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  • Neoplasm also commonly referred to as a tumor or tumour is an abnormal growth of tissue.

  • This abnormal growth usually but not always forms a mass.

  • The World Health Organization classifies neoplasms into four main groups: benign neoplasms, in

  • situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. A malignant

  • neoplasm is a cancer. Prior to abnormal growth, cells often undergo

  • an abnormal pattern of growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia

  • do not always progress to neoplasia. The growth of neoplastic cells exceeds, and is not coordinated

  • with, that of the normal tissues around it. The growth persists in the same excessive

  • manner even after cessation of the stimuli. It usually causes a lump or tumor.

  • In modern medicine, the term tumour means a neoplasm that has formed a lump. In the

  • past, the term tumour was used differently, referring to a lump of any cause. Some neoplasms

  • do not cause a lump.

  • Types A neoplasm can be benign, potentially malignant,

  • or malignant. Benign neoplasms include uterine fibroids

  • and melanocytic nevi. They are circumscribed and localized and do not transform into cancer.

  • Potentially malignant neoplasms include carcinoma in situ. They do not invade and destroy but,

  • given enough time, will transform into a cancer. Malignant neoplasms are commonly called cancer.

  • They invade and destroy the surrounding tissue, may form metastases and eventually kill the

  • host. Secondary neoplasm refers to any of a class

  • of cancerous tumor that is either a metastatic offshoot of a primary tumor, or an apparently

  • unrelated tumor that increases in frequency following certain cancer treatments such as

  • chemotherapy or radiotherapy. Definition

  • Because neoplasia includes very different diseases, it is difficult to find an all-encompassing

  • definition. The definition of the British oncologist R.A. Willis is widely cited: "A

  • neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated

  • with that of the normal tissues, and persists in the same excessive manner after cessation

  • of the stimulus which evoked the change." This definition is criticized because some

  • neoplasms, such as nevi, are not progressive. Clonality

  • Neoplastic tumors often contain more than one type of cell, but their initiation and

  • continued growth is usually dependent on a single population of neoplastic cells. These

  • cells are presumed to be clonalthat is, they are descended from a single progenitor

  • cell. Sometimes, the neoplastic cells all carry

  • the same genetic or epigenetic anomaly that becomes evidence for clonality. For lymphoid

  • neoplasms, e.g. lymphoma and leukemia, clonality is proven by the amplification of a single

  • rearrangement of their immunoglobulin gene or T-cell receptor gene. The demonstration

  • of clonality is now considered to be necessary to identify a lymphoid cell proliferation

  • as neoplastic. It is tempting to define neoplasms as clonal

  • cellular proliferations but the demonstration of clonality is not always possible. Therefore,

  • clonality is not required in the definition of neoplasia.

  • Neoplasia vs. tumor Tumor originally meant any form of swelling,

  • neoplastic or not. Current English, however, both medical and non-medical, uses tumor as

  • a synonym of neoplasm. Some neoplasms do not form a tumor. These

  • include leukemia and most forms of carcinoma in situ.

  • A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size.Tumor

  • is not synonymous with cancer. While cancer is by definition malignant, a tumor can be

  • benign, pre-malignant, or malignant. The terms "mass" and "nodule" are often used

  • synonymously with "tumor". Generally speaking, however, the term "tumor" is used generically,

  • without reference to the physical size of the lesion. More specifically, the term "mass"

  • is often used when the lesion has a maximal diameter of at least 20 millimeters in greatest

  • direction, while the term "nodule" is usually used when the size of the lesion is less than

  • 20 mm in its greatest dimension. Causes

  • A neoplasm can be caused by an abnormal proliferation of tissues, which can be caused by genetic

  • mutations. Not all types of neoplasms cause a tumorous overgrowth of tissue, however.

  • Recently, tumor growth has been studied using mathematics and continuum mechanics. Vascular

  • tumors are thus looked at as being amalgams of a solid skeleton formed by sticky cells

  • and an organic liquid filling the spaces in which cells can grow. Under this type of model,

  • mechanical stresses and strains can be dealt with and their influence on the growth of

  • the tumor and the surrounding tissue and vasculature elucidated. Recent findings from experiments

  • that use this model show that active growth of the tumor is restricted to the outer edges

  • of the tumor, and that stiffening of the underlying normal tissue inhibits tumor growth as well.

