Melanoma , also known as malignant melanoma , is a type of cancer that develops from pigment-containing cells known as melanocytes. Melanoma usually occurs in the skin, but may rarely occur in the mouth, intestine, or eyes. In women, they are most common in the legs, while in men they are most common in the back. Sometimes they develop from a mole by observing changes including increased size, irregular edges, discoloration, itching, or skin damage.
The main cause of melanoma is exposure to ultraviolet (UV) rays in those with low skin pigment levels. UV light can come from the sun or from other sources, such as tanning devices. About 25% develop from moles. Those with multiple moles, a history of affected family members, and those with poor immune function are at greater risk. A number of rare genetic defects such as xeroderma pigmentosum also increase the risk. Diagnosis is performed by biopsy of each skin lesion.
Using sunscreen and avoiding UV rays can prevent melanoma. Treatment is usually performed surgically. In those with slightly larger cancers, nearby lymph nodes may be tested for spreading. Most people recover if the spread has not occurred yet. For those who have melanoma spread, immunotherapy, biological therapy, radiation therapy, or chemotherapy can improve survival. With treatment the five-year survival rate in the United States is 98% among those with localized disease and 17% of those who spread have occurred. The likelihood that it will return or spread depends on how thick the melanoma is, how fast the cells divide, and whether the skin on it has been damaged.
Melanoma is the most dangerous type of skin cancer. Globally, in 2012, it just happened to 232,000 people. In 2015 there are 3.1 million with active disease resulting in 59,800 deaths. Australia and New Zealand have the highest levels of melanoma in the world. There is also a high level in Northern Europe and North America, while it is less common in Asia, Africa, and Latin America. Melanoma is more common in men than women. Melanoma has become more common since the 1960s in areas where most people are white.
Video Melanoma
Signs and symptoms
The early signs of melanoma are changes in the shape or color of the existing mole or, in the case of nodular melanoma, the appearance of new bumps anywhere on the skin. At a later stage, the mole may be itchy, slit or bleed. Early signs of melanoma are summarized by mnemonic "ABCDE":
- A symmetry The
- B command (irregular with sides and corners)
- C olor (multiform)
- D iameter (greater than 6 mm (0.24 inches), the size of a pencil eraser)
- E repeats from time to time
However, this classification does not apply to the most dangerous forms of melanoma, nodular melanoma, which has its own classification:
- E hovering over the skin surface
- F irm to touch
- G paddle
Metastatic melanoma can cause nonspecific paraneoplastic symptoms, including loss of appetite, nausea, vomiting and fatigue. Metastasis from early melanoma is possible, but relatively rare: less than a fifth of melanoma diagnosed early into metastasis. Brain metastases are very common in patients with metastatic melanoma. It can also spread to the liver, bone, abdomen or distant lymph nodes.
Maps Melanoma
Cause
Melanoma is usually caused by DNA damage due to exposure to ultraviolet light from the sun. Genetics also plays a role.
Having more than fifty moles indicates an increased risk of melanoma may appear. A weakened immune system makes it easier for cancer to appear because of the weak body's ability to fight cancer cells.
UV radiation
Ultraviolet radiation from tanning beds increases the risk of melanoma. The International Agency for Research on Cancer found that tanning beds are "carcinogenic in humans" and people who start using tanning equipment before the age of thirty are 75% more likely to develop melanoma.
Those working on aircraft also appear to have an increased risk, believed to be due to greater exposure to UV.
UVB ultraviolet light (wavelength between 315-280 m) of the sun is absorbed by the DNA of skin cells and produces a kind of direct DNA damage called cyclobutane pyrimidine dimers (CPD). The thymine, cytosine or cytosine dimers are formed by the incorporation of two adjacent pyrimidine bases in the DNA strand. Somewhat similar to UVB, UVA rays (longer wavelengths between 400-315 nm) from the sun or from tanning beds can also be directly absorbed by skin DNA (about 100 to 1000 times lower efficiency than absorbed UVB).
Studies show that exposure to ultraviolet radiation (UVA and UVB) is one of the major contributors to the development of melanoma. Sometimes extreme sun exposure (producing "sunburn") is causally associated with melanoma. The most common melanoma in the backs in men and in the legs of women (areas of intermittent sun exposure). Risks appear to be strongly influenced by socio-economic conditions rather than indoor versus outdoor work; this is more common in professional and administrative workers than in unskilled workers. Other factors are the mutation or total loss of tumor suppressor genes. The use of sunbeds (with deep penetrating UVA rays) has been linked to the development of skin cancers, including melanoma.
Possible key elements in determining risk include the intensity and duration of sun exposure, the age at which sun exposure occurs, and the rate of skin pigmentation. The melanoma rate tends to be highest in countries inhabited by migrants from Northern Europe who have large amounts of intense direct sunlight so that the settlers' skin is not adapted to, notably Australia. Exposure during childhood is a more important risk factor than exposure in adulthood. This is seen in migration studies in Australia.
