Increased Angiogenesis and Lymphangiogenesis in Metastatic Sentinel Lymph Nodes Is Associated With Nonsentinel Lymph Node Involvement and Distant Metastasis in Patients With Melanoma.

Lymph node angio- and lymphangio-genesis have been shown to play an important role in the premetastatic niche of sentinel lymph nodes. In the current study we have investigated the association of angio- and lympangio-genesis related parameters in metastatic sentinel lymph nodes of patients with melanoma with the presence of nonsentinel and distant organ metastasis. Peritumoral and intratumoral relative blood and lymphatic vessel areas (evaluated by Chalkley method), blood and lymphatic microvessel densities, and the rates of blood and lymphatic vessel proliferation were assessed in primary tumors and sentinel lymph node metastasis of 44 patients with melanoma using CD34/Ki-67 and D240/Ki-67 immunohistochemical double staining. Primary melanoma exhibited significantly higher rate of lymphatic proliferation compared with its lymph node metastasis (P < 0.05), while lymph node metastasis showed significantly higher rate of blood vessel proliferation (P < 0.05). Using multivariate logistic regression model, the rate of peritumoral lymphatic proliferation was inversely associated with positive nonsentinel lymph node status (P < 0.05), whereas the rate of intratumoral blood vessel proliferation was associated with distant organ metastasis (P < 0.05). Using multivariate Cox regression analysis, the rate of intratumoral blood vessel proliferation was also inversely associated with overall survival of patients with melanoma (P < 0.05).

Peritumoral D2-40 Chalkley score independently predicts metastases and survival in patients with cutaneous malignant melanoma.

BACKGROUND: Many observational studies investigated the prognostic significance of angiogenesis and lymphangiogenesis in patients with melanoma. However, the obtained results are rather contradictory, probably due to the lack of the consensus methodology. METHODS: To investigate the prognostic significance of angiogenesis and lymphangiogenesis-related parameters in patients with melanoma, we performed a retrospective investigation following the consensus recommendations for angiogenesis and lymphangiogenesis quantification in solid tumors and reporting recommendations for tumor marker (REMARK) criteria for reporting the results. Blood and lymphatic vessel Chalkley scores, endothelial cell proliferation fractions and microvessel densities were quantified using a double immunostaining for endothelial marker CD34 or lymphendothelial marker D240 and the proliferation marker Ki-67 in 196 patients with melanoma. These parameters were evaluated separately for peritumoral (PT) and intratumoral areas and were correlated with outcome. RESULTS: In multivariate analysis PT D240 Chalkley score was identified as a strongest predictor for sentinel lymph node metastases, non-sentinel lymph node metastases, distant metastases, disease free survival and overall survival in patients with melanoma. CONCLUSIONS: If additional studies corroborate our findings, we believe that the inclusion of PT D240 Chalkley counts to the routine pathology examination of melanoma samples would provide additional information for identifying high-risk patients.

Lesión crónica en pabellón auricular de 30 años de evolución / Chronic lesion in the pinna of the ear of 30 years’ evolution

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