Chapter 19 Goals Page 799 Students will be able to:

Chapter 19 Goals Page 799 Students will be able to:
Identify medical terms that describe the growth & spread of tumors. Recognize terms related to the causes, diagnosis, & treatment of cancer Review how tumors are classified & described by pathologists. Describe x-ray studies, laboratory tests, & other procedures used by physicians for determining the presence & extent of spread (staging) of tumors. Apply your new knowledge to understanding medical terms in their proper contexts, such as medical reports & records.

Cancer Medicine (Oncology)
Chapter 19 Pages 799 – 848

Introduction Cancer = disease caused by abnormal & excessive cell growth. It may arise in any tissue & appear at any time of life, although it occurs most frequently in older people. More than ½ of all patients who develop cancer are cured. About 550,000 people die of cancer each year. Most common causes of cancer death: women: Lung, followed by breast & colorectal cancers men: lung, colorectal, & prostate cancers Malignant tumors compress, invade, & ultimately destroy the surrounding tissue. In addition to local growth, cancerous cells spread throughout the body by way of the bloodstream or lymphatic vessels. In some patients, the spread of caners from the site of origin to distant organs occurs early in the course of tumor growth & ultimately results in death.

Characteristics of Tumors
Page 800 Characteristics of Tumors Tumors are new growths that arise from normal tissue. They may be either malignant or benign. There are several differences between these two tumors. Some of these differences are: Benign tumors grow slowly, & malignant tumor cells multiply rapidly. Benign tumors are often encapsulated, so that the tumor cells do not invade the surrounding tissue. Malignant tumors characteristically are invasive & infiltrative, extending into neighboring normal tissue. Tumors = neoplasms malignant = capable of invasion & spread of surrounding or more distant sites benign = noninvasive & not spreading to other sites encapsulated = contained within a fibrous capsule or cover

Characteristics of Tumors: Cont.
Pages 800 – 801 Characteristics of Tumors: Cont. Benign tumors are composed of organized & differentiated cells that closely resemble the normal, mature tissue from which they are derived. Malignant tumors are composed of cancerous cells that resemble primitive cells & lack the capacity to perform mature cell functions. This characteristic of malignant tumors is called anaplasia. Cells from benign tumors do not metastasize to form secondary tumor masses in distant places in the body. Cells from malignant tumors do. The secondary growth is called a metastasis. Differentiated = specialized undifferentiated = reverting to a less specialized state hyperchromatic = stain excessively with dyes that recognize genetic material, DNA metastasize = spread

Carcinogenesis Page 802 What Causes Cancer?
The causes of transformation from a normal cell to a cancerous one are only partly understood. What is clear is that malignant transformation results from damage to the DNA of the cell. In order to understand what causes cancer, it is necessary to learn more about DNA & its functions in a normal cell. DNA (deoxyribonucleic acid) = genetic material (is a string of coded nucleotides)

Carcinogenesis: Cont. Pages 802 – 803
DNA has two main functions in a normal cell. To control cell division When a cell divides, the DNA in each chromosome copies itself so that exactly the same DNA is passed on to two new daughter cells. To control the protein synthesis Each gene contains the code for making a single protein. That protein carries out an important specific function in the cell. Central Dogma: Transcription (DNA → RNA) & Translation (RNA → Protein). DNA (deoxyribonucleic acid) = genetic material (is a string of coded nucleotides) Strands of DNA in the cell nucleus form chromosomes, which become readily visible under a microscope when a cell is preparing to divide into two (daughter) cells. cell division = the production of new cells. The process of cell division mentioned here is called mitosis. nucleotides = containing a sugar, phosphate, & a base, such as adenine, guanine, thymine, or cytosine protein synthesis = the production of new proteins in the cell. specific proteins (such as hormones & enzymes) Gene = DNA piece - There are 20,000 to 25,000 human protein-coding genes. Genes are composed of an arrangement of units called nucleotides. DNA sends a molecular message outside the nucleus to the cytoplasm of the cell, directing the synthesis of specific proteins essential for normal cell function & growth. RNA = ribonucleic acid

Carcinogenesis: Cont. Page 803
When a cell becomes malignant the processes of mitosis & protein synthesis are disrupted. Cancer cells reproduce almost continuously, & abnormal proteins are made. Malignant cells are anaplastic. Various kinds of damage to DNA result in malignancy. The damage may be caused by toxic chemicals, sunlight, tobacco smoke, & viruses. It usually involves changes in the cell’s DNA codes, creating abnormal genes call mutations. Mutations interfere with the accurate synthesis of new proteins & can be passed on to new cells during cell division. Anaplastic = their DNA stops making normal codes that allow cells to carry on the function of differentiating mature cells. Instead, new signals lead to malignant growth & spread of tumor cells.

