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Skin cancer is the most common type of cancer in the United States caused by abnormal stem cells that begin to grow out of control in the epidermis. There are three main types of skin cancer, Basal Cell Carcinoma (BCC), Squamous Cell Carcinoma (SCC), and melanoma. BCC and SCC are the most common forms of skin cancer and are highly treatable when caught early. Melanoma is less common but is considered more dangerous because it has a greater chance of metastasis or migrating to other parts of the body.
Skin cancer has two main causes, unprotected overexposure to the sun’s ultraviolet (UV) rays and artificial UV sources like tanning beds. The UV rays damage the DNA in the stem cells of the skin, making them susceptible to transformation into cancer. Skin cancer most commonly occurs in sun-exposed areas of the body, especially the head, neck, and arms.
According to the American Academy of Dermatology, 1 in 5 Americans will develop skin cancer in their lifetime and approximately 9,500 people in the U.S. are diagnosed with skin cancer every day. An estimated 3 million Americans are affected by BCC and SCC every year. Nonmelanoma skin cancer is more common among women than men, however, invasive melanoma is the fifth most common cancer for men (about 60,000 cases a year) and the sixth most common for women (about 40,000 cases a year). States like Colorado have mores cases of skin cancer due to the abundance of sun and high altitudes. Sun exposure is more intense and damaging at higher elevations.
When detected and treated early skin cancer is highly curable. For example, the estimated five-year survival rate for patients who get treatment for localized melanoma is 99%.
The skin is one of the largest organs of the body and the first line of protection against the outside world. The skin has many important functions including:
The skin is made up of two parts, an outer part called the epidermis, and an inner part called the dermis. The epidermis is made up of a single basal layer closest to the dermis and several layers of maturing suprabasal cells that become flat squamous cells. The epidermis is made up of several types of cells. They all have different functions, but keratinocytes are the most abundant and critical for skin barrier function. Melanocytes on the other hand are less abundant, but produce melanin, the brownish pigment that gives skin its color and allows the skin to tan. Other cell types include hair follicle, oil and sweat gland, sensory and immune cells. The Dermis contains a lot of connective tissue and blood vessels. It contains cells like fibroblasts, fat, nerve, and immune cells that provide the necessary nutrients and support for the epidermis to function properly.
One of the incredible facts about the skin is that the epidermis renews itself about every one and a half months. It is the job of professional stem cells in the basal layer of the skin to make more skins cells. They are immature cells that can either make more of themselves or change as they are needed into the mature squamous cells. Stem cells can also be found in the hair follicles. These stem cells help in fixing damaged skin during wounding. Once a basal stem cell decides to become a squamous cell through a process called differentiation, it will continue to move up the skin until it reaches the very top of the epidermis and dies. These dead cells are eventually lost. Exfoliation helps speed up dead skin cell removal. Unlike the transient nature of squamous cells, the stem cells live in the epidermis for many years. Because of this, stem cells live long enough to accumulate changes that make them susceptible to becoming cancer.
The CU Cancer Center is the only National Cancer Institute (NCI) Comprehensive Cancer Centers in Colorado. We have doctors who are providing top-notch, multidisciplinary, patient-centered care and treatment options not available at most other medical centers in the country.
The CU Cancer Center is one of 31 leading cancer centers part of the National Comprehensive Cancer Network (NCCN) advisory panel. NCCN cancer centers are dedicated to patient care, research and education. The advisory panel establishes treatment guidelines that doctors all across the United States use as a reference.
There are a number of skin cancer clinical trials and research studies currently being offered by CU Cancer Center members, giving patients many different treatment options.
Basal Cell Carcinoma is a type of skin cancer that can begin in stem cells of the basal layers and in hair follicle tissue. BCC occurs most often on sun-exposed areas of the skin like the face, head, and neck and usually appears as a raised, pearly white, skin-colored, or pink bump on the skin. BCC are the most common type of skin cancer with a diagnosis rate of about 8 out of 10 skin cancers. This type of skin cancer grow very slowly and rarely spread to other parts of the body but can be locally invasive and disfiguring if left untreated.
