The skin is the largest organ of the body and consists of three main layers:

• Epidermis: It is a very thin outer layer of the skin that acts as a barrier to environmental infections and controls the amount of water that evaporates from the body.
• Dermis: The middle and thicker layer of the skin that contains hair follicles as well as nerves and a large number of blood and lymph vessels embedded in a framework of collagen.
• Hypodermis: the deepest layer of the skin, which is rich in fat and collagen and has many blood and lymphatic vessels.

Most skin cancers appear from the cells in the epidermis layer. Keratinocytes are the main cells in this layer of the skin. Deep in the epidermis and near the dermis layer, these cells grow and actively produce new skin cells. This layer is the basal cell layer. Over time, these cells migrate to the surface of the skin and become squamous cells. Among the basal cells, there are brown pigments called melanin that make up the melanocyte cells. These are located close to other cells that remove foreign substances such as bacteria or cancer cells from the skin and deliver them to the lymph nodes through the lymphatic vessels (ie Langerhans cells of the skin).

The lymphatic vessels of the skin reach the lymph nodes of the groin, armpit, and neck. These vessels carry lymph fluid and are one of the fluid circulation systems in the body. This system is considered part of the body’s immune system, but at the same time, it is a pathway that skin cancer cells can use to spread throughout the body. Lymph nodes act as a filter and trap these cells. The proliferation of these cells in the lymph nodes causes the lymph nodes to enlarge.

There are two types of skin cancer based on the type of cells involved:

This type of skin cancer includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). These are the most common forms of skin cancer. These are more likely to develop in areas of the body that are exposed to sunlight more, i.e. the head and neck. In this form of skin cancer, the probability of the spread of cancer cells and the death of the patient is less than in other types, but if it is not treated, it may grow and spread to other parts of the body.

Squamous cell cancer: This type of cancer occurs in the outer layer of the skin and is usually more aggressive than basal cell cancer. This disease may appear as red and scaly lesions on the skin.

Squamous cell skin cancer

Basal cell cancer: The most common form of skin cancer is basal cell cancer, which accounts for 90% of all skin cancer cases. These are slow-growing lumps that often appear in the head and neck area.

Basal cell skin cancer

The second type of skin cancer is melanoma. This type of cancer is related to melanocytes. Benign moles created by melanocytes can become cancerous. These moles can form anywhere on the body, but they are more likely to develop on the chest and back. In women, the possibility of forming these moles on the legs is more. Most melanomas are curable if diagnosed and treated promptly. If left untreated, they can spread to other areas of the body and become more difficult to treat. This type of skin cancer is more likely to spread than basal cell cancer and squamous cell cancer. This type of skin cancer is less common, but it is considered the most dangerous type of skin cancer. In fact, melanoma only accounts for one percent of skin cancers, but the majority of skin cancer-related deaths each year are related to this disease.

Melanoma cancer

There are types of skin lesions that are a subset of skin cancer. All of these are not skin cancers, but they can become cancerous. One of these cases is actinic keratosis: these red or pink lesions on the skin are not cancerous but are considered a precancerous condition. If left untreated, it can turn into squamous cell carcinoma.

Actinic keratosis is a precancerous condition that can develop into squamous cell carcinoma if left untreated.

All skin cancers are not the same and may cause different symptoms. However, abnormal changes in the skin can be a warning sign for different types of skin cancer. Awareness of the condition of the skin can help diagnose the disease faster.

• Skin lesions: A new mole, abnormal growth, bump, sore, skin patch, or dark spot that appears and does not go away.
• Asymmetry: both sides of skin lesions or moles are not the same.
• Edges: The edges of the skin lesions are jagged and the edges are not equal.
• Color: The stain has an unusual color such as white, black, blue or red.
• Diameter: The thickness of the stain is more than half a centimeter.
• Change: A visible change in the size, color, or shape of a mole.

Moles and skin lesions that can be related to skin cancer often look like moles and skin spots that are not cancerous at all, so you must see a doctor for diagnosis.

