Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2024;14(3):e2024135 1 Evaluation of Demographic and Clinical Characteristics of Turkish Patients With Primary Cutaneous Melanoma: A 5-Year Experience of a Tertiary Referral Center Irfan Gahramanov1, Gulsen Akoglu1, Eda Karaismailoglu2, Nuri Karadurmus3 1 Department of Dermatovenereology, University of Health Sciences, Gulhane School of Medicine, Ankara, Turkey 2 Department of Medical Informatics, University of Health Sciences, Gulhane School of Medicine, Ankara, Turkey 3 Department of Medical Oncology, University of Health Sciences, Gulhane School of Medicine, Ankara, Turkey Key words: melanoma, primary cutaneous melanoma, staging, survival Citation: Gahramanov I, Akoglu G, Karaismailoglu E, Karadurmus N. Evaluation of Demographic and Clinical Characteristics of Turkish Patients With Primary Cutaneous Melanoma: A 5-Year Experience of a Tertiary Referral Center. Dermatol Pract Concept. 2024;14(3):e2024135. DOI: https://doi.org/10.5826/dpc.1403a135 Accepted: January 3, 2024; Published: July 2024 Copyright: ©2024 Gahramanov et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Gulsen Akoglu, MD, MSc, University of Health Sciences, Gulhane School of Medicine, Ankara, Turkiye. E-mail: gusemd@yahoo.com, drakoglu@gmail.com Introduction: Data about the demographic and clinical characteristics of melanoma patients in Turkey is limited. Objectives: Data about the demographic and clinical characteristics of melanoma patients in Turkey is limited. We aimed to review the features of patients with primary cutaneous melanoma (PCM) diag- nosed and treated in a tertiary referral center. Methods: The medical records of melanoma patients followed up by the Departments of Dermatology and Medical Oncology were retrospectively reviewed. Results: Within a 5-year period, 180 patients had been diagnosed with melanoma. Of all, 158 (87.8%) had PCM, 9 (5%) had mucosal melanoma, 9 (5%) had unknown primary melanoma, and 4 (2.2%) had ocular melanoma. Of 146 patients with PCM, 32.9% had stage I, 28.8% had stage II, 17.8% had stage III, and 20.5% had stage IV disease. The most common subtype was superficial spreading melanoma (38.8%). A statistically significant correlation was found between the patients Breslow thickness and lymph node involvement, histopathological subtype, and tumor ulceration (P < 0.001). Among all PCM patients, those in stage IV had the lowest 5-year survival rate when compared to the other disease stages (P < 0.001). ABSTRACT 2 Original Article | Dermatol Pract Concept. 2024;14(3):e2024135 Introduction Various genetic and environmental factors, such as UV radi- ation, induce uncontrolled malignant proliferation of mela- nocytes, resulting in melanoma. Although the frequency of melanoma is as low as 1.3% among all skin cancers, it is responsible for about 75% of skin cancer-related deaths [1]. The incidence of melanoma is variable due to geographical and ethnic factors; however, current data points out a re- markable increase every year around the world. There are few studies on melanoma patients’ demographic and clinical characteristics in Turkey [2-5]. Therefore, in this study, we aimed to analyze the demographic and clinicopathological characteristics of Turkish patients with primary cutaneous melanoma [PCM] who were diagnosed and followed up in a tertiary referral hospital over 5 years. Objectives We aimed to review the features of patients with primary cutaneous melanoma (PCM) diagnosed and treated in a ter- tiary referral center. Methods The medical records of melanoma patients who sought care at our center from October 2016 to October 2021 under- went a comprehensive review. Demographic, clinical (age at the time of diagnosis, survival time, localization of the tumor, stage of