'Malignant melanoma microecosystem': Immunohistopathological insights into the stromal cell phenotype.

Cutaneous malignant melanoma (MM) is rooted in the dermal connective tissue, which consists of apparently unremarkable stromal cells as they appear upon regular histopathological examination. However, a number of in vitro studies have shown that these cells produce diverse types of cytokines, growth factors and enzymes in excess. In addition, they store and probably release various structural components of the extracellular matrix (ECM). Most of the current information comes from in vitro experiments, and these findings do not always correlate with investigations carried out using excised human MM tissue. The MM-stroma connection appears crucial to the regulation of neoplastic growth, invasiveness and initial metastatic spread. However, little is known about the in vivo intracellular storage and extracellular deposits of specific ECM macromolecules located inside and around MM lesions. This review summarizes various distinct features of the peri-MM stroma, which shows an intracytoplasmic abundance of Factor XIIIa, versican and various α (IV) collagen chains. The area exhibiting such changes corresponds to the location where neoangiogenesis commonly develops and where extravascular unicellular metastatic MM lesions are possibly found. Some of these inconspicuous migratory malignant melanocytes may actually correspond to MM stem cells. Their presence was found to be significantly associated with an increased risk for distant metastases, particularly in the sentinel lymph nodes. Although much remains to be learned, active intervention of the ECM appears likely in the inconspicuous early dermal metastatic migration of MM cells.