Cutaneous melanoma metastases: Clinical and dermoscopic findings.

BACKGROUND: About 2%-20% of melanoma patients will develop cutaneous melanoma metastases (CMM). Their clinical diagnosis still remains challenging because of the variation of clinical and dermoscopic characteristics. Until today, few studies exist concerning the dermoscopic image of CMM but no one has focused on its possible association with clinicopathological melanoma characteristics. METHODS: Between 2002 and 2019, 42 patients diagnosed with melanoma at Andreas Syggros Hospital developed CMM. We studied the dermoscopic presentation of these metastases and its possible association with the clinical and histologic characteristics of the underlying melanoma. RESULTS: There were 20 male and 22 female patients with a mean age of 64.02 years. Nineteen patients developed satellites and 23 in transit metastases. Mean Breslow index was estimated at 2.93 mm and ulceration was observed in half of the tumours (50%). Almost half of the patients developed cutaneous metastases on the lower limbs (45.24%). We identified 5 dermoscopic patterns of CMM: saccular, amelanotic, homogenous, vascular and polymorphic. Homogenous (30.95%) and amelanotic (28.57%) were the most common patterns. Homogenous pattern was the most common in satellite metastases while amelanotic was mostly observed in in-transit metastases. Homogenous pattern was more frequent among superficial spreading melanomas. Patients with thin (<1 mm) and medium depth (1-2 mm) melanomas mostly developed metastases with saccular pattern. Vascular pattern was only present in metastases of tumours with Breslow index 2-4 mm. Homogenous and amelanotic were the only patterns found in tumours with Breslow index >4 mm. CONCLUSIONS: We observed that vascular structures were more frequent in metastases of deeper tumours while nevus-like structures were more common in metastases of thinner tumours. CMM occasionally may constitute the first clinical sign of melanoma disease. Therefore, it is important for clinicians to recognize their dermoscopic patterns which seem to be associated with some of the clinical and histological characteristics of cutaneous melanomas.

Serum Total 25-Hydroxyvitamin D Levels in Patients With Cutaneous Malignant Melanoma: A Case-Control Study in a Low-Risk Southern European Population.

BACKGROUND: Recent data have shown an inverse association between serum 25-hydroxyvitamin D concentration and incidence of several cancers, including cutaneous malignant melanoma (CMM). In addition, lower serum 25-hydroxyvitamin D levels have been associated with thicker or higher stage melanomas and worse survival in observational studies. MATERIALS AND METHODS: Ninety-nine patients diagnosed with primary CMM and 97 matched healthy controls entered the study. Demographic characteristics, risk factors for CMM, and clinical and histological characteristics were recorded for patients with primary CMM. Total serum 25-hydroxyvitamin D levels of melanoma patients measured by fully automated chemiluminescent vitamin D total immunoassay (Elecsys vitamin D total, Roche) at the time of diagnosis were compared with those of healthy controls. In addition, we tested the association of serum total 25-hydroxyvitamin D levels at melanoma diagnosis with known risk and prognostic factors for CMM. RESULTS: Of the melanoma patients, 49 (49.49%) had deficient serum total 25-hydroxyvitamin D levels (<20 ng/mL), 23 (23.23%) had insufficient levels (21-29 ng/mL), and 27 (27.27%) had adequate levels (>30 ng/mL). The median serum total 25-hydroxyvitamin D levels were significantly lower in melanoma patients (20.62 ng/mL) compared with healthy controls (24.71 ng/mL), but statistical significance was not reached (chi-square test, P = 0.051) No statistically significant association was found between serum total 25-hydroxyvitamin D levels and demographic characteristics; risk factors for CMM; prognostic factors, such as Breslow thickness and ulceration; as well as clinical characteristics, such as melanoma stage, clinical type, and location. CONCLUSIONS: Lower serum 25-hydroxyvitamin D levels were found in our Greek cohort of melanoma patients compared with healthy controls, without reaching, however, statistical significance; these levels were not statistically associated with established risk and prognostic factors for CMM.

CDKN2A/CDK4 Status in Greek Patients with Familial Melanoma and Association with Clinico-epidemiological Parameters.