  • Benign conditions that are not associated with an abnormal proliferation of tissue can

  • also present as tumors, however, but have no malignant potential. Breast cysts are another

  • example, as are other encapsulated glandular swellings.

  • Encapsulated hematomas, encapsulated necrotic tissue, keloids and granulomas may also present

  • as tumors. Discrete localized enlargements of normal

  • structures due to outflow obstructions or narrowings, or abnormal connections, may also

  • present as a tumor. Examples are arteriovenous fistulae or aneurysms, biliary fistulae or

  • aneurysms, sclerosing cholangitis, cysticercosis or hydatid cysts, intestinal duplications,

  • and pulmonary inclusions as seen with cystic fibrosis. It can be dangerous to biopsy a

  • number of types of tumor in which the leakage of their contents would potentially be catastrophic.

  • When such types of tumors are encountered, diagnostic modalities such as ultrasound,

  • CT scans, MRI, angiograms, and nuclear medicine scans are employed prior to biopsy and/or

  • surgical exploration/excision in an attempt to avoid such severe complications.

  • The nature of a tumor is determined by imaging, by surgical exploration, and/or by a pathologist

  • after examination of the tissue from a biopsy or a surgical specimen.

  • Malignant neoplasms DNA damage

  • DNA damage is considered to be the primary underlying cause of malignant neoplasms known

  • as cancers. Its central role in progression to cancer is illustrated in the figure in

  • this section, in the box near the top. DNA damage is very common. Naturally occurring

  • DNA damages occur at a rate of more than 60,000 new damages, on average, per human cell, per

  • day [also see article DNA damage ]. Additional DNA damages can arise from exposure to exogenous

  • agents. Tobacco smoke causes increased exogenous DNA damage, and these DNA damages are the

  • likely cause of lung cancer due to smoking. UV light from solar radiation causes DNA damage

  • that is important in melanoma. Helicobacter pylori infection produces high levels of reactive

  • oxygen species that damage DNA and contributes to gastric cancer. Bile acids, at high levels

  • in the colons of humans eating a high fat diet, also cause DNA damage and contribute

  • to colon cancer. Katsurano et al. indicated that macrophages and neutrophils in an inflamed

  • colonic epithelium are the source of reactive oxygen species causing the DNA damages that

  • initiate colonic tumorigenesis. Some sources of DNA damage are indicated in the boxes at

  • the top of the figure in this section. Individuals with a germ line mutation causing

  • deficiency in any of 34 DNA repair genes are at increased risk of cancer. Some germ line

  • mutations in DNA repair genes cause up to 100% lifetime chance of cancer. These germ

  • line mutations are indicated in a box at the left of the figure with an arrow indicating

  • their contribution to DNA repair deficiency. About 70% of malignant neoplasms have no hereditary

  • component and are called "sporadic cancers". Only a minority of sporadic cancers have a

  • deficiency in DNA repair due to mutation in a DNA repair gene. However, a majority of

  • sporadic cancers have deficiency in DNA repair due to epigenetic alterations that reduce

  • or silence DNA repair gene expression. For example, for 113 sequential colorectal cancers,

  • only four had a missense mutation in the DNA repair gene MGMT, while the majority had reduced

  • MGMT expression due to methylation of the MGMT promoter region. Five reports present

  • evidence that between 40% and 90% of colorectal cancers have reduced MGMT expression due to

  • methylation of the MGMT promoter region. Similarly, out of 119 cases of mismatch repair-deficient

  • colorectal cancers that lacked DNA repair gene PMS2 expression, PMS2 was deficient in

  • 6 due to mutations in the PMS2 gene, while in 103 cases PMS2 expression was deficient

  • because its pairing partner MLH1 was repressed due to promoter methylation. In the other

  • 10 cases, loss of PMS2 expression was likely due to epigenetic overexpression of the microRNA,

  • miR-155, which down-regulates MLH1. In further examples [tabulated in the article