Having some severe sunburns increases the likelihood that future sunburns develop into melanoma due to cumulative damage. The sun and tanning beds are the main source of UV radiation that increases the risk of melanoma and living near the equator increases UV radiation exposure.
Genetics
A number of rare mutations, which often occur in families, greatly increase the susceptibility of melanoma. Some genes increase the risk. Some rare genes have a relatively high risk of causing melanoma; some of the more common genes, such as a gene called MC1R that causes red hair, have a relatively lower risk of height. Genetic tests can be used to find mutations.
One mutation class affects the CDKN2A gene. A mutation of alternative reading frames in this gene leads to the destruction of p53, the transcription factors involved in apoptosis and in fifty percent of human cancers. Other mutations in the same gene result in a nonfunctional inhibitor of CDK4, a cyclin-dependent kinase that induces cell division. Mutations that cause skin conditions xeroderma pigmentosum (XP) also increase the susceptibility of melanoma. Scattered throughout the genome, this mutation reduces the cell's ability to repair DNA. Both CDKN2A and XP mutations are highly penetrant (likely carriers to express high phenotypes).
Familial melanoma is genetically heterogeneous, and locus for familial melanoma appears on the arm of chromosome 1p, 9p and 12q. Genetic events have been associated with the pathogenesis of melanoma (disease progression). The multiple suppressor 1 gene (CDKN2A/MTS1) encodes p16INK4a - a low molecular weight protein inhibitor of the cyclic-dependent protein kinase (CDKs) - that has been localized to the p21 region of human chromosome 9.
Other mutations carry a lower risk, but are more common in the population. People with mutations in the MC1R gene, for example, are two to four times more likely to develop melanoma than those with two types of wild type (typical of unaffected type). MC1R mutations are very common; In fact, everyone with red hair has a copy of that mutation. Mutation of the MDM2 SNP309 gene is associated with an increased risk for younger women.
People with white hair and red hair, people with some atypical nevi or dysplastic naevi and people born with giant congenital melanocytic naevi have an increased risk.
Family history of melanoma greatly increases one's risk because mutations in some genes have been found in families susceptible to melanoma. People with a history of one melanoma are at an increased risk of developing a second primary tumor.
Bright skin is the result of having less melanin in the skin, which means there is less protection from UV radiation. Family history may indicate a genetic predisposition to melanoma.
Pathophysiology
The initial stage of melanoma begins when melanocytes start growth out of control. Melanocytes are found between the outer layer of skin (epidermis) and the next layer (dermis). The initial stage of the disease is called the radial growth phase, when the tumor is less than 1 mm. Because cancer cells have not reached the deeper blood vessels in the skin, it is highly unlikely that the early stages of melanoma will spread to other parts of the body. If melanoma is detected at this stage, it can usually be removed completely by surgery.
When tumor cells start moving in different directions - vertically to the epidermis and into dramatic dermal-papillary behavior changes.
The next step in evolution is the invasive radial growth phase, which is a confusing term; However, this explains the process of radial growth, in which individual cells begin to gain invasive potential. From this point on the melanoma is able to spread. The depth of the Breslow lesion is usually less than 1 mm (0.04 inches), while the Clark level is usually 2.
The following vertical growth phase (VGP) is invasive melanoma. The tumor can grow into surrounding tissue and can spread throughout the body through blood vessels or lymph. The thickness of the tumor is usually more than 1 mm (0.04 inches), and the tumor involves a deeper portion of the dermis.
The host elicits an immunologic reaction to the tumor during VGP, which is assessed by the presence and activity of lymphocyte infiltration tumors (TIL). These cells sometimes completely destroy the primary tumor; this is called regression, which is the last stage of development. In certain cases, the primary tumor is completely destroyed and only metastatic tumors are found. About 40% of human melanoma contains an active mutation that affects the structure of the B-Raf protein, producing a constitutive signal via the Raf line to the MAP kinase.
In general, cancer is caused by DNA damage. UVA rays primarily cause thymine-thymine dimers. UVA also produces reactive oxygen species and this causes other DNA damage, especially single-strand breaks, oxidized pyrimidine and oxidized oxidizable oxide (mutagenic DNA change) on 1/10, 1/10 and 1/3 of UVA frequency -dimediated thymine- thymine dimers, respectively.
If not corrected, CPD photoproducts may cause mutations by inaccurate transect synthesis during DNA replication or repair. The most frequent mutation due to inaccurate synthesis of the preceding CPD is cytosine against a thymine transition mutation (C & gt; T) or CC & gt; TT. This is often called the UV fingerprint mutation, because it is the most specific mutation caused by UV, which is often found in sun-exposed skin but is rarely found in internal organs. Errors in DNA repair of UV photoproducts, or inaccurate synthesis passing through these photoproducts, may also lead to the removal, insertion and translocation of chromosomes.
