Cancer is a class of diseases characterized by uncontrolled division of cells and the ability of these cells to invade other tissues, either by direct growth into adjacent tissue (invasion) or by implantation into distant sites (metastasis). This unregulated growth is caused by damage to DNA, resulting in mutations to genes that control cell division. Several mutations may be required to transform a normal cell into a malignant cell. These mutations are often caused by chemicals or physical agents called carcinogens. Some mutations occur spontaneously, or they can be inherited (germ line mutations.)

Cancer can cause many different symptoms, depending on the site and character of the malignancy and whether there is metastasis. Cancer may be painless. A definitive diagnosis usually requires the histologic examination of tissue by a pathologist. This tissue is obtained by biopsy or surgery. Once diagnosed, cancer is usually treated with surgery, chemotherapy, or radiation.

If untreated, cancers may eventually cause death. Cancer is mainly a disease of later years, and is one of the leading causes of death in developed countries. Most cancers can be treated and many cured, especially if treatment begins early.

Cancer Terminology

The following closely related terms may be used to designate abnormal growths:

· Neoplasia and neoplasm are the accurate, scientific names for this group of diseases as defined in the first paragraph above. This group contains a large number of different diseases; the usual classification is listed below. Neoplasms can be benign or malignant.

· Cancer is a widely used word that is usually understood as synonymous with malignant neoplasm. Occasionally, it is used instead of carcinoma, a sub-group of malignant neoplasms. Because of its overwhelming popularity relative to 'neoplasia', it is used frequently instead of 'neoplasia', even by scientists and physicians, especially when discussing neoplastic diseases as a group.

· Tumor in medical language simply means swelling or lump, either neoplastic, inflammatory or other. In common language, however, it is synonymous with 'neoplasm', either benign or malignant. This is inaccurate since some neoplasms usually do not form tumors, for example leukemia or carcinoma in situ.

Classification and Nomenclature:

Cancers are classified by the type of cells that resemble the tumor and thereby the tissue is presumed to be the origin of the tumor. The following general categories are usually accepted:

· Carcinoma: malignant tumors derived from epithelial cells. This group represent the most common cancers, including the common forms of breast, prostate, lung and colon cancer.

· Lymphoma and Leukemia: malignant tumors derived from blood and bone marrow cells

· Sarcoma: Malignant tumors derived from connective tissue, or mesenchymal cells

· Mesothelioma: tumors derived from the mesothelial cells lining the peritoneum and the pleura.

· Glioma: tumors derived from brain cells

· Germ Cell Tumors: tumors derived from germ cells, normally found in the testicle and ovary

· Choriocarcinoma: malignant tumors derived from the placenta

In males, most common tumors are prostate cancer, lung cancer, colorectal cancer, and bladder cancer. In females, most common tumors are breast cancer, lung cancer, colorectal cancer, and endometrial cancer. Cancer can also occur in young children and adolescents, but it is rare. The age of peak incidence of cancer in children occurs during the first year of life. 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.

Origin of Cancer

Cell division (proliferation) is a physiological process that occurs in almost all tissues and under many circumstances. Normally the balance between proliferation and cell death is tightly regulated to ensure the integrity of organs and tissues. Mutations in DNA that lead to cancer disrupt these orderly processes. The uncontrolled and often rapid proliferation of cells can lead to either a benign tumor or a malignant tumor (cancer). Benign tumors do not spread to other parts of the body or invade other tissues, and they are rarely a threat to life unless they extrinsically compress vital structures. Malignant tumors can invade other organs, spread to distant locations (metastasize) and become life-threatening.

Prevention

Cancer prevention is defined as active measures to decrease the incidence of cancer. This can be accomplished by avoiding carcinogens or altering their metabolism, pursuing a lifestyle or diet that modifies cancer-causing factors and/or medical intervention (chemoprevention, treatment of premalignant lesions).

Diagnosing Cancer

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.

1. 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.

· 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 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.

2. 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. The tissue diagnosis 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 choose the best treatment. Cytogenetics and immunohistochemistry may provide information about future behavior of the cancer (prognosis) and best treatment.

