Periodic acid Schiff loops and blood lakes associated with metastasis in cutaneous melanoma.

Aggressive melanoma cells are able to form alternative routes for angiogenesis. The formation of extracellular matrix-rich vasculogenic-like networks [periodic acid Schiff (PAS) loops] and expression of endothelial-associated genes [allowing direct contact of erythrocytes (blood lakes)] are forms of vasculogenic mimicry (VM). The detection of these alternative routes may be used as an additional staging factor for cutaneous melanoma and predicts the route of metastasis in melanoma. We studied the association of the presence of VM with metastasis (lymphogenous and/or haematogenous) in patients diagnosed with cutaneous malignant melanoma in het Groene Hart Hospital, the Netherlands, between 1995 and 2000. Tumour tissue samples of 123 patients were assessed on PAS loops and blood lakes and correlated to clinical data. VM was detected in 42 (34%) and proven metastasis developed in 23 patients (18.7%). VM was associated with shorter survival (P<0.001). In 36 tumours, PAS loops were detected. PAS loops were correlated with the presence of lymphogenous as well as haematogenous metastasis (P=0.062 and 0.013). In 20 tumours, blood lakes were detected and correlated with haematogenous metastasis (P<0.001). In multivariate analyses, the detected blood lakes were significantly associated with haematogenous metastasis (P<0.001, adjusted odds ratio 6.8, 95% confidence interval 1.47-31). Blood lakes were strongly correlated with haematogenous metastasis of cutaneous melanoma and were an independent determinant for survival. These interesting findings need further investigation, although we believe that implementation of this detection can directly lead to better staging of cutaneous melanoma.