The entire genome of 25 melanomas is sorted. On average, about 80,000 mutated bases (mostly C & gt; T transitions) and about 100 structural rearrangements are found per melanoma genome. This is much higher than about 70 mutations across generations (parent to child). Among 25 melanomas, about 6,000 protein coding genes experience missense, nonsense, or mutation of the splice site. Transcripts of more than 100 melanomas have also been sequenced and analyzed. Almost 70% of all human protein coding genes are expressed in melanoma. Most of these genes are also expressed in normal tissues and other cancers, with about 200 genes showing a more specific expression pattern in melanoma than with other forms of cancer. Examples of specific genes of melanoma are tyrosinase, MLANA and PMEL.
UV radiation causes damage to cell DNA, usually thymine dimerization, which when not repaired can create mutations in the cell gene. As cells divide, these mutations are propagated to new cell generations. If a mutation occurs in a protooncogene or tumor suppressor gene, the mitotic rate in the mutated cells can become uncontrolled, leading to tumor formation. Data from patients showed that levels deviating from active transcription factors in melanoma cell nuclei were associated with increased metastatic activity of melanoma cells; studies of mice on skin cancer tend to confirm the role to activate the transcription factor-2 in cancer progression.
Cancer stem cells can also be involved.
Diagnosis
Visual inspection is the most common diagnostic technique. Irregular moles in color or shape are usually treated as candidates. To detect melanoma (and improve survival rate), it is recommended to learn to recognize it (see "ABCDE" above), to regularly check the mole for changes (shape, size, color, itching or bleeding) and to consult a qualified physician when a candidate appears.
ABCDE
The popular method for remembering the signs and symptoms of melanoma is "ABCDE" mnemonic:
- Symmetrical skin lesions.
- B the order of irregular lesions.
- C olor: melanoma usually has many colors.
- D iameter: mole greater than 6 mm more likely to melanoma than a small mouse.
- E nlarging: Zoom in or evolve
However, many melanomas are present as lesions smaller than 6 mm in diameter; and all malignant melanomas when they first appear as small dots. Doctors usually check all moles, including less than 6 mm. Seborrhoeic keratosis may meet some or all of the ABCD criteria, and may cause false alarms. Doctors can usually distinguish seborrheic keratosis from melanoma during examination, or by dermatoscopy.
Some supporters replace the enlargement with evolution. Of course the changed and evolved mole will be a concern. Or, some practitioners prefer elevation. Altitude may help identify melanoma, but lack of elevation does not mean that the lesion is not a melanoma. Most melanomas in the US are detected before they become elevated. At the time of visible elevation, they may have progressed to a more dangerous invasive stage.
Nocular melanoma does not meet these criteria, has their own mnemonic, "EFG":
- E is released: the lesion is raised on the surrounding skin.
- F irm: solid nodules to touch.
- G paddle: the larger the nodule.
Ugly duck
The new and new methods are "bad duck marks". It's simple, easy to teach, and very effective. Correlation of generalized lesion characteristics was made. Lesions that deviate strongly from common characteristics are labeled "Ugly Duckling", and further professional examination is required. The "Red Red Riding Hood" sign indicates that individuals with bright skin and light-colored hair may have difficulty diagnosing amelanotic melanoma. Extra attention is required when examining such individuals, as they may have some very dysplastic melanomas and nevi. Dermatoscopes should be used to detect "bad ducks", as many melanomas in these individuals resemble non-melanoma or are considered "wolf in sheep's clothing". These white individuals often have mild or amelanotic pigmented melanomas that do not provide changes and color variations that are easily observed. Their boundaries are often unclear, complicating visual identification without a dermatoscope.
Amelanotic melanomas and melanomas that occur in skinned individuals are very difficult to detect, as they fail to show many characteristics in the ABCD rule, breaking the "Ugly Duckling" sign and are difficult to distinguish from acne scars, insect bites, dermatofibromas. , or lentigine.
Biopsy
After visual examination and dermatoscopy examination, or an in vivo diagnostic tool like confocal microscopy, the doctor may perform a biopsy on a suspicious mole. Skin biopsy performed under local anesthesia is often necessary to assist in making or confirming the diagnosis and in determining the severity. Elliptical excision biopsy can remove the tumor, followed by histologic analysis and Breslow score. An incisional biopsy such as a biopsy punch is usually contraindicated in suspect melanoma, due to the possibility of sampling error or local implantation leading to estimation error of tumor thickness. However, the concern that such biopsies may increase the risk of metastatic disease seems unfounded.