Although most DNA mutations lead to higher- than-normal rates of growth, some mutations found in cancer cells actually prevent the cells from dying. In recent years, scientists have recognized that in some types of cancers, the normal blueprints that direct aging or damaged cells to die are missing. Normal cells undergo apoptosis. Some cancer cells have lost elements of this program & thus can live indefinitely. Normal cells undergo apoptosis = spontaneous disintegration or programed cell death.

Carcinogenesis: Cont. Page 803 Environmental Agents
Carcinogens = environmental agents that can damage DNA (producing cancer). Examples of carcinogens: Chemicals (hydrocarbons, insecticides, dyes, industrial chemicals, asbestos as in insulation, & hormones) can cause cancer Radiation (Sunlight, x-rays, radioactive substances) can damage DNA & lead to cancer Viruses can damage DNA causing mutations which lead to cancer. Carcinogens examples: chemicals, drugs, tobacco smoke, radiation, & viruses Chemicals - hydrocarbons are in cigarette, cigar, & pipe smoke & automobile exhaust. Hormones such as estrogens can cause cancer by stimulating growth of cells in the lining of the uterus or in milk glands of the breast Radiation = consists of waves of energy. Leukemia used to be an occupational hazard of radiologists, who were routinely exposed to x-rays. There is a high incidence of leukemia & other cancers among survivors of atomic bomb explosions, as at Hiroshima & Nagasaki. Ultraviolet radiation in sunlight can cause skin cancer, especially in persons with fair skin. Viruses. The human T cell leukemia virus (HTLV1) causes a form of leukemia in adults, herpes virus type 8 causes Kaposi sarcoma, human papillomavirus (HPV) causes cervical cancer & hepatitis B & C viruses cause liver cancer.

Carcinogenesis: Cont. Page 804 Oncogenes
Oncogenes are pieces of normal DNA that when activated by a mutation, can convert a normal cell to a cancerous cell. Some examples of oncogenes are ras (colon cancer), myc (lymphoma), & abl (chronic myeloid leukemia or CML). In chronic myeloid leukemia, the oncogene abl is activated when pieces from two different chromosomes switch locations. This mutation is called a translocation. What happens is that the oncogene abl on chromosome 9 moves to a new location next to a gene called bcr on chromosome 22. When bcr (breakpoint cluster region) & abl are near each other, they cause the production of an abnormal protein that makes the leukocyte divide & cause a malignancy CML. The new chromosome formed from the translocation is called the Philadelphia chromosome (it was discovered in 1970 in Philadelphia).

Carcinogenesis: Cont. Pages 804 – 805 Heredity
Cancer also may be caused by transmission from parents to offspring through defects in the DNA of the egg or sperm cells. Although most caners result from chance mutations in body cells during a lifetime, examples of known inherited cancers are retinoblastoma, adenomatous polyposis coli syndrome, & certain forms of colon, breast, & kidney cancer. retinoblastoma (tumor of the retina of the eye) adenomatous polyposis coli syndrome (premalignant polyps that grow in the colon & rectum)

In many cases, it is believed that these tumors arise because of inherited or acquired abnormalities in certain genes called suppressor genes. In normal persons, these suppressor genes regulate growth, promote differentiation, & suppress oncogenes from causing cancer. Loss of a normal suppressor gene takes the brake off the process of cell division & leads to cancer. Examples of suppressor genes are the retinoblastoma (Rb) type 1 gene (Rb1) & the TP53gene, which leads to brain tumors or breast cancer. Because inherited changes can be detected by analyzing DNA in any tissue of the body, not simply cancerous cells, blood cells from family members may be tested to determine whether a person has inherited the cancer-causing gene. This is known as genetic screening. Affected patients may be watched carefully to detect tumors at an early stage or elect to have prophylactic removal of organs or tissue that may become cancerous.

Classification of Cancerous Tumors
Page 805 Classification of Cancerous Tumors Almost one half of all cancer death are caused by malignancies that originate in lung, breast, or colon; however, in all there are more than 100 distinct types of cancer, each having a unique set of symptoms & requiring a specific type of therapy. It is possible to divide these types of cancer into three broad groups on the basis of histogenesis – that is, by identifying the particular type of tissue from which the tumor cells arise. These major groups are carcinomas, sarcomas, & mixed-tissue tumors.

