Neoplasm

A neoplasm is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, which may be called a tumour or tumor.
ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers and are the focus of oncology.
Prior to the abnormal growth of tissue, such as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia does not always progress to neoplasia and can occur in other conditions as well. The word neoplasm is from Ancient Greek νέος- 'new' and πλάσμα 'formation, creation'.

Types

A neoplasm can be benign, potentially malignant, or malignant.

Benign tumors include uterine fibroids, osteophytes, and melanocytic nevi. They are circumscribed and localized and do not transform into cancer.
Potentially-malignant neoplasms include carcinoma in situ. They are localised, and do not invade and destroy but in time, may transform into cancer.
Malignant neoplasms are commonly called cancer. They invade and destroy the surrounding tissue, may form metastases and, if untreated or unresponsive to treatment, will generally prove fatal.
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.
Rarely there can be a metastatic neoplasm with no known site of the primary cancer and this is classed as a cancer of unknown primary origin.
Clonality

Neoplastic tumors are often heterogeneous and contain more than one type of cell, but their initiation and continued growth are usually dependent on a single population of neoplastic cells. These cells are presumed to be monoclonal – that is, they are derived from the same cell, and all carry the same genetic or epigenetic anomaly – evident of 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.

Neoplasm vs. tumor

The word tumor or tumour comes from the Latin word for swelling, which is one of the cardinal signs of inflammation. The word originally referred to any form of swelling, neoplastic or not. In modern English, tumor is used as a synonym for a neoplasm that appears enlarged in size. Some neoplasms do not form a tumor; these include leukemia and most forms of carcinoma in situ. Tumor is also not synonymous with cancer. While cancer is by definition malignant, a tumor can be benign, precancerous, 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 the 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

Tumors in humans occur as a result of accumulated genetic and epigenetic alterations within single cells, which cause the cell to divide and expand uncontrollably. 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, similarities between neoplasmic growths and regenerative processes, e.g., dedifferentiation and rapid cell proliferation, have been pointed out.
Tumor growth has been studied using mathematics and continuum mechanics. Vascular tumors such as hemangiomas and lymphangiomas 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 or surgical exploration/excision in an attempt to avoid such severe complications.

Malignant neoplasms

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 10,000 new damages, on average, per human cell, per day. 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 germline mutation causing deficiency in any of 34 DNA repair genes are at increased risk of cancer. Some germline mutations in DNA repair genes cause up to 100% lifetime chance of cancer. These germline 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, of 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, 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, including breast, ovarian, colorectal, and head and neck cancers. Two or three deficiencies in expression of ERCC1, XPF 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 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 tumor heterogeneity, 59 mutations shared by some, and 29 "private" mutations only present in one of the areas of the cancer.