Introduction

Malignant melanoma accounts for only approximately 1% of skin cancers and is not a common type of skin cancer [1]. However, it is a skin cancer with the highest mortality rate due to poor prognosis. Furthermore, the incidence rates and primary sites differ according to race [2]. Therefore, there is a large body of research on the prognosis and incidence of malignant melanoma.

In Asia, from 1992 to 2002, the annual average incidence rate of malignant melanoma was 1.0 per 100,000 people, which is even rarer than that in Caucasians [3]. According to GLOBOCAN 2020 data, the age-standardized incidence and mortality rates of malignant melanoma worldwide are 3.4 and 0.56 per 100,000 people, respectively. In Asia, these rates are lower at 0.42 and 0.21, respectively, than those found globally. However, according to the GLOBOCAN data, the incidence of melanoma is generally on an upward trend both worldwide and in Asia. According to the Korean Statistical Information Service, the age-standardized incidence rate of malignant melanoma in Korea has steadily increased from 0.8 in 1999 to 1.2 in 2020. Additionally, when comparing the mortality rates of patients with malignant melanoma in 31 countries from 1985 to 2015, most countries showed an increase in mortality rates, and particularly Korea showed the highest increase rate for both men and women [4].

However, the incidence of prostate, ovarian, and breast cancers gradually increases in Asians. Additionally, as one of the causes, the Westernized lifestyle is drawing attention. The composition of Korean diets has changed, and the number of overweight patients has increased. This can also be applied to patients with malignant melanoma [5].

Due to its increasing incidence and mortality, the analysis and follow-up of the characteristics of malignant melanoma along a regular cycle are important. Furthermore, since melanoma in Korean patients differs from that of those in Western countries regarding the location and characteristics, and there have not been many large-scale studies, this study aimed to investigate the characteristics of melanoma in Korean patients and compare them with those in patients from other countries [6].

This study analyzed 200 patients and secured the largest number of cases consecutively treated by one surgeon at a single institution in Korea. Additionally, considering that most previously reported large-scale cohort studies are multi-center studies, it is significant that this study can achieve a higher level of data quality. Through this study, the characteristics of malignant melanoma in Korea were confirmed, and the trend of malignant melanoma in Korea was validated by comparing 100 patients who visited the Pusan National University Hospital before 2014 with 100 who came after.

Patients and Methods

Overall, 200 consecutive patients with malignant melanoma who underwent surgery at the Pusan National University Hospital from 2000 to 2022 were investigated. All patients were admitted to the hospital and underwent surgery by a single surgeon who provided continuous care. The historical medical records of each patient were used to obtain information on sex and age, tumor stage, primary lesion site, histopathological subtype, Breslow tumor thickness, Clark level, and survival period.

The histologic subtype was categorized according to the World Health Organization classification as follows: superficial spreading melanoma (SSM), nodular melanoma (NM), acral lentiginous melanoma (ALM), lentigo maligna melanoma (LMM), and mucosal melanoma (MM). According to the American Joint Committee on Cancer (AJCC) staging system, tumor thickness and invasion were assessed using the staging systems of Breslow and Clark, respectively. The interval between the date of diagnosis of the primary cutaneous melanoma and the registered date of death or the date of the last consultation was defined as the survival time.

The 100 patients who visited before 2014 were designated as the A group, and the 100 patients who visited after 2014 were the B group, a total of 200 patients. These groups were compared to confirm whether there were any changes in the characteristics of malignant melanoma over the years.

Statistical Analysis

Multivariate Cox proportional hazard analysis was used. The associations were summarized using a hazard ratio with 95% confidence intervals. The Kaplan–Meier method was used to analyze the survival rate. Furthermore, the associations were summarized according to sex, age, location, type, tumor stage, Breslow thickness, and Clark level. Moreover, the associations were determined using the Kaplan–Meier method (log-rank test) and Gehan–Breslow–Wilcoxon test. The differences were calculated, with the significance being P < 0.05. The statistical analyses were performed using SAS software (version 9.4; SAS Institute, Cary, NC, USA).

Ethics Statement

The Institutional Review Board of Pusan National University Hospital reviewed and approved this study (IRB No. 2201–011-111).