Squamous Cell Carcinoma is a type of skin cancer that can form in both the basal and maturing suprabasal layers. SCC most commonly occur on sun-exposed areas of the body like the head, neck, arms, and back of the hands. About 2 out of 10 skin cancers are squamous cell carcinomas. Immunocompromised individuals like organ transplant recipients are more likely to have an aggressive SCC than the general population. SCC are not usually life-threatening, but account for most of the death associated with Non-melanoma skin cancers. Thus, they can be very aggressive and if left untreated can grow large and spread to other parts of the body. SCC can be found in many places on the body and can appear as a rough, scaly patch or a firm red nodule. Pre-cancerous and other skin conditions related to SCC include:
Actinic keratosis (solar keratosis), a pre-cancerous skin condition resulting from overexposure to the sun. These pre-cancerous rough and scaly patches can range in color from brown to pink and usually start on the face, ears, backs of the hands, and arms. These patches grow slowly and do not usually cause symptoms. Actinic keratoses are considered precursors to SCC and are often treated, although their risk for conversion is low.
Squamous cell carcinoma in situ (Bowen disease), the earliest form of squamous cell skin cancer, meaning the cancer cells are only in the epidermis and have not yet invaded to deeper layers. This skin condition appears as reddish, scaly patches and doesn’t usually cause symptoms. Bowen disease is often treated because it can progress to SCC.
Keratoacanthoma, dome-shaped tumors found on sun-exposed skin, grow quickly and can be hard to differentiate from SCC. Doctors take a cautious approach to treating keratoacanthoma in the case the tumors turn out to be SCC.
Melanoma is the most serious type of skin cancer that develops in the melanocytes that produce melanin, the pigment that gives the skin color. Melanoma can be found anywhere on the body. In recent years, the risk of melanoma has been increasing in people under 40, especially women. Melanomas can develop anywhere on the body and most often appear as an existing mole that has changed or a new pigmented, unusual-looking growth.
Other less common types of skin cancer include:
Kaposi sarcoma, a skin cancer that develops in the skin’s blood vessels and causes purple or red patches on the skin.
Merkel cell carcinoma, causes shiny, firm nodules that occur on or just beneath the skin and around hair follicles. They arise from touch sensing cells in the skin.
Sebaceous gland carcinoma, this aggressive form of skin cancer originates in the oil glands of the skin associated with hair follicles and appears as hard, painless nodules. Most commonly found on the eyelid.
Skin cancer is mainly caused by the accumulation of mutations in the DNA of skin stem cells and changes in the micro-environment of the skin that promote the growth of abnormal cells. DNA contains genes that tell healthy cells what to do. Some of these genes act as tumor suppressors to block abnormal cell growth. Other genes (oncogenes) when mutated or changed promote the abnormal cell growth. Skin cancers typically inactivate tumor suppressor genes and activate oncogenes. While the accumulation of mutations is an important step in the transformation of skin cells, mutated skin cells also need a further push to become cancer. For example, excessive skin inflammation can promote the growth of abnormal skin cells. So, it may take years for abnormal skin cells to become a full-blown cancer. For these reasons, skin cancer generally is more prevalent in older individuals, although rates in younger people have been increasing in recent years.
Most commonly, damage to DNA is caused by overexposure to ultraviolet (UV) rays from the sun or the lights used in tanning beds. Tanning is actually a response to DNA damage of epidermal cells. UV damaged cells tell melanocyte to produce and secrete melanin, making skin darker. If the damage to the skin is too great, then burning and pealing can happen. This also activates skin inflammation. On top of this, UVA rays can damage the dermis. This can induce changes in the micro-environment of the skin that can promote the growth of abnormal skin cells.
Unfortunately, UV radiation is not the only culprit for the formation of skin cancer. Toxic chemicals in our environment can also contribute to skin cancer and tumors can develop on skin not ordinarily exposed to sunlight.
There are several factors that might increase the chance of developing liver cancer. These risk factors include:
Ultraviolet light exposure: Exposure to UVA and UVB rays is thought to be the most significant risk for developing most skin cancer types. Though UV rays make up only a small portion of the sun’s rays, they are the main cause of damage that occurs to DNA of cells and skin tissues.
