Malignancy

Malignancy
Other namescancer, malignant neoplasm
Malignant tumor (right) spreads uncontrollably and invades the surrounding tissues; benign tumor (left) remains self-contained from neighbouring tissue
Pronunciation
SpecialtyOncology
SymptomsFatigue, lump(s), change in skin, abnormal bleeding, prolonged cough, unexplained weight loss[1]
Risk factorsSmoking, sun exposure, genetics - history of malignancy, solid organ transplantation (post-transplant malignancy), infectious diseases
Diagnostic methodBiopsy
TreatmentPhotoradiation therapy, surgery, chemotherapy, hyperthermia
Frequency442.4 per 100,000 per year [2]
Deaths~10 million per year [3]

Malignancy (from Latin male 'badly', and -gnus 'born') is the tendency of a medical condition to become progressively worse.

Malignancy is most familiar as a characterization of cancer. 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 has none of those properties.

Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis.[4] Malignant tumors are also characterized by genome instability, so that cancers, as assessed by whole genome sequencing, frequently have between 10,000 and 100,000 mutations in their entire genomes.[5] Cancers usually show tumour heterogeneity, containing multiple subclones.[6] They also frequently have reduced expression of DNA repair enzymes due to epigenetic 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.[7] In cases where there is no obvious representation of a lump, a mammogram or an MRI test can be used to determine the presence of a tumour.[7] In the case of an existing tumour, a biopsy would be then required to make a diagnosis as this detects if the tumour is malignant or benign.[7] This involves examination of a small sample of the tissue in a laboratory.[7] If detected as a malignant tumour, treatment would be necessary. Treatment during early stages is most effective.[7] 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.[8] On the other hand, symptoms are felt internally by the individual such as fatigue or changes in appetite.[8] A general list of common signs and symptoms includes pain (headaches or bone aches), skin changes (new moles or bumps), coughing and unusual bleeding.[1] There are also signs and symptoms specific to females including belly pain and bloating or breast changes i.e., the formation of a lump.[1] Signs and symptoms specific to men include pain or growths in the scrotum or difficulty urinating.[1]

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 play a role in the development of malignancy, with agents of infectious disease being able to produce a multitude of malignant cells.[9] These include bacterial causes, fungal and parasitic causes and, viral causes.[9] Bacteria, fungi and similar pathogens have the ability to form an environment within states of chronic inflammation which gives rise to oncogenic potential.[9] Viral agents are able to assist the formation of malignant tumours due to a mechanism of cell transformation.[9] This cell transformation can occur through either "DNA integration or cellular-DNA alteration of growth regulator genes".[9] Inflammation can also play a role in triggering malignancy as it can promote stages of tumour formation.[10] The main purpose of inflammation is to repair tissue, defend the body against pathogens and regenerate cells.[10] At the same time, inflammatory cells can also interact with malignant cells to form an inflammatory tumour microenvironment.[10] This environment increases the likelihood of forming malignant cells through blockage of anti-tumour immunity.[10] Once this occurs, the inflammatory tumour microenvironment begins to send out tumour-promoting signals to epithelial cells, triggering the formation of malignant cells.[10]

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.[11]

Post-Transplant Malignancy

Individuals who undergo organ transplant surgery have an increased risk of developing malignancy in comparison to the general population.[11] The most common form of malignancy being "nonmelanoma skin cancer and, posttransplant lymphoproliferative disorders".[11] The different types of malignancy developed post-transplant depend on which organ was transplanted.[12] 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.[11]

Management

There are various treatment forms available to help manage malignancy. Common treatments include chemotherapy, radiation and surgical procedures. Photoradiation and hyperthermia 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.[13]

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.[14][15] When undertaking surgery for malignancy, there are six major objectives which are considered.[13] These include "prevention of cancer, diagnosis and staging of disease, disease cure, tumour debulking, symptom palliation and patient rehabilitation".[13]

Surgical prevention of cancer largely consists of removing the organ at risk of developing malignancy.[13] This would occur if an individual is predisposed to the formation of malignant cells as a result of inherited genetic mutations and, acquired diseases.[13]

Surgical diagnosis of malignancy involves completing a biopsy.[13] This process requires a sufficient amount of tissue to make a confident diagnosis and, the handling of specimen to expand information provided from testing.[13] Biopsies are categorised into four different processes: "fine-needle aspirate (FNA), core needle, incisional and, excisional".[13]

Curative surgery (also known as primary surgery) can be conducted when the malignant tumour has only invaded one area of the body.[14][15] 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.[14][15]