Approximately 5-10% of melanoma cases occur in a familial context. CDKN2A/CDK4 were the first high-penetrance melanoma genes identified. The aims of this study were to evaluate CDKN2A/CDK4 variants in Greek familial melanoma patients and to correlate the mutational status with specific clinico-epidemiological characteristics. A cross-sectional study was conducted by genotyping CDKN2A/CDK4 variants and selected MC1R polymorphisms in 52 melanoma-prone families. Descriptive statistics were calculated and comparisons were made using the χ2 test, Fisher's exact test and Student's t-test for statistical analysis, as appropriate. CDKN2A variants were detected in 46.2% of melanoma-prone families, while a CDK4 variant was found in only one family. This study confirmed that, in the Greek population, the age at melanoma diagnosis was lower in patients carrying a variant in CDKN2A compared with wild-type patients. No statistically significant associations were found between CDKN2A mutational status and MC1R polymorphisms.

Prediction of Melanoma Risk in a Southern European Population Based on a Weighted Genetic Risk Score.

Many single nucleotide polymorphisms (SNPs) have been described as putative risk factors for melanoma. The aim of our study was to validate the most prominent genetic risk loci in an independent Greek melanoma case-control dataset and to assess their cumulative effect solely or combined with established phenotypic risk factors on individualized risk prediction. We genotyped 59 SNPs in 800 patients and 800 controls and tested their association with melanoma using logistic regression analyses. We constructed a weighted genetic risk score (GRSGWS) based on SNPs that showed genome-wide significant (GWS) association with melanoma in previous studies and assessed their impact on risk prediction. Fifteen independent SNPs from 12 loci were significantly associated with melanoma (P < 0.05). Risk score analysis yielded an odds ratio of 1.36 per standard deviation increase of the GRSGWS (P = 1.1 × 10(-7)). Individuals in the highest 20% of the GRSGWS had a 1.88-fold increase in melanoma risk compared with those in the middle quintile. By adding the GRSGWS to a phenotypic risk model, the C-statistic increased from 0.764 to 0.775 (P = 0.007). In summary, the GRSGWS is associated with melanoma risk and achieves a modest improvement in risk prediction when added to a phenotypic risk model.

Risk associations of melanoma in a Southern European population: results of a case/control study.

OBJECTIVES: Limited data exist about the risk factors of melanoma in the Greek population. We investigated the association of melanoma with phenotypic and solar indices in this darker skin population residing in an environment of high ambient ultraviolet radiation. METHODS: Our study included 200 sporadic melanoma cases and 200 age-, sex-matched control subjects. Information on history of sun exposure patterns and cutaneous reaction to sunlight was obtained and a clinical evaluation of pigmentary traits, pigmented lesions, and actinic keratoses was performed. RESULTS: In the multivariate analysis, fair skin (OR: 4.63, for fair skin versus light brown, 95% CI: 1.54-13.92), intermittent sun exposure during childhood (OR: 3.33, >2 weeks/year of sun exposure versus < or =2 weeks/year 95% CI: 1.37-8.09), and outdoor leisure activities (OR: 2.74, 95% CI: 1.28-5.89), but not skin phototype or sunburns, were positively related to the risk of melanoma. In addition to an elevated count of common melanocytic nevi (OR: 6.27, > or =10 nevi versus no nevi, 95% CI: 1.65-23.76) and the presence of clinically atypical nevi (OR: 2.84, 95% CI: 1.16-6.98), solar lentigenes were an independent risk factor of melanoma (OR: 4.33, 95% CI: 1.67-11.22). CONCLUSIONS: Intermittent sun exposure of moderate intensity during childhood/adolescence and outdoor leisural activities, in conjunction with a more resistant skin phenotype to acute sunburns and a strong association with nevi and solar lentigenes was a prominent determinant of melanoma risk in our population.

Seasonal pattern of the diagnosis of cutaneous melanoma: a hospital-based study in a Mediterranean country.

