![]() Thus, Cady maintained that the lymph node was the marker but not the governor of cancer spread. Despite adequate resection of the primary site and radical regional lymph node dissection, systemic recurrence still occurs. The impact by Halsted was so profound that radical lymph node dissections became standard for different types of cancer such as esophagus, gastric, colon, gynecological cancers and others. The importance of lympatic system to cancer metastasis has been emphasized and described in detail by Haagensen et al. Thus, Halstad promoted radical mastectomy with a complete axillary lymph node dissection for breast cancer and Snow championed en bloc resection of the primary melanoma along with a radical regional lymph node dissection. In the pre-sentinel node era, it was assumed that cancer would spread from the primary site to the regional lymph nodes first, then to the distant sites. To date, the molecular mechanisms of cancer spread from the cancer microenvironment to the sentinel lymph node and distant sites are still poorly understood and their elucidation should take major priority in cancer metastasis research. The goal of this review article is to emphasize the complexity of the lymphatic system. Knowledge from melanoma and breast cancer spread to the sentinel lymph node may establish the basic principles of cancer metastasis. The lymphatic systems of the internal organs are much more complicated and difficult to study. Using melanoma and breast cancer sentinel lymph node model systems, the spread of early cancer through the lymphatic system is progressive in a majority of cases. This review article emphasizes the structural integrity of the lymphatic system through which cancer cells may spread. Occasionally, the cancer cells may enter the blood vessels. In general, the lymph nodes may serve as a gateway in the majority of cases in early cancer. Taking advantage of the drainage system of the lymphatics, cancer cells enter the lymphatic vessels and then the lymph nodes. In addition, the lymphatic system includes the mucosa-associated lymphoid tissue, such as tonsils, adenoids, Peyers patches in the small bowel and even the appendix. The lymph nodes serve as a filter, thus, when the lymph fluid returns to the heart, it is completely sterile. The lymphatic system is a complicated system consisting of the lymphatic vessels and lymph nodes draining the extracellular fluid containing cellular debris, excess water and toxins to the circulatory system.
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