Benignity
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Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not self-limited in its growth, is capable of invading into adjacent tissues, and may be capable of spreading to distant tissues. A
benign tumor A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize (spread throughout the body). Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have re ...
has none of those properties. Malignancy in cancers is characterized by anaplasia, invasiveness, and
metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
. Malignant tumors are also characterized by
genome instability Genome instability (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneup ...
, so that cancers, as assessed by
whole genome sequencing Whole genome sequencing (WGS), also known as full genome sequencing, complete genome sequencing, or entire genome sequencing, is the process of determining the entirety, or nearly the entirety, of the DNA sequence of an organism's genome at a s ...
, frequently have between 10,000 and 100,000 mutations in their entire genomes. Cancers usually show tumour heterogeneity, containing multiple subclones. They also frequently have reduced expression of DNA repair enzymes due to
epigenetic In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
methylation of DNA repair genes or altered microRNAs that control DNA repair gene expression. Tumours can be detected through the visualisation or sensation of a lump on the body. In cases where there is no obvious representation of a lump, a
mammogram Mammography (also called mastography) is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast for diagnosis and screening. The goal of mammography is the early detection of breast cancer, typically through d ...
or an MRI test can be used to determine the presence of a tumour. In the case of an existing tumour, a
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
would be then required to make a diagnosis as this detects if the tumour is malignant or benign. This involves examination of a small sample of the tissue in a laboratory. If detected as a malignant tumour, treatment would be necessary. Treatment during early stages is most effective. Forms of treatment include chemotherapy, surgery, photoradiation and hyperthermia, amongst various others.


Signs and symptoms

When malignant cells form, symptoms do not typically appear until there has been a significant growth of the mass. Once signs and symptoms do arise, they are dependent on the location, size and type of malignancy. Usually, it is quite general and can be associated with other illnesses or diseases and thus, can be difficult to diagnose or can be misdiagnosed. Signs include observable or measurable aspects such as weight loss (without trying), a fever or unusual bleeding. On the other hand, symptoms are felt internally by the individual such as fatigue or changes in appetite. A general list of common signs and symptoms includes pain (headaches or bone aches), skin changes (new moles or bumps), coughing and unusual bleeding. There are also signs and symptoms specific to females including belly pain and bloating or breast changes i.e., the formation of a
lump Lump may refer to: * "Lump" (song), a 1995 song by The Presidents of the United States of America * ''Lump'' (compilation album), a 2000 best-of album by The Presidents of the United States of America * Lump (dog), a dog who inspired Pablo Pic ...
. Signs and symptoms specific to males include pain or growths in the scrotum or difficulty urinating.


Causes

Malignant cells often evolve due to a combination of reasons rather than one definitive reason. Reasons which can explain their development include genetics and family history, triggers such as infectious diseases, and exposure to risk factors.


Triggers

Infectious diseases An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
play a role in the development of malignancy, with agents of infectious disease being able to produce a multitude of malignant cells. These include bacterial causes, fungal and parasitic causes and, viral causes.
Bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
,
fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
and similar pathogens have the ability to form an environment within states of chronic inflammation which gives rise to oncogenic potential. Viral agents are able to assist the formation of malignant tumours due to a mechanism of cell transformation. This cell transformation can occur through either "DNA integration or cellular-DNA alteration of growth regulator genes".
Inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
can also play a role in triggering malignancy as it can promote stages of tumour formation. The main purpose of inflammation is to repair tissue, defend the body against pathogens and regenerate cells. At the same time, inflammatory cells can also interact with malignant cells to form an inflammatory tumour microenvironment. This environment increases the likelihood of forming malignant cells through blockage of anti-tumour immunity. Once this occurs, the inflammatory tumour microenvironment begins to send out tumour-promoting signals to
epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
cells, triggering the formation of malignant cells.


Risk factors

Traditional risk factors of developing malignancy include smoking, sun exposure and, having a history of cancer in the family. Other risk factors include developing post-transplant malignancy which occurs subsequent to solid organ transplantations.


