Overview
A type of pleural effusion caused by a malignant tumor invading the pleura.
The main symptoms are dyspnea, chest pain and dry cough.
Caused by malignant tumor invasion
The main treatments include local therapy and anti-tumor systemic therapy.
Definition
Malignant pleural effusion (MPE) is a pleural effusion caused by a primary or secondary malignant tumor of the pleura.
Once a lung cancer or extrapulmonary tumor presents with MPE, the disease is already in advanced stage, and the patient is already difficult to be cured, and the prognosis is extremely poor.
Classification
According to the presence or absence of symptoms at the time of diagnosis, MEP can be categorized into symptomatic MPE and asymptomatic MPE.
Most patients with MPE have clinical symptoms, but about 25% of patients may also be asymptomatic, and MPE is detected incidentally by physical examination or X-ray chest radiography.
Morbidity
MPE accounts for approximately 20% of all pleural effusions. In adults, MPE accounts for 38% to 52% of all pleural effusions.
Pleural metastases from malignant tumors account for more than 90% of the etiology of MPE, most notably due to direct invasion or metastasis of lung, breast, and lymphoma to the pleura, which accounts for about 75% of MPE.
Primary tumor foci cannot be found in 5% to 10% of MPE.
Etiology
Pleural metastasis of malignant tumors or invasion of the pleura by malignant pleural mesothelioma leads to excessive production or underabsorption of fluid in the thoracic cavity, which eventually causes pleural effusion.
Causes
Common causes of MPE are lung cancer, breast cancer, lymphoma, gynecologic malignancies and malignant pleural mesothelioma.
Lung cancer
Lung cancer is the number one cause of MPE.
A small percentage of lung cancer patients already have pleural effusion at the time of first diagnosis.
As the disease progresses, pleural effusion will occur in some patients, and in the advanced stage of lung cancer, a higher percentage of pleural effusion occurs.
Breast cancer
Breast cancer is the second most common cause of MPE.
In metastatic breast cancer, MPE occurs in about 48% of cases, and nearly half of these cases have a large pleural effusion.
Pleural effusion occurs ipsilateral to the breast cancer in 58% of cases, contralateral in 26%, and bilateral in 16%.
The average time between the diagnosis of breast cancer and the development of pleural effusion is 2 years, and in a few patients it may occur after 20 years.
Lymphoma
The third leading cause of MPE is lymphoma, primarily mediastinal lymphoma.
Most patients with lymphoma do not have pleural effusions at the time of initial diagnosis, but develop them as the disease progresses, and the majority of pleural effusions are celiac.
Gynecologic malignancies
The third leading cause of MPE is gynecologic malignancy, primarily ovarian cancer.
It is usually common in patients who present with metastases from ovarian cancer.
Malignant pleural mesothelioma
MPE is almost always present in patients with malignant pleural mesothelioma.
Pathogenesis
The mechanisms by which malignant tumors produce pleural effusion are complex and diverse, and the main mechanisms are as follows.
Impaired lymphatic fluid return
Disruption of the lymphatic return system in the pleural cavity is the predominant mechanism by which MPE arises.
Damage to any part of the lymphatic system between the pleura and mediastinal lymph nodes disrupts its integrity, leading to the production of pleural effusion.
Embolization of the lymphatic vessels between the small pleural foramina and the mediastinal lymph nodes by tumor cells exacerbates the obstruction of lymphatic drainage and contributes to the increase in pleural fluid. If the malignant tumor invades the thoracic duct leading to obstruction, compression or destruction, it can directly cause increased pleural effusion.
Enlargement of lymph nodes in the mediastinal hilar, infiltration of the pleura or lungs, which affects lymphatic return, or due to the obstruction of the thoracic duct triggers pleural effusion.
Pleural metastases from malignant tumors
Malignant tumors invading both the visceral and mural pleura, and the implantation of cancer cells in the pleural cavity can cause an inflammatory response and exudation, which is the second important mechanism leading to MPE.
This is because the metastasis of neoplastic organisms to the pleura can cause an inflammatory reaction, increase the permeability of capillaries, and allow fluid to leak into the pleural cavity.
