In most cases, malignant cells can be found in the pleural effusion. If the pleural effusion is accompanied by metastatic nodules in the mediastinum or pleural surface, malignant pleural effusion can be diagnosed regardless of whether malignant cells can be found in the pleural effusion.
Approximately 40% of clinically significant pleural effusions seen are caused by malignant tumors, the most common being lung cancer, breast cancer, and lymphoma. There are some differences in tumor types between males and females, with males commonly having lung cancer and lymphoma, and gastrointestinal tract tumors; females commonly having breast cancer, female genital tract tumors, lung cancer, and lymphoma.
I. Etiology
Malignant pleural effusion accounts for 38% to 53% of all pleural effusions, among which metastatic tumors of the pleura and diffuse malignant mesothelioma of the pleura are the main causes of malignant pleural effusion.
II. Pathogenesis
Under normal circumstances, the adult pleural cavity can produce 100-200ml of pleural fluid in 24h, which is filtered out by the wall pleura and then reabsorbed by the small pores of the wall pleura, while the formation and reabsorption of pleural fluid by the dirty pleura is in a very small dynamic balance. The main driving forces of pleural fluid circulation are the hydrostatic pressure in the pleural capillaries and pleural cavity, the negative pressure in the pleural cavity and the patency of lymphatic reflux.
The average negative pressure within the pleural cavity in normal subjects is -0.49 kPa (-5 cmH2O) The pleural fluid protein content is small, about 1.7%, and the colloid osmotic pressure it has is 0.78 kPa (8 cmH2O). The capillary hydrostatic pressure of the wall pleura with blood supply from the body circulation is 1.078 kPa (11 cmH2O) and the colloid osmotic pressure in the capillaries of both the wall and dirty pleura is 3.33 kPa (34 cmH2O). The normal human pleural cavity contains only a small amount (5-15 ml) of fluid to reduce the mutual friction between the wall pleura and the dirty pleura during respiration.
Pleural effusion can be caused when any of the above major driving forces regulating pleural fluid dynamics become abnormal. Malignant pleural effusions arise from a variety of complex mechanisms, which are summarized as follows.
1, the most common causative factor
are metastases from mural and/or visceral pleural tumors. These metastases destroy capillaries and thus lead to fluid or blood leakage, often causing hemorrhagic pleural effusion.
2.Drainage disorder of lymphatic system
Lymphatic drainage disorder is the main mechanism of malignant pleural effusion. Tumors involving the pleura, whether they originate in the pleura or metastasize to the pleura, can block the lymphatic vessels on the surface of the pleura and disrupt the normal circulation of the pleural fluid, thus producing pleural effusion; in addition, the lymphatic drainage of the wall pleura mainly enters the mediastinal lymph nodes, and malignant tumor cells can cause obstruction in any part between the pleural pores and the mediastinal lymph nodes, including the formation of tumor cell embolism in the lymphatic vessels and mediastinal lymph node metastasis, which can cause pleural effusion. All of them can cause the obstruction of reabsorption of fluid in the pleural cavity and lead to pleural effusion.
3.Large amount of protein in tumor cells enter the pleural cavity
The tumor tissue on pleura grows too fast and the cells are easily shed. The tumor cells entering the pleural cavity enter the pleural cavity due to the lack of blood transport and the necrosis and decomposition of protein in the tumor cells, which increases the colloid osmotic pressure in the pleural cavity and produces pleural effusion.
4.Increased permeability of pleura
Malignant tumor invading dirty layer and wall layer pleura, tumor cells planted in pleural cavity can cause inflammatory reaction of pleura, capillary permeability increases, liquid infiltration into pleural cavity primary lung cancer or lung metastatic tumor causes obstructive pneumonia and produces pleural effusion similar to pneumonia.
5.Decrease in intrapleural pressure and increase in hydrostatic pressure of pleural capillaries
Lung cancer causes bronchial obstruction and distal pulmonary atelectasis, resulting in the decrease of intrapleural pressure. When the intrapleural pressure drops from -1.176kPa (-12cmH2O) to -4.7kPa (-48cmH2O) there will be about 200ml of fluid accumulation in the pleural cavity. Malignant tumors in the lungs can invade the vena cava or pericardium, causing venous return obstruction, capillary hydrostatic pressure on the pleural surface increases, and pleural effusion arises.
6.Other
Tumor cells invade blood vessels to form tumor thrombus and then produce pulmonary embolism and pleural effusion; malignant tumor consumption causes hypoproteinemia and decrease in plasma colloid osmotic pressure, resulting in pleural effusion; pleural cavity exudative effusion can be produced after thoracic or mediastinal radiation treatment.
