|Year : 2014 | Volume
| Issue : 1 | Page : 38-42
A single institution retrospective analysis of malignant melanoma
Department of Radiation Oncology, Oncology Hospital of Ankara, Mehmet Akif Ersoy Street, Yenimahalle, 06105, Ankara, Turkey
|Date of Web Publication||23-Apr-2014|
Department of Radiation Oncology, Oncology Hospital of Ankara, Mehmet Akif Ersoy Street, Yenimahalle, 06105, Ankara
Source of Support: None, Conflict of Interest: None
Background: The incidence of melanoma is rising at a rate greater than any other malignancy, although much of this increase is due to the more frequent diagnosis of patients with the earlier stages of melanoma.
Objective: In this study, patient and tumor-related characteristics and their effects on survival were evaluated.
Materials and Methods: The data was drawn from the patients' records with histologically proven primary cutaneous melanomas treated at the Ankara Oncology Hospital between January 2003 and December 2010. Sixty-nine patients (48 men and 21 women) were included in this study. 17 of the patients had already distant metastases at the time of diagnosis. While 45 of all patients had undergone surgery alone, 17 had received only palliative radiotherapy, and 7 had received primary radiotherapy. Survival curves were determined from the time of diagnosis.
Results: A total of 69 cutaneous melanoma cases were evaluated. While there was a predominance of males in all body sites, especially in the head and neck regions, the number of male patients was 5 times higher than females. Diseases located on the head tended to present a significantly higher rate in older patients (P = 0.009). Overall survival rates for 1 and 3 years were 79% and 44%, respectively. Distant metastatic melanoma was significantly related with poor prognosis (P < 0.001). Anatomic location showed a borderline significancy as a prognostic factor for overall survival (P = 0.053).
Conclusion: Cutaneous melanomas developing at different body sites are associated with distinct patterns of survival outcomes. In this retrospective analysis, melanomas of the head and neck and limb, which are regional melanoma, appear to have better survival outcomes.
Keywords: Age, gender, malignant melanoma, survival
|How to cite this article:|
Ozgen A. A single institution retrospective analysis of malignant melanoma. J Can Res Ther 2014;10:38-42
| > Introduction|| |
In Europe, the incidence of melanoma has been increasing steadily since the 1950s with a great geographical disparity. 
Melanoma is a malignant tumor that originates from melanocytic cells and primarily affects the skin. The most essential exogenous etiological factor is exposure to ultraviolet radiation although the relationship between risk and exposure is complex.  Different studies have shown that the pattern of exposure has changed in recent decades from effectively occupational to effectively recreational sun exposure, thus influencing the incidence of melanoma in developed countries.  Besides, the decreased rates of incidence in young adults with melanoma in northern European countries and increased mortality rates in patients with melanoma in eastern and southern parts of Europe were described in 2003. 
Diagnosis of melanoma is established by its clinical features, and the A-B-C-D rule is helpful in identifying suspicious pigmented lesions for melanoma (Asymmetry, Border irregularity, Color inhomogeneous, and Diameter more than 5 mm). Almost 90% of melanomas are diagnosed as primary tumors without any evidence of metastasis. The tumor-specific 10-year survival rate for such cases is between 75%-85%. The most crucial prognostic factors for primary melanoma without metastases are vertical tumor thickness (Breslow depth) as measured on the histological specimen; existence of histopathologically recognised ulceration; primary tumor mitotic rate and identification of micro metastases in the regional lymph nodes via sentinel lymph node biopsy. Melanomas can metastasize either via the lymphatic or hematogenous routes. Almost two-thirds of metastases are originally bound to the drainage area of regional lymph nodes.
Although very few developments have been recorded in the treatment of melanoma, survival rates have improved significantly in developed countries.  It is thought that this improvement was due to increased public awareness of the effects of excessive sun exposure, as well as earlier detection of melanoma, thus diagnosing thinner tumors.
The aim of this study is to evaluate the incidence and survival of patients diagnosed with melanoma from 2003 to 2010 in our center.
| > Materials and Methods|| |
The data was drawn from patients' records with histologically proven primary cutaneous melanomas treated at the Ankara Oncology Hospital from January 2003 to December 2010. Both the patients' folders and our electronic database system were used for data collection. A total of sixty-nine patients with cutaneous melanoma have been treated between these dates and all of them had follow-up data.