Classification of Cancerous Tumors: Cont.
Page 806 Classification of Cancerous Tumors: Cont. Carcinomas – Approx. 90% of all malignancies Carcinomas, the largest group, are solid tumors that are derived from epithelial tissue that lines external & internal body surfaces, including skin, glands, & digestive, urinary, & reproductive organs. Benign tumors of epithelial origin are usually designated by the term adenoma, which indicates that the tumor is of epithelial or glandular origin. Malignant tumors of epithelial original are named by using the term carcinoma & adding the type of tissue in which the tumor occurs. Benign = For example, a gastric adenoma is a benign tumor of the glandular epithelial cells lining the stomach. Malignant = Thus, a gastric adenocarcinoma is a cancerous tumor arising from glandular cells lining the stomach.

Page 807 Classification of Cancerous Tumors: Cont. Sarcomas – malignant tumors but less common than carcinomas They derive from connective tissues in the body, such as bone, fat, muscle, cartilage, & bone marrow & from cells of the lymphatic system. Benign tumors of connective tissue origin are named by adding the suffix –oma to the type of tissue in which the tumor occurs. Malignant tumors of connective tissue origin are frequently named using the term sarcoma. Mesodermal = middle Benign = For example, a benign tumor of bone is called an osteoma. Malignant = For example, an osteosarcoma is a malignant tumor of the bone. Often, the term mesenchymal tissue is used to describe embryonic connective tissue from which sarcomas are derived. The mesodermal layer of the embryo gives rise to the connective tissues of the body as well as to blood & lymphatic vessels

Page 808 Classification of Cancerous Tumors: Cont. Mixed-Tissue Tumors Mixed-tissue tumors are derived from tissue that is capable of differentiating into both epithelial & connective tissue. These uncommon tumors are thus composed of several different types of cells Examples of mixed-tissue tumors are found in the kidney, ovaries, & testes.

Pathologic Descriptions
Pages 808 – 809 Pathologic Descriptions Gross Descriptions cystic Forming large open spaces filled with fluid fungating Mushrooming pattern of growth in which tumor cells pile one on top of another & project from a tissue surface inflammatory Having the features of inflammation - that is, redness, swelling, & heat medullary Large, soft, fleshy tumors necrotic Containing dead tissue

Pathologic Descriptions: Cont.
Page 809 Pathologic Descriptions: Cont. Gross Descriptions polypoid Growths that form projections extending outward from a base ulcerating Characterized by an open, exposed surface resulting from the death of overlaying tissue verrucous Resembling a wart-like growth

Pages 809 – 810 Pathologic Descriptions: Cont. Microscopic Descriptions alveolar Tumor cells form patterns resembling small sacs carcinoma in situ Referring to localized tumor cells that have not invaded adjacent structures diffuse Spreading evenly throughout the affected tissue dysplastic Containing abnormal-appearing cells that are not clearly cancerous epidermoid Resembling squamous epithelial cells follicular Forming small glandular sacs

Page 810 Pathologic Descriptions: Cont. Microscopic Descriptions papillary Forming small, finger-like or nipple-like projections of cells pleomorphic Composed of a variety of types of cells scirrhous Densely packed tumors, due to dense bands of fibrous tissue undifferentiated Lacking microscopic structures typical of normal mature cells

Grading & Staging Systems
Page 811 Grading & Staging Systems In grading & staging systems, doctors classify tumors on the basis of microscopic appearance (grade) & the extent of spread (stage). These two properties influence the diagnosis, treatment, & prognosis for cancer patient.

Grading & Staging Systems: Cont.
Page 811 Grading & Staging Systems: Cont. Grading Grading often is of value in determining the prognosis for certain types of cancers, such as cancer of the urinary bladder, prostate gland, & ovary & brain tumors. Patients with grade I tumors have a high survival rate, & patient with grade II, III, & IV tumors have an increasingly poorer survival rate. Grading also is used in evaluating cells obtained from body fluids in preventive screening tests, such as Pap smears of the uterine cervix. Pap smears = Papanicolaou When grading a tumor, the pathologist is concerned with the microscopic appearance of the tumor cells, specifically with their degree of maturity & differentiation. Often, three or four grades are used. Grade I tumors are very well differentiated, so that they closely resemble normal cells. Grade IV tumors are so undifferentiated or anaplastic that even recognition of the tumor’s tissue of origin may be difficult. Grade II & III are intermediate in appearance, moderately or poorly differentiated, as opposed to well differentiated (grade I) & undifferentiated (grade IV).

Page 811 Grading & Staging Systems: Cont. Staging The staging of cancerous tumors is based on the extent of spread of the tumor. It relies on careful definition of the size & possible metastatic spread of the tumor, using computed tomography (CT), combination position emission tomography (PET-CT), & magnetic resonance imaging (MRI) scans & radionuclide (radioactive) bone scans. An example of staging system is the tumor-node-metastasis (TNM) International Staging System. It has been applied to malignancies such as lung & breast cancer, as well as to many other tumors.