Total body photography, which involves photography documentation as much as possible body surface, is often used during follow-up for high-risk patients. This technique has been reported to enable early detection and provide a cost-effective (with digital camera) approach, but its efficacy has been questioned for its inability to detect macroscopic changes. The diagnostic method should be used in conjunction with (and not in place of) dermoscopic imaging, with a combination of the two methods that appear to provide a very high detection rate.
Classification
Melanoma is divided into the following types:
- Lentigo maligna
- Lentigo maligna melanoma
- Superficial melanoma spreads
- Acral lentiginous melanoma
- Mucosal melanoma
- Nodular melanoma
- Polypoid melanoma
- Desmoplastic melanoma
See also:
- Melanoma with small nevus-like cells
- Melanoma with features from Spitz nevus
- Uveal melanoma
- Vaginal melanoma
Laboratory
Lactate dehydrogenase (LDH) tests are often used to screen metastases, although many patients with metastasis (even end-stage) have normal LDH; Extremely high LDH often indicates the spread of the disease to the liver metastatically.
It is common for patients diagnosed with melanoma to have chest X-rays and LDH tests, and in some cases CT, MRI, PET and/or PET/CT scans. Although controversial, sentinel lymph node biopsy and lymph node examination are also performed on patients to assess spread to the lymph nodes. Diagnosis of melanoma is supported by the presence of S-100 protein marker.
HMB-45 is a monoclonal antibody that reacts to antigens present in melanocytic tumors such as melanoma. This is used in anatomical pathology as a marker for the tumor. The antibodies are produced to the melanoma extract. It reacts positively to melanocytic tumors but not other tumors, thus indicating specificity and sensitivity. Antibodies also react positively to junctional nevus cells but not intradermal nevi, and fight fetal melanocytes but not normal adult melanocytes.
HMB-45 is not reactive with almost all non-melanoma human malignancies, with the exception of rare tumors that exhibit evidence of melanogenesis (eg, pigmented schwannoma, clear cell sarcoma) or tumors associated with the tuberous sclerosis complex (angiomyolipoma and lymphangiomyoma).
Staging
Further contexts about the stage of cancer are available in TNM.
Also notable are the "Clark levels" and the "Breslow depth", which refers to the microscopic depth of tumor invasion.
Melanoma stages: 5-year survival rate:
Stage 0 : Melanoma in place (Clark Level I), 99.9% survival
Stage I/II : Invasive melanoma, survival 89-95%
- T1a: The thickness of the primary tumor is less than 1.0 mm, without ulceration, and mitosis & lt; 1/mm2
- T1b: Less than 1.0 mm primary tumor thickness, with ulceration or mitosis> = 1/mm2
- T2a: 1.01-2.0Ã, mm thickness of primary tumor, without ulceration
Stage II : High-risk melanoma, 45-79% survival thickness of primary tumor, with ulceration
Phase III : Regional metastasis, 24-70% survival
- N1: One positive lymph node
- N2: Two or three positive lymph nodes or regional skin/transit metastasis
- N3: Four positive lymph nodes or a lymph node and a regional skin/transit metastasis
Stage IV : distant metastasis, 7-19% survival
- M1a: Leaf skin metastasis, normal LDH
- M1b: Pulmonary metastases, normal LDH
- M1c: distant metastases or distant metastases with high LDH
Based on AJCC's five-year survival from early diagnosis of melanoma with appropriate treatment.
Prevention
Avoiding ultraviolet radiation
Minimizing exposure to sources of ultraviolet radiation (sun and sunbeds), following sun protection measures and wearing sun-protective clothing (long-sleeved shirts, long pants, and wide-brimmed hat) can offer protection.
Using artificial light for tannery is believed to help prevent skin cancer, but can actually lead to an increased incidence of melanoma.
The body uses UV light to produce vitamin D so there is a need to balance getting enough sunlight to maintain healthy vitamin D levels and reduce the risk of melanoma; it takes about half an hour of sunlight for the body to produce vitamin D for the day and it is about the same amount of time for white people to get sunburn. Sun exposure can be intermittent, and not just once at a time.
Sunscreen
Sunscreen seems to effectively prevent melanoma. In the past, the use of sunscreen with a sun protection rating (SPF) rating of 50 or higher in the affected area is recommended; because older sunscreens are more effective at blocking UVA with higher SPF. Currently, newer sunscreens (avobenzone, zinc oxide, and titanium dioxide) effectively block UVA and UVB even in lower SPFs. Sunscreen also protects against squamous cell carcinoma, other skin cancers.
Concern has been raised that sunscreen might create a false sense of security against sun damage.