Results

The epidemiological characteristics of the 200 patients who visited Pusan National University Hospital and underwent surgery between September 2000 and May 2022 were analyzed. The median follow-up period was 33 months. All patients' 1-year and 5-year overall survival was 95.5% and 76.5%, respectively. In group A, 64 women and 36 men indicated a man-to-woman ratio of 1:1.78. However, in group B, 57 women and 43 men showed a man-to-woman ratio of 1:1.33.

The mean age of all patients was 63.23(standard deviation [SD] 13.67) years. The average age of the patients in groups A and B was 60.25 (SD 13.71) years and 66.21 (SD 12.97) years, respectively, which indicated a gradual increase in the age of the patients (Table 1). The largest number of patients was those in their 70’s (59, 29.5%), followed by 56 (28%) in their 60’s and 30 (15%) in their 50’s. Moreover, according to the AJCC staging system, stage 2 was the most common (61 patients, 30.5%), followed by stage 3 with 54 (27%) and stage 1 with 46 (23%). (Table 2).

Table 1 Demographics and characteristics of 200 patients with malignant melanoma
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Table 2 Cancer stage according to the age of 200 patients with malignant melanoma
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The most common site of the primary tumor was the lower extremity (119 cases, 59.5%), which included the foot (105 cases, 52.5%). The next most common site was the upper extremity (36 cases, 18%), with the same order in groups A and B. There were more patients in the order of the head and neck (28 cases, 14%) and the trunk (17 cases, 8.5%). In group A, there were more patients with sites in the trunk, while in group B, the number of patients with sites in the head, neck, and upper extremities was the same.

Compared with histopathological subtypes, the most common subtype was ALM (122 cases, 61%). The next most common subtypes were 36 cases of NM (18%), 28 of superficial spreading type (14%), 12 of LMM (6%), and two of MM (1%). The prevalence in group A was high in the order ofALM, NM, SSM, and LMM, and in group B ALM, SSM, LMM, NM, and MM. Accordingly, the prevalence of SSM and LMM increased, and the nodular type decreased.

Regarding Breslow thickness, there were 30 cases of in situ melanoma, 28 cases were ≤ 1 mm, 27 were 1–2 mm, 44 were 2–4 mm, and 71 were ≥ 4 mm. A Breslow thickness of ≥ 4 mm was the most common, followed by cases with a thickness of 2–4 mm. When groups A and B were compared, most of the patients were the same, with ≥ 4 mm, while the second most common was 2–4 mm in group A; however, in situ, group B had more cases.

Based on invasion level, when the Clark level was compared, the most frequent type of cases was Level 4, which had 69 cases, followed by Level 5, 45, Level 1, 34, Level 3, 27, and Level 2, 25. Level 4 was the most common type, followed by Level 5 and Level 1 in the order of the number of cases. In groups, A and B, most cases and the second cases were the same.

When the survival rate postoperatively was compared, sex and Breslow thickness were the indicators that showed a significant association with the survival rate. The survival rate of men was lower than that of women (P = 0.042).

The deeper the Breslow depth, the lower the survival rate. From 36 months postoperatively, the survival rate decreased rapidly in patients with a Breslow depth of 1–2 mm and when the survival rate was investigated. However, when the survival rate by age (P = 0.096), Clark level (P = 0.059), Cancer stage (P = 0.063), histological type (P = 0.491), and the primary location of malignant melanoma (P = 0.209) was compared, no significant associations were confirmed (Fig. 1).

Fig. 1
figure 1

a Kaplan–Meier curves showing survival rates in patients according to sex. Sex: men (blue line) and women (red line). b Kaplan–Meier curves showing survival rates in patients according to Breslow thickness. Breslow thickness: under 1.00 mm (blue line), 1.01–2.00 mm (green line), 2.01–4.00 mm (pink line), >4.00 mm (red line). c Kaplan–Meier curves showing survival rates in patients according to age. Age: under 50 (blue line), 50–60 (green line), 60–70 (pink line), 70–80 (purple line), and over 80 years (red line). d Kaplan–Meier curves showing survival rates in patients according to Clark level. Clark level: Clark Level 1 (blue line), Clark Level 2 (green line), Clark Level 3 (pink line), Clark Level 4 (purple line), Clark Level 5 (red line). e Kaplan–Meier curves showing survival rates in patients according to cancer stage. Cancer stage: Stage 0 (blue line), Stage 1 (green line), Stage 2 (pink line), Stage 3 (purple line), Clark Level 4 (red line). f Kaplan–Meier curves showing survival rates in patients according to histological type. Histological type: ALM, acral lentiginous melanoma (blue line); SSM, superficial spreading melanoma (green line); LM, lentigo melanoma (pink line); NM, nodular melanoma (red line). g Kaplan–Meier curves showing survival rates in patients according to tumor location. Tumor location: Head and neck (blue line), upper extremity (purple line), trunk (green line), lower extremity (red line)