the disease according to the AJCC 8th mela- noma staging system; the number of lymph nodes and met- astatic organ involvement.), and histopathological features (Breslow thickness, tumor ulceration status, melanoma sub- type, BRAF mutation status if available) of the patients were all noted. Statistical analyses were performed with the IBM SPSS 25.0 (SPSS Inc) program. Mean ± standard deviation (SD) or median and minimum-maximum values were used for continuous variables, and frequencies (N) and percent- ages (%) were used for categorical variables. Categorical variables were compared by Pearson chi-square or Fisher exact test. The normality of the continuous variables was evaluated by Kolmogorov-Smirnov test. Differences between the groups for continuous variables were determined by independent samples t-test. Overall survival was estimated by the Kaplan-Meier method and survival curves were com- pared by the Log-rank test. P values of 0.05 and below were considered statistically significant. The study was approved by the local ethics committee (Date: 25/11/2021; #379). Results Of 180 patients, 158 (87.8%) had PCM, 9 (5%) had muco- sal melanoma, 9 (5%) had melanoma of unknown primary, and 4 (2.2%) had ocular melanoma. The age of diagnosis ranged from 4 years to 92 years (N=177; mean ± SD: 54.7 ± 18.7 years). The mean age at diagnosis was statistically similar in both genders (55.5±18.1 years for males versus 53.7±19.5 years for females; P = 0.540). When the character- istics of patients with PCM were detailed (Table 1), 81 were males and 77 were females (1.05/1). The age of PCM diagno- sis ranged from 4 to 92 years (mean ± SD: 53.8 ± 19 years); the mean age at diagnosis was statistically similar in both genders (mean ±S D: 54.8 ± 18.8 years for males versus mean ± SD: 52.3 ± 19.5 years for females P = 0.440). The most common histopathological subtype was superficial spread- ing melanoma (SSM) (38.8%). When evaluated according to the AJCC 8th guideline, most patients (61.7%) were in the early local stage (I and II), 17.8% of the patients were in the nodal stage (III) and 20.5% of the patients were diag- nosed with metastatic melanoma (IV), respectively (Table 1). Anatomical localization of PCM was similar in both gen- ders (P = 0.341). The lower extremities were the most fre- quently involved, followed by trunk involvement (Table 2). The range of tumor Breslow thickness was 0.15-20.00 mm (mean ± SD: 3.72 ± 3.98 mm) in 137 patients. The most common T stages in men were T3 (64.1%) and T4 (55.3%), while T1 (58.8%) and T2 (56.0%) stages were most common in women (Table  3). However, the T stage did not differ between genders (P = 0.196). While Breslow thickness correlated considerably with histopathological subtype (P  <  0.001) (Table 3), lymph node involvement (P < 0.001), ulceration (P < 0.001), and 5-year overall sur- vival (P = 0.014), no correlation was found with anatomical location and Breslow thickness. Due to technical and insur- ance issues, the BRAF mutation analyses could be performed in only 53 patients. The data revealed wild type in 54.7% and mutant type in 45.3%. Lymph nodes were involved in 50 of 147 patients with PCM (34%). The lymph node involvement Conclusions: Relatively younger age at melanoma diagnosis, frequent presence of thick (> 4 mm) tumor, and frequent acral lentiginous subtype are the most remarkable features that suggest the low awareness and knowledge of melanoma in our population. Original Article | Dermatol Pract Concept. 