Treatment
Confirmation of clinical diagnosis is done by skin biopsy. This is usually followed by a wider excision of the scar or tumor. Depending on the stage, sentinel lymph node biopsy is performed, too, despite controversy surrounding trial evidence for this procedure. Treatment of advanced malignant melanoma is done from a multidisciplinary approach.
Surgery
Excision biopsy may remove the tumor, but further surgery is often needed to reduce the risk of recurrence. Complete surgical excision with adequate surgical limits and assessment for the presence of metastatic disease detected along with short and long-term follow-up are standard. Often this is done by wide local excision (WLE) with a margin of 1-2 cm (0.4-0.8 inches). Melanoma-in-situ and malignant lentigo are treated with narrower surgical margins, typically 0.2-0.5 cm (0.1-0.2 inches). Many surgeons consider 0.5 cm (0.2 in) standard treatment for standard melanoma-in-situ excision, but 0.2 cm (0.1 inches) margin may be acceptable for controlled margin surgery (Mohs surgery, or technique bladed with margin control). Broad excision aims to reduce tumor recurrence rates at the site of the original lesion. This is a common pattern of treatment failure in melanoma. A considerable study aims to explain the right margin for excision with a general trend toward less aggressive treatment over the last few decades.
Mohs surgery has been reported with a cure rate as low as 77% and as high as 98.0% for melanoma-in-situ. CCPDMA and "double-scalpel" round-trip circumferential surgery are equivalent to effective Mohs surgery on this "intra-epithelial" melanoma type.
The spread melanoma usually does so to the lymph nodes in the tumor area before it spreads to other sites. Efforts to improve survival by removing lymph nodes through surgery (lymphadenectomy) are associated with many complications, but there is no overall survival benefit. More recently, sentinel lymph node biopsy techniques have been developed to reduce complications of lymph node surgery while allowing assessment of gland involvement with tumors.
Sentinel lymph node biopsy is a widely used procedure when treating skin melanoma.
Both sentinel lymph node biopsy and other diagnostic tests should be performed to evaluate early, thin melanoma, including in situ melanoma, T1a melanoma or T1b melanoma <= 0.5 mm. People with this condition are unlikely to have cancer spread to their lymph nodes or elsewhere and already have a 97% 5-year survival rate. Because of these things, sentinel lymph node biopsy does not need health care for them. In addition, baseline blood and radiographic studies should not be performed solely on the identification of this type of melanoma, as there are more accurate tests for cancer detection and these tests have a high false positive rate. For false positives of false positives, gene expression profiles can be used as additional testing for ambiguous and small lesions.
Sentinel lymph node biopsy is common, especially for T1b/T2 tumors, mucosal tumors, ocular melanoma and tumors of the limbs. A process called lymphoscintigraphy is performed in which a radioactive tracer is injected at the site of the tumor to localize the sentinel node. Further accuracy is given using blue tracking dye, and surgery is performed for node biopsy (s). Regular hepaticoxylin and eosin (H & amp; E) and immunoperoxidase staining will be sufficient to exclude nodal involvement. A polymerase chain reaction (PCR) test of the node, usually done to test admission to clinical trials, now shows that many patients with negative sentinel lymph nodes actually have a small number of positive cells in their glands. Alternatively, a fine needle aspiration biopsy may be performed and often used to test the mass.
If the lymph node is positive, depending on the extent of spreading of the lymph nodes, radical lymph node dissection will be frequent. If the disease is fully resected, the patient will be considered for adjuvant therapy. Excisional skin biopsy is the management of choice. Here, the suspect's lesion is completely removed with an adequate (but minimal, usually 1 or 2 mm) ellipse from the skin and surrounding tissue. To avoid disturbance of local lymphatic drainage, the preferred surgical limit for early biopsy should be narrow (1 mm). The biopsy should include a layer of epidermis, skin, and subcutaneous skin. This allows the histopathologist to determine the thickness of melanoma by microscopic examination. This is explained by the thickness of Breslow (measured in millimeters). However, for large lesions, such as suspected lentigo maligna, or for lesions in difficult areas of surgery (face, toes, fingers, eyelids), small punch biopsies in the representative area will provide adequate information and will not interfere with late-stage determination or determination depth. Under no circumstances should an initial biopsy cover surgical deadline (0.5 cm, 1.0 cm, or 2 cm), because misdiagnosis can cause scarring and excessive morbidity of the procedure. A large initial excision will interfere with local lymphatic drainage and may adversely affect lymphangiogram lymph node dysfunction. A small punch biopsy can be used anytime where for logistical and personal reasons, the patient rejects a more invasive excision biopsy. Small punch biopsies are minimally invasive and recover quickly, usually without real scarring.