3. Screening

Cancer screening is an attempt to detect unsuspected cancers in the population. Screening tests suitable for large numbers of healthy people must be relatively affordable, safe, noninvasive procedures with acceptably low rates of false positive results. If signs of cancer are detected, more definitive and invasive follow up tests are performed to confirm the diagnosis.

Treatment of Cancer

Cancer can be treated by surgery, chemotherapy, radiation therapy, immunotherapy 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.

Surgery

In theory, 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.

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.

Chemotherapy

Chemotherapy is the treatment of cancer with drugs ("anticancer drugs") that can destroy cancer cells. It interferes 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. 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.

Immunotherapy

Immunotherapy is the use of immune mechanisms against tumors. These are used in various forms of cancer, such as breast cancer (trastuzumab/Herceptin®) but also in leukemia. The agents are monoclonal antibodies directed against proteins that are characteristic to the cells of the cancer in question, or cytokines that modulate the immune system's response.

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 localized 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. In addition, they cut off the blood supply to the cancer cells causing them to die in a process called necrosis. 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.

Hormonal suppression

The growth of nearly all tissues, including cancers, can be accelerated or inhibited by providing or blocking certain hormones. This allows an additional method of treatment for many cancers. Common examples of hormone-sensitive tumors include certain types of breast, prostate, and thyroid cancers. Removing or blocking estrogen, testosterone, or TSH, respectively, is often an important additional treatment.

Complementary and alternative medicine

Complementary and alternative medicine (CAM) treatments are the diverse group of medical and health care systems, practices, and products that are not presently considered to be effective by the standards of conventional medicine. Some non-conventional treatment methods are used to "complement" conventional treatment, to provide comfort or lift the spirits of the patient, while others are offered as alternatives to be used instead of conventional treatments in hope of curing the cancer. They include traditional Chinese medicine, megavitamin therapy and many others.

Cancer vaccines

Considerable research effort is now devoted to the development of vaccines (to prevent infection by oncogenic infectious agents, as well as to mount an immune response against cancer-specific epitopes) and to potential venues for gene therapy for individuals with genetic mutations or polymorphisms that put them at high risk of cancer. No cancer vaccines are presently in use, and most of the research is still in its initial stages.

Oncology

Oncology is the medical subspecialty dealing with the study and treatment of cancer. A physician who practices oncology is an oncologist. The term originates from the Greek onkos (ονκος), meaning bulk, mass, or tumor and the suffix -ology, meaning "study of."

Oncologists may be divided on the basis of the type of treatment provided.

Surgical oncologists: who are surgeons who specialize in tumor removal.
Medical oncologists: who deal with using medication or chemotherapy to treat cancer.
Radiation oncologists: people who specialize in the treatment of cancer with radiation, a process called radiotherapy.
N.B. In the UK, the majority of oncologists are known as Clinical Oncologists, and are fully qualified to practice both chemotherapy and radiotherapy. In most other countries these disciplines are more clearly segregated.

Oncologists may also be categorized on the basis of the patient type.

· Gynecologic oncologist: who specialize in the treatment of cancer in women. He/She can performs and give chemotherapy and assists in radiation therapy for these cancers in women.

· Pediatric oncologist: who specialize in the care of children with cancer.

Oncology is concerned with:

· The diagnosis of cancer

· Therapy (e.g. surgery, chemotherapy, radiotherapy and other modalities)

· Follow-up of cancer patients after successful treatment

· Palliative care of patients with terminal malignancies

· Ethical questions surrounding cancer care

· Screening efforts:

· of populations, or

· of the relatives of patients (in types of cancer that are thought to have a heritable basis, such as breast cancer.)

The oncologist often coordinates the multidisciplinary care of cancer patients, which may involve physiotherapy, counseling, clinical genetics, to name but a few. On the other hand, the oncologist often has to liaise with pathologists on the exact biological nature of the tumor that is being treated.

