Saturday, September 1, 2012

Carcinoma





Carcinoma (Gk. karkinos, or "crab", and -oma, "growth") is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during embryogenesis. More specifically, a carcinoma is tumor tissue derived from putative epithelial cells whose genome has become altered or damaged to such an extent that the cells become transformed, and begin to exhibit abnormal malignant properties. 
Carcinoma of unknown primary (CUP)


The term carcinoma has also come to encompass malignant tumors composed of transformed cells whose origin or developmental lineage is unknown (see CUP), but that possess certain specific molecular, cellular, and histological characteristics typical of epithelial cells. This may include the production of one or more forms of cytokeratin or other intermediate filaments, intercellular bridge structures, keratin pearls, and/or tissue architectural motifs such as stratification or pseudo-stratification.

Pathogenesis of cancer

Cancer occurs when a single progenitor cell accumulates mutations and other changes in the DNA, histones, and other biochemical compounds that make up the cell's genome. The cell genome controls the structure of the cell's biochemical components, the biochemical reactions that occur within the cell, and the biological interactions of that cell with other cells. Certain combinations of mutations in the given progenitor cell ultimately result in that cell (also called a cancer stem cell) displaying a number of abnormal, malignant cellular properties that, when taken together, are considered characteristic of cancer, including:
1.the ability to continue to divide perpetually, producing an exponentially (or near-exponentially) increasing number of new malignant cancerous "daughter cells" (uncontrolled mitosis);

2.the ability to penetrate normal body surfaces and barriers, and to bore into or through nearby body structures and tissues (local invasiveness);

3.the ability to spread to other sites within the body (metastasize) by penetrating or entering into the lymphatic vessels (regional metastasis) and/or the blood vessels (distant metastasis).
    If this process of continuous growth, local invasion, and regional and distant metastasis is not halted via a combination of stimulation of immunological defenses and medical treatment interventions, the end result is that the host suffers a continuously increasing burden of tumor cells throughout the body. Eventually, the tumor burden increasingly interferes with normal biochemical functions carried out by the host's organs, and death ultimately ensues.

    Pathogenesis of carcinoma

    Carcinoma is but one form of cancer - one composed of cells that have developed the cytological appearance, histological architecture, or molecular characteristics of epithelial cells. A progenitor carcinoma stem cell can be formed from any of a number of oncogenic combinations of mutations in a totipotent cell,a multipotent cell,or a mature differentiated cell.

    Epidemiology of carcinoma

    1.Demography (Age, Race, Gender, etc.)

    While cancer is generally considered a disease of old age, children can also develop cancer.In contrast to adults, carcinomas are exceptionally rare in children.

    2.Causes
    Smoking, environment, etc.

    Classification of carcinomas

    Malignant neoplasms are exceptionally heterogeneous entities, reflecting the wide variety, intensity, and potency of various carcinogenic promoters.To date, no simple and comprehensive method for classifying them has yet been devised and accepted within the scientific community.Traditionally, however, malignancies have generally been classified into various taxa using a combination of criteria, including:

    One commonly used classification scheme classifies these major cancer types on the basis of cell genesis, specifically:
    Their (putative) cell (or cells) of origin
    Epithelial cells => carcinoma
    Non-hematopoietic mesenchymal cells => sarcoma
    Hematopoietic cells
    bone marrow-derived cells that normally mature in the bloodstream => Leukemia
    bone marrow-derived cells that normally mature in the lymphatic system => Lymphoma
    Germ cells => Germinoma

    Other criteria that play a role in a cancer diagnosis include:
    1.The degree to which the malignant cells resemble their normal, untransformed counterparts
    2.the appearance of the local tissue and stromal architecture
    3.the anatomical location from which tumors arise
    4.genetic, epigenetic, and molecular features

    Histological types and variants of carcinoma

    Adenocarcinoma(adeno = gland) Refers to a carcinoma featuring microscopic glandular-related tissue cytology, tissue architecture, and/or gland-related molecular products, e.g., mucin.Squamous cell carcinoma.Refers to a carcinoma with observable features and characteristics indicative of squamous differentiation (intercellular bridges, keratinization, squamous pearls).

    Adenosquamous carcinoma

    Refers to a mixed tumor containing both adenocarcinoma and squamous cell carcinoma, wherein each of these cell types comprise at least 10% of the tumor volume.

    Anaplastic carcinoma

    Refers to a heterogeneous group of high-grade carcinomas that feature cells lacking distinct histological or cytological evidence of any of the more specifically differentiated neoplasms. These tumors are referred to as Anaplastic or Undifferentiated carcinomas.

    Large cell carcinoma

    Composed of large, monotonous rounded or overtly polygonal-shaped cells with abundant cytoplasm.

    Small cell carcinoma

    Cells are usually round and are less than approximately 3 times the diameter of a resting lymphocyte and little evident cytoplasm. Occasionally, small cell malignancies may themselves have significant components of slightly polygonal and/or spindle-shaped cells.There are a large number of rare subtypes of anaplastic, undifferentiated carcinoma. Some of the more well known include the lesions containing pseudo-sarcomatous components: spindle cell carcinoma (containing elongated cells resembling connective tissue cancers), giant cell carcinoma (containing huge, bizarre, multinucleated cells), and sarcomatoid carcinoma (mixtures of spindle and giant cell carcinoma). Pleomorphic carcinoma contains spindle cell and/or giant cell components, plus at least a 10% component of cells characteristic of more highly differentiated types (i.e. adenocarcinoma and/or squamous cell carcinoma). Very rarely, tumors may contain individuals components resembling both carcinoma and true sarcoma, including carcinosarcoma and pulmonary blastoma.

    Frequent organ sites of carcinoma

    Lung: Carcinoma comprises >98% of all lung cancers.
    Breast: Nearly all breast cancers are ductal carcinoma.
    Prostate: The most common form of carcinoma of the prostate is adenocarcinoma.
    Colon and rectum: Nearly all malignancies of the colon and rectum are either adenocarcinoma or squamous cell carcinoma.
    Pancreas: Pancreatic carcinoma is almost always of the adenocarcinoma type and is highly lethal.

    Some carcinomas are named for their or the putative cell of origin, (e.g.hepatocellular carcinoma, renal cell carcinoma).

    Invasion and metastasis of carcinomas



    The hallmark of a malignant tumor is its tendency to invade and infiltrate local and adjacent structures and, eventually, spread from the site of its origin to non-adjacent regional and distant sites in the body, a process called metastasis. If unchecked, tumor growth and metastasis eventually creates a tumor burden so great that the host succumbs. Carcinoma metastasizes through both the lymph nodes and the blood.

    Diagnosis

    Carcinomas can be definitively diagnosed through biopsy, including fine-needle aspiration (FNA), core biopsy, or subtotal removal of single node,. Microscopic examination by a pathologist is then necessary to identify molecular, cellular, or tissue architectural characteristics of epithelial cells.

    Staging

    Staging of carcinoma refers to the process of combining physical/clinical examination, pathological review of cells and tissues, surgical techniques, laboratory tests, and imaging studies in a logical fashion to obtain information about the size of the neoplasm and the extent of its invasion and metastasis.

    Carcinomas are usually staged with Roman numerals. In most classifications, Stage I and Stage II carcinomas are confirmed when the tumor has been found to be small and/or to have spread to local structures only. Stage III carcinomas typically have been found to have spread to regional lymph nodes, tissues, and/or organ structures, while Stage IV tumors have already metastasized through the blood to distant sites, tissues, or organs.

    In some types of carcinomas, Stage 0 carcinoma has been used to describe carcinoma in situ, and occult carcinomas detectable only via examination of sputum for malignant cells (in lung carcinomas).

    In more recent staging systems, substages (a, b, c) are becoming more commonly used to better define groups of patients with similar prognosis or treatment options.

    Carcinoma stage is the variable that has been most consistently and tightly linked to the prognosis of the malignancy.

    The criteria for staging can differ dramatically based upon the organ system in which the tumor arises. For example, the colon and bladder cancer staging system relies on depth of invasion, staging of breast carcinoma is more dependent on the size of the tumor, and in renal carcinoma, staging is based on both the size of the tumor and the depth of the tumor invasion into the renal sinus. Carcinoma of the lung has a more complicated staging system, taking into account a number of size and anatomic variables.

    The UICC/AJCC TNM systems are most often used. For some common tumors, however, classical staging methods (such as the Dukes classification for colon cancer) are still used.

    Grading

    Grading of carcinomas refers to the employment of criteria intended to semi-quantify the degree of cellular and tissue maturity seen in the transformed cells relative to the appearance of the normal parent epithelial tissue from which the carcinoma derives.

    Grading of carcinoma is most often done after a treating physician and/or surgeon obtains a sample of suspected tumor tissue using surgical resection, needle or surgical biopsy, direct washing or brushing of tumor tissue, sputum cytopathology, etc. A pathologist then examines the tumor and its stroma, perhaps utilizing staining, immunohistochemistry, flow cytometry, or other methods. Finally, the pathologist classifies the tumor semi-quantitatively into one of three or four grades, including:
    Grade 1, or well differentiated: there is a close, or very close, resemblance to the normal parent tissue, and the tumor cells are easily identified and classified as a particular malignant histological entity;
    Grade 2, or moderately differentiated: there is considerable resemblance to the parent cells and tissues, but abnormalities can commonly be seen and the more complex features are not particularly well-formed;
    Grade 3, or poorly differentiated: there is very little resemblance between the malignant tissue and the normal parent tissue, abnormalities are evident, and the more complex architectural features are usually rudimentary or primitive;
    Grade 4, or undifferentiated carcinoma: these carcinomas bear no significant resemblance to the corresponding parent cells and tissues, with no visible formation of glands, ducts, bridges, stratified layers, keratin pearls, or other notable characteristics consistent with a more highly differentiated neoplasm.

