European consensus-based interdisciplinary guideline for diagnosis, treatment and prevention of actinic keratoses, epithelial UV-induced dysplasia and field cancerization on behalf of European Association of Dermato-Oncology, European Dermatology Forum, European Academy of Dermatology and Venereology and Union of Medical Specialists (Union Européenne des Médecins Spécialistes).

A collaboration of multidisciplinary experts from the European Association of Dermato-Oncology, the European Dermatology Forum, the European Academy of Dermatology and Venereology, and the European Union of Medical Specialists was formed to develop European recommendations on AK diagnosis and treatment, based on current literature and expert consensus. This guideline addresses the epidemiology, diagnostics, risk stratification and treatments in immunocompetent as well as immunosuppressed patients. Actinic keratoses (AK) are potential precursors of cutaneous squamous cell carcinoma (cSCC) and display typical histopathologic and immunohistochemical features of this malignancy in an early stage. They can develop into cSSC in situ and become invasive in a low percentage of cases. AK is the most frequent neoplasia in white populations, frequently occurring within a cancerous field induced by ultraviolet radiation. Since it cannot be predicted, which lesion will progress to cSCC and when treatment is usually recommended. The diagnosis of AK and field cancerization is made by clinical examination. Dermatoscopy, confocal microscopy, optical coherence tomography or line-field confocal-OCT can help in the differential diagnosis of AK and other skin neoplasms. A biopsy is indicated in clinically and/or dermatoscopically suspicious and/or treatment-refractory lesions. The choice of treatment depends on patients' and lesion characteristics. For single non-hyperkeratotic lesions, the treatment can be started upon patient's request with destructive treatments or topical treatments. For multiple lesions, field cancerization treatment is advised with topical treatments and photodynamic therapy. Preventive measures such as sun protection, self-examination and repeated field cancerization treatments of previously affected skin areas in high-risk patients are advised.

Dermatoscopic and clinical features of congenital or congenital-type nail matrix nevi: A multicenter prospective cohort study by the International Dermoscopy Society.

BACKGROUND: Congenital nail matrix nevi (NMN) are difficult to diagnose because they feature clinical characteristics suggestive of adult subungual melanoma. Nail matrix biopsy is difficult to perform, especially in children. OBJECTIVE: To describe the initial clinical and dermatoscopic features of NMN appearing at birth (congenital) or after birth but before the age of 5 years (congenital-type). METHODS: We conducted a prospective, international, and consecutive data collection in 102 hospitals or private medical offices across 30 countries from 2009 to 2019. RESULTS: There were 69 congenital and 161 congenital-type NMNs. Congenital and congenital-type NMN predominantly displayed an irregular pattern of longitudinal microlines (n = 146, 64%), reminiscent of subungual melanoma in adults. The distal fibrillar ("brush-like") pattern, present in 63 patients (27.8%), was more frequently encountered in congenital NMN than in congenital-type NMN (P = .012). Moreover, congenital NMN more frequently displayed a periungual pigmentation (P = .029) and Hutchinson's sign (P = .027) than did congenital-type NMN. LIMITATIONS: Lack of systematic biopsy-proven diagnosis and heterogeneity of clinical and dermatoscopic photographs. CONCLUSION: Congenital and congenital-type NMN showed worrisome clinical and dermatoscopic features similar to those observed in adulthood subungual melanoma. The distal fibrillar ("brush-like") pattern is a suggestive feature of congenital and congenital-type NMN.

Time to Procedure, Nuclear Imaging and Clinicopathological Characteristics as Predictive Factors for Sentinel Lymph Node Metastasis in Cutaneous Melanoma: A Single-Center Analysis.

