Malignant pleural mesothelioma is an uncommon type of cancer that begins in the mesothelial cells of the pleura. The pleura is a thin membrane that surrounds the lungs and lines the chest cavity. The pleura consists of a visceral surface, which covers the lungs and a parietal surface, which lines the walls of the chest cavity and covers the upper surface of the diaphragm and lungs. The two layers are one continuous sheet of tissue that contains mesothelial cells. There is normally a very small amount of watery fluid within the pleural cavity that lubricates the pleural surfaces and allows the lungs to move freely over the inner surface of the chest wall during breathing.
Malignant pleural mesothelioma is predominantly caused by exposure to asbestos. The association between inhaled asbestos particles and mesothelioma was recognized in 1960.1 Asbestos exposure is also associated with:
Doctors classify pleural mesothelioma into 3 distinct categories: epithelioid, sarcomatoid, and mixed-type. Epithelioid is the most common, occurring in 60-70% of patients. However, it may be confused with another type of lung cancer called adenocarcinoma; therefore, special tests are necessary to confirm a diagnosis. The sarcomatoid type (10-20%) is the least common and most aggressive. Mixed-type (20-30%) shows features of both epithelioid and sarcomatoid. Before considering treatment options, patients must have a confirmed diagnosis of mesothelioma and accurate staging of the disease performed.
The following sections are included in this overview:
The majority of patients with malignant pleural mesothelioma experience shortness of breath and a third of patients experience chest pain. Patients may also experience weight loss, cough, weakness, fever, and loss of appetite. A pleural effusion (fluid between the lungs and chest wall) is also present in the majority of patients.2 Most patients have a significant history of asbestos exposure, which occurred 30-40 years prior to exhibiting signs of the disease. Men are three times more likely to have the disease than women because of work related exposure in high-risk occupations, such as mining, manufacturing, and ship construction.
Determining the presence of malignant pleural mesothelioma and the type of mesothelioma requires examination of tissues removed from the lung. Sometimes this can be accomplished by looking for cancer cells in the sputum or by the removal of fluid from a pleural effusion (thoracentesis) for evaluation under a microscope. More commonly however, a biopsy which is the removal of a small piece of tissue for examination under a microscope is required. While there was once a concern that needle biopsy could spread the cancer, research indicates that a needle biopsy of the pleura is a safe procedure and it detects malignant mesothelioma approximately 86% of the time.3 A biopsy can be obtained using one or more of the following procedures.
Bronchoscopy: During a bronchoscopy, a surgeon inserts a bronchoscope (thin, lighted tube) through the nose or mouth into the trachea (windpipe) and bronchi (air passages that lead to the lung). Through this tube, the surgeon can examine the inside of the trachea, bronchi and lung and collect cells or small tissue samples.
Fine Needle Aspiration: During this procedure, a surgeon inserts a needle through the chest into the area suspected of cancer in order to remove a tissue sample for examination under the microscope.
Thoracotomy: A thoracotomy is a major surgery, which involves opening the chest in order to remove a sample of tissue.
Sputum Cytology: Sputum cytology is a procedure used to examine mucus that is coughed up from the lungs or breathing tubes. The mucus is examined under a microscope in order to detect cancer cells.
Thoracentesis: During a thoracentesis, a needle is inserted through the chest wall into the pleural space in order to remove a sample of the fluid that surrounds the lungs in order to check for the presence of cancer cells.
Once cancer has been diagnosed, a careful evaluation will be made to determine how far the cancer has spread (also called stage). In order to begin evaluating and discussing treatment options with their healthcare team, patients need to know the correct stage of their cancer. The following tests may be performed to accurately stage mesothelioma:
Chest x-ray: A chest radiograph may show pleural effusions or pleural thickening.
Computed tomography (CT): A CT scan may show whether there is fluid, thickening, or irregularities in the pleural. CT may also be helpful for determining whether the cancer has spread beyond the pleura into the chest wall, pericardium (sack around the heart), diaphragm (breathing muscle), or the lymph nodes.