BACKGROUND: Several investigators have described a seasonal variation in the diagnosis of cutaneous melanoma. Limited data exist on the seasonality of melanoma diagnosis in Southern European countries. PATIENTS AND METHODS: The seasonal pattern of diagnosis was analyzed in 404 Greek patients diagnosed with cutaneous melanoma (CM) between 1996 and 2004. A summer-to-winter ratio was determined overall and in relation to gender, age, anatomic site, histopathologic type, and tumor thickness. RESULTS: The summer-to-winter ratio was 1.53 for all patients (95% CI [confidence interval]: 1.15-2.02) with a ratio of 1.83 for women (95% CI: 1.20-2.78) and 1.28 for men (95% CI: 0.87-1.88). A seasonal pattern of melanoma diagnosis was observed for patients younger than 50 years of age (1.70, 95% CI: 1.05-2.74) and between 50 and 69 years (1.64, 95% CI: 1.05-2.56), for melanoma located on the upper or lower extremities (2.50, 95% CI: 1.12-5.56 and 2.23, 95% CI: 1.19-4.18, respectively), for superficial spreading and nodular melanomas (1.73, 95% CI: 1.12-2.69 and 1.52 95% CI: 0.96-2.41) and for melanomas with a tumor thickness of 1-2 mm (1.69, 95% CI: 0.91-3.12) and > 4 mm (2.13, 95% CI: 1.04-4.35). CONCLUSIONS: No major differences were seen in the seasonal distribution of CM diagnosis in a Mediterranean population compared to previously reported results. A better ascertainment of the skin during the summer and an increased awareness due to the melanoma screening campaigns are the more likely reasons for the seasonality of melanoma diagnosis in Greece.

Melanocortin receptor-1 gene polymorphisms and the risk of cutaneous melanoma in a low-risk southern European population.

Individuals with melanocortin 1 receptor (MC1R) gene variants have been shown to carry an increased risk for the development of melanoma. In this study, we investigated the relationship of MC1R gene variants and the risk of melanoma in 123 melanoma patients and 155 control subjects from Greece. The entire MC1R gene was sequenced for polymorphisms and the results were correlated with host factors and pigmentary characteristics. MC1R polymorphisms were present in 59.4% of melanoma patients compared to 37.5% of controls, yielding an odds ratio (OR) of 2.43 (95% confidence interval (CI) = 1.50-3.96, P < 0.001) for melanoma among MC1R carriers. The risk of melanoma was enhanced in individuals carrying multiple variant alleles (OR = 6.97; 95% CI = 1.86-26.12, P = 0.004). Only the Val60Leu, Arg142His, and Arg151Cys variants were significantly associated with melanoma risk. In stratified analysis, the risk of melanoma among MC1R carriers was not influenced by skin phototype, skin color, or hair color. No association was found between MC1R genotype and the age of onset of melanoma, the tumor location, or the tumor thickness. In conclusion, MC1R polymorphisms are a predisposing factor of melanoma in a southern European population with a relatively low incidence of the disease.

Association of clinical progression in classic Kaposi's sarcoma with reduction of peripheral B lymphocytes and partial increase in serum immune activation markers.

OBJECTIVE: To evaluate various immunologic markers in the peripheral blood of patients with early and advanced classic Kaposi's sarcoma (CKS). DESIGN: Cross-sectional study. SETTING: A major referral center for skin and venereal diseases. PATIENTS: Sixty-eight patients with histologically confirmed CKS staged according to a modified version of the Mitsuyasu-Groopman classification in stage I-II (cutaneous involvement only) and stage IV (skin and systemic involvement). MAIN OUTCOME MEASURES: Concentrations of neopterin and beta2-microglobulin, titer of anti-human herpesvirus 8 antibodies, number of natural killer cells, and numbers of total lymphocytes, B lymphocytes, T lymphocytes, and their subsets in peripheral blood. RESULTS: The median values of beta2-microglobulin and neopterin were elevated in patients with CKS in stage IV (median, 3.679 microg/mL [312.72 nmol/L] and 14.0 nmol/L, respectively) compared with patients in stage I-II (median, 2.406 microg/mL [204.51 nmol/L] and 6.5 nmol/L, respectively). A statistically significant reduction in total lymphocyte and B-lymphocyte counts was observed in patients with advanced-stage CKS (1679/microL and 79/microL, respectively) compared with patients in earlier stages of the disease (2142/microL and 224/microL, respectively). The human herpesvirus 8 antibody titer, determined by latent immunofluorescent assay, decreased from stage I-II to stage IV, although not at a statistically significant level (P = .14). CONCLUSION: The evolution of CKS from the early stages of the disease to the more advanced may be associated with a partial activation of the immune system and a gradual decrease in the number of total and B lymphocytes.