2024;14(3):e2024135 3 significantly correlated with tumor ulceration status, pres- ence of metastasis, histopathological subtype, and age at diagnosis (all P < 0.05) (Table 4). Compared with patients with SMM, patients with ALM and patients with NM had more lymph node involvement (60%, P = 0.002 and 42.6%, P < 0.001, respectively). The patients over 45 years had more lymph node involvement than younger ones (P = 0.015), whereas it did not differ for both genders and localizations of tumors (P > 0.05). Of all PCM patients for whom staging information was available, 30 (20.5%) had distant metasta- ses. Within the 30 (20.5%) patients diagnosed with stage IV metastatic PCM, metastatic organ data were available for 22 individuals, revealing that eight patients presented with multiple organ metastases, while 14 patients exhibited sin- gle organ involvement (Table 5). The overall survival data of 178 patients with melanoma was evaluated at the time of the study. According to the statistical analysis, the median follow-up period was 32.5 months (range 1-162 months). During the follow-up, 41 patients have died. The estimate of the mean overall survival time was 50 months (95% confi- dence interval: 46.6 – 52.5). For PCM patients, 27 patients have died during the follow-up time. The estimate of the mean overall survival time was 53 months (95% confidence interval: 50 – 55). For all PCM patients, the 5-year survival rate of T1 was significantly higher than T2, T3, and T4 (P = 0.016) (Figure 1A). The 5-year survival rate was highest in T1 patients (100%), 87% in T2, 77.1% in T3, and 76.0% in T4 patients, respectively. The results of the log-rank test regarding death for each Breslow thickness stage showed that the survival rate of T1 was the highest compared to pa- tients in other stages (P = 0.016). When the 5-year survival is analyzed based on the stage determined by AJCC 8th for all PCM patients, the survival rate of stage IV patients was the lowest compared to patients in other melanoma stages (P < 0.001). The estimate of the mean overall survival time for stage IV was 32.8 months (95% confidence interval: 32.8 – 48.1). In the context of the 5-year survival analysis concerning factors influencing overall survival in melanoma, a significant relationship was observed with ulceration (P < 0.001), Breslow thickness (P = 0.016), AJCC 8th stage (P < 0.001), and age (P = 0.008). However, there was no sig- nificant relationship detected concerning gender (P = 0.374) and localization (P = 0.540) (Figure 1, A-F). Conclusions Our findings, indicating a mean age of melanoma diagnosis at 54.7 years, align closely with prior research conducted in Turkey [2-5], which is younger than the most recent data of the American Cancer Society reporting the average age of diagnosis for melanoma as 65 years [6]. Notably, the mean age of melanoma diagnosis in Turkey is younger than in the Table 1. Patient and Tumor Characteristics of Primary Cutaneous Melanoma Patients. Features N (%) Histopathological Subtype (N = 152) SSM 59 38.8 NM 51 33.6 ALM 26 17.1 LMM 8 5.3 Others 8 5.3 Age (N = 155), years <18 1 0.6 18-30 23 14.8 31-45 32 20.6 46-65 49 31.6 >65 50 32.3 Gender (N = 158) Male 81 51.3 Female 77 48.7 Breslow thickness (N = 137) T1 (≤ 1 mm) 37 27.0 T2 (1.1-2 mm) 23 16.8 T3 (2.1-4 mm) 35 25.5 T4 (>4 mm) 42 30.7 Ulceration (N = 92) Present 51 55.4 Absent 41 44.6 Lymph node involvement (N = 147) N0 97 66.0 N1 23 15.6 N2 4 2.7 N3 23 15.6 Metastasis (N = 151) M0 121 80.1 M1 30 19.9 BRAF mutation (N = 53) Wild type 29 54.7 Mutant type 24 45.3 Overall survival (N = 158) Alive 131 82.9 Dead 27 17.1 Stage (N = 146) I 48 32.9 II 42 28.8 III 26 17.8 IV 30 20.5 Sentinel lymph node involvement (N = 55) Negative 34 61.8 Positive 21 38.2 ALM = acral lentiginous melanoma; LMM = lentigo malignant melanoma; NM = nodular melanoma; SSM = superficial spreading melanoma. 4 Original Article | Dermatol Pract Concept. 