| Cancer Classification and external resources |
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| When normal cells are damaged beyond repair, they are eliminated by apoptosis (A). Cancer cells avoid apoptosis and continue to multiply in an unregulated manner (B). | |
| DiseasesDB | 28843 |
| MedlinePlus | 001289 |
| MeSH | D009369 |
Contents |
Classification
Cancer is generally classified according to the tissue from which the cancerous cells originate, the primary tumor, as well as the normal cell type they most resemble. These are location and histology, respectively.
Nomenclature
The following closely related terms may be used to designate abnormal growths:
- Tumor or tumour: originally, it meant any abnormal swelling, lump or mass. In current English, however, the word tumor has become synonymous with neoplasm, specifically solid neoplasm. Note that some neoplasms, such as leukemia, do not form tumors.
- Neoplasm: the scientific term to describe an abnormal proliferation of genetically altered cells. Neoplasms can be benign or malignant:
- Malignant neoplasm or malignant tumor: synonymous with cancer.
- Benign neoplasm or benign tumor: a tumor (solid neoplasm) that stops growing by itself, does not invade other tissues and does not form metastases.
- Invasive tumor is another synonym of cancer. The name refers to invasion of surrounding tissues.
- Pre-malignancy, pre-cancer or non-invasive tumor: A neoplasm that is not invasive but has the potential to progress to cancer (become invasive) if left untreated. These lesions are, in order of increasing potential for cancer, atypia, dysplasia and carcinoma in situ.
The following terms can be used to describe a cancer:
- Screening: a test done on healthy people to detect tumors before they become apparent. A mammogram is a screening test.
- Diagnosis: the confirmation of the cancerous nature of a lump. This usually requires a biopsy or removal of the tumor by surgery, followed by examination by a pathologist.
- Surgical excision: the removal of a tumor by a surgeon.
- Surgical margins: the evaluation by a pathologist of the edges of the tissue removed by the surgeon to determine if the tumor was removed completely ("negative margins") or if tumor was left behind ("positive margins").
- Grade: a number (usually on a scale of 3) established by a pathologist to describe the degree of resemblance of the tumor to the surrounding benign tissue.
- Stage: a number (usually on a scale of 4) established by the oncologist to describe the degree of invasion of the body by the tumor.
- Recurrence: new tumors that appear at the site of the original tumor after surgery.
- Metastasis: new tumors that appear far from the original tumor.
- Transformation: the concept that a low-grade tumor transforms to a high-grade tumor over time. Example: Richter's transformation.
- Chemotherapy: treatment with drugs.
- Radiation therapy: treatment with radiations.
- Adjuvant therapy: treatment, either chemotherapy or radiation therapy, given after surgery to kill the remaining cancer cells.
- Prognosis: the probability of cure after the therapy. It is usually expressed as a probability of survival five years after diagnosis. Alternatively, it can be expressed as the number of years when 50% of the patients are still alive. Both numbers are derived from statistics accumulated with hundreds of similar patients to give a Kaplan-Meier curve.
Cancers are classified by the type of cell that resembles the tumor and, therefore, the tissue presumed to be the origin of the tumor. Examples of general categories include:
- Carcinoma: Malignant tumors derived from epithelial cells. This group represents the most common cancers, including the common forms of breast, prostate, lung and colon cancer.
- Sarcoma: Malignant tumors derived from connective tissue, or mesenchymal cells.
- Lymphoma and leukemia: Malignancies derived from hematopoietic (blood-forming) cells
- Germ cell tumor: Tumors derived from totipotent cells. In adults most often found in the testicle and ovary; in fetuses, babies, and young children most often found on the body midline, particularly at the tip of the tailbone; in horses most often found at the poll (base of the skull).
- Blastic tumor or blastoma: A tumor (usually malignant) which resembles an immature or embryonic tissue. Many of these tumors are most common in children.
Malignant tumors (cancers) are usually named using -carcinoma, -sarcoma or -blastoma as a suffix, with the Latin or Greek word for the organ of origin as the root. For instance, a cancer of the liver is called hepatocarcinoma; a cancer of the fat cells is called liposarcoma. For common cancers, the English organ name is used. For instance, the most common type of breast cancer is called ductal carcinoma of the breast or mammary ductal carcinoma. Here, the adjective ductal refers to the appearance of the cancer under the microscope, resembling normal breast ducts.
