Regional lymph node metastases, a singular manifestation of the process of clinical metastases in cancer: contemporary animal research and clinical reports suggest unifying concepts.

The multistep complex metastatic cascade in cancer has been extensively studied in recent years. In addition, the concept of metastatic organ specificity has been elaborated. Histological studies in clinical situations have become far more sophisticated, enabling the frequent discovery of minor collections of cells in bone marrow and lymph nodes. Pertinent clinical evidence of the selective nodal metastatic pattern exists in differentiated thyroid cancer in younger, low-risk patients, yet none of the published risk group definitions indicate that lymph node metastases have a relationship to thyroid cancer survival. This unique clinical situation with very frequent nodal metastases but excellent survival is replicated in carcinoid cancers of the gastrointestinal tract. The lymph node metastatic frequency without distant organ metastases in these two human cancers help cement the understanding gained from laboratory and animal research regarding metastatic specificity and hopefully will help place the role of lymph node metastases generally and their surgical removal on a more scientifically and logically based understanding. More broadly, the elaboration of the frequency of metastatic cell dissemination to distant organs as well as lymph nodes, and comprehension of the metastatic cascade with metastatic specificity may reorient our understanding of the evolution from metastatic cells to clinical metastatic disease. Additionally, these concepts reemphasize that lymph node metastases are indicators, not governors, of distant metastases and survival, and add the assumption that metastatic tumor cells and tumor cell clusters, and perhaps even micrometastases in other organs, are themselves only indicators and not governors of distant metastases and survival in human cancers since they represent dormant metastases prior to their host microenvironmental changes that, on rare occasions, lead to angiogenesis and clinical metastases. Thus, the future may allow us to abandon some aspects of our surgical or systemic attack on clinical cancer metastases, such as lymph node removal or use of toxic chemotherapy, but open the door to more physiological and hopefully less traumatic approaches to the highly manipulable multistep genetic and physiological process of metastatic development. The future biological models of clinical cancer behavior will have to incorporate aspects of understanding the intricate metastatic cascade, and particularly the host microenvironmental factors that permit or prevent progressive growth of dormant cells or cell clusters to clinical metastases.