread?
- Body cavity aka transcelomic spread aka seeding
- Hematogenous spread
- Lymphatic spread
What two types of cancers most often spread by body cavity aka transcelomic spread aka seeding?
Ovarian carcinomas, melanomas
What type of cancer often spreads by hematogenous spread? Name two organs in which cancers spread by this route.
Sarcomas. Lungs and liver are susceptible to hematogenous spread due to their dual blood supply.
What type of cancer often spreads by lymphatic spread?
Carcinomas
What is a sentinel lymph node?
The first node in a regional lymphatic drainage that receives lymph from a primary tumor
Within a tumor there are _____ cells that have the capacity to initiate and sustain the tumor. These cells must be eliminated in order to cure the patient.
stem
What is the difference between incidence and prevalance? Which one indicates the level of burden of a disease on a population?
Incidence is the number of NEW cases per 100,000 people. Prevalence is new + preexisting cases and indicates the level of burden.
What is the predominant cause of the most common sporadic cancers?
Environmental factors
Only _____% of all cancers are thought to be due to genetic predisposition.
5-10%
Name two examples of autosomal dominant inherited cancer syndrome.
- Retinoblastoma
2. Familial adenomatous polyposis
Name two examples of cancer involving defective DNA repair genes.
Hereditary non-polyposis colon cancer (HNPCC) and xeroderma pigmentosum
What is leukoplakia?
Thick white patches on gums or tongue that has an association with cancer
What are the six hallmarks of cancer?
- Evading apoptosis
- Self-sufficiency in growth signals
- Insensitivity to anti-growth signals
- Tissue invasion and metastasis
- Limitless replicative potential
- Sustained angiogenesis
Name the four classes of regulatory genes that, when mutated, can result in tumor formation.
- Growth-promoting proto-oncogenes
- Tumor-suppressor genes
- Apoptosis genes
- DNA repair genes
Do neoplasms have heterogenous cell populations even though they arose from a single progenitor cell?
Yeah
True or false: Neoplastic progression is a result of the accumulation of mutations within a cell population.
True
What is the difference between a proto-oncogene and an oncogene?
Proto-oncogenes are normal genes that function to regulate growth and proliferation. Oncogenes are mutated proto-oncogenes, allowing unregulated cell growth - called “gain of function.”
How many proto-oncogene alleles need to be mutated for autonomous growth to occur?
One
What are the four mechanisms of oncogenes?
- Abnormal growth factor or GF receptor function or expression.
- Signaling molecule gene mutations.
- Abnormal transcription factor activity.
- Cyclin gene mutations (2nd messenger stuff).
How many tumor suppressor alleles must be mutated for autonomous growth to occur? What is this hypothesis called? Name one example.
Two - called Knudson’s two hit hypothesis. E.g. retinoblastoma
CDKN2A, cyclin D, and CDK4 are involved in what cellular process? What is the defect in the RB protein when its mutated?
Involved in RB protein product gene transcription. When RB is hyperphosphorylated it can’t bind to E2F so E2F can push the cell from G1 to S in the cell cycle (G1 checkpoint is disabled).
Which gene is the most commonly mutated gene in cancer (~70%)?
p53
p53 assists in DNA ______ by causing G1 arrest.
repair
How many alleles of p53 need to be mutated for disordered growth to occur?
two
What syndrome is characterized by familial loss of p53?
Li-Fraumeni Syndrome
What is H1F1alpha involved in? What is von-Hippel-Lindau protein (VHL)?
H1F1alpha is involved in hypoxia-induced angiogenesis (important in tumor angiogenesis). VHL is a tumor suppressor that suppresses angiogenesis and when it is mutated can cause a variety of tumors.