OBJECTIVE: Sentinel lymph node (SLN) biopsy is a widely accepted staging procedure for cutaneous melanoma patients who are at risk of clinically occult nodal metastases. Numerous predictive factors for regional lymph node metastases have been identified; however, few have been found to be reproducibly significant. Also, the role of blue dye in identification was questioned in recent trials. Time to procedure was also found to be predictive of SLN positivity, but this was not confirmed in other studies. In our study, predictive factors for metastatic involvement of SLN were analyzed, together with the role of addition blue dye in imaging on detection rate and false-negative SLN rate. An impact of time interval to procedure on the rate of SLN positivity was also explored. METHODS: Data analysis was done in 362 cutaneous melanoma patients who underwent lymphoscintigraphy and SLN biopsy at our institution from 2010 to 2016, with a median follow-up of 29 months (1-98 months). To delineate the relation of each variable (demographical, time to procedure, and clinical and pathological variables, as well as the presence of in-transit nodes, the number of draining basins, and SLN localization on scintigraphy) with positive SLN status, we used univariate logistic regression with odds ratios representing effect size. RESULTS: Metastatic involvement SLN was found in 67 (18.8%) of 356 patients. Detection rate was similar with or without further intraoperative SLN identification with blue dye (98.8% vs 98.17%, P > 0.05). Time to procedure was not associated with higher SLN positivity rate (P > 0.05). In univariate analysis, Breslow thickness (P < 0.001), primary ulceration lesion (P = 0.001), and lymphovascular invasion (P = 0.006) were strongly correlated with SLN positivity, as well as the site of primary tumor (P = 0.024), tumor-infiltrating lymphocytes (TILs) (P = 0.021), and sex (P = 0.026). In multivariate analysis, Breslow thickness and TILs were found to be significant independent predictors of SLN status (P < 0.05). CONCLUSIONS: Addition of blue dye did not improve SLN detection rate; time to procedure was not found to be associated with higher SLN biopsy positivity rates. Breslow thickness and TILs, as a marker of immune response to tumor, were consistently found to be significant independent predictors of SLN status.

A subpopulation that may correspond to granulocytic myeloid-derived suppressor cells reflects the clinical stage and progression of cutaneous melanoma.

Seventy-eight melanoma patients and 10 healthy individuals were examined. Follow-up examinations of all melanoma patients were performed regularly every three months. Myeloid-derived suppressor cells (MDSC) were defined as lineage negative (CD3(-), CD19(-), CD56(-)), HLA-DR(-/low), CD11b(+) and CD33(+). Classification of granulocytic (GrMDSC) and monocytic (MoMDSC) subsets was based on the CD15 and CD14 expression, respectively. Unlike the MoMDSC, that were present in 60% of healthy controls and 15% of melanoma patients, the GrMDSC were present in all examined participants, and the melanoma patients were found to have statistically higher frequencies compared with healthy controls. Accordingly, we kept focused on GrMDSC frequencies in relation to the melanoma stages and course of the disease. The GrMDSC values are highest in stage IV melanoma patients, with statistical significance compared with stages IA, IB, IIA and IIB. Patients with progression had statistically higher GrMDSC counts comparing with those with stable disease (P = 0.0079). Patients who had progression-free interval (PFI) < 12 months showed significantly higher GrMDSC values compared with those with PFI > 12 months (P = 0.0333). GrMDSC showed significant negative correlation with PFI intervals (P = 0.0095). The GrMDSC subset was predominant in all our patients. We confirmed that GrMDSC do accumulate early in the peripheral blood of melanoma patients and their frequencies correlate narrowly with the clinical stage and the spread of the disease. The increase in GrMDSC frequencies correlates well with a progressive disease and could be considered a potential predictive biomarker of high-risk melanoma cases that are more likely to have a shorter PFI.

Lymphoscintigraphy and sentinel lymph node biopsy, in cutaneous melanoma staging and treatment decisions.

OBJECTIVE: Sentinel lymph node biopsy (SLNB) is a widely accepted method in the management of clinically localized cutaneous melanomas. The aim of this study was to report the results on patients scheduled for preoperative lymphoscintigraphy and SLNB for staging and further treatment planning. SUBJECTS AND METHODS: Two hundred and one patients (115 male and 86 female, median age 57 years, range 9-81) with cutaneous melanoma having undergone SLB at Military Medical Academy between November 2010 and October 2014, were recruited for retrospective study. Dual labeling method (Tc-99m Nanocolloid (blue dye) was used. In order to delineate the relation between patients' tumors and scintigraphic characteristics with positive SLN findings, we examined all variables by univariate logistic regression with odd ratios representing the size effect. RESULTS: The overall identification rate of SLN was 98.5%. One or more positive SLN were seen in 47 (23.4%) of the patients. Drainage to one regional basin was noticed in 176 (88%) and multiple drainage regions, up to three, was noticed in 24 patients (12%). Transit lymph nodes were detected in 20 patients (10%). The characteristics that were assotiated significatly with sentinel lymph node metastases were Breslow thickness, nodular melanoma histological subtype and acral localization. CONCLUSION: Besides the well established primary tumor thickness being a predictor of SLN malignancy, we observed: acral body site location and nodular melanoma histological subtype to be significant independent factors in increasing the risk for regional metastases. Our results suport the clinical usefulness of SLNB within a multidisciplinary approach (dermatooncology, plastic/head and neck surgery, pathology, nuclear medicine), as a reliable method in staging and for treatment planning in melanoma patients.