Post-transplant malignancy

Individuals who undergo organ transplant surgery have an increased risk of developing malignancy in comparison to the general population. The most common form of malignancy being " nonmelanoma skin cancer and, posttransplant lymphoproliferative disorders". The different types of malignancy developed post-transplant depend on which organ was transplanted. This is linked to recipients being at a higher risk when exposed to traditional risk factors as well as, the type and intensity of the operation, the duration of their immunosuppression post-operation and, the risk of developing oncogenic viral infections.


Management

There are various treatment forms available to help manage malignancy. Common treatments include
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
,
radiation In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or through a material medium. This includes: * ''electromagnetic radiation'', such as radio waves, microwaves, infrared, visi ...
and surgical procedures. Photoradiation and
hyperthermia Hyperthermia, also known simply as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme ...
are also used as treatment forms to kill or reduce malignant cells. A large portion of patients are at risk of death when diagnosed with malignancy as the disease has usually progressed for a number of years before detection.


Surgery

Surgery can help manage or treat malignancy by either removing the tumour, localising it and/or determining whether there has been a spread to other organs. When undertaking surgery for malignancy, there are six major objectives which are considered. These include "prevention of cancer, diagnosis and staging of disease, disease cure, tumour debulking, symptom palliation and patient rehabilitation". Surgical prevention of cancer largely consists of removing the organ at risk of developing malignancy. This would occur if an individual is predisposed to the formation of malignant cells as a result of inherited genetic mutations and, acquired diseases. Surgical diagnosis of malignancy involves completing a
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
. This process requires a sufficient amount of tissue to make a confident diagnosis and, the handling of specimen to expand information provided from testing. Biopsies are categorised into four different processes: "fine-needle aspirate (FNA), core needle, incisional and, excisional". Curative surgery (also known as primary surgery) can be conducted when the malignant tumour has only invaded one area of the body. The objective is to remove the entirety of the malignant cells without violating the tumour; if the tumour is violated, the risk of both tumour spillage and wound implantation would increase. The surgical procedure of tumour debulking can be undertaken to increase the effectiveness of postoperative forms of treatment. Symptom palliation and patient rehabilitation do not play a role in controlling or reducing malignancy growth rather, they increase the patient's quality of life.


Photoradiation

Hematoporphyrin derivative (HPD) is a drug which was developed to be absorbed by malignant cells and only becomes active when exposed to light. It is commonly used to identify and localise cancers as when it is under activation of blue light the red fluorescence of the malignant tumour (due to the HPD) can be observed easily. The combination of HPD with red light (photoradiation) has been used on various malignant tumours including malignant
melanomas Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye (u ...
and carcinomas on a range of different organs including the breast and colon. This form of treatment produces a
singlet oxygen Singlet oxygen, systematically named dioxygen(singlet) and dioxidene, is a gaseous inorganic chemical with the formula O=O (also written as or ), which is in a quantum state where all electrons are spin paired. It is kinetically unstable at ambie ...
through the photodynamic process; where the oxygen molecule exists in an electronically excited state. The singlet oxygen is a cytotoxic agent which holds the ability to eradicate malignant cells by preventing both
nucleic acid Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main cl ...
and
protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...
. The treatment process also utilises HPD's capability of accumulating at higher levels in malignant tissues compared to most other tissues. In the case of deeply pigmented or larger tumours, a stronger course of this treatment process is required in order to be effective.


Hyperthermia

Malignancy can be treated through the use of hyperthermia by applying either surgical perfusion or interstitial techniques to the body. The use of this treatment type largely depends on the fact that malignant and normal cells have differing responses to the energy source used. This dependency is due to the intracellular changes which occur during hyperthermia; as the nucleic acids,
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
and
cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
within each cell is affected indirectly and/or through multiple pathways. The combination of these intracellular changes means there is no specific target of cell death in the hyperthermic process.


