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
Anaplasia (from grc, ἀνά ''ana'', "backward" + πλάσις ''plasis'', "formation") is a condition of cells with poor cellular differentiation, losing the morphological characteristics of mature cells and their orientation with respect to e ...
, 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
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 ...
, 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
microRNA
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...
s 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
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
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 transplantation
Organ transplantation is a medical procedure in which an organ (anatomy), organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organ ...
s.
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
Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...
and, posttransplant
lymphoproliferative disorders
Lymphoproliferative disorders (LPDs) refer to a specific class of diagnoses, comprising a group of several conditions, in which lymphocytes are produced in excessive quantities. These disorders primarily present in patients who have a compromised i ...
".
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
Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...
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
Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...
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
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mit ...
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
Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesoderm ...
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
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 clas ...
,
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
The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesothel ...
(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
Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (t ...
,
gastrointestinal
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
problems and
alopecia
Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarri ...
.
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
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...
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
Nitrogen mustards are cytotoxic organic compounds with the chloroethylamine (Cl(CH2)2NR2) functional group. Although originally produced as chemical warfare agents, they were the first chemotherapeutic agents for treatment of cancer. Nitrogen m ...
, 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
220 px, chemotherapeutic agent by virtue of its antitumour activity. Aziridines are organic compounds containing the aziridine functional group, a three-membered heterocycle with one amine (-NR-) and two methylene bridges (--). The parent compou ...
."
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
The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...
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
Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, ab ...
''
*''
Malignant transformation
Malignant transformation is the process by which cells acquire the properties of cancer. This may occur as a primary process in normal tissue, or secondarily as ''malignant degeneration'' of a previously existing benign tumor.
Causes
There are ...
''
Non-oncologic disorders referred to as "malignant" include:
*''
Malignant hypertension
A hypertensive emergency is very high blood pressure with potentially life-threatening symptoms and signs of acute damage to one or more organ systems (especially brain, eyes, heart, aorta, or kidneys). It is different from a hypertensive urgency ...
''
*''
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 i ...
''
*''
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
Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fas ...
''
See also
*
Precancerous condition
A precancerous condition is a condition, tumor or lesion involving abnormal cells which are associated with an increased risk of developing into cancer. Clinically, precancerous conditions encompass a variety of abnormal tissues with an increased ...
References
{{Portal bar, Biology, Medicine
Medical terminology
Oncology
ja:悪性腫瘍