Clinical Staging, Histopathological Features and Treatment Outcomes in Malignant Melanoma: A 10-Year Retrospective Single-Center Study

Malignant melanoma is an aggressive form of skin cancer that originates from the malignant transformation of melanocytes, the pigment-producing cells in the epidermis. Although its incidence is relatively low in Turkey, melanoma contributes substantially to skin cancer-related mortality due to its high metastatic potential and frequent late-stage diagnosis.^[1] Early detection is crucial for improving prognosis, as patients diagnosed in primary care settings are more likely to present with early-stage disease and have better outcomes.^[2] Prognosis is strongly influenced by clinical stage at diagnosis, anatomical location of the lesion and histopathological features such as Breslow thickness, Clark level, ulceration, mitotic index and growth pattern.^[3] These parameters not only reflect tumor biology but also guide treatment strategies.

This study aimed to retrospectively assess the clinical staging, histopathological characteristics and treatment outcomes of patients diagnosed with malignant melanoma at Van YüzüncüYıl University Hospital over a 10-year period. By presenting single-center data from a low-incidence region, this study aims to contribute to the limited body of national data on melanoma in Turkey.

This retrospective descriptive study included adult patients (≥18 years old) diagnosed with malignant melanoma at Van YüzüncüYıl University Hospital between January 2010 and December 2019. A totalof 95 patientswereidentifiedthroughhospitalmedicalrecords. Histopathological parameters such as Breslow thickness, Clark level, ulceration, mitotic index and growth pattern were evaluated when available. Tumor staging, including histopathological assessment, lymph node involvement and distant metastasis, was performed according to the AJCC T, N and M classifications (Tables 1–3).

Demographic and clinical data were collected, including age, sex, year of diagnosis, melanoma subtype, tumor location and clinical stage according to the 2017 American Joint Committee on Cancer (AJCC) staging system.^[4] The distribution of clinical stages is summarized in Table 4. Treatment strategies and survival outcomes were documented for all patients. Surgical margin assessments were performed in accordance with World Health Organization (WHO) guidelines (Table 5). Treatment protocols administered to each patient subgroup are summarized in Table 6. Statistical analysis was conducted using IBM SPSS Statistics, version 25.0. A p-value <0.05 was considered statistically significant.

All statistical analyses were performed using IBM SPSS Statistics, version 25.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were used to summarize the demographic and clinical data. Categorical variables were expressed as frequencies and percentages and continuous variables as mean±standard deviation. Kaplan-Meier survival analysis was used to estimate overall survival and differences between groups were compared using the log-rank test. A *p*-value <0.05 was considered statistically significant.

This study included 95 patients, comprising 50 males (52.6%) and 45 females (47.4%), with a mean age of 56.9±16.4 years (range: 24-90). Detailed demographic characteristics are presented in Table 7.

Melanoma Subtypes and Localization Cutaneous melanoma was the most common subtype (81.1%, n=73), followed by ocular (10.0%, n=9) and mucosal melanoma (8.9%, n=8). In five patients, the primary tumor site could not be identified. Nodular melanoma was the most prevalent histological subtype (46.7%, n=28), followed by lentigo maligna (21.7%, n=13), superficial spreading melanoma (13.3%, n=8) and acral lentiginous melanoma (13.3%, n=8). Information on histological subtype was missing in 35 cases. The extremities were the most frequent tumor location (33.7%, n=32), with the lower limbs accounting for 71.8% of these cases, followed by the head and neck region (22.1%) and the trunk (9.5%).

Breslow thickness was available in 43 patients: 24.5% had tumors

≤1 mm, 18.9% were 1.01-2.00 mm, 11.3% were 2.01-4.00 mm and 45.3% were >4 mm. Clark level was documented in 42 patients, with level IV being most common (54.7%). Ulceration was present in 39.7% of evaluable cases (n=27/68). Vertical growth was observed in 78.6% of cases (n=48/61). The mean mitotic index was 13.39±17.12. Pathological features are summarized in Table 8. Staging and Survival Outcomes Based on AJCC 2017 criteria, 43.2% of cutaneous melanoma patients were diagnosed at stage IV, 32.8% at stage II, 19.4% at stage I and 4.4% at stage III. The median follow-up period was 24.4 months (range: 0.1-222.8). During follow-up, 35.7% (n=34) of patients died. The median overall survival among deceased patients was 11.3 months, with a mean survival of 20.6 months. The Kaplan-Meier curve for overall survival is shown in Figure 1. The 5-year survival rate was 63.6%.

Figure 1:
Kaplan-Meier overall survival curve for all patients with malignant melanoma (n=95). The median overall survival was 11.3 months (95% CI: 8.5-14.2). Censored data are indicated with vertical ticks.

Survival was significantly associated with melanoma subtype (*p*<0.001). Median survival was 24 months for cutaneous melanoma, 11 months for mucosal melanoma and not reached for ocular melanoma.^[5] The distribution of clinical stages at initial diagnosis is illustrated in Figure 2. Among cutaneous subtypes, mean survival was 27.1 months (acral lentiginous), 26.7 months (lentigo maligna), 24.4 months (superficial spreading) and 13.5 months (nodular). Lesion location (*p*<0.05), lymph node involvement (median survival 24.4 months vs. 6.27 months) and distant metastasis (*p*<0.05) were also significant prognostic factors.

Figure 2:
Distribution of patients by AJCC clinical stage at initial diagnosis. Stage IV was the most frequently observed (43.2%), followed by Stage III (25.3%). The percentage of patients in each stage is shown.

Five patients received adjuvant interferon therapy. Among 17 patients with metastatic cutaneous melanoma, 11 were treated with temozolomide, 4 with nivolumab, 4 with ipilimumab and 2 with vemurafenib. All ocular melanoma cases underwent surgical enucleation. Treatment strategies are summarized in Table 9.

A notable limitation of our study was the incomplete documentation of histopathological data, such as missing values for Breslow thickness and histological subtype in a significant proportion of patients. Additionally, as a retrospective study conducted at a single tertiary center, selection and information bias may have influenced the results. Lack of access to novel therapies and variability in treatment protocols over the 10-year study period may also limit the generalizability of our findings. Recent clinical trials have demonstrated improved survival with immunotherapy and targeted therapies such as nivolumab, ipilimumab, and vemurafenib in advanced melanoma cases. ^[6–10]

This study provides a comprehensive overview of malignant melanoma cases diagnosed over a decade at a tertiary center in Eastern Turkey. Nodular melanoma emerged as the most prevalent histological subtype, with a substantial proportion of patients presenting at advanced clinical stages. Tumor localization and disease stage were identified as key prognostic factors influencing survival outcomes.

These findings underscore the critical importance of early detection, standardized histopathological evaluation and equitable access to contemporary systemic therapies. Public health strategies aimed at enhancing awareness and facilitating timely dermatological consultations, along with national policies to improve the availability of targeted and immunotherapeutic agents, are essential for optimizing outcomes in similarly low-incidence regions.

The authors thank the medical records and pathology departments of Van Yüzüncü Yıl University Hospital for their support in data retrieval and verification.