Neoplasia Flashcards
What are disorders of growth due to?
- Abnormalities in regulations of cell size -> reduction in tissue mass
- Cell proliferation -> increases in tissue mass
- Differentiation resulting in abnormality of tissue mass/function/morphological appearance -> changes in tissue mass
What are the 3 types of reduction in tissue mass?
- Agenesis - congenital absence (unilateral renal agenesis)
- Hypoplasia - congenital reduction in size (testes in Klinefeleters)
- Atrophy - shrinkage due to decreased size of cells (disuse)
What are the 3 types of increases in tissue mass?
- Hyperplasia - increase in number of cells
- Hypertrophy of cells - increase in size of cells (permanent cells cannot increase cell number)
- Hypertrophy of parts - increase in size (may be hyperplastic or hypertrophic)
What are the 2 changes in tissue mass?
- Metaplasia - change in type of mature tissue
- Dysplasia - partial transformation to malignancy
What kind of change is columnar epithelium -> stratified squamous in smokers?
Metaplasia (endothelium -> endothelial type of adjacent tissue)
Are metaplasias reversible? Malignant?
- Benign and generally reversible
- Some types carry increased risk of malignancy (may be due to acquired genetic abnormalities, or due to irritant stimuli + tissue damage)
Are dysplasias malignant?
Genetic alteration to cell w/ loss of tumor supressor genes (and/or activation of oncogenes) but NOT sufficient for malignancy
- May occur w/ increase in tissue mass, or may be associated w/ microscopic lesion
What is the extreme end of dysplasia?
Carcinoma in situ
Identify the type of disorder of growth
- Hyperplasia
- Mild dysplasia
- Carcinoma in situ (severe dysplasia)
- Cancer (invasive)
What does neoplasm literally mean?
“New growth”
- Abnormal mass of tissue that results when cells divide more than they should/do not die when they should
- Also called a tumor
Are neoplasms benign or malignant?
May be both
- Benign neoplasia = loss of control -> stable, non-spreading mass
- Malignant neoplasia = more control loss -> expansion, infiltration, metastasis
What is severe displasia?
Flat neoplastic change that is typically precancerous
What is a tumor?
Neoplastic mass of cells (benign/malignant)
What is cancer?
Malignant neoplasm
- Latin “crab” - seize upon adjacent tissues w/ pincher-like outgrowths
- Does not describe biological behavior (slow growing/indolent v. spread rapidly to many parts of body/rapidly cause death)
What are the 2 mechanisms by which cancer is capable of spreading throughout the body?
- Invasion - direct migration/penetration by cancer cells into neighboring tissues
- Metastasis - penetration into lymphatic/blood vessels -> circulate throughout bloodstream -> invade normal tissues elsewhere in body
Who was the 1st to recognize that cancer (and all disease) was a cellular disorder and it could be dx’d at microscopic level based on cellular appearance/arrangement?
Virchow
How are cancer cells clonal?
All cancerous cells in a tumor are derived from a single cell
- Single cell -> cancerous cell occurs in steps w/ each step governed by a mutation
- Several subclones may appear before one that has cancerous characteristics
What are characteristics of a benign neoplasm?
- Well-defined margins of tumor (encapsulated)
- Neoplastic cells grow only locally
- Slow rate of growth, may cease
- Generally have good pronosis (lead only rarely to death)
What are characteristics of a malignant neoplasm?
- Poorly defined margins of tumor (infiltrative)
- Rapid rate of growth, progressive
- Neoplastic cells growing into and destroying surrounding tissue (morbidity)
- Major cause of death (mortality)
What does the incidence of each type of cancer vary according to?
Age, gender, social class, ethnic origin, geographical location
T or F: Most cancers are age related.
T; more yrs of cell divison, cancer evolves slowly due to prolonged exposure to environmental carcinogens
How is cancer distributed between genders?
Cancer used to be more common in females than males (b/c of freq of cervical and breast CA, and rarity of lung cancer) -> now reversed in most countries
- CAs that have higher incidence in females = gall bladder, thyroid, malignant melanoma of skin
What has been found in population studies of cancer incidence?
