Pleural mesothelioma is a type of malignant neoplasm originating from the serous membrane lining the thoracic cavity. In general, development of pleural mesothelioma is associated with prolonged exposure to asbestos.
Most commonly, PM patients present with non-specific respiratory symptoms and chest pain. These are clinically indistinguishable from complaints associated with asbestosis, other forms of pneumoconiosis and even pneumonia or congestive heart failure. This fact underlines the need for a detailed anamnesis that may reveal previous exposure to asbestos or erionite.
Most affected individuals are elder men who experience exertional dyspnea that progressively worsens until breathing difficulties are noted at rest. Lung function impairment may also be related to dry cough, wheezing and hoarseness. Some patients report hemoptysis. Pleural tumors like PM may interfere with production and clearance of pleural fluid, which results in malignant pleural effusion. Adhesions between both layers of the pleura as well as infiltration of the thoracic wall and irritation of intercostal nerves are the pathophysiological equivalents of chest pain.
Workup consists in diagnostic imaging, obtainment and analysis of tissue samples as well as an assessment of the patient's overall condition.
Computed tomography scans are the diagnostic approach of choice since plain radiography is not sufficiently sensitive for detection or exclusion of PM. However, plain radiographic images may reveal increased quantities of pleural fluid, and the presence of pleural effusion does not only indicate the site of lesion but also serves to evaluate the patient's condition during follow-ups.
Analyses of fine-needle aspirates may suffice to confirm a tentative diagnosis of PM in patients with an occupational history of asbestos exposure. Though, in general, a reliable diagnosis can't be made without obtaining a biopsy sample. This is usually done by means of thoracoscopy, a procedure that simultaneously allows for the drainage of excess pleural fluid, possibly pleurodesis and tumor staging . In case a thoracoscopy is contraindicated, an ultrasound-guided Tru-Cut biopsy should be obtained for subsequent histopathological analysis.
Laboratory analyses of blood samples are usually conducted. Frequent findings are leukocytosis and elevated concentrations of inflammatory markers like acute-phase proteins. Patients may also present anemia and thrombocytosis, which are considered to be adverse prognostic factors . Levels of serum lactate dehydrogenase are often increased. With regards to tumor markers, levels of soluble mesothelin-related protein are elevated in PM patients while concentrations of carcinoembryonic antigen aren't .
Although complete surgical resection is recommended, it is often not feasible due to diagnostic delays and either primary or secondary diffuse tumor growth. In this context, pleurectomy is to be performed. Extrapleural pleuropneumectomy is sometimes advised to minimize the likelihood of residual tumor cells being left behind, but this radical surgical intervention requires highly specialized surgeons, is still associated with high mortality, and does not prolong median survival times .
Chemotherapy is not recommended if the patient's Karnofsky score is below 60%, unless their life quality is severely restricted by aggressive and rapid tumor growth that cannot be controlled by any other means. Similarly, irradiation is usually applied as a palliative measure. Additionally, adjuvant radiotherapy may prevent local recurrence if the tumor could be resected in its entirety.
PM patients that suffer from malignant pleural effusion may benefit from pleurodesis, a procedure that may hinder the renewed accumulation of pleural fluid. In contrast, symptoms of restrictive lung disease resulting from fibrotic tissue covering the lobes of the lung may indicate decortication.
Since patients suffering from PM present with unspecific symptoms and generally don't report exposure to asbestos or similar minerals that occurred decades ago, diagnosis of PM is usually delayed by several months after the onset of symptoms. Consequently, even non-diffuse mesothelioma are often unresectable at the time of diagnosis and only palliative treatment can be provided. Thus, the patient's prognosis is often poor, with median survival times of only 4 to 12 months . Male sex, old age, chest pain, loss of appetite, weight loss and impairment of lung function have been shown to be unfavorable prognostic factors . Additionally, more severe alterations of blood cell counts and levels of inflammatory markers are likely associated with a poorer prognosis .
The single most important risk factor for PM is exposure to asbestos, and furthermore, a causative role in PM pathogenesis has been proven for erionite .
To date, it is not known whether radiation exposure or viral infectious diseases predispose for PM. Infection with Simian virus 40 has repeatedly been related to PM pathogenesis . Possibly, virus infection further increases the risk of developing pleural neoplasms after exposure to the aforedescribed minerals, rather than directly inducing malignant transformation of epithelial cells.
As has been indicated above, exposure to asbestos is the main risk factor for PM. Asbestos has been used in construction and textile industry, in paper production and ship building, among others, after being extracted in asbestos mines. Accordingly, miners, employees of the construction and processing industries and eventually those people using the respective end products are at highest risks of exposure to asbestos. Most of these people are males, and this may partially explain while four out of five PM patients are men .
