Skin cancer

Skin cancer is a malignant growth on the skin which can have many causes. Skin cancer generally develops in the epidermis (the outermost layer of skin), so a tumor is usually clearly visible. This makes most skin cancers detectable in the early stages. There are three common types of skin cancer, each of which is named after the type of skin cell from which it arises. Cancers caused by UV exposure may be prevented by avoiding exposure to sunlight or other UV sources, and wearing sun-protective clothes. The use of sunscreen is recommended by medical organizations as a measure that helps to protect against skin cancer (see sunscreen).

Unlike many other cancers, including those originating in the lung, pancreas, and stomach, only a small minority of those afflicted will actually die of the disease. Skin cancers are the fastest growing type of cancer in the United States. Skin cancer represents the most commonly diagnosed malignancy, surpassing lung, breast, colorectal and prostate cancer. More than 1 million Americans will be diagnosed with skin cancer in 2008.

Risk factors
Skin cancer is most closely associated with chronic inflammation of the skin. This includes:


 * 1) Overexposure to UV-radiation can cause skin cancer either via the direct DNA damage or via the indirect DNA damage mechanism. UVA &amp; UVB have both been implicated in causing DNA damage resulting in cancer. Sun exposure between 10AM and 4PM is most intense and therefore most harmful. Natural (sun) &amp; artificial UV exposure (tanning salons) are associated with skin cancer. Since sunbeds cause mostly indirect DNA damage (free radicals) their use is associated with the deadliest form of skin cancer, malignant melanoma.
 * 2) Chronic non-healing wounds, especially burns. These are called Marjolin's ulcers based on their appearance, and can develop into squamous cell carcinoma.
 * 3) Genetic predisposition, including "Congenital Melanocytic Nevi Syndrome". CMNS is characterized by the presence of "nevi" or moles of varying size that either appear at or within 6 months of birth. Nevi larger than 20 mm (3/4") in size are at higher risk for becoming cancerous.
 * 4) Skin cancer is one of the potential dangers of ultraviolet germicidal irradiation.

Skin can be protected by avoiding sunlight entirely, or wearing protective clothing while outdoors. Skin cancer is usually caused by exposing skin to UV rays excessively.

Types
The most common types of skin cancer are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) which may be locally disfiguring but are unlikely to metastasize (spread to other parts of the body). The most dangerous type of skin cancer is malignant melanoma. This form of skin cancer is causing the major part of all skin cancer fatalities.

More rare types of skin cancer include:


 * Dermatofibrosarcoma protuberans
 * Merkel cell carcinoma
 * Kaposi's sarcoma

The BCC and the SCC often carry a UV-signature mutation indicating that these cancers are caused by UV-B radiation via the direct DNA damage. However the malignant melanoma is predominantly caused by UV-A radiation via the indirect DNA damage. The indirect DNA damage is caused by free radicals and reactive oxygen species. It has been shown, 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.

Skin cancer as a group
Many laymen and even professionals consider the basal cell carcinoma, the squamous cell carcinoma and the malignant melanoma as one group - namely skin cancer. This grouping is problematic for two reasons:


 * the mechanism that generates the first two forms is different from the mechanism that generates the melanoma. The direct DNA damage is responsible for BCC and SCC while the indirect DNA damage causes melanoma.
 * the mortality rate of BCC and SCC is around 0.3 causing 2000 deaths per year in the US. In comparison the mortality rate of melanoma is 15-20% and it causes 138000 deaths per year.

Even though it is rare, malignant melanoma is responsible for 75 % of all skin cancer related death cases.

While sunscreen has been shown to protect against BCC and SCC it may not protect against malignant melanoma. When sunscreen penetrates into the skin it generates reactive chemicals. It has been found that sunscreen use is correlated with malignant melanoma. However, it is not likely that sunscreen use causes melanoma.

Signs and symptoms
There are a variety of different skin cancer symptoms. These include crabs or changes in the skin that do not heal, ulcers in the skin, discoloration, and changes in existing moles.


 * Basal cell carcinoma usually looks like a raised, smooth, pearly bump on the sun-exposed skin of the head, neck or shoulders. Sometimes small blood vessels 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.


 * Squamous cell carcinoma is commonly a red, scaling, thickened patch on sun-exposed skin. Ulceration and bleeding may occur. When SCC is not treated, it may develop into a large mass.


 * Most melanomas are brown to black looking lesions. Signs that might indicate a malignant melanoma include change in size, shape, color or elevation of a mole. The appearance of a new mole during adulthood, or new pain, itching, ulceration or ble

Treatment
Most skin cancers can be treated by removal of the lesion, making sure that the edges (margins) are free of the tumor cells. These excisions provide the best cure for both early and high-risk disease.

For low-risk disease, radiation therapy and cryotherapy (freezing the cancer off) can provide adequate control of the disease; both, however, have lower overall cure rates than surgery.

Mohs' micrographic surgery is a technique used to remove the cancer with the least amount of surrounding tissue and the edges are checked immediately to see if tumor is found. This provides the opportunity to remove the least amount of tissue and provide the best cosmetically favorable results. This is especially important for areas where excess skin is limited, such as the face. Cure rates are equivalent to wide excision. Special training is required to perform this technique.

In the case of disease that has spread (metastasized) further surgical or chemotherapy may be required.

Scientists have recently been conducting experiments on what they have termed "immune- priming". This therapy is still in its infancy but has been shown to effectively attack foreign threats like viruses and also latch onto and attack skin cancers. More recently researchers have focused their efforts on strengthening the body's own naturally produced "helper T cells" that identify and lock onto cancer cells and help guide the killer cells to the cancer. Researchers infused patients with roughly 5 billion of the helper T cells without any harsh drugs or chemotherapy. This type of treatment if shown to be effective has no side effects and could change the way cancer patients are treated.

Reduction of risk
Although it is impossible to completely eliminate the possibility of skin cancer, the risk of developing such a cancer can be reduced significantly with the following steps:


 * reducing exposure to ultraviolet (UV) radiation, especially in early years
 * avoiding sunburns (Recent studies have shown that sunscreen does not protect from melanoma.)
 * avoiding sun exposure during the day (usually from 10 AM to 3 PM), when the sun is highest in the sky
 * wearing protective clothing (long sleeves and hats) when outdoors
 * using a broad-spectrum sunscreen that blocks both UVA and UVB radiation
 * use a sun block of about SPF 50
 * reapply sun block every 2 hours and after swimming

Although it is generally accepted that UV exposure is the greatest risk factor in melanoma development, some skeptics say that there is no proven data that links moderate sun exposure with the appearance of melanoma.

Pathology
Squamous cell carcinoma is a malignant epithelial tumor which originates in epidermis, squamous mucosa or areas of squamous metaplasia.

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.