Abstract
Objectives
Cutaneous melanoma (CMM) is an aggressive malignancy whose incidence continues to rise worldwide. Ultraviolet (UV) radiation from natural and artificial sources is a major environmental risk factor and is classified as a Group 1 carcinogen by the International Agency for Research on Cancer. The present study aimed to evaluate the association between sun exposure patterns and the clinicopathological characteristics of patients with cutaneous melanoma, focusing on tumor thickness and markers of tumor aggressiveness.
Materials and methods
This retrospective cohort study included 115 patients with histologically confirmed primary cutaneous melanoma treated in our Plastic Surgery Department between January 2018 and December 2022. Demographic, clinical and histopathological data were collected from medical records and Breslow thickness was categorized as thin (≤2 mm) or thick (>2 mm). Statistical analysis included chi-square and Mann–Whitney U tests, followed by multivariate logistic regression to identify predictors of increased tumor thickness. A p-value < 0.05 was considered statistically significant.
Results
Statistically significant associations were identified between several clinicopathological variables and melanoma characteristics. Sun exposure pattern was significantly associated with tumor anatomical location [χ²(6) = 85.11, p < 0.001], with chronic exposure predominantly linked to melanomas of the posterior trunk, while intermittent exposure was more frequently observed in melanomas of the lower limbs. Patients with thick melanoma were significantly older than those with thin tumors (p = 0.032). Melanoma thickness was also significantly associated with histological subtype (p = 0.002), ulceration (p < 0.001), and mitotic activity (p = 0.002), with nodular melanoma, ulcerated tumors, and lesions with increased mitotic activity more frequently presenting greater Breslow thickness. Metastatic disease occurred more often in patients with thick melanomas (p = 0.046). In multivariate analysis, mitotic activity remained an independent predictor of thick melanoma [OR = 1.75, p < 0.001], while ulceration showed borderline significance (odds ratio [OR) = 4.14, p = 0.050]. Overall, sun exposure pattern was associated with melanoma location but not with markers of tumor aggressiveness.
Conclusion
Sun exposure pattern was associated with melanoma anatomical location but not with tumor aggressiveness. Increased mitotic activity was the strongest independent predictor of thick melanoma, while ulceration showed borderline significance. These findings suggest that intrinsic tumor characteristics play a greater role in melanoma progression than sun exposure patterns.
Keywords: cutaneous melanoma, Breslow thickness, sun exposure, tumor thickness, prognostic factors, intermittent sun exposure, chronic sun exposure
INTRODUCTION
Cutaneous melanoma (CMM) is one of the most aggressive skin malignancies and represents a major cause of skin cancer–related mortality worldwide (1, 2). The incidence continues to rise globally, with a 161% increase in prevalence since 1990 and projections indicating sustained growth through 2045 (3). In the United States, annual cases among white populations are projected to rise from approximately 70,000 in 2007–2011 to more than 116,000 in 2026–2031, with nearly 79% of this increase attributed to rising age-specific incidence rates and only 21% to population growth and aging (4).
Ultraviolet (UV) radiation from solar exposure and artificial sources such as tanning beds is a well-established environmental risk factor for skin malignancies, including cutaneous melanoma. Consequently, the International Agency for Research on Cancer (IARC) has classified UV radiation as a Group 1 carcinogen (5).
Individual sun exposure is generally classified into two major patterns: intermittent exposure, involving short but intense episodes typically related to recreational activities such as sunbathing or outdoor leisure, and chronic exposure, which reflects continuous exposure, most often associated with occupational outdoor activities (6).
The present study aimed to evaluate the association between sun exposure patterns and the clinicopathological characteristics of patients diagnosed with cutaneous melanoma, with particular emphasis on tumor thickness and indicators of tumor aggressiveness.
MATERIALS AND METHODS
This retrospective cohort study was conducted at the "Prof. Dr. Agrippa Ionescu" Clinical and Emergency Hospital, Bucharest, Romania, and included patients admitted to the Plastic Surgery Department between January 2018 and December 2022 with histologically confirmed primary cutaneous melanoma.
The study protocol was approved by the hospital's Ethics Committee (Approval No. 21126, issued 17 January 2022) and adhered to the principles of the Declaration of Helsinki. All participants provided written informed consent for the use of anonymized clinical data in research.
