Malignant pleural effusion: would the real cause please stand up?

Pleural effusions in patients with malignant disease are not invariably due to metastatic spread to the pleura and thus, they are not always incurable. For example, about 5% of patients with effusions due to lung cancer have subsequently been found to be operable and curable [1]. It is, therefore, important to assess the potential curability in all cancer patients with cytologically negative effusions, since they may not only be free from pleural metastases but also from tumour spread elsewhere. On the other hand, autopsy studies indicate that only about 55‐60% of patients with proven pleural metastases develop pleural effusions. What are the mechanisms that cause the development of an effusion in one patient with malignant involvement of the pleura and what prevents it in another? In this issue of the Journal, SAHN [2] suggests that neoplastic involvement of the lymphatic drainage system, either in the parietal pleura and/or in the mediastinum, is the primary mechanism by which pleural metastases cause pleural effusions. This leads to accumulation of the fluid which normally leaves the pleural space. These conclusions are based primarily on postmortem studies in which the presence of pleural effusions was correlated with the autopsy findings [3, 4]. If the lymphatic clearance is normal, excess fluid that enters the pleural space can usually be removed, since the maximum capacity of the lymphatics for fluid removal is up to 25 times the normal rate of fluid formation [5]. Therefore, unless the amount of pleural fluid being formed is very high, pleural fluid will accumulate only if there is also decreased lymphatic clearance. Indeed, it has been shown that the clearance of fluid from the pleural space is decreased in patients with malignant pleural effusions [6]. However, there are several observations that seem to be incompatible with the theory that lymphatic obstruction is solely responsible for the pleural fluid accumulation.