Add to care
High-risk melanoma may require adjuvant treatment, although attitudes toward it vary across countries. In the United States, the majority of otherwise healthy patients will start one year with high-dose interferon therapy, which has severe side effects, but can improve the patient's prognosis slightly. However, the British Association of Dermatologists guidelines on melanoma suggest that interferon is not recommended as a standard adjuvant treatment for melanoma. A 2011 meta-analysis shows that interferon can prolong the time before melanoma returns but improves survival by only 3% at 5 years. Unpleasant side effects also greatly decrease the quality of life.
In Europe, interferon is not usually used outside the scope of clinical trials.
Metastatic melanoma can be detected by X-ray, CT scan, MRI, PET and PET/CT, ultrasound, LDH testing and photoacoustic detection.
Chemotherapy and immunotherapy
Various chemotherapy agents, including temozolomide, dacarbazine (also called DTIC), immunotherapy (with interleukin-2 (IL-2) or interferon (IFN)), as well as local perfusion, are used by various centers. The overall success in metastatic melanoma is very limited.
IL-2 (Proleukin) is the first approved new therapy (1990 Europe, 1992 USA) for the treatment of metastatic melanoma in 20 years. Studies have shown that IL-2 offers the possibility of a complete and long-lasting remission of the disease, although only in a small percentage of patients. IL-2 intralesi for metastasis in transit has a high complete response rate ranging from 40 to 100%.
In 2005 a number of new agents and new approaches are being evaluated and show promise.
In 2009, the participation of clinical trials was considered a standard of care for metastatic melanoma.
Therapies for metastatic melanoma include ipilimumab biological immunotherapy agents, pembrolizumab, and nivolumab; BRAF inhibitors, such as vemurafenib and dabrafenib; and mEK trametinib inhibitors.
Ongoing research is to seek treatment with transfer of cell lift. For this purpose, the application of stimulated or modified T cells or dendritic cells is possible.
Lentigo maligna
Standard excision is still performed by most surgeons. Unfortunately, the recurrence rate is very high (up to 50%). This is due to an apparently unclear operation limit, and the location of the face of the lesion (often forcing the surgeon to use narrow surgical margins). The narrow surgical margin used, combined with the standard "bread-misfortune" of fixed tissue histology techniques - results in a high "false negative" error rate, and often recurs. Margins control (margin edge) is required to eliminate false negative errors. If loafing loaf is used, the distance from the portion should be close to 0.1 mm to ensure that the method approaches the complete margin control.
Mohs surgery has been performed with a reported cure rate as low as 77%, and as high as 95% by other authors. The "double scalpel" controlled marginal control method approximates the Mohs method in margin control, but requires familiar pathologists familiar with the complexity of managing vertical margins on thin peripheral parts and staining methods.
Some melanocytic naevi, and melanoma-in-situ (lentigo maligna) have healed with experimental treatment, imiquimod topical cream (Aldara), immune-boosting substances. Some skin surgeons combine two methods: surgically exclude the cancer and then treat the area with Aldara cream after surgery for three months.
Radiation therapy
Radiation therapy is often used after surgical resection for patients with advanced or regional melanoma or for patients with distant, inoperable metastases. Kilovoltage x-ray beam is often used for this treatment and has properties of maximum radiation doses that occur close to the skin surface. This can reduce the local recurrence rate but not prolong survival. Radioimmunotherapy of metastatic melanoma is currently under investigation. Radiotherapy has a role in metastatic melanoma paliation.
Prognosis
The features that affect the prognosis are tumor thickness in millimeters (Breslow depth), depth associated with skin structure (Clark level), type of melanoma, presence of ulcers, lymphatic/perineural invasion, presence of tumor infiltrate lymphocytes (if present, better prognosis) location of lesions, presence of satellite lesions, and presence of regional or distant metastases. Certain types of melanoma have a worse prognosis but this is explained by the thickness. Interestingly, a less invasive melanoma even with lymph node metastasis carries a better prognosis than inner melanoma without regional metastases at the time of staging. Local recurrence tends to behave similarly to the primary unless they are in a large local excisional location (compared with gradual excision or punch/excision shaving) as this recurrence tends to indicate lymphatic invasion.
When melanoma has spread to the lymph nodes, one of the most important factors is the number of nodes with malignancy. The degree of malignancy in the nodes is also important; micrometastases in which only microscopic malignancies have a more favorable prognosis than macrometastases. In some cases micrometastases can only be detected by specific staining, and if the malignancy is detected only by a rare test known as polymerase chain reaction (PCR), the prognosis is better. Macrometastases in which the malignancy is clinically apparent (in some cases the cancer actually replaces the node) have a much worse prognosis, and if the node is matted or if there is an extracapsular extension, the prognosis is still worse. In addition to these variables, the level of expression and variation in the number of copies of a number of relevant genes can be used to support the assessment of malignant melanoma prognosis.
