37 Neoplasias – Learning Objectives
Zoë Soon
Learning Outcomes and Specific Learning Objectives Study Guide
Learning Outcomes:
By the end of this section you will be able to:
Describe key aspects of Neoplasms including:
- Benign and Malignant tumors
- Common tumors and cancers: e.g. cervical cancer, skin cancer, ovarian cancer, breast cancer, prostate cancer, and benign prostate hypertrophy
- Aspects of etiology, risk factors, pathogenesis, and treatment options
Specific Learning Objectives – Study Guide:
By the end of this section you will be able to:
Describe and explain the following terms:
- Cell Type: there are over 200 different cell types in the human body, each expressing unique proteins and having unique structure that allow it to fulfill its functions and role in the human body.
- Tissue Types: There are 4 categories of tissue types, each one containing different types of cells and having different physical and functional properties:
- Epithelial tissue (e.g. dermis, endothelial tissue, mucosa membranes of GI tract and respiratory tract, apical layer of serous membranes, and synovial membranes)
- Connective tissue (areolar, adipose, reticular, dense regular, dense irregular, elastic, hyaline cartilage, elastic cartilage, fibrocartilage, bone, blood, and lymph fluid)
- Muscle tissue (skeletal muscle, cardiac muscle, and smooth muscle)
- Nervous tissue (neurons and neuroglial cells)
- Cell Division/Cell Multiplication/Proliferation – the process of mitosis
- Cell Cycle – the stages of cell division which most often involves an immature cell or stem cell dividing into two genetically identical cells. Cell Cycling includes:
- G1 phase – cell functions normally, but grows, duplicating organelles and synthesizing proteins; lasts 8+ hours
- S phase – duplication of DNA and centrioles; synthesis of histones; lasts 8+ hours
- G2 phase – growth and protein synthesis; lasts 2-5hrs
- Mitosis – Prophase, Metaphase, Anaphase, Telophase
- Cytokinesis – pinching of cell membrane into two daughter cells
- Go phase – cells exit cell cycle and mature/differentiate to become fully functional cells that no longer go through cell cycling.
- Cell Differentiation
- DNA duplication: performed by DNA polymerase with assistance of DNA helicase & DNA ligase as well as enzymes that check for duplication errors and induce apoptosis if the errors can not be fixed. DNA duplication errors may lead to mutations that give rise to non-functional enzymes that compromise the cell’s ability to survive/function. Mutations can also give rise to cells that are cancerous.
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Telomeres: are the end caps of chromosomes that are added by telomerase until adulthood, at which time, telomerase is inactivated, and telomeres become shorter with each round of cell division. Once telomeres have shortened to a certain length, the cell becomes dormant and dies. This is thought to help old/worn out/less-functional cells be eliminated. Additionally, each round of cell division, is susceptible to DNA errors which make cells more and more at risk for developing a mutation that makes the cell cancerous.
- Telomerase re-activation: has occurred in 90% of all cancers. In these cancerous cells the telomeres do not shorten and apoptosis is not triggered, making these cells immortal.
By the end of this section you will be able to list:
Cancers with Highest Incidence Rates in Canada:
- Skin Cancer
- Breast Cancer
- Prostate Cancer
- Lung and Bronchus
- Colon and Rectum
Cancers with Highest Mortality Rates in Canada:.
- Lung and Bronchus
- Breast
- Prostate
- Colon and Rectum
- Pancreas
- Ovary
- Leukemia
By the end of this section you will be able to:
Describe and explain the following terms:
- Carcinogens: factors, chemicals, etc. that increase risk of DNA mutations that put cells more susceptible to becoming cancerous.
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- Cigarette smoking – increases risk of developing all cancers (not just lung cancer)
- Cancer = a group of almost 100 genetic diseases (genetic = gene mutation ≠ not necessarily inherited). In cancer:
- Cell growth (mitosis) becomes uncontrolled either because:
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- Cell Cycle Regulator genes (coding for growth factors and growth inhibiting factors) that control the rate of mitosis have been mutated or
- Apoptosis Regulator genes (controlling the rate of apoptosis) have been mutated
- DNA mutation can be caused by:
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- Viruses
- Radiation (UV, x-ray, gamma rays)
- Chemicals (e.g. nickel, asbestos, benzene solvents, aniline dyes, rubber, formaldehyde, chemotherapy drugs)
- Spontaneous errors during normal DNA synthesis
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- Rapid rates of mitosis during injury repair may increase the risk of errors occurring.
