Epidemiological and clinical characteristics of malignant melanoma in Southeast Anatolia in Turkey

Introduction The present study aimed to establish the epidemiological and clinical characteristics of patients who were histopathologically diagnosed with malignant melanoma (MM). Methods The present study retrospectively analyzed the data of 78 patients who were histopathologically diagnosed with MM in Dicle University Medical Faculty, Dermatology and Medical Oncology departments between 2005 and 2014. Results The study included 78 patients in total with 44 (56.4%) male and 34 (43.6%) female. Median age of the patients was 62.50 years (range: 27 - 84 years). Of the patients, 78.2% (n = 61) had cutaneous melanoma, 8.9% had solid organ melanoma, and 2.5% had ocular and mucosal melanoma. The most common tumor localization among the patients was the lower extremities with 29.4% (n = 23). The most common histopathological type was nodular malignant melanoma with 35.8% (n = 28). Based on TNM, Clark and Breslow classifications, 26.9% (n = 21) of the patients were stage 4, 26.9% (n = 21) were Clark stage 4, and 37.1% (n = 29) were Breslow stage 4. Median overall survival in all patients was 14.9 months (95% CI 10.9 - 18.8 months). In the multivariate Cox analysis, only stage statistically significantly affecting survival [odds ratio (OR): 0.54; (95% CI 0.16-1.82, p = 0.02)]. Conclusion Malignant melanoma data are also important for the optimal utilization of effective methods and healthcare resources to prevent the disease. In order to minimize MM mortality and morbidity, not only the society but also physicians from primary and secondary care hospitals should become familiar with melanoma.


Introduction
Malignant melanoma (MM) is a malignant tumor resulting from melanocytes and nevus cells that are considered to be formed through melanocyte differentiation. MM is the fifth most common cancer in males and the sixth most common cancer in females accounts for 5% of all newly-diagnosed cancers [1]. The estimated lifetime risk for developing invasive melanoma is 1:1,500 in the US.
The incidence increases with age, particularly in males. In the US, the melanoma incidence under the age of 40 years is higher in females, whereas it is higher in males above the age of 40 years [1]. The melanoma incidence has shown a significant increase for the last few decades around the world. It exhibits significant differences in race and demographics, and it is one of the most common malignancies in Europe, North America, Australia, and New Zealand, especially in light-skinned individuals. It is more rarely seen in Africans, Latin Americans, Asians and dark-skinned individuals [2,3]. Australia Queensland is considered the place with the highest MM incidence (51/100,000) in the world. For melanoma incidence, the worldwide annual mean is 3-7% in Caucasians and one-or two-fold increase is estimated once in 10 to 20 years [4,5].
Seventy-five percent of deaths from skin cancers are due to melanoma. Due to the poor prognosis and fast course, it is also an important public health issue. Despite this, there are few studies demonstrating the epidemiology of cutaneous malignant melanoma in Turkey. A study that was conducted in 2006 in Turkey by collecting data from eight residential areas (Izmir, Eskisehir, Erzurum, Bursa, Edirne, Antalya, Trabzon, and Samsun), reported the melanoma incidence as 1.4/100,000. Based on the data from the Ministry of Health, melanoma incidence was 2.1/100,000 in males and 1.6/100,000 in females in 2009 in Turkey. Additionally, when 2009 data were compared to 2004 data (1.5/100,000 in males and 1.2/100,000 in females), it was seen that MM incidence has increased over the last six years [6,7]. The present study aimed to establish the epidemiological and clinical characteristics of patients who were histopathologically diagnosed with MM in the Dermatology and Medical Oncology departments of our university and to contribute to MM epidemiology through the data obtained.

Methods
The present study retrospectively analyzed the data of 78 patients who were histopathologically diagnosed with MM at Dicle University

Results
The study included 78 patients in total with 44 (56.4%) males and 34 (43.6%) females. The median age of the patients was 62.50 years (range: 27 -84 years). The male/female ratio was 1:1.29.
When patients were evaluated based on age groups, the most common age range was 61-70 years with 28.2%, as seen in Figure   1 19.4 months at stage 3 (95% CI 0.0 -42.5), and 9.3 months at stage 4 (95% CI 6.9 -11.7). As is seen, there was a significant reduction in survival time at stage 4 (p=0.012, Figure 3