In addition a large number of proteins in tumor cells enter the pleural cavity, increasing the osmotic pressure of the fluid in the pleural cavity and prompting the accumulation of pleural fluid in the pleural cavity.
Invasion of blood vessels by malignant tumors
Tumors can directly invade blood vessels, causing obstruction of small veins or triggering tumor trophoblastic angiogenesis, which leads to MPE due to increased vascular permeability caused by the release of vasoactive substances, and this effusion is often bloody.
Other mechanisms
Complete obstruction of the main bronchus or lobar bronchus by the tumor causes pulmonary atelectasis in the distal lung and increased negative pressure in the ipsilateral pleural cavity, resulting in pleural effusion.
Invasion of pericardium by malignant tumor increases hydrostatic pressure in pulmonary circulation, which can also cause pleural effusion.
Obstructive pneumonia caused by carcinoma produces a pleural effusion similar to that of a parapneumonic pleural effusion.
In patients with malignant tumors, invasion of tumor cells into blood vessels to form cancerous emboli leads to an increased incidence of pulmonary embolism, and pleural leakage from pulmonary infarction can result in pleural effusion.
Patients with thoracic tumors receiving radiation therapy can produce pleural cavity exudative effusion.
Malignant tumors often cause hypoproteinemia due to tumor consumption and insufficient intake of nutrients caused by a variety of factors, and plasma colloid osmotic pressure is reduced, resulting in pleural effusion.
Symptoms
Some patients with MPE are initially asymptomatic and are detected only on physical examination.
When a significant amount of MPE is present, the most common symptoms are exertional dyspnea, chest pain, and dry cough, which progressively worsen as the disease progresses.
Common Symptoms
Dyspnea
If the amount of fluid is small or the rate of formation is slow, dyspnea can be unremarkable, with the patient experiencing only chest tightness and shortness of breath.
If the pleural fluid is formed quickly and in large quantities, and the lungs are severely compressed, the dyspnea will be significant, and the patient may even experience sitting breathing (i.e., being forced to breathe in a semi-sitting or sitting position) and cyanosis (an abnormality in which the skin and the mucous membranes of the lips of the mouth show a bluish color).
Chest pain
Chest pain is also a common symptom and is mainly associated with pleural metastases and pleural inflammation.
Persistent pain in the chest is a consequence of mural pleural metastasis, and the pain can radiate to the ipsilateral shoulder when the pleura is invaded.
When the tumor invades the ribs and spine, the pain is severe.
If the chest pain is caused by pleural effusion, the chest pain is obvious when the amount is small, and it can be relieved or even disappear as the amount of effusion increases.
Dry cough
Dry cough is often caused by pleural effusion irritating the pleura or compressing the bronchial wall.
Accompanying symptoms
Since MPE is often seen in the advanced stage of malignant tumors, the following accompanying symptoms are often present:
Chronic disease appearance, loss of appetite, fever, etc.
For metastatic MPE, most of the patients have extensive metastasis, which belongs to the advanced stage of the disease, so the general condition is poorer, and even malignant disease, which manifests as weight loss, early satiety, anorexia, muscle and fat tissue depletion, and fatigue.
Consultation
Department of Medicine
Depending on the primary malignant tumor, MPE is often diagnosed and treated in the corresponding departments.
Department of Medical Oncology
When symptoms such as dyspnea, chest pain and dry cough occur, especially if they worsen in a short period of time and if there is a history of malignant tumor, we should be highly vigilant for the occurrence of MPE, and recommend that we seek medical treatment as soon as possible.
Thoracic surgery
MPE caused by lung cancer can be treated in the departments of thoracic surgery and respiratory medicine.
Breast Surgery
MPE caused by breast cancer is usually treated in breast surgery, medical oncology and other departments.
Preparation for medical treatment
Preparation for medical consultation: registration, preparation of documents, FAQs
Tips for the doctor
It is recommended to wear clothes that are easy to put on and take off before the visit so that the doctor can perform a physical examination.