Chemotherapy

Chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
is commonly used as either the primary treatment or in conjunction with other treatment forms such as radiotherapy or surgery. It can be administered through "injection, intra-arterial (IA), intraperitoneal (IP),
intrathecal Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF) and is useful in spinal anesthesia, chemotherapy, or pain man ...
(IT),
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
(IV), topical or oral". The purpose of chemotherapy is to use
cytotoxic agents Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells ...
which kill rapidly dividing cells within the body. It targets the cellular mechanisms which allow the development of malignancy throughout the body. There are no specific areas which are targeted and so, there is a lack of differentiation between normal and malignant cells, resulting in a range of side effects. This includes bone marrow suppression, gastrointestinal problems and alopecia. Some side effects are specific to the anticancer drug used, the most common being bone marrow suppression as bone marrow has the ability to divide rapidly due to high growth fraction. This is because anticancer drugs have the highest activity in high growth fraction tissues. Alkylating agents are used in chemotherapy as these are chemically reactive drugs which form
covalent bond A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atoms ...
s when reacting with DNA. This results in breaks within DNA strands causing either inter-strand or intra-strand DNA cross-linking. The sub-classes of alkylating agents are " nitrogen mustards, oxazaphosphorines, alkyl alkane, sulphonates,
nitrosoureas Nitrosourea is both the name of a molecule, and a class of compounds that include a nitroso (R-NO) group and a urea. Examples Examples include: * Arabinopyranosyl-''N''-methyl-''N''-nitrosourea (Aranose) * Carmustine (BCNU, BiCNU) * Chlorozoto ...
,
tetrazines Tetrazine is a compound that consists of a six-membered aromatic ring containing four nitrogen atoms with the molecular formula C2 H2 N4. The name ''tetrazine'' is used in the nomenclature of derivatives of this compound. Three core-ring isome ...
and aziridines."


Epidemiology

Malignancy has been a constant global health concern for a number of years, resulting in significant social and economic impacts on individuals with malignancy and their families. The risk of developing malignancy is 20.2%. In 2018, 18 million patients were diagnosed with a malignant tumour with lung, breast and prostate being the most common form. Additionally, there were approximately 10 million mortalities due to cancer in 2020 and, there is an overall trend which demonstrated that malignant mortality has increased by 28% over the past 15 years. Lung cancer has the highest mortality rate in comparison to other forms of cancer, with the leading cause of development due to smoking. The number of smokers in China is rapidly increasing with tobacco killing approximately 3000 people each day. The diagnosis of lung cancer is most common within the 50–59-year age bracket. Further, it caused 1.8 million deaths in 2020 alone. In those aged 14 or younger,
leukaemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
is the most frequent form of malignancy with the brain and nervous system subsequent. These individuals account for approximately 1% of the cancer mortality rate – about 110,000 children each year. The 15-49-year-old age bracket most common form of malignancy is
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
with
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
and
lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...
following. Finally, those aged 60 and over mainly develop
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
,
colorectal The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before being ...
, stomach and
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
malignancy. Uses of "malignant" in
oncology Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''ó ...
include: *''Malignancy'', ''malignant neoplasm'' and ''malignant tumor'' are synonymous with
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
*''Malignant ascites'' *'' Malignant transformation'' Non-oncologic disorders referred to as "malignant" include: *'' Malignant hypertension'' *''
Malignant hyperthermia Malignant hyperthermia (MH) is a type of severe reaction that occurs in response to particular medications used during General anaesthesia, general anesthesia, among those who are susceptible. Symptoms include tetany, muscle rigidity, hyperthermia ...
'' *''
Malignant otitis externa Otitis externa, also called swimmer's ear, is inflammation of the ear canal. It often presents with ear pain, swelling of the ear canal, and occasionally decreased hearing. Typically there is pain with movement of the outer ear. A high fever is ...
'' *'' Malignant tertian malaria'' (malaria caused specifically by ''
Plasmodium falciparum ''Plasmodium falciparum'' is a Unicellular organism, unicellular protozoan parasite of humans, and the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female ''Anopheles'' mosqu ...
'') *'' Neuroleptic malignant syndrome''


See also

* Precancerous condition


References

{{Portal bar, Biology, Medicine Medical terminology Oncology ja:悪性腫瘍