Skin cancers encompass a range of malignancies that can affect individuals worldwide. Skin cancer incidence and mortality rates vary depending on several factors, including geographical location, sun exposure, skin type, and preventive measures. Skin cancers are among the most commonly diagnosed cancers globally. Non-melanoma skin cancers (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are more prevalent than melanoma ^[1][12]. On the other hand, melanoma, although less common than NMSC, is more aggressive and has a higher potential for metastasis. Over the past few decades, there has been a notable rise in the incidence of melanoma, particularly among fair-skinned populations with significant sun exposure ^[2][13]. However, studies indicate that there will be a projected decline in melanoma rates in the future ^[3][14].

Basal cell carcinoma (BCC) is derived from immature pluripotent cells of the lower layers of the epidermis. The etiology is multifactorial. Exposure to UV radiation is the most important cause, as BCC occurs predominantly in places exposed to the sun. Previous exposure to chemical carcinogens, ionizing radiation or phototherapy for skin diseases, chronic inflammatory changes, or trauma can also contribute to BCC. A higher incidence of BCC is observed in immunocompromised patients. Multipotent differentiation potential is reflected in great clinical diversity and morphology, including nodular—solid and cystic BCC, ulcerative, superficial, morphea-like sclerosing, keratotic, and pigment variant. The ulcerative BCC can lead to extremely extensive lesions. Metastases are extremely rare, and the morbidity associated with BCC is related to local tissue invasion and destruction ^[4][5][6][15,16,17].

Actinic keratosis (AK) is the proliferation of cytologically atypical keratinocytes. Nowadays AK is considered an early in situ squamous cell carcinoma. Age, the cumulative dose of UV radiation, outdoor activities, male gender, solar lentigines, and patient’s immunological condition are considered risk factors. Scaly or hyperkeratotic brown-red, brown-yellow macules, or papules with an erythematous base, usually less than 1 cm in diameter, in sun-exposed parts of the body. AKs can either rare spontaneously regress, they can remain stable without significant change, or progress to invasive squamous cell carcinoma ^[7][8][9][18,19,20].

Squamous cell carcinoma (SCC) represents the most aggressive type of non-melanoma skin cancer. Up to 60% of invasive SCCs arise from previous AK. Actinic keratosis, radiation (arsenic) keratosis, Bowen disease, Bowenoid papulosis, actinic cheilitis, and Queyrat erythroplasia are considered to be its in situ variants. The etiology is multifactorial and includes mainly chronic exposure to UV radiation, light phototype, long-term previous phototherapy for other dermatoses, professional exposure to X-ray radiation or radiation for internal malignancies, chemical carcinogens, chronic inflammatory skin changes, immunosuppression, and infection with HPV viruses. It grows de novo from a previous precancer. Initially, indurated, painless papules or macules of grayish, brownish-yellow, and reddish skin color may progress to nodular lesions with crusts and ulceration on the surface. The tumor grows quickly, disintegrates, and can outgrow soft tissues, cartilage, and bone. It can metastasize to regional lymph nodes, and later also to other organs. The prognosis depends on the location, size, and degree of tumor differentiation ^[9][10][11][20,21,22].

Early and correct diagnosis of NMSCs is a basic prerequisite for their successful treatment. The gold standard for the diagnosis of BCC, SCC, and AK is histopathological examination. The choice of individual therapeutic strategies depends on the anatomical location, the thickness of the tumor, the affected area of the skin surface, the histological type of the tumor, patient comorbidity, and the availability of the method. Surgical excision is still the predominant therapeutic strategy. Other treatment possibilities include curettage, electrodesiccation, cryotherapy, and radiotherapy. Only a few drugs meet the criteria for field treatment: 5% fluorouracil, 3% diclofenac in a gel with hyaluronic acid, photodynamic therapy, chemical peeling (destruction is achieved with 35% trichloroacetic acid, alpha-hydroxy acids, zinc chloride, and phenolic acid), retinoids (topical or systemic), and 5% imiquimod in cream ^{[9][10][11][12][13][14]}[20,21,22,23,24,25].

Melanoma is a malignant skin tumor that arises from the malignant transformation of melanocytes anywhere in the human body. It is mainly localized in the skin, but it also often appears in the eye or mucous membranes. It belongs to the most insidious tumors due to its ability to quickly form metastases. One-third of melanomas arise from various pigment nevi, and two-thirds of melanomas arise from so-called “de novo”—without a pre-existing pigmented lesion on clinically normal skin. Melanoma is considered to be the human tumor with the greatest immunogenic response. The incidence of melanoma is increasing more than the incidence of any other malignancy ^[15][16][26,27].

The causes of the malignant transformation of a melanocyte into a melanoma cell are still unclear. The genetic predisposition of an individual with a positive family history of melanoma in combination with the influences of the external environment plays an important role in the development of melanoma. UV radiation is one of the best-documented risk factors for the development of melanomas—whether from existing dysplastic nevi or arising de novo. Other risk factors include burning the skin at a young age, phototherapy, repeated use of tanning beds, immunosuppressive therapy, acquired and congenital disorders of the immune system, and oncological diseases treated with aggressive chemotherapy or immunotherapy ^[17][18][28,29].

Clinical diagnosis is also based on the ABCDEF criteria, which in many cases will help to diagnose developing melanoma. These criteria include asymmetry of the lesion, borders irregularity, color variety, diameter larger than 5 mm, and firm (nodular) or funny-looking lesion or ugly duckling sign (different from the others) ^[15][26]. Cutaneous melanoma occurs as an irregular oval or polycyclic lesion with a typical variety of colors (brown, gray, blue-black, whitish, pink). In the beginning, horizontal growth of the tumor prevails, the progression will show vertical growth and the formation of the nodular lesion, with a tendency to ulcerate and bleed after minimal trauma which signals the growth of the tumor in depth and thus a worse prognosis of the disease. A rare amelanotic or a hypomelanotic subtype of melanoma due to lack of pigmentation can mimic other benign and malignant conditions ^[19][20][30,31]. Melanoma can occur anywhere on the skin, on the mucous membranes, in the iris of the eye, in the soft coverings of the brain, in the heart, in the urogenital tract, and in the lymph node ^[17][28].

Early surgical extirpation of the primary tumor with a sufficient safety margin with the extirpation of the adjacent subcutaneous tissue is currently the only curative treatment for this cancer. After a precise histological examination, the TNM staging and the further course of treatment are determined. If a complete examination (using sonography, CT, or PET/CT) does not detect metastatic spread of the disease, patients remain in follow-up with their oncologist/oncodermatologist. In case of evidence of metastases, adequate surgical treatment, radiotherapy, chemotherapy, or biological treatment is chosen. For unresectable or distant metastatic disease, a combination therapy with nivolumab/ipilimumab has been a recommended option for first-line, second-, or subsequent-line systemic therapy. Patients diagnosed with melanoma should be regularly examined ^[21][22][23][32,33,34].