Melanoma is a malignant tumor of melanocytes. Melanocytes predominantly occur in the skin but can be found elsewhere, especially the eye. The vast majority of melanomas originate in the skin. Melanomas are the most lethal form of skin cancer. As with most forms of cancer, earlier detection gives patients a better chance of survival. The following codes are used with International Statistical Classification of Diseases and Related Health Problems. ... // C00-D48 - Neoplasms (C00-C14) Malignant neoplasms, lip, oral cavity and pharynx (C00) Malignant neoplasm of lip (C01) Malignant neoplasm of base of tongue (C02) Malignant neoplasm of other and unspecified parts of tongue (C03) Malignant neoplasm of gum (C04) Malignant neoplasm of floor of mouth (C05) Malignant neoplasm of... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The International Classification of Diseases for Oncology (ICD-O) is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems for tumor diseases. ... The International Classification of Diseases for Oncology (ICD-O) is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems for tumor diseases. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Diseases Database is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... MedlinePlus (medlineplus. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Tumor (American English) or tumour (British English) originally means swelling, and is sometimes still used with that meaning. ... Melanocytes are cells located in the bottom layer of the skins epidermis. ... Diagram of the layers of human skin In zootomy and dermatology, skin is an organ of the integumentary system composed of a layer of tissues that protect underlying muscles and organs. ... To meet Wikipedias quality standards, this article or section may require cleanup. ...

Causes

Epidemiologic studies from Australia suggest that exposure to ultraviolet radiation is one of the major contributors to the development of melanoma. Few dermatologists question the association between sunlight and melanoma. It is widely believed that occasional extreme sun exposure (resulting in "sunburn") is causally related to melanoma. Those with more chronic long term exposure (outdoor workers) may develop protective mechanisms. Melanoma is most common on the back in men and on legs in women (areas of intermittent sun exposure) and is more common in indoor workers than outdoor workers (in a British study). Other factors are mutations in or total loss of tumor suppressor genes. Use of sunbeds (with deeply penetrating UVA rays) has been linked to the development of skin cancers, including melanoma. Epidemiology (Greek epi = upon, among; demos = people, district; logos = word, discourse), defined literally, is the study of epidemics in humans. ... UltraViolet is a 2006 action film in the science fiction genre. ... Dermatology is a branch of medicine dealing with the skin, its structure, functions, and diseases (from Greek derma, skin), as well as its appendages (nails, hair, sweat glands). ... In biology, mutations are changes to the genetic material (usually DNA or RNA). ... A tumor suppressor gene is a gene that reduces the probability that a cell in a multicellular organism will turn into a tumor cell. ... A sunbed with lights off. ...

Possible significant elements in determining risk include the intensity and duration of sun exposure, the age at which sun exposure occurs, and the degree of skin pigmentation. Historical data for native populations collected by R. Biasutti prior to 1940. ...

Exposure during childhood is a more important risk factor than exposure in adulthood. This is seen in migration studies in Australia where people tend to retain the risk profile of their country of birth if they migrate to Australia as an adult.

Fair and red-headed people are at greater risk for developing melanoma. A person with multiple atypical nevi or dysplastic nevi are at a significant risk. Although constant exposure to sun can cause melanoma, it is a larger risk factor for other less serious skin cancers, such as basal cell carcinoma and squamous cell carcinoma. Individuals with blistering or peeling sunburns (especially in the first twenty years of life) have a significantly greater risk for melanoma. It has been suggested that this article or section be merged with Birthmark. ... Basal cell carcinoma (BCC) is the most common skin cancer. ... In medicine, squamous cell carcinoma is a form of cancer of the carcinoma type that may occur in many different organs, including the skin, the esophagus, the lungs, and the cervix. ...

A family history of melanoma greatly increases a person's risk. It is critical that individuals with family members who have been diagnosed with melanoma be checked regularly for skin cancer.

Prevention

Primary

To prevent or detect melanomas (and increase survival rates), it is recommended that the public:

• Learn what they look like (see "ABCDE" mnemonic below.)
• Are aware of moles and check for changes (shape, size, color, itching or bleeding)
• Show any suspicious moles to a doctor (preferably a dermatologist).
• Minimize exposure to sources of ultraviolet radiation (the sun and sunbeds)
• Follow sun protection measures. Wearing protective clothing (long-sleeved shirts, long trousers, and broad-brimmed hats.) offers the best protection. Use a sunscreen with an SPF rating of 30 or better on exposed areas.

