Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a rare and aggressive form of cancer that originates in the pleura within the chest cavity. The pleura is a thin cellular lining than envelops both the lung (termed the "visceral" pleura) and chest wall (the "parietal" pleura), as well as the diaphragm, and the heart and major blood vessels in the central portion of the chest. Transformation of the pleura into cancer, therefore, will form a layer of tumor that covers, and may in fact grow directly into any of these vital structures.

There are three major subtypes of MPM, which are defined by their histology (appearance under the microscope). Epithelial MPM is the most common form and makes up about 60% of all cases. Sarcomatoid MPM comprises about 10% of all cases, and these tumors display a somewhat more aggressive behavior. The remainder of cases are comprised of the Mixed, or Biphasic variant of MPM that contains elements of both Epithelial and Sarcomatoid MPM.

Approximately 85% of cases of MPM are thought to be due to past exposure to asbestos, which is usually occupation related. Occupations associated with asbestos exposure include shipbuilding, construction, plumbing, and work with insulation. This disease has a long latency period, which means that it may not become apparent until 15 to 50 years after the initial asbestos exposure. Less common risk factors include high-dose radiation, a particular virus called simian virus 40, and hereditary factors.

The most common symptom of MPM is shortness of breath that is typically caused by a pleural effusion. This effusion is fluid that accumulates around the lung due to secretion of fluid by tumor cells, and the fluid does not allow the lung to fully expand. Chest pain, cough, weight loss, generalized malaise, and occasionally fevers may also be present.

The diagnosis of MPM is often first suspected based in imaging studies. A chest x-ray may first reveal a pleural effusion and lead to further workup. A computed tomography (CT) scan most often reveals diffuse thickening of the pleura (Figure 2), although minimal or mild thickening associate with pleural effusion may be the only finding. PET scanning is an imaging technique that highlights tumors based upon their increased energy utilization. In MPM, PET scanning is useful in conjunction with CT to determine the amount of disease within the chest, and it also helps to investigate the possibility of disease spread outside of the chest. MRI is sometimes utilized to evaluate invasion into the chest wall or through the diaphragm into the abdomen.

The ultimate diagnosis of MPM relies on microscopic tissue evaluation. Therefore, obtaining a tissue biopsy is critical. This is often done by VATS (video-assisted thoracic surgery) biopsy techniques and sometimes by a CT-guided needle biopsy. Pleural effusions can be drained using needle techniques and sampled for the presence of MPM cells. However, the effusions of MPM will commonly not contain cancerous cells and more than simple needle drainage is therefore often needed to establish the diagnosis.

Staging systems for cancers are meant to grade the spectrum of early to advanced disease in order to guide appropriate therapy. The two most important factors in the staging of MPM are (1) the degree of invasion of surrounding structures and (2) the presence or absence of involvement to mediastinal lymph nodes. Mediastinal lymph nodes are lymph nodes of the central chest that thoracic tumors can spread to beyond the earliest stages.

Imaging studies such as CT, PET, and MRI are routinely used to assess tumor burden and invasion. Early stage tumors may present as focal areas of pleural thickening, and later stages may present as large masses or tumors that completely encase the lung and invade major structures in the chest. To assess the involvement of mediastinal lymph nodes by MPM, PET scanning is useful. However, the most accurate method of assessment is mediastinoscopy, a surgical biopsy technique to sample these nodes for microscopic evaluation.

Generally, stage I MPM represents early disease with low tumor burden; stage II MPM represents more locally advanced disease with a greater tumor burden; stage III MPM represents locally advanced disease with significant invasion of surrounding structures or spread to mediastinal lymph nodes; and stage IV MPM represents a technically unresectable tumor or spread to the abdomen or other side of the chest.

The treatment of MPM depends on the tumor stage and the patient's age and overall condition. Treatment strategies for MPM include chemotherapy, radiation, surgery, or a combination of these approaches. At Stanford, we believe in a surgery-based multimodality treatment approach, whenever possible. Drs. Leah Backhus and Mark Berry have special interest in this disease process.

The principle of surgical resection for MPM is to remove all macroscopic (visible) tumor with the hope that chemotherapy and/or radiation can eliminate residual microscopic disease. The two main procedures to accomplish this are Pleurectomy & Decortication (P/D) and Extrapleural Pneumonectomy (EPP). Each of these procedures is performed through an open incision in the chest, called a thoracotomy. P/D involves removal of all gross tumor by careful stripping of the pleura from the lung surface, chest wall, and diaphragm, avoiding removal of the lung itself. This sometimes requires additional resection and reconstruction of the diaphragm and pericardium if these structures are involved with tumor. EPP is a more extensive procedure, with somewhat higher risks, that involves complete resection of the entire lung and pleural surface of the chest wall, as well as resection and reconstruction of the diaphragm and pericardium.

The diagnosis of MPM can be devastating. At Stanford, our patients are evaluated by a multidisciplinary team of specialists that includes surgeons, medical oncologists, radiation oncologists, and radiologists. This close collaboration ensures a cohesive and personalized care experience for our patients. Our team of experts coordinates a comprehensive treatment plan using state-of-the-art technology to patients with MPM.  

Diagnosis: We routinely perform minimally invasive VATS procedures to obtain an adequate tissue biopsy for diagnosis. If adequate tissue has already been obtained at another institution, we will arrange review by our Stanford pathology team.

Staging: Chest CT and PET scans are utilized to evaluate the distribution of disease, and this is sometimes supplemented with MRI. We recommend and perform cervical mediastinoscopy to evaluate potential spread to mediastinal lymph nodes (N2 disease), and this can often be performed at the same time as the VATS biopsy.

Treatment: Whenever possible, we believe in a surgery-based multi-modality treatment program for MPM:

For Stage I-III disease without the presence of disease in the mediastinal lymph nodes (N2 negative), we recommend surgical resection (either P/D or EPP, depending upon extent of disease and patient health status) and adjuvant (postoperative) chemotherapy and possibly radiation. When the character of the tumor is resectable by P/D, this is our favored approach. However, when significant invasion of the lung is present, EPP is recommended in sufficiently healthy patients.

For patients in whom N2 disease is present, our treatment pathway entails preoperative chemotherapy, still possibly followed by surgical resection, and potential adjuvant radiotherapy.

For patients with Stage IV disease or those not medically fit for surgery, we generally recommend chemotherapy, with or without state-of-the-art radiotherapy, and aggressive control of symptoms.