Diagnosis

The most important diagnostic tool remains the medical history: the character of the complaints and any specific symptoms (fatigue, weight loss, unexplained anemia, paraneoplastic phenomena and other signs). Often a physical examination will reveal the location of a malignancy.

Diagnostic methods include:

Biopsy, either incisional or excisional;
Endoscopy, either upper or lower gastrointestinal, bronchoscopy, or nasendoscopy;
X-rays, CT scanning, MRI scanning, ultrasound and other radiological techniques;
Scintigraphy, Positron emission tomography and other methods of nuclear medicine; Blood tests, including Tumor markers, which can increase the suspicion of certain types of tumors or even be pathognomonic of a particular disease.

Cancer Therapy

It depends completely on the nature of the tumor identified what kind of therapeutical intervention will be necessary. Certain disorders will require immediate admission and chemotherapy (such as ALL or AML), while others will be followed up with regular physical examination and blood tests.

Often, surgery is attempted to remove a tumor entirely. This is only feasible when there is some degree of certainty that the tumor can in fact be removed. When it is certain that parts will remain, curative surgery is often impossible, e.g. when there are metastases elsewhere, or when the tumor has invaded a structure that cannot be operated upon without risking the patient's life. Occasionally surgery can improve survival even if not all tumour tissue has been removed; the procedure is referred to as "debulking" (i.e. reducing the overall amount of tumour tissue). Surgery is also used for the palliative treatment of some of cancers, e.g. to relieve biliary obstruction, or to relieve the problems associated with some cerebral tumors. The risks of surgery must be weighed up against the benefits.

Chemotherapy and radiotherapy are used as a first-line radical therapy in a number of malignancies. They are also used for adjuvant therapy, i.e. when the macroscopic tumor has already been completely removed surgically but there is a reasonable statistical risk that it will recur. Chemotherapy and radiotherapy are commonly used for palliation, where disease is clearly incurable: in this situation the aim is to improve and prolong quality of life.

Hormone manipulation is well established, particularly in the treatment of breast and prostate cancer.

There is currently a rapid expansion in the use of monoclonal antibody treatments, notably for lymphoma (Rituximab), and breast cancer (Trastuzumab).

Vaccine and other immunotherapies are the subject of intensive research.

The application of ultrasound in the form of HIFU to solid tumors is under investigation.

Tumor

Tumor or tumour literally means "swelling", and is sometimes still used with that meaning. Tumor meaning swelling is one of the five classical characteristics of inflammation. However, the term is now primarily used to denote abnormal growth of tissue. This growth can be either malignant or benign. It is similar in meaning to a neoplasia.

Benign

Benign can refer to any medical condition which, untreated or with symptomatic therapy, will not become life-threatening. It is used in particular in relation to tumors, which may be benign or malignant. Benign tumors do not invade surrounding tissues and do not metastasize to other parts of the body. The word is slightly imprecise, as some benign tumors can, due to mass effect, cause life-threatening complications. The term therefore applies mainly to their biological behaviour.

Tumors may be benign but at risk for degeneration into malignancy. These are termed "premalignant".

Benign can also mean something, such as a substance, practice or policy, that is not considered harmful.

Premalignant condition

A premalignant condition is a disease, syndrome, or finding that, if left untreated, may lead to cancer. Examples of pre-malignant conditions include actinic keratosis and Barrett's esophagus.

Carcinoma in situ

Carcinoma in situ (CIS) is an early form of carcinoma defined by the absence of invasion of surrounding tissues. In other words, the neoplastic cells proliferate in their normal habitat, hence the name 'in situ' (Latin for 'in its place'). For example, carcinoma in situ of the skin, also called 'Bowen's disease' is the accumulation of neoplastic epidermal cells within the epidermis only.

For this reason, CIS will usually not form a tumor. Rather, the lesion is flat (in the skin, cervix, etc) or follows the existing architecture of the organ (in the breast, lung, etc). Some CIS, however, form tumors, for example colon polyps or papillary cancer of the bladder.

