Cutaneous melanoma: pathology, relevant prognostic indicators and progression.

Malignant melanoma, one of the most rapidly increasing malignancies in man, has recently received substantial attention in the world literature concerning application of traditional morphologic and newer immunologic and molecular biologic methods of predicting progression and ultimate clinical outcome. Although clinical features of patient sex, age and anatomic site of the lesion are important, classic morphologic variables defining prognosis remain the cornerstone of predicting disease outcome. Extent of radial growth phase and the two microstaging methods of measuring tumor thickness and determining level of invasion remain the critical disease progression predictors. Assessment of mitotic rate, number of tumor infiltrating lymphocytes, and determining the presence of regression, ulceration, and epithelioid cell component, microscopic satellites and vascular invasion are also important. More recently a variety of molecular and biochemical prognostic markers have been cited for prediction of disease recurrence and metastasis. Both overexpression and down regulation of a variety of cell adhesion molecules have been implicated in disease progression as has alterations in the plasminogen activation system. A series of growth factors, growth factor receptors, oncogenes and tumor suppressor genes have also been considered. Structural and numerical genomic DNA abnormalities, cell proliferation markers and DNA ploidy status have also been considered. Recently a variety of serum and blood markers indicating disease persistence or progression have been studied including melanin synthesis precursors and intermediate compounds of melanogenesis. Molecular detection by PCR of melanogenesis specific mRNA may become the most sensitive prognostic marker of the future. At present histopathologic and clinical criteria remain the cornerstones of predicting prognosis in malignant melanoma.