Cancers arise w/ diff frequencies in diff areas of the world
- Japan = stomach cancer
- US = colon cancer
- Australia = skin
- Japanese fams that move to US -> higher rate of colon cancer/lower rate of stomach cancer (NOT just heredity -> could involve cultural, behavioral, envir factors)
What is a low-strength type of radiation that can cause cancer?
Sunlight (UV radiation)
What is a high-strength form of radiation that can increase rates of cancer?
X-rays or radiation emitted from unstable atoms called radioisotopes
What are chemicals and radiation that are capable of triggering the development of cancer called?
Carcinogens
Why do carcinogens have a “lag time”?
They act through a multistep process that initiates a series of genetic mutations and stimulates cells to proliferate (this requires a prolonged period of time)
- Young ppl exposed to carcinogens from smoking cigarettes generally don’t develop cancer for 20-30 yrs
How do cancer viruses cause cells to become malignant?
Some of the viral genetic info carried in the nuclei acids is inserted into the chromosomes of the infected cell
- Viruses can’t reproduce on their own, they enter into living cells -> infected cell to produce more copies of the virus (in this case more copies of the cancer)
People who develop AIDs after being infected w/ HIV are at high risk for developing what type of cancer?
Kaposi’s sarcoma - malignant tumor of blood vessels located in the skin
- Not directly caused by HIV, but immune deficiency makes people more susceptible to viral infx called KSHV (Kaposi’s sarcoma-associated herpes virus)
What bacteria has been associated w/ the development of cancer?
H. pylori (which causes stomach ulcers) -> increased risk for stomach cancer
What percentage of people w/ no family h/o the disease does cancer occur in?
80-90%
What percentage of breast cancers are thought to be due to a “breast CA susceptibility gene”?
5%
What type of cancer does hereditary retinoblastoma increase the risk for?
Retinoblastoma
What type of cancer does xeroderma pigmentosum increase the risk for?
Skin
What type of cancer does Wilms’ tumor increase the risk for?
Kidney
What type of cancer does Li-Fraumeni syndrome increase the risk for?
Sarcomas, brain, breast, leukemia
What type of cancer does familial adenomatous polyposis increase the risk for?
Colon, rectum
What type of cancer does Paget’s disease of bone increase the risk for?
Bone
What type of cancer does Fanconi’s aplastic anemia increase the risk for?
Leukemia, liver, skin
What is the greatest public health hazard among various factors that cause cancer?
Tobacco
- Contains >24 diff chemicals capable of causing cancer
- 80-90% of lung cancers
The prefix “adeno” means the cancer began its unchecked growth where?
Gland cells
The prefix “chondro” means the cancer began its unchecked growth where?
Cartilage cells
The prefix “erythro” means the cancer began its unchecked growth where?
RBCs
The prefix “hemangio” means the cancer began its unchecked growth where?
Blood vessel cells
The prefix “hepato” means the cancer began its unchecked growth where?
Liver cells
The prefix “lipo-“ means the cancer began its unchecked growth where?
Fat cells
The prefix “lympho” means the cancer began its unchecked growth where?
Lymphocyte cells
The prefix “melano” means the cancer began its unchecked growth where?
Pigment cells
The prefix “myelo” means the cancer began its unchecked growth where?
Bone marrow cells
The prefix “myo” means the cancer began its unchecked growth where?
Muscle cells
The prefix “osteo” means the cancer began its unchecked growth where?
Bone cells
What are the most common types of cancer? Where do they arise?
Carcinomas; from cells that cover external/internal body surfaces
- Lung, breast, colon = most frequent CAs of this type in the US
What cancers arise from cells found in the supporting tissues of the body (bone, cartilage, fat, CT, and muscle)?
Sarcomas
What are cancers that arise in the lymph nodes/tissues of the body’s immune sx called?
Lymphomas
What are cancers of the immature blood cells that grow in the bone marrow and tend to accumulate in large #s in the bloodstream called?
Leukemias
How can malignancy of carcinomas be diagnosed?
Invasion through tissue layers (basement membrane, muscularis mucosae)
How do carcinomas typically spread?
By lymphatics to lymph nodes, then later via blood stream to liver, other viscera and bones
What is the tx for carcinomas?
Surgical resection (response to radiation/chemotherapy varies w/ type)
How do carcinoma cells grow?