Many forms of cancer originate from a 'carcinomas in situ' (CIS) lesion. Therefore, CIS is considered a precursor that may, if left untreated long enough, transform into a more malignant form of neoplasm, invasive carcinoma or, in common language, "cancer".

Many doctors will not refer to 'carcinoma in situ' as "cancer" when explaining a laboratory report to a patient. However, because most forms of CIS have a real potential to turn into invasive carcinoma, CIS is usually treated much the same way as a malignant tumor.

Dysplasia vs carcinoma in situ vs invasive carcinoma

These terms are related since they represent the three steps of the progression toward cancer:

· Dysplasia, Latin for 'bad form', is the earliest form of pre-cancerous lesion recognizable in a biopsy by a pathologist. Dysplasia can be low grade or high grade. The risk of low-grade dysplasia transforming into high-grade dysplasia and, eventually, cancer is low. Treatment is usually easy.

· Carcinoma in situ is synonymous with high-grade dysplasia in most organs. The risk of transforming into cancer is high. Treatment is still usually easy.

· Invasive carcinoma, commonly called cancer, is the final step in this sequence. It is a disease that, when left untreated, will invade the host (hence its name) and will probably kill him. It can often, but not always, be treated successfully.

Examples of carcinomas in situ

1. Many bladder cancers are CIS.

2. Cervical cancer is often predated by cervical intraepithelial neoplasia (CIN), also called dysplasia. It is this lesion that is detected with the pap smear.

3. Ductal carcinoma in situ (DCIS) of the breast is a rather frequent disease with a high probability of transforming into true breast cancer if untreated.

4. Bowen's disease is squamous carcinoma in situ of the skin.

5. Colon polyps often contain areas of CIS that will almost always turn into colon cancer if left untreated.

Bronchioalveolar carcinoma of the lung is the only form of CIS that can kill, because it fills the lungs and prevents breathing. Thus, it is malignant, but not invasive. For this reason, this unusual form of carcinoma is seen as CIS by pathologists, not by oncologists or surgeons.

Malignant

In medicine, malignant is a clinical term that is used to describe a clinical course that progresses rapidly to death. It is typically applied to neoplasms that show aggressive behavior characterized by local invasion or distant metastasis.

The change of cells from benign to malignant behavior is called malignant transformation. Usually this diagnosis is made by pathologic examination of tissues. However, often the physician during the history and physical examination can find that there have been changes in size or patient sensation and upon direct examination that there has been a change in the lesion itself.

Malignant transformation is a synonym for progression to malignancy. Transformation may take place as a primary or a secondary process. Malignant qualities in cancer may be due to still multiplying cells, or cells that break off from the main tumour and enter the blood stream, being transported elsewhere where the cells that broke off are able to reproduce further, thus spreading the cancer.

Cancer Staging

The stage of a cancer is a descriptor (usually numbers I to IV) of how much the cancer has spread. The stage often takes into account the size of a tumor, how deep it has penetrated, whether it has invaded adjacent organs, if and how many lymph nodes it has metastasized to, and whether it has spread to distant organs. Staging of cancer is important because the stage at diagnosis is the biggest predictor of survival, and treatments are often changed based on the stage.

Clinical staging and pathological staging

Cancer staging can be divided into a clinical stage and a pathologic stage. In the TNM (Tumor, Node, Metastasis) system, clinical stage and pathologic stage are denoted by a small 'c' or 'p' before the stage, e.g. cT3N1M0 or pT2N0.

· Clinical stage is based on all of the available information obtained before a surgery to remove the tumor. Thus, it may include information about the tumor obtained by physical examination, radiologic examination, and endoscopy.

· Pathologic stage adds additional information gained by examination of the tumor microscopically by a pathologist.

Because they use different information, clinical stage and pathologic stage are often different. Pathologic staging is usually considered the "better" or "truer" stage because it allows direct examination of the tumor and its spread, contrasted with clinical staging which is limited by the fact that the information is obtained by making indirect observations at a tumor which is still in the body. However, clinical staging and pathologic staging should complement each other. Not every tumor is treated surgically, so sometimes pathologic staging is not available. Also, sometimes surgery is preceded by other treatments such as chemotherapy and radiation therapy which shrink the tumor, so the pathologic stage may underestimate the true stage.