The cause of melanoma is not clear. Most moles don’t turn into melanoma, and researchers aren’t sure why in some cases they do become cancerous. Like basal cell cancer and squamous cell cancer, melanoma may be caused by UV radiation. However, melanoma can also develop in parts of the body that are not normally exposed to sunlight.

Moles are usually harmless and rarely turn into skin cancer. If a mole becomes cancerous, it becomes melanoma. There is a precancerous stage called a dysplastic mole where the mole is no longer normal. An early sign of melanoma is a change in a mole: asymmetry, abnormal edges, changes in color, increased diameter, or other changes in condition can indicate that the mole has turned into melanoma. Moles never develop into basal cell carcinoma or squamous cell carcinoma. In the figure below, a normal mole (top row) is compared to a cancerous mole (bottom row).

If a person notices suspicious spots and lumps on their skin or if they notice a change in spots that were already there, they should see a doctor. The specialist doctor examines the shape, size, color, and texture of the suspicious area on the skin, and if he suspects that the area is cancerous, he may perform a biopsy (tissue sampling). During this simple and safe procedure, a sample of suspicious tissue is isolated and examined. With this examination, it is determined whether a person has skin cancer or not. If a person is diagnosed with skin cancer, other tests may be needed to determine how far the disease has progressed. The patient’s treatment plan depends on the type, stage of the disease, and other factors.

Screening for skin cancer by a dermatologist is quick and easy. The patient is asked to remove his clothes and the doctor looks all over his skin for unusual spots and moles. Early detection is the best way to ensure successful skin cancer treatment. Unlike other organs, the skin is always visible so that anyone can notice unusual changes or changes in the condition of their skin.

To determine the stage or severity of skin cancer, the doctor pays attention to the size of the tumor, and its status in terms of spreading to the lymph nodes and other parts of the body. Skin cancers are divided into two main groups in terms of stage of development: non-melanoma skin cancer and melanoma skin cancer.

Non-melanoma skin cancers include basal and squamous cell cancers, which have the following stages:

• Stage zero: Abnormal cells have not spread beyond the outer layer of the skin, the epidermis.
• Stage one: The cancer may have reached the next layer of the skin, the dermis, but its thickness is not more than two centimeters.
• Stage two: In this stage, the tumor has a size of more than two centimeters, but it has not yet reached the surrounding areas or lymph nodes.
• Stage three: The cancer has spread from the primary site to the adjacent tissue or bone and its size is more than three centimeters.
• Stage four: The cancer has spread to more distant areas than the primary tumor and has entered the lymph nodes, bone, and tissue. The size of the tumor is more than three centimeters.

Melanoma includes the following stages:

• Stage zero: This non-invasive type of skin cancer has not yet penetrated the lower part of the epidermis.
• Stage one: The cancer may have penetrated the second layer of the skin, the dermis, but its size is small.
• Stage two: The cancer has not spread beyond the primary tumor, but it is larger and thicker, and other signs and symptoms such as bleeding or scaling may also be seen.
• Stage three: The cancer has spread and entered the lymph nodes or adjacent tissue and skin.
• Stage four: It is the most advanced form of melanoma. In stage four, the cancer has spread beyond the primary tumor and is seen in lymph nodes, organs, or tissues far from the original cancer site.

If the cancer comes back after treatment, it is called recurrent skin cancer. There is a possibility of cancer returning in any person whose skin cancer has been diagnosed and treated, so it is necessary to conduct investigations in this field on these patients.

The treatment method for this disease depends on various factors such as the size, location, type, and stage of the disease. After considering these factors, the medical team may recommend one or more of the following treatments:

Micrographic Maze surgery: the desired area is locally numbed and the surgeon removes the tumor along with a small amount of surrounding healthy tissue. The tissue is quickly examined under a microscope and areas that still contain microscopic remnants of the tumor are removed and reexamined until no trace of tumor-related cells is seen (figure below). This complex and expensive treatment option is the treatment of choice in cases where it is critical to preserve the healthy tissues around the tumor, as well as in the cases where the borders of the tumor are not well defined, as well as in the cases of tumors that have been treated before but have recurred.

