The prognostic significance of microsatellites in cutaneous melanoma.

Microscopic satellite metastases are an adverse prognostic feature in primary cutaneous melanoma patients. The prognostic significance of microsatellites, including their number, size and distance from the primary melanoma, using the 8th edition American Joint Committee on Cancer definition, has not previously been evaluated. This study sought to determine the prognostic significance of microsatellites in histopathologically reviewed cases. Eighty-seven cases of primary cutaneous melanoma with the presence of microsatellites documented in the original pathology report and all histopathology slides available were reviewed and the findings were correlated with clinical outcome. Matched control cases were selected for all confirmed microsatellites cases. The presence of microsatellites was confirmed in 69 cases. The microsatellite group had significantly worse prognosis, with 21% 5-year disease-free survival compared with 56% in the control group (p < 0.001). The 5-year melanoma-specific survival was 53% in the microsatellites group and 73% in the control group (p = 0.004). Increasing distance (mm) of the microsatellite from the primary melanoma was found to adversely influence disease-free survival (HR = 1.24, 95% CI: 1.13-1.36, p < 0.001), overall survival (HR = 1.26 95%CI: 1.13-1.40, p < 0.001), and melanoma-specific survival (HR = 1.27 95% CI: 1.11-1.45, p < 0.001). Number and size of microsatellites were not significant prognostic factors. The presence of microsatellites was the only factor that proved to be an independent predictor of sentinel node positivity in multivariate analysis (OR 4.64; 95% CI 1.66-12.95; p = 0.003). Microsatellites were significantly associated with more loco-regional recurrences (p < 0.001) but not distant metastases (p = 0.821). Melanomas with microsatellites as defined by the 8th edition American Joint Committee on Cancer staging system are thus aggressive tumors, associated with significantly worse disease-free survival, overall survival and melanoma-specific survival. The presence of microsatellites is also associated with sentinel node-positivity and local and in-transit recurrence. Increasing distance of the microsatellite from the primary tumor is an independent adverse prognostic factor that warrants further evaluation.

Cigarette Smoking and the Risk of Cutaneous Melanoma: A Case-Control Study.

OBJECTIVE: Previous studies regarding cigarette smoking causing a lower risk of melanoma are inconclusive. Here, we re-examined melanoma risk in relation to cigarette smoking in a large, case-control study. METHODS: In total 1,157 patients with melanoma diagnosed between 2003 and 2011 in the Netherlands and 5,595 controls from the Nijmegen Biomedical Study were included. Information concerning smoking habits and known risk factors for melanoma were obtained through self-administered questionnaires. Logistic regression analyses stratified by gender were performed to study the risk of cigarette smoking on melanoma risk, adjusted for age, marital status, highest level of education, skin type, sun vacation, use of solarium, time spent outdoors, and sun protective measures. RESULTS: Among men, current and former smokers did not have a higher risk of melanoma compared to never smokers: adjusted odds ratio (OR) = 0.56 (95% confidence interval [CI]: 0.40-0.79) and adjusted OR = 0.50 (95% CI: 0.39-0.64), respectively. With an increasing number of years smoked the risk of melanoma decreased: <20 years: OR = 0.61 (95% CI: 0.46-0.80); 21-40 years: OR = 0.50 (95% CI: 0.37-0.68); >40 years: OR = 0.26 (95% CI: 0.15-0.44). No clear trend was found for the number of cigarettes smoked. Results for females were less clear and not statistically significant (current smoker: adjusted OR = 0.96, 95% CI: 0.74-1.26, former smoker: adjusted OR = 0.89, 95% CI: 0.73-1.08). CONCLUSION: This study shows a strong inverse association between cigarette smoking and melanoma risk in men. Fundamental laboratory research is necessary to investigate the biological relation between smoking cigarettes and melanoma.

The optimum excision margin and regional node management for primary cutaneous T3 melanomas (2-4 mm in Thickness): a retrospective study of 1587 patients treated at a single center.

OBJECTIVE: To determine the optimum excision margin and nodal management for patients with primary cutaneous melanomas 2.01- to 4.00-mm thick (T3 melanomas). BACKGROUND: Currently available evidence does not reliably define the minimum safe excision margin and best nodal management for patients with primary cutaneous T3 melanomas. METHODS: A retrospective study was conducted, analyzing data on 1587 patients with melanomas 2.01- to 4.00-mm thick treated at a single center. RESULTS: A histopathologic excision margin of 8 mm or more (equivalent to a ≥1 cm surgical margin) was associated with increased local and in-transit recurrence-free survival [hazard ratio (HR) = 0.54; P = 0.008] and disease-free survival (DFS) (HR = 0.59; P = 0.001) compared with a less than 8-mm margin. The <8-mm group had reduced distant recurrence-free survival (DRFS) compared with the 8- to 16-mm group (HR = 1.63; P = 0.038). On multivariate analysis, patients with a positive sentinel lymph node (SLN) had significantly reduced melanoma-specific survival (MSS), DFS, regional node recurrence-free survival (RNRFS) and DRFS compared with patients with a negative SLN, unless an immediate completion lymph node dissection was performed. Patients in whom an SLN biopsy was not performed had significantly reduced MSS (HR = 2.10; P < 0.001), DFS (P < 0.001), RNRFS (P < 0.001), and DRFS (P = 0.010) compared with patients who received an SLN biopsy. CONCLUSIONS: A histopathologic excision margin of 8 mm or more (corresponding to a ≥1 cm surgical excision margin) combined with SLN biopsy (followed by an immediate completion lymph node dissection if positive) provided T3 melanoma patients with optimum local, regional, and distant disease control and resulted in enhanced melanoma-specific survival.