Lymphatic metastasis is an important mechanism in the spread of human cancer. During its course, tumor cells first penetrate the basement of membrane of the epithelium, in which they arise, and then the underlying connective tissue, carried partly by hydrostatic pressure. They enter the lymphatic partly by active movement, pass up the lymphatic trunk; they then settle and proliferate in the subcapsular sinus, penetrate its endothelium and proliferate and destroy the node. There are varied forms of immune response in the node and in human nodes often a complex fibrous and vascular response. The degree of lymphocytic response may be important for prognosis. The nodal reaction may be stimulated by release of antigens from the tumor. One of the most studied animal models of lymphatic metastasis is that which occurs in the politeal node after injection of tumor into the footpad. This model has been used to show that tumor cells enter lymphatics through gaps in endothelium, probably between endothelial cells, and that lymph nodes can destroy small numbers of tumor cells. Local immunotherapy and chemotherapy can sterilize a lymph node of tumor cells; the modes of treatment used have included intralymphatic injection and encapsulation of chemotherapeutic agents in liposomes. Prior radiotherapy may accelerate metastasis possibly by making tumor cells shed into lymphatic vessels. Lymph nodes are rather poor barriers to tumor cells. The prognostic significance of lymph node metastasis varies within tumor type; if hematogenous metastasis is early, then the presence of lymph node metastasis is of lesser prognostic significance. Lymph nodes can probably destroy only small numbers of tumor cells. Tumor cell heterogeneity is of importance in many aspects of metastasis; while clonal variation may be of importance in determining lymph node metastasis, it is not yet clear how important this is, nor whether specific clones metastasize specifically to lymph nodes. Lymphography is well established in diagnosis of lymphatic metastasis. A recent interesting development has been to inject antibodies labeled with a radioactive label, and image the label in lymph nodes with a gamma-camera. If anti-tumor antibodies are used in this way it may be possible to detect lymph node metastasis. Within the expanding field of tumor metastasis, lymphatic metastasis needs much more attention, particularly in relation to the diagnosis and treatment of the lymphatic spread of human cancer.
