Introduction
Background
Mesothelioma is a malignant neoplasm originating from