Fair skin: People with lighter skin have a much higher risk of developing skin cancer than people with naturally darker skin. Melanin has a protective effect in people with darker skin. Fair-skinned people with blue or green eyes and naturally red or blonde hair are at especially high risk of developing skin cancer.
Age: The risk of developing non-melanoma skin cancers increases in the older population because of the buildup of sun exposure over time. These cancers, however, are becoming more common in younger people due to increased sun exposure. Excessive exposure at a young age can also increase the risk of getting skin cancer later in life.
Gender: Men are more likely than women to get basal and squamous cell cancers.
Moles: People with many moles are at an increased risk of developing skin cancer. Larger, irregular-looking moles are more likely than others to become cancerous.
Exposure to chemicals: Exposure to large amounts of arsenic increases the risk of getting skin cancer. Arsenic is naturally found in well water and is used in some pesticides.
Exposure to radiation: People who have received radiation treatment have a higher risk of developing skin cancer in the area they received the treatment.
Sunny or high-altitude climates: People who live in high-altitude, sunny climates, like Colorado, are exposed to stronger UV sunlight than people at lower elevations. The exposure to UV is greater at higher elevations.
Weakened immune system: The immune system helps fight off cancer cells. People with weakened immune systems, either from certain diseases like HIV/AIDS or from medical treatments like immunosuppressants, are more likely to develop skin cancer.
Pre-cancerous skin lesions: Skin lesions like actinic keratoses can increase the risk of developing skin cancer.
A personal or family history of skin cancer: Those who have previously developed skin cancer or have parents or siblings with skin cancer, are at greater risk of reoccurrence.
The most important way to reduce the risk of developing skin cancer is to limit exposure to Ultraviolet (UV) rays.
Avoid tanning beds: Tanning beds and sun lamps give off UV rays, similar to the sun, causing long-term skin damage that can contribute to skin cancer.
Avoid mid-day sun exposure: For most of the Continental United States, including Colorado, the sun’s rays are strongest between about 10 a.m. and 4 p.m. Avoiding the sun at its strongest will help prevent sunburns that cause skin damage that increases the risk of developing skin cancer.
Wear sunscreen year-round: Consistently using a broad-spectrum sunscreen with SPF of at least 30, even on cloudy days, can help reduce skin damage. The best sunscreens block or absorb UVA and UVB radiation, but don’t completely filter out the UV light. They do help with overall sun protection.
Protective clothing: To help avoid harmful UV exposure, cover your skin with dark, tightly woven or UV resistant clothing that covers exposed areas. Wide-brimmed hats can also provide more protection to the face, ears, and neck. Sunglasses help protect the eyes from both UVA and UVB rays.
Sun-sensitizing medications: Some prescription and over-the-counter drugs can make skin more sensitive to sunlight. Take extra precautions or stay out of the sun when taking prescriptions that increase sensitivity to sunlight.
Check your skin regularly: Examine the skin often for new growths, abnormal areas, changes in existing moles, freckles, bumps, and birthmarks. If you have previously had skin cancer or have a family history of skin cancer talk to your doctor about yearly exams with your dermatologist.
Skin cancer primarily develops on sun-exposed areas including, the scalp, face, lips, ears, chest, shoulders, arms, and hands. In some cases, skin cancer can develop in places that rarely see sunlight, like the palms, between the toes, fingernails, and toenails. Skin cancer can also develop at burns, wounds, or areas of inflamed skin. People of all skin tones can develop skin cancer, but people with fair skin are most susceptible. Skin cancers don’t often cause symptoms until they’ve grown large. Some skin cancers may itch, hurt, or bleed. They are typically discovered long before reaching this point.
Basal cell carcinoma can appear as:
Basal cell carcinomas are commonly discovered because they are fragile and might bleed after shaving or a minor injury and the sore or cut won’t heal.
Basal cell and squamous cell carcinomas are commonly found early when they are easier to treat. According to the American Cancer Society, it is recommended to self-check the skin once a month in a well-lit room in front of a full-length mirror. All areas of the skin should be checked, including the palms and soles, scalp, ears, nails, and back. Areas of the skin that are new or changing in size, shape, or color should be shown to a primary care physician or dermatologist.