The surgical procedure of tumour debulking can be undertaken to increase the effectiveness of postoperative forms of treatment.[13] 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.[13]

Photoradiation

Hematoporphyrin derivative (HPD) is a drug which was developed to be absorbed by malignant cells and only becomes active when exposed to light.[16] 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.[17]

The combination of HPD with red light (photoradiation) has been used on various malignant tumours including malignant melanomas and carcinomas on a range of different organs including the breast and colon.[17] This form of treatment produces a singlet oxygen through the photodynamic process;[17] where the oxygen molecule exists in an electronically excited state.[18] The singlet oxygen is a cytotoxic agent [17] which holds the ability to eradicate malignant cells by preventing both nucleic acid and protein synthesis.[19] The treatment process also utilises HPD's capability of accumulating at higher levels in malignant tissues compared to most other tissues.[17]

In the case of deeply pigmented or larger tumours, a stronger course of this treatment process is required in order to be effective.[17]

Hyperthermia

Malignancy can be treated through the use of hyperthermia by applying either surgical perfusion or interstitial techniques to the body.[20] The use of this treatment type largely depends on the fact that malignant and normal cells have differing responses to the energy source used.[20] This dependency is due to the intracellular changes which occur during hyperthermia; as the nucleic acids, cell membrane and cytoskeleton within each cell is affected indirectly and/or through multiple pathways.[20] The combination of these intracellular changes means there is no specific target of cell death in the hyperthermic process.[20]

Chemotherapy

Chemotherapy is commonly used as either the primary treatment or in conjunction with other treatment forms such as radiotherapy or surgery.[21] It can be administered through “injection, intra-arterial (IA), intraperitoneal (IP), intrathecal (IT), intravenous (IV), topical or oral”.[21]

The purpose of chemotherapy is to use cytotoxic agents which kill rapidly dividing cells within the body.[22] It targets the cellular mechanisms which allow the development of malignancy throughout the body.[23] There are no specific areas which are targeted and so, there is a lack of differentiation between normal and malignant cells,[23] resulting in a range of side effects. This includes bone marrow suppression, gastrointestinal problems and alopecia.[22] 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.[22] This is because anticancer drugs have the highest activity in high growth fraction tissues.[22]

Alkylating agents are used in chemotherapy as these are chemically reactive drugs which form covalent bonds when reacting with DNA.[23] This results in breaks within DNA strands causing either inter-strand or intra-strand DNA cross-linking.[23] The sub-classes of alkylating agents are “nitrogen mustards, oxazaphosphorines, alkyl alkane, sulphonates, nitrosoureas, tetrazines and aziridines.”[23]

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.[24] The risk of developing malignancy is 20.2%.[25] In 2018, 18 million patients were diagnosed with a malignant tumour with lung, breast and prostate being the most common form.[25] Additionally, there were approximately 10 million mortalities due to cancer in 2020[3] and, there is an overall trend which demonstrated that malignant mortality has increased by 28% over the past 15 years.[25]

Lung cancer has the highest mortality rate in comparison to other forms of cancer, with the leading cause of development due to smoking.[26] The number of smokers in China is rapidly increasing with tobacco killing approximately 3000 people each day.[26] The diagnosis of lung cancer is most common within the 50–59-year age bracket.[25] Further, it caused 1.8 million deaths in 2020 alone.[3]

In those aged 14 or younger, leukaemia is the most frequent form of malignancy with the brain and nervous system subsequent.[25] These individuals account for approximately 1% of the cancer mortality rate – about 110,000 children each year.[27] The 15-49-year-old age bracket most common form of malignancy is breast cancer with liver and lung cancer following.[25] Finally, those aged 60 and over mainly suffer lung, colorectal, stomach and liver malignancy.[25]

Uses of "malignant" in oncology:

Non-oncologic disorders referred to as "malignant":