Preparation List
Symptom list
Time of onset of symptoms, special manifestations, etc.
Is there any difficulty in breathing, such as chest tightness, shortness of breath, etc.?
Is there chest pain and on which side?
Is there a dry cough?
When did these discomforts begin?
Were there any aggravating or relieving factors for these discomforts?
Medical History Checklist
Is there a past history of malignancy?
Any history of food or drug allergies?
Checklist
Test results from the last six months, which can be brought to the doctor’s office
Laboratory tests: tumor markers.
Imaging tests: MRI, CT, PET-CT.
Pathological examination: histopathological examination.
Diagnosis
Diagnostic basis
The diagnosis of MPE requires a combination of medical history, physical examination and appropriate laboratory tests.
MPE should be highly suspected if a patient over 40 years of age presents with a bloody pleural effusion without fever; or if a patient with a well-defined primary cancer is combined with bloody exudate, or a fast-growing pleural effusion.
Medical history
Patients may have a history of malignant tumor, such as lung cancer, breast cancer or lymphoma.
Clinical manifestations
Patients may have the following symptoms or signs.
Symptoms
There may be symptoms such as dyspnea, chest pain, or dry cough.
Signs
When the amount of MPE is small, there may be no physical signs.
At the time of initial diagnosis, when the majority of pleural effusions are >500 ml, physical examination reveals all the appropriate signs.
About 1/3 of patients have malignant manifestations and superficial lymph node enlargement at the initial diagnosis.
Occasionally, there is chest wall tenderness and pleural friction on the affected side.
Other signs include emaciation, anemic appearance, and cachexia.
Imaging examination
Ultrasonography
Ultrasonography is an effective method of diagnosing pleural effusion, which can determine not only the presence or absence of pleural effusion, but also the presence or absence of pleural mass.
Ultrasound can show the width, range and depth of the pleural fluid plane from the surface of the body, assisting in localization and guiding puncture and fluid extraction.
Ultrasound can visualize the chest wall and pleura, as well as masses obscured by pleural fluid, and guide biopsy of subpleural masses.
Chest X-ray
X-ray is the basic method of detecting pleural effusion.
It can detect the location, size and extent of the lesion in the lungs, pleural cavity and mediastinum, as well as its relationship with the surrounding neighboring tissues and organs.
Chest CT
CT can correctly show the pleural adhesion, invasion or extensive metastasis of bronchial lung cancer, which is quite important for the etiologic diagnosis of MPE, the staging of lung cancer and the choice of treatment plan.
On CT, pleural invasion of the tumor can be judged as complete contact between the tumor and the pleural surface, irregular thickening of the local pleura, and blunting of the angle between the tumor and the pleura.
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) complements CT scanning in the diagnosis of MPE.
In the imaging of diffuse malignant pleural mesothelioma, MRI can better evaluate apical, diaphragmatic, and subdiaphragmatic involvement and determine whether the tumor invades structures such as the mediastinum and chest wall.
Thoracentesis and pleural fluid examination
Thoracentesis is one of the main methods of diagnosing pleural effusion. The line of pleural fluid withdrawn may be examined as follows.
Pleural fluid routine
Specific gravity, protein characterization test, cell count and classification.
Biochemical examination
Protein quantification of pleural fluid, pH, glucose determination, and examination of enzymes such as lactate dehydrogenase (LDH) and its isoenzymes, amylase, and acid phosphatase.
Tumor Marker Tests
Certain tumor markers such as carcinoembryonic antigen (CEA), cytokeratin fragment 21-1, and glycan antigens (e.g., CA125, CA15-3, CA19-9, etc.) contribute to the diagnosis of MPE.
The sensitivity of these indicators is generally not high, mostly 40% to 60%, but the specificity is relatively high, up to 80% to 90%, so they have a certain reference value. Combined testing of multiple tumor markers can improve its diagnostic rate.
Pathologic examination
Pleural fluid cytology is the simplest way to diagnose MPE, and its diagnostic rate is related to the type of primary tumor and its differentiation degree, which is 62%～90%. Multiple cytologic examinations increase the positive rate.