Benign tumors (which are not cancers) are named using -oma as a suffix with the organ name as the root. For instance, a benign tumor of the smooth muscle of the uterus is called leiomyoma (the common name of this frequent tumor is fibroid). Unfortunately, some cancers also use the -oma suffix, examples being melanoma and seminoma.
Adult cancers
In the U.S. and other developed countries, cancer is presently responsible for about 25% of all deaths.[4] On a yearly basis, 0.5% of the population is diagnosed with cancer. The statistics below are for adults in the United States, and may vary substantially in other countries:
| Male | Female | |||
|---|---|---|---|---|
| most common (by occurrence) | most common (by mortality)[4] | most common (by occurrence) | most common (by mortality)[4] | |
| prostate cancer (33%) | lung cancer (31%) | breast cancer (32%) | lung cancer (27%) | |
| lung cancer (13%) | prostate cancer (10%) | lung cancer (12%) | breast cancer (15%) | |
| colorectal cancer (10%) | colorectal cancer (10%) | colorectal cancer (11%) | colorectal cancer (10%) | |
| bladder cancer (7%) | pancreatic cancer (5%) | endometrial cancer (6%) | ovarian cancer (6%) | |
| cutaneous melanoma (5%) | leukemia (4%) | non-Hodgkin lymphoma (4%) | pancreatic cancer (6%) | |
Child cancers
Cancer can also occur in young children and adolescents, but it is rare (about 150 cases per million yearly in the US). Statistics from the SEER program of the US NCI demonstrate that childhood cancers increased 19% between 1975 and 1990, mainly due to an increased incidence in acute leukemia. Since 1990, incidence rates have decreased.[5]
Children living near nuclear facilities face an increased risk of cancer.[6]
Infant cancers
The age of peak incidence of cancer in children occurs during the first year of life, in infants. The average annual incidence in the United States, 1975-1995, was 233 per million infants.[5] Several estimates of incidence exist. According to SEER,[5] in the United States:
- Neuroblastoma comprised 28% of infant cancer cases and was the most common malignancy among these young children (65 per million infants).
- The leukemias as a group (41 per million infants) represented the next most common type of cancer, comprising 17% of all cases.
- Central nervous system malignancies comprised 13% of infant cancer, with an average annual incidence rate of nearly 30 per million infants.
- The average annual incidence rates for malignant germ cell and malignant soft tissue tumors were essentially the same at 15 per million infants. Each comprised about 6% of infant cancer.
According to another study:[4]
- Leukemia (usually ALL) is the most common infant malignancy (30%), followed by the central nervous system cancers and neuroblastoma. The remainder consists of Wilms' tumor, lymphomas, rhabdomyosarcoma (arising from muscle), retinoblastoma, osteosarcoma and Ewing's sarcoma.
Teratoma (a germ cell tumor) often is cited as the most common tumor in this age group, but most teratomas are surgically removed while still benign, hence not necessarily cancer. Prior to the widespread routine use of prenatal ultrasound examinations, the incidence of sacrococcygeal teratomas diagnosed at birth was 25 to 29 per million births.
Female and male infants have essentially the same overall cancer incidence rates, a notable difference compared to older children.
White infants have higher cancer rates than black infants. Leukemias accounted for a substantial proportion of this difference: the average annual rate for white infants (48.7 per million) was 66% higher than for black infants (29.4 per million).[5]
Relative survival for infants is very good for neuroblastoma, Wilms' tumor and retinoblastoma, and fairly good (80%) for leukemia, but not for most other types of cancer.
Signs and symptoms
Roughly, cancer symptoms can be divided into three groups:
- Local symptoms: unusual lumps or swelling (tumor), hemorrhage (bleeding), pain and/or ulceration. Compression of surrounding tissues may cause symptoms such as jaundice (yellowing the eyes and skin).
- Symptoms of metastasis (spreading): enlarged lymph nodes, cough and hemoptysis, hepatomegaly (enlarged liver), bone pain, fracture of affected bones and neurological symptoms. Although advanced cancer may cause pain, it is often not the first symptom.