Discussion
A malignant melanoma is a tumor with poor prognosis, which develops mostly from the skin, but also from other tissues containing melanocyte such as mucosa, eye, and meninges. The study by Chang et al. reported that 91.2% of the patients had skinbased melanoma, 5.3% had ocular melanoma, 1.3% had mucosal melanoma, and 2.2% had melanoma of unknown primary origin [8].
In the present study, the most common was cutaneous MM (78.2%). Most of MMs are seen in adults; however, there may be cases in children, especially developing from congenital nevi. Three hundred fifty-five melanoma patients are under the age of 45 years.
The mean age at diagnosis is 52 years. The female/male ratio is approximately 1:1 in USA and Australia [1,2,9]. Studies from Turkey reported the mean age to be 45-60 years. With a slightly higher male number in male/female ratio, Simsek et al. found a higher number of females in their study [10][11][12][13]. Studies from Italy, Holland, Spain, and Portugal reported that patients were mostly within the age range of 40-70 years and MM was more common in females [14][15][16][17]. In Asia, Chi et al. reported that 82.2% of 522 MM patients were aged 65 years and above [3]. Seventy-five percent of our patients were aged 50-80 years and the male/female ratio was In Australia, MM was reported mostly as the superficial type, located in the trunk in males and the lower extremities in females [4,5].
Studies from Europe (Italy, Holland, Spain, and Portugal) reported that the most common MM type was superficial with the most common tumor localization in the trunk and lower extremities [14][15][16][17]. Studies from Asia found acral lentiginous MM as the most common type and palmoplantar region as the most common localization [3]. The study by Moreno et al. from Brazil and studies from Argentina, Uruguay, and Chile found that the most common histological type was superficial MM and the most common localization was extremities and trunk in females and males [5,18].
Studies from Turkey reported nodular MM as the most common MM type, whereas Tas et al. reported superficial MM as the most common type [10]. The most common localizations were the lower extremities and the head-neck region [10][11][12][13]. The present study found nodular MM as the most common type, consistent with studies from Turkey but different from studies from Europe and the US. In terms of localization, the most common region was the lower extremities and the head-neck region, consistent with the results of all studies. Concerning the localisation of the tumour, it was observed to involve different regions of the gastrointestinal system (GIS) (i.e. stomach, rectum, liver and ileum) following the involvement of extremities, head & neck and truncal region.
Anorectal region is only the third to skin and eye as the most frequent locations of melanomas [19]. Primary malignant melanoma of the GIS is a rare occurrence. Lesions observed in the GIS usually represent the metastases of melanomas on the skin with no identifiable primary focus [20]. Melanoma of the stomach is one of the common types of melanomas that involve the GIS. The primary origin of a melanoma of the stomach is very unlikely and can be accepted only in the confirmed absence of any other primary lesions [21]. One of our patients had stomach involvement.
One of the histological characteristics of MM is Breslow thickness (invasion depth) and it is the strongest determinant for lifetime.
Additionally, multiple histological characteristics should be specified, including Clark´s level of invasion, ulceration, presence of tumorinfiltrating lymphocytes, mm2/mitoses, regression, vascular invasion, perineural invasion, and microscopic satellites. For staging, the TNM (tumor-lymph node-metastasis) staging system is used, which was established by the AJCC [22]. In studies from the US and Europe, MM is usually diagnosed in the early stage. A study from the US reported that 62.6% of the patients were diagnosed at TNM stage 0 and 1. In studies from Europe, the most common were Breslow 1, Clark IV, and TNM stage 1 [14][15][16][17]. In Africa, most of the MM cases were found at TNM stage 3 or higher [5]. In Brazil, Moreno et al. reported Breslow 1, Clark IV, and TNM stage 1 as the most common, whereas Clark 3-4 was the most common in Australia [18]. In studies from Asia, the most common were Breslow 1, Clark stage 3, and TNM stage 2 [3]. Studies from Turkey reported that most of the patients were at Breslow stage 3-5, Clark stage IV, and TNM stage 3-4 [10][11][12][13]. In the present study, the findings for Breslow 4, Clark IV, and TNM stage 4 were consistent with data reported from Turkey. These results suggest that MM is diagnosed late in Turkey compared to other countries and developed countries in particular. First metastasis in MM is frequently sentinel by lymphatic spread, i.e. to the first lymph node along the tumor´s lymphatic drainage. In the advanced stage of the disease, the skin, soft tissue, lung, liver, brain, bone, and bowel metastases are common sites through hematogenous spread. It rarely metastasizes to heart and breast [9,22]. As reported by Tas et al. lung metastasis was the most common site in our patients [10].

Conclusion
Malignant melanoma data are also important for the optimal utilization of effective methods and healthcare resources to prevent the disease. In order to minimize MM mortality and morbidity, not only society but also the physicians from primary and secondary care hospitals should become familiar with melanoma, awareness should be raised, and the importance of UV exposure should be expressed. In this respect, a significant role falls into dermatologists and dermatology society in particular. The primary preventive strategy should aim for sun protection and avoiding sunburns, especially in children and adolescents. Additionally, individuals who are light-skinned and in the at-risk group should be periodically checked, these data should be recorded, and the patients and their families should be warned in this regard.
What is known about this topic • The melanoma incidence has shown a significant increase for the last few decades around the world; • Seventy-five percent of deaths from skin cancers are due to melanoma. Due to the poor prognosis and fast course, it is also an important public health issue.
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What this study adds
• In order to minimize MM mortality and morbidity, not only the society but also physicians from primary and secondary care hospitals should become familiar with melanoma; • Individuals who are light-skinned and in the at-risk group should be periodically checked, these data should be recorded, and the patients and their families should be warned in this regard.

Competing interests
The authors declare no competing interest.  Table 1: Demographic and pathological characteristics of patients