A popular method for remembering the signs and symptoms of melanoma is the mnemonic "ABCDE": Dermatology (from Greek derma, skin) is a branch of medicine dealing with the skin and its appendages (hair, nails, sweat glands etc). ... // History The ancient Greeks used olive oil as a type of sunscreen. ...

• Asymmetrical skin lesion.
• Border of the lesion is irregular.
• Color: melanomas usually have multiple colors.
• Diameter: moles greater than 5mm are more likely to be melanomas than smaller moles.
• Evolution: The evolution (ie change) of a mole or lesion may be a hint that the lesion is becoming malignant.

If you have a personal or family history of skin cancer or of dysplastic nevus syndrome (multiple atypical moles) you should see a dermatologist at least once a year. A dysplastic nevus, (or naevus; pl. ...

Diagnosis

Any mole that is irregular in color or shape should be examined by a doctor to determine if it is a malignant melanoma, the most serious and life-threatening form of skin cancer. Following a visual examination and a dermatoscopic exam (an instrument that illuminates a mole, revealing its underlying pigment and vascular network structure), the doctor may biopsy the suspicious mole. If it is malignant, the mole and an area around it needs excision. This may require a referral to a surgeon or dermatologist. Dermatoscopy (also known as epiluminescence microscopy) is the examination of cutaneous lesions with a dermatoscope, a magnifier with a light and a liquid medium between the instrument and the skin, thus illuminating the lesion without reflected light. ...

The diagnosis of melanoma requires experience, as early stages may look identical to harmless moles or not have any color at all. Where any doubt exists, the patient will be referred to a specialist dermatologist. Beyond this expert knowledge a biopsy performed under local anesthesia is often required to assist in making or confirming the diagnosis and in defining the severity of the melanoma. Melanocytic naevus A mole or melanocytic naevus is a small, dark spot on the skin. ... A biopsy (in Greek: bios = life and opsy = look/appearance) is a medical test involving the removal of cells or tissues for examination. ... Local anesthesia is any technique to render part of the body insensitive to pain without affecting consciousness. ... Diagnosis (from the Greek words dia = by and gnosis = knowledge) is the process of identifying a disease by its signs, symptoms and results of various diagnostic procedures. ...

One method is a punch biopsy, using a surgical punch (an instrument similar to a tiny cookie cutter with a handle, with an opening ranging in size from 1 to 6 mm). The punch is used to remove a plug of skin (down to the subcutaneous layer) from a portion of a large suspicious lesion, or to completely remove a smaller lesion. Preferably, an excisional biopsy can be performed, where the suspect lesion is totally removed by cutting an ellipse of tissue around it. Both methods will include the epidermal, dermal, and subcutaneous layers of the skin in the biopsy specimen, enabling the pathologist to determine the depth of penetration of the melanoma by microscopic examination. This is described by Clark's level (involvement of skin structures) and Breslow's depth (measured in millimeters). Pathology (from Greek pathos, feeling, pain, suffering; and logos, study of; see also -ology) is the study of the processes underlying disease and other forms of illness, harmful abnormality, or dysfunction. ...

Lactate dehydrogenase (LDH) tests are often used to screen for metastases, although many patients with metastases (even end-stage) have a normal LDH; extraordinarily high LDH often indicates metastatic spread of the disease to the liver. It is common for patients diagnosed with melanoma to have chest X-rays and an LDH test, and in some cases CT, MRI, PET and/or PET/CT scans. Although controversial, sentinel lymph node biopsies and examination of the lymph nodes are also performed in patients to assess spread to the lymph nodes. Lactate dehydrogenase (LDH) is an enzyme (EC 1. ... Metastasis (Greek: change of the state) is the spread of cancer from its primary site to other places in the body. ... CT apparatus in a hospital Computed tomography (CT), originally known as computed axial tomography (CAT) and body section roentgenography, is a medical imaging method employing tomography where digital geometry processing is used to generate a three-dimensional image of the internals of an object from a large series of two... The mri are a fictional alien species in the Faded Sun Trilogy of C.J. Cherryh. ... Image of a typical positron emission tomography (PET) facility Positron emission tomography (PET) is a nuclear medicine medical imaging technique which produces a three dimensional image or map of functional processes in the body. ... Structure of the lymph node. ...