As cohesive groups of polygonal cells that may produce keratin (squamous cell) or mucin (adenocarcinoma)
- Cells stain for epithelial cell markers - cytokeratin, epithelial membrane antigen
How do melanocytic tumors spread?
Through lymphatics to regional lymph nodes, and via the bloodstream to a number of sites (skin, brain, viscera - small bowel, spleen)
How are melanocytic tumors treated?
By surgery, w/ radiotherapy and chemotherapy in disseminated cases
How are melanoma cells characterized?
They are round or spindle-shaped w/ nuclear enlargement, pleomorphism + high mitotic activity
- Fine brown melanin may be seen in cytoplasm
Are connective tissue tumors common?
Benign CT tumors are very common particularly (lipomas) while sarcomas are rare (1% of malignant tumors)
Where do sarcomas typically occur? How do they spread?
- In the deep tissues of the limbs/retroperitoneum, less commonly in head/neck/viscera
- Spread through blood stream (lymph node involvment is rare)
How are sarcomas treated?
Resection combined w/ radiation + chemotherapy
How are sarcoma cells characterized?
More cellular than normal CTs -> these cells may be spindle-shaped, round or bizarre and pleomorphic
What are lymphomas?
Common tumors that may also involve extranodal sites (skin, stomach, small intestine)
- NO in-situ/benign phase is recognizable
- Tx: chemotherapy + radiotherapy w/ resection for localized extranodal lymphomas
- Consist of masses of non-cohesive round cells
What is leukemia?
Neoplasms of hematopoietic cells that infiltrate/replace bone marrow
- May arise from extramedullary sites sometimes
- Tx: chemotherapy
What are glial tumors?
Arise from astrocytes, oligodendrocytes and ependymal cells
- Most are diffusely infiltrative, but respond to radiation + chemo
- Prognosis varies according to grade
What is a teratoma?
Overgrowth of very specific cell
What are the 3 kinds of genes that are targets for carcinogenic transformation?
- Proto-oncogenes
- Tumor suppressor genes
- DNA repair genes
What kinds of genes promote cell growth and require the alteration of only 1 allele to create out of control cellular growth (dominant gene)?
Proto-oncogenes
What kinds of genes inhibit cell growth and require alteration of both alleles to affect cell growth (recessive oncogenes)?
Tumor supressor genes
What are genes that code for proteins whose normal function is to correct errors that arise when cells duplicate their DNA prior to cell division?
DNA repair genes
What does tumor progression refer to?
Ability of transformed cells to acquire further abnormal characteristics over time, independent of tumor size
- Includes ability to invade, metastatic spread, further anaplasia
- These characteristics are acquired through mutations within the tumor leading to subgroups of cells w/ varying characteristics
At the time of diagnosis, most tumors are ______ and have multiple cell lines present.
Heterogenous
What may contribute to the increased instability of DNA in tumors?
Absence of p53
- Tumor supressor genes = normal genes whose ABSENCE can lead to cancer
- p53 is a tumor supressor gene that can trigger cell suicide (apoptosis) in cells that have undergone DNA damage
How are proto-oncogenes part of normal cell growth?
GFs bind to receptors on cell surface -> activate signaling ezymes inside the cell -> activate special proteins called transcription factors inside the cell’s nucleus -> “turn on” genes required for cell growth/proliferation
What are 3 ways that proto-oncogenes becomes oncogenes?
- A mutation
- A chromosomal translocation
- An increase in amount of certain proteins (increase protein expression/gene duplication)
What can mutations in DNA repair genes lead to?
Failure in repair -> subsequent mutations accumulate
What gene defect exists in xeroderma pigmentosum?
Infected defect in a DNA repair gene -> cannot effectively repair DNA damage that normally occurs when skin cells are exposed to sunlight -> abnormally high incidence of skin cancer
How does cancer tend to involve multiple mutations?
Mutation inactivates suppressor gene -> cells proliferate -> mutations inactive DNA repair genes -> proto-oncogenes mutate to oncogenes -> more mutations, more genetic instability, metastatic disease
What is peto’s paradox?