    Although there is definite and convincing statistical correlation between carcinoma grade and tumor prognosis for some tumor types and sites of origin, the strength of this association can be highly variable. It may be stated generally, however, that the higher the grade of the lesion, the worse is its prognosis.

    Types of carcinoma (by ICD-O code)


    (8010-8045) Epithelial neoplasms, NOS
    (8050-8080) Squamous cell neoplasms
    (M8070/3) Squamous cell carcinoma, NOS
    (8090-8110) Basal cell neoplasms
    (M8090/3) Basal cell carcinoma, NOS
    (8120-8130) Transitional cell carcinomas
    (8140-8380) Adenocarcinomas
    (M8140/3) Adenocarcinoma, NOS
    (M8142/3) Linitis plastica
    (M8155/3) Vipoma
    (M8160/3) Cholangiocarcinoma
    (M8170/3) Hepatocellular carcinoma, NOS
    (M8200/3) Adenoid cystic carcinoma
    (M8312/3) Renal cell carcinoma
    (M8312/3) Grawitz tumor
    (8390-8420) Adnexal and Skin appendage Neoplasms
    (8430-8439) Mucoepidermoid Neoplasms
    (8440-8490) Cystic, Mucinous and Serous Neoplasms
    (8500-8540) Ductal, Lobular and Medullary Neoplasms
    (8550-8559) Acinar cell neoplasms
    (8560-8580) Complex epithelial neoplasms

      Friday, August 31, 2012

      Lung cancer


      Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary lung cancers, are carcinomas that derive from epithelial cells. The main types of lung cancer are small cell lung carcinoma (SCLC), also called oat cell cancer, and non-small cell lung carcinoma (NSCLC). The most common cause of lung cancer is long-term exposure to tobacco smoke.Nonsmokers account for 15% of lung cancer cases, and these cases are often attributed to a combination of genetic factors,radon gas, asbestos and air pollution including secondhand smoke.
      The most common symptoms are coughing (including coughing up blood), weight loss and shortness of breath. Lung cancer may be seen on chest radiograph and computed tomography (CT scan). The diagnosis is confirmed with a biopsy. This is usually performed by bronchoscopy or CT-guided biopsy. Treatment and prognosis depend on the histological type of cancer, the stage (degree of spread), and the patient's general wellbeing, measured by performance status. Common treatments include surgery, chemotherapy, and radiotherapy. NSCLC is sometimes treated with surgery, whereas SCLC usually responds better to chemotherapy and radiotherapy.Survival depends on stage, overall health, and other factors. Overall, 15% of people in the United States diagnosed with lung cancer survive five years after the diagnosis. Worldwide, lung cancer is the most common cause of cancer-related death in men and women, and is responsible for 1.38 million deaths annually, as of 2008.

      Classification

      Lung cancers are classified according to histological type. This classification has important implications for clinical management and prognosis of the disease. The vast majority of lung cancers are carcinomas—malignancies that arise from epithelial cells. Lung carcinomas are categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope. The two broad classes are non-small cell and small cell lung carcinoma.

      Non-small cell lung carcinoma
       There are three main sub-types: adenocarcinoma, squamous cell lung carcinoma, and large cell lung carcinoma.Nearly 40% of lung cancers are adenocarcinoma. This type of cancer usually originates in peripheral lung tissue.Most cases of adenocarcinoma are associated with smoking; however, among people who have smoked fewer than 100 cigarettes in their lifetimes ("never-smokers"), adenocarcinoma is the most common form of lung cancer. A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have different responses to treatment.Squamous cell carcinoma accounts for about 30% of lung cancers. They typically occur close to large airways. A hollow cavity and associated necrosis are commonly found at the center of the tumor.About 9% of lung cancers are large cell carcinoma. These are so named because the cancer cells are large, with a lot of cytoplasm, large nuclei and conspicuous nucleoli.

      Small cell lung carcinoma
      In small-cell lung carcinoma (SCLC), the cells contain dense neurosecretory granules (vesicles containing neuroendocrine hormones), which give this tumor an endocrine/paraneoplastic syndrome association. Most cases arise in the larger airways (primary and secondary bronchi).These cancers grow quickly and spread early in the course of the disease. 60–70% have metastatic disease at presentation. This type of lung cancer is strongly associated with smoking .

       Others
      Four main histological subtypes are recognized, although some cancers may contain a combination of different subtypes. Rare subtypes include glandular tumors, carcinoid tumors, and undifferentiated carcinomas.

      Metastasis

      The lung is a common place for metastasis of tumors from other parts of the body. Secondary cancers are classified by the site of origin; e.g., breast cancer that has spread to the lung is called metastatic breast cancer. Metastases often have a characteristic round appearance on chest radiograph.

      Primary lung cancers themselves most commonly metastasize to the brain, bones, liver, and adrenal glands.Immunostaining of a biopsy is often helpful to determine the original source.

      Signs and symptoms

      If the cancer grows in the airway, it may obstruct airflow, causing breathing difficulties. The obstruction can lead to accumulation of secretions behind the blockage, and predispose to pneumonia.

      Depending on the type of tumor, so-called paraneoplastic phenomena may initially attract attention to the disease. In lung cancer, these phenomena may include Lambert–Eaton myasthenic syndrome (muscle weakness due to auto-antibodies), hypercalcemia, or syndrome of inappropriate antidiuretic hormone (SIADH). Tumors in the top (apex) of the lung, known as Pancoast tumors, may invade the local part of the sympathetic nervous system, leading to Horner's syndrome as well as damage to the brachial plexus.

      Many of the symptoms of lung cancer (poor appetite, weight loss, fever, fatigue) are nonspecific.In many patients, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of metastasis include the brain, bone, adrenal glands, contralateral (opposite) lung, liver, pericardium, and kidneys.About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiograph.

      Causes

      Cancer develops following genetic damage to DNA. This genetic damage affects the normal functions of the cell, including cell proliferation, programmed cell death (apoptosis) and DNA repair. As more damage accumulates, the risk of cancer increases.

      Smoking


      Smoking, particularly of cigarettes, is by far the main contributor to lung cancer.Cigarette smoke contains over 60 known carcinogens, including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue. Across the developed world, 91% of lung cancer deaths in men during the year 2000 were attributed to smoking (71% for women). In the United States, smoking accounts for 80–90% of lung cancer cases.

      Passive smoking—the inhalation of smoke from another's smoking—is a cause of lung cancer in nonsmokers. A passive smoker can be classified as someone living or working with a smoker. Studies from the U.S.,Europe, the UK, and Australia have consistently shown a significantly increased risk among those exposed to passive smoke.Those who live with someone who smokes have a 20–30% increase in risk while those while those who work in an environment with second hand smoke have a 16–19% increase in risk. Investigations of sidestream smoke suggests that it is more dangerous than direct smoke. Passive smoking causes about 3,400 deaths from lung cancer each year in the USA.

      Radon gas

      Radon is a colorless and odorless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the Earth's crust. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous. Radon is the second most common cause of lung cancer in the USA, after smoking. The risk increases 8–16% for every 100 Bq/m³ increase in the radon concentration .Radon gas levels vary by locality and the composition of the underlying soil and rocks. For example, in areas such as Cornwall in the UK (which has granite as substrata), radon gas is a major problem, and buildings have to be force-ventilated with fans to lower radon gas concentrations. The United States Environmental Protection Agency (EPA) estimates that one in 15 homes in the U.S. has radon levels above the recommended guideline of 4 picocuries per liter (pCi/L) (148 Bq/m³).

      Asbestos

      Asbestos can cause a variety of lung diseases, including lung cancer. There is a synergistic effect between tobacco smoking and asbestos in the formation of lung cancer. Asbestos can also cause cancer of the pleura, called mesothelioma (which is different from lung cancer).

      Air pollution

      Outdoor air pollution has a small effect on increasing the risk of lung cancer. Fine particulates (PM2.5) and sulfate aerosols, which may be released in traffic exhaust fumes, are associated with slightly increased risk.For nitrogen dioxide, an incremental increase of 10 parts per billion increases the risk of lung cancer by 14%.Outdoor air pollution is estimated to account for 1–2% of lung cancers.

      Genetics

      There is a genetic predisposition to lung cancer. In relatives of people with lung cancer, the risk is increased 2.4 times. This may be due to genetic polymorphisms

      Pathogenesis

      Main article: Carcinogenesis

      Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes.Oncogenes are genes that are believed to make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens. Mutations in the K-ras proto-oncogene are responsible for 10–30% of lung adenocarcinomas. The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion. Mutations and amplification of EGFR are common in non-small-cell lung cancer and provide the basis for treatment with EGFR-inhibitors. Her2/neu is affected less frequently.Chromosomal damage can lead to loss of heterozygosity. This can cause inactivation of tumor suppressor genes. Damage to chromosomes 3p, 5q, 13q, and 17p are particularly common in small-cell lung carcinoma. The p53 tumor suppressor gene, located on chromosome 17p, is affected in 60-75% of cases. Other genes that are often mutated or amplified are c-MET, NKX2-1, LKB1, PIK3CA, and BRAF.

      Diagnosis


      Prevention

      See also: Smoking ban

      Prevention is the most cost-effective means of mitigating lung cancer development. While in most countries industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and smoking cessation is an important preventive tool in this process.

