What causes skin cancer?

All forms of skin cancer have been associated with exposure to ultraviolet light as their principle causative factor. However, the details of each type of cancer’s association to the sun and their other possible causes differ amongst the different types.

The main cause of basal cell carcinoma is sun exposure. Besides causing direct cellular damage, ultraviolet light is responsible for a decreased immune surveillance in the skin. The immune system often picks out damaged cells and fixes them. Thus, ultraviolet light can be blamed for not only damaging the cells’ genetic material but impairing the body’s mechanism of fixing them as well. This explains why basal cell carcinoma is found to occur on sun-exposed areas in light-skinned people and there is a higher incidence of the tumors in people who inhabit sunny locations. The continuing depletion of ozone from the earth’s atmospheric layer is often cited as a causative factor in the rise in the incidence of skin cancer.

The cause of squamous cell carcinoma has been determined to be mainly due to prolonged repeated exposure to ultraviolet light as well. Other environmental exposures leading to SCC include hydrocarbons (pitch, coal tar, mineral oils), arsenic (sheep dip workers, Fowler’s solution, pesticides for vineyards and cigarette smoke), and ionizing radiation (over 1000 rems). SCCs are also increased in psoriasis patients treated with PUVA (psoralen plus UVA light) for long periods of time. Chronic injury to the skin, such as a burn scar, or a long-standing leg ulcer seem to predispose to the development of squamous cell carcinoma. Finally, immunosuppression is a well-recognized cause of SCC. This would consist mainly of the group of individuals who are on drugs that suppress the immune system, such as organ transplant or cancer treatment patients.

Malignant melanoma has multiple potential causes, the two most important of which are sun exposure and genetics. Melanoma clearly runs in families. There are some families who have 3 or more members with melanoma and are considered to be extremely high-risk “melanoma families.” The genetic basis for familial melanoma has been firmly established as a defect in a specific tumor suppressive gene. Others have more sporadic cases of melanoma which still raises the risk of having a melanoma in another family member about 4-fold. The relationship between melanoma and sun exposure is well established yet not totally understood. Melanoma is more common in light-skinned individuals with red hair and blue eyes as well as in areas of the world closer to the equator. Caucasians living in Australia, a country near the equator with a high degree of UV exposure, have the highest rate of skin cancer in the world. Still, the degree of increase incidence of melanoma in tropical latitudes is less than that with nonmelanoma skin cancer. Recent experiments with an animal model (the fish Xiphophorus) have revealed that melanoma is caused more by UVA (ultraviolet in the A wavelength range) and some visible rays than UVB (ultraviolet in the B wavelength range). The implications of this finding are phenomenal. The most important is that sunscreen needs to be able to block out all of the UVA rays in order to prevent melanoma, and perhaps even some visible rays. The sunscreen labeling in the United States, the SPF or Sun Protection Factor number only indicates the degree of effectiveness with respect to UVB radiation. There is much speculation that part of the increasing incidence of melanoma over the past 2 decades may be due to the fact that available sunscreens enable their users to stay out in the sun longer without sunburn, thus resulting in increased exposure to long wavelengths of UVA light. It also would mean that ozone depletion would have little effect on melanoma incidence since ozone does not absorb UVA. Another implication would be that exposure to tanning beds, promoted as “safe” by their users and owners due to their use of UVA and not UVB radiation, could result in a definite increased risk of melanoma. Finally, one must consider practicing sun avoidance at all times of the day and year, as UVA is not increased during the mid-day peak of sun exposure or mid-summer but tends to be even all day and all year round. Melanoma is more often associated with intermittent exposure to sun, such as vacations at the beach, and sunburns. It is believed this is due to the fact that the thicker and tanned epidermis present in someone with regular constant UV exposure does not allow the UVA to filter down to the melanocyte (pigment-producing cell) which is present at the base of the top layer of skin (epidermis). It is believed that it is damage to the melanocyte that leads to melanoma. The immune system is involved in the etiology of melanoma also. Even the number of nevi (moles) and dysplastic nevi (abnormal or precancerous moles) was increased in people on immunosuppressive drugs following their kidney transplant, indicating the importance of immune surveillance on the establishment of precursors to melanoma.

