Lymphatic Drainage of the Pleura and Its Effect on Tumor Metastasis and Spread

The pleura is the serous membrane that covers the lung parenchyma, mediastinum, diaphragm, and rib cage. The pleura is divided into the visceral pleura, which covers the lung parenchyma and inter-lobar fi ssures, and the parietal pleura that lines the inside of each hemithorax along the chest wall. These pleura fuse at the hilum where they form the pulmonary ligament (1). Visceral and parietal pleura are both derived from intraembryonic coelom which is already covered by mesothelial cells by the 7th gestational week. The coelom is divided into the pleural and peritoneal cavities by the septum transversum which arises from the ventral, left and right pleuroperitoneal folds and from the posterior walls. This process ultimately separates the two pleural cavities from the pericardial cavity (1). Normal pleura exhibits 5 layers via light microscopy; 1. a single layer of mesothelial cells; 2. a thin submesothelial connective tissue layer, including a basal lamina; 3. a thin superfi cial elastic layer; 4. a loose connective tissue layer; and 5. a deep fi broelastic layer. It is the loose connective tissue layer that serves as the plane of dissection for extrapleural pneumonectomies (1). Pleural fl uid is present between the visceral and parietal pleural layers and is responsible for lubrication. Mesothelial cells line the pleural cavity and are characterized by abundant microvilli and pinocytotic vesicles, with cells at the cranial aspect having less microvilli than those in the caudal portion. Water, and small molecules less than 4 nm, can pass freely between the mesothelial cells and across the basal lamina, whereas particles of 1000 nm, are engulfed but not transported. Lastly, removal of large particles or cells from the pleural cavity depends on transport via the pleural lymphatics, which cycle pleural fl uid at a rate of 0.4 mL/kg/h (2). The lymphatics within the parietal pleura run along the intercostal spaces and are virtually absent over the ribs. These lymphatic vessels drain ventrally toward nodes along the internal thoracic artery and dorsally toward the internal intercostal lymph nodes near the heads of the ribs. In contrast, the visceral pleura is very rich in lymphatic vessels, with an intercommunicating “network” arranged over the lung surface and penetrating into the lung parenchyma to join the bronchial lymph vessels with drainage to the various hilar nodes. The larger lymphatic vessels in the visceral pleura have one-way valves which also direct fl ow toward the hilum of the lung (3). Understanding lymphatic drainage of the lung and pleura is important in the proper assessment and oncologic management of patients with intrathoracic malignancies and there are a few studies investigating the dynamics of pleural lymphatic drainage in vivo. For example, Miura T et al, designed an experimental model utilizing the injection of carbon particles into the pleural cavity of Japanese monkeys. The entrance of carbon particles were identifi ed in the subpleural lymphatic lacunae using stereoscopy and scanning electron microscopy (SEM) studies. These studies defi ned two populations of mesothelial cells, one rich in microvilli and the other with stomata. The stomata-rich mesothelial cells, present on the parietal pleura, were found to