Solitary Basaloid Follicular Hamartoma: A Report of Two Cases.

Basaloid follicular hamartoma (BFH) is rare benign follicular malformation that is often clinically misdiagnosed. Patients with BFH demonstrate a variety of clinical manifestations and associated abnormalities. BFH may be a familial, congenital, or acquired condition with localized or generalized distribution. Several clinical variants of generalized BFH are known, and they can be associated with a diverse spectrum of abnormalities. Herein, we report two cases of solitary BFH in pediatric patients, both documented dermoscopically.

Pembrolizumab-induced lichen planus in patients with metastatic melanoma: a report of two cases and prognostic implications of cutaneous immune-related adverse events.

Patients receiving immune checkpoint inhibitors (ICIs) commonly experience cutaneous immune-related adverse events (irAEs). We present two cases, a 51-year-old female and a 70-year-old male, that were undergoing treatment with pembrolizumab for metastatic melanoma and developed scaly, erythematous papules on their skin. Following skin biopsies, histological analysis confirmed the diagnosis of lichen planus. In the first patient, acitretin at a dosage of 25 mg/day was administered for 6 months, resulting in complete resolution of lichen lesions. Imaging scans showed no signs of melanoma. The second patient was treated with topical betamethasone dipropionate ointment for several weeks, which led to a favorable therapeutic response. During follow-up, a thoracic CT scan showed several micronodular lesions in the right lung, whereas brain and abdomen CT scans showed no signs of the disease. Lichen planus is not a commonly reported irAE in patients treated with ICIs. This report underscores the importance of conducting skin biopsies in patients receiving ICI therapy and highlights the potential prognostic importance of skin irAEs in patients with melanoma receiving such treatment.

European consensus-based interdisciplinary guideline for diagnosis and treatment of basal cell carcinoma-update 2023.

Basal cell carcinoma (BCC) is the most common malignant tumour in white populations. Multidisciplinary experts from European Association of Dermato-Oncology (EADO), European Dermatology Forum, European Society for Radiotherapy and Oncology (ESTRO), Union Européenne des Médecins Spécialistes, and the European Academy of Dermatology and Venereology developed updated recommendations on diagnosis and treatment of BCC. BCCs were categorised into 'easy-to-treat' (common) and 'difficult-to-treat' according to the new EADO clinical classification. Diagnosis is based on clinico-dermatoscopic features, although histopathological confirmation is mandatory in equivocal lesions. The first-line treatment of BCC is complete surgery. Micrographically controlled surgery shall be offered in high-risk and recurrent BCC, and BCC located on critical anatomical sites. Topical therapies and destructive approaches can be considered in patients with low-risk superficial BCC. Photodynamic therapy is an effective treatment for superficial and low-risk nodular BCCs. Management of 'difficult-to-treat' BCCs should be discussed by a multidisciplinary tumour board. Hedgehog inhibitors (HHIs), vismodegib or sonidegib, should be offered to patients with locally advanced and metastatic BCC. Immunotherapy with anti-PD1 antibodies (cemiplimab) is a second-line treatment in patients with a progression of disease, contraindication, or intolerance to HHI therapy. Radiotherapy represents a valid alternative in patients who are not candidates for or decline surgery, especially elderly patients. Electrochemotherapy may be offered when surgery or radiotherapy is contraindicated. In Gorlin patients, regular skin examinations are required to diagnose and treat BCCs at an early stage. Long-term follow-up is recommended in patients with high-risk BCC, multiple BCCs, and Gorlin syndrome.

Regional lymph node metastases in cutaneous melanoma: a single-center analysis from southeast europe.

