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

Research results from laboratory animals and human clinical reports provide insight into cancer cell disseminations and elaborate the complex metastatic cascade of cells into both regional lymph nodes and other distant organs. Critical appraisal of clinical trials indicates that lymph node metastases are themselves non-lethal, but indicate prognosis, confirming laboratory conclusions. Distant vital organ metastases can be resected with long term survival in highly selective situations, demonstrating metastatic specificity in oligometastatic disease. Appreciating lymphatic system embryology, anatomy, and physiology is necessary for understanding lymph node metastases. The primary lymphatic system function was to return interstitial fluid to the circulation. Later evolutionary insertion of lymphocyte collections in lymph nodes interrupting lymph flow completed a system of analyzing external antigens to enable adaptive immunologic responses. Human cancers seldom elicit major immunological responses; they are not generally "foreign" enough. Therefore, lymphatic metastases have little meaning in evolutionary terms. Organ specificity of both lymphatic and distant metastases occurs as metastatic cells lie dormant, but grow selectively only in liver, lung, bone, or lymph nodes. These organ specific metastatic cells have little ability to produce different organ site clinical metastases. Thus, laboratory findings and clinical correlations emphasize that surgical lymph node removal should be de-emphasized or omitted. More physiological approaches to the highly manipulable multi-step processes of clinical metastases arising from host microenvironments will eventually prevail.