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Cox’s multivariate analysis identified the following variables as risk factors for malignant melanoma: sex (P = 0.046), Breslow depth of 1–2 mm (P = 0.032) and ≥ 4 mm (P = 0.010), Clark Level 5 (P = 0.019), and cancer stage 4 (P = 0.011) (Table 3).

Table 3 Cox multivariate analysis of clinicopathologic variables associated with malignant melanoma
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Discussion

Malignant melanoma is a skin cancer with a high mortality rate, and the location of the onset and the most common types are different in the East and the West. The incidence and mortality rate has also changed gradually over time. Therefore, it is necessary to constantly update the data and understand the trend.

Thus, we analyzed 200 consecutive patients who visited a single institution and obtained a sufficiently large number of statistically significant cases. Additionally, since the patients were operated on by one surgeon who visited the hospital continuously, the survival rate, according to epidemiology, was compared by excluding the factors due to surgical treatment.

Furthermore, it was possible to confirm relatively accurately whether the epidemiological factors changed over time. Moreover, we compared our findings with those of other previously published studies to confirm the characteristics of malignant melanoma in Korean patients (Online Resource 1).

Through a previous study, we have confirmed that the characteristics of patients with malignant melanoma in Korea are similar to those in Asia [6]. Accordingly, this research of our center, which investigated Koreans, will be the same as the characteristics of Asians.

Our results showed that the average age of the patients was 63.2 years old, with the average age in groups A and B being 60.2 years and 66.2 years, respectively, which showed an increasing trend in the average age of patients. The average age of onset of patients with malignant melanoma in Korea has been gradually increasing in previously published reports of patients with malignant melanoma in Korea [6,7,8,9,10].

Regarding the gender ratio, the man-to-woman ratio was 1:78 and 1:33 in groups A and B, respectively, which indicated that while there were more women than men, the incidence rate of female patients decreased gradually. In Korea, according to our survey and previous reports, the prevalence of malignant melanoma in women was higher than that in men [6,7,8,9,10]. Generally, men are more likely to have melanoma, and this tendency has been found to increase as the age of onset increases [11]. In other Asian countries, the man-to-woman ratio in Singapore and Taiwan was 1.7:1 and 1.2:1, respectively. Thus, there have been more female patients, particularly in Korea [12,13,14].

Regarding the Breslow thickness, a deep depth of 4 mm or more was the most common, and no significant differences were found between groups A and B. Regarding the Clark Level, Levels 4 and 5 were high, and it has been demonstrated that the Clark level in Korean patients was higher than that of those from the West [6, 15, 16].

The most common primary tumor site was the lower extremity, which accounted for 59.5% of 119 cases. This number included the foot (105 cases, 52.5%), while the lower extremity, excluding the foot, comprised 14 cases (7%), which suggested that most of the malignant melanomas occurred in the foot. The upper extremity was the second most common site with 36 cases (18%); among these, the hand accounted for a high proportion (25 cases, 12.5%). From the results of this study and other reports published in Korea, it can be confirmed that the most common site of malignant melanomas in Korean patients was the foot area [6,7,8,9,10].

ALM was shown to be the most frequent subtype of melanoma in Asian populations, comprising 41.8%, 86.6%, 50.8%, 47%, and 50% of the patients with melanoma in China, Korea, Hong Kong, Japan, and Singapore, respectively [17, 18]. In most reports, ALM was the most common type in Korea, followed by nodule melanoma and SSM [6,7,8,9,10]. Our findings supported these results. When groups A and B were compared, the ratio of NM decreased in group B, whereas that of SSM and LMM increased. Thus, while ALM was still the most common in Korean patients with melanoma, the ratio of the other subtypes changed.

We investigated the association between age, sex, tumor location, histological subtype, cancer stage, Clark level, Breslow thickness, and survival rate and confirmed that sex and Breslow thickness were significant prognostic factors in the survival rate. Furthermore, considering that this study was a large-scale cohort study of 200 patients, it was confirmed that there was a numerical significance according to age, Clark level, and cancer stage (P < 0.1). However, no significant association was found between the histological type and tumor location (P > 0.1).

