Skin cancer

A basal cell carcinoma, one of the most common types of skin cancer.

Skin cancer is a malignant growth on the skin which can have many causes. The most common skin cancers are basal cell cancer, squamous cell cancer, and melanoma. 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. Melanoma is the least common skin cancer but it is potentially the most serious: there are over 8,000 new cases each year in the UK and 1,800 deaths. More people now die of Melanoma in the UK than in Australia. It is the second most common cancer in the young population (20 – 39 age group). It is estimated that approximately 85% of cases are caused by too much sun. Non-melanoma skin cancers are the commonest skin cancers. The majority of these are called Basal Cell Carcinomas. These are usually localised growths caused by excessive cumulative exposure to the sun and do not tend to spread.

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 & 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) & 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.
   1. UVA rays affect the skin at a deeper level than UVB rays, reaching through the epidermis and the dermis to the hypodermis where connective tissues and blood vessels are located. UVA activates the melanin of the epidermis causing changes in pigmentation as well as loss of elasticity of the skin, which contributes to premature wrinkling, sagging and aging of the skin.
   2. UVB rays primarily affect the epidermis causing sunburns, redness, and blistering of the skin. The melanin of the epidermis is activated with UVB just as with UVA; however, the effects are longer lasting with pigmentation continuing over 24 hours.
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. Human papilloma virus (HPV) is often associated with squamous cell carcinoma of the genital, anal, oral, pharynx, and fingers. It is believed that the HPV vaccine might help to prevent these cancers as well as cervical cancers.
5. Skin cancer is one of the potential dangers of ultraviolet germicidal irradiation.

Many believe that skin cancer can be prevented altogether by avoiding sunlight entirely, or wearing protective clothing while outdoors. However, studies show that Melanoma Skin Cancer is more common in those who work indoors. Skin Cancer is most common on areas of the body that are not normally exposed to the sun, and then exposing the skin to UV rays excessively.

Skin cancer generally has a 20- to 30-year latency period. The rates of skin cancer we are seeing today in older individuals mostly are a function of the ignorant misbehavior of the 1970s and early 1980s. Recall: Society used to view sunburns as an inconvenient right of spring, or as a “precursor” to developing a summer tan. Severe burns were commonplace. Today we know how reckless that approach was, and the incidence rates of skin cancer today in those over 50 years of age reflect that ignorance

Types

The most common types of skin cancers are:

• Basal Cell Carcinoma
• Squamous Cell Carcinoma
• Melanoma

Basal cell carcinomas (BCC) are the most common. They present on sun exposed areas of the skin, especially the face. They rarely metastasize, and rarely causes death. They are easily treated with surgery or radiation. Squamous cell carcinomas(SCC) are common, but much less common than basal cell cancers. They metastasize more frequently than BCC's. Even then, the metastasis rate is quite low, with the exception of SCC's of the lip, ear, and in immunosuppressed patients. Melanomas are the least frequent of the 3 common skin cancers. They frequently metastasize, and are deadly once spread.

Less common skin cancers include: Dermatofibrosarcoma protuberans,Merkel cell carcinoma,Kaposi's sarcoma, keratoacanthoma, spindle cell tumors, sebaceous carcinomas, microcystic adnexal carcinoma, merkel cell carcinoma, Pagets's disease of the breast, atypical fibroxanthoma, leimyosarcoma, and angiosarcoma

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. ^[1]

Skin cancer as a group

Many laymen and even professionals consider the basal cell carcinoma (BCC), the squamous cell carcinoma (SCC) 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 138001 deaths per year.^[2]

Even though it is rare, malignant melanoma is responsible for 75 % of all skin cancer related death cases^[3].

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^[1]. It has been found that sunscreen use is correlated with malignant melanoma. ^{[4][5][6][7][8][9]} The lab-experiments and the epidemiological studies suggests that sunscreen use correlates with melanoma incidence. The question that has to be asked is: "Are sunscreen users also the ones with the highest lifetime exposure to ultraviolet lights?" or are sun screens tumor promoters or carcinogens themselves. Logics might suggest that sunscreen users also are the ones most likely to be burned or have been burned by sun light. If it is true that some suncreen induces the formation of skin cancers, the physical sunscreen which are metallic in nature (zinc and titanium) are likely safer and likely to be inert. In the past, most sunscreens were chemical blockers (benzones, etc.).

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 bleeding.

Diagnosis

Diagnosis is only can be confirmed with a skin biopsy. Most skin biopsies are done under local anesthetic with an injection. A shave biopsy is good for diagnosing basal cell carcinoma, while not as well for squamous cell carcinoma. A punch biopsy is preferred for diagnosing squamous cell carcinoma and melanoma over the shave biopsy technique. Excisional biopsy (where the entire lesion is removed down to the deep dermis and subcutanous fat) is the method of choice for diagnosing melanomas. However, for cosmetic reason and practical reasons, a punch biopsy is often used to initially diagnose many large melanomas or melanomas of cosmetically important anatomic locations (nose, face, eyelids, nails, fingers and toes).

Treatment

Treatment is dependent on type of cancer, location of the cancer, age of the patient, and if the cancer is primary or recurrence. One should look at the specific type of skin cancer (basal cell carcinoma, squamous cell carcinoma, or melanoma) of concern in order to determine the correct treatment required. An example would be a small basal cell cancer on the cheek of a young man, where the treatment with the best cure rate (Mohs surgery) might be indicated. In the case of an elderly frail man with multiple complicating medical problems, a difficult to excise basal cell cancer of the nose might warrant radiation therapy (slightly lower cure rate) or no treatment at all. Topical chemotherapy might be indicated for large superficial basal cell carcinoma for good cosmetic outcome, whereas it might be inadequate for invasive nodular basal cell carcinoma or invasive squamous cell carcinoma.

For low-risk disease, radiation therapy, topical chemotherapy (imiquimod or 5-fluorouracil) and cryotherapy (freezing the cancer off) can provide adequate control of the disease; both, however, may have lower overall cure rates than certain type of surgery. Other modalities of treatment such as photodynamic therapy, topical chemotherapy, electrodessication and curettage can be found in the discussions of basal cell carcinoma and squamous cell carcinoma.

Mohs' micrographic surgery (mohs 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 procedures or chemotherapy may be required.^[10]

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. ^[11]

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.^[12])
• 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
• chemoprevention using topical imiquimod or 5-fluorouracil

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

Australian scientist Ian Frazer who developed a vaccine for cervical cancer, says that a vaccine effective in preventing for certain types of skin cancer has proven effective on animals and could be available within a decade. The vaccine would only be effective against Squamous Cell Carcinoma.^[13]

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.^[14]

See also

• Mohs surgery
• Sun protective clothing
• Sunscreen controversy

References