      Policy interventions to decrease passive smoking in public areas such as restaurants and workplaces have become more common in many Western countries.Bhutan has had a complete smoking ban since 2005 . India introduced a ban on smoking in public in October 2008.

      The World Health Organization has called for governments to institute a total ban on tobacco advertising to prevent young people from taking up smoking. They assess that such bans have reduced tobacco consumption by 16% where instituted.

      The long-term use of supplemental vitamin A, vitamin C, vitamin D or vitamin Edoes not reduce the risk of lung cancer. Some studies suggest that people who eat diets with a higher proportion of vegetables and fruit tend have a lower risk. However this is likely due to confounding. More rigorous studies have not demonstrated a clear association.

      Screening

      Main article: Lung cancer screening

      Screening refers to the use of medical tests to detect disease in asymptomatic people. Possible screening tests for lung cancer include sputum cytology, chest radiograph, and computed tomography (CT). Screening programs using CXR or cytology have not demonstrated any benefit. Screening those at high risk (i.e. age 55 to 79 who have smoked more than 30 pack years or those who have had previous lung cancer) annually with low does CT scans may reduce the chance of death from lung cancer by an absolute amount of 0.3% (relative amount of 20%).The potential risks of screening however are not well known.

      Surgery

      If investigations confirm non-small cell lung cancer, the stage must be re-assessed to determine whether the disease is localized and amenable to surgery or whether it has spread to the point where it cannot be cured surgically. CT scan and positron emission tomography (PET) are used. If mediastinal lymph node involvement is suspected, mediastinoscopy may be used to sample the nodes and assist staging.Blood tests and pulmonary function testing are also necessary to assess whether the patient is well enough to be operated on.If pulmonary function tests reveal poor respiratory reserve, surgery may be contraindicated.In most cases of early stage non-small cell lung cancer, removal of a lobe of lung (lobectomy) is the surgical treatment of choice. In patients who are unfit for a full lobectomy, a smaller sublobar excision (wedge resection) may be performed. However wedge resection has a higher risk of recurrent disease than lobectomy.Radioactive iodine brachytherapy at the margins of wedge excision may reduce the risk of recurrence.Rarely, removal of a whole lung (pneumonectomy) is performed.Video-assisted thoracoscopic surgery and VATS lobectomy use a minimally invasive approach to lung cancer surgery. VATS lobectomy is equally effective compared to conventional open lobectomy, and with less post-operative illness.

      In small-cell lung carcinoma (SCLC), chemotherapy and/or radiotherapy is typically used.However the role of surgery in SCLC is being reconsidered. Surgery might improve outcomes when added to chemotherapy and radiation in early stage SCLC.

      Radiotherapy

      Radiotherapy is often given together with chemotherapy, and may be used with curative intent in patients with non-small cell lung carcinoma who are not eligible for surgery. This form of high intensity radiotherapy is called radical radiotherapy.A refinement of this technique is continuous hyperfractionated accelerated radiotherapy (CHART), in which a high dose of radiotherapy is given in a short time period.Post-operative thoracic radiotherapy generally should not be used after curative intent surgery for non-small cell lung carcinoma.Some patients with mediastinal N2 lymph node involvement might benefit from post-operative radiotherapy.For small cell lung carcinoma cases that are potentially curable, chest radiotherapy is often recommended in addition to chemotherapy.If cancer growth blocks a short section of bronchus, brachytherapy (localized radiotherapy) may be given directly inside the airway to open the passage.Compared to external beam radiotherapy, brachytherapy allows a reduction in treatment time and reduced radiation exposure to healthcare staff.Prophylactic cranial irradiation (PCI) is a type of radiotherapy to the brain, used to reduce the risk of metastasis. PCI is most useful in small cell lung carcinoma. In limited stage disease, PCI increases three-year survival from 15% to 20%; in extensive disease, one-year survival increases from 13% to 27%.Recent improvements in targeting and imaging have led to the development of stereotactic radiation in the treatment of early-stage lung cancer. In this form of radiotherapy, high doses are delivered in a small number of sessions using stereotactic targeting techniques. Its use is primarily in patients who are not surgical candidates due to medical comorbidities.For both non-small cell lung carcinoma and small cell lung carcinoma patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy) .                                               

      Non-small cell lung carcinoma

      In advanced non-small cell lung carcinoma, chemotherapy improves survival and is used as first-line treatment, provided the patient is well enough for the treatment.Typically, two drugs are used, of which one is often platinum-based (either cisplatin or carboplatin). Other commonly used drugs are gemcitabine, paclitaxel and docetaxel.Advanced non-small cell lung carcinoma is often treated with cisplatin or carboplatin, in combination with gemcitabine, paclitaxel, docetaxel, etoposide, or vinorelbine. Recently, pemetrexed has become available.

      Adjuvant chemotherapy

      Adjuvant chemotherapy refers to the use of chemotherapy after apparently curative surgery to improve the outcome. In non-small cell lung carcinoma, samples are taken of nearby lymph nodes during surgery to assist staging. If stage II or III disease is confirmed, adjuvant chemotherapy improves survival by 5% at 5 years.The combination of vinorelbine and cisplatin is more effective than older regimens.

      Adjuvant chemotherapy for patients with stage IB cancer is controversial, as clinical trials have not clearly demonstrated a survival benefit. Trials of preoperative chemotherapy (neoadjuvant chemotherapy) in resectable non-small-cell lung carcinoma have been inconclusive .

      History

      Lung cancer was uncommon before the advent of cigarette smoking; it was not even recognized as a distinct disease until 1761. Different aspects of lung cancer were described further in 1810.Malignant lung tumors made up only 1% of all cancers seen at autopsy in 1878, but had risen to 10–15% by the early 1900s. Case reports in the medical literature numbered only 374 worldwide in 1912, but a review of autopsies showed that the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952. In Germany in 1929, physician Fritz Lickint recognized the link between smoking and lung cancer, which led to an aggressive antismoking campaign.The British Doctors Study, published in the 1950s, was the first solid epidemiological evidence of the link between lung cancer and smoking. As a result, in 1964 the Surgeon General of the United States recommended that smokers should stop smoking.The connection with radon gas was first recognized among miners in the Ore Mountains near Schneeberg, Saxony. Silver has been mined there since 1470, and these mines are rich in uranium, with its accompanying radium and radon gas.Miners developed a disproportionate amount of lung disease, eventually recognized as lung cancer in the 1870s.Despite this discovery, mining continued into the 1950s, due to the USSR's demand for uranium. Radon was confirmed as a cause of lung cancer in the 1960s.The first successful pneumonectomy for lung cancer was performed in 1933. Palliative radiotherapy has been used since the 1940s.Radical radiotherapy, initially used in the 1950s, was an attempt to use larger radiation doses in patients with relatively early stage lung cancer but who were otherwise unfit for surgery.In 1997, continuous hyperfractionated accelerated radiotherapy (CHART) was seen as an improvement over conventional radical radiotherapy.With small cell lung carcinoma, initial attempts in the 1960s at surgical resection and radical radiotherapy were unsuccessful. In the 1970s, successful chemotherapy regimens were developed.

       

      Skin cancer

      Skin neoplasms (also known as "skin cancer") are skin growths with differing causes and varying degrees of malignancy. The three most common malignant skin cancers are basal cell cancer, squamous cell cancer, and melanoma, each of which is named after the type of skin cell from which it arises.


      Skin cancer generally develops in the epidermis (the outermost layer of skin), so a tumor can usually be seen. This means that it is often possible to detect skin cancers at an early stage. Unlike many other cancers, including those originating in the lung, pancreas, and stomach, only a small minority of those affected will actually die of the disease,though it can be disfiguring. Melanoma survival rates are poorer than for non-melanoma skin cancer, although when melanoma is diagnosed at an early stage, treatment is easier and more people survive.Skin cancer is the most commonly diagnosed type of cancer. Melanoma and non-melanoma skin cancers combined are more common than lung, breast, colorectal, and prostate cancer.Melanoma is less common than both basal cell carcinoma and squamous cell carcinoma, but it is the most serious — for example, in the UK there were over 11,700 new cases of melanoma in 2008, and over 2,000 deaths.It is the second most common cancer in young adults aged 15–34 in the UK.Most cases are caused by over-exposure to UV rays from the sun or sunbeds.Non-melanoma skin cancers are the most common skin cancers. The majority of these are basal cell carcinomas. These are usually localized growths caused by excessive cumulative exposure to the sun and do not tend to spread. 

      1.Basal cell carcinoma 
      Note the pearly translucency to fleshy color, tiny blood vessels on the surface, and sometime ulceration which can be characteristics. The key term is translucency.
      2.Squamous cell carcinoma
      Commonly presents as a red, crusted, or scaly patch or bump. Often a very rapid growing tumor.

      3.Malignant melanoma
      The common appearance is an asymmetrical area, with an irregular border, color variation, and often greater than 6 mm diameter.



      Basal cell carcinomas are present on sun-exposed areas of the skin, especially the face. They rarely metastasize and rarely cause death. They are easily treated with surgery or radiation. Squamous cell carcinomas (SCC) are common, but much less common than basal cell cancers. They metastasize more frequently than BCCs. Even then, the metastasis rate is quite low, with the exception of SCCs of the lip, ear, and in immunosuppressed patients. Melanomas are the least frequent of the 3 common skin cancers. They frequently metastasize, and could potentially cause death once they spread.

