**2. Pathogenesis**

Pathophysiology of MPE has not been fully understood yet and is still on debate. There are many hypotheses on the pathogenesis of MPE in cancer. It commonly results from disruption of normal starling forces regulating pleural fluid absorption by obstruction of mediastinal lymphatics, which drain the pleural space [9]. There is a strong relationship between media‐ stinal metastasis and development of MPE [12, 13]. Other causes of MPE include direct invasion (e.g. lung cancer, breast cancer, chest wall neoplasms), hematogenous spread of tumor to the pleura (eg, metastasis, non-Hodgkin's lymphoma), or increased capillary permeability caused by tumor invasion-related local inflammatory changes or vascular endothelial growth factor production [14]. Just the presence of metastasis does not seem sufficient to explain the pathogenesis of pleural effusions. In fact, only about 60% of patients with proven pleural metastases develop pleural effusions [15, 16].

Indeed, the accumulation of excess pleural fluid associated with cancer may be the result of a number of separate factors in an individual patient [16]. Postmortem studies have demon‐ strated a strong relationship between carcinomatous infiltration of the mediastinal lymph nodes and the occurrence of pleural effusion [11,15]. This finding suggests an important role of the impaired lymphatic drainage in the pathogenesis of MPE. However, if this was to be the only mechanism, one would expect MPEs to be transudative, but instead, the majority of these effusions are exudates [16].



All fluids of pleura may not be malignant in patients with malignancy. The effusion caused by a neoplasm without the evidence of malignant cells in the pleural effusion as well as sur‐ rounding tissues is called as "paramalignant" effusion. Presence of paramalignant effusion is not a contraindication for the surgery. Obstructive pneumonia or atelectasia, lymphatic obstruction, cheilothorax caused by the invasion of thoracic duct, trapped lung, pulmonary embolism, hypoalbuminemia, cachexia, radiotherapy and, chemotherapeutics such as bleo‐ mycin, methotrexate and cyclophosphamide are the well known causes of para-malignant effusion [17].