Sometimes the skin lesion may bleed, itch, or ulcerate, although this is a very late sign. A slow-healing lesion should be watched closely, as that may be a sign of melanoma. Be aware also that in circumstances that are still poorly understood, melanomas may "regress" or spontaneously become smaller or invisible - however the malignancy is still present. Amelanotic (colorless or flesh-colored) melanomas do not have pigment and may not even be visible. Lentigo maligna, a superficial melanoma confined to the topmost layers of the skin (found primarily in older patients) is often described as a "stain" on the skin. Some patients with metastatic melanoma do not have an obvious detectable primary tumor. Lentigo is a type of brown skin lesion. ...

Types of Primary Melanoma

In the skin:

• Superficial spreading malignant melanoma (SSMM)
• Nodular melanoma
• Acral lentiginous melanoma
• Lentigo maligna melanoma
• Amelanotic melanoma
• Minimal deviation melanoma
• Desmoplastic melanoma

Elsewhere: Superficial spreading malignant melanoma is the most common form of cutaneous melanoma in Caucasians. ... Nodular melanoma is the most aggressive form of melanoma. ... Acral lentiginous melanoma is a kind of skin melanoma. ... Lentigo maligna is a melanoma in situ, meaning it consists of malignant cells but does not show invasive growth. ...

• Melanoma of soft parts
• Mucosal melanoma
• Ocular melanoma

Prognostic factors

Features that affect prognosis are tumor thickness in millimeters (Breslow's depth), depth related to skin structures (Clark level), type of melanoma, presence of ulceration, presence of lymphatic/perineural invasion, presence of tumor infiltrating lymphocytes (if present, prognosis is better), location of lesion, presence of satellite lesions, and presence of regional or distant metastasis. Prognosis (older Greek πρόγνωσις, modern Greek πρόγνωση - literally fore-knowing, foreseeing) is a medical term denoting the doctors prediction of how a patients disease will progress, and whether there is chance of recovery. ... In medicine, Breslows depth is used as a prognostic factor in predicting the 5-year survival rate in humans who have malignant melanoma of the skin by calculating the risk of metastasis. ... Lymphocyte A lymphocyte is a small white blood cell (leukocyte). ... Metastasis (Greek: change of the state) is the spread of cancer from its primary site to other places in the body. ...

Certain types of melanoma have worse prognoses. For example, minimal deviation melanomas have a much better prognosis than superficial spreading melanomas or even lentigo maligna melanomas. Interestingly, less invasive melanomas even with lymph node metastases carry a better prognosis than deep melanomas without regional metastasis at time of staging. Local recurrences tend to behave similar to a primary unless they are at the site of a wide local excision (as opposed to a staged excision or punch/shave excision) since these recurrences tend to indicate lymphatic invasion.

When melanomas have spread to the lymph nodes, one of the most important factors is the number of nodes with malignancy. Extent of malignancy within a node is also important; micrometastases in which malignancy is microscopic only have a more favorable prognosis than macrometastases. In some cases micrometastases may only be detected by special staining, and if malignancy is only detectable by a rarely-employed test known as polymerase chain reaction (PCR), the prognosis is good. Macrometastases in which malignancy is clinically apparent (in some cases cancer completely replaces a node) have a far worse prognosis, and if nodes are matted or if there is extracapsular extension, the prognosis is worse. Polymerase chain reaction (PCR) is a molecular biology technique for enzymatically replicating DNA without using a living organism, such as E. coli or yeast. ...

When there is distant metastasis, the cancer is generally considered incurable. The five year survival rate is less than 10%. The median survival is 6 to 12 months. Treatment is palliative, focusing on life-extension and quality of life. In some cases, patients may live many months or even years with metastatic melanoma (depending on the aggressiveness of the treatment). Metastases to skin and lungs have a better prognosis. Metastases to brain, bone and liver are associated with a worse prognosis.

There is not enough definitive evidence to adequately stage, and thus give a prognosis for ocular melanoma and melanoma of soft parts, or mucosal melanoma (e.g. rectal melanoma), although these tend to metastasize more easily. Even though regression may increase survival, when a melanoma has regressed, it is impossible to know its original size and thus the original tumor is often worse than a pathology report might indicate.