- Mutations in genes that are in sperm or oocytes that are then passed to offspring can mean that cancers can at times be inherited
- The above 4 factors (viruses, chemicals, radiation, spontaneous) are thought to be involved in mutating or changing the expression levels of specific genes, such as:
- >40 Proto-oncogenes: genes that stimulate cell division & inhibit both cell differentiation & death – when these proto-oncogenes mutate they are typically a dominant mutation and are then called Oncogenes. Oncogenes stimulate increased cell division, and decrease cell differentiation & death
- Tumor suppressor genes (TSG): genes that normally slow down cell division, and promote apoptosis; when these genes mutate & are turned off; cells can become immortal → cancer (e.g.TSG p53 is essential for regulating DNA repair and cell division, it has been nicknamed the “guardian of the genome); most cancers have a p53 mutation. BRCA1 and BRCA2 are TSGs
- Stability Genes: that normally repair DNA and other genes that control the rate of mutation. These genes do not have a direct impact on rate of mitosis or apoptosis. (FYI: 30-50% cancers have p53 mutation)
- Describe Types of DNA mutations:
- Synonymous – no change, codes for same amino acid sequence
- Non-synonymous – change, codes for different same amino acid sequence
- Insertion – results in frame shift if in coding region of DNA
- Substitution – may result in amino acid substitution if in coding region of DNA
- Deletion – results in frame shift if in coding region of DNA
- Describe Possible Effects of DNA mutation:
- No effect, as mutation is in non-coding region
- No effect, on the amino acid sequence (as each amino acid is coded for by 2-4 different codons, e.g. GAA and GAG both code for the amino acid Glutamine)
- Production of Dysfunctional Protein/Enzyme
- Increased/decreased production of protein/enzyme
- Describe Properties of Neoplasm or tumor = new growth
- Cellular growth that no longer responds to normal genetic controls
- Cell continues to reproduce, without the need for them to reproduce
- Increase in number of cells that are immature and cell cycling
- Deprives other cells of nutrition… decreasing their function/abilities
- Neoplasms may consist of atypical or immature cells.
- In a young healthy person, usually abnormal or cancerous cells will be recognized by the immune system and destroyed. However, at times, cancerous cells evade the immune system.
Describe Characteristics of each tumor, which depend on:
1. Type of cell from which the tumor arises
2. Unique structure and growth pattern
- Benign tumors: not considered cancer; slow-growing;
- composed of differentiated cells growing faster than normal;
- are often encapsulated; and are freely moveable on palpation;
- don’t metastasize; and once removed usually doesn’t recur;
- any tissue damage results from compression on adjacent structures (e.g. blood vessels); can be fatal in the brain (due to ↑ICP, intracranial pressure)
- have tissue name plus the suffix -oma (e.g., adenoma) – exceptions! Glioma, Lymphoma….
- effects are more often local rather than systemic
- Malignant tumors (cancers): invade surrounding tissues and are characterized by
- atypical, immature, undifferentiated, nonfunctional dysplastic cells
- rapid reproduction; no cell-cell contact inhibition; lack of apoptosis;
- cancerous cells having abnormal cell membranes; altered surface antigens; and not adhering to each other as normal cells do; so cancerous cells often break loose from mass and invade other tissues; may spread to distant sites via blood or lymph
- often having systemic effects; have the tissue name plus the suffix -carcinoma (e.g., adenocarcinoma); and can recur if removed
- Malignant (cancerous) cells often have an abnormal number of chromosomes = aneuploidy
- Abnormal shaped nuclei = pleomorphism
Describe Types of Cancers: Cancers are named by the cell type that becomes cancerous
- Carcinomas: epithelial cancers; 90% of cancers
- Adenocarcinomas: epithelial cancers in a gland
- Squamous cell carcinoma: epithelial cancers originating in the skin
- Melanomas: epithelial cancers originating in the melanocytes of the skin
- Sarcomas: Tumors of mesenchymal tissue (e.g. bone, muscle, cartilage, blood vessels); usually malignant.