Magnetic resonance imaging (MRI): An MRI scan can be particularly useful to determine how extensive the cancer is and whether it can be removed with surgery. In addition to identifying the extent and whether the cancer can be removed with surgery, a special type of MRI, called contrast-enhanced MRI, is also helpful for differentiating mesothelioma from other types of cancer.
Positron emission tomography (PET): Unlike techniques that provide anatomical images, such as X-ray, CT and MRI, PET shows chemical and physiological changes related to metabolism. This is important because these functional changes often occur before structural changes in tissues. PET images may therefore show abnormalities long before they would be revealed by X-ray, CT, or MRI. PET can sometimes distinguish between malignant and non-malignant fibrous processes in the pleura.4
Following a tissue diagnosis of mesothelioma, it is important to accurately determine the stage of cancer in order to begin treatment planning.
The stage describes how far the cancer has spread and each stage of cancer may be treated differently. There are many staging systems, but TNM is the most common. “T” refers to the size of the tumor, “N” to the number of lymph nodes involved, and “M” to metastasis. TNM staging measures the extent of the disease by evaluating these three aspects and assigning a stage, which is usually between 0-4. Generally, the lower the stage, the better the treatment prognosis (outcome) is.
A new international staging system for malignant pleural mesothelioma that is TNM-based was created in June 1994 at the Seventh World Conference of the International Association for the Study of Lung Cancer.5 There are currently six stages of malignant pleural mesothelioma: IA, IB, II, III, IV and Occult. While a higher stage number generally correlates with a worse prognosis, this system is relatively new and outcomes cannot be predicted with certainty. Determining mesothelioma stage requires obtaining a sample of lung and lymph nodes, which is typically performed during thoracentesis, and evaluating them under a microscope. Treatment details specific to disease stage may refer to the following:
Patients with stage I-III disease have cancer that can potentially be removed with surgery.
Stage IA: Patients with stage IA disease have cancer limited to the pleura on one side of the chest with no involvement of lymph nodes and no spread to other sites.
Stage IB: Patients with stage IB disease have cancer that has spread to the parietal pleura, including mediastinal and diaphragmatic pleura on one side of the chest and can have scattered foci of tumor also involving the visceral pleura. There is no involvement of lymph nodes or distant spread.
Stage II: Patients with stage II disease have cancer involving both parietal and visceral pleura and can have involvement of diaphragmatic muscle or extension into the lung. There can be lymph node involvement, but there is no distant spread.
Stage III: Patients with stage III cancer have locally advanced but potentially surgically resectable cancer. They have cancer involving parietal, mediastinal, diaphragmatic, and visceral pleura. They can also have spread to fascia, mediastinal fat, and soft tissue of the chest wall or involvement of the pericardium. These patients can have spread to the bronchopulmonary or hilar lymph nodes or to subcarinal or mediastinal lymph nodes, including the internal mammary nodes. They do not have spread to the opposite side of the chest or distant metastasis.
Patients with stage IV disease have cancer that cannot be typically removed with surgery. They have spread of cancer to the mediastinal, internal mammary or supraclavicular lymph nodes on the side of the chest opposite to the original cancer. Distant metastasis can also be present.
Patients with recurrent cancer have disease recurrence after primary treatment or failed primary treatment.
1 Antman KH, Pass HI, DeLaney T, et al. Benign and malignant mesothelioma. In: Devita VT Jr, Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 4th Edition Philadelphia, PA:JB Lippincott Co;1993:1489-1508.
2 Ruffie P, Feld R, Minkin S, et al. Diffuse Malignant Mesothelioma of the Pleura in Ontario and Quebec: A Retrospective Study of 332 Patients. Journal of Clinical Oncology 1989;7:1168-1168.
3 Adams RF, Gray W, Davies RJ, et al. Percutaneous image-guided cutting needle biopsy of the pleura in the diagnosis of malignant mesothelioma. Chest. 2001;120:1798-802.
4 Eibel R, Tuengerthal S, Schoenberg SO. The Role of New Imaging Techniques in Diagnosis and Staging of Pleural Mesothelioma. Current Opinion in Oncology. 2003;15:131-138.
5 Rusch VW. A Proposed New International TNM Staging System for Malignant Pleural Mesothelioma. Chest 1995;108:1122-1128.
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