Staging

Further context on cancer staging is available at TNM. The stage of a cancer is a descriptor (usually numbers I to IV) of how much the cancer has spread. ... TNM Classification of Malignant Tumours (TNM) is the system developed and maintained by the International Union Against Cancer (UICC) to maintain consensus on one globally recognised standard for categorising cancer. ...

Stage 0: Melanoma in Situ (Clark Level I), 100% Survival

Stage I/II: Invasive Melanoma, 85-95% Survival

• T1a: Less than 1.00 mm primary, w/o Ulceration, Clark Level II-III
• T1b: Less than 1.00 mm primary, w/Ulceration or Clark Level IV-V
• T2a: 1.00-2.00 mm primary, w/o Ulceration

Stage II: High Risk Melanoma, 40-85% Survival

• T2b: 1.00-2.00mm primary, w/ Ulceration
• T3a: 2.00-4.00 mm primary, w/o Ulceration
• T3b: 2.00-4.00 mm primary, w/ Ulceration
• T4a: 4.00mm or greater primary w/o Ulceration
• T4b: 4.00mm or greater primary w/ Ulceration

Stage III: Regional Metastasis, 25-60% Survival

• N1: Single Positive Lymph Node
• N2: 2-3 Positive Lymph Nodes OR Regional Skin/In-Transit Metastasis
• N3: 4 Positive Lymph Nodes OR Lymph Node and Regional Skin/In Transit Metastases

Stage IV: Distant Metastasis, 9-15% Survival (10-Year Survival ~0%)

• M1a: Distant Skin Metastasis, Normal LDH
• M1b: Lung Metastasis, Normal LDH
• M1c: Other Distant Metastasis OR Any Distant Metastasis with Elevated LDH

Based Upon AJCC 5-Year Survival With Proper Treatment

Treatment

Treatment of malignant melanoma is best performed from a multidisciplinary approach including dermatologists, medical oncologists, radiation oncologists, surgical oncologists, general surgeons, neurologists, neurosurgeons, otorynolaryngologists, radiologists, pathologists/dermatopathologists, research scientists, nurse practitioners and physician assistants, and palliative care experts. Nurse practitioners (NPs) and physician assistants (PAs) are qualified to evaluate and treat patients on behalf of their supervising physicians, so it should not be a surprise when visiting a dermatologist to see an NP or PA. Oncology is the medical subspecialty dealing with the study and treatment of cancer. ... A neurologist is a physician who is specialized in the diagnosis and treatment of neurologic diseases. ... Radiology is the branch of medical science dealing with the medical use of x-ray machines or other such radiation devices for the purpose of obtaining visual information as part of medical imaging. ... Max Bielschowsky Paul Ehrlich - (1854 - 1915) Gustav Giemsa - (1867 - 1948) (see Giemsa stain) Ludwig Grünwald William Boog Leishman - (1865 - 1926) (see leishmaniasis) Richard May Frank Burr Mallory (1862 - 1941) (see Mallory bodies) George Nicolas Papanicolaou (1883 - 1962) (see Pap smear) Artur Pappenheim Carl von Rokitansky Dmitri Leonidovich Romanowsky - (1861... A Nurse Practitioner (NP) is a Registered Nurse who has completed advanced education [generally a minimum of a masters degree] and training in the diagnosis and management of common medical conditions, including chronic illnesses. ... In the United States, physician assistants (PAs) are non-physicians licensed to practice medicine with a physicians supervision. ... Palliative care (from Latin palliare, to cloak) is any form of medical care or treatment that concentrates on reducing the severity of the symptoms of a disease or slows its progress rather than providing a cure. ...

Surgery

Diagnostic punch or excisional biopsies may appear to excise (and in some cases may indeed actually remove) the tumor, but further surgery is often necessary to reduce the risk of recurrence.

Complete surgical excision with adequate margins and assessment for the presence of detectable metastatic disease along with short and long term follow up is standard. Often this is done by a "wide local excision" (WLE) with 1.0 cm margins.

More recently, Mohs micrographic surgery is becoming increasingly popular for smaller melanomas, especially of the face. In this surgery, performed by specially-trained dermatologists, a small layer of tissue is excised and prepared as a frozen tissue section. This section can be prepared and examined by the dermatologist/dermatopathologist within one hour, and the patient will return for further stages of excision as needed, with each excised tissue layer being examined until clear margins are obtained. Although the amount of stages required can range from one to five or more, on average only two stages will be necessary to excise the tumor. If a tumor is found to be more invasive or widespread than previously thought, a WLE may on rare occasions be performed after Mohs surgery has begun. Although the risk of recurrence is slightly higher, the procedure is much less invasive and patients undergoing Mohs surgery have a similar survival rate to patients undergoing WLE.

