Pleural effusion is the abnormal accumulation of fluid in the space surrounding the lungs. When caused by cancer, it is termed malignant pleural effusion (MPE), a common and serious complication of advanced malignancy. MPE develops in up to 15-20% of all cancer patients, most frequently due to lung or breast cancer. The presence of this excess fluid severely impairs lung function, leading to shortness of breath, and generally indicates a poor prognosis. Understanding the mechanisms by which cancer disrupts fluid balance is crucial for effective diagnosis and palliative treatment.
The Pleural Space and Normal Fluid Balance
The lungs and the inner surface of the chest wall are lined by two thin membranes known as the pleura. The visceral pleura covers the lungs, while the parietal pleura lines the chest cavity; the narrow gap between them is the pleural space. This space normally contains only 10 to 20 milliliters of lubricating fluid, which allows the lungs to expand and contract without friction during breathing.
The fluid volume is regulated by a continuous turnover process. Fluid is primarily secreted from systemic capillaries within the parietal pleura, driven by hydrostatic and oncotic pressures. Fluid removal is handled by lymphatic vessels, which are located mostly on the parietal pleura. The lymphatic system reabsorbs fluid through specialized pores, called stomata, which is the primary control mechanism preventing fluid accumulation.
Direct Tumor Effects Disrupting Drainage
Cancer causes malignant pleural effusion primarily through mechanical obstruction of the fluid drainage pathways. Tumor cells often metastasize and seed directly onto the pleural surfaces, which increases the rate of fluid production. This growth of malignant cells, known as pleural carcinomatosis, overwhelms the space’s normal capacity for fluid removal.
The physical presence of the tumor cells directly interferes with the lymphatic system. Malignant cells infiltrate and block the stomata, the tiny openings on the parietal pleura that act as one-way valves for fluid reabsorption. This disruption of parietal lymphatic drainage ensures that the secreted fluid cannot be cleared from the pleural space.
Furthermore, the cancer can obstruct the larger lymph nodes located in the chest cavity, particularly the mediastinal lymph nodes. These nodes are the final collection points for the fluid draining from the entire pleural space. When a tumor mass blocks this downstream drainage system, it causes a back-up of lymphatic fluid. This mechanical blockage is a significant factor in the development of MPE, especially in cancers like lung cancer and lymphoma.
Systemic Contributions to Fluid Leakage
Beyond physical obstruction, cancer contributes to fluid accumulation through systemic and molecular effects that cause the blood vessels to become leaky. Cancer cells and associated immune cells release inflammatory signaling molecules, such as cytokines and Vasoactive Endothelial Growth Factor (VEGF). VEGF specifically targets the blood vessels that supply the pleura, increasing their permeability.
This increased permeability allows large protein molecules to leak out of the blood capillaries and into the pleural space. The resulting fluid is classified as an exudate because it is rich in protein and cellular debris, which is characteristic of most MPEs. The protein molecules draw water along with them, increasing the volume of fluid in the pleural space.
In some cases, advanced cancer can lead to a transudative component. Advanced malignancy may be associated with systemic malnutrition or liver dysfunction, resulting in low levels of serum albumin, a protein that maintains oncotic pressure in the blood. When serum albumin is low, the oncotic pressure decreases, making it easier for fluid to leak out of the capillaries.
Diagnosis and Treatment Approaches
The initial step in diagnosing a suspected pleural effusion involves imaging tests such as a chest X-ray or a computed tomography (CT) scan. These images confirm the presence of excess fluid and can provide clues, such as pleural nodules or thickening, that suggest a malignant cause. However, imaging alone cannot definitively confirm MPE.
A diagnostic and therapeutic procedure called thoracentesis is then performed, which involves inserting a needle to drain a fluid sample. This fluid is sent for laboratory analysis, where a cytopathology team searches for malignant cancer cells to confirm the diagnosis of MPE. The fluid chemistry is also analyzed using criteria, such as Light’s criteria, to classify the fluid as an exudate, typical of malignancy due to its high protein and lactate dehydrogenase (LDH) content.
Management for MPE is primarily palliative, focused on relieving the patient’s symptoms. Therapeutic thoracentesis provides immediate relief by draining the fluid, but it often reaccumulates quickly. For recurrent effusions, two primary treatment options are utilized: an indwelling pleural catheter (IPC) or pleurodesis.
Indwelling Pleural Catheter (IPC)
An IPC can be inserted for intermittent, at-home drainage.
Pleurodesis
Pleurodesis aims to prevent fluid recurrence by fusing the visceral and parietal pleura together. This is achieved by draining the fluid completely and then instilling a chemical irritant, such as sterile talc, into the pleural space. The talc creates an inflammatory reaction that causes the two pleural layers to adhere, obliterating the space and preventing future fluid accumulation.