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. It occurs when skin cells grow uncontrollably, forming malignant tumors. The primary cause of skin cancer is prolonged exposure to ultraviolet (UV) radiation from the sun or tanning devices. Skin cancer is the most commonly diagnosed form of cancer in humans. There are three main types of skin cancers: basal-cell skin cancer (BCC), squamous-cell skin cancer (SCC) and melanoma. The first two, along with a number of less common skin cancers, are known as nonmelanoma skin cancer (NMSC). Basal-cell cancer grows slowly and can damage the tissue around it but is unlikely to spread to distant areas or result in death. It often appears as a painless raised area of skin that may be shiny with small blood vessels running over it or may present as a raised area with an ulcer. Squamous-cell skin cancer is more likely to spread. It usually presents as a hard lump with a scaly top but may also form an ulcer. Melanomas are the most aggressive. Signs include a mole that has changed in size, shape, color, has irregular edges, has more than one color, is itchy or bleeds.
More than 90% of cases are caused by exposure to ultraviolet radiation from the Sun. This exposure increases the risk of all three main types of skin cancer. Such exposure has increased since the beginning of the industrial revolution, partly due to ozone depletion. Tanning beds are another common source of ultraviolet radiation. For melanomas and basal-cell cancers, exposure during childhood is particularly harmful. For squamous-cell skin cancers, total exposure, irrespective of when it occurs, is more important. Between 20% and 30% of melanomas develop from moles. People with lighter skin are at higher risk as are those with poor immune function such as from medications or HIV/AIDS. Diagnosis is by biopsy.
Decreasing exposure to ultraviolet radiation and the use of sunscreen appear to be effective methods of preventing melanoma and squamous-cell skin cancer. It is not clear if sunscreen affects the risk of basal-cell cancer. Nonmelanoma skin cancer is usually curable. Treatment is generally by surgical removal but may, less commonly, involve radiation therapy or topical medications such as fluorouracil. Treatment of melanoma may involve some combination of surgery, chemotherapy, radiation therapy and targeted therapy. In those people whose disease has spread to other areas of the body, palliative care may be used to improve quality of life. Melanoma has one of the higher survival rates among cancers, with over 86% of people in the UK and more than 90% in the United States surviving more than 5 years.
Skin cancer is the most common form of cancer, globally accounting for at least 40% of cancer cases. The most common type is nonmelanoma skin cancer, which occurs in at least 2–3 million people per year. This is a rough estimate; good statistics are not kept. Of nonmelanoma skin cancers, about 80% are basal-cell cancers and 20% squamous-cell skin cancers. Basal-cell and squamous-cell skin cancers rarely result in death. In the United States, they were the cause of less than 0.1% of all cancer deaths. Globally in 2012, melanoma occurred in 232,000 people and resulted in 55,000 deaths. White people in Australia, New Zealand and South Africa have the highest rates of melanoma in the world. The three main types of skin cancer have become more common since late 20th century, especially in regions where the population is predominantly white.
Classification
There are three main types of skin cancer: basal-cell skin cancer (basal-cell carcinoma) (BCC), squamous-cell skin cancer (squamous-cell carcinoma) (SCC) and melanoma. Cancer Description Illustration Basal-cell carcinoma Note the pearly translucency to fleshy color, tiny blood vessels on the surface, and sometimes ulceration which can be characteristics. The key term is translucency. Squamous-cell skin carcinoma Commonly presents as a red, crusted, or scaly patch or bump. Often a very rapidly growing tumor. Melanoma These are commonly asymmetrical in shape and/or pigment distribution, with an irregular border, color variation, and often greater than 6 mm diameter.
Basal-cell carcinomas are most commonly present on sun-exposed areas of the skin, especially the face. They rarely metastasize and rarely cause death. They are easily treated with surgery or radiation. Squamous-cell skin cancers are also common, but much less common than basal-cell cancers. They metastasize more frequently than BCCs. Even then, the metastasis rate is quite low, with the exception of SCC of the lip or ear, and in people who are immunosuppressed. Melanoma are the least frequent of the three common skin cancers. They frequently metastasize, and can cause death once they spread.
Less common skin cancers include: Merkel cell carcinoma, Paget's disease of the breast, atypical fibroxanthoma, porocarcinoma, spindle cell tumors, sebaceous carcinomas, microcystic adnexal carcinoma, keratoacanthoma, and skin sarcomas, such as angiosarcoma, dermatofibrosarcoma protuberans, Kaposi's sarcoma, leiomyosarcoma.
BCC and SCC often carry a UV-signature mutation indicating that these cancers are caused by UVB radiation via direct DNA damage. However, melanoma is predominantly caused by UVA radiation via indirect DNA damage. The indirect DNA damage is caused by free radicals and reactive oxygen species. Research indicates that the absorption of three sunscreen ingredients into the skin, combined with a 60-minute exposure to UV, leads to an increase of free radicals in the skin, if applied in too little quantity and too infrequently. However, the researchers add that newer creams often do not contain these specific compounds, and that the combination of other ingredients tends to retain the compounds on the surface of the skin. They also add that frequent re-application reduces the risk of radical formation.