We also found that in Korean patients with malignant melanoma, it tended to occur more frequently in women, while men diagnosed with cutaneous melanoma had poorer clinical outcomes and higher disease recurrence, disease progression, and mortality than women.9 This supported the finding of a previous study that indicated that mortality rate ratios were significantly greater in men than in women in the East Asian populations of Japan, Korea, Hong Kong, and Singapore [19].

Breslow thickness has also been found to be the most powerful prognostic factor [20]. If the Breslow thickness was < 0.75 mm, most patients survived; if the Breslow thickness was ≥ 3 mm, the survival rate was approximately 50% [21, 22]. In our study, the mortality rate was higher in patients with a Breslow thickness of ≥ 1 mm than in those with a Breslow thickness of < 1 mm.

The significance of age, Clark level, and cancer stage, 0.05 < P value < 0.1, was not confirmed. However, since this was a large-scale cohort study, it was considered to have numerical significance. Age is a factor that increases the risk of local recurrence; particularly, old age has been associated with a worse prognosis in previous studies [13, 23]. Moreover, studies have suggested that the association with poor prognosis in old age may have been due to a high rate of adverse prognostic features, such as late diagnosis, low awareness of early signs and symptoms of melanoma, ulcers, and high mitotic rates [13]. Although age was not a significant poor prognostic factor in our study (P = 0.096), it was confirmed that older people tended to have a lower survival rate.

The Clark level was the method used before the Breslow method for measuring the depth of invasion. Conversely, due to the difficulty of measurement, it is usually used together with Breslow thickness [24]. However, while the Breslow thickness has been suggested as the most powerful prognostic indicator for survival in the early stage, in the case of the Clark level, according to the findings of some studies, the significance was sometimes not confirmed [25, 26]. In this study, Clark's level was not a significant prognostic factor but had a numerical significance(P = 0.059). Therefore, the deeper the invasion depth measured at the Clark level, the higher the mortality rate. Thus, it can be confirmed that the deeper the malignant melanoma's invasion depth, the higher the mortality rate.

Based on analyses of the AJCC Melanoma Staging Database, cancer stage was a prognostic factor for malignant melanoma [27]. Recently, studies have been conducted to elucidate the correlation between lymph node invasion and poor prognosis [27]. Furthermore, studies on the survival rate and benefit according to whether a sentinel lymph node biopsy was performed are also being conducted [13, 28]. In our study, the higher the cancer stage, the higher the mortality rate, confirming that the cancer stage has a numerical significance (P = 0.063). However, since we did not separate and analyze the cancer stage and the lymph node independently, it is unknown whether the lymph node is a major independent predictor of survival among all patients.

In contrast, in this study, no significant results were found according to the histological type and location of melanoma. Due to the inconsistent statistical data observed in previous studies, it remains controversial whether the anatomic site of melanoma is a significant predictor of survival [29]. Although the discrepancies between these studies have yet to be explained, they may be caused by the diverse sample sizes, inconsistent study designs, and different confounding factors used in the previous studies [13].

The histological type is a frequently mentioned prognostic factor of malignant melanoma.

While some studies have suggested that prognosis may be associated with histologic subtype (e.g., patients with NMs were believed to have a worse prognosis than those with SSM) [10, 30], more recent multivariate analyses have demonstrated that these prognostic differences were more likely to be due to other histologic features, such as Breslow thickness and ulceration histological type [23]. In this study, the survival rate of the nodular type tended to be lower than that of the other histological subtypes. However, no significant results were found according to the histological type of melanoma (P = 0.209). We believe that the ALM type was overly compared to other subtypes, reducing its precise statistical significance.

There is a limitation to this study. The utilization of a hospital-based case series may limit the generalizability of our findings to the broader epidemiology of the entire Korean population. To address this limitation, we included comparisons with our previous hospital-based case series and other Korean studies published at different time intervals, incorporating a substantial number of patients, specifically 200 individuals [6,7,8,9,10].

In conclusion, we confirmed that the characteristics of malignant melanoma in Asian patients were maintained without significant change. We also confirmed that sex and Breslow were significant prognostic factors for survival. But age, Clark level, cancer stage, site of the primary lesion, and histological type were not statistically significant prognostic factors. Therefore, further studies regarding these factors are needed to unveil more details.