2024;14(3):e2024135 of cutaneous and non-cutaneous melanoma patients and distribution of histopathological subtypes of PCM our find- ings are compatible with the results of related literature [14], the ALM subtype remarkably emerged as the third most prevalent subtype within our study population (17.1%). According to population-based data, ALM accounts for ap- proximately 5% of melanoma cases among the four major histologic subtypes of PCM in the USA [14]. In contrast, it appears to be relatively more common among African Americans, constituting approximately 36% of melanoma cases [15]. The striking frequency of ALM in our cohort pa- tients may be related to the data of a referral hospital serving with an experienced multidisciplinary approach to a consid- erable number of patients applying from various regions of our country. Nevertheless, further investigations are needed USA and England [7,8]. Intense sun exposure starting from an early age and low awareness of UV protection may be the main reasons for younger melanoma diagnoses in our coun- try. The incidence studies conducted in different countries re- vealed different male/female ratios. While most western and northern European countries report higher incidence rates in women than in men [9], most eastern, southern, and central European countries have reported higher incidences of mela- noma in men [10]. However, our data is similar to the gender ratios of melanoma patients diagnosed in the USA, eastern Europe, and Australia [11]. In the existing literature, the distribution of melanoma is documented with approximately 90-95% cutaneous, 5% in ocular, 3% metastases from an unknown primary site, and 1% in mucosal tissues [12,13]. When compared, percentages Table 2. Tumor Localization Distribution Across Gender Groups. Parameters Involved site N (%) PHead-neck Trunk Upper extremity Lower extremity Total Gender Male 16 (20.3) 26 (32.9) 9 (11.4) 28 (35.4) 79 (100) 0.341 Female 12 (17.1) 17 (24.3) 14 (20.0) 27 (38.6) 70 (100) Total 28 (18.8) 43 (28.9) 23 (15.4) 55 (36.9) 149 (100) Table 3. Breslow Thickness Distribution Across Gender, Histopathological Subtype of Primary Cutaneous Melanoma, Lymph Node Involvement, Ulceration, 5-Year Overall Survival, and Tumor Localization. Parameters ≤1 mm N (%) 1.1-2 mm N (%) 2.1-4 mm N (%) >4 mm N (%) P Gender Male 14 (41.2) 11 (44.0) 25 (64.1) 21 (55.3) 0.196 Female 20 (58.8) 14 (56.0) 14 (35.9) 17 (44.7) Histopathological subtype SSM 25 (46.3) 14 (25.9) 11 (20.4) 4 (7.4) <0.001 NM 1 (2.1) 2 (4.3) 22 (46.8) 22 (46.8) ALM 5 (26.3) 6 (31.6) 2 (10.5) 6 (31.6) LMM 1 (16.7) 1 (16.7) 2 (33.3) 2 (33.3) Othersa 2 (28.6) 1 (14.3) 2 (28.6) 2 (28.6) Lymph node involvement (-) 32 (97.0) 21 (84.0) 21 (56.8) 18 (48.6) <0.001 (+) 1 (3.0) 4 (16.0) 16 (43.2) 19 (51.4) Ulceration (+) 0 (0) 7 (46.7) 14 (53.8) 18 (64.3) <0.001 (-) 21 (100) 8 (53.3) 12 (46.2) 10 (35.7) Overall survival Died 0 (0) 3 (13.0) 10 (27) 10 (23.8) 0.014 Alive 37 (100) 20 (87.0) 27 (73) 32 (76.2) Localization Head-Neck 4 (13.3) 2 (8.0) 7 (18.9) 11 (29.7) 0.194 Trunk 12 (40.0) 9 (36.0) 13 (35.1) 5 (13.5) Upper extremity 4 (13.3) 5 (20.0) 7 (18.9) 5 (13.5) Lower extremity 10 (33.3) 9 (36.0) 10 (27.0) 16 (43.2) aRare subtypes (amelanotic, animal type, desmoplastic) ALM = acral lentiginous melanoma; LMM = lentigo malignant melanoma; NM = nodular melanoma; SSM = superficial spreading melanoma. Original Article | Dermatol Pract Concept. 