      Less common skin cancers include: Dermatofibrosarcoma protuberans, Merkel cell carcinoma, Kaposi's sarcoma, keratoacanthoma, spindle cell tumors, sebaceous carcinomas, microcystic adnexal carcinoma, Pagets's disease of the breast, atypical fibroxanthoma, leimyosarcoma, and angiosarcoma.

      The BCC and the SCC often carry a UV-signature mutation indicating that these cancers are caused by UV-B radiation via the direct DNA damage. However the malignant melanoma is predominantly caused by UV-A radiation via the indirect DNA damage.The indirect DNA damage is caused by free radicals and reactive oxygen species. Research indicates that the absorption of three sunscreen ingredients into the skin, combined with a 60-minute exposure to UV, leads to an increase of free radicals in the skin, if applied in too little quantities and too infrequently.However, the researchers add that newer creams often do not contain these specific compounds, and that the combination of other ingredients tends to retain the compounds on the surface of the skin. They also add the frequent re-application reduces the risk of radical formation.

      Signs and symptoms

      There are a variety of different skin cancer symptoms. These include changes in the skin that do not heal, ulcering in the skin, discolored skin, and changes in existing moles, such as jagged edges to the mole and enlargement of the mole.

      Basal cell carcinoma

      Basal cell carcinoma usually presents as a raised, smooth, pearly bump on the sun-exposed skin of the head, neck or shoulders. Sometimes small blood vessels can be seen within the tumor. Crusting and bleeding in the center of the tumor frequently develops. It is often mistaken for a sore that does not heal. This form of skin cancer is the least deadly and with proper treatment can be completely eliminated, often without scarring.

      Squamous cell carcinoma

      Squamous cell carcinoma is commonly a red, scaling, thickened patch on sun-exposed skin. Some are firm hard nodules and dome shaped like keratoacanthomas. Ulceration and bleeding may occur. When SCC is not treated, it may develop into a large mass. Squamous cell is the second most common skin cancer. It is dangerous, but not nearly as dangerous as a melanoma.

      Melanoma

      Most melanomas are brown to black looking lesions. Unfortunately, a few melanomas are pink, red or fleshy in color; these are called amelanotic melanomas. These tend to be more aggressive. Warning signs of malignant melanoma include change in the size, shape, color or elevation of a mole. Other signs are the appearance of a new mole during adulthood or new pain, itching, ulceration or bleeding. An often-used mnemonic is "ABCDE", where A= asymmetrical, B= "borders" (irregular= "Coast of Maine sign"), C= "color" (variegated), D= "diameter" (larger than 6 mm—the size of a pencil eraser) and E= "evolving."

      Causes

      Ultraviolet radiation from sun exposure is the primary cause of skin cancer.Other factors that play a role include:
      1.Smoking tobacco
      2.HPV infections increase the risk of squamous cell carcinoma.
      3.Some genetic syndromes including congenital melanocytic nevi syndrome which is characterized by the presence of nevi (birthmarks or moles) of varying size which are either present at birth, or appear within 6 months of birth. Nevi larger than 20 mm (3/4") in size are at higher risk for becoming cancerous.
      4.Chronic non-healing wounds.These are called Marjolin's ulcers based on their appearance, and can develop into squamous cell carcinoma.
      5.Ionizing radiation, environmental carcinogens, artificial UV radiation (e.g. tanning beds), aging, and light skin color.
      6.The use of many immunosuppressive medication increase the risk of skin cancer. Cyclosporin A, a calcineurin inhibitor for example increases the risk approximately 200 times, and azathioprine about 60 times.

      Pathophysiology


      Prevention

      Sunscreen is effective and thus recommended to prevent melanoma and squamous cell carcinoma.There is little evidence that it is effective in preventing basal cell carcinoma. Other advice to reduce rates of skin cancer includes: avoiding sunburning, wearing protective clothing, sunglasses and hats, and attempting to avoid periods of peak sun exposure.The U.S. Preventive Services Task Force recommends that people aged between 9 and 25 years of age are advised to avoid ultraviolet light.

      The risk of developing skin cancer can be reduced through a number of measures including: Decreasing indoor tanning and mid day sun exposure and increasing the use of sunscreen Avoiding the use of tobacco products.

      There is insufficient evidence to recommend for or against screening for skin cancer.Vitamins and antioxidants have not been found to have an effect in prevention.

      Reconstruction

      Currently, surgical excision is the most common form of treatment for skin cancers. The goal of reconstructive surgery is restoration of normal appearance and function. The choice of technique in reconstruction is dictated by the size and location of the defect. Excision and reconstruction of facial skin cancers is generally more challenging due to presence of highly visible and functional anatomic structures in the face.When skin defects are small in size, most can be repaired with simple repair where skin edges are approximated and closed with sutures. This will result in a linear scar. If the repair is made along a natural skin fold or wrinkle line, the scar will be hardly visible. Larger defects may require repair with a skin graft, local skin flap, pedicled skin flap, or a microvascular free flap. Skin grafts and local skin flaps are by far more common than the other listed choices.Skin grafting is patching of a defect with skin that is removed from another site in the body. The skin graft is sutured to the edges of the defect, and a bolster is placed atop the graft for seven to ten days, to immobilize the graft as it heals in place. There are two forms of skin grafting: split thickness and full thickness. In a split thickness skin graft, a shaver is used to shave a layer of skin from the abdomen or thigh. The donor site, regenerates skin and heals over a period of two weeks. In a full thickness skin graft, a segment of skin is totally removed and the donor site needs to be sutured closed.

      Split thickness grafts can be used to repair larger defects, but the grafts are inferior in their cosmetic appearance. Full thickness skin grafts are more acceptable cosmetically. However, full thickness grafts can only be used for small or moderate sized defects.

      Local skin flaps are a method of closing defects with tissue that closely matches the defect in color and quality. Skin from the periphery of the defect site is mobilized and repositioned to fill the deficit. Various forms of local flaps can be designed to minimize disruption to surrounding tissues and maximize cosmetic outcome of the reconstruction. Pedicled skin flaps are a method of transferring skin with an intact blood supply from a nearby region of the body. An example of such reconstruction is a pedicled forehead flap for repair of a large nasal skin defect. Once the flap develops a source of blood supply form its new bed, the vascular pedicle can be detached.

      Prognosis

      The mortality rate of basal cell and squamous cell carcinoma are around 0.3% causing 2000 deaths per year in the US. In comparison the mortality rate of melanoma is 15-20% and it causes 6500 deaths per year. Even though it is much less common, malignant melanoma is responsible for 75% of all skin cancer-related deaths.

      Stomach cancer

      Stomach cancer, or gastric cancer, refers to cancer arising from any part of the stomach. Stomach cancer causes about 800,000 deaths worldwide per year.

      Signs and symptoms

      Stomach cancer is often either asymptomatic (producing no noticeable symptoms) or it may cause only nonspecific symptoms (symptoms which are not specific to just stomach cancer, but also to other related or unrelated disorders) in its early stages. By the time symptoms occur, the cancer has often reached an advanced stage (see below) and may have also metastasized (spread to other, perhaps distant, parts of the body), which is one of the main reasons for its relatively poor prognosis.Stomach cancer can cause the following signs and symptoms:

      Stage 1 (Early)


      1.Indigestion or a burning sensation (heartburn)
      2.Loss of appetite, especially for meat
      3.Abdominal discomfort or irritation

        Stage 2 (Middle)


        1.Weakness and fatigue
        2.Bloating of the stomach, usually after meals

          Stage 3 (Late)


          1.Abdominal pain in the upper abdomen
          2.Nausea and occasional vomiting
          3.Diarrhea or constipation
          4.Weight loss
          5.Bleeding (vomiting blood or having blood in the stool) which will appear as black. This can lead to anemia.
          6.Dysphagia; this feature suggests a tumor in the cardia or extension of the gastric tumor in to the esophagus.

          Note that these can be symptoms of other problems such as a stomach virus, gastric ulcer or tropical sprue.

          Causes

          Infection by Helicobacter pylori is believed to be the cause of most stomach cancer while autoimmune atrophic gastritis, intestinal metaplasia and various genetic factors are associated with increased risk levels. The Merck Manual states that diet plays no role in the genesis of stomach cancer.However, the American Cancer Society lists the following dietary risks, and protective factors, for stomach cancer: "smoked foods, salted fish and meat, and pickled vegetables (appear to increase the risk of stomach cancer.) Nitrates and nitrites are substances commonly found in cured meats. They can be converted by certain bacteria, such as H. pylori, into compounds that have been found to cause stomach cancer in animals. On the other hand, eating fresh fruits and vegetables that contain antioxidant vitamins (such as A and C) appears to lower the risk of stomach cancer." A December 2009 article in American Journal of Clinical Nutrition found a statistically significant inverse correlation between higher adherence to a Mediterranean Dietary Pattern and stomach cancer.

          In more detail, H. pylori is the main risk factor in 65–80% of gastric cancers, but in only 2% of such infections.The mechanism by which H. pylori induces stomach cancer potentially involves chronic inflammation, or the action of H. pylori virulence factors such as CagA. Approximately ten percent of cases show a genetic component.Some studies indicate that bracken consumption and spores are correlated with incidence of stomach cancer, though causality has yet to be established.

          A very important but preventable cause of gastric cancer is tobacco smoking. Smoking increases the risk of developing gastric cancer considerably; from 40% increased risk for current smokers to 82% increase for heavy smokers which is nearly twice the risk for non-smoking population. Gastric cancers due to smoking mostly occur in upper part of stomach near esophagus Another lifestyle cause of gastric cancer besides smoking is consumption of alcohol. Alcohol along with tobacco smoking increase the risk of developing other cancers as well.Gastric cancer shows a male predominance in its incidence as up to three males are affected for every female. Estrogen may protect women against the development of this cancer form.A very small percentage of diffuse-type gastric cancers (see Histopathology below) are thought to be genetic. Hereditary Diffuse Gastric Cancer (HDGC) has recently been identified and research is ongoing. However, genetic testing and treatment options are already available for families at risk.

