Pathology of tumor-stroma interaction in melanoma metastatic to the skin.

Tumor invasion and metastasis formation largely depend on tumor-stroma interaction. In the present study morphological correlates of tumor-stroma interaction were examined in 344 melanoma lesions metastatic to the skin. In particular, the presence of simple infiltration into the surrounding dermis or subcutis without evident stromal reaction, the incorporation of pre-existent dermal collagen or subcutaneous fat cells into the tumor bulk, and the formation of a peritumoral capsule or intratumoral fibrous septa were evaluated. Our results showed that simple infiltration into the surrounding tissue as well as the incorporation of pre-existent stroma tissue without destruction is associated with poor outcome, whereas capsule and fibrous septa are favorable prognostic signs, particularly in subcutaneous lesions. Remarkably, simple infiltration is a prognostic indicator independent of the location of the metastasis (locoregional or distant), as shown by multivariate analysis. These data indicate that morphological aspects of tumor-stroma interaction in metastatic skin lesions of melanoma may reflect biological behavior of the tumor cells, may facilitate a pathological subclassification of metastatic melanoma in addition to clinical data, and are directly related to the patient's outcome.