Clinical details including location, histopathological features and tumor thickness were assessed by histopathological examinations. Primary tumor location was exhibited with the use of ICD-10 (International Classification of Disease, 10 th revision) and cases were categorized according to the site of the tumor in the head and neck, trunk, extremities and overlapping (WHO)  Melanoma subtype was determined according to Clark with the categories a) superficial spreading melanoma (SSM), b) nodular melanoma (NM), c) lentigo maligna melanoma (LMM) and d) acral lentiginous melanoma (ALM). Tumor thickness was measured in millimeters as reported by Breslow.
Patient and tumor-related characteristics (age, gender, primary anatomic site) and their relation to each other were examined. The influence of age was analyzed by categorizing the cohort into two age groups: ≤50 years, and >50 years. The American Joint Committee on Cancer (AJCC) staging system (7 th edition) was applied for either clinical or pathological staging.  For externally referred patients without pathological evaluation of the Breslow thickness, clinical stages were defined based on the available T-category, regional lymph node involvement, as well as status of distant metastasis. Stage was grouped into two categories; (1) regional melanoma: stage I, stage II, regional metastatic melanoma (stage III) defined as any stage without distant metastatic disease and (2) distant metastatic melanoma (stage IV) as any stage with distant metastases.
While twenty-four patients were treated with radiotherapy; forty-five patients were treated with only surgery. Of the 24 patients who received radiotherapy, 7 had received primary radiotherapy and 17 had received radiotherapy with palliative intent. [Table 1] lists patient and treatment characteristics. Seven patients received radiotherapy with 6-12 MV megavoltage linear accelerator, and seventeen patients received radiotherapy with 60Co photon beam. Primary tumor and, if present, lymph node metastases were involved in the treatment field. Median radiotherapy dose for patients treated with primary radiotherapy was 46 Gy and for palliative radiotherapy was 30 Gy.
Survival curves were determined from the time of diagnosis of primary melanoma, and deemed censored for patients alive at last follow-up or deceased without evidence of melanoma. Univariate analyses of end points for survival were achieved by using the Kaplan-Meier method and the log-rank test. SPSS 13 was used for statistical analysis. For the survival analyses, the following variables were included: Sex (male, female), age (≤50, >50 years), location of the melanoma (extremities, trunk, head and neck), clinically identified regional lymph node metastases (+,-), clinically identified distant metastases (+,-), and distant metastases (brain, lung, bone, and multiple). The Pearson Chi-squared test was performed to investigate associations between the different patient and tumor characteristics. A value of P < 0.05 was considered significant. In addition, comparison of patient characteristics in two different age categories were analyzed using T test for means and Pearson Chi-squared test for categorical variables.
| > Results|| |
Between January 2003 and December 2010, a total of 69 consecutive and non-selected cases of malignant melanoma with pathologic confirmation were established and reviewed.
Of the 51 patients for whose tumors' Breslow thickness was measured, the mean and median Breslow thicknesses were 3.5 mm and 2.5 mm, respectively; whereas in 18 patients, Breslow thickness was not specified in the pathological reports.
Since Breslow thickness was available in 51 of the 69 patients, clinical staging was based on the available knowledge of T-category, regional nodal status, and distant metastasis. Fifty-two patients presented with primary disease based on pathology study but no evidence of regional or distant metastasis were staged as stage I, II disease. A total of 17 patients with regional lymph adenopathy without distant metastasis, and 17 patients with distant metastasis were staged as stage III and stage IV diseases, respectively, according to the AJCC clinical classification for melanoma.
A total of 69 patients (48 males and 21 females) with cutaneous melanoma were evaluated. For all cases, a higher rate of the females were in the age group > 50 compared to the males, but significant differences weren›t observed [Figure 1] (P = 0.98). The results were as follows: Rate of females: ≤50 = 42.9%, >50 = 57.1%. Rate of males: ≤50 = 44.2%, >50 = 55.8%. A higher rate of the males were in the age group > 50 compared to the age group of ≤ 50. In this study population, in all disease sites, there was a male predominancy. Between female patients the disease presented on the overlapping areas (43%) was more than other locations (limbs 24%, H + N 19%) [Figure 2]. At the time of diagnosis females were more likely to have distant metastatic melanoma than males (33% of females vs. 21% of males), but did not differ significantly [Figure 3] (P = 0.27). Also, the diseases located on the head and neck areas tended to present significantly in older patients (P = 0.009) [Figure 4].