2024;14(3):e2024135 5 to explain the reasons for the high frequency of ALM pa- tients, including detailed clinical characteristics and risk fac- tors. In our analysis, lower extremities predominated as the most common site, followed by the trunk in both genders, diverging from reports indicating a primary involvement of the trunk in males and lower extremities in females [16]. We observed that our patients’ tumors were mainly thicker than 4 mm in contrast to studies conducted in western countries; most of their patients were diagnosed at an early stage [17]. Male gender is a poor prognostic criterion for Breslow thickness [18]. As the tumor thickness increases in PCM, malignant cells are more likely to spread to regional lymph nodes by lymphatic invasion. The analysis of our study data also pointed out the correlation between tumor thickness Table 4. Lymph Node Involvement According to Subtype, Ulceration, Age, Metastasis Status, Localization and Gender. Lymph Node Involvement Subtype LN (-) LN (+) Total PN (%) N (%) N (%) SMM 49 (86.0) 8 (14.0) 57 (100) <0.001 NM 27 (57.4) 20 (42.6) 47 (100.0) ALM 10 (40.0) 15 (60.0) 25 (100.0) LMM 3 (42.9) 4 (57.1) 7 (100.0) Rare subtypea 5 (55.6) 4 (44.4) 9 (100.0) Ulceration Present 41 (80.4) 1 (19.6) 51 (100.0) <0.001 Absent 23 (52.3) 21 (47.7) 44 (100.0) Age group 18-30 19 (86.4) 3 (13.6) 22 (10) 0.015 31-45 24 (70.6) 10 (29.4) 34 (100) 46-65 28 (52.8) 25 (47.2) 53 (100) >65 27 (51.9) 25 (48.1) 52 (100) Metastasis status Present 97 (78.2) 27 (21.8) 124 (100) <0.001 Absent 2 (5.4) 35 (94.6) 37 (100) Localization Head-Neck 18 (64.3) 10 (35.7) 28 (100) 0.491 Trunk 31 (73.8) 11 (26.2) 42 (100) Upper extremities 1 3(59.1) 9 (40.9) 22 (100) Lower extremities 31 (59.6) 21 (40.4) 52 (100) Gender Male 4 (57.0) 37 (43.0) 86 (100) 0.251 Female 50 (65.8) 26 (34.2) 76 (100) aRare subtypes (amelanotic, animal type, desmoplastic) ALM = acral lentiginous melanoma; LMM = lentigo malignant melanoma; LN = lymph node; NM = nodular melanoma; SSM = superficial spreading melanoma. Table 5. Metastatic Sites of Stage IV Patients With Primary Cutaneous Melanoma. Metastatic site N % Lung 10 45 Brain 9 40 Liver 5 23 Bone 7 32 Single organ/tissue involved 14 64 Lung 7 32 Brain 4 18 Liver 2 9 Bone 1 4 Multiple organ/tissue involvement 8 36 6 Original Article | Dermatol Pract Concept. 2024;14(3):e2024135 is the small number of patients having BRAF mutation anal- ysis. Although limited data was available, mutant BRAF was positive in 45.3% of 53 patients in our study population. Of our study patients, 32.9% had stage I, 28.8% had stage II, 17.8% stage III, and 20.5% had stage IV PCM. In contrast, patients in stage IV were reported to be higher at 25% to 48.7% in different patient study groups [9]. The distribu- tion of melanoma patients data in Turkish studies is com- plex, reflecting diverse data sources encompassing multiple medical departments such as oncology, dermatology, and plastic surgery. Our data align with findings from specialized and regional lymph node involvement and ulceration. As expected, in our study, locoregional spread was higher in ulcerated than non-ulcered tumors. The most common his- topathological subtype to be associated with lymph node involvement is ALM [19]. Similarly, in our study group, pa- tients with ALM and LMM had more common lymph node involvement than patients with SSM and NM. Detection of BRAF mutation in melanoma patients gives them a chance for targeted immunotherapy [20]. Helen Davies et al [21] reported a 50% and 60% mutation rate in all human cancers and 66% in melanoma. One of the limitations of our study 1,0 0,8 0,6 0,4 0,2 0,0 ,00 10,00 20,00 30,00 TIME Survival Functions C um S ur vl va l 40,00 50,00 60,00 T 1 2 3 4 1-censored 2-censored 3-censored 4-censored 1,0 0,8 0,6 0,4 0,2 0,0 ,00 10,00 20,00 30,00 TIME Survival Functions C um S ur vl va l 40,00 50,00 60,00 LOCALIZATION 1 2 3 4 1-censored 2-censored 3-censored 4-censored 1,0 0,8 0,6 0,4 0,2 0,0 ,00 10,00 20,00 30,00 TIME Survival Functions C um S ur vl va l 40,00 50,00 60,00 STAGE 1 2 3 4 1-censored 2-censored 3-censored 4-censored 1,0 0,8 0,6 0,4 0,2 0,0 ,00 10,00 20,00 30,00 TIME Survival Functions C um S ur vl va l 40,00 50,00 60,00 AGE 1,00 2,00 3,00 4,00 5,00 1,00-censored 2,00-censored 3,00-censored 4,00-censored 