- Systemic symptoms: weight loss, poor appetite, fatigue and cachexia (wasting), excessive sweating (night sweats), anemia and specific paraneoplastic phenomena, i.e. specific conditions that are due to an active cancer, such as thrombosis or hormonal changes.
Every symptom in the above list can be caused by a variety of conditions (a list of which is referred to as the differential diagnosis). Cancer may be a common or uncommon cause of each item.
Diagnosis
Most cancers are initially recognized either because signs or symptoms appear or through screening. Neither of these lead to a definitive diagnosis, which usually requires the opinion of a pathologist, a type of physician (medical doctor) who specializes in the diagnosis of cancer and other diseases.
Investigation
People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, CT scans and endoscopy.
Biopsy
A cancer may be suspected for a variety of reasons, but the definitive diagnosis of most malignancies must be confirmed by histological examination of the cancerous cells by a pathologist. Tissue can be obtained from a biopsy or surgery. Many biopsies (such as those of the skin, breast or liver) can be done in a doctor's office. Biopsies of other organs are performed under anesthesia and require surgery in an operating room.
The tissue diagnosis given by the pathologist indicates the type of cell that is proliferating, its histological grade and other features of the tumor. Together, this information is useful to evaluate the prognosis of this patient and to choose the best treatment. Cytogenetics and immunohistochemistry are other types of testing that the pathologist may perform on the tissue specimen. These tests may provide information about future behavior of the cancer (prognosis) and best treatment.
Treatment
Cancer can be treated by surgery, chemotherapy, radiation therapy, immunotherapy, monoclonal antibody therapy or other methods. The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient (performance status). A number of experimental cancer treatments are also under development.
Complete removal of the cancer without damage to the rest of the body is the goal of treatment. Sometimes this can be accomplished by surgery, but the propensity of cancers to invade adjacent tissue or to spread to distant sites by microscopic metastasis often limits its effectiveness. The effectiveness of chemotherapy is often limited by toxicity to other tissues in the body. Radiation can also cause damage to normal tissue.
Because "cancer" refers to a class of diseases, it is unlikely that there will ever be a single "cure for cancer" any more than there will be a single treatment for all infectious diseases.
Surgery
In theory, non-hematological cancers can be cured if entirely removed by surgery, but this is not always possible. When the cancer has metastasized to other sites in the body prior to surgery, complete surgical excision is usually impossible. In the Halstedian model of cancer progression, tumors grow locally, then spread to the lymph nodes, then to the rest of the body. This has given rise to the popularity of local-only treatments such as surgery for small cancers. Even small localized tumors are increasingly recognized as possessing metastatic potential.
Examples of surgical procedures for cancer include mastectomy for breast cancer and prostatectomy for prostate cancer. The goal of the surgery can be either the removal of only the tumor, or the entire organ. A single cancer cell is invisible to the naked eye but can regrow into a new tumor, a process called recurrence. For this reason, the pathologist will examine the surgical specimen to determine if a margin of healthy tissue is present, thus decreasing the chance that microscopic cancer cells are left in the patient.
In addition to removal of the primary tumor, surgery is often necessary for staging, e.g. determining the extent of the disease and whether it has metastasized to regional lymph nodes. Staging is a major determinant of prognosis and of the need for adjuvant therapy.
Occasionally, surgery is necessary to control symptoms, such as spinal cord compression or bowel obstruction. This is referred to as palliative treatment.
Radiation therapy
Radiation therapy (also called radiotherapy, X-ray therapy, or irradiation) is the use of ionizing radiation to kill cancer cells and shrink tumors. Radiation therapy can be administered externally via external beam radiotherapy (EBRT) or internally via brachytherapy. The effects of radiation therapy are localised and confined to the region being treated. Radiation therapy injures or destroys cells in the area being treated (the "target tissue") by damaging their genetic material, making it impossible for these cells to continue to grow and divide. Although radiation damages both cancer cells and normal cells, most normal cells can recover from the effects of radiation and function properly. The goal of radiation therapy is to damage as many cancer cells as possible, while limiting harm to nearby healthy tissue. Hence, it is given in many fractions, allowing healthy tissue to recover between fractions.
Radiation therapy may be used to treat almost every type of solid tumor, including cancers of the brain, breast, cervix, larynx, lung, pancreas, prostate, skin, stomach, uterus, or soft tissue sarcomas. Radiation is also used to treat leukemia and lymphoma. Radiation dose to each site depends on a number of factors, including the radiosensitivity of each cancer type and whether there are tissues and organs nearby that may be damaged by radiation. Thus, as with every form of treatment, radiation therapy is not without its side effects.
