Chapter 4 Flashcards
What are neoplasms?
Uncontrolled “New growth” of cells that cannot be adequately controlled by normal regulatory mechanisms in the body.
How are human tumors classified?
Autonomous: Growing independently of normal cell growth factors and stimuli.
Excessive: Unceasing growth even in the presence of normal cellular proliferation regulators.
Disorganized: Growth not following the normal rules of tissue formation or organ development.
What are the main differences between benign and malignant tumors?
(Macro, Micro, Cellular differences)
**Benign: **Limited growth potential and good outcomes.
Macro: Clearly demarcated and usually encapsulated. Expansive growth compresses local tissue.
Micro: Differentiated, resemble the tissues from which they arose.
Cellular: Uniform features. Nucleuses might have different shapes but are around the same size. Chromatin evenly distributed.
**Malignant: **Uncontrollable growth that will eventually murder the host.
Macro: Lack capsule or clear demarcation. Invasive growth infiltrates surrounding tissue without sharp borders. Lymphatic invasion.
Micro: Undifferentiated, demonstrate anaplasia, new features not seen in the normal tissue they arose from.
Cellular: Pleomorphism, cells are heterogeneous in size, shape and function. Typically-high nuclear-to-cytoplasmic ration (N/C ratio). Hyperchromatic. Vessel invasion. Internal necrosis. Hemorrhage.
How do tumors metastasize?
- Primary tumor growth: “Normal” cancer growth
- Metastatic clone: Tumor cell becomes capable of metastasis.
- Proliferation of clone: Invades local vessel/Otherwise leaves area
- Transport by circulation (Lymph/Blood/Seeding surfaces in cavity)
- Embolization
- Invasion of tissue around embolization
- Hooray! New tumor!… wait.
List a few benign mesenchymal cells and their malignant equivalents.
Benign:
- Fibroma (Fibroblast)
- Lipoma (Fatty tissue)
- Hemangioma (Endothelial cell of blood vessel)
- Leiomyoma (Smooth muscle)
- Rhabdomyoma (Striated muscle)
- Chondroma (Cartilage)
- Osteoma (Osteoma)
Malignant:
- Fibrosarcoma
- Liposarcoma
- Angiosarcoma
- Etc Just add sarcoma
List a few benign epithelial cells and their malignant equivalents.
Benign:
- Epithelioma/Papilloma (Squamous epithelium)
- Transitional cell papilloma (Transitional epithelium)
- Adenoma (Glandular/ductal epithelium)
- Carcinoid (Neuroendocrine cells)
- Liver cell adenoma
- Renal cell adenoma
Malignant:
- Squamous cell carcinoma
- … add carcinoma.
How do carcinomas differ from sarcomas?
**Carcinoma: **Cancerous epithelial cells
**Sarcoma: **Cancerous cells of the mesenchymal
Lymphoma
Malignant lymphoid tumor
Glioma
Malignant glial cell
Seminoma
Malignant testicular seminferous epithelial cell
Teratoma
“Monster” germ line tumors that create embryonic cells that differentiate into various cell types and tissues. Skin, hair, teeth… your basic Carpenter Thing critter.
Teratoma versus mixed tumor
Mixed tumors only have one epithelial or mesenchymal neoplastic component whereas teratomas tend to have several types of cells.
Typical: Benign salivary gland mixed tumor.
Not typical: Malignant carcinosarcomas in the uterus
Eponymic tumors
Tumors that defy standard schemes and criteria so they get their own fancy names.
Ex.
Hodgkin’s lymphoma of the lymph nodes
Ewing’s sarcoma of the bones
Kaposi’s sarcoma of the skin
Difference between tumor stage and grading?
Staging: Clinically assessing extent of tumor spread. Exam, x-ray, biopsy, surgical exploration.
TNM Staging: T (tumor size), N (Lymph node involvement), M(distant metastases)
Grading: Histological exam
Grade I: Well differentiated
Grade II: Moderately well differentiated
Grade III: Undifferentiated
Both are used to decided prognosis or outcome but staging has the most predictive value. One crappy looking cell does not a death cancer make.
Are there definitive or absolute biochemical differences between normal and neoplastic cells?
No and as such there are no biochemical tests that can positively ID them as such.
What are some biochemical and structural differences between normal and malignant cells?
Pg. 76 for more detail but briefly:
Major differences are all relative and qualitative. Malignant cells are generally somewhat simpler, designed to survive on their own under unfavorable conditions and maybe have such features as:
- Fewer mitochondria
- Intercellular contact sites
- Hyperchromatin
- Free ribosomes
- CEA (tumor antigen)
- AFP (alpha-fetoprotein. Normally only seen in fetal cells)
How do tumor cells grow in vitro?
**Grow autonomously. **
Well and easily because their metabolic needs are much simpler than a normal cell. The only need a basic bath of carbs, proteins, vitamins, and essential minerals.
Tumor cells lack **contact inhibition **and will continues to try and grow despite coming on contact with vessel walls.
They also don’t exhibit anchorage dependent growth or the cell adhesion seen in normal cells.
Many also secrete their own growth hormones: **Autocrine stimulation. **
Most important exogenous and endogenous causes of cancer?
**Exogenous = Cancerogenic factors **
Chemicals/physical agents/Viruses
Endogenous: Residing in the genome of the cell
Confusing bit: **Oncogenes **cause cancer but are identical to exogenous virus genes.
How do we identify causes of cancer?
- Clinical studies
- Epi studies
- Experimental studies
Examples of chemical carcinogens and their mechanism?
Polycyclic aromatic hydrocarbons: From tar/smoke. Mimic structure of sex hormones which can induce tumors in sensitive tissues.