The prevention of skin cancer is based on sun protection, sun avoidance and regular evaluation by a physician, preferably a dermatologist. Studies have shown that dermatologists are more accurate in their ability to recognize skin cancer than primary care physicians are. It is recommended that a person of low risk (no personal or family history of skin cancer, normal number of moles) have a total body skin examination every three years. People with a history of skin cancer either personally or in their family should be seen at least once per year as well as perform a self-body examination once per month. A self-body examination consists of getting naked in front of a full-length mirror and methodically examining all surfaces of your body to the best of your ability to detect new growths or changes in color, shape or size in existing ones. Avoiding the sun at the peak hours of UVB intensity (10 AM – 2 PM) is a well-known and useful strategy to limit the harmful effects of the sun’s rays. Sun protective clothing is gaining favor. Tightly woven but breathable fabrics have been developed by reputable clothing companies and have been approved by the FDA as medical devices for the prevention of skin cancer. Light-weight and high quality, this is an effective way to protect oneself from the sun. (For more information on these or to purchase them go to www.sunprecautions.com). These have been shown to provide very effective sun protection. Limiting the number of hours of exposure is also useful. Hats are important, especially of the wide brimmed variety (although these will not protect your face adequately by themselves due to reflected ultraviolet light, so sunscreen should be applied as well). Sunscreen is an important part of every skin cancer prevention program. However, there are many reasons why sunscreens are less than perfect as sun protection. People don’t like to apply them – this is a major problem! In addition, people use less than that applied during tests to rate the sunscreens for SPF numbers. This results in only achieving one-third to half of the SPF number present on the front label of the sunscreen in real life conditions. Also, sunscreen needs to be applied 30 minutes prior to exposure for adequate absorption and reapplied frequently if there is a prolonged ultraviolet exposure. Finally, it is crucial to choose a sunscreen that can adequately protect you. Pick the highest SPF you can (preferably a 30 or above) and one which has complete UVA protection (contains zinc oxide).

What is skin cancer?

Skin cancer is a growing concern and widespread condition in the United States and elsewhere. In the US there are over 1 million people diagnosed with basal cell carcinoma and 50,000 people diagnosed with melanoma every year. With early detection and treatment the vast majority of skin cancers are curable with surgery alone. It is believed that practicing judicial sun avoidance and sun protection over one’s lifetime can prevent many skin cancers.

Are there different types of skin cancer?

Many types of skin cancer go through a precancerous stage prior to becoming full-blown cancer. Part of any early detection effort, therefore, is focused on eradicating these precursor lesions before they have a chance to undergo a malignant transformation. One common precancerous growth is called an actinic keratosis or solar keratosis (actinic, solar = referring to the sun, keratosis = scaly spot). These are usually small scaly patches which are sometimes pink or red but occasionally can be felt more easily than seen and occur commonly in sun exposed areas like the face, chest, and forearms. They can be quite numerous or occur singly. Actinic keratoses consist of superficial skin cells that are damaged and arranged in a disorderly fashion on a microscopic level. Actinic keratoses may degenerate into truly malignant cells called squamous cell carcinoma, either on their own or because of continued sun exposure. Some have argued that actinic keratoses are an early form of squamous cell carcinoma as opposed to being pre-malignant. Most dermatologists agree that the treatment of actinic keratoses is an important weapon in the prevention of squamous cell carcinoma.

Another type of growth with abnormal cells that is not frankly cancerous is called a dysplastic nevus. This is a mole in which the cells are dispersed irregularly in the skin and/or the cell shapes are not uniform. Not all dysplastic nevi progress to melanoma, but it does happen. Dysplastic nevi are also considered markers for high-risk individuals. This means that people with many dysplastic nevi have been identified as having an increased risk for developing melanoma and therefore need to be examined frequently for changes in their moles. It can be difficult to differentiate dysplastic nevus from melanoma by appearance alone since dysplastic nevi have many of the characteristics we attribute to melanoma. These include irregular shape, pigment or asymmetry; however, these changes often are not as severe as they are in melanoma. I always follow people with dysplastic nevi closely and remove moles that have changed or appear to be suspicious fairly aggressively. My rationale is one of attempting to remove active or threatening precursor lesions to take away their chance to turn into melanoma.

Basal cell carcinoma (BCC) is the most common type of skin cancer, as over 1 million people in the United States have one diagnosed each year. These usually present as a “pearly” appearing bump or a non-healing spot on a sun exposed area such as the face. They can occur on the nose, eyelids, cheeks, neck, scalp, back, chest, arms and legs. These common tumors are believed to be caused principally by the sun and are much more common in people with fair skin who burn easily. They also occur in people who have been exposed to radiation or who are on immunosuppressive drugs. Basal cell carcinoma rarely metastasize, thus are not usually life-threatening, although they can create a large degree of localized tissue destruction if not removed promptly when discovered.