Chemotherapy
Chemotherapy is the treatment of cancer with drugs ("anticancer drugs") that can destroy cancer cells. In current usage, the term "chemotherapy" usually refers to cytotoxic drugs which affect rapidly dividing cells in general, in contrast with targeted therapy (see below). Chemotherapy drugs interfere with cell division in various possible ways, e.g. with the duplication of DNA or the separation of newly formed chromosomes. Most forms of chemotherapy target all rapidly dividing cells and are not specific for cancer cells, although some degree of specificity may come from the inability of many cancer cells to repair DNA damage, while normal cells generally can. Hence, chemotherapy has the potential to harm healthy tissue, especially those tissues that have a high replacement rate (e.g. intestinal lining). These cells usually repair themselves after chemotherapy.
Because some drugs work better together than alone, two or more drugs are often given at the same time. This is called "combination chemotherapy"; most chemotherapy regimens are given in a combination.
The treatment of some leukaemias and lymphomas requires the use of high-dose chemotherapy, and total body irradiation (TBI). This treatment ablates the bone marrow, and hence the body's ability to recover and repopulate the blood. For this reason, bone marrow, or peripheral blood stem cell harvesting is carried out before the ablative part of the therapy, to enable "rescue" after the treatment has been given. This is known as autologous stem cell transplantation. Alternatively, hematopoietic stem cells may be transplanted from a matched unrelated donor (MUD).
Targeted therapies
Targeted therapy, which first became available in the late 1990s, has had a significant impact in the treatment of some types of cancer, and is currently a very active research area. This constitutes the use of agents specific for the deregulated proteins of cancer cells. Small molecule targeted therapy drugs are generally inhibitors of enzymatic domains on mutated, overexpressed, or otherwise critical proteins within the cancer cell. Prominent examples are the tyrosine kinase inhibitors imatinib (Gleevec/Glivec) and gefitinib (Iressa).
Monoclonal antibody therapy is another strategy in which the therapeutic agent is an antibody which specifically binds to a protein on the surface of the cancer cells. Examples include the anti-HER2/neu antibody trastuzumab (Herceptin) used in breast cancer, and the anti-CD20 antibody rituximab, used in a variety of B-cell malignancies.
Targeted therapy can also involve small peptides as "homing devices" which can bind to cell surface receptors or affected extracellular matrix surrounding the tumor. Radionuclides which are attached to this peptides (e.g. RGDs) eventually kill the cancer cell if the nuclide decays in the vicinity of the cell. Especially oligo- or multimers of these binding motifs are of great interest, since this can lead to enhanced tumor specificity and avidity.
Photodynamic therapy (PDT) is a ternary treatment for cancer involving a photosensitizer, tissue oxygen, and light (often using lasers). PDT can be used as treatment for basal cell carcinoma (BCC) or lung cancer; PDT can also be useful in removing traces of malignant tissue after surgical removal of large tumors.[7]
Immunotherapy
Cancer immunotherapy refers to a diverse set of therapeutic strategies designed to induce the patient's own immune system to fight the tumor. Contemporary methods for generating an immune response against tumours include intravesical BCG immunotherapy for superficial bladder cancer, and use of interferons and other cytokines to induce an immune response in renal cell carcinoma and melanoma patients. Vaccines to generate specific immune responses are the subject of intensive research for a number of tumours, notably malignant melanoma and renal cell carcinoma. Sipuleucel-T is a vaccine-like strategy in late clinical trials for prostate cancer in which dendritic cells from the patient are loaded with prostatic acid phosphatase peptides to induce a specific immune response against prostate-derived cells.
Allogeneic hematopoietic stem cell transplantation ("bone marrow transplantation" from a genetically non-identical donor) can be considered a form of immunotherapy, since the donor's immune cells will often attack the tumor in a phenomenon known as graft-versus-tumor effect. For this reason, allogeneic HSCT leads to a higher cure rate than autologous transplantation for several cancer types, although the side effects are also more severe.
Tags: cancer, oncology, tumors, infecticus, genome, radiation, genetic
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