Tumor destruction by curettage and electrocautery (EDC): The tumor area is numbed using a local anesthetic and scraped repeatedly using a sharp blade, and then the edges of the wound are cauterized using an electric needle (electrode). The advantage of this method is that it is fast, easy, and relatively cheap. The problem with this method is that the scar is usually unpleasant and the probability of recurrence is 15%.

In the EDC method, first, the infected area is repeatedly scraped using a sharp blade to remove abnormal tissues.

The edges of the wound are cauterized with an electric needle to remove the remnants of cancer cells.

Surgical tumor removal: First, the tumor area is numbed using a local anesthetic. A ball-like section of skin, which includes the tumor, is removed from the skin, and then the edges of the wound are sutured. In the case of large tumors, a skin graft may be needed to close the wound. The advantage of this method of treatment is that its success rate is more than 90% and the surgeon can simultaneously check whether the entire tumor has been removed or not. The wound created in this way is better than the wound produced by the EDC method, but it has more complexity and cost.

Drug therapy: In the case of superficial basal cell cancer, some creams, gels, and solutions such as Imiquimod (Aldara) can be used. The way these drugs work is to stimulate the patient’s immune system to produce interferon. Interferons are proteins that attack cancer cells. Another effective drug in this field is fluorouracil (5-FU), which is a chemotherapy drug. Some patients do not experience any side effects from these topical treatments, but some may experience redness, inflammation, and skin irritation. One of the disadvantages of topical drugs is that because no tissue is available for examination, it is not possible to determine whether the tumor has been completely removed or not.

Cryotherapy: In this method, the tissue is frozen and destroyed using liquid nitrogen. The doctor sprays liquid nitrogen on the infected area and some of the surrounding areas. This causes a burning or stinging sensation in the person, which disappears within a few minutes. Liquid nitrogen freezes and kills the abnormal cells, creating a sore that will be red for several days and may blister and ooze. The area may be swollen for a few days, and in some cases this may need to be repeated. A crust will form over the wound and the dead tissue will fall off within one to four weeks, depending on the size of the treated area. After that, healthy skin cells grow and a scar may remain. Healing may take several weeks, and the healed skin will likely be paler than the surrounding area.

In the cryotherapy method, liquid nitrogen is used to freeze and destroy tissue

Photodynamic therapy (PDT): In this method of treatment, a drug and a special type of light are used. The drug is a chemical that sensitizes the skin to light. This drug is called a photosensitizing agent. The light can be a laser or another type of light. The drug can be used as a cream on the skin or injected into the bloodstream. By absorbing the drug, the cells become sensitive to light. Then the doctor shines light on the desired area and destroys the cancer cells.

To reduce the risk of skin cancer, long-term exposure to sunlight and other sources of ultraviolet radiation should be avoided. for example:

It is also important to check your skin regularly to see if there are any lesions on the skin or if the previous spots and moles have changed.

Certain factors increase the risk of skin cancer. For example, a person is more likely to develop skin cancer if:

• Have a family history of skin cancer.
• exposed to certain substances such as arsenic compounds, radium, bitumen, and creosote.
• exposed to radiation, for example, during special treatments for acne and eczema.
• exposed to excessive sunlight, tanning lamps, and other similar factors.
• Live in sunny, hot climates or high altitudes.
• Be constantly engaged in outdoor work.
• Have a history of severe burns.
• They have many large and abnormal moles.
• The skin is pale and has freckles.
• Have skin that gets sunburned easily.
• Have natural blonde or red hair.
• Have blue or green eyes.
• Have precancerous skin lesions.
• Have a weak immune system, for example, have HIV infection.
• Have a history of organ transplantation and taking immunosuppressive drugs.

The use of sunglasses with 100% UVB and UVA protection is recommended to prevent skin cancer.

If a person is diagnosed with skin cancer, a group of doctors may help the patient with different aspects of the condition. for example:

• A dermatologist who treats skin diseases.
• A cancer surgeon who treats cancer through surgery.
• A radiation therapy specialist who treats cancer using radiation therapy.
• A cancer drug treatment specialist who treats cancer using targeted drug therapies, immunotherapy, chemotherapy, or other drugs.