Physical exam: Having regular skin exams performed by a health care professional is especially important for people who are at high risk of skin cancer. During a skin exam, the doctor will note the size, shape, color, and texture of the areas of concern. The rest of the body will be checked for moles and other spots that also could be related to skin cancer. Dermatologists use a technique called dermoscopy to see areas of the skin closer. During this procedure, a dermatologist will use a dermascope, a special magnifying lens, to more clearly see the skin.
Skin biopsy: For any suspicious-looking skin, a doctor may remove a skin sample for lab testing and examination by a dermatopathologist. A biopsy will help determine if the abnormal skin is cancer. There are several types of biopsies that can be performed based on the suspected type of skin cancer, where the cancer is located on the body, and its size. Skin biopsies are performed using a local anesthetic injected into the area with a small needle.
After skin cancer has been diagnosed, doctors will try to determine if the cancer has spread, and if so, how far. Doctors use a variety of methods to classify a patient’s tumor. This includes histological grade and staging. A cancer’s stage describes the size of the tumor and where in the body the cancer is located or spread to. The stage is based on the results of a physical exam, skin biopsy, and imaging tests, if they are done.
Basal cell carcinomas are almost always cured before they spread to other body parts, rarely needing to be staged. Squamous cell carcinomas are more likely to spread.
The most commonly used staging system for skin cancer is the American Joint Committee on Cancer. The TNM system assesses the size and extent of the tumor (T-tumor), if the tumor has grown deeper into nearby structures or tissues; whether the cancer has spread to nearby lymph nodes (N-node); and the presence of metastasis (M-metastasis) to distant parts of the body.
Once the T, N, and M categories have been determined, the information is combined in a process called stage grouping to assign the overall stage. Roman numerals I through IV are used to indicate the cancer’s stage. Stage I cancers are small and limited to the area where they started. Stage IV indicates the cancer is in an advanced stage and has spread to other parts of the body.
Treatment options for skin cancer and precancerous skin lesions vary, depending on the size, type, depth, and location of the growths. Some small skin cancers limited to the surface of the skin may only require an initial skin biopsy to remove the entire
Cryotherapy is most often used for low-risk pre-cancerous lesions like actinic keratosis, small basal, and squamous cell carcinomas. During this treatment liquid nitrogen is applied to the tumor to freeze and kill the cancer cells. After the frozen, dead skin thaws, the area will swell, blister, and crust over. The treatment will most likely leave a scar and have less pigment after treatment.
Photodynamic therapy (PDT) is a treatment for basal and squamous cell carcinomas that uses a drug applied to the skin in the form of a gel or liquid. The drug collects in the tumor cells over several hours or days and then becomes
very sensitive to certain types of light. This special light source is then focused on the affected areas, which kills the cancer cells. PDT can cause redness and swelling in the areas where it was used and can make the skin extra sensitive to sunlight.
Topical chemotherapy uses drugs put directly on the skin to kill cancer cells.
5-fluorouracil (5-FU) is the drug most commonly used in topical chemotherapy for basal and squamous cell carcinomas. 5-FU is used directly on the skin to kill tumor cells on or near the skin’s surface. Because topical
chemotherapy cannot penetrate deeper into the skin, it is generally used for pre-cancerous conditions. The treatment can leave the skin red and sensitive for several weeks.
Diclofenac (Solaraze) is a gel sometimes used to treat pre-cancerous conditions. This drug is applied twice daily for two to three months and can take longer to work than 5-FU.
Immune response modifiers are drugs that boost the body’s response to fight and help shrink cancer cells.
Imiquimod (Zyclara) is a topical cream that can be used to treat early basal cell carcinomas. The drug causes the immune system to react to the lesion and kill it. This treatment is applied a few times a week over several weeks and can cause skin redness and sensitivity.
Interferon is an immune system protein injected into the tumor. This treatment is an option when surgery isn’t possible but may not be as effective as other treatments.
