Metastases of malignant neoplasms: Historical, biological, & clinical considerations

The metastasis of neoplastic cells from their site of origin to distant anatomic locations continues to be the principal cause of death from malignant tumors, and that fact has been recognized by physicians for over a century. After the work done by Halsted in the treatment of breast cancer in the 1880s, accepted surgical canon held that metastasis occurred in a linear fashion, with centrifugal "growth in continuity" from the primary neoplasm that first involved regional lymph nodes. Those structures were considered to then be the sources of more distant, visceral metastases. With that premise in mind, radical and "ultra-radical" surgical procedures were devised to remove as many lymph nodes as possible in the treatment of carcinomas and melanomas. However, such interventions were ineffective in altering tumor-related mortality. This review considers the details of the historical material just mentioned. It also reviews currently-held concepts on biological mechanisms of metastasis, the "sentinel" lymph node biopsy technique, and the important topic of metastatic tumor "dormancy" as the cause of surgical treatment failure. Finally, predictive models of tumor behavior are discussed, which are based on gene signatures. These will likely be the key to identifying malignant lesions of low surgical stage that ultimately prove fatal through later manifestation of metastasis.