          The International Cancer Genome Consortium is leading efforts to map stomach cancer's complete genome.

          Diagnosis

          To find the cause of symptoms, the doctor asks about the patient's medical history, does a physical exam, and may order laboratory studies. The patient may also have one or all of the following exams:

          1.Gastroscopic exam is the diagnostic method of choice. This involves insertion of a fiber optic camera into the stomach to visualize it.
          2.Upper GI series (may be called barium roentgenogram)
          3.Computed tomography or CT scanning of the abdomen may reveal gastric cancer, but is more useful to determine invasion into adjacent tissues, or the presence of spread to local lymph nodes.

          Abnormal tissue seen in a gastroscope examination will be biopsied by the surgeon or gastroenterologist. This tissue is then sent to a pathologist for histological examination under a microscope to check for the presence of cancerous cells. A biopsy, with subsequent histological analysis, is the only sure way to confirm the presence of cancer cells.Various gastroscopic modalities have been developed to increased yield of detect mucosa with a dye that accentuates the cell structure and can identify areas of dysplasia. Endocytoscopy involves ultra-high magnification to visualize cellular structure to better determine areas of dysplasia. Other gastroscopic modalities such as optical coherence tomography are also being tested investigationally for similar applications.A number of cutaneous conditions are associated with gastric cancer. A condition of darkened hyperplasia of the skin, frequently of the axilla and groin, known as acanthosis nigricans, is associated with intra-abdominal cancers such as gastric cancer. Other cutaneous manifestations of gastric cancer include tripe palms (a similar darkening hyperplasia of the skin of the palms) and the sign of Leser-Trelat, which is the rapid development of skin lesions known as seborrheic keratoses.

          Various blood tests may be done; including: Complete Blood Count (CBC) to check for anemia. Also, a stool test may be performed to check for blood in the stool.

          Histopathology


          Gastric adenocarcinoma is a malignant epithelial tumor, originating from glandular epithelium of the gastric mucosa. Stomach cancers are overwhelmingly adenocarcinomas (90%).Histologically, there are two major types of gastric adenocarcinoma (Lauren classification): intestinal type or diffuse type. Adenocarcinomas tend to aggressively invade the gastric wall, infiltrating the muscularis mucosae, the submucosa, and thence the muscularis propria. Intestinal type adenocarcinoma tumor cells describe irregular tubular structures, harboring pluristratification, multiple lumens, reduced stroma ("back to back" aspect). Often, it associates intestinal metaplasia in neighboring mucosa. Depending on glandular architecture, cellular pleomorphism and mucosecretion, adenocarcinoma may present 3 degrees of differentiation: well, moderate and poorly differentiated. Diffuse type adenocarcinoma (mucinous, colloid, linitis plastica, leather-bottle stomach) Tumor cells are discohesive and secrete mucus which is delivered in the interstitium producing large pools of mucus/colloid (optically "empty" spaces). It is poorly differentiated. If the mucus remains inside the tumor cell, it pushes the nucleus to the periphery- "signet-ring cell".
          Around 5% of gastric malignancies are lymphomas (MALTomas, or MALT lymphoma).
          Carcinoid and stromal tumors may also occur.

            Staging

            If cancer cells are found in the tissue sample, the next step is to stage, or find out the extent of the disease. Various tests determine whether the cancer has spread and, if so, what parts of the body are affected. Because stomach cancer can spread to the liver, the pancreas, and other organs near the stomach as well as to the lungs, the doctor may order a CT scan, a PET scan, an endoscopic ultrasound exam, or other tests to check these areas. Blood tests for tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) may be ordered, as their levels correlate to extent of metastasis, especially to the liver, and the cure rate.Staging may not be complete until after surgery. The surgeon removes nearby lymph nodes and possibly samples of tissue from other areas in the abdomen for examination by a pathologist.

            The clinical stages of stomach cancer are:
            • Stage 0. Limited to the inner lining of the stomach. Treatable by endoscopic mucosal resection when found very early (in routine screenings); otherwise by gastrectomy and lymphadenectomy without need for chemotherapy or radiation. 
            • Stage I. Penetration to the second or third layers of the stomach 
            •  (Stage 1A) or to the second layer and nearby lymph nodes (Stage 1B). Stage 1A is treated by surgery, including removal of the omentum. Stage 1B may be treated with chemotherapy (5-fluorouracil) and radiation therapy.
            • Stage II. Penetration to the second layer and more distant lymph nodes, or the third layer and only nearby lymph nodes, or all four layers but not the lymph nodes. Treated as for Stage I, sometimes with additional neoadjuvant chemotherapy.
            • Stage III. Penetration to the third layer and more distant lymph nodes, or penetration to the fourth layer and either nearby tissues or nearby or more distant lymph nodes.
            • Stage IV. Cancer has spread to nearby tissues and more distant lymph nodes, or has metastatized to other organs. A cure is very rarely possible at this stage. Some other techniques to prolong life or improve symptoms are used, including laser treatment, surgery, and/or stents to keep the digestive tract open, and chemotherapy by drugs such as 5-fluorouracil, cisplatin, epirubicin, etoposide, docetaxel, oxaliplatin, capecitabine, or irinotecan.
              The TNM staging system is also used.

              In a study of open-access endoscopy in Scotland, patients were diagnosed 7% in Stage I 17% in Stage II, and 28% in Stage III.A Minnesota population was diagnosed 10% in Stage I, 13% in Stage II, and 18% in Stage III.However in a high-risk population in the Valdivia Province of southern Chile, only 5% of patients were diagnosed in the first two stages and 10% in stage III.

              Management

              As with any cancer, treatment is adapted to fit each person's individual needs and depends on the size, location, and extent of the tumor, the stage of the disease, and general health. Cancer of the stomach is difficult to cure unless it is found in an early stage (before it has begun to spread). Unfortunately, because early stomach cancer causes few symptoms, the disease is usually advanced when the diagnosis is made. Treatment for stomach cancer may include surgery, chemotherapy, and/or radiation therapy. New treatment approaches such as biological therapy and improved ways of using current methods are being studied in clinical trials.An antibody-drug conjugate IMGN242 is in phase II clinical trials.

              Surgery

              Surgery is the most common treatment. The surgeon removes part or all of the stomach, as well as the surrounding lymph nodes, with the basic goal of removing all cancer and a margin of normal tissue. Depending on the extent of invasion and the location of the tumor, surgery may also include removal of part of the intestine or pancreas. Tumors in the lower part of the stomach may call for a Billroth I or Billroth II procedure.

              Endoscopic mucosal resection (EMR) is a treatment for early gastric cancer (tumor only involves the mucosa) that has been pioneered in Japan, but is also available in the United States at some centers. In this procedure, the tumor, together with the inner lining of stomach (mucosa), is removed from the wall of the stomach using an electrical wire loop through the endoscope. The advantage is that it is a much smaller operation than removing the stomach. Endoscopic submucosal dissection (ESD) is a similar technique pioneered in Japan, used to resect a large area of mucosa in one piece. If the pathologic examination of the resected specimen shows incomplete resection or deep invasion by tumor, the patient would need a formal stomach resection.Surgical interventions are currently curative in less than 40% of cases, and, in cases of metastasis, may only be palliative.

              Chemotherapy

              The use of chemotherapy to treat stomach cancer has no firmly established standard of care. Unfortunately, stomach cancer has not been particularly sensitive to these drugs, and chemotherapy, if used, has usually served to palliatively reduce the size of the tumor, relieve symptoms of the disease and increase survival time. Some drugs used in stomach cancer treatment have included: 5-FU (fluorouracil) or its analog capecitabine, BCNU (carmustine), methyl-CCNU (Semustine), and doxorubicin (Adriamycin), as well as Mitomycin C, and more recently cisplatin and taxotere, often using drugs in various combinations. The relative benefits of these different drugs, alone and in combination, are unclear.Clinical researchers have explored the benefits of giving chemotherapy before surgery to shrink the tumor, or as adjuvant therapy after surgery to destroy remaining cancer cells. Combination treatment with chemotherapy and radiation therapy has some activity in selected post surgical settings. For patients who have HER2 overexpressing metastatic gastric or gastroesophageal (GE) junction adenocarcinoma, who have not received prior treatment for their metastatic disease, the US Food and Drug Administration granted approval (2010 October) for trastuzumab (Herceptin, Genentech, Inc.) in combination with cisplatin and a fluoropyrimidine (capecitabine or 5-fluorouracil). This was based on an improvement of the median overall survival (OS) of 2.5 months with trastuzumab plus chemotherapy treatment compared to chemotherapy alone (BO18255 ToGA trial). The combination of Herceptin with chemotherapy for treating metastatic gastric cancer was also sanctioned by the European regulatory authorities (2010 January). Doctors have also tested putting the anticancer drugs directly into the abdomen, often with warmed solutions of the medication (intraperitoneal hyperthermic chemoperfusion).

              Radiation

              Radiation therapy (also called radiotherapy) is the use of high-energy rays to damage cancer cells and stop them from growing. When used, it is generally in combination with surgery and chemotherapy, or used only with chemotherapy in cases where the individual is unable to undergo surgery. Radiation therapy may be used to relieve pain or blockage by shrinking the tumor for palliation of incurable disease.