5,00-censored 1,0 0,8 0,6 0,4 0,2 0,0 ,00 10,00 20,00 30,00 TIME Survival Functions C um S ur vl va l 40,00 50,00 60,00 ULCERATION 0 1 0-censored 1-censored 1 2 1-censored 2-censored 1,0 0,8 0,6 0,4 0,2 0,0 ,00 10,00 20,00 30,00 TIME Survival Functions C um S ur vl va l 40,00 50,00 60,00 GENDER Figure 1. Kaplan-Meier survival plots of overall survival according to: (A) Breslow thickness (P = 0.016; log rank test); (B)  Localization—1 head and neck, 2 trunk, 3 upper extremities, and 4 lower extremities (P = 0.540, log rank test); (C) AJCC 8th stage (P = 0.001, log rank test); (D) Age group: (group 1: <18, group 2: 18-20, group 3: 30-45, group 4: 45-65, and group 5: >65) (P = 0.008, log rank test); (E) Tumor ulceration status (1 ulcerated, 0 not ulcerated) (P = 0.001, log rank test); (F) Gender—1 male, 2 female (P = 0.374, log rank test). Original Article | Dermatol Pract Concept. 2024;14(3):e2024135 7 3. CELIK MSSKİ. Retrospective evaluation of malignant mela- noma patients: A single-center experience. Family Practice and Palliative Care. 2021. 4. Gamsizkan M, Yilmaz I, Buyukbabani N, et al. A retrospective multicenter evaluation of cutaneous melanomas in Turkey. Asian Pac J Cancer Prev. 2014;15(23):10451-6. DOI: 10.7314/apjcp .2014.15.23.10451. PMID: 25556491. 5. Can Baykal BNA, Tugba Atci. Is the frequency of primary cutaneous melanoma increasing in Turkey? An evaluation of the experiences of two dermatology centers. Journal of Oncological Sciences. 2018;4(1):19-23. 6. Society AC. Key Statistics for Melanoma Skin Cancer 2022. Available from: https://www.cancer.org/cancer/melanoma-skin- cancer/about/key-statistics.html. Accessed November 1st, 2023 7. Research UC. Melanoma skin cancer incidence statistics 2018 Accessed 1st November, 2023. Available from: https://www .cancerresearchuk.org/health-professional/cancer-statistics /statistics-by-cancer-type/melanoma-skin-cancer/incidence#ref-1. Accessed November 1st, 2023 8. Paulson KG, Gupta D, Kim TS, et al. Age-Specific Incidence of Melanoma in the United States. JAMA Dermatol. 2020; 156(1):57-64. PMID: 31721989 9. Forsea AM. Melanoma Epidemiology and Early Detection in Europe: Diversity and Disparities. Dermatol Pract Concept. 2020;10(3):e2020033. PMID: 32642304 10. Olsen CM, Thompson JF, Pandeya N, Whiteman DC. Evalua- tion of Sex-Specific Incidence of Melanoma. JAMA Dermatol. 2020;156(5):553-60.PMID: 32401272 11. Marks R. The changing incidence and mortality of melanoma in Australia. Recent Results Cancer Res. 2002;160:113-21.PMID: 12079205 12. Bolognia JL, Schaffer JV. DERMATOLOGY. 4th ed2018 2008-9 p. 13. Del Fiore P, Rastrelli M, Dall’Olmo L, et al. Melanoma of Unknown Primary: Evaluation of the Characteristics, Treatment Strategies, Prognostic Factors in a Monocentric Retrospective Study. Front Oncol. 2021;11:627527.PMID: 33747946 14. Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1998;83(8):1664-78.PMID: 9781962 15. Bradford PT, Goldstein AM, McMaster ML, Tucker MA. Acral lentiginous melanoma: incidence and survival patterns in the United States, 1986-2005. Arch Dermatol. 2009;145(4):427-34. PMID: 19380664 16. Stanienda-Sokół K, Salwowska N, Sławińska M, al. e. Primary Lo- cations of Malignant Melanoma Lesions Depending on Patients’ Gender and Age. Asian Pac J Cancer Prev. 2017;18(11):3081-6. PMID: 29172282 17. Kruijff S, Bastiaannet E, Francken AB, et al. Breslow thickness in the Netherlands: a population-based study of 40 880 patients comparing young and elderly patients. Br J Cancer. 2012;107(3): 570-4.PMID: 22713665 18. Bellenghi M, Puglisi R, Pontecorvi G, al. e. Sex and Gender Disparities in Melanoma. Cancers (Basel). 2020;12(7). PMID: 32645881 19. Marek AJ, Ming ME, Bartlett EK, Karakousis GC, Chu EY. Acral Lentiginous Histologic Subtype and Sentinel Lymph Node Posi- tivity in Thin Melanoma. JAMA Dermatol. 