|Figure 2: Gender variations in the anatomic area of disease. (H + N: head and neck, nos/overlapping: not otherwise specified (nos) or overlapping areas)|
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|Figure 4: Correlation between anatomical area and age of patients. (H + N: head and neck, nos/overlapping: not otherwise specified (nos) or overlapping areas)|
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After treatment, regional lymph node metastases outside the treatment field and distant metastases developed in 9 patients (13%) and 33 patients (48%), respectively. [Figure 5] shows overall survival of all patients. Most of the regional lymph node metastases and distant metastases developed within 2 years after the initial treatment. Overall survival rates for 1-year and 3-years were 79% and 44%, respectively. Overall survival rates for 1-year and 3-years of treatment with surgery alone were 88% and 74%, respectively.
The results of univariate analysis for overall survival are shown in [Table 2]. Distant metastatic melanoma was significantly related to worse prognosis (P < 0.001) [Figure 6]. Anatomic location showed borderline significance as a prognostic factor for overall survival (P = 0.053) [Figure 7]. The disease located on the trunk tended to relate worse prognosis. None of the other factors were found to be effective on overall survival.
|Figure 7: The effect of anatomical area on survival. (H + N: head and neck, nos/overlapping: not otherwise specified (nos) or overlapping areas)|
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| > Discussion|| |
Using data from southern European countries,  a rising trend in melanoma mortality has been reported. We constructed a retrospective study for the risk of melanoma incorporating traditional epidemiologic risk factors. We want to highlight a significant increase in both incidence and mortality in our country for greater awareness of the impact of early diagnosis of melanoma on the quality of life. Referral rates in our country vary according to geography and gender. Fewer referrals were observed in areas where there is less access to a major cancer center. Fewer referrals were also observed for females.
SEER data between 1999 and 2001 demonstrated an increased incidence of melanoma by age.  The data also showed the same incidence of melanoma for women and men up to 49 years of age, and a higher incidence of melanoma for men than women at ages older than 50 years. We found a similar incidence of melanoma for women and men for all ages.
As noted in other studies, the anatomic incidence of melanoma varies between the two genders. Presentation differs between the genders, with men more likely to present with melanomas on the trunk, whereas women tend to have a disease on the lower limbs. , In our study, diseases located on the head and neck tended to present in males (83%), and diseases located on the trunk and limbs also tended to present in males (67% and 69%, respectively). The referral rates for each gender were different, with 70% of males and 30% of females referred to the hospital. This may explain the differences between the two genders for trunk and limbs according to the literature.
A study from England showed that several factors had a negative impact on survival, including having a tumor located on the trunk and being male.  We observed the same negative impact on survival from having a tumor located on the trunk. Whereas both incidence and mortality are decreasing in younger age groups, rates are still increasing in older age groups. , The continuous downward trend of the tumor thickness was observed during the time period in all age classes by Buettner and his group.  Nevertheless, tumor thickness remained higher in the older age group than in the younger age group. Older patients had greater possibility for accumulating high levels of sun exposure. This may explain the higher mortality rates in the older age group. We didn't find the same significance for survival in our age groups. However, as in the literature,  we did observe that melanoma was located predominantly on the head and neck and occurred later in life.
The growth of distant metastases after treatment is a serious problem associated with this disease. A study by Mandolis et al., demonstrated the average distant metastasis rate after treatment to be 51.5%.  In the present study, the 2-year distant metastasis-free survival rate was 50%, and most distant metastases were detected within 2 years following the initial treatment.
Patient and tumor related characteristics of malignant melanoma diagnosed in our institute was the focus of the study. Demographical patterns of melanoma in Turkey are similar compared with the general literature data from Western countries , One of the interesting issue that needs further research is the influence of sunlight to the incidence of cutaneous melanoma in Turkey. Currently, there is not enough epidemiologic research reported from Turkey in region wise that has addressed the cause-effect relation between sun exposure and cutaneous melanoma. In addition, a regional statistical investigation and active planning to address the epidemiology of malignant melanoma more effectively are needed.
We feel it is possible, as other authors  have observed, that the increase in the rate of early stage incidence cases is the result of the adoption of new screening and diagnostic practices and greater awareness of the impact of early melanoma diagnosis on the quality of life. Enhanced public awareness about the consequences of excessive exposure to the sun and the use of better sun protection may lead to a decrease in melanoma cases.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2]