Skin cancer

Introduction and incidence

The skin is the largest organ in the human body, and malignant skin tumors are very common, and there are several types, depending on the cells from which they arise. Taken together, they account for more cases of cancer than all other types of cancer combined. So why is skin cancer less talked about than some other types of cancer? The answer lies in the fact that most skin tumors are simply treated locally (for example, with minor surgery) and a small proportion of patients die from them, so they are excluded from the data when presenting data on the most common types of cancer. Basal cell carcinoma is the most common type of skin cancer, with as many as 4.3 million new cases in the United States each year (Figure 1). It arises from the basal cells of the skin, round cells that are found in the lower part of the epidermis (the outer layer of the skin, Figure 2). The next most common is squamous cell carcinoma with just over 1 million cases per year in the United States, which arises from the thin, flat cells on the surface of the epidermis. Unlike these two types, which generally have a good prognosis (also called non-melanoma skin tumors), melanoma is a very aggressive malignant tumor, but fortunately it is much rarer. However, its incidence is constantly increasing. Melanoma arises from melanocytes, cells in the lower part of the epidermis that produce melanin, the pigment responsible for darkening the skin. There are other rarer types of skin cancer, such as Merkel cell carcinoma.

Risk factors

The main risk factor for the development of skin cancer is UV radiation, including natural (sun) and artificial (sunbeds). People with fair skin, light eyes, and red or blond hair are particularly sensitive to UV radiation. Everyone should avoid excessive sun exposure and sunburn. In rare cases, skin cancer can also be a consequence of genetics (for example, nevoid basal cell carcinoma syndrome). You can read more about risk factors for developing cancer in a separate article.

Figure 1. Basal cell carcinoma in the nasal area. Any skin change that does not go away should be reported to a doctor.

Signs and Symptoms

Non-melanoma skin cancer can present with a variety of skin changes, from sores that do not heal, areas that are raised, smooth and pearly, changes that bleed and peel... Any change that does not go away within a few weeks should definitely be shown to your dermatologist. Non-melanoma skin tumors most often occur in areas that are most exposed to the sun, such as the nose, ears, lower lip and upper arm. Melanoma, on the other hand, can be suspected in dark skin changes, especially if they are asymmetrical, have irregular edges, have several different color tones, are the size of a pencil eraser or larger, or grow over time - the so-called ABCDE rule (Figure 3). In addition to the skin, melanoma can also occur in the eye and mucous membranes (for example, the lining of the mouth), and in these cases it is particularly aggressive.

​Diagnosis

The basis is a detailed examination of the patient and taking a thorough medical history. As a rule, the first specialist to examine the patient is a dermatologist, while an oncologist is involved if skin cancer is confirmed. It should be noted that most skin changes are not skin cancer. The dermatologist will examine the patient's entire skin (not just the affected area), and suspicious changes can be additionally examined with a dermatoscope (with magnification). If any of the changes look suspicious, a biopsy will be performed, which is necessary to confirm the diagnosis, because the presence of skin cancer cannot be declared with 100% certainty based on appearance alone. After the diagnosis is made, other tests (such as CT) may be ordered if necessary based on the biopsy findings to assess the possible spread of the disease, especially in melanoma. In most cases, this will not be necessary for non-melanoma tumors, as they rarely metastasize. In melanomas suspected of possible spread to the lymph nodes, a sentinel lymph node biopsy is also performed, in which a radioactive substance and/or blue dye is injected into the area around the melanoma, which can identify the first lymph node in the path of lymph drainage from the tumor. If the node is affected, there is a significant possibility that other lymph nodes will also be affected. Tumor markers used in melanoma include S-100 (more in Interesting Facts at the bottom of the page) and lactate dehydrogenase (LDH). You can read more about cancer diagnostics in a separate article.

Figure 2. Display of skin strains. Malignant skin tumors usually arise in the epidermis. (source: National Cancer Institute)

Treatment

Patients with localized disease (isolated skin lesions) have several treatment options. Surgical treatment is the mainstay of treatment for most non-melanoma skin tumors, and by removing the lesion in this way, treatment is complete and most patients can be considered cured. There are several types of surgical treatment (simple excision, Mohs surgery, curettage and electrodesiccation, cryosurgery, laser surgery, dermabrasion), and the choice of method depends primarily on the size/advancedness of the skin lesion. In melanoma, after the initial surgical removal, if the diagnosis of melanoma is confirmed, a second extended surgery (wider margins of healthy tissue) will be necessary to reduce the risk of disease recurrence. Radiotherapy also plays an important role in the treatment of non-melanoma skin tumors. It can be used as an effective method instead of surgery, especially for lesions located in surgically technically demanding locations or when surgery would leave a significant cosmetic defect. It is sometimes used after surgery (also in melanoma) to reduce the risk of disease recurrence. Chemotherapy is used less frequently, and is mostly applied topically in the form of creams or lotions directly to the skin lesion. Photodynamic therapy uses a light-sensitive substance that is injected into the patient. The skin tumor is then illuminated with laser light, and the injected drug is activated and destroys the tumor tissue. Topical imiquimod (cream) is used for immunotherapy.

On the other hand, patients with locally advanced or metastatic disease have a significantly worse prognosis. Fortunately, such patients make up a smaller proportion. Targeted therapy is an option for treating patients with locally advanced and metastatic basal cell carcinoma (sonidegib and vismodegib are in use), while systemic chemotherapy (intravenous), interferon immunotherapy, and retinoids can be used for squamous cell carcinoma. Melanoma is primarily treated with targeted therapy (so-called BRAF and MEK inhibitors in patients with a BRAF gene mutation) and immunotherapy (pembrolizumab, nivolumab, a combination of nivolumab + ipilimumab...), while chemotherapy is used in patients whose disease has progressed on previous therapies. New forms of melanoma treatment have brought significant progress, and some of the patients treated with newer therapies can be cured even in the stage of metastatic disease.

Figure 3. Typical presentation of melanoma. The lesion is asymmetrical, has irregular edges, is multi-colored, and is large. (Source: Wikipedia)

Additional interesting facts

May is Skin Cancer, Brain Tumors, and Bladder Cancer Awareness Month.

The country with the highest rate of new cancer cases in the world according to recent data (2018) is, believe it or not, Australia, and this is true for both sexes. The age-standardized cancer rate in Australia is 468 per 100,000 people per year, and this is largely due to the large increase in skin cancer due to increased exposure to sunlight.

​The tumor marker S-100 is measured in the blood. The S-100 protein is actually not a single protein, but a family of low-molecular-weight proteins. So far, at least 21 different S-100 proteins are known, so they are called, for example, S-100A1, S-100A2, etc. It should be noted that S-100 is normally present in several types of cells, especially those that originate from the neural crest. In case of elevated values, S-100 may indicate the presence of malignant disease, especially melanoma and some rare tumors such as schwannoma, neurofibroma and histiocytoma. However, it should be remembered that S-100 values ​​can also be elevated in some inflammatory diseases.

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