When there is a distant metastasis, cancer is generally considered incurable. The five-year survival rate is less than 10%. The average survival is 6-12 months. Treatment is palliative, focused on extending life and quality of life. In some cases, patients may live for months or even years with metastatic melanoma (depending on treatment aggressiveness). Metastases to the skin and lungs have a better prognosis. Metastases to the brain, bone and liver are associated with a poor prognosis. Survival is better with metastasis where the location of the primary tumor is unknown.
There is not enough definitive evidence for sufficient stages, and thus provides a prognosis for ocular, melanoma and melanoma of the soft part, or mucous melanoma (eg rectal melanoma), although this tends to metastasize more easily. Although regression may improve survival, when melanoma regresses, it is impossible to know its original size and thus indigenous tumors are often worse than may be indicated by pathology reports.
About 200 prognostic genes in melanoma, with both unfavorable genes in which high expression correlate with poor survival and favorable genes where high expression is associated with longer survival time. Examples of unfavorable genes are MCM6 and TIMELESS and examples of beneficial genes are WIPI1.
Epidemiology
Globally, in 2012, melanoma occurred in 232,000 people and resulted in 55,000 deaths. Australia and New Zealand have the highest levels of melanoma in the world. This has become more common in the last 20 years in most Caucasian areas.
The rate of melanoma has increased in recent years, but it is unclear to what extent behavioral changes, in the environment, or in early detection are involved.
Australia
Australia has a very high and increasing rate of melanoma. In 2012, deaths from melanoma occur at 7.3-9.8 per 100,000 population. In Australia, melanoma is the third most common cancer in both sexes; indeed, the incidence is higher than lung cancer, although the latter causes more deaths. It is estimated that by 2012, more than 12,000 Australians are diagnosed with melanoma: given Australia's modest population, this is best expressed as 59.6 new cases per 100,000 population per year; & gt; 1 in 10 new cases of cancer is melanoma. The incidence of melanoma in Australia is a significant problem, for the following reasons:
- The incidence of Australian melanoma has increased by more than 30 percent between 1991 and 2009.
- The incidence rate of Australian standard melanoma, in 2008, was at least 12 times higher than the world average.
- The incidence of Australian melanoma, with some margin, is highest in the world.
- The overall incidence of standard cancers in Australia is the highest in the world, and this is due to melanoma alone. The overall cancer incidence of age standard is similar to New Zealand, but there is a statistically significant difference between Australia and all other parts of developed countries including North America, Western Europe, and the Mediterranean.
United States
In the United States about 9,000 people die from melanoma a year. In 2011 it affected 19.7 per 100,000, and resulted in deaths at 2.7 per 100,000.
In 2013:
- 71,943 people in the United States were diagnosed with skin melanoma, including 42,430 men and 29,513 women.
- 9394 people in the United States die of skin melanoma, including 6,239 men and 3,155 women.
Estimates of the American Cancer Society for the incidence of melanoma in the United States for 2017 are:
- About 87,110 new melanomas will be diagnosed (about 52,170 in men and 34,940 in women).
- Approximately 9,730 people are thought to have died of melanoma (about 6,380 men and 3,350 women).
Melanoma is more than 20 times more common in whites than in African Americans. Overall, the lifetime risk of getting melanoma is about 2.5% (1 in 40) for whites, 0.1% (1 in 1,000) for African Americans, and 0.5% (1 in 200) for Hispanics.
The risk of melanoma increases with age. The average age of people when the disease is diagnosed is 63.
History
Although melanoma is not a new disease, evidence for events in ancient times is somewhat rare. One example, however, lies in the 1960s examination of nine Peruvian mummies, radiocarbon dating back to about 2400 years, showing signs of melanoma: the melanotic mass in the skin and metastasis spreading to the bone.
John Hunter was reported to be the first to operate on metastatic melanoma in 1787. Although not exactly what it was, he described it as "fungous cancer excretion". Cut tumors are preserved at the Hunterian Museum of the Royal College of Surgeons of England. Only in 1968 microscopic examination of the specimen revealed it to be an example of metastatic melanoma.
French doctor Renà © Å © Laennec is the first to describe melanoma as a disease entity. His report was originally presented during his lecture to the faculty of Death de Paris declared in 1804 and subsequently published as a bulletin in 1806. The first English report of melanoma was presented by a British general practitioner from Stourbridge, William Norris in 1820. In work later in 1857 he said that there is a family trend for the development of melanoma ( Eight Cases of Melanosis with Pathological and Therapeutical Description on the Disease ). Norris is also a pioneer in suggesting a link between naevi and melanoma and the possible link between melanoma and environmental exposure, noting that most of the patients had pale skin. He also explained that melanomas can become amelanotic and then show the nature of metastatic melanoma by observing that they can spread to other visceral organs.