Signs and symptoms There are a variety of different skin cancer symptoms. These include changes in the skin that do not heal, ulcering in the skin, discolored skin, and changes in existing moles, such as jagged edges to the mole, enlargement of the mole, changes in color, the way it feels or if it bleeds. Other common signs of skin cancer can be painful lesion that itches or burns and large brownish spot with darker speckles.
Basal-cell skin cancer Basal-cell skin cancer (BCC) usually presents as a raised, smooth, pearly bump on the sun-exposed skin of the head, neck, torso or shoulders. Sometimes small blood vessels (called telangiectasia) can be seen within the tumor. Crusting and bleeding in the center of the tumor frequently develops. It is often mistaken for a sore that does not heal. This form of skin cancer is the least deadly, and with proper treatment can be eliminated, often without significant scarring.
Squamous-cell skin cancer Squamous-cell skin cancer (SCC) is commonly a red, scaling, thickened patch on sun-exposed skin. Some are firm hard nodules and dome shaped like keratoacanthomas. Ulceration and bleeding may occur. When SCC is not treated, it may develop into a large mass. Squamous-cell is the second most common skin cancer. It is dangerous, but not nearly as dangerous as a melanoma.
Melanoma Most melanoma consist of various colours from shades of brown to black. A small number of melanoma are pink, red or fleshy in colour; these are called amelanotic melanoma and tend to be more aggressive. Warning signs of melanoma include change in the size, shape, color or elevation of a mole. Other signs are the appearance of a new mole during adulthood or pain, itching, ulceration, redness around the site, or bleeding at the site. An often-used mnemonic is "ABCDE", where A is for "asymmetrical", B for "borders" (irregular: "Coast of Maine sign"), C for "color" (variegated), D for "diameter" (larger than 6 mm – the size of a pencil eraser) and E for "evolving."
Other Merkel cell carcinomas are most often rapidly growing, non-tender red, purple or skin colored bumps that are not painful or itchy. They may be mistaken for a cyst or another type of cancer.
Causes Ultraviolet radiation from sun exposure is the primary environmental cause of skin cancer. This can occur in professions such as farming. Other risk factors that play a role include: Light skin color Age Smoking tobacco HPV infections increase the risk of squamous-cell skin cancer. Some genetic syndromes including congenital melanocytic nevi syndrome which is characterized by the presence of nevi (birthmarks or moles) of varying size which are either present at birth, or appear within 6 months of birth. Nevi larger than in size are at higher risk for becoming cancerous. Chronic non-healing wounds. These are called Marjolin's ulcers based on their appearance, and can develop into squamous-cell skin cancer. Ionizing radiation such as X-rays, environmental carcinogens, and artificial UV radiation (e.g. tanning beds). It is believed that tanning beds are the cause of hundreds of thousands of basal and squamous-cell skin cancer. The World Health Organization now places people who use artificial tanning beds in its highest risk category for skin cancer. Alcohol consumption, specifically excessive drinking increase the risk of sunburns. The use of many immunosuppressive medications increases the risk of skin cancer. Cyclosporin A, a calcineurin inhibitor for example increases the risk approximately 200 times, and azathioprine about 60 times. Deliberate exposure of sensitive skin not normally exposed to sunlight during alternative wellness behaviors such as perineum sunning.
UV-induced DNA damage
UV-irradiation of skin cells causes damage to DNA through photochemical reactions. Cyclobutane pyrimidine dimers formed by adjacent thymine bases, or by adjacent cytosine bases, are frequent types of DNA damage induced by UV. Human skin cells are capable of repairing most UV-induced damage by nucleotide excision repair, a process that protects against skin cancer, but may be inadequate at high levels of exposure.
Pathophysiology
A malignant epithelial tumor that primarily originates in the epidermis, in squamous mucosa or in areas of squamous metaplasia is referred to as a squamous-cell carcinoma.
Macroscopically, the tumor is often elevated, fungating, or may be ulcerated with irregular borders. Microscopically, tumor cells destroy the basement membrane and form sheets or compact masses which invade the subjacent connective tissue (dermis). In well differentiated carcinomas, tumor cells are pleomorphic/atypical, but resembling normal keratinocytes from prickle layer (large, polygonal, with abundant eosinophilic (pink) cytoplasm and central nucleus).
Their disposal tends to be similar to that of normal epidermis: immature/basal cells at the periphery, becoming more mature to the centre of the tumor masses. Tumor cells transform into keratinized squamous cells and form round nodules with concentric, laminated layers, called "cell nests" or "epithelial/keratinous pearls". The surrounding stroma is reduced and contains inflammatory infiltrate (lymphocytes). Poorly differentiated squamous carcinomas contain more pleomorphic cells and no keratinization.
A molecular factor involved in the disease process is mutation in gene PTCH1 that plays an important role in the Sonic hedgehog signaling pathway.
Diagnosis Diagnosis is by biopsy and histopathological examination.
Non-invasive skin cancer detection methods include photography, dermatoscopy, sonography, confocal microscopy, Raman spectroscopy, fluorescence spectroscopy, terahertz spectroscopy, optical coherence tomography, the multispectral imaging technique, thermography, electrical bio-impedance, tape stripping and computer-aided analysis.