OBJECTIVE: Sentinel lymph node biopsy is the standard of care for nodal staging in clinically node-negative melanoma patients. Our goal was to present 10-year results of sentinel lymph node biopsy at our institution and to evaluate the clinicopathologic factors as potential predictors of sentinel lymph node and non-sentinel lymph node metastatic involvement in patients with cutaneous melanoma. METHODS: We have analyzed clinicopathologic and lymphoscintigraphic characteristics in 420 patients with cutaneous melanoma who underwent sentinel lymph node biopsy between 2010 and 2019. In addition, we have examined the results of group of patients with positive sentinel lymph node biopsy undergoing complete lymph node dissection. RESULTS: The overall detection rate of sentinel lymph node biopsies was 97.1%, of which 18.8% was metastatic. Drainage to one regional basin was seen in 345 patients (83.1%) and to multiple drainage regions in 71 patients (17%). In-transit lymph nodes were detected in 20 patients. On univariate logistic regression analysis, male gender, primary tumor thickness with nodular histology, acral location, presence of ulceration, and the number of nodes harvested were significantly associated with sentinel lymph node biopsy status (p < 0.05). On multivariate analysis, the Breslow thickness was the only independent predictor of sentinel lymph node biopsy status. The metastases in non-sentinel lymph node found in 26 patients with positive sentinel lymph node (35.6%) correlated on univariate, as well as on multivariate logistic regression, with tumor subtype and number of sentinel lymph node harvested. CONCLUSIONS: In addition to the well-established primary tumor thickness as a predictor of sentinel lymph node biopsy positivity, we observed acral location and nodular melanoma subtype to significantly enhance the risk of metastases in sentinel lymph node(s). Primary tumor histology and number of nodes harvested were the only statistically significant variables predicting the non-sentinel lymph node status on multivariate analysis. Lymphoscintigraphy imaging characteristics were not significantly associated with sentinel lymph node status.

DNMT1 and DNMT3B genetic polymorphisms affect the clinical course and outcome of melanoma patients.

The aberrant DNA methylation plays a critical role in a number of different malignancies, including melanoma. DNA methylation is catalyzed by DNA methyltransferases (DNMTs), involved in methylation maintenance (DNMT1) and de novo DNA methylation (DNMT3A and DNMT3B). The current study investigated the association of genetic variants in the DNMT1 and DNMT3B with the clinicopathologic features and the clinical course of melanoma patients. In the present study, DNMT1 (rs2228612, rs2228611, and rs2114724) and DNMT3B (rs406193 and rs2424932) polymorphisms were examined in 123 melanoma patients. Single nucleotide polymorphisms were assessed using TaqMan SNPs Genotyping Assays according to the manufacturer's protocols. The carriers of the variant genotype of DNMT1 rs2228612 had poorer overall survival and recurrence-free survival, (P = 0.000 and 0.000, respectively), and an increased risk for adverse outcome [hazard ratio (HR) = 6.620, 95% confidence interval (CI): 2.214-19.791, P = 0.001]. DNMT1 rs2228612 was also associated with ulceration (P = 0.045), nodal status (P = 0.030), progression (P = 0. 007), and stage of disease (P = 0.003). Univariate analysis indicated that tumor-infiltrating lymphocytes could be a marker of good prognosis in melanoma patients (HR = 0.323, 95% CI: 0.127-0.855, P = 0.025), whereas the genotype distribution of the DNMT3B rs406193 polymorphism correlated significantly with the presence of tumor-infiltrating lymphocytes (P = 0.012). The multivariate analysis showed that the DNMT1 rs2228612 polymorphism (HR = 12.126, 95% CI: 2.345-62.715, P = 0.003) is an independent predictor of poor overall survival in melanoma patients. As expected, disease progression was also found to be an independent prognostic factor in melanoma patients (HR = 37.888, 95% CI: 3.615-397.062, P = 0.002). DNMT1 rs2228612 was found to be an independent predictor of poor overall survival in melanoma patients. DNMTs polymorphisms could serve as a potential target for novel therapeutic approaches.

Association Between Oxidative Stress and Melanoma Progression.

BACKGROUND: Overproduction of free radicals accompanied with their insufficient removal/neutralization by antioxidative defense system impairs redox hemostasis in living organisms. Oxidative stress has been shown to be involved in all the stages of carcinogenesis and malignant melanocyte transformation. The aim of this study was to examine association between oxidative stress development and different stages of melanoma. METHODS: The measured oxidative stress parameters included: superoxide anion radical, total and manganese superoxide dismutase, catalase and malondialdehyde. Oxidative stress parameters were measured spectrophotometrically in serum samples from melanoma patients (n=72) and healthy control subjects (n=30). Patients were classified according to AJCC clinical stage. RESULTS: Average superoxide anion and malondialdehyde concentrations were significantly higher in melanoma patients than in control group, with the highest value of superoxide anion in stage III, while malondialdehyde highest value was in stage IV. The activity of total and manganese superoxide dismutase was insignificantly higher in melanoma patients than in control group, while catalase activity was significantly higher. The highest activity of total activity of manganese superoxide dismutase was in stage IV. Catalase activity was increasing with the disease progression achieving the maximum in stage III. CONCLUSION: Results of our study suggest that melanoma is oxidative stress associated disease, as well as deteriorated cell functioning at mitochondrial level.