              Multimodality therapy

              While previous studies of multimodality therapy (combinations of surgery, chemotherapy and radiation therapy) gave mixed results, the Intergroup 0116 (SWOG 9008) study showed a survival benefit to the combination of chemotherapy and radiation therapy in patients with nonmetastatic, completely resected gastric cancer. Patients were randomized after surgery to the standard group of observation alone, or the study arm of combination chemotherapy and radiation therapy. Those in the study arm receiving chemotherapy and radiation therapy survived on average 36 months; compared to 27 months with observation.

              Brain tum


              A brain tumor, or tumour, is an intra cranial solid neoplasm, a tumor (defined as an abnormal growth of cells) within the brain or the central spinal canal.

              Brain tumors include all tumors inside the cranium or in the central spinal canal. They are created by an abnormal and uncontrolled cell division, usually in the brain itself, but also in lymphatic tissue, in blood vessels, in the cranial nerves, in the brain envelopes (meninges), skull, pituitary gland, or pineal gland. Within the brain itself, the involved cells may be neurons or glial cells (which include astrocytes, oligodendrocytes, and ependymal cells). Brain tumors may also spread from cancers primarily located in other organs (metastatic tumors).Any brain tumor is inherently serious and life-threatening because of its invasive and infiltrative character in the limited space of the intracranial cavity. However, brain tumors (even malignant ones) are not invariably fatal, especially lipomas which are inherently benign. Brain tumors or intracranial neoplasms can be cancerous (malignant) or non-cancerous (benign); however, the definitions of malignant or benign neoplasms differs from those commonly used in other types of cancerous or non-cancerous neoplasms in the body. Its threat level depends on the combination of factors like the type of tumor, its location, its size and its state of development. Because the brain is well protected by the skull, the early detection of a brain tumor occurs only when diagnostic tools are directed at the intracranial cavity. Usually detection occurs in advanced stages when the presence of the tumor has caused unexplained symptoms.

              Primary (true) brain tumors are commonly located in the posterior cranial fossa in children and in the anterior two-thirds of the cerebral hemispheres in adults, although they can affect any part of the brain.

              Signs and symptoms

              Visibility of signs and symptoms of brain tumors mainly depends on two factors: tumor size (volume) and tumor location. The moment that symptoms will become apparent, either to the person or people around him (symptom onset) is an important milestone in the course of the diagnosis and treatment of the tumor. The symptom onset - in the timeline of the development of the neoplasm - depends in many cases on the nature of the tumor but in many cases is also related to the change of the neoplasm from "benign" (i.e. slow-growing/late symptom onset) to more malignant (fast growing/early symptom onset).Symptoms of solid neoplasms of the brain (primary brain tumors and secondary tumors alike) can be divided in 3 main categories :
              • Consequences of intracranial hypertension : The symptoms that often occur first are those that are the consequences of increased intracranial pressure: Large tumors or tumors with extensive perifocal swelling (edema) inevitably lead to elevated intracranial pressure (intracranial hypertension), which translates clinically into headaches, vomiting (sometimes without nausea), altered state of consciousness (somnolence, coma), dilation of the pupil on the side of the lesion (anisocoria), papilledema (prominent optic disc at the funduscopic eye examination). However, even small tumors obstructing the passage of cerebrospinal fluid (CSF) may cause early signs of increased intracranial pressure. Increased intracranial pressure may result in herniation (i.e. displacement) of certain parts of the brain, such as the cerebellar tonsils or the temporal uncus, resulting in lethal brainstem compression. In very young children, elevated intracranial pressure may cause an increase in the diameter of the skull and bulging of the fontanelles.
              • Dysfunction : depending on the tumor location and the damage it may have caused to surrounding brain structures, either through compression or infiltration, any type of focal neurologic symptoms may occur, such as cognitive and behavioral impairment (including impaired judgment, memory loss, lack of recognition, spatial orientation disorders), personality or emotional changes, hemiparesis, hypoesthesia, aphasia, ataxia, visual field impairment, impaired sense of smell, impaired hearing, facial paralysis, double vision, dizziness, but more severe symptoms might occur too such as: paralysis on one side of the body hemiplegia or impairment to swallow . These symptoms are not specific for brain tumors — they may be caused by a large variety of neurologic conditions (e.g. stroke, traumatic brain injury). What counts, however, is the location of the lesion and the functional systems (e.g. motor, sensory, visual, etc.) it affects. A bilateral temporal visual field defect (bitemporal hemianopia—due to compression of the optic chiasm), often associated with endocrine disfunction—either hypopituitarism or hyperproduction of pituitary hormones and hyperprolactinemia is suggestive of a pituitary tumor.
              • Irritation : abnormal fatigue, weariness, absences and tremors, but also epileptic seizures.
                The above symptoms are true for ALL types of neoplasm of the brain (including secondary tumors). It is common that a person carry a primary benign neoplasm for several years and have no visible symptoms at all. Many present some vague and intermittent symptoms like headaches and occasional vomiting or weariness, which can be easily mistaken for gastritis or gastroenteritis. It might seem strange that despite having a mass in his skull exercising pressure on the brain the patient feels no pain, but as anyone who has suffered a concussion can attest, pain is felt on the outside of the skull and not in the brain itself. The brain has no nerve sensors in the meninges (outer surface) with which to feel or transmit pain to the brain's pain center; it cannot signal pain without a sensory input. That is why secondary symptoms like those described above should alert doctors to the possible diagnosis of a neoplasm of the brain.

                When a person suffering from a metastasized cancer is diagnosed, a scan of the skull frequently reveals secondary tumors.

                In a recent study by the Dutch GP Association, a list of causes of headaches was published, that should alert GP's to take their diagnosis further then to choose for symptomatic treatment of headaches with simple pain medication (note the occurrence of brain tumors as possible cause):

                Cause

                Aside from exposure to vinyl chloride or ionizing radiation, there are no known environmental factors associated with brain tumors. Mutations and deletions of so-called tumor suppressor genes are thought to be the cause of some forms of brain tumors. People with various inherited diseases, such as Von Hippel-Lindau syndrome, multiple endocrine neoplasia, neurofibromatosis type 2 are at high risk of developing brain tumors.

                Although studies have not shown any link between cell phone radiation and brain tumors,the World Health Organization has classified mobile phone radiation on the IARC scale into Group 2B - possibly carcinogenic. That means that there "could be some risk" of carcinogenicity, so additional research into the long-term, heavy use of mobile phones needs to be conducted.

                Anatomy

                From the brain-Wikipedia article and for the purpose of understanding this article some summary notes about the brain and its different types of organic tissues will be provided.

                When reading the human brain in the picture on the right, only a few of the areas are really of interest to us. The first type of tissue encountered beneath the skullbone in the intracranial cavity is actually not shown on this picture: the meninges. This is what is inflamed in meningitis.

                Meninges

                Human brains are surrounded by a system of connective tissue membranes called meninges that separate the skull from the brain. This three-layered covering is composed of (from the outside in) the dura mater ("hard mother"), arachnoid mater ("spidery mother"), and pia mater ("soft mother"). The arachnoid and pia are physically connected and thus often considered as a single layer, the pia-arachnoid. Below the arachnoid is the subarachnoid space which contains cerebrospinal fluid, which circulates in the narrow spaces between cells and through cavities called ventricles, and serves to nourish, support, and protect the brain tissue. Blood vessels enter the central nervous system through the perivascular space above the pia mater. The cells in the blood vessel walls are joined tightly, forming the blood–brain barrier which protects the brain from toxins that might enter through the blood. Tumors of the meninges are meningioma and are often benign neoplasms.

                Brain matter

                The brains of vertebrates (including humans) are made of very soft tissue, with a texture that has been compared to gelatin. Living brain tissue is pinkish on the outside and mostly white on the inside, with subtle variations in color. Three separate brain areas make up the majority of brain volume:
                ·          

                • telencephalon (cerebral hemispheres or cerebrum)
                • mesencephalon (midbrain)
                • cerebellum
                  These areas are composed of two broad classes of cells: neurons and glia. These two types are equally numerous in the brain as a whole, although glial cells outnumber neurons roughly 4 to 1 in the cerebral cortex. Glia come in several types, which perform a number of critical functions, including structural support, metabolic support, insulation, and guidance of development.

                  Primary tumors of the glial cells are called Glioma and often are malignant by the time they are diagnosed.

                  Spinal cord and other tissues

                  • The pink area in picture is called the pons and is a specific region that consists of myelinated axons much like the spinal cord
                  • The yellow region is the diencephalon (thalamus and hypothalamus) which consist also of neuron and glial cell tissue with the hypophysis (or pituitary gland) and pineal gland (which is glandular tissue) attached at the bottom; tumors of the pituitary and pineal gland are often benign neoplasms
                  • The turquoise region or medulla oblongata is the end of the spinal cord and is composed mainly of neuron tissue enveloped in Schwann cells and meninges tissue. Our spinal cord is made up of bundles of these axons. Glial cells such as Schwann cells in the periphery or, within the cord itself, oligodendrocyte, wrap themselves around the axon, thus promoting faster transmission of electrical signals and also providing for general maintenance of the environment surrounding the cord, in part by shuttling different compounds around, responding to injury, etc.

                    Diagnosis

                    Although there is no specific or singular clinical symptom or sign for any brain tumors, the presence of a combination of symptoms and the lack of corresponding clinical indications of infections or other causes can be an indicator to redirect diagnostic investigation towards the possibility of an intracranial neoplasm.