- Osteosarcoma: Cancer of the bone
- Rhabdomyosarcoma: Cancer of the striated muscle
- Chondrosarcoma: Cancer of the cartilage
- Glioma: Cancers of neuroglial cells (e.g. astrocytoma, ependyoma)
- Several malignant tumors have unique names: Hodgkin’s disease, Wilms’ tumor, Leukemia, Lymphoma
Describe Possible Effects of Cancers including:
- Mass compresses blood vessels.
- Leads to necrosis and inflammation around tumor
- Tumor cells may secrete enzymes (e.g. collagenase) or hormones or their own growth factors.
- Break down of proteins and surrounding cells
- Systemic effects, such as altered calcium levels
- Inflammation and loss of normal cells
- Lead to progressive reduction in organ integrity and function
- Angiogenesis: Promoted by growth factors that some tumor cells secrete that stimulate the development of new capillaries in the tumor
- Some new drugs mimic human antiangiogensis factors to block this & starve cancer! – good idea! but…
- Not as effective as hoped, as without blood vessels, chemotherapy drugs can’t get to the cancer
Explain Signs & Symptoms of Cancers:
- Unusual bleeding or discharge
- Diarrhea, Constipation, Dysuria, Frequency
- Change in mole/wart
- Sore that doesn’t heal
- Unexplained weight loss
- Cachexia, Anorexia
- Anemia, persistent fatigue
- Lumps (painless or painful)
- Breathing/swallowing obstructions
- Frequent infections
- Emotional lability
- Paraneoplastic Syndrome: associated with certain tumor types (para = alongside)
- Tumor secretes hormones, or peptides, or cytokines that alter either cellular function of different tissue or alter immune responses
- Common Example: Tumor cells release substances that may have hormonal effects.
Eg. Bronchogenic carcinoma: may produce ACTH (adrenocorticotropic hormone) causing symptoms of Cushing’s Syndrome (a condition in which excessive glucocorticoids (hydrocortisone or cortisol) are produced causing:a) catabolic effects leading to fragile skin, osteoporosis, delayed healing)b) Increased gluconeogenesis & insulin resistance which may cause diabetes mellitus and leads toc) Retention of Na & H2O – leading to hypertension, edema (puffy face & torso), & possibly hypokalemiad) Suppression of the immune responsee) Stimulation of RBC productionf) Emotional lability & euphoria
Explain Spread of malignant tumors:
- Invasion of local tissue (e.g. using lytic enzymes, collagenase)
- Metastasis (spread to distant sites) via blood, lymph, peritoneal cavity fluid etc.