Side effects of skin cancer include the following:

• Disease recurrence means the return of cancer after treatment
• Local recurrence means the spread of cancer to nearby tissues
• Cancer progression in which cancer cells spread to the muscles, nerves, or other organs of the body.

If a person has skin cancer, there is a high risk that the disease will reappear in another part of his body.

Since most types of skin cancer are caused by exposure to ultraviolet light, they are generally not considered hereditary skin cancers. But the fact that skin cancer is more common among people with less skin pigmentation, and skin color trait is an inherited trait, so it can be said that the role of genetics is important. There are several rare genetic syndromes that lead to an increased frequency of skin cancer cases among those with these syndromes. There is a type of hereditary melanoma called FAM-M syndrome, which is caused by a mutation in the CDKN2A gene located on chromosome 9. This mutation is also called the p16 mutation.

In general, the prognosis for non-melanoma skin cancer is excellent. Both basal cell carcinoma and squamous cell carcinoma are highly treatable. Almost no death occurs from basal cell cancer, and rarely, death can occur from squamous cell cancer, which is mainly in people who are immunosuppressed. Depending on the treatment method and the location and type of skin cancer, the probability of recurrence of a skin cancer treated in the maze surgery method is 1-2% and in the electric burning and curettage method it is about 10-15%. Early detection of skin cancers can lead to better treatment outcomes.

Statistics show strong evidence that drinking water contaminated with arsenic compounds increases the risk of skin cancer. Arsenic contamination is common in underground water and arsenic contamination of drinking water is significant in some areas. At least 140 million people in 50 countries of the world are consuming drinking water whose concentration of arsenic compounds exceeds the set limit (10 micrograms per liter). Arsenic is one of the natural compounds of the earth’s crust and is widely present in the air, water, and soil. This substance is very toxic in its inorganic form. People are exposed to high levels of inorganic arsenic through drinking contaminated water, using contaminated water to prepare food and irrigate agricultural crops, industrial activities, eating contaminated food, and using tobacco. Long-term exposure to inorganic arsenic, mainly through consumption of contaminated food and water, can lead to chronic arsenic poisoning. Skin lesions and skin cancer are some of the undesirable effects of this substance. In Iran, few researches have been conducted in the field of arsenic contamination of drinking water in different regions. In a study conducted in Ardabil City in 2017, it was found that the concentration of arsenic in the drinking water of this region is higher than the standard (with an average of 15 micrograms per liter). In a similar study in Kashmir city, the presence of high concentrations of arsenic compounds in drinking water was confirmed.

Skin lesions and skin cancer are the main characteristics of arsenic pollution

Being taller at puberty also increases the risk of developing malignant melanoma. Beta-carotene supplementation has no significant effect on increasing the risk of non-melanoma skin cancer. Drinking coffee may reduce the risk of malignant melanoma in women and may reduce the risk of basal cell carcinoma in men and women. There is also evidence that drinking alcoholic beverages may increase the risk of malignant melanoma and basal cell carcinoma.

In general, melanoma skin cancer is the 15th most common cancer among men and women. The prevalence of both melanoma and non-melanoma skin cancer has increased in recent decades. Currently, about 2 to 3 million cases of non-melanoma skin cancer and 132,000 cases of melanoma skin cancer occur worldwide every year. One out of every three cancers diagnosed is skin cancer, and one in five Americans will develop skin cancer in their lifetime. In 2018, 300,000 new cases of this cancer have been diagnosed. Australia, New Zealand, Norway, Denmark, and the Netherlands are among the countries in the world with the highest prevalence of this disease.

With the process of destroying the ozone layer, the atmosphere loses its protective layer and more ultraviolet rays reach the earth’s surface. It is estimated that a ten percent decrease in the ozone layer will lead to the occurrence of 300,000 cases of non-melanoma skin cancer and 4,500 cases of melanoma skin cancer. The global prevalence of melanoma is increasing, although the main predisposing factors for the development of melanoma appear to be related to recreational exposure to sunlight and having a history of sunburn. The responsibility for these factors lies with the people themselves.