Page 811 Grading & Staging Systems: Cont. Notations in a staging system are: T = tumor (size & degree of local extension) N = nodes (number of regional lymph nodes invaded by tumor cells) M = metastases (spread of tumor cells to distant sites) Stage groupings I-IV indicate tumor progression. Thus a stage II group may be designated as T2, N1, M0. Stage IV group indicates any T, any N, & distant metastases.

Cancer Treatment Major approaches to cancer treatment are surgery, radiation therapy, chemotherapy, molecularly targeted therapy, & immunotherapy. Each modality (method) may be used alone, but often they are used together in combined-modality regimens to improve the overall diagnosis & treatment result.

Cancer Treatment: Cont.
Page 812 Cancer Treatment: Cont. Surgery In many patients with cancer, the tumor is discovered before it has spread, & it may be cured by surgical excision. In patients who have metastases, surgical removal of the primary tumor prevents local spread or complications, even in the presence of distant disease. After removal of the primary tumor, the patient often receives adjuvant (assisting) radiation therapy &/or chemotherapy to prevent recurrence at local & distant sites. Some common cancers in which surgery may be curative are those of the stomach, breast, colon, lung, & uterus. A debulking procedure may be used to remove as much of the primary tumor mass as possible, even if the tumor is attached to a vital organ & cannot be completely removed.

Page 812 Cancer Treatment: Cont. cauterization Destruction of tissue by burning core needle biopsy Placement of a large-bore needle that extracts a thin core of tissue cryosurgery Use of subfreezing temperature to destroy tissue en bloc resection Tumor is removed along with a large area of surrounding tissue containing lymph nodes. excisional biopsy Removal of tumor & a margin of normal tissue

Page 812 Cancer Treatment: Cont. exenteration Wide resection involving removal of the tumor, its organ of origin, & all surrounding tissue in the body space. fine needle aspiration Placement of a very thin needle inside the tumor mass & extracting cells for microscopic evaluation fulguration Destruction of tissue by electric sparks generated by a high-frequency current incisional biopsy Piece of tumor is removed for examination to establish a diagnosis

Page 812 Cancer Treatment: Cont. Radiation Therapy (Radiation Oncology) The goal of radiation therapy (RT) is to deliver a maximal dose of ionizing radiation to the tumor tissue & a minimal dose to the surrounding normal tissue. High-dose irradiation destroys tumor cells & produces damage to DNA. Newer techniques of irradiation use high-energy beams of protons to improve the uniformity of dose & to limit damage to normal tissues. protons (subatomic particles) uniformity (conformality) High-dose irradiation (exposure of tissue to radiation)

Page 813 Cancer Treatment: Cont. brachytherapy Implantation of small, sealed containers or seeds of radioactive material directly into the tumor; or in a cavity of the tumor. electron beams Low-energy beams for treatment of skin or surface tumors external beam irradiation Radiation therapy applied to a tumor from a distant source fields Dimensions of the size of radiation area used to treat a tumor from a specific angle teletherapy

Page 813 Cancer Treatment: Cont. fractionation A method of dividing radiation into small, repeated doses rather than fewer large doses. gray (Gy) Unit of absorbed radiation dose linear accelerator Large electronic device that produces high-energy x-ray beams for the treatment of deep-seated tumors. photon therapy Radiation therapy using x-rays or gamma rays

Page 814 Cancer Treatment: Cont. proton therapy Small subatomic positively charged particles produced by a cyclotron deposit all the energy at a focused finite point. radiocurable tumor Tumor that can be completely eradicated by radiation therapy radioresistant tumor Tumor that requires large doses of radiation to produce death of the cells radiosensitizer Drugs that increase the sensitivity of tumors to x-rays

Page 814 Cancer Treatment: Cont. radiosensitive tumor Tumor in which irradiation can cause that death of cells without serious damage to surrounding tissue simulation An imaging study performed before radiation therapy using CT scan &/or MRI to map the area to receive treatment. stereotactic radiosurgery Single large dose of radiation is delivered under precise three-dimensional guidance from multiple angles to destroy vascular abnormalities & small brain tumors.