The previously given description applies to several millions of workers worldwide. Nevertheless, PM is a rare type of neoplasm. Highest incidence rates are reported in Australia and Great Britain . In both countries, the overall incidence is 29 per 1,000,000 inhabitants. During the last years, slight increases have been observed in PM incidence, but this development is mainly ascribed to improved diagnostics and more reliable identification of PM patients. In general, it is to be expected that PM incidence rates decrease in industrialized nations due to the reduction of asbestos use in these geographical regions. However, this trend will only become observable after a time lag of about 40 years, which is the mean time from asbestos exposure to diagnosis of PM. In large parts of the developing world, asbestos use continues unchanged.
It has been estimated that 43,000 people die each year from PM , but according to the World Health Organization, the overall mortality due to PM is more than twice as high .
The pleura consists of a parietal and visceral layer that line the thoracic cavity and those organs it contains, respectively. The outermost layer of the pleura is the mesothelium, a single layer of epithelial cells. Parietal and visceral mesothelium are separated by a very thin film of pleural fluid, and only few cell layers are between the visceral mesothelium and the alveolar sacs. These short distances are easily overcome by asbestos fibrils and similar carcinogenic crystals. Thus, exposure to asbestos is not only related to an increased risk of pulmonary cancer but also of PM.
Minerals that reach the pleural space are deposited on the mesothelium and constitute a persistent stimulus of macrophages, which aim at clearing those crystals. Distinct pro-inflammatory factors, e.g., interleukins and tumor necrosis factor-α (TNF-α), are released by activated macrophages and induce a chronic inflammation . Moreover, mesothelial cells augment their expression of TNF-α receptors, and binding of that cytokine provokes the activation of NF-κB signaling pathways, which ultimately enhances the survival of mesothelial cells after exposure to asbestos . Besides the activation of intracellular pathways and subsequent overexpression of oncogenes and proto-oncogenes, asbestos fibrils may also directly interact with nucleic acids of exposed cells . Consequently, exposure to asbestos increases the risk of mesothelial cells with reduced capacities of apoptosis to accumulate chromosomal aberrations and gene defects. Monosomy of chromosome 22 as well as extensive rearrangements on chromosomes 1, 3, 6 and 9 are aberrations commonly found in PM.
Since asbestos exposure is the main risk factor for PM, any measure to reduce and replace asbestos-containing materials at people's workplaces and homes also contributes to decreasing their individual risk of this disease. To this end, modern standards have been implemented in construction and processing industries, and national laws regulate maximum times of exposure depending on the local asbestos burden. The interested reader is encouraged to consult applicable regulations with the respective authorities in their home country. Ideally, asbestos exposure is avoided completely because the one-hit theory applies to the development of PM.
To date, screening programs to detect PM in patients with a known history of asbestos exposure have not been implemented.
Mesothelium is the technical term for the single epithelial layer of serous membranes like pleura, peritoneum and pericardium. Neoplasms originating from the mesothelium are generally malignant and the vast majority of mesothelioma affect the pleura . Nevertheless, pleural mesothelioma (PM) is still a rare entity. Increasing incidence rates presumably result from improved diagnostics and a heightened awareness of the disease.
PM is a form of occupational cancer, typically associated with previous exposure to asbestos fibres and dust. Since several decades may pass from exposure to this carcinogenic material until malignant transformation of mesothelial cells, it is often a major challenge to establish the link between a patient's working environment and chest pain, dyspnea and further respiratory symptoms.
According to the aforedescribed etiology of PM, it may also be considered a late sequelae of asbestosis, a form of pneumoconiosis. It is generally diagnosed in elder men; their prognosis is poor. Median survival times after diagnosis are less than a year because tumors are typically non-resectable. Patients may benefit from surgery, chemo- and radiotherapy as well as palliative treatment, though, since these measures may provide relieve from symptoms and improve life quality.
Mesothelium is the medical term for the epithelial layer of serous membranes lining the thoracic and abdominal cavity as well as the heart sac. In detail, these membranes are referred to as pleura, peritoneum and pericardium. Tumors originating from the mesothelium are called mesothelioma; and if they affect the inner lining of the thoracic wall or lungs, they are designated pleural mesothelioma (PM).
PM are rare malignant neoplasms, most commonly induced by prolonged and intense exposure to asbestos. However, inhalation of asbestos fibers and dust does not immediately provoke tumor growth, but several decades may pass until first symptoms manifest. Thus, PM are typically diagnosed in elder patients with an occupational history of asbestos exposure.
Initially, patients may merely experience breathing difficulties under exercise, but symptoms progressively worsen. Non-productive cough, bloody sputum and wheezing may be noted. Many PM patients additionally claim chest pain. Because these non-specific symptoms don't allow for a reliable diagnosis of PM, computed tomography scans and biopsies have to be carried out.
Since treatment options are very limited - often only palliative therapy can be provided - preventive measures are of utmost importance to avoid the development of PM. In this context, reduction of asbestos exposure and replacement of asbestos-containing materials is highly recommended. Ideally, asbestos fibers and dust are not inhaled at all.