The first official admission of advanced melanoma as untreatable came from Samuel Cooper in 1840. He stated that the only chance for healing depended on the initial removal of the disease (ie, the early excision of a malignant mole)... '
Over a century and a half later, the situation remains largely unchanged.
The word melanoma comes from the Greek ????? weld which means "dark".
Research
Pharmacotherapy research for inoperable or metastatic malignant melanoma is ongoing.
Targeted therapies
In clinical studies other therapeutic arrangements, such as lifting or gene therapy, are being tested.
Two types of experimental treatments developed at the National Cancer Institute (NCI), have been used in metastatic melanoma with temporary success.
The first treatment involves elevated cell therapy (ACT) using immune TIL cells (tumor infiltrating lymphocytes) isolated from a person's melanoma tumor. These cells grow in large quantities in the laboratory and are returned to the patient after treatment which temporarily reduces normal T cells in the patient's body. TIL therapy after lymphodepletion can produce a long lasting response in a variety of settings.
The second treatment, adaptive transfer of genetically altered autologous lymphocytes, depends on the transmission of the encoding gene called the T cell receptor (TCR), to the patient's lymphocyte. After that, the lymphocyte manipulation recognizes and binds to certain molecules found on the surface of melanoma cells and kills them.
The cancer vaccine showed a modest benefit in late-stage testing in 2009 against melanoma.
BRAF inhibitors
About 60% of melanomas contain mutations in the B-Raf gene. Preliminary clinical trials show that B-Raf inhibitors including Plexxicon vemurafenib can cause substantial tumor regression in most patients if their tumors contain B-Raf mutations. In June 2011, major clinical trials confirmed positive findings from previous trials.
In August 2011 Vemurafenib received FDA approval for the treatment of end-stage melanoma. In May 2013 the US FDA approved dabrafenib as a single-agent treatment for patients with BRAF V600E sophisticated melanoma-positive mutations.
Some researchers believe that combination therapy that simultaneously blocks multiple pathways can improve efficacy by making it more difficult for tumor cells to mutate before being destroyed. In October 2012, a study reported that combining Dabrafenib with MEK trametinib inhibitors led to better results. Compared to Dabrafenib alone, progression-free survival increased to 41% from 9%, and mean progression-free survival increased to 9.4 months compared with 5.8 months. Some of the side effects, however, increased in the combined study.
In January 2014, the FDA approved a combination of dabrafenib and trametinib for the treatment of patients with BRAF V600E/K-mutant metastatic melanoma.
The resistance occurring in BRAF and MEK inhibitors may be due to a surface cell protein known as EphA2 currently under investigation.
Ipilimumab
At the American Society of Clinical Oncology Conference in June 2010, the Bristol-Myers Squibb pharmaceutical company reported the clinical findings of their drug ipilimumab. The study found an average survival increase of 6.4 to 10 months in patients with advanced melanoma treated with monoclonal ipilimumab, compared with experimental vaccine. It also found a one-year survival rate of 25% in the control group using vaccines, 44% in the vaccine group and ipilimumab, and 46% in the ipilimumab-treated group alone. However, some have raised concerns about the study because of its use in the unconventional control group, rather than comparing drugs with placebo or standard treatment. The criticism is that although Ipilimumab performs better than vaccines, the vaccine has never been tested before and may cause toxicity, making the drug look better than it is.
Ipilimumab was approved by the FDA in March 2011 to treat patients with end-stage melanoma that has spread or can not be removed surgically.
In June 2011, ipilimumab plus dacarbazine clinical trials combined this immune system booster with standard chemotherapy drugs targeting cell division. This shows an average survival increase for these late-stage patients for up to 11 months instead of the 9 months normally seen. The researchers also hope that perhaps 10-20% of patients can live long. Some serious side effects of revving the immune system are seen in some patients. The cost of treatment is $ 120,000. The brandname of the drug is Yervoy.
Surveillance methods
Progress in high resolution ultrasound scanning has enabled the monitoring of metastatic burden to sentinel lymph nodes. Screening and Surveillance of Ultrasound in Melanoma trial (SUNMEL) is evaluating ultrasound as an alternative to invasive surgical methods.
Oncolytic virotherapy
In some countries the oncolytic virotherapy method is studied and used to treat melanoma. Oncolytic virotherapy is a promising branch of virotherapy, in which oncolytic virus is used to treat disease; viruses can increase metabolism, reduce anti-tumor immunity and disrupt blood vessels. Talimogene laherparepvec (T-VEC) (which is a type of herpes simplex virus 1-derived from oncolytic immunotherapy), has been shown to be useful against metastatic melanoma by 2015 with a 4.4 month survival increase.
References
External links
Definition of melanoma dictionary in Wiktionary
Media related to Melanoma in Wikimedia Commons
- Melanoma in Curlie (based on DMOZ)
Source of the article : Wikipedia
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