Collision skin lesions-results of a multicenter study of the International Dermoscopy Society (IDS).

BACKGROUND: Collision lesions as two independent and unrelated skin tumors often manifest an atypical morphology. OBJECTIVE: To determine the combinations of collision skin lesions (CSLs). METHODS: Twenty-one pigmented lesion clinics in nine countries included 77 histopathologically proven CSLs in this retrospective observational study. RESULTS: Seventy-seven CSLs from 75 patients (median age 59.8 years) were analyzed; 24.7% of CSLs were located on the head and neck area, 5.2% on the upper extremities, 48.1% on the trunk, and 11.7% on the lower extremities; 40.3% revealed a melanocytic component (median age 54.7 years), followed by 45.5% with a basal cell carcinoma (BCC) (median age 62.4 years) and 11.7% with a seborrheic keratosis (median age 64.7 years). CSLs with a BCC component were more often found on the head and neck area compared to tumors with a melanocytic component (34.3% versus 16.1%). Lesions with a melanocytic component were more often detected on the trunk compared to lesions with a BCC (64.5% versus 37.1%). Patients with CSLs with epidermal-epidermal cell combination were older than patients with epidermal-dermal cell combination (63 versus 55.2 years), were more often male than female (63% versus 43.3%), more often had the lesion on the head and neck area (32.6% versus 13.3%), and less often on the upper (2.2 % versus 10%) or lower extremities (8.7% versus 16.6%). CONCLUSIONS: CSLs consist of a heterogeneous group of lesions of varying cell types. They are associated with advancing age and cumulative UV-exposure. CSLs manifest a complex morphology making it challenging to diagnose correctly.

High Interleukin 27 Production is Associated with Early Clinical Stage and Localized Disease in Patients with Melanoma.

BACKGROUND: The immune response in patients with melanoma is an important focus of research due to the tumor's resistance and immunotherapy possibilities. IL-27 is one of the cytokines with antitumor properties. The role of IL-27 in the pathogenesis of melanoma is still unclear. The aim of this study was to examine the association between serum IL-27 levels and the clinical parameters of melanoma patients. METHODS: The IL-27 concentration was determined by com mercial ELISA in serum samples from melanoma patients (n=72) and healthy control subjects (n=44). Patients were classified according to AJCC clinical stage, TNM stage, the length of progression-free interval (PFI) and the extent of the disease (localized or widespread). RESULTS: Average IL-27 values were increased in patients with early stages of melanoma compared to patients with terminal stages and control values. The highest IL-27 concentration was found in stage IIa. Patients in stages III and IV had significantly lower values of IL-27 compared to control. Patients with localized melanoma and shorter PFI had insignificantly increased IL-27 levels compared to patients with widespread disease and longer PFI. Patients with metastatic disease and stage TNM4 had significantly lower average IL-27 values compared to control. Patients with high production of IL-27 (>1000 pg/mL) were most numerous in IIa AJCC stage, with initial tumor size TNM2 and in the group of patients with localized disease. CONCLUSIONS: High levels of IL-27 in patients with melanoma are associated with the initial stages and lo calized disease.

Association of vascular endothelial growth factor expression with patohistological parameters of cutaneous melanoma.

