Lymphatic spread is more typical of carcinomas, whereas hematogenous spread is favored by sarcomas. There are numerous interconnections, however, between the lymphatic and vascular systems, so all forms of cancer may disseminate through either or both systems. The pattern of lymph node involvement depends principally on the site of the primary neoplasm and the natural pathways of local lymphatic drainage. Lung carcinomas arising in the respiratory passages metastasize first to the regional bronchial lymph nodes and then to the tracheobronchial and hilar nodes. Carcinoma of the breast usually arises in the upper outer quadrant and first spreads to the axillary nodes. However, medial breast lesions may drain through the chest wall to the nodes along the internal mammary artery. Thereafter, in both instances, the supraclavicular and infraclavicular nodes may be seeded. In some cases, the cancer cells seem to travel in lymphatic channels within the immediately proximate nodes to be trapped in subsequent lymph nodes, producing so-called “skip metastases.” The cells may traverse all of the lymph nodes ultimately to reach the vascular compartment by way of the thoracic duct.
A “sentinel lymph node” is the first regional lymph node that receives lymph flow from a primary tumor. It can be identified by injection of blue dyes or radiolabeled tracers near the primary tumor. Biopsy of sentinel lymph nodes allows determination of the extent of spread of tumor and can be used to plan treatment.
Of note, although enlargement of nodes near a primary neoplasm should arouse concern for metastatic spread, it does not always imply cancerous involvement. The necrotic products of the neoplasm and tumor antigens often evoke immunologic responses in the nodes, such as hyperplasia of the follicles (lymphadenitis) and proliferation of macrophages in the subcapsular sinuses (sinus histiocytosis). Thus, histopathologic verification of tumor within an enlarged lymph node is required.
While hematogenous spread is the favored pathway for sarcomas, carcinomas use it as well. As might be expected, arteries are penetrated less readily than are veins. With venous invasion, the bloodborne cells follow the venous flow draining the site of the neoplasm, with tumor cells often stopping in the first capillary bed they encounter. Since all portal area drainage flows to the liver, and all caval blood flows to the lungs, the liver and lungs are the most frequently involved secondary sites in hematogenous dissemination. Cancers arising near the vertebral column often embolize through the paravertebral plexus; this pathway probably is involved in the frequent vertebral metastases of carcinomas of the thyroid and prostate glands.
Certain carcinomas have a propensity to grow within veins. Renal cell carcinoma often invades the renal vein to grow in a snakelike fashion up the inferior vena cava, sometimes reaching the right side of the heart. Hepatocellular carcinomas often penetrate and grow within the radicles of portal and hepatic veins, eventually reaching the main venous channels. Remarkably, such intravenous growth may not be accompanied by widespread dissemination.
Many observations suggest that the anatomic localization of a neoplasm and its venous drainage cannot wholly explain the systemic distributions of metastases. For example, prostatic carcinoma preferentially spreads to bone, bronchogenic carcinoma tends to involve the adrenal glands and the brain, and neuroblastoma spreads to the liver and bones. Conversely, skeletal muscles, although rich in capillaries, are rarely sites of tumor metastases. The molecular basis of such tissue-specific homing of tumor cells is discussed later.
Thus, numerous features of tumors (
Fig. 6.12 ) usually permit the differentiation of benign and malignant neoplasms.