                    The diagnosis will often start with an interrogation of the patient to get a clear view of his medical antecedents, and his current symptoms. Clinical and laboratory investigations will serve to exclude infections as the cause of the symptoms. Examinations in this stage may include the eyes, otolaryngological (or ENT) and/or electrophysiological exams. The use of electroencephalography (EEG) often plays a role in the diagnosis of brain tumors.

                    Swelling, or obstruction of the passage of cerebrospinal fluid (CSF) from the brain may cause (early) signs of increased intracranial pressure which translates clinically into headaches, vomiting, or an altered state of consciousness, and in children changes to the diameter of the skull and bulging of the fontanelles. More complex symptoms such as endocrine dysfunctions should alarm doctors not to exclude brain tumors.

                    A bilateral temporal visual field defect (due to compression of the optic chiasm) or dilatation of the pupil, and the occurrence of either slowly evolving or the sudden onset of focal neurologic symptoms, such as cognitive and behavioral impairment (including impaired judgment, memory loss, lack of recognition, spatial orientation disorders), personality or emotional changes, hemiparesis, hypoesthesia, aphasia, ataxia, visual field impairment, impaired sense of smell, impaired hearing, facial paralysis, double vision, or more severe symptoms such as tremors, paralysis on one side of the body hemiplegia, or (epileptic) seizures in a patient with a negative history for epilepsy, should raise the possibility of a brain tumor.

                    Imaging plays a central role in the diagnosis of brain tumors. Early imaging methods—invasive and sometimes dangerous— such as pneumoencephalography and cerebral angiography, have been abandoned in recent times in favor of non-invasive, high-resolution techniques, such as computed tomography (CT)-scans and especially magnetic resonance imaging (MRI). Neoplasms will often show as differently colored masses (also referred to as processes) in CT or MRI results.
                    • Benign brain tumors often show up as hypodense (darker than brain tissue) mass lesions on cranial CT-scans. On MRI, they appear either hypo- (darker than brain tissue) or isointense (same intensity as brain tissue) on T1-weighted scans, or hyperintense (brighter than brain tissue) on T2-weighted MRI, although the appearance is variable.
                    • Contrast agent uptake, sometimes in characteristic patterns, can be demonstrated on either CT or MRI-scans in most malignant primary and metastatic brain tumors.
                    • Perifocal edema, or pressure-areas, or where the brain tissue has been compressed by an invasive process also appears hyperintense on T2-weighted MRI, they might indicate the presence a diffuse neoplasm (unclear outline)
                      This is because these tumors disrupt the normal functioning of the blood–brain barrier and lead to an increase in its permeability. However it is not possible to diagnose high versus low grade gliomas based on enhancement pattern alone.

                      Glioblastoma multiforme and anaplastic astrocytoma have been associated with the genetic acute hepatic porphyrias (PCT, AIP, HCP and VP), including positive testing associated with drug refractory seizures.Unexplained complications associated with drug treatments with these tumors should alert physicians to an undiagnosed neurological porphyria.

                      The definitive diagnosis of brain tumor can only be confirmed by histological examination of tumor tissue samples obtained either by means of brain biopsy or open surgery. The histological examination is essential for determining the appropriate treatment and the correct prognosis. This examination, performed by a pathologist, typically has three stages: interoperative examination of fresh tissue, preliminary microscopic examination of prepared tissues, and followup examination of prepared tissues after immunohistochemical staining or genetic analysis.

                      Pathology


                      Micrograph of an oligodendroglioma, a type of brain cancer. Brain biopsy. H&E stain.Tumors have characteristics that allow determination of its malignacy, how it will evolve and it will allow the medical team to determine the management plan.Anaplasia: or dedifferentiation; loss of differentiation of cells and of their orientation to one another and blood vessels, a characteristic of anaplastic tumor tissue. Anaplastic cells have lost total control of their normal functions and many have deteriorated cell structures. Anaplastic cells often have abnormally high nuclear-to-cytoplasmic ratios, and many are multinucleated. Additionally, the nuclei of anaplastic cells are usually unnaturally shaped or oversized nuclei. Cells can become anaplastic in two ways: neoplastic tumor cells can dedifferentiate to become anaplasias (the dedifferentiation causes the cells to lose all of their normal structure/function), or cancer stem cells can increase in their capacity to multiply (i.e., uncontrollable growth due to failure of differentiation).

                      Atypia: is an indication of abnormality of a cell (which may be indicative for malignancy). Significance of the abnormality is highly dependent on context.

                      Neoplasia: is the (uncontrolled) division of cells; as such neoplasia is not problematic but its consequences are: the uncontrolled division of cells means that the mass of a neoplasm increases in size, and in a confined space such as the intracranial cavity this quickly becomes problematic because the mass invades the space of the brain pushing it aside, leading to compression of the brain tissue and increased intracranial pressure and destruction of brain parenchyma. Increased Intracranial pressure (ICP) may be attributable to the direct mass effect of the tumor, increased blood volume, or increased cerebrospinal fluid (CSF) volume may in turn have secondary symptoms

                      Necrosis: is the (premature) death of cells, caused by external factors such as infection, toxin or trauma. Necrotic cells send the wrong chemical signals which prevents phagocytes from disposing of the dead cells, leading to a build up of dead tissue, cell debris and toxins at or near the site of the necrotic cellsArterial and venous hypoxia, or the deprivation of adequate oxygen supply to certain areas of the brain, occurs when a tumor makes use of nearby blood vessels for its supply of blood and the neoplasm enters into competition for nutrients with the surrounding brain tissue.

                      More generally a neoplasm may cause release of metabolic end products (e.g., free radicals, altered electrolytes, neurotransmitters), and release and recruitment of cellular mediators (e.g., cytokines) that disrupt normal parenchymal function.

                      Secondary brain tumors

                      Secondary tumors of the brain are metastatic tumors that invaded the intracranial sphere from cancers originating in other organs. This means that a cancerous neoplasm has developed in another organ elsewhere in the body and that cancer cells have leaked from that primary tumor and then entered the lymphatic system and blood vessels. They then circulate through the bloodstream, and are deposited in the brain. There, these cells continue growing and dividing, becoming another invasive neoplasm of the primary cancer's tissue. Secondary tumors of the brain are very common in the terminal phases of patients with an incurable metastasized cancer; the most common types of cancers that bring about secondary tumors of the brain are lung cancer, breast cancer, malignant melanoma, kidney cancer and colon cancer (in decreasing order of frequency).Secondary brain tumors are the most common cause of tumors in the intracranial cavity.The skull bone structure can also be subject to a neoplasm that by its very nature reduces the volume of the intracranial cavity, and can damage the brain.

                      By behavior

                      Brain tumors or intracranial neoplasms can be cancerous (malignant) or non-cancerous (benign). However, the definitions of malignant or benign neoplasms differs from those commonly used in other types of cancerous or non-cancerous neoplasms in the body. In cancers elsewhere in the body, three malignant properties differentiate benign tumors from malignant forms of cancer: benign tumors are self-limited and do not invade or metastasize. Characteristics of malignant tumors include:
                      • uncontrolled mitosis (growth by division beyond the normal limits)
                      • anaplasia: the cells in the neoplasm have an obviously different form (in size and shape). Anaplastic cells display marked pleomorphism. The cell nuclei are characteristically extremely hyperchromatic (darkly stained) and enlarged; the nucleus might have the same size as the cytoplasm of the cell (nuclear-cytoplasmic ratio may approach 1:1, instead of the normal 1:4 or 1:6 ratio). Giant cells - considerably larger than their neighbors - may form and possess either one enormous nucleus or several nuclei (syncytia). Anaplastic nuclei are variable and bizarre in size and shape.
                      • invasion or infiltration (medical literature uses these terms as synonymous equivalents. However, for clarity, the articles that follow adhere to a convention that they mean slightly different things; this convention is not followed outside these articles):
                      • Invasion or invasiveness is the spatial expansion of the tumor through uncontrolled mitosis, in the sense that the neoplasm invades the space occupied by adjacent tissue, thereby pushing the other tissue aside and eventually compressing the tissue. Often these tumors are associated with clearly outlined tumors in imaging.
                      • Infiltration is the behavior of the tumor either to grow (microscopic) tentacles that push into the surrounding tissue (often making the outline of the tumor undefined or diffuse) or to have tumor cells "seeded" into the tissue beyond the circumference of the tumorous mass; this does not mean that an infiltrative tumor does not take up space or does not compress the surrounding tissue as it grows, but an infiltrating neoplasm makes it difficult to say where the tumor ends and the healthy tissue starts.
                      • metastasis (spread to other locations in the body via lymph or blood).
                      • Of the above malignant characteristics, some elements do not apply to primary neoplasms of the brain:
                      • Primary brain tumors rarely metastasize to other organs; some forms of primary brain tumors can metastasize but will not spread outside the intracranial cavity or the central spinal canal. Due to the blood–brain barrier cancerous cells of a primary neoplasm cannot enter the bloodstream and get carried to another location in the body. (Occasional isolated case reports suggest spread of certain brain tumors outside the central nervous system, e.g. bone metastasis of glioblastoma multiforme.)
                      • Primary brain tumors generally are invasive (i.e. they will expand spatially and intrude into the space occupied by other brain tissue and compress those brain tissues), however some of the more malignant primary brain tumors will infiltrate the surrounding tissue.
                      Of numerous grading systems in use for the classification of tumor of the central nervous system, the World Health Organization (WHO) grading system is commonly used for astrocytoma. Established in 1993 in an effort to eliminate confusion regarding diagnoses, the WHO system established a four-tiered histologic grading guideline for astrocytomas that assigns a grade from 1 to 4, with 1 being the least aggressive and 4 being the most aggressive.