When cytopathology is suspicious or unconfirmed, further immunocytology will be helpful in aiding the diagnosis.
Thoracoscopy
This test has the highest rate of etiologic diagnosis of MPE and provides a basis for developing a treatment plan. Appropriate treatment (drainage of fluid, removal of adhesions and septations, etc.) can also be performed thoracoscopically.
Bronchoscopy
Bronchoscopy should be routinely performed to assist in the etiologic diagnosis of patients with unexplained pleural effusions accompanied by abnormal chest radiographs, especially when lung cancer is suspected.
Differential diagnosis
The main disease that needs to be differentiated from MPE is tuberculous exudative pleurisy with pleural effusion.
Patients with tuberculous pleurisy tend to have the following characteristics: the majority of cases occur in young adults, and in recent years there has been an increase in the incidence of middle-aged and elderly people. It is often accompanied by symptoms of tuberculosis intoxication, such as fever, night sweats, and fatigue.
Bacteriologic, cytologic or histopathologic examination of pleural fluid or pleural tissue can distinguish tuberculous pleurisy from MPE.
The diagnosis of tuberculous pleurisy is favored if experimental antituberculous therapy is effective.
Treatment
Aim of treatment: to relieve the symptoms of dyspnea and improve the quality of life.
Treatment principle: Once the diagnosis of MPE is clear, palliative care should be considered as early as possible. A comprehensive assessment of the patient’s symptoms, general condition and expected survival time should be carried out, and then a treatment plan should be formulated.
Initial treatment of MPE
Initial therapeutic pleurodesis is generally recommended for most patients with symptomatic MPE, and only a few patients with MPE whose primary tumor has been clearly identified but who are asymptomatic may be considered for clinical observation on medical advice.
Pleurodesis should be performed under ultrasound guidance, and in a few cases an indwelling chest drain is performed. However, regardless of the drainage method, patients should also receive concomitant treatment for the primary malignancy if necessary.
Therapeutic pleurodesis
Therapeutic pleurodesis is the first line of treatment for symptomatic MPE and is usually performed under ultrasound guidance using a needle or drain.
Pleurodesis can be used to determine the effect of drainage on symptomatic improvement, the ability of the lungs to fully reexpand, and the rate of subsequent reaccumulation of fluid; all of which can guide more radical treatment in the event of future reaccumulation of fluid.
Treatment of Primary Malignant Tumors
In certain tumor types, treatment of the primary malignancy may be effective in preventing recurrence.
Malignancies that respond to antineoplastic therapy include breast, ovarian, prostate, germ cell tumors, lymphomas, and small cell lung cancer.
However, in many cases antineoplastic therapy is ineffective against the cancer or the cancer still recurs after treatment.
Systemic Anti-tumor Drug Therapy
Certain tumors such as MPE due to pleural metastasis of small cell lung cancer may respond better to chemotherapy, and systemic treatment can be considered if there is no contraindication, combined with thoracentesis or pleural fixation.
Chemotherapy is also effective for MPE combined with breast cancer and lymphoma, and may be effective for MPE associated with prostate cancer, ovarian cancer, thyroid cancer, and embryonal cell tumors.
In addition, targeted therapy may be tried in selected suitable patients.
Radiotherapy
For patients with predominantly mediastinal lymphadenopathy (e.g., lymphoma), radiotherapy targeting the primary tumor may be helpful in eliminating MPE.
Intrathoracic drug therapy
When the malignant tumor is confined to the thoracic cavity, intrathoracic injection of antitumor drugs may treat the tumor itself in addition to reducing pleural fluid exudate.
In order to achieve maximum antitumor activity with minimal systemic side effects, chemotherapeutic agents with high local distribution concentrations and low systemic distribution concentrations need to be injected intrathoracically.
In the past, some scholars injected IL-2, IFNβ, IFNγ, etc. directly into the thoracic cavity to treat MPE and mesothelioma.
