The Epidemiology and Biology of Pulmonary Metastases

Our goal in this chapter is to explore the complex processes of metastasis and why there is a predisposition for this to occur in the lung. In addition, we aim to describe the incidence of pulmonary metastases in various contexts and based on the origin of the primary tumor. There are unique characteristics of the pulmonary system that make metastases more likely to occur in the lung than anywhere else in the body. Some of these characteristics include receiving the entire cardiac output every minute, having the densest capillary bed in the body, and being the first reservoir of most lymphatic drainage entering the venous system. There are multiple postulated routes of metastasis to the pulmonary system including hematogenous and lymphatic routes with early or late dissemination. The vascularization of pulmonary metastases is variable and complex, often recruiting supply from bronchial and pulmonary origin. There are also many biochemical factors in the tumor microenvironment that play a key role in the development of lung metastases including vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), very late antigen 4 (VLA-4) and intercellular adhesion molecule 1 (ICAM-1). Studies vary widely in reported rates of pulmonary metastases due to differences in clinical study design, however, it is commonly accepted that up to half of autopsies performed on patients who died of malignancy have pulmonary metastases. In a surgical series describing the incidence of primary cancer types with resected pulmonary metastases the most common sites were thyroid, colon, breast, genitourinary tract, skin, liver, breast, and adrenal glands.