                      Treatment

                      When a brain tumor is diagnosed, a medical team will be formed to assess the treatment options presented by the leading surgeon to the patient and his/her family. Given the location of primary solid neoplasms of the brain in most cases a "do-nothing" option is usually not presented. Neurosurgeons take the time to observe the evolution of the neoplasm before proposing a management plan to the patient and his/her relatives. These various types of treatment are available depending on neoplasm type and location and may be combined to give the best chances of survival:
                      • surgery: complete or partial resection of the tumor with the objective of removing as many tumor cells as possible
                      • radiotherapy: the most commonly used treatment for brain tumours, the tumour is target at with alpha and beta rays to shrink the tumour. The tumour is aimed at with the rays in a circular motion to minimize damage to the surrounding cells.
                      • chemotherapy: is a treatment option for cancer, however it is seldom used to treat brain tumours as the blood and brain barrier prevents the drugs from reaching the cancerous cells. Chemotherapy can be thought of as a poison that prevents the growth and division of all cells in the body including cancerous cells. Thus the significant side effects associated and experienced by patients undergoing chemotherapy.
                      • A variety of experimental therapies are available through clinical trials
                        Survival rates in primary brain tumors depend on the type of tumor, age, functional status of the patient, the extent of surgical tumor removal and other factors specific to each case.

                        Surgery

                        The primary and most desired course of action described in medical literature is surgical removal (resection) via craniotomy. Minimally invasive techniques are being studied but are far from being common practice. The prime remediating objective of surgery is to remove as many tumor cells as possible, with complete removal being the best outcome and cytoreduction ("debulking") of the tumor otherwise. In some cases access to the tumor is impossible and impedes or prohibits surgery.

                        Many meningiomas, with the exception of some tumors located at the skull base, can be successfully removed surgically. Most pituitary adenomas can be removed surgically, often using a minimally invasive approach through the nasal cavity and skull base (trans-nasal, trans-sphenoidal approach). Large pituitary adenomas require a craniotomy (opening of the skull) for their removal. Radiotherapy, including stereotactic approaches, is reserved for inoperable cases.

                        Several current research studies aim to improve the surgical removal of brain tumors by labeling tumor cells with 5-aminolevulinic acid that causes them to fluoresce.Postoperative radiotherapy and chemotherapy are integral parts of the therapeutic standard for malignant tumors. Radiotherapy may also be administered in cases of "low-grade" gliomas, when a significant tumor burden reduction could not be achieved surgically.Any person undergoing brain surgery may suffer from epileptic seizures. Seizures can vary from absences to severe tonic-clonic attacks. Medication is prescribed and administered to minimize or eliminate the occurrence of seizures.Multiple metastatic tumors are generally treated with radiotherapy and chemotherapy rather than surgery and the prognosis in such cases is determined by the primary tumor, but is generally poor.

                        Radiation therapy

                        The goal of radiation therapy is to selectively kill tumor cells while leaving normal brain tissue unharmed. In standard external beam radiation therapy, multiple treatments of standard-dose "fractions" of radiation are applied to the brain. This process is repeated for a total of 10 to 30 treatments, depending on the type of tumor. This additional treatment provides some patients with improved outcomes and longer survival rates.

                        Radiosurgery is a treatment method that uses computerized calculations to focus radiation at the site of the tumor while minimizing the radiation dose to the surrounding brain. Radiosurgery may be an adjunct to other treatments, or it may represent the primary treatment technique for some tumors.

                        Radiotherapy may be used following, or in some cases in place of, resection of the tumor. Forms of radiotherapy used for brain cancer include external beam radiation therapy, brachytherapy, and in more difficult cases, stereotactic radiosurgery, such as Gamma knife, Cyberknife or Novalis Tx radiosurgery.

                        Radiotherapy is the most common treatment for secondary brain tumors. The amount of radiotherapy depends on the size of the area of the brain affected by cancer. Conventional external beam 'whole brain radiotherapy treatment' (WBRT) or 'whole brain irradiation' may be suggested if there is a risk that other secondary tumors will develop in the future. Stereotactic radiotherapy is usually recommended in cases involving fewer than three small secondary brain tumors.

                        In 2008 a study published by the University of Texas M. D. Anderson Cancer Center indicated that cancer patients who receive stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) for the treatment of metastatic brain tumors have more than twice the risk of developing learning and memory problems than those treated with SRS alone.

                        Chemotherapy

                        Patients undergoing chemotherapy are administered drugs designed to kill tumor cells. Although chemotherapy may improve overall survival in patients with the most malignant primary brain tumors, it does so in only about 20 percent of patients. Chemotherapy is often used in young children instead of radiation, as radiation may have negative effects on the developing brain. The decision to prescribe this treatment is based on a patient’s overall health, type of tumor, and extent of the cancer. The toxicity and many side effects of the drugs, and the uncertain outcome of chemotherapy in brain tumors puts this treatment further down the line of treatment options with surgery and radiation therapy preferred.UCLA Neuro-Oncology publishes real-time survival data for patients with a diagnosis of glioblastoma multiforme. They are the only institution in the United States that displays how brain tumor patients are performing on current therapies. They also show a listing of chemotherapy agents used to treat high grade glioma tumors.

                        Other

                        A shunt is used not as a cure but to relieve symptoms by reducing hydrocephalus caused by blockage of cerebrospinal fluid.

                        Researchers are presently investigating a number of promising new treatments including gene therapy, highly focused radiation therapy, immunotherapy and novel chemotherapies. A variety of new treatments are being made available on an investigational basis at centers specializing in brain tumor therapies.

                        Prognosis

                        The prognosis of brain cancer varies based on the type of cancer. Medulloblastoma has a good prognosis with chemotherapy, radiotherapy, and surgical resection while glioblastoma multiforme has a median survival of only 12 months even with aggressive chemoradiotherapy and surgery. Brainstem gliomas have the poorest prognosis of any form of brain cancer, with most patients dying within one year, even with therapy that typically consists of radiation to the tumor along with corticosteroids. However, one type of brainstem glioma, a focal seems open to exceptional prognosis and long-term survival has frequently been reported.

                        Glioblastoma multiforme

                        Main article: Glioblastoma multiforme

                        Glioblastoma multiforme is the deadliest and most common form of malignant brain tumor. Even when aggressive multimodality therapy consisting of radiotherapy, chemotherapy, and surgical excision is used, median survival is only 12–17 months. Standard therapy for glioblastoma multiforme consists of maximal surgical resection of the tumor, followed by radiotherapy between two and four weeks after the surgical procedure to remove the cancer. This is followed by chemotherapy. Most patients with glioblastoma take a corticosteroid, typically dexamethasone, during their illness to palliate symptoms. Experimental treatments include gamma-knife radiosurgery, boron neutron capture therapy and gene transfer.

                        Oligodendrogliomas

                        Main article: Oligodendroglioma

                        Oligodendroglioma is an incurable but slowly progressive malignant brain tumor. They can be treated with surgical resection, chemotherapy, and/or radiotherapy. For suspected low-grade oligodendrogliomas in select patients, some neuro-oncologists opt for a course of watchful waiting, with only symptomatic therapy. Tumors with the 1p/19q co-deletion have been found to be especially chemosensitive, and one source reports oligodendrogliomas to be "among the most chemosensitive of human solid malignancies".A median survival of up to 16.7 years has been reported for low grade oligodendrogliomas.

                        Epidemiology

                        The incidence of low-grade astrocytoma has not been shown to vary significantly with nationality. However, studies examining the incidence of malignant CNS tumors have shown some variation with national origin. Since some of these high-grade lesions arise from low-grade tumors, these trends are worth mentioning. Specifically, the incidence of CNS tumors in the United States, Israel, and the Nordic countries is relatively high, while Japan and Asian countries have a lower incidence. These differences probably reflect some biological differences as well as differences in pathologic diagnosis and reporting.
                        Worldwide data on incidence of cancer can be found at the WHO (world health organisation) and is handled by the AIRC (Agency for Interanctional Research on Cancer) located in France.Figures for incidences of cancers of the brain show a significant difference between more and less developed countries (i.e. the less-developed countries have lower incidences of tumors of the brain) this could be explained by undiagnosed tumor-related deaths (patient in extreme poor situations do not get diagnosed simply because they do not have access to the modern diagnostic facilities required to diagnose a brain tumor) and by deaths caused by other poverty related causes that preempt a patients life before tumors develop or tumors become life threatening. Nevertheless studies have been made that certain forms of primary brain tumors are more prevalent among certain groups of the population.

                        In children

                        A brainstem glioma in four year old. MRI sagittal, without contrast

                        In the US, about 2000 children and adolescents younger than 20 years of age are diagnosed with malignant brain tumors each year. Higher incidence rates were reported in 1985–94 than in 1975–83. There is some debate as to the reasons; one theory is that the trend is the result of improved diagnosis and reporting, since the jump occurred at the same time that MRIs became available widely, and there was no coincident jump in mortality. The central nervous system (CNS) cancer survival rate in children is approximately 60%. The rate varies with the type of cancer and the age of onset: younger patients have higher mortality.

                        In children under 2, about 70% of brain tumors are medulloblastoma, ependymoma, and low-grade glioma. Less commonly, and seen usually in infants, are teratoma and atypical teratoid rhabdoid tumor.Germ cell tumors, including teratoma, make up just 3% of pediatric primary brain tumors, but the worldwide incidence varies significantly.