Eligible participants were adults (≥18 years) with primary cutaneous melanoma who underwent surgical treatment in the department and had complete demographic and histopathological data. Patients with ocular or mucosal melanomas, metastatic melanoma of unknown primary origin, or incomplete clinical or pathological records were excluded. After applying these criteria, 115 patients were included in the final analytic cohort.
Data were collected from hospital electronic databases, pathology archives and patient medical records. Demographic variables included age and sex. Clinical variables included tumor location, T stage, sun exposure pattern and the presence of regional or distant metastases. Information regarding sun exposure was obtained through patient interviews and classified as intermittent or chronic based on self-reported exposure patterns. Histopathological variables included melanoma subtype, Breslow thickness, ulceration and mitotic count. For the main analytical model, tumor thickness was further dichotomized into thin (<2 mm) and thick (≥2 mm) melanomas. Clinical staging was performed according to the eighth edition of the AJCC guidelines.
This study aimed to evaluate the relationship between sun exposure patterns and the clinicopathological characteristics of cutaneous melanoma, with particular emphasis on tumor thickness and markers of tumor aggressiveness.
All statistical analyses were performed using IBM SPSS Statistics (version 31.0.1.0; IBM Corp., Armonk, NY, USA). Continuous variables were expressed as medians and interquartile ranges (IQR) and compared using the Mann–Whitney U test. Categorical variables were presented as frequencies and percentages, and comparisons between groups were performed using the chi-square test or Fisher's exact test when appropriate. The strength of associations between categorical variables was assessed using Cramer's V.
For analytical purposes, Breslow thickness was categorized into thin melanoma (≤2 mm) and thick melanoma (>2 mm). Multivariate binary logistic regression was performed to identify predictors of thick melanoma, including sun exposure pattern, age, sex, ulceration and mitotic activity as independent variables. Additional logistic regression models were used to evaluate whether sun exposure pattern predicted ulceration, mitotic activity and metastases.
All statistical tests were two-sided, and p < 0.05 was considered statistically significant.
RESULTS
Patient characteristics
Between 1 January 2018 and 31 December 2022, a total of 115 consecutive patients with primary cutaneous melanoma were treated, including 57 men (49.6%) and 58 women (50.4%). The mean age of participants in the current study was 59.6 ± 13.9 years, ranging from 26 to 93 years. Melanoma was most frequently diagnosed in patients aged 51–60 years (33 patients, 28.7%), followed by those aged 61–70 years (30 patients, 26.1%).
Patients aged between 51 and 70 years accounted for more than half of the cohort (54.8%), whereas younger patients were rarely affected, with only three cases (2.6%) observed in the 21–30 age group. Of the 115 patients included in the study, 83 (72.2%) lived in urban areas and 32 (27.8%) in rural areas.
The baseline demographic, clinical and histopathological characteristics of the study population are summarized in Table 1.
Sun exposure patterns
Regarding sun exposure patterns, 48 patients (41.7%) reported chronic sun exposure, whereas 67 patients (58.3%) reported intermittent sun exposure.
A statistically significant association was observed between sun exposure pattern and tumor anatomical location (χ²(6) = 85.11, p < 0.001, Cramer's V = 0.860) as illustrated in Figure 1. Chronic sun exposure was predominantly associated with melanomas located on the posterior trunk (72.9%), whereas intermittent sun exposure was more frequently associated with melanomas of the lower limbs (47.8%).
The figure illustrates the distribution of tumor anatomical locations in patients reporting chronic and intermittent sun exposure. Chronic sun exposure was predominantly associated with melanomas located on the posterior trunk, whereas intermittent exposure was more frequently observed among melanomas of the lower limbs.
No statistically significant association was observed between sun exposure pattern and sex [χ²(1) = 1.47, p = 0.225] or living environment [χ²(1) = 2.01, p = 0.157].
Similarly, sun exposure pattern was not significantly associated with histological subtype [χ²(2) = 1.60, p = 0.449], ulceration [χ²(1) = 2.66, p = 0.103], mitotic activity [χ²(1) = 0.20, p = 0.651], metastatic disease [χ²(1) = 2.15, p = 0.143], or melanoma thickness [χ²(1) = 0.48, p = 0.487].