The second most common tumor, squamous cell carcinoma (SCC), occurs on sun-exposed areas in individuals with a long history of prolonged exposure or an outdoor profession. It appears as a non-healing sore or a crusted bump or nodule on a sun-exposed area. It can also occur in an old scar or long-standing leg ulcer. More common in older individuals, SCC does have the potential to spread to other parts of the body. Some areas of higher risk for spread are the lips and the ears. This was the first type of cancer linked to an environmental cause, when Sir Percival Potts noted an increased incidence of scrotal SCC in chimney sweeps exposed regularly to tar.

Melanoma is the most feared of the skin cancers, as it can metastasize and be fatal. Its appears as an irregularly pigmented and shaped spot that is often flat but may be raised. It can arise in a pre-existing mole that undergoes changes or it can arise de novo (without a pre-existing mole). About 50,000 melanomas are diagnosed each year in the United States alone, 92,000 worldwide. 8000 people die of melanoma in the US each year, representing 4 out of 5 skin cancer deaths. There are four main types of melanoma: superficial spreading, nodular, lentigo maligna, and acral lentiginous melanoma. The most common type of melanoma is superficial spreading and comprises probably 80-85% of all melanomas. This type of melanoma starts in the surface layer of skin and grows towards the sides (lateral growth phase), hence the name superficial spreading. This takes place for a variable period of time, in some cases years, and corresponds to the time when the appearance of an existing mole may be undergoing a change. At some point the melanoma then enters a radial growth phase, that is, the tumor begins to invade the skin vertically. This is a critical point because it is at this time that the tumor has become more aggressive and can spread via the lymphatic and blood vessels in the skin. The most aggressive type of melanoma is the nodular variety, which comprises approximately 10% of melanomas. This usually does not arise in a preexisting mole but appears immediately as a rapidly growing bump or nodule (blue, black, purple or no pigment). These types of melanomas are more aggressive as they do not have the long horizontal growth phase of the superficial spreading type but are in the vertical invasive mode from the beginning. Lentigo maligna melanoma usually begins on a highly sun-exposed area, typically the face, as a flat freckle that becomes larger and develops irregular pigmentation. These are usually found in older individuals and have a horizontal growth phase prior to becoming invasive. Another type of melanoma is called acral-lentiginous type. This refers to the fact that the melanoma occurs on the hands or feet. Although relatively uncommon, this is the most common type of melanoma in people of color. The rarest types and the ones most difficult to diagnose are the amelanotic, subungual and mucosal melanomas. These may present as a growing flesh colored bump, a non-healing area under a nail or a sore or lump inside the mouth. Since these are rarely pigmented, they are often misdiagnosed in initial stages. Melanoma occurs more commonly on the trunk and ear in men and on the lower leg in women. There is also a 13-fold higher incidence in whites compared with blacks. This makes sense since blacks, with a higher pigment content in the skin, have a better inborn defense against sun damage.

How can I treat skin cancer?

The treatment of skin cancer is principally surgical. The vast majority of skin cancers are curable by surgery alone. The exception is when the skin cancer has already spread or metastasized.

The treatment of basal cell carcinoma or squamous cell carcinoma can be accomplished by excisional surgery or Mohs surgery. Excisional surgery means the tumor is removed with a scalpel and sutured closed. Usually a rim of normal tissue called a margin, is also removed, to ensure a low recurrence rate. The specimen is sent to a laboratory where the tissue is processed and a dermatopathologist (a pathologist specializing in dermatology or a dermatologist specializing in pathology) reviews the slides and establishes the diagnosis as well as determines whether the tumor was successfully and completely removed. Sometimes, there are special circumstances necessitating a slightly different form of surgery. Mohs surgery, named for its inventor, Dr. Frederick Mohs, is a microscopically-oriented section-controlled surgery. This means that the tumor is removed in stages and mapped. Each section or quadrant of tumor is then processed in a special way and the frozen sections are reviewed for the presence of tumor. The surgery then proceeds in the sections that have tumor remaining. This is the most precise way of removing non-melanoma skin cancer and boasts a 99% cure rate. (Traditional excision has a cure rate of approximately 95%). It is warranted when the skin cancer is larger than 2 centimeters in diameter, a particularly aggressive tumor type, a recurrent skin cancer, in a high-risk area or an area where it is difficult to take an adequate margin of tumor.

Another method of removal is by radiation therapy. This is helpful when the tumor is very large, has spread into the surrounding nerves or when there is some reason why it would be difficult for a person to undergo even a local surgery. However, in one study the long-term side effects were greater and the cosmetic results were not as good as with surgical removal.

