Malignant Melanoma: Risk Factors, Incidence and Mortality - Essay Example

? Table of Contents Introduction 2 Malignant Melanoma: 2 Risk factors, incidence and mortality of Malignant Melanoma: 3 UV light exposure: 3 Mole: 3 Fair skin, freckling, and light hairs: 3 Family history of Melanoma: 4 Personal history: 4 Molecular changes in melanoma 6 Cancer biology in Malignant Melanoma 7 Diagnosis of Malignant Melanoma 8 Treatment 10 Conclusion 10 References 12 Introduction Skin is the largest organ of the body and it protects the body from many pathogens and injury and also acts as a thermo regulator as well as serving excretory functions. Malignant Melanoma: A malignant tumor is one of the solid tumors of the body that is dangerous that basal cell or squamous cell carcinoma. It is actually cancer of skin cells known as melanocytes that produces a pigment known as melanin. Melanin gives skin a characteristic color. Apart of skin, melanocytes are also present in the retina of the eye and bowel. Melanoma can originate in any part of the body containing melanocytes. It can be more dangerous than the remaining skin cancers as it metastasize to different body parts. Nowadays it can be treated surgically. Figure 1.1 shows the naked eye view of malignant melanoma. Cutaneous melanomas are divided as: 1- Superficial spreading melanoma 2- Nodular melanoma 3- Lentigomaligna melanoma 4- Acrllentigious melanoma 5- Miscellaneous types Risk factors, incidence and mortality of Malignant Melanoma: Following are the factors that may increase the risk of this disease: UV light exposure: The major risk factor for most of the melanomas is exposure to ultraviolet (UV) rays. The main source of UV rays is sunlight (Wang & Setlow, 2001). It has been observed that tanning lamps and beds are also a source of Ultraviolet rays. People who face a lot of UV exposure from all these sources are at greater risk for melanoma. UV rays targets the DNA of skin cells and damage it. Melanoma begins when this damage affects the growth controlling genes of DNA (Oliveria, 2006). Some factors may hinder or reduces the effect of UV rays on the skin. These include clothing, the time for exposure and the strength of the rays. More the time for exposure more will be the damage. Strength or intensity of the UV rays is directly proportional to the risk of melanoma. Mole: A mole (nevus) is a benign pigmented tumor that is not present on birth usually but appears in later life. It has been observed that people who have many moles are more likely to develop malignant melanomas. Chance of any single mole turning into a cancer is low as compared to anyone with many irregular moles. Persons suffering from giant congenital melanocytic nevi are at high risk of melanomas. Fair skin, freckling, and light hairs: Studies show that the risk of melanoma is 10 times higher in whites than for African Americans. Whites with red or blond hair who have blue or green eyes or fair skin that freckles or burns or numerous moles are at increased risk (Bliss & Ford, 1995). Family history of Melanoma: Melanomas will be greater if one or more first relatives like parent, brother, sister, or child has had melanoma once. Approximately, 10% of all the people with melanoma have a family history of the disease (Miller & Mihm, 2006). This increased risk is due to shared family lifestyle including frequent sun exposure or a family tendency of having fair skin, or may be a combination of factors. It may be genetic as 10% to 40% of families have this high rate of melanoma. Personal history: 5% of the people with primary melanoma developed secondary melanoma in their late age. Immunosuppression: Immuno-compromised patients are also at high risk. Gender: In USA, men are at higher risks of having melanomas than females in late age after 40s. Females of less than 40 years are at increased risk. As far as the mortality rates are concerned, depending upon the age and severity of condition, they are higher in older patients and compared to young once and in males as compared to females. Figure 1.2 shows the graphical representation of increasing the incidence of malignant carcinoma with age. It has been recently updated that Australia and New Zealand are the two countries with high rates of melanoma in the world. In every year, more than 10,000 people are diagnosed with melanoma in Australia. It is the fourth most common cancer in both men and women and accounts for 10% of all cancer diagnoses made. Before the age of 85, one in 19 Australians will be diagnosed with melanoma. Malignant melanoma the most common type of cancer in young Australians aged 15 to 44years. Molecular changes in melanoma The cell cycle is regulated by cyclins and cyclin dependant kinases CDKs. During cell cycle, interaction between cyclins and their respective cyclin dependant kinases results in phosphorylation of the target proteins. This phosphorylation results in cell cycle progression (Saelens X, 2004). When cell cycle inhibitors attack, they block the complex formation between the cyclins and cyclin dependant kinases. This causes inhibition of phosphorylation and ultimately the events occurring during the cell cycle. Impaired cell cycle and inhibition of cellular events leads to unchecked and uncontrolled cell proliferation with dangerous consequences. Such errors and mistakes cause oncogenesis in melanoma. A mutation in genetic locus of CDKN2A is the major and common aberration (Kamb & Gruis, 1994). As normally it controls the RB and p53 genes. RB is the governor gene of the cell and p53 is the guardian gene of the cell. Loss of control results in abnormal growth (Bullock & Fersht, 2001). Somatic mutations in proto-onco-genes BRAF or NRAS are also observed. Studies show that mutations in CDKN2A are due to silencing of this gene by methylation of the gene (Kumar et al, 2013). This causes cancer. Xeroderma pigmentosum is also a skin cancer condition in which the cell loses its ability to repair the damaged DNA or