III. Clinical manifestations
Most patients are mostly cachectic manifestations of advanced tumor, such as weight loss, wasting and weakness, anemia, etc. About 1/3 of patients with tumor pleural effusion have no obvious clinical symptoms, and pleural effusion is only found during physical examination. The remaining 2/3 of patients mainly present with progressively worsening dyspnea chest pain and dry cough. The degree of dyspnea is related to the amount of pleural effusion, the rate of formation of pleural fluid and the patient’s own lung function status. When the amount of fluid accumulation is small or the rate of formation is slow, the clinical dyspnea is mild, with only chest tightness and shortness of breath.
If the amount of fluid is large and the lungs are under obvious pressure, the clinical dyspnea will be heavy, and even telangiectatic breathing and cyanosis will occur; although the amount of fluid is not large, it will be formed rapidly in a short period of time, and it will also be clinically manifested as heavy dyspnea, especially if the lung function is poorly compensated. Patients with large amount of pleural effusion prefer to take the affected side to lie down, which can reduce the respiratory movement of the affected side and help the compensatory breathing of the healthy side of the lung and relieve the respiratory difficulty. Tumor invasion of the pleura, pleural inflammation and large pleural effusion causing wall pleural traction can all cause chest pain.
When the wall pleura is invaded, it is mostly persistent chest pain; when the diaphragmatic pleura is invaded, the pain radiates to the affected scapula; when a large amount of pleural fluid stretches the wall pleura, it often causes fullness and hidden pain. The cough is mostly an irritating dry cough, caused by the compression of the bronchial wall by the stimulation of the pleural fluid. During physical examination, it can be found that the respiratory movement on the affected side is weakened, the intercostal space is full, the trachea is displaced to the healthy side, the effusion area is percussed with turbid sounds, and the breath sounds disappear.
IV. Diagnosis
The diagnosis of effusion is often not very important when pleural effusion appears in the course of the disease in patients with clear metastatic cancer. Treatment of the primary tumor is the main focus, and systematic systemic treatment should be taken before respiratory symptoms appear. When effusion causes respiratory distress in patients and local treatment is required, there should be a clear diagnosis of pleural effusion before treatment is started.
When a new pleural effusion develops in a patient without malignancy, the underlying cause of the leaking fluid should be sought first. Thoroughly excluding heart failure, tuberculosis and other causes of idiopathic pleural effusion, thoracentesis and biochemical analysis and tumor cell examination of pleural effusion, or closed pleural biopsy can generally confirm the diagnosis of malignant pleural effusion.
1.Symptoms and signs: a small amount of effusion is asymptomatic. There is shortness of breath and palpitations that gradually increase when there is moderate or large amount of effusion. Physical examination shows intercostal fullness on the affected side, reduced respiratory motion, reduced or absent fibrillation, trachea and mediastinum shifted to the opposite side, solid percussion, and reduced or absent breath sounds.
2.Auxiliary examinations.
① Chest x-ray examination. In a small amount of effusion, the angle of the rib diaphragm becomes blunt; in a medium amount of effusion, the middle and lower part of the lung field shows a uniform dense shadow, and the upper edge shows a high and low depression; in a large amount of effusion, the affected side shows a dense shadow, and the mediastinum is shifted to the healthy side. In the case of subpulmonary effusion, there is an artifact of diaphragm elevation, which can be determined by projection in lateral or horizontal position. In the case of interlobular encapsulated effusion, there are nearly circular or oval shadows in different parts of the pleural cavity or interlobular space, and the location can be determined by lateral film.
②Pleural fluid examination. Depending on color, property, specific gravity, mucin characterization test, cell count classification, smear to check pathogenic bacteria, sugar, protein determination, etc. can be initially determined as exudate, leaky fluid. Specific gravity >1.018, white blood cell >100×106, protein quantification 30g/l, pleural fluid protein quantification/serum protein quantification >0.5, pleural fluid lactate dehydrogenase/serum lactate dehydrogenase >0.6, pleural fluid lactate dehydrogenase amount >200u/l is exudate, and vice versa is leaky fluid.
③Ultrasonic sounding. The puncture site can be selected more accurately, which is helpful for diagnosis and differential diagnosis.
④Pleural biopsy. Pleural biopsy is feasible when it is difficult to make a clear diagnosis by the above-mentioned tests.
⑤CT, mri examination. It has diagnostic value for pleural effusion caused by pleural mesothelioma.
3.Characteristics of pleural effusion in common diseases
(1)Pleural effusion in combination with heart failure, liver cirrhosis, nephrotic syndrome, etc. is leaking fluid.
(2) Tuberculous pleurisy effusion is exudate with increased leukocytes, mainly lymphocytes, increased lactate dehydrogenase and increased lysozyme.
(3) Pleural effusion accompanied by pneumonia is a modified fluid with a small amount of leukocytosis, mainly neutrophils, and pathogenic bacteria may be detected by smear or culture.