Overall stage grouping

Overall Stage Grouping is also referred to as Roman Numeral Staging. This system uses numerals I, II, III, and IV to describe the progression of cancer.

· Stage I cancers are localized to one part of the body.

· Stage II cancers are locally advanced, as are Stage III cancers. Whether a cancer is designated as Stage II or Stage III can depend on the specific type of cancer; for example, in Hodgkin's Disease, Stage II indicates affected lymph nodes on only one side of the diaphragm, whereas Stage III indicates affected lymph nodes above and below the diaphragm. The specific criteria for Stages II and III therefore differ according to diagnosis.

· Stage IV cancers have often metastasized, or spread to other organs or throughout the body.

Within the OSG system, a cancer may also be designated as recurrent, meaning that it has appeared again after being in remission or after all visible tumor has been eliminated. Recurrence can either be local, meaning that it appears in the same location as the original, or distant, meaning that it appears in a different part of the body.

TNM staging

TNM Staging is used for solid tumors, and is an acronym for the words Tumor, Nodes, and Metastases.

TNM Classification of Malignant Tumors (TNM) is the cancer staging system developed and maintained by the International Union Against Cancer (UICC) to maintain consensus on one globally recognized standard for categorizing cancer. The TNM classification is also used by the American Joint Committee on Cancer (AJCC) and the International Federation of Gynecology and Obstetrics (FIGO). In 1987, the UICC and AJCC staging systems were unified into a single staging system.

Broad outline

Each tumor has its own TNM classification. Not all tumors have TNM classifications, but most do. For instance, there is no TNM classification for brain tumors.

The general outline for the TNM classification is below. The values given in parenthesis give a range of what can be used for all cancer types, but not all cancers use this full range.

Mandatory parameters ('T', 'N', and 'M')

· T (a, is, (0), 1-4): size of the tumor Relates to Tumour size and local spread.

· N (0-3): spreading into lymphatic nodes.

· M (0/1): spreading into other organs metastasis.

Other parameters

· G (1-4): the grade of the cancer cells (i.e. they are "low grade" if they appear similar to normal cells, and "high grade" if they appear poorly differentiated.

· R (0/1/2): the completeness of the operation (resection-boundaries free of cancer cells or not)

· L (0/1): invasion into lymphatic vessels.

· V (0/1): invasion into veins.

· C (1-4): a modifier of the certainty (quality) of the last mentioned parameter

Prefix modifiers

· c: stage given by clinical examination of a patient. The c-prefix is implicit in absence of the p-prefix

· p: stage given by pathologic examination of a surgical specimen

· y: stage assessed after neoadjuvant therapy

For the T, N and M parameters exist sub-classifications for some cancer-types (e.g. T1a, Tis, N1i).

Examples

· Small, low grade cancer, no metastasis, no spreading to lymph nodes, cancer completely removed, resection material seen by pathologist - pT1 pN0 M0 R0 G1

· Big, high grade cancer, with spread to lymph nodes and other organs, not completely removed, seen by pathologist - pT4 pN2 M1 R1 G3

Systems of Staging

Staging systems are specific for each type of cancer (e.g. breast cancer and lung cancer). Some cancers, however, don't have a staging system. Often competing staging systems exist for the same type of cancer; however, the universally-accepted staging system is that of the UICC, which has merged its staging system with that of the AJCC.

Blood

· Lymphoma: uses Ann Arbor staging

· Hodgkin's Disease: Follows a scale from I-IV and can be indicated further by an A or B, depending on whether a patient is asymptomatic or has symptoms such as fevers. It is known as the "Cotswold System" or "Modified Ann Arbor Staging System".

Solid

For solid tumors, TNM is by far the most commonly used system, but it has been adapted for some conditions.

