**3. The possible signs and symptoms of melanoma**

of new specific treatment alternatives, which are targeted at specific receptors or the genes of tumor cells. In 2011, new molecules were discovered and designed on the basis of new knowledge in the molecular biology of melanoma. These new facts have resulted in the existence of two new approaches to therapy: immunotherapy and targeted therapy of melanoma.

Melanoma is derived from melanocytes—normal pigment cells of the skin. Most commonly, melanoma arises from epidermal skin melanocytes, but primary tumors can also be found lining the choroidal layer of the eye (uveal melanoma) or the mucosal surfaces of the respiratory, genitourinary, and gastrointestinal surfaces [5]. Melanoma is much less common than basal cell and squamous cell skin cancers, but it is far more dangerous. Like basal cell and squamous cell cancers, melanoma is almost always curable in its early stages. However, it is much more likely to spread to other parts of the body than basal or squamous cell cancer if not caught early. Melanocytes that produce melanin are usually uniformly localized at the interface of the dermis and epidermis of the skin. If the melanocytes are found in denser groups, they create different forms of birthmarks—nevus. Later, they may be the cause of developing

The term "dysplastic nevus" implies that this nevus exists as a distinct and defined entity of potential detriment to its host. Rosendahl et al. examine the current data, which suggest that this entity exists as histologically and possibly genetically different from common nevus, with some overlapping features. Studies show that a melanoma associated with a nevus is just as

Human nevi are benign tumors of melanocytes that are frequently associated with oncogenic mutations predominantly in BRAF V600E. However, nevi typically remain in a growth-arrested state for decades and only rarely progress into malignant melanoma. Very important features of nevus include oncogene-induced senescence [8] and oncogene-induced trans-lineage differen-

In recent years, researchers have learned a great deal about how certain changes in DNA can make normal cells become cancerous. Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes. Changes in several different genes are usually needed for a cell to become cancerous. Damage of DNA may be in the form of inherited genetic mutation, but in most cases it occurs gradually over the life due to the influence of

There are two melanin pigments synthesized in the melanocytes: eumelanin, a dark brown-black insoluble polymer, and pheomelanin, light red-yellow sulfur containing soluble polymer [13]. Pheomelanin has a weak shielding capacity against ultraviolet radiation compared to eumelanin, and has been shown to amplify ultraviolet-A-induced reactive oxygen species. Mitra et al. suggested that the pheomelanin pigment pathway produces ultraviolet-radiation independent carcinogenic contributions to melanomagenesis by a mechanism of oxidative damage [14].

**2. Genesis of melanoma**

110 Human Skin Cancers - Pathways, Mechanisms, Targets and Treatments

benign skin tumors—dysplastic nevus [6].

likely to arise in a common nevus as in dysplastic nevus [7].

tiation [9], which prevent benign nevi from malignant transformation.

environmental factors, such as UV rays from the sun [10–12].

The possible signs and symptoms of melanoma are new moles or spots on the surface of skin that are changing in size, shape and color. Another important sign is a spot that looks different from all of the other spots on skin. There are the **ABCDE** criteria for these signs, which guide to the usual signs of melanoma:

**A** – Asymmetry; one half of a nevi or birthmark does not match the other.

**B** – Border; the edges are irregular, jagged, or blurred.

**C** – Color; the color is not the same all over and may include shades of brown or black, or sometimes with patches of pink, red, white, or blue.

**D** – Diameter; the spot is larger than 6 mm across, although melanomas can sometimes be smaller than this.

**E** – Evolving; the nevi are changing in size, shape, or color.
