Malignant melanoma is the deadliest type of skin cancer due to its ability to evade all treatment attempts. It accounts for 75% of mortalities associated with skin cancer though it only constitutes 4% of total dermatological cancer incidences (Davis et al. 1367). CDC research statistics show that melanoma’s annual incidences and mortality rates have considerably increased in the last few decades. As of 2019, in every 100,000 people in the US, 22.1 are diagnosed with malignant melanoma (Davis et al. 1367). This dramatic increase in incidences can be attributed to modern-culture behaviors of sun-seeking and the migration of fair-skinned populations to regions near the equator (Davis et al. 1366). Given the high prevalence and mortality rates of melanoma, information about the risk factors and effects of this neoplasm is valuable in improving understanding of the disease. This essay reviews the causes of melanoma, including the genetic aberrations involved, and discusses some of the effects of this cancer.
Melanoma arises from complex interactions between genetic and environmental factors. In the genetic aspect, the majority of the cases are due to inherited or acquired mutations in the MAP kinase pathway (Davis et al. 1368). MAPK contributes to carcinogenesis by disrupting the cell cycle and inhibiting apoptosis (Leonardi et al. 8). Epidemiological research implicates intense Ultraviolet radiation as the main cause of acquired mutations (Davis et al. 1368). This comes about due to intensive sun exposure and the acquisition of sunburns early in life (Liu and Sheikh 3). According to Davis et al., sunburns in childhood or early adolescence doubles the risk for melanoma in adult life (1367). Ultraviolet radiation increases the risk for skin cancers through DNA mutations, that is, by inducing the formation of pyrimidine dimers in DNA (Davis et al. 1367). Alternatively, UV rays facilitate tumorigenesis through the deamination of the cytosine base pair into thymidine. UV mutagenic effects are very potent to the point that the base pair alteration rate in malignant melanoma exceeds that of any other solid cancer.
Malignant melanoma can also occur due to hereditary or familial mutations. According to Davis et al., 8-12% of patients with melanoma have a family history of this neoplasm (1368). Patients in this category are highly sensitive to UV rays, which are present in childhood. Importantly, malignant melanomas emanate from moles, and individuals from families with a history of melanoma develop numerous moles. Genetic profiling also shows there are different mutations in hereditary melanoma compared to the non-hereditary type. Approximately 40 % of familial melanoma shows a somatic mutation in the CDKN2A gene (Davis et al. 1369). This genetic aberration causes defects in tumor suppressor protein (P53) that regulate the G1-S checkpoint, causing uncontrolled cell proliferation. Hereditary melanomas develop earlier (average age 65 years) and present as multiple cancer lesions.
Melanocytic nevi (benign lesions) predisposes patients to malignant melanoma. Nevi, colloquially known as birthmark or mole, are dark pigmentations on the skin composed of aggregates of melanocytes (Davis et al. 1370). When the quantity of nevi increases, more often than not, it signifies an increased predisposition to melanoma. Similarly, if a mole changes color, shape, or texture, it is pathognomonic for the onset of melanoma (Leonardi et al. 8). Epidemiological studies show that nearly 81% of patients with melanoma noticed nevi changes at the site of the malignant lesion (Davis et al., 1370). Moles prove valuable in the early diagnosis and prevention of skin cancer. However, not all changing nevi indicate (or progress to) melanoma.
The effects of melanoma are somewhat similar to those of other forms of cancer. For instance, melanoma patients present with cachexia and lymphadenitis (Davis et al. 1371). Cancer cachexia is more common in metastatic melanomas, and it impairs the patient’s work capacity. Lymphadenitis is commonly due to cancer dissemination to sentinel and distant lymph nodes and is an indicator of poor prognosis. Another effect of melanoma is increased susceptibility to other types of skin cancer. Research evidence reveals that poor management of melanoma increases the risk of another melanoma different from the first one (Davis et al. 1372). There is also a substantial risk of developing other malignancies such as salivary gland cancer and small intestine tumors. Organ failure is also a potential consequence of malignant melanoma. Neoplastic cells metastasize to distant organs like the liver, brain, heart, and spinal cord via the lymphatic and hematogenous routes, and by invading these organs, they disrupt their physiological functions (Davis et al. 1372). Metastasis in melanoma is very common and causes physiological derangements in other organs more often than not.
Dermatological disfigurement and scarring are potential consequences of malignant melanoma. Neoplastic growth may present as cutaneous lesions which damage skin appearance (Davis et al. 1374). Similarly, 64-71% of melanoma patients develop skin rashes or proliferative lesions following treatment (Davis et al. 1374). Other potential effects of melanoma include verrucous keratosis, photosensitivity, and hyperkeratosis, most of which are exacerbated by treatment. Malignant melanoma also increases the global burden of the disease since many resources are directed toward its treatment and management (Davis et al. 1376). Melanoma is aggressive cancer; therefore, more research on preventive and curative measures is needed to reduce its incidences.
Works Cited
Davis, Lauren, et al. “Current State of Melanoma Diagnosis and Treatment.” Cancer Biology & Therapy, 2019, Web.
Leonardi, Giulia, et al. “Cutaneous Melanoma: From Pathogenesis to Therapy (Review).” International Journal of Oncology, vol. 52, no. 4, 2018, Web.
Yuxin Liu and M Saeed Sheikh. “Melanoma: Molecular Pathogenesis and Therapeutic Management.” Molecular and cellular pharmacology vol. 6, no. 3 (2014): 228. Web.