Tumor characteristics
The distribution of melanoma according to anatomical location showed that tumors were most frequently located on the posterior trunk (33.9%), followed by the lower limbs (28.7%) and the head (17.4%). Less frequent locations included the upper limbs (9.6%), anterior trunk (7.0%), neck (2.6%) and abdomen (0.9%).
Histopathological examination revealed that the most common subtype was superficial spreading melanoma (53.9%), followed by nodular melanoma (32.2%). Other subtypes included acral melanoma (5.2%), lentiginous melanoma (2.6%) and nevoid melanoma (2.6%), while desmoplastic melanoma (1.7%), melanoma not otherwise specified (0.9%) and melanoma arising on a dysplastic compound nevus (0.9%) were rarely observed.
The median tumor thickness measured as Breslow thickness was 2.8 mm.
Tumor staging according to the AJCC classification showed that T4 melanomas were the most frequent (41 cases, 35.7%), followed by T3 tumors (28 cases, 24.3%). Early-stage tumors were less common, with 22 cases (19.1%) classified as T1, 17 cases (14.8%) as T2 and seven cases (6.1%) corresponding to melanoma in situ (Tis).
For analytical purposes, tumors were categorized into thin melanomas (≤2 mm) and thick melanomas (>2 mm). Based on this classification, 46 patients (40.0%) had thin melanoma, while 69 patients (60.0%) presented with thick melanoma.
Histopathological examination revealed ulceration in 51 cases (44.3%), whereas 64 tumors (55.7%) were non-ulcerated.
Data regarding mitotic activity were available for 99 of the 115 patients included in the study. Among these cases, 91 tumors (91.9%) showed mitotic activity, while eight tumors (8.1%) had no detectable mitoses.
During the study period, 43 out of 115 patients (37.4%) developed metastatic disease, while the remaining patients showed no evidence of metastases during follow-up.
Factors associated with melanoma thickness
The association between sex and melanoma thickness (≤2 mm vs >2 mm) was assessed using the chi-square test. No statistically significant association was identified [χ²(1) = 3.34, p = 0.068].
Age differed significantly between melanoma thickness groups. The median age was 54.5 years (IQR 48.8–68.0) in patients with thin melanoma and 63.0 years (IQR 53.5–71.0) in those with thick melanoma (Mann–Whitney U = 1211, Z = −2.15, p = 0.032).
Melanoma thickness did not differ significantly according to tumor anatomical location [χ²(6) = 6.14, p = 0.408].
A statistically significant association was observed between histological subtype and melanoma thickness [χ²(2) = 12.87, p = 0.002, Cramer's V = 0.335]. Nodular melanoma was more frequently associated with thick tumors, with 83.8% of nodular melanomas presenting a Breslow thickness >2 mm, compared with 48.4% of superficial spreading melanomas and 50.0% of other histological subtypes.
A strong association was observed between ulceration and melanoma thickness [χ²(1) = 22.57, p < 0.001, Cramer's V = 0.443]. Thick melanomas were present in 84.3% of ulcerated tumors, compared with 40.6% of non-ulcerated tumors.
Mitotic activity was also significantly associated with melanoma thickness [χ²(1) = 9.84, p = 0.002, Cramer's V = 0.315]. Thick melanomas were present in 68.1% of tumors with increased mitotic activity, compared with 12.5% among tumors with low or absent mitotic activity.
Patients with metastatic disease more frequently presented with thick melanomas, with 79.1% of metastatic cases having a Breslow thickness >2 mm, compared with 50.0% among patients without metastases [χ²(1) = 3.997, p = 0.046].
Factors associated with melanoma thickness are presented in Table 2.
Multivariate analysis
A multivariate logistic regression model was performed to identify predictors of thick melanoma (>2 mm). Mitotic activity emerged as an independent predictor of tumor thickness [odds ratio (OR) = 1.75, p < 0.001], while ulceration showed borderline significance (OR = 4.14, p = 0.050). Sun exposure pattern, age and sex were not significantly associated with melanoma thickness.
Additional logistic regression models were performed to evaluate whether sun exposure predicted tumor ulceration, mitotic activity, or metastatic disease. None of these models showed significant associations, and all demonstrated low explanatory power (Nagelkerke R² values ranging from 0.005 to 0.058).