Laser surgery uses a laser light to destroy cancer cells. This treatment can only be used for squamous cell carcinoma in situ and surface-level basal cell carcinomas.
Chemical peeling is a technique where a chemical like trichloroacetic acid is applied to the skin cancer, killing the tumor cells over the course of serval days.
Surgery is a common and effective treatment option for basal cell and squamous cell carcinomas. There are several surgical techniques that can be deployed, but the options depend on the type of skin cancer, how large it is, and where it’s located.
In most cases, the procedures can be performed in a hospital clinic using local anesthetic.
Excision is a procedure to remove basal and squamous cell carcinomas after the cancer stage has been determined. During this procedure, the skin is numbed with a local anesthetic and the tumor is cut out along with some surrounding
Curettage and electrodesiccation are treatments where the cancer cells are removed by scraping the cancer off with a long, thin instrument with a sharp looped edge on one end. Once the cancer cells have been removed the area is treated with an electric needle to destroy any remaining cancer cells.
Mohs surgery is sometimes used when there is a high risk of cancer reoccurrence, when the extent of the cancer is unknown, or in order to save as much healthy tissue as possible. This procedure is done by removing a thin layer of
skin with the tumor and then checking the sample under a microscope for cancer cells. This procedure is repeated until the skin samples are free of cancer cells. This is a very slow procedure, however, it helps save more normal skin near the tumor.
This procedure also results in better outcomes than other treatments.
Lymph node surgery is conducted when lymph nodes near a basal or squamous cell carcinoma are enlarged. Many lymph nodes may be removed at once during a procedure called lymph node dissection. This type of operation is usually more
extensive and done under general anesthesia.
Radiation therapy is a treatment for basal and squamous cell skin cancers that uses high-energy rays like x-rays to destroy cancer cells. Radiation is commonly used for very large tumors or in areas where the cancer may be more difficult to remove with surgery. Radiation can be a useful treatment for patients who cannot have surgery. Radiation may sometimes be used after surgery as an adjuvant treatment to kill any remaining cancer cells in the area.
These drugs target the specific molecular changes in skin cancer cells and are selective for each type of cancer. Typically, targeted therapies are used to treat more advanced or aggressive tumors where first-line treatments are not effective or recommended.
Hedgehog pathway inhibitors
Vismodegib (Erivedge) and sonidegib (Odomzo) are targeted drugs that treat advanced BCC. BCCs are characterized by mutations or changes in the genes the regulate the hedgehog cell signaling pathway. This pathway
helps to regulate how skin cells grow. Visodegib and Sonidegib help to block the overactivation of the hedgehog pathway, helping to shrink tumor mass.
SCC have overactivation of certain growth pathways governed by the protein called EGFR. Drugs like cetuximab (Erbitux) bind and inactivate the EGFR protein to block the overactivation of the pathway, helping to shrink the tumor.
Immunotherapy uses drugs to stimulate the immune system to enhance the body’s ability to fight cancer cells. Immunotherapy has been successfully used to treat Melanoma and may be useful in treating advanced BCC and SCC.
Immune checkpoint inhibitors help restore the body’s immune response to cancer cells by targeting checkpoint proteins and helping the immune system recognize and attack cancer cells.
Cemiplimab (Libtayo) and pembrolizumab (Keytruda) are drugs that target PD-1, a checkpoint protein on T cells that keeps these cells from attacking cancer cells. PD-1 function like a lock. Cancer cells express
a protein (the key) that interacts with PD-1 to prevent T cells from attacking the cancers cells. The checkpoint inhibitors help to disrupt this “lock and key” interaction to unmask cancer cells to the immune system.
Chemotherapy uses anti-cancer drugs injected into a vein or taken by mouth to attack cancer cells that have spread to lymph nodes and other organs. For cancers on the top layer of the skin, lotions or creams that contain anti-cancer agents may
be applied directly to the skin.
The University of Colorado (CU) Cancer Center partners with UCHealth, Children’s Hospital Colorado, and Rocky Mountain Regional VA to provide clinical care. Please make an appointment with one of our clinical partners to be seen by a CU Cancer Center doctor.