(4) Cancerous pleural effusion is rapidly growing, mostly bloody, and the nature of the effusion is often between exudate and leaky fluid, and tumor cells can often be found in the chest wave for multiple times. Carcinoembryonic antigen (cea) is often increased.
V. Examination
1.Checking the nature of pleural fluid
(1) Routine examination: malignant pleural effusion is usually exudate. Exudative pleural fluid is characterized by a protein content of more than 3g/100ml or a specific gravity of more than 1.016 in some patients with long-term pleural leakage, because the rate of absorption of fluid in the pleural cavity is greater than the rate of protein absorption protein concentration in the pleural fluid will also increase, and can be easily confused with exudate, so check the level of protein and lactate dehydrogenase (LDH) in pleural fluid and serum, for distinguishing exudate from leakage A 99% correct pleural effusion is an exudate if it has one or more of the following characteristics.
① pleural fluid protein/serum protein >0.5;
② pleural fluid LDH/serum LDH>0.6;
③ pleural fluid LDH>2/3 of the upper limit of serum LDH.
Most of the pleural exudate is foggy because it contains leukocytes. Cytological examination of exudative pleural effusion with a leukocyte count in the range of (1-10)×109/L leukocyte count L is leaky fluid while >1×109/L is pustulous pleural fluid. A pleural fluid with predominantly neutrophils suggests inflammatory disease, while a predominantly lymphocyte count is more likely to be seen in progressive tuberculosis lymphoma and cancer a complete blood pleural fluid with a red blood cell count above 1×1012/L is seen in trauma, pulmonary infarction or cancer.
Glucose levels in pleural fluid lower than blood glucose levels are seen in tuberculosis, rheumatoid arthritis, pustular chest, and cancer. Pleural fluid pH is usually parallel to arterial blood pH, but is usually below 7.20 in rheumatoid arthritis, tuberculosis and cancerous pleural fluid.
(2) Cytological examination: In patients with cancerous pleural effusion, cancer cells can be detected in the first specimen sent to about 60% of patients, and the positive rate can reach 90% if three consecutive separate samples are taken. Taking several specimens during split sampling helps to improve the diagnostic rate because the specimens taken in duplicates contain fresher cells early degenerated cells were removed in the previous thoracentesis. Mechanisms of pleural effusion due to cancer include lymphatic or bronchial obstruction, hypoproteinemia in addition to direct invasion of the pleura. It should be noted that cytological examination of pleural effusion in patients with lymphoma is unreliable.
2.Pleural biopsy
The positive rate of pleural biopsy is about 46%. Pleural fluid cytology combined with pleural biopsy can make the positive rate reach 60%-90%.
VI. Treatment
Whether aggressive treatment is performed depends on the degree of respiratory symptoms produced by the malignant pleural effusion. If the patient has no respiratory symptoms or is in the end stage, no specific local treatment is required. When the clinical situation is uncertain, simple thoracentesis is appropriate If the patient’s respiratory symptoms do not improve after removal of a certain amount of pleural fluid in the chest, it is possible that the patient’s condition is due to an underlying pulmonary disease, such as emphysema or a primary or secondary malignant lung tumor. In such cases, local treatment is also contraindicated.
Chemotherapy and radiation therapy for the tumor causing the pleural effusion can help eliminate the pleural effusion and improve respiratory symptoms. For pleural effusions arising from lymphoma, lung cancer and breast cancer obstructing lymphatic vessels, radiation therapy can be effective in removing the cause of obstruction and reconstructing and improving pleural fluid dynamics. For life-threatening pleural effusions affecting respiratory dynamics, thoracentesis can help control symptoms until other effective treatments are found.
1.Etiological treatment: Active treatment of the primary disease.
2.Elimination of effusion: a small amount of effusion can be left untreated to be absorbed naturally; if a moderate amount of effusion or more has symptoms of compression, thoracentesis should be performed to extract the effusion 2 to 3 times a week. The amount of fluid should not be too much and too fast to prevent pleural shock and ipsilateral dilated pulmonary edema.
3.Drug injection: Dexamethasone can be injected after puncture for tuberculous pleurisy, antibiotics can be injected for septic pleurisy, anti-cancer drugs can be injected for cancerous pleurisy, or tetracycline can be injected after thorough drainage to produce chemical stimulation causing adhesions to reduce the compression symptoms caused by excessive growth of cancerous pleural fluid.
4.Pleural cavity intubation and drainage: When repeated aspiration of cancerous effusion is not effective, a thin catheter can be inserted for closed drainage, and the above drugs can be injected after striving for complete drainage in about 72 hours.
5.Surgery: If the medical treatment of chronic abscess chest is not complete, surgical treatment can be considered.