A new technique in the treatment of skin cancer is called photodynamic therapy. This is a procedure where a photosensitizing chemical is either topically applied or injected and a specialized light or laser source is then used to expose the tumor. Some studies show a high response rate within 4-8 weeks with a good cosmetic outcome.

Finally, it is now possible to treat superficial basal cell carcinoma with a topical medication. Superficial basal cell carcinomas are very low grade tumors that only involve the top layer of skin (epidermis) and are not invasive. These tumors have been shown to succumb to the prescription cream imiquimod (Aldara), an agent which stimulates the local immune response in the skin. Studies have shown that use of this cream 3 times per week for 3-4 months have been able to completely eradicate these tumors.

The treatment of melanoma is also surgically based. The principal treatment is excision, the removal of the tumor and a margin of normal tissue surrounding the tumor. The excision margin is typically wider than that used for non-melanoma tumors and is also deeper. It is recommended that an excision for melanoma include the full thickness of fat, all the way down to the fascial layer (a membrane covering the muscle). The most important piece of information when choosing therapy for melanoma is the measured depth of the tumor. At the time of diagnosis, the dermatopathologist measures abnormal cells from the top of the skin to the base of the deepest part of skin involvement and this is called the Breslow depth. Although other factors come into play, this one number is the basis for determination of treatment as well as prognostic information. It is generally recommended at the current time that any tumor with a Breslow depth of less than 1.0cm is primarily excised with a 1 cm. margin. Anything greater than 1 cm warrants a 2.0 cm. margin. The recommended excision margins have changed over the years and also are different for different levels of melanoma. It used to be that there was a 5 centimeter margin recommended for the removal of all melanomas. This resulted in a defect that was at minimum 10 cm., or roughly 4.5 inches. Since these were rather deforming surgeries, many academic centers undertook studies and have shown convincingly that these wide margins are not necessary. Another important decision is whether or not to evaluate the lymph nodes. Melanoma usually spreads first to lymph nodes. In the past a procedure performed called “elective lymph node dissection” (ELND) was often performed. This consisted of removing most of the lymph nodes in the area expected to be associated with the tumor. This procedure generated much controversy as studies to determine whether it actually helped the person’ ultimate outcome were numerous and contradictory. This procedure resulted in many side effects such as lymphedema, an uncomfortable swelling in the associated part which is difficult to treat. More recently we have advanced to the sentinel lymph node procedure. This procedure involves injecting a dye or radioactive material into the area of the melanoma and then watching where the dye diffuses. The first lymph node the dye reaches is called the sentinel lymph node. Many studies have confirmed that this lymph node is highly predictive of the presence or absence of spread (metastases) to the tissues. Whether this node is positive or negative probably has the greatest single effect on the prognosis of an individual with melanoma. If this node is positive, it is likely the tumor has spread further, and often all the lymph nodes in the area are removed both for staging and for therapeutic reasons. If the lymph node is negative, there is reasonable certainty that the melanoma was removed before it had a chance to spread, making it likely that the surgery was curative. Sentinel lymph nodes are not usually performed on tumors that are less than 0.75mm in Breslow depth as they are rarely, if ever, positive. Exceptions to this rule would be if the tumor appears to be deeper in the skin than the Breslow depth would indicate (a Clarke level III or IV tumor- Clarke levels refer to what portion of the skin the tumor has penetrated to), or if the tumor is ulcerated (an open wound). However, in all other cases it makes sense, especially since this is a simple surgical procedure with few if any adverse effects. It is hoped that by identifying people with early spread of their melanoma we may be able to increase the cure rate and offer adjuvant therapy sooner in the course, when there is less tumor to overcome. Finally, melanoma that has spread or metastasized may be treated systemically, usually either by an immunologic stimulant or by a vaccine. The drug interferon is now approved by the FDA for the treatment of advanced melanoma. Although relatively toxic in the dosages required for this purpose, there is a small but substantial number of people who can increase their survival time and a small number who develop a durable complete remission. Another promising treatment is melanoma vaccines. These involve injecting treating melanoma cells in an attempt to get person’s own immune system to attack the tumor. Although there have been some promising results and this may be available soon, this treatment is still considered experimental and has not been approved yet by the FDA. One more potential new therapy for advanced melanoma is photodynamic therapy with a laser light which seems to be preferentially absorbed by melanoma tissue. Although apparently exciting results have been achieved in animals, studies in humans are pending. Researchers have recently found a gene they call RhoC which causes mildly malignant cells to become aggressive and invasive. This discovery could lead to more specific cancer treatments for melanoma.