mutated DNA. Both the conditions have high penetrance. Morphologically, melanoma cells exhibit striking variations in pigmentation. Cells have higher chromatin to cytoplasm ratio (Harland, 2005). Enlarged nucleus is seen. Atypical mitosis and pleomorphism are other salient features of melanoma. Chromatin is clumped at the periphery of the nuclear membrane and prominent “cherry red” eosinophilic nucleoli are visible. Malignant cells grow as a poorly formed nest or as an individual at all levels of the dermis. Cancer biology in Malignant Melanoma Early stage of melanoma starts when the melanocytes begin to grow abnormally. Melanocytes are located between the epidermis (the outer layer of the skin) and the dermis (the next layer).This primary stage of the disease is called the radial growth phase of melanoma, and it grows horizontally within the epidermis (carcinoma in situ, it occurs when all the epidermal cells are converted to malignant cells). The size of tumor at this stage is less than 1 mm. Cancer cells at this stage lacks the capacity of metastasis and angiogenesis as the blood vessels are lower down in the skin. The melanoma detected at this stage is removed surgically. The MAPK (mitogen activated protein kinase) signal transduction pathway plays a key role in the proliferation of melanoma. It is due to the mutations in the genes controlling these signaling pathways leading to excessive, unchecked and abnormal cell growth of mutated cells. The intrinsic pathway of apoptosis of cells in the maintenance of tissue and cell growth is disturbed leading to increase in anti-apoptotic genes and inhibition or suppression of pro-apoptotic genes. This leads to survival of abnormal mutated cells. The extrinsic pathway of apoptosis may also play some role (Degterev, 2003). With time, the tumor cells start moving in a different direction. This stage of tumor growth is called as a vertical growth phase in which the tumor extends vertically up into the epidermis and down into the papillary dermis (Fulda, 2006). The invasive potential in the tumor evokes at this stage of oncogenesis. It grows into the surrounding tissue and spread to various parts of the body through the lymph or blood. Now the thickness of the tumor is usually more than 1 mm and involves the deeper parts of the skin. Meanwhile, all this activity leading to an immunological reaction against the tumor cells which can be estimated by the presence and activity of tumor infiltrating lymphocytes (TILs). On primary stage they completely destroy the tumor. This process is called as tumor regression. It is also the latest stage of the development of melanoma. Sometimes the primary tumor is destroyed completely but it leaves secondary metastatic tumors. Figure 1.3 shows the cell-cell adhesion and proliferation of the carcinoma by angiogenesis, cell-matrix interactions and intercellular communications (Veira & Kroemer, 1999). Diagnosis of Malignant Melanoma The most common method used by medicine and health professionals for the diagnosis of malignant melanomas is still visual or naked eye diagnosis. Moles or nevus that are uneven in color, shape or size are often treated as risk of melanoma. To differentiate between the primary small melanomas from benign tumors of the skin is a difficult task and it needs knowledge, understanding and capability, as the diagnosis is tough. A visit to a dermatologist once a year is necessary for the persons or families with a past history of melanoma or dysplastic nevus syndromes. Blood tests are not helpful for this kind of diagnosis. The general method for the detection melanomas (and to increase the survival rates), is to learn about their external appearance as in what and how they look like, be conscious of moles and its kinds and check for variations in color, shape, size, itching or any kind of bleeding and also show any doubtful moles to senior doctors. The most popular method for the diagnosis is ABCDE: Asymmetrical: Skin lesion of asymmetrical texture. Border: Irregular border of the lesion. Color: of melanomas is usually multiple. Diameter: Greater than 6mm size of a mole should be considered as a melanoma and should be treated immediately. Enlarging: Increasing or evolving character. Figure 1.3 shows the ABCDE rule of diagnosis. Top left shows asymmetrical texture, second left shows irregular border, last left show notched melanoma and on the top right, we can see the diameter changes and below is the change in color. Laboratory tests are further performed as: Skin biopsy as a confirmatory test. For the screening of metastases Lactate Dehydrogenase test is used. Chest X-ray and LDH are the most common tests for the patients with melanoma. CT, PET/CT or MRI scans are also recommended. Biopsies of sentinel lymph nodes are also performed for the assessment of secondary spread. S-100 is a marker for melanoma. Immunological reactions are also important. The level of antibody to the antigen is measured. Treatment It may involve the following steps: 1. Complete surgical removal of melanoma with adequate surgical margins. Assessment for the presence of any detectable metastatic disease. Follow up should be taken seriously. 2. High-dose interferon as an adjuvant treatment along with the surgical excision. 3. Sessions of chemotherapy before and after the removal of melanoma. 4. Immunotherapy, if required, should also be done. 5. Radiation therapy should be given to the patient after surgery locally as well as the prescribed parts by the surgeon. Conclusion As a conclusion, malignant melanoma is one of the solid tumors that is less common but much more deadly than any other skin carcinoma. Today, as a result of increased public awareness of the earliest signs of skin melanomas, most of the melanomas are cured by surgery at their early stages. Nonetheless, the incidence of these lesions has increased dramatically over past few decades due to environmental changes. 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