Page 816 Cancer Treatment: Cont. Chemotherapy Cancer chemotherapy is the treatment of cancer using chemical. It is the standard treatment for many types of cancer, & is curative in a number of them, such as testicular cancer, acute lymphocytic leukemia, & Hodgkin lymphoma, & large cell lymphomas. Chemotherapy may be used alone or in combination with surgery & irradiation to improve cure rates. Apoptosis = self-destruction

Pages 816 – 817 Cancer Treatment: Cont. Drugs cause tumor cells to die by damaging their DNA. Tumor cells with damage DNA undergo apoptosis. This means that they have less capacity to repair their DNA &, in general are less able to survive DNA damage caused by drugs & radiation. The ideal is to administer drugs that kill large numbers of tumor cells without harming normal cells. However, rapidly dividing normal cells, such as in the bone marrow & gastrointestinal lining, can suffer considerable damage from chemotherapeutic drugs. Apoptosis = self-destruction

Page 816 Cancer Treatment: Cont. Research physicians measure drug levels & disappearance from the bloodstream & tissues. They use information from animal experiments & clinical trails to design better routes & schedules of administration to achieve the greatest tumor kill with the least toxicity to normal cells. Combination chemotherapy is the use of two or more drugs together to kill tumors. Apoptosis = self-destruction Drugs are given according to a written protocol, or plan, that details the route, schedule, & frequency of doses. Usually, drug therapy is continued until the patient achieves a complete remission (absence of all signs of disease). Adjuvant chemotherapy is the administration of drug treatment after surgery to kill any residual cancer cells. Neoadjuvant chemotherapy is administrated before surgery to reduce the size of a tumor, such as breast or head & neck cancer. Neoadjuvant drug treatment allows for a lesser surgery & improvement of outcome.

Page 817 Cancer Treatment: Cont. categories of cancer chemotherapeutic agents Alkylating agents These drugs cause crosslinks & breaks in DNA that interfere with cell division Antibiotics These drugs are produced by bacteria or fungi & inhibit cell division by causing breaks in DNA strands. Antimetabolites These drugs blocks synthesis of DNA components & prevent cells from dividing

Page 817 Cancer Treatment: Cont. categories of cancer chemotherapeutic agents Antimitotics These chemcials block the function of a protein that is necessary for mitosis. Hormonal agents These drugs block hormone receptors on cells so that growth is inhibited

Page 819 Cancer Treatment: Cont. Muscularly Targeted Therapy Molecularly targeted cancer therapy uses drugs to attack specific mutations that drive cancer growth. When these targets are blocked by drugs, the cancer cells dies. Some of the targets are absolutely unique to tumor cells & not found in normal tissues. Thus, in contrast with chemotherapy, blocking these targets will have little or no effect on normal cells. Chemotherapeutic drugs normally are delivered by intravenous infusions, whereas molecularly targeted drugs often are given orally, in pill form.

Page 819 Cancer Treatment: Cont. Immunotherapy Immunotherapy is the use of immune cells or antibodies, to kill tumors. Examples: T cells that have been modified in a laboratory to recognize & destroy a patient’s own tumor. This therapy is effective against ALL & CLL. Herceptin blocks a receptor & destroys a growth factor on the surface of breast cancer cells. Nivolumb works by blocking a protein on tumor cells. It is effective against melanoma, lung cancer, bladder cancer, kidney cancer, & Hodgkin lymphoma. acute lymphoid leukemia (ALL) chronic lymphoid leukemia (CLL) An antibody that will attack a target on the tumor cell surface.

Laboratory Tests cytogentic analysis Chromosomes of normal or tumor cells are examined for breaks immunohistochemistry Localization of antigens or proteins in tissues using labeled (colored or fluorescent) antibodies. protein marker tests Measures the level of proteins in the blood or on the surface of tumor cells

Clinical Procedures Pages 826 – 827
bone marrow biopsy Aspiration of bone marrow tissue & examination under a microscope for evidence of malignant cells bone marrow or stem cell transplantation Bone marrow or stem cells are infused intravenously into a patient core needle biopsy Insertion of a large-bore needle into tissue to remove a core of cells for microscopic examination exfoliative cytology Cells are scraped from the region of suspected disease & examined under a microscope CT (computed tomography) PET (positron emission tomography) Radioactive substances (radionuclides) scans (images)

Clinical Procedures: Cont.
Pages 827 – 828 Clinical Procedures: Cont. fiber-optic colonoscopy Visual examination of the colon using a fiber-optic instrument laparoscopy Visual examination of the abdominal cavity using small incisions & a laparoscope mammography X-ray examination of the breast to detect breast cancer PET-CT Scan Diagnostic procedure combining CT & PET radionuclide scans Radioactive substances are injected intravenously, & scans of organs are obtained. CT (computed tomography) PET (positron emission tomography) Radioactive substances (radionuclides) scans (images)

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