Incidence of cancer in organisms does NOT relate to # of cells
- Elephants have 20 copies of TP53 and humans only have 1
What 3 things does tumor invasion require?
- Attachment of cancer cell to basement membrane - laminin receptors and integrins are important (also in migration/adhesion to endothelial cells)
- Proteolysis of basement membrane w/ hydrolytic enzymes
- Migration through the gap into surrounding CTs
What is loss of basement membrane in malignancy due to?
Both a decrease in production of membrane components and an increased degradation by hydrolytic enzymes
What leads to firmness/fixation of a tumor?
Local spread is by direct invasion of surrounding tissues (note that some are more resistant)
What is the process whereby a tumor spreads to distant sites via lymphatic vessels, blood vessels, and through body cavities?
Metastasis
What are the steps of metastasis?
- Invasion of CT matrix (stroma)
- Invasion of blood + lymphatic vessels
- Circulation of tumor cells
- Invasion from blood vessels into tissues
- Angiogenesis
How does cancer change its environment?
- Cancer cell loses receptors that normally respond to neighboring cells that call for growth to stop -> tumors amplify their own supply of growth signals
- Flood their neigbors w/ other signals (cytokines) + enzymes (proteases) -> destroys basement membrane + surrounding matrix
What is lymphatic spread?
- Tumor cells that invade a lymphatic vessel may colonize nearest lymph node -> continue to spread from node to node -> circulation
- Prognosis may depend on lymph node invasion
- Occurs mainly in epithelial malignancies
What is venous spread?
Direct route to distant sites
- Main route of dissemination of sarcomas (lymphatic spread rare)
- Involvement of liver (stomach, large bowel) is due to portal vein
How does cancer spread through body cavities?
- Usually in serosa-lined cavities, but also in the CSF (high grade gliomas)
- Spread through mucose-lined cavities has not been demonstrated
What is spread by implantation?
Iatrogenic spread/implantation facilitated by surgery
What tumors are the lymph nodes metastatic sites for?
Carcinomas, melanoma
What metastatizes in the brain?
Carcinomas, melanoma (perineural spread of prostate cancer)
What metastasizes in the bone?
Cancer of the breast, prostate, kidney, stomach
What metastasizes in the liver?
Abdominal carcinomas, ovarian, breast
What metastasizes in the lung?
Most tumors
What is the tumor grade?
Measure of the rate of tumor growth based on tumor histology
- Provides info regarding likely behavior of a tumor/responsiveness to tx
- Low number grade (grade I or II) = cancers w/ fewer cell abnormalities than those w/ higher numbers (grade III, IV)
What is the tumor stage?
Measure of the extent of the tumor, based on clinical/radiological/pathological features
- How large is the tumor/how deeply has it invaded surrounding tissues
- Have cancer cells spread to regional lymph nodes
- Has the cancer metastasized to other regions of body
What is the clinical stage based on?
Clinical and radiological grounds (before biopsy)
- Key part of deciding the best tx
- Also baseline used for comparison when looking at cancer’s response to tx
What is the pathological stage?
Relies on what is learned about the cancer during surgery
- Often this is surgery to remove the cancer and nearby lymph nodes, but sometimes surgery may be done to just look at how much cancer is in the body and take out tissue samples
What is stage 0?
Carcinoma in situ - early form
- For colorectal cancer: only in the innermost lining of the colon or rectum
What is stage I?
Localized
- In colorectal cancer: cancer has not spread beyond inner wall of colon/rectum
What is stage II?
Early locally advanced
- In colorectal cancer: cancer has spread into the muscle layer of the colon/rectum
What is stage III?
Late locally advanced
- In colorectal cancer: cancer has spread to one + lymph nodes in the area
What is stage IV?
Metastasized
- In colorectal cancer: cancer has spread to other parts of the body, such as liver, lung or bones
- Does NOT depend on how deep the tumor has penetrated or if the disease has spread to the lymph nodes near the tumor
What are signs/sx of cancer?
- Fatigue
- Unexplained weight loss
- Weakness
- Dizziness
- Fever
- Pain
- Skin changes
- Darker looking skin (hyperpigmentation)
- Yellowish skin/eyes (jaundice)
- Reddened skin (erythema)
- Pruritus
- Excessive hair growth