- Seeding
- Role of Sentinel lymph nodes
Explain Diagnostic Tests including:
- Routine Screening (e.g. mammogram, Pap test, Stool test, Colonoscopy, Self-examination)
- Genetic Testing (e.g. BRAC1, BRAC2, Philadelphia chromosome)
- Imaging
- Cytological tests (e.g. biopsy analysis)
- Growth Promoter Sensitivity tests (e.g. estrogen-dependence)
- Blood tests (e.g. levels of hemoglobin, RBCs, WBCs, and tumor markers)
- Tumor markers: elevated levels of proteins – being produced by the cancer (usually fetal in nature – as cells have regressed), for example:
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CEA (carcino-embryonic antigen): colon cancer
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PSA (prostate specific antigen) test: high PSA in prostate cancer
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hCG (human chorionic gonadotropin) test: testicular cancer
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CA125: ovarian cancer
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AFP (alpha-fetoprotein): hepatocellular cancer
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Explain Grading and Staging of Cancers, including:
- Grading Cancer – based on microscopic analysis of how different they look from normal, differentiated cells:
- Grades I-IV:
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Grade I = well-differentiated cells similar to normal cells
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Grade IV = undifferentiated cells (anaplasia); likely will be highly malignant
- TMN Staging of Cancer:
- Size of primary tumor (T)
- Involvement of regional lymph nodes (N)
- Spread (metastasis) of tumor (M)
- Stages 0-4:
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Stage 0 – carcinoma in situ
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Stages I and II – cancer is limited to organ or location where it began or it may have spread to a nearby structure (localized spread)
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Stage III – cancer has spread further into a surrounding structure or regional lymph nodes (regional spread)
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Stage IV – the cancer has spread to a distant site in the body (metastatic spread)
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List risk factors, including:
- high-fat diet, smoked foods → colon cancer
- estrogen → endometrial cancer
- HPV → cervical cancer
- HSVII → cervical cancer
- hepatitis virus → liver cancer
- UV → skin cancer
- gamma radiation → leukemia
- HIV → Kaposi’s sarcoma
- smoke → lung cancer
- air pollution → lung cancer, bladder cancer
- age
- immediate family incidence
- genetic factors
- hormone levels
Define:
- procarcinogens = cause first unrepaired DNA mutation
- promoters = hormones and environmental chemicals that cause further DNA mutations
- oncovirus
- radioresistant
- cancer-free state: generally defined as 5-year survival without recurrence
- some cancers such as childhood leukemias can be considered cured after a 10-year, cancer-free period.
- remission: no clinical signs of cancer
- Explain how carcinogenesis/oncogenesis is multistage
- Explain how the following cancer therapies work:
Describe Treatment Options:
- Surgery
- with or without laparoscopy
- with Radiofrequency Ablation (RFA)
- with use of CT and ultrasound imaging
- Chemotherapy
- antimitotics, antimetabolites
- delivery via: oral, subcutaneous, intravenous, intramuscular, intralesional, intrathecally (subarachnoid), intraperitoneal, intraventricular
- Radiation Therapy
- with use of x-rays, gamma rays (radioactive radium or cobalt, high-energy electrons/protons)
- Cobalt machine
- Brachytherapy
- Radioactive gold salt solutions
- Oral radioactive iodine
- Immunotherapy
- Curative vs. Palliative
- Nutrition, Counselling, Physiotherapy, Speech Therapy, Support
- Other drugs:
- Hormones:
- glucocorticoids (prednisone): ↓ mitosis, ↑ RBC, ↑ appetite, ↓ inflammation around tumor
- sex hormones: estrogens slow prostate cancer; estrogen-blocking agent slow estrogen-dependent breast cancer
- Antibodies: block receptors for growth promoters on cancer cells & target cell for destruction
- Radiolabeled antibodies: specific to cancer cells, bind them & irradiate/destroy targeted cancer cell
- Biological Response Modifiers (BRMs): ↑ natural immune response (e.g. interferons , BCG, Bacillus Calmette-Guerin vaccine – normally used for tuberculosis)
- Angiogenesis inhibitors: inhibits growth of new blood vessels which starves cancer (but also ↓ chemo delivery)
- Analgesics: however, be careful – narcotics *may cause nausea, constipation, drowsiness & respiratory depression; tolerance occurs with long-term use, which can lead to larger & more dangerous doses
- Anti-emetics
- Antibiotics
- Hormones:
Complementary Therapies:
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Massage
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Meditation
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Counseling
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Exercise
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Therapeutic touch
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Explain the adverse effects of radiation & chemotherapy:
The following adverse effects are – due to highly mitotic cells (e.g. epithelial & epithelial glandular cells, endothelial cells, RBCs) being destroyed by chemotherapy/radiation and not able to replace themselves quickly enough
- Bone marrow depression (↓ #WBCs—increase risk of infection; Risk of pneumonia and septicemia; ↓ #RBCs—fatigue, tissue breakdown; ↓ #WBCs—increase risk of infection; Risk of pneumonia and septicemia; ↓ #RBCs—fatigue, tissue breakdown; ↓ #platelets—excessive bleeding; ↓ #platelets—excessive bleeding)Nadir: is point of lowest WBC count which occurs after each chemotherapy treatment (neutropenia, leukopenia)
- Vasculitis (blood vessel inflammation)
- Alopecia (hair loss)
- Xerostomia (dry mouth, reduced mucus production)
- Stomatitis (mouth inflammation) & oral fungal infections (e.g. Candidiasis)
- Dysphagia (difficulty swallowing possibly due to swollen throat)
- Dyspnea (difficulty swallowing possibly due to swollen bronchi/bronchioles)
- Constipation, GI ulcers (reduced mucus production)
- Cystitis – due to irritation/cell damage by radiation/chemotherapy and/or UTI (due to immunosuppression)
- Infertility – due to abdominal radiation
- Adhesions, obstructions – due to scarring and/or constipation
- Immunosuppresion – Increased risk of infections (pneumonia, septicemia) – due to bone marrow depression including neutropenia, and/or malnourishment, and/or cancer-damaged tissue.