2016;152(7):836-7. PMID: 27096552 referral hospitals, particularly within oncology and derma- tology departments [2-5]. Based on melanoma patients di- agnosed in the USA between 2012 and 2018, according to the SEER [Surveillance, Epidemiology, and End Results] data of the American Cancer Society, the 5-year relative survival rate in the localized stage is 99%, 71% in the regional, and 32% in the distant stage, respectively [22]. In the context of global melanoma survival studies, several factors consis- tently emerge as adverse prognostic indicators for survival, including age, male gender, Breslow thickness, advanced dis- ease stage, the presence of ulceration, and the localization of tumors on the trunk and head-neck regions [12]. However, the results of our study deviate from this established pattern, as we found no statistically significant difference in 5-year survival rates concerning gender and localization character- istics of PCM. Instead, the results align with existing litera- ture, underscoring the significance of Breslow thickness, the presence of ulceration, advanced disease stage, and patient age as critical criteria for predicting poor prognosis. On the other hand, relatively higher overall survival (35%) for stage IV patients may depend on the launch of new thera- peutic agents (immunotherapies and targeted therapies) in 2015, which positively affected the survival of our patients whose data between 2016 and 2021 were studied. Among the recent studies reported from the UK, the 5-year overall survival increases up to 52% in patients using current prom- ising treatments such as ipilimumab and nivolumab [23]. It is predicted that in the future, more updated SEER data will report an increase in the 5-year survival rate of IV stage mel- anoma patients [22]. The results of this study show that patients with PCM followed up in one of the referral health centers of Turkey have a relatively young age at melanoma diagnosis, fre- quent presence of thick tumor (>4 mm), and frequent ALM subtype. All these data suggest that patients might have ex- perienced critical environmental triggers such as intense ul- traviolet exposure from a very young age, living in a country with relatively long and sunny days, climate changes, and ignorance of effective protective behaviors from sunlight. Future studies comprehensively analyzing the risk factors of the patients are needed especially for ALM, that is an histo- pathological subtype with an etiology less related to acute and chronic sun exposure. References 1. Surveillance, Epidemiology, and End Results (SEER) [Internet]. Accessed November 1st, 2023. Available from: https://seer .cancer.gov/statfacts/html/melan.html. 2. Abali H, Celik I, Karaca B, et al. Cutaneous melanoma in Turkey: analysis of 1157 patients in the Melanoma Turkish Study. J BUON. 2015;20(4):1137-41. PMID: 26416068. 8 Original Article | Dermatol Pract Concept. 2024;14(3):e2024135 22. Survival Rates for Melanoma Skin Cancer [Internet]. 2023. Available from: https://www.cancer.org/cancer/types/melanoma-skin-cancer/ detection-diagnosis-staging/survival-rates-for-melanoma-skin- cancer-by-stage.html. Accessed November 1st, 2023 23. James Larkin FRCP, Ph.D., Vanna Chiarion-Sileni, M.D., Rene Gonzalez, M.D., Jean-Jacques Grob, M.D. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. The New England Journal of Medicine. 2019;381.PMID: 31562797 20. Grant A McArthur 1 PBC, Caroline Robert 3, James Larkin 4, John B Haanen 5, Reinhard Dummer 6. Safety and effi- cacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. The Lancet Oncology. 2014;15(3):323-32.PMID: 24508103 21. Davies H, Bignell GR, Cox C, al. e. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949-54.PMID: 12068308