BACKGROUND/AIM: Melanoma is the most aggresive malignant tumor of the skin. Contradictory data was published on vascular endothelial growth factor (VGEF) in tumor samples and its role in skin melanoma progression and prognosis. The aim of this study was to investigate the significance of VEGF expression as a prognostic parameter in melanoma. METHODS: The experimental group included 81 patients with primary skin melanomas treated from 2009 to 2013 at the Military Medical Academy, Belgrade. The control group included 20 patients with dysplastic and 20 with benign naevi. Stratification was done according to gender, age, clinical and patological stage, localization, histologic type, Clark's, Breslow, mitotic count, regression and ulceration, tumor infiltrating lymphocytes and metastatic spread.Immunohistochemical staining was performed on skin biopsies using DAKO anti-VEGF antibodies (Ab), LSAB+HRP, DAB and microvawe antigen (Ag) retrieval in DAKO pH 9.0 solution. For statistical data analysis was done with ANOVA, Bonferroni, Mann Whitney and Wilcox on test. RESULTS: The mean intensity of VEGF staining was statistically significantly higher in melanomas than in benign or dysplastic naevi. Furthermore, the highest recorded values were in Ia and IV clinical stages. The majority of melanomas with high intensity of VEGF staining were in pT1a pathological stage. Melanomas with the highest mitotic count (> 6) had a significantly higher intensity of VEGF staining than those with < 2 mitoses. The higest intensity of staining was in melanomas without significant lymphocytic infiltrate and the lowest was in those with brisk lymphocytic infiltrate, thus a statistical difference was siginifant. The mean intensity of VEGF staining was highest in melanomas with lymphovascular invasion. There was no statistically significant difference between VEGF and any other parameter. CONCLUSION: VEGF in primary skin melanomas plays an important role in tumor progression and is linked to the absence if tumor infiltrating lymphocytes and the presence of lymphovascular invasion. More detailed studies have to be done on VEGF prognostic value in melanoma on a larger number of patients.

Melanoma risk is associated with vitamin D receptor gene polymorphisms.

Previous studies have reported that vitamin D receptor (VDR) gene polymorphisms are associated with the occurrence of various cancers, including melanoma. The aim of the current study was to investigate the association of VDR gene polymorphisms with melanoma risk, clinicopathological characteristics, and vitamin D levels. The study group included 117 patients (84 patients with superficial spreading melanoma and 33 patients with nodular melanoma). The control group included 122 sex-matched and age-matched healthy-blood donors of the same ethnicity. VDR gene polymorphisms FokI, EcoRV, TaqI, and ApaI were genotyped by real-time PCR. In 60 patients, the total 25-hydroxyvitamin D levels were evaluated in serum samples by direct chemiluminescence. Associations among parameters were considered to be significant if the P value was less than 0.05. Significant differences in the frequencies of VDR genotypes were observed between cases and the control group for FokI and TaqI polymorphisms (P<0.0001; P=0.005, respectively). Heterozygous Ff as well as mutant FF genotypes of the FokI polymorphism were associated with increased melanoma risk compared with the wild-type form [odds ratio (OR)=3.035, P=0.003; OR=9.276, P<0.0001, respectively]. A significantly increased melanoma risk was observed for the heterozygous Tt (OR=2.302, P=0.011) and the mutated variant tt (OR=3.697, P=0.003) of the TaqI polymorphism in comparison with the wild-type genotype. None of the polymorphisms studied was associated with clinicopathological characteristics and vitamin D serum level. Our results suggest that FokI and TaqI polymorphisms in the VDR gene may be considered as potential biomarkers for melanoma susceptibility. Low vitamin D levels in melanoma patients indicate the need for vitamin D supplementation.

Melanoma in South-East Europe: epidemiological data from the central cancer registry and clinicopathological characteristics from the hospital-based registry in Serbia.

BACKGROUND: Melanoma in South-East Europe shows varying incidence from 1.7 per 100,000 in Albania to 14.5 per 100,000 in Slovenia, but more detailed data from this region are scarce. In this study, we report epidemiological and clinicopathological characteristics of melanoma in central Serbia. MATERIALS AND METHODS: Epidemiological data were retrieved from the Cancer Registry of Central Serbia and clinicopathological data from the hospital-based registry. RESULTS: The ASR(W) incidence rate of melanoma was 4.2/100,000 (males) and 3.9/100,000 (females), and ASR(W) mortality rates were 1.9/100,000 (males) and 1.4/100,000 (females), with recorded rising trends in both of them. Data from the hospital-based registry revealed a total of 266 patients treated from 2005 to 2010, with the median age at diagnosis of 57 (13-86) years. The most frequent histopathological subtype was superficial spreading melanoma (SSM; 63.53%), and ulceration was present in 40.6% of primary tumors. Median Breslow thickness was 3 mm (0.1-25 mm). Primary tumors with thickness of more than 4 mm were found in 31.95% of patients, and in this group statistically significant difference was found for younger age in patients with SSM (55 years vs. 61 years, P = 0.04). CONCLUSION: Low incidence rates in central Serbia and probably other countries of South-East Europe are accompanied by a large percentage of thick tumors and a significant proportion of younger patients with thick tumors. This points to the urgent need for more effective primary and secondary prevention of melanoma in these countries.