Other Negative Side Effects of Chemotherapy and Radiation:
- Bleeding (due to thrombocytopenia or cellular damage)
- Nausea due to chemicals, anxiety, and mucosal inflammation
- Fibrosis (scarring)
- Change in taste sensation
- Anorexia
- Fatigue, lethargy
- Mood depression
- Vomiting and/or diarrhea from treatments
- Sore mouth or loss of teeth
- Pain (due to cellular damage)
- Malabsorption caused by inflammation in the digestive tract
- Permanent damage to organs that do not regenerate (heart, kidneys, lungs, brain etc.)
Describe risk factors, pathogenesis, signs/symptoms, detection, prognosis, treatment of more common neoplasms in Canada:
- Skin cancers (Basal Cell Carcinoma, Squamous Cell Carcinoma, Melanoma)
- Common Risk Factors: UV exposure
- Signs & Symptoms: Moles that get larger in size, have irregular borders and colourations, bleed.
- Pathogenesis: UV causes mutations in genes responsible for regulating appropriate levels of cell cycling and/or apoptosis. Mutated cells become undifferentiated and immortal, continuing to cell cycle producing non-functional cycling daughter cells that accumulate and spread through the body.
- Diagnostic Tools: Visual inspection, biopsy and microscopic analysis
- Treatments: Depends on the extent of metastasis: Surgical removal, chemotherapy, Radiation and other accompanying therapies – see above for list.
- Lung cancer
- Common Risk Factors: exposure to inhaled carcinogens (e.g. smoking, industrial pollutants, asbestos, coal dust)
- Signs & Symptoms: Asymptomatic, coughing, dyspnea, wheezing, hemoptysis
- Pathogenesis: carcinogens causes mutations in genes responsible for regulating appropriate levels of cell cycling and/or apoptosis. Mutated cells become undifferentiated and immortal, continuing to cell cycle producing non-functional cycling daughter cells that accumulate and spread through the body.
- Diagnostic Tools: Imaging (e.g. X-ray, CT scan), biopsy and microscopic analysis
- Treatments: Depends on the extent of metastasis: Surgical removal, Chemotherapy, Radiation, and other accompanying therapies – see above for list.
- Ovarian cancer
- Common Risk Factors: family history (genetic/lifestyle susceptibilities), Breast Cancer 1 or 2 (BRCA1 or BRCA2) mutations, high saturated fat diet, early menarche, late menopause, nonparity,
- Signs & Symptoms: Asymptomatic, abdominal pain, urinary frequency, as metastasis to fallopian tubes, uterus, and intrpaeritoneal organs occu, the following may occur: ascites, intestinal obstruction, nutritional deficiencies, cachexia, fatigue.
- Pathogenesis: mutations in genes responsible for regulating appropriate levels of cell cycling and/or apoptosis. Mutated cells become undifferentiated and immortal, continuing to cell cycle producing non-functional cycling daughter cells that accumulate and spread through the body.
- Diagnostic Tools: Imaging (e.g. transvaginal ultrasound, MRI), genetic testing, biopsy and microscopic analysis
- Treatments: Depends on the extent of metastasis: Surgical removal, Chemotherapy, Radiation and other accompanying therapies – see above for list.