Overall, sun exposure pattern was associated with melanoma location but not with markers of tumor aggressiveness.
TABLE 1.
Baseline demographic and clinicopathological characteristics of patients with cutaneous melanoma
FIGURE 1.
Distribution of melanoma anatomical location according to sun exposure pattern
TABLE 2.
Factors associated with melanoma thickness (≤2 mm vs >2 mm)
DISCUSSION
The aim of this study was to evaluate the association between sun exposure patterns and the clinicopathological characteristics of cutaneous melanoma, with particular emphasis on tumor thickness and markers of tumor aggressiveness. To address this objective, we conducted an observational cohort study including 115 consecutive patients with histologically confirmed primary cutaneous melanoma treated between 1 January 2018 and 31 December 2022 in our department. The study included 57 men (49.6%) and 58 women (50.4%); sun exposure pattern did not differ significantly by sex [χ²(1) = 1.47, p = 0.225].
Among our study population, 48 patients (41.7%) reported chronic sun exposure, while 67 patients (58.3%) reported intermittent sun exposure. Sun exposure patterns have been associated with several clinical characteristics of melanoma. In the literature chronic cumulative sun exposure is associated with Lentigo Maligna Melanoma (LMM), whereas Superficial Spreading Melanoma (SSM) and Nodular Melanoma (NM) typically develop on intermittently exposed skin in younger individuals (7). Higher sunbathing frequency after the age of 20 was associated with a lower risk of thick melanoma (8). Similar findings were reported by Gandini et al, who observed an inverse association between sunny holidays prior to diagnosis and unfavorable prognostic factors such as Breslow thickness and ulceration. Nevertheless, the authors cautioned that these results do not imply a causal relationship between sun exposure and melanoma prognosis (9). In our study cohort, no significant associations were observed between sun exposure pattern and histological subtype, ulceration, mitotic activity, metastatic disease, or melanoma thickness (all p > 0.05). Logistic regression analyses assessing whether sun exposure predicted tumor ulceration, mitotic activity, or metastatic disease also showed no statistically significant associations.
Among the study population, 83 patients (72.2%) resided in urban areas, while 32 patients (27.8%) lived in rural areas. No statistically significant association was identified between sun exposure pattern and living environment in our cohort [χ²(1) = 2.01, p = 0.157]. In contrast, several previous studies have reported higher odds of skin cancer among rural populations, often attributed to greater occupational and recreational sun exposure as well as a higher prevalence of sun-related risk behaviors in rural settings (10, 11). Moreover, research conducted in Cluj and Bihor counties, Romania, demonstrated that individuals residing in rural areas reported a significantly higher frequency of more than ten lifetime sunburn episodes compared with urban residents (12).
The median tumor thickness measured as Breslow thickness was 2.8 mm. For analytical purposes, tumors were categorized as thin melanomas (≤2 mm) and thick melanomas (>2 mm). Based on this classification, 46 patients (40.0%) had thin melanoma, while 69 patients (60.0%) presented with thick melanoma. This distribution contrasts with findings reported in other populations. For example, those reported in a cohort study from Australia by Pandeya et al, in which the majority of melanomas were diagnosed at an early stage, with 82.2% of tumors presenting a Breslow thickness ≤1 mm and only 8% exceeding 2 mm (13). This difference may partly reflect the impact of long-standing public awareness campaigns and well-established skin cancer screening programs in Australia, which facilitate earlier detection of melanoma.
Increased TNM T stage at diagnosis is strongly associated with worse prognosis. In a large retrospective cohort study, Seringe et al demonstrated that the 30-year cumulative incidence of melanoma-specific mortality increased progressively with tumor thickness, reaching 7.1% for T1, 21.6% for T2, 34.2% for T3 and 44.3% for T4 tumors (14).
A multivariate logistic regression model was performed to identify predictors of thick melanoma (>2 mm). Mitotic activity emerged as an independent predictor of tumor thickness (OR = 1.75, p < 0.001), while ulceration showed borderline significance (OR = 4.14, p = 0.050). In contrast, sun exposure pattern, age, and sex were not significantly associated with melanoma thickness. These findings suggest that tumor thickness may be more strongly influenced by intrinsic tumor characteristics than by patterns of sun exposure. Similar observations have been reported in previous studies. Rodríguez-Lomba et al found that tumor diameter and lesion palpability were the only clinical variables significantly associated with increased melanoma thickness (P = .001 for both) (15).