Medication/chemotherapy

Some superficial melanomas (lentigo maligna melanoma) have resolved with imiquimod (Aldara®) topical cream, an immune enhancing agent. Application of this cream has been shown to decrease tumor size prior to surgery, reducing the invasiveness of the procedure. This treatment is used especially for smaller melanoma in situ lesions located in cosmetically sensitive regions. Several published studies demonstrate a 70% cure rate with this topical treatment. With lentigo maligna, surgical cure rates are no higher. Some dermasurgeons are combining the 2 methods: surgically excise the cancer, then treat the area with Aldara® cream post-operatively for 3 months. Melanomas with greater involvement may require referral to a medical or surgical oncologist. Imiquimod (Aldaraâ„¢) is a prescription medication used to treat certain diseases of the skin, including skin cancer (malignant melanoma and actinic keratosis) as well as genital warts. ...

Although controversial and without prolonging survival, "sentinel lymph node" biopsy is often performed, especially for T1b/T2+ tumors, mucosal tumors, ocular melanoma and tumors of the limbs. A process called "lymphoscintigraphy" is performed in which a mildly radioactive tracer is injected at the tumor site in order to localize the "sentinel node(s)". Surgery is performed to biopsy the node(s). Routine H&E staining, and immunoperoxidase staining will be adequate to rule out node involvement. PCR (Polymerase Chain Reaction) tests on nodes, usually performed to test for entry into clinical trials, now demonstrate that many patients with a negative SLN actually had a small amount of malignancy in their nodes. Alternatively, a fine-needle aspiration may be performed, and is often used to test masses. If a lymph node is positive, depending on the extent of lymph node spread, a radical lymph node dissection will often be performed, and most patients in otherwise good health will begin up to a year of high-dose interferon treatment, which despite side effects, greatly improves a patient's prognosis. Interferons (IFNs) are natural proteins produced by the cells of the immune systems of most animals in response to challenges by foreign agents such as viruses, bacteria, parasites and tumor cells. ...

Metastatic melanomas can be detected by X-rays, CT scans, MRIs, PET and PET/CTs, ultrasound, and LDH testing. Various chemotherapy agents are used, including dacarbazine (also termed DTIC), immunotherapy (with interleukin-2 (IL-2) or interferon (IFN)) as well as local perfusion are used by different centers. They can occasionally show dramatic success, but the overall success in metastatic melanoma is quite limited. IL-2 (Proleukin®)is the first new therapy approved for the treatment of metastatic melanoma in 20 years. Studies have demonstrated that IL-2 offers the possibility of a complete and long-lasting remission in this disease. Currently in clinical trials are a combination of dacarbazine and oblimersen. [3] Chemotherapy is the use of chemical substances to treat disease. ... Dacarbazine (da-KAR-ba-zeen) (brand names DTIC, DTIC-Dome; also known as DIC or Imidazole Carboxamide) is an antineoplastic chemotherapy drug used in the treatment of various cancers, among them malignant melanoma (a form of skin cancer which can spread to other parts of the body). ... Cancer Immunotherapy is the use of the immune system to reject cancer. ... Interleukin-2 (IL2) is an interleukin, a type of biological response modifier that can improve the bodys natural response to disease. ... Interferons (IFNs) are natural proteins produced by the cells of the immune systems of most animals in response to challenges by foreign agents such as viruses, bacteria, parasites and tumor cells. ...

Radiation therapy

Radiation therapy is often used after surgical resection for patients with locally or regionally advanced melanoma or for patients with unresectable distant metastases. In research setting other therapies, such as gene therapy, may be tested. Clinac 2100 C accelerator Radiation therapy (or radiotherapy) is the medical use of ionising radiation as part of cancer treatment to control malignant cells (not to be confused with radiology, the use of radiation in medical imaging and diagnosis). ... Gene therapy using an Adenovirus vector. ...

Radioimmunotherapy of metastatic melanoma is currently under investigation. Radioimmunotherapy (RIT) utilizes an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target cell (1). ...

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