Domestic scholars have also tried to inject Staphylococcus aureus or mushroom polysaccharide into the thoracic cavity, and scholars have also tried to treat MPE with localized thermal perfusion in the thoracic cavity.
The efficacy of all these methods varies and is controversial. Whether they are suitable for use or not, it is necessary to consult the doctor in detail and strictly follow the doctor’s instructions.
Treatment of recurrent MPE
More than half of MPEs recur after initial pleurodesis and antitumor therapy, and up to 2/3 of these recur rapidly within 1 month.
For patients with recurrence, treatment options include repeat pleurodesis, indwelling chest drains, pleural fixation, combination therapy, complete or partial pleurectomy combined with pleurodesis, and thoracoabdominal shunt.
Treatment of refractory MPE
There is no authoritative consensus or guidelines for patients with refractory MPE.
For most patients with refractory MPE, repeated pleurodesis, prolonged indwelling chest drains, or pleural immobilization are often attempted first, followed by thoracoabdominal shunt or pleurodesis after ineffective treatment.
However, the effectiveness of the above methods is unclear and controversial, and the suitability of their use requires detailed consultation with a physician and strict adherence to medical advice.
Prognosis
MPE is mostly caused by the progression of malignant tumors and is a common complication of advanced malignant tumors. The prognosis for patients diagnosed with MPE is generally poor.
Survival
Survival
Survival after the development of MPE has been reported in the literature to range from 1 to 20 months, with an average survival time of only 3.1 months.
Patients with breast cancer complicating MPE have the best prognosis, with a survival period of 7 to 15 months and a 3-year survival rate of up to 20%.
The average survival time after diagnosis of lung cancer complicating MPE is 2 months, and about 2/3 of patients die within 3 months; a few patients with a large number of bilateral MPE can die within 1 week.
Survival of patients with malignant mesothelioma complicating MPE is about 10 months, and survival of the epithelial type is about twice as long as that of the sarcomatoid type. All patients who survive more than 3 years almost always have epithelial-type mesothelioma.
Prognostic factors
Correct diagnosis of malignant tumor cell and tissue types and timely, rational and effective treatment are important for relieving symptoms, alleviating pain, improving quality of survival, and prolonging life.
Daily
Daily Management
Mindset and Emotions
Good emotion and mindset cannot be replaced by drugs.
After diagnosis, patients may develop a sense of fear and may be afraid of pain, abandonment and death. Family members should pay attention to listen to the patient and strengthen mutual communication to improve the patient’s mental ability and relieve anxiety symptoms.
Family members should do their best to help the patient so that he or she can face all kinds of treatments positively with a good mindset.
During the period between treatments and after treatment, family members are advised to encourage the patient to do work and household chores that are within his/her ability, so as to reintegrate into his/her social role.
Daily care
Positional care
Adopt appropriate position according to the location of pleural effusion, usually in semi-recumbent position or on the affected side, to minimize the pressure of pleural effusion on the healthy side of the lung.
Keep the airway open
Encourage the patient to actively expel sputum and keep the airway open.
Breathing exercise
Slow abdominal breathing can be performed under doctor’s instruction. Regular breathing exercises can reduce the occurrence of pleural adhesions and improve ventilation.
Rehabilitation exercise
After the body temperature returns to normal and pleural fluid is aspirated or absorbed, encourage the patient to get out of bed gradually to increase lung capacity.
Dietary management
Reasonable adjustment of diet should be made, with high-calorie, high-protein and vitamin-rich food to strengthen the body resistance.
Follow-up examination
Strictly follow the doctor’s prescription for review, can refer to the review plan of primary malignant tumor.
If there is aggravation of dyspnea or shortness of breath, cough and hemoptysis, it may be the recurrence of pleural effusion, and timely consultation is needed.
Prevention
MPE is mostly a complication of advanced malignant tumors, so there is no special preventive measure at present.
Regular medical checkups: Early detection of precancerous lesions or malignant tumors can enhance the cure rate and avoid the occurrence of MPE.
Improvement of life style: avoid bad life habits, such as staying up late, smoking, drinking, etc., and enhance physical exercise to improve self physical fitness.