Angiotropism is an Independent Predictor of Local Recurrence and In-transit Metastasis in Primary Cutaneous Melanoma

Abstract

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.

Lymphatic invasion and angiotropism in primary cutaneous melanoma

“…The detection of angiotropism within a primary melanoma may have an impact on the planning of surgical margins. 10 Furthermore, understanding the underlying molecular mechanisms of intravascular dissemination and EVMM, and the relationship between these processes, may also have therapeutic implications for melanoma patients.…”

Atypical Spitzoid Melanocytic Neoplasms With Angiotropism: A Potential Mechanism of Locoregional Involvement

“…12 A more recent case-control study examined only patients with recurrent melanoma (local metastases) or in-transit metastases; angiotropism strongly correlated with the latter end points. 13 In an important general mechanistic sense, there is increasing experimental evidence that the molecular basis of such tumor cell migration is closely linked to the developmental biology of the neural crest (NC), that is, the migration of NC stem cells from the NC in the embryo. 2 Therefore, a better understanding of such mechanisms of cellular migration may be fundamental not only to melanoma metastasis but also as a means of explaining the migration of melanocytes in general and in other melanocytic neoplasms.…”

Pilot Study on “Pericytic Mimicry” and Potential Embryonic/Stem Cell Properties of Angiotropic Melanoma Cells Interacting with the Abluminal Vascular Surface

“…During EVMM, angiotropic MC migrate along the abluminal surfaces of vessels in a pericytic location, without intravasation, recapitulating embryonic migration in order to reach secondary sites [4]. Interestingly, angiotropism has been shown to be a prognostic factor for melanoma metastasis [4][5][6], as well as a microscopic marker of EVMM in in vitro and in vivo experiments [4,[7][8][9]. Furthermore, a recent study has demonstrated the perivascular localization of malignant tumor cells along the celiac trunk in patients with pancreatic carcinoma, consistent with EVMM [10].…”