A review by A.M. Forsea highlights marked East–West disparities in melanoma across Europe. Central and Eastern European countries have lower incidence but higher mortality and poorer survival compared to Western Europe, largely due to more frequent diagnosis at advanced stages. Slower declines in fatality rates are attributed to limited public awareness, delayed presentation, under-resourced healthcare systems, and historically weaker cancer registries and early detection programs (16). Our findings are consistent with this regional pattern, as the majority of melanomas in our cohort were diagnosed at a relatively advanced stage.
Sun exposure pattern was significantly associated with tumor anatomical location in our cohort [χ²(6) = 85.11, p < 0.001; Cramer's V = 0.860]. Chronic exposure was most frequently reported among patients with melanomas of the posterior trunk, whereas intermittent exposure was more common in melanomas of the lower limbs. This distribution differs partially from patterns reported in previous epidemiological studies, where intermittent exposure has often been associated with trunk melanomas. These findings may nevertheless be interpreted in the context of the divergent pathway model proposed by Whiteman et al, which suggests that melanoma may arise through at least two etiological pathways. In nevus-prone individuals, melanoma tends to develop on the trunk following early-life sun exposure, whereas individuals with a lower propensity to develop nevi require cumulative and chronic sun exposure, leading to melanomas arising predominantly on chronically sun-exposed sites such as the head and neck. Burning and tanning represent markers of sun sensitivity that may facilitate the early initiation of melanocytes along these pathways (17).
The differences observed in our cohort may reflect regional variations in sun exposure behaviors or population characteristics. Similar findings have been reported in a pooled analysis of 15 case-control studies conducted by Chang et al, including 5700 melanoma cases and 7216 controls, which showed that recreational sun exposure was associated with an increased risk of melanoma on the trunk (pOR = 1.7; 95% CI: 1.4–2.2) and limbs (pOR = 1.4; 95% CI: 1.1–1.7), but not on the head and neck (18).
Sunburn history represents a well-established risk factor for cutaneous melanoma. Although sunburn history was not directly analyzed as a predictor of tumor thickness in our study, previous Romanian data suggest that intense intermittent UV exposure is common in this population. In a Romanian cohort, Apostu et al (2025) reported a high prevalence of sunburn episodes among patients with melanoma, with 62.8% experiencing more than ten lifetime sunburn episodes. These findings suggest that intense intermittent UV exposure may represent an important modifiable risk factor in this population and highlight the need for improved preventive strategies aimed at reducing sunburn incidence.
Collectively, these findings support the concept that while ultraviolet radiation is a well-established risk factor for melanoma development, it does not appear to directly influence the biological aggressiveness of the tumor once it has developed. Instead, tumor-specific characteristics such as mitotic activity, ulceration, and clinical morphology seem to be more closely related to Breslow thickness. This study has several limitations, including its retrospective design, single-center setting, and relatively small sample size. In addition, sun exposure patterns were based on self-reported data, which may introduce recall bias. Future multicenter prospective studies with larger cohorts are needed to further investigate the relationship between sun exposure and melanoma characteristics.
CONCLUSIONS
In conclusion, sun exposure pattern was associated with the anatomical distribution of cutaneous melanoma but showed no significant relationship with markers of tumor aggressiveness. Tumor thickness was primarily linked to intrinsic histopathological characteristics such as ulceration and mitotic activity, suggesting that melanoma progression may be driven more by tumor biology than by patterns of ultraviolet exposure.
Ethical statement
This study was approved by the Ethics Commission of "Prof. Dr. Agrippa Ionescu" Clinical and Emergency Hospital, Bucharest, Romania (Approval Number 21126, dated January 17, 2022).
Data availability
The datasets used and/or analyzed during the current study are available upon reasonable request from the corresponding author.
Conflicts of interest
none declared.
Financial support
none declared.
Acknowledgements
This study forms part of the doctoral research of Dr. Luiz-Sorin Vasiu, PhD candidate at the Department of Plastic Surgery, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analyzed during the current study are available upon reasonable request from the corresponding author.