The migration of melanoma cells along the external surface of blood vessels (angiotropism) has recently been proposed as a mechanism for melanoma metastasis (termed extravascular migratory metastasis). To determine whether the presence of angiotropism, as seen in the routine hematoxylin and eosin sections of primary cutaneous melanomas (PCMs), predicts the development of local or in-transit melanoma recurrence, 32 patients with a PCM who developed local or in-transit recurrence were matched for Breslow thickness with 59 "control" patients with a PCM who did not. The slides from both groups of patients were analyzed in a "blinded" manner for evidence of angiotropism. Other histologic and clinical variables were also assessed. Angiotropism was found more often in patients who developed local or in-transit recurrence (cases) compared with those patients who did not (controls) (P=0.02). Variables that showed a statistically significant association with angiotropism on univariate analysis were: increasing Breslow thickness (P<0.0001), greater Clark level (P<0.001), increasing mitotic index (P<0.0001), presence of ulceration (P<0.01), and absence of regression (P<0.05). The median disease-free survival was 72 months for patients with angiotropism and 104 months for those without (P=0.02). On multivariate analysis the presence of angiotropism was an independent predictor of decreased disease-free survival (P=0.02). This is the first reported study to identify a statistically significant association between the development of local or in-transit recurrence of PCM and the histologic presence of angiotropism and that angiotropism is an independent predictor of decreased disease-free survival, as far as we are aware. Our findings support the hypothesis that angiotropism represents a pathogenic mechanism for metastasis in patients with PCM.

Melanoma is comprised of biologically distinct subtypes. The defining clinical, histomorphologic, and molecular features are not fully established. This study sought to validate the association between genetic and histomorphologic features previously described and to determine their reproducibility and association with important clinical variables. Detailed clinical and histomorphologic features of 365 primary cutaneous melanomas were assessed by 11 pathologists and correlated with mutation status of BRAF and NRAS. There was substantial agreement in the quantitative assessment of histomorphologic features showing similar or better interobserver reproducibility than the established World Health Organization classification scheme. We confirmed that melanomas with BRAF mutations showed characteristic morphologic features (P < 0.0001) and metastasized more frequently to regional lymph nodes (P = 0.046). Importantly, melanomas without mutations were a heterogeneous group, with a subset having very similar clinical and morphological features as those with BRAF mutation raising the possibility that they are biologically related. Our study confirms an association between histomorphologic features, mutation status, and pattern of metastasis, providing criteria for a refined melanoma classification aimed at defining biologically homogeneous disease subgroups.

MPC exhibits a spectrum of growth patterns that overlap with MF. Tumours can be designated as MPC or MF depending on the predominant growth pattern.

A weighted score (N-SNORE) based on clinicopathologic characteristics accurately stratifies risk of NSN involvement in patients with melanoma. If validated in future studies, N-SNORE will better predict prognosis, aid in management decisions, and stratify patient groups for entry into clinical trials.

The results suggest that alterations at the G(1)/S transition of the cell cycle play an important role in the progression of PTs.

The evolution and progressive refinement of an internationally accepted melanoma staging system over the last 50 years has resulted in much greater accuracy and increased utility, but the staging process has become more complex and less intuitive. This raises the question of whether melanoma staging should continue to develop with ever-increasing levels of complexity, or whether attempts should be made to produce an alternative system that is simpler and more intuitive. The current, TNM-based American Joint Committee on Cancer (AJCC) staging system for melanoma incorporates only some of the prognostic factors of proven significance. However, the information that is now available about these and other, well-documented prognostic factors allows accurate prediction of an individual melanoma patient's prognosis using a computer-generated estimate. Thus an alternative staging strategy that could be considered in the future would be to use such an estimate to obtain a numerical score for each patient, based on all available information agreed to be of prognostic relevance. A stage grouping could then be assigned on the basis of that score, according to previously determined score ranges for each stage and substage. The advantages of such a system would be that it would allow more reliable comparison of treatment results within and between institutions, and would provide more equivalent stratification groups for patients entering clinical trials of new therapies and those entering adjuvant therapy trials. A further advantage would be that because there would be a direct link between staging and prognostic estimate, such a system would be more readily able to be understood in an intuitive fashion.

8509 Background: In a previous immunohistochemical study of dendritic cells (DCs) in sentinel lymph nodes (SLNs) draining regressing melanomas we found that the accumulation of mature DC-LAMP+ DCs in SLNs was associated with local expansion of antigen- specific memory effector cytotoxic T lymphocytes and the absence of metastasis in downstream lymph nodes. The aim of this study was to investigate the prognostic importance of the maximal density of mature DCs in SLNs using the anti-DC LAMP antibody. Methods: 458 consecutive patients with micrometastatic melanoma within SLNs and 3 yrs follow-up after SLN procedure or death within 3 yrs were eligible for analysis. Semi-quantitative evaluation of mature DC DC-LAMP+ maximum density was made as follows: the slide was examined at intermediate magnification (x100) to select the area containing the maximum number of DC-LAMP+ DCs, the number of DC-LAMP+ cells per mm 2 was then determined at high magnification (x400) in 3 mm 2 in high density areas. Results were reported as number of cells /mm2. The maximal density of mature DC-LAMP+ DCs was evaluated by three independent observers and categorized into three classes (&lt;100/mm 2 , 100- &lt;200/mm 2 , ≥200/mm 2 ) according to previously reported cutpoints. Results: There was excellent inter-observer reproducibility for maximum density of mature DC-LAMP+ DCs scores (kappa score = 0.82). There were differences in the maximal density scores and staining intensity according to the center (P&lt;0.001). The higher the mature DC density in the SLN the longer the duration of survival [p=0.047; hazard ratio (95% CI) = 0.70 (0.50–1.00)]. Conclusions: This study is the first to report the prognostic value of DC-LAMP+ DC counts in SLNs containing metastatic melanoma. Patients with a high density of mature DCs (≥200/mm 2 ) have the lowest risk of death. It also provides evidence that a lack of DC maturation in the SLNs is important in biological facilitation of melanoma progression. No significant financial relationships to disclose.