- Brain tumor
- Common Risk Factors: for most common form, gliobastoma = biological sex (males), immunosuppresion, children and adults,
- Signs & Symptoms: headaches, seizure, ataxia, weakness, increased ICP (vomiting, headache), cognitive/behavioural changes, parestehsai, visual/auditory/speech disturbances.
- Pathogenesis: mutations in genes responsible for regulating appropriate levels of cell cycling and/or apoptosis. Mutated cells become undifferentiated and immortal, continuing to cell cycle producing non-functional cycling daughter cells that accumulate and spread through the body.
- Diagnostic Tools: Imaging, reduce ICP (e.g. corticosteroids, diuretics, craniotomy)
- Treatments: Depends on the extent of metastasis: Surgical removal, Chemotherapy, Radiation and other accompanying therapies – see above for list.
- Breast Cancer
- Common Risk Factors: biological sex (female), family history (genetic/lifestyle susceptibility), age>40yr, early menarche, late menopause, nulliparity, obesity (particularly in waist), high-fat diet, alcohol, exposure to toxins (e.g. pesticides), radiation, mutations in BRCA1 or BRCA2, p53
- Signs & Symptoms: painless firm, irregular immovable lump in breast or armpit, dimpling in breast, nipple discharge, inflammation, ulceration. Metatstatic signs & symptoms include: shortness of breath bone pain, abdominal distention, jaundice, cognitive changes, headache
- Pathogenesis: UV causes mutations in genes responsible for regulating appropriate levels of cell cycling and/or apoptosis. Mutated cells become undifferentiated and immortal, continuing to cell cycle producing non-functional cycling daughter cells that accumulate and spread through the body.
- Diagnostic Tools: Imaging (e.g. mammogram=x-ray, ultrasound), biopsy and microscopic analysis
- Treatments: Depends on the extent of metastasis: Surgical removal (Mastectomy), Chemotherapy, Radiation, Hormone Therapy (estrogen or progesterone blockers, if cancer is found to be estrogen or progesterone-dependent, removal of ovaries (hysterectomy) to remove source of endogenous estrogen and progesterone, Human Epidermal Growth Factor Receptor, HER2 blockers if cancer is dependent on HEGF), and other accompanying therapies – see above for list.
- Benign Prostatic Hypertrophy
- Common Risk Factors: age, changes in hormone balance, increased androgens (testosterone), estrogen, family history (genetic/lifestyle susceptibility)
- Signs & Symptoms: Urinary urgency, frequency, nocturia, dysuria, hesitancy, retention, driblling; Ejaculation dysfunction
- Pathogenesis: UV causes mutations in genes responsible for regulating appropriate levels of cell cycling and/or apoptosis. Mutated cells become undifferentiated and immortal, continuing to cell cycle producing non-functional cycling daughter cells that accumulate and spread through the body.
- Diagnostic Tools: Urinalysis (to rule ot UTI or treat accompanying UTI), uroflowmetry, serum marker PSA test, digital rectal exam to feel for enlarged prostate, biopsy and microscopic analysis
- Treatments: Transurethral Incision of the Prostate (TUIP) or other forms of surgery (Transurethral Resection of the Prostate, TURP or prostatectomy).
- Prostate Cancer
- Common Risk Factors: age (due to lifetime exposure to potential carcinogens, plus # of mitotic events increases chances of DNA mutations), viruses, family history (genetic/lifestyle susceptibilities), high-fat diet, smoking, obesity
- Signs & Symptoms: Urine retention, urgency, requency, nocturia, dysuria, hematuria, back pain.
- Pathogenesis: Mutations in genes responsible for regulating appropriate levels of cell cycling and/or apoptosis. Mutated cells become undifferentiated and immortal, continuing to cell cycle producing non-functional cycling daughter cells that accumulate and spread through the body.
- Diagnostic Tools: PSA test, digital rectal exam (feel for hard lumps), transrectal ultrasound and other imaging, biopsy and microscopic anallysis
- Treatments: Depends on the extent of metastasis: Surgical removal, Chemotherapy, Radiation,Hormone Therapy (GnRH agonists, androgen blockers), and other accompanying therapies – see above for list.