See also

References

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  2. ↑ "Cancer statistics". National Cancer Institution. 2 April 2015.
  3. 1 2 3 "Cancer". World Health Organisation (WHO). 21 September 2021.
  4. ↑ Wilkins EM (April 2008). "The Patient with Cancer". Clinical Practice of the Dental Hygienist Workbook. Lippincott Williams & Wilkins. pp. 858–869. ISBN 978-1-58255-838-7.
  5. ↑ Tuna M, Amos CI (November 2013). "Genomic sequencing in cancer". Cancer Letters. 340 (2): 161–170. doi:10.1016/j.canlet.2012.11.004. PMC 3622788. PMID 23178448.
  6. ↑ Swanton C (October 2012). "Intratumor heterogeneity: evolution through space and time". Cancer Research. 72 (19): 4875–4882. doi:10.1158/0008-5472.CAN-12-2217. PMC 3712191. PMID 23002210.
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  8. 1 2 "Signs and Symptoms of Cancer – Do I have cancer?". American Society of Clinical Oncology (ASCO). Archived from the original on 2020-11-30. Retrieved 2021-05-31.
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  10. 1 2 3 4 5 Greten FR, Grivennikov SI (July 2019). "Inflammation and Cancer: Triggers, Mechanisms, and Consequences". Immunity. 51 (1): 27–41. doi:10.1016/j.immuni.2019.06.025. PMC 6831096. PMID 31315034.
  11. 1 2 3 4 Rossi AP, Klein CL (February 2019). "Posttransplant Malignancy". The Surgical Clinics of North America. 99 (1): 49–64. doi:10.1016/j.suc.2018.09.004. PMID 30471741. S2CID 53756320.
  12. ↑ Collett D, Mumford L, Banner NR, Neuberger J, Watson C (August 2010). "Comparison of the incidence of malignancy in recipients of different types of organ: a UK Registry audit". American Journal of Transplantation. 10 (8): 1889–1896. doi:10.1111/j.1600-6143.2010.03181.x. PMID 20659094. S2CID 40192165.
  13. 1 2 3 4 5 6 7 8 9 10 Donohue JH (2008). "Principles of cancer surgery.". In Norton JA, et al. (eds.). Surgery. New York, NY: Springer. pp. 1965–1984. doi:10.1007/978-0-387-68113-9_95. ISBN 978-0-387-30800-5.
  14. 1 2 3 "What is cancer surgery?". American Society of Clinical Oncology (ASCO). 31 March 2011.
  15. 1 2 3 "How Surgery Is Used for Cancer?". American Society of Clinical Oncology (ASCO).
  16. ↑ "Hematoporphyrin derivative". NCI Dictionary of Cancer Terms. 2021. Retrieved 23 April 2021.
  17. 1 2 3 4 5 6 Dougherty TJ, Kaufman JE, Goldfarb A, Weishaupt KR, Boyle D, Mittleman A (August 1978). "Photoradiation therapy for the treatment of malignant tumors". Cancer Research. 38 (8): 2628–2635. PMID 667856.
  18. ↑ Hrycay EG, Bandiera SM (2015). "Involvement of Cytochrome P450 in Reactive Oxygen Species Formation and Cancer". In Hardwick JP (ed.). Cytochrome P450 Function and Pharmacological Roles in Inflammation and Cancer. Advances in Pharmacology. Vol. 74. pp. 35–84. doi:10.1016/bs.apha.2015.03.003. ISBN 9780128031193. PMID 26233903.
  19. ↑ Papadimitraki ED, Bertsias G, Chamilos G, Boumpas DT (January 2011). "Systemic Lupus Erythematosus". Academic Press. pp. 1083–1108. doi:10.1016/B978-0-12-374994-9.10058-0. ISBN 9780123749949. {{cite book}}: Missing or empty |title= (help)
  20. 1 2 3 4 Christophi C, Winkworth A, Muralihdaran V, Evans P (1998). "The treatment of malignancy by hyperthermia". Surgical Oncology. 7 (1–2): 83–90. doi:10.1016/s0960-7404(99)00007-9. PMID 10421511.
  21. 1 2 Nazzario B (8 February 2021). "Chemotherapy: How it works and how you'll feel". WebMD – Cancer Centre.
  22. 1 2 3 4 MacDonald V (June 2009). "Chemotherapy: managing side effects and safe handling". The Canadian Veterinary Journal. 50 (6): 665–668. PMC 2684058. PMID 19721789.
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  24. ↑ "Cancer data in Australia, cancer incidence and survival by stage data visualisation". Australian Institute of Health and Welfare.
  25. 1 2 3 4 5 6 7 Mattiuzzi C, Lippi G (December 2019). "Current Cancer Epidemiology". Journal of Epidemiology and Global Health. 9 (4): 217–222. doi:10.2991/jegh.k.191008.001. PMC 7310786. PMID 31854162.
  26. 1 2 Bender E (September 2014). "Epidemiology: The dominant malignancy". Nature. 513 (7517): S2–S3. doi:10.1038/513S2a. PMID 25208070. S2CID 577152.
  27. ↑ Roser M, Ritchie H (2015). "Cancer". Our World in Data.
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