Malignant pleural effusions are a common complication of malignancy, and malignancy is a common cause of pleural effusions in general. Malignancy accounts for roughly 40% of symptomatic pleural effusions, with congestive heart failure and infection being the other leading causes. Lung cancer, breast cancer, lymphoma, and leukemia account for approximately 75% of all malignancy-associated effusions. Significant use of health care resources is attributable to malignant effusions, with approximately 100,000 cases per year being diagnosed in the United States and 43 cases being detected per 100,000 hospital admissions.
There are several types of plasma cell neoplasms. These diseases are all associated with a monoclonal (or myeloma) protein (M protein). They include monoclonal gammopathy of undetermined significance (MGUS), isolated plasmacytoma of the bone, extramedullary plasmacytoma, and multiple myeloma.
(Refer to the Lymphoplasmacytic Lymphoma (Waldenström Macroglobulinemia) section in the PDQ summary on Adult Non-Hodgkin Lymphoma Treatment for more information.)
Incidence and Mortality
The normal pleural fluid space is occupied with approximately 10 cc of fluid with 2 g/dL protein. A pleural effusion is an accumulation of an abnormal amount of fluid between the visceral and parietal pleura of the chest. Normally, pleural fluid is absorbed by pulmonary venous capillaries (80%–90%), with some of it also absorbed by pleural lymphatics. Malignant effusions are usually exudative rather than transudative. Exudative effusions exhibit any one of the following characteristics:
Pleural fluid:serum protein ratio greater than 0.5.
Pleural fluid:serum lactate dehydrogenase (LDH) ratio greater than 0.6.
Pleural fluid LDH greater than two thirds of the upper limit of serum LDH.
These exudative malignant effusions are generally caused by pleural metastases, disruption of pulmonary capillary endothelium, or malignant obstruction of pleural lymphatics. Paramalignant effusions may result from chemotherapy, radiation therapy, atelectasis, and/or lymph node involvement.
Common symptoms associated with malignant pleural effusions include dyspnea, cough, and chest discomfort. About 20% of patients may experience weight loss and malaise. A chest x-ray is most commonly used for radiographic assessment. About 175 cc of pleural fluid will cause a blunted costophrenic angle discernible on chest radiography. A chest computerized tomography scan is more sensitive than a simple chest x-ray and is often used for assessment of loculated effusions because, in some instances, up to 500 cc of loculated fluid can be obscured behind the dome of the diaphragm.
Not all pleural effusions detected in cancer patients will turn out to be malignant effusions. Cancer patients are prone to developing conditions such as congestive heart failure, pneumonia, pulmonary embolism, malnutrition, and associated low serum albumin, each of which may cause a symptomatic effusion for which the clinical management would substantially differ from the management of a malignant effusion. For this reason, cytologic assessment is important. Pleural fluid cytology requires a minimum sample of 250 cc. The morphology of cells obtained from the pleural space can be difficult to assess because of mesothelial and macrophage abnormalities. The diagnostic sensitivity of pleural fluid cytology is approximately 65%, with a specificity of 97%. Flow cytometry can be applied to these specimens and is often useful, especially for assessment of lymphomas. Thoracoscopy and pleural biopsy are rarely needed for definitive diagnosis, but these techniques may be useful when routine pleural fluid collection and assessment are difficult because of loculation of the effusion. Thoracoscopy-guided biopsy is generally performed under local anesthesia and has a yield of more than 80%, with a lower risk of complications than thoracotomy.