  • Epigenetics], epigenetic defects were found at frequencies of between 13%-100% for the

  • DNA repair genes BRCA1, WRN, FANCB, FANCF, MGMT, MLH1, MSH2, MSH4, ERCC1, XPF, NEIL1

  • and ATM. These epigenetic defects occurred in various cancers. Two or three deficiencies

  • in expression of ERCC1, XPF and/or PMS2 occur simultaneously in the majority of the 49 colon

  • cancers evaluated by Facista et al. Epigenetic alterations causing reduced expression of

  • DNA repair genes is shown in a central box at the third level from the top of the figure

  • in this section, and the consequent DNA repair deficiency is shown at the fourth level.

  • When expression of DNA repair genes is reduced, DNA damages accumulate in cells at a higher

  • than normal level, and these excess damages cause increased frequencies of mutation and/or

  • epimutation. Mutation rates strongly increase in cells defective in DNA mismatch repair

  • or in homologous recombinational repair. During repair of DNA double strand breaks,

  • or repair of other DNA damages, incompletely cleared sites of repair can cause epigenetic

  • gene silencing. DNA repair deficiencies cause increased DNA damages which result in increased

  • somatic mutations and epigenetic alterations. Field defects, normal appearing tissue with

  • multiple alterations, are common precursors to development of the disordered and improperly

  • proliferating clone of tissue in a malignant neoplasm. Such field defects may have multiple

  • mutations and epigenetic alterations. Once a cancer is formed, it usually has genome

  • instability. This instability is likely due to reduced DNA repair or excessive DNA damage.

  • Because of such instability, the cancer continues to evolve and to produce sub clones. For example,

  • a renal cancer, sampled in 9 areas, had 40 ubiquitous mutations, demonstrating tumour

  • heterogeneity, 59 mutations shared by some, and 29 “privatemutations only present

  • in one of the areas of the cancer. Field defects

  • Various other terms have been used to describe this phenomenon, including "field effect",

  • "field cancerization", and "field carcinogenesis". The termfield cancerizationwas first

  • used in 1953 to describe an area orfieldof epithelium that has been preconditioned

  • by largely unknown processes so as to predispose it towards development of cancer. Since then,

  • the termsfield cancerizationandfield defecthave been used to describe pre-malignant

  • tissue in which new cancers are likely to arise.

  • Field defects are important in progression to cancer. However, in most cancer research,

  • as pointed out by RubinThe vast majority of studies in cancer research has been done

  • on well-defined tumors in vivo, or on discrete neoplastic foci in vitro. Yet there is evidence

  • that more than 80% of the somatic mutations found in mutator phenotype human colorectal

  • tumors occur before the onset of terminal clonal expansion. Similarly, Vogelstein et

  • al. point out that more than half of somatic mutations identified in tumors occurred in

  • a pre-neoplastic phase, during growth of apparently normal cells. Likewise, epigenetic alterations

  • present in tumors may have occurred in pre-neoplastic field defects.

  • An expanded view of field effect has been termed "etiologic field effect", which encompasses

  • not only molecular and pathologic changes in pre-neoplastic cells but also influences

  • of exogenous environmental factors and molecular changes in the local microenvironment on neoplastic

  • evolution from tumor initiation to patient death.

  • In the colon, a field defect probably arises by natural selection of a mutant or epigenetically

  • altered cell among the stem cells at the base of one of the intestinal crypts on the inside

  • surface of the colon. A mutant or epigenetically altered stem cell may replace the other nearby

  • stem cells by natural selection. Thus, a patch of abnormal tissue may arise. The figure in

  • this section includes a photo of a freshly resected and lengthwise-opened segment of

  • the colon showing a colon cancer and four polyps. Below the photo there is a schematic

  • diagram of how a large patch of mutant or epigenetically altered cells may have formed,

  • shown by the large area in yellow in the diagram. Within this first large patch in the diagram,

  • a second such mutation or epigenetic alteration may occur so that a given stem cell acquires

  • an advantage compared to other stem cells within the patch, and this altered stem cell

  • may expand clonally forming a secondary patch, or sub-clone, within the original patch. This

  • is indicated in the diagram by four smaller patches of different