Breast cancer: Uses TNM
Cervical cancer: uses "FIGO" (similar to TNM). For premalignant dysplastic changes, the CIN (cervical intraepithelial neoplasia) grading system is used.
Colon cancer: originally consisted of four stages: A, B, C, and D (the "Duke Staging System"). More recently, colon cancer staging is indicated either by the original A-D stages or by TNM.
Kidney cancer: uses TNM
Cancer of the larynx: Uses TNM
Liver cancer: uses Stages I-IV
Lung cancer: uses TNM
Malignant melanoma: TNM used. Also of importance are the "Clark level" and "Breslow depth" which refer to the microscopic depth of tumor invasion ("Microstaging").
Prostate cancer: outside of US, TNM almost universally used. Inside US, Jewett-Whitmore sometimes used.
Skin cancer: uses TNM

Ann Arbor Staging

The principal stage is determined by location of the tumor:

· Stage I indicates that the cancer is located in a single region, usually one lymph node and the surrounding area. Stage I often will not have outward symptoms.

· Stage II indicates that the cancer is located in two separate regions, an affected lymph node or organ within the lymphatic system and a second affected area, and that both affected areas are confined to one side of the diaphragm - that is, both are above the diaphragm, or both are below the diaphragm.

· Stage III indicates that the cancer has spread to both sides of the diaphragm, including one organ or area near the lymph nodes or the spleen.

· Stage IV indicates diffuse or disseminated involvement of one or more extralymphatic organs, including any involvement of the liver, bone marrow, or nodular involvement of the lungs.

Modifiers

These letters can be appended to some stages:

· A or B: the absence of constitutional (B-type) symptoms is denoted by adding an "A" to the stage; the presence is denoted by adding a "B" to the stage.

· E: is used if the disease is "extranodal" (not in the lymph nodes) or has spread from lymph nodes to adjacent tissue.

· X: is used if the largest deposit if >10 cm large ("bulky disease"), or whether · the mediastinum is wider than 1/3 of the chest on a chest X-ray.

Ann Arbor staging is the staging system for lymphomas, both in Hodgkin's disease and non-Hodgkin's lymphoma. It was initially developed for Hodgkin's, but has some use in NHL. It has roughly the same function as TNM staging in solid tumors.

Grading (tumors)

Grading is a measure of the progress of tumors.

An important part of evaluating a cancer is to determine its histologic grade. Grade is a marker of how differentiated a cell is. Grade is rated numerically (Grade 1-4) or descriptively (e.g., "high grade" or "low grade"). The higher the numeric grade, the more "poorly differentiated" is the cell, and it is called "high grade". A low-grade cancer has a low number and is "well-differentiated." Grade is most commonly given on a three-tier scale. A cancer that is very poorly differentiated is called anaplastic. Tumors may be graded on four-tier, three-tier, or two-tier scales, depending on the institution and the tumor type. A three-tier scale is most commonly used.

Examples of Grading Schemes

Four-tier grading scheme

Grade 1	Low grade	Well-differentiated
Grade 2	Intermediate grade	Moderately-differentiated
Grade 3	High grade	Poorly-differentiated
Grade 4	Anaplastic	Anaplastic

Three-tier grading scheme

Grade 1	Low grade	Well-differentiated
Grade 2	Intermediate grade
Grade 3	High grade	Poorly-differentiated

Two-tier grading scheme

Grade 1	Low grade	Well-differentiated
Grade 2	High grade	Poorly-differentiated

BX	Bx, biop., biopsy.
Ca	Cancer.
CEA	Carcinoembryonic antigen.
CMF	Cytoxan, methotrexate and 5-fluorouracil.
DES	Diethylstilbestrol.
DNA	Deoxyribonucleic acid.
ER/PR	Estrogen/progesterone.
NED	No evidence of disease.
NHL	Non-Hodgkin's lymphoma.
Pap	Papanicolaou smear.
PR	Partial response / partial remission.
prot	Protocol.
PSA	Prostate-specific antigen.
RNA	Ribonucleic acid.
TNM	Tumor, nodes, metastases.
XRT	Radiotherapy.