Aromatic amines: From dye and rubber. Excreted in urine = bladder cancer
Nitrosamines: Food additives. Procarcinogen converted by gut bacteria = Intestinal cancer
Steroid hormones: Ovary/adrenal injections. Stimulates endometrium = Endometrial carcinoma
Metals and inorganic compounds: Pesticides/ore. Skin contact/inhalation = skin/nasal cancer
How does UV light cause cancer?
DNA damage
People with xeroderma pigmentosum are extra screwed because they don’t have DNA repair enzymes
Compare oncogenic RNA and DNA viruses.
Acute-transforming RNA viruses:
Transduction: Oncogene exists in host and is incorporated by transcription into RNA viral genome. Virus enters new host cell and transduces oncogene into otherwise healthy cell.
Slow-transforming RNA viruses:
Insertion of RNA promoter gene: Viral promoter integrated into host DNA and activates oncogene in host cell.
DNA Viruses:
Integration: DNA virus genome integrated into host cell, causes host cell to become malignant. (Ex. EBV, HPV, HBV, HTLV-1)
Human DNA viruses linked to cancer?
HPV: HPV type 16 is linked to 60% of cervical carcinoma
EBV: Burkitt’s lymphoma (endemic type, Sub-Saharan African children and nasopharyngeal carcinoma.
HBV: Integrates into the DNA of neoplastic cells, implicated in liver cancer but exact mechanism is unknown (HBV does not have oncogenes).
HTLV-1: Human T-Cell Lymphoma/Leukemia Virus 1. HIV-lite that causes rare adult T-Cell leukemia
How do proto-oncogenese convert into oncogenes?
Proto-oncogenes: Normal genes that can be mutated into an oncogene.
- Point mutation: Single base sub (ex. *ras *gene)
- **Gene amplification: **Increased # of proto-oncogenes until malignant. (neuroblastoma in children)
- **Chromosomal rearrangement: **DNA gets mangled in various ways so that normally distant portions of genome touch each other. Fragment could act as a promoter for a proto-oncogene (Burkitt’s Lymphoma)
- **Insertion of the viral genome: **Typically from slow-transforming viruses, disrupts normal cellular regulation.(HBV)
What are tumor suppresor genes and how do they cause cancer?
Tumor Suppressor Genes: Genes that protect cells from activated or acquired oncogenes.
If they are absent they… fail to suppress the malignancy and you get cancer.
Ex. Rb-1 is a tumor suppressor in the eye (mostly) without it children can develop retinoblastoma.
The role of heredity in cancer
- Lacking a tumor suppressor gene.
Neurofibromatosis type 1 (Most common autosomal dominant disease) results from the lack of a NF1 gene which regulates ras oncogene
Familial adenomatous polyposis coli: Numerous intestinal polyps from childhood. => Wilms’ tumor eventually develops due to lack of WT-1.
- Metabolic errors
Xeroderma pigmentosum: Lack DNA repair enzyme.
Chromosomal fragility syndromes: (Blooms/Fanconi syndrome)
- Polygenic factors
Breast cancer/colon cancer risk is inherited but not necessarily associated with a single gene. Other factors at play.
Describe the immune response to tumors and explain its clinical significance.
If a tumor becomes significantly different than the original cell it will have tumor antigens which triggers the cell mediated response. They may also produce other antigens that can be tested for in the lab.
Ex. CEA normally only fetal intestine cells abnormal in adults
AFP: fetal liver cells
Common warning signs of neoplasia
CAUTION (The book lies and doesn’t have a box for it)
Change in bowel or bladder habits
A sore that does not heal
Unusual bleeding or discharge
Thickening or lump in the breast, testicles, or elsewhere
Indigestion or difficulty swallowing
Obvious change in the size, color, shape, or thickness of a wart, mole, or mouth sore
Nagging cough or hoarseness
Explain the pathogenesis of tumor-induced cachexia and hypercoagulability.
Cachexia = Generalized Weakness
Is a secondary effect of the wasting associated with cancer. Cancer isn’t playing on your team anymore so it consumes resources just like a parasite.
Depending on location, it could also directly interfere with absorption of nutrients. Ex. Trouble swallowing, cancer of intestines, etc.
Hypercoagulability
Tumor degradation products entering into blood stream. Could cause Trousseau’s syndrome aka migratory thrombosis; thrombosis that affects veins sequentially but at random times and order.
Paraneoplastic syndromes
Various endocrine, hematologic, neuromusclar, cardiovascular etc problems are that caused by tumur secretions.
Endocrine: Lung tumor = increased ACTH = hyper stimulation of adrenal gland = Cushing’s syndrome
Neuromuscular: Breast cancer = hypercalcemia
Hematological: Hypercoagulation/Trousseau’s
Risk factors for common cancers
Smoking = Lung
Family history of cancer = Breast
Family history of polyps = Colon
Promiscuity = Cervical
Hormonal imbalance and treatment = Uterus
Sun exposure, fair skin = Skin
Old age = Prostate
What is the difference between incidence and prevalence of cancer?
Incidence = Number of new cases over a specific time and a specific population. Varies geographically, Japan has a lot of gastric cancer.
Prevalence = Number of ALL cases of cancer, new and old within a specific population over a specific time.
The incidence of which cancers and increased and decreased over the last 60 years?
Increased: Lung cancer
Decreased: Gastric cancer
Safeguards against cancer
Most of these are pretty obvious (stop smoking, routine checks) so I’m just going to list the ones with actual treatment guidelines:
Breast: Mammograms starting at age 40.
Colon-rectum: Colorectal testing at age 50
Cervix: Beginning 3 years after becoming sexually activeor no later than age 21. Regular pap = ever 1-2 years. At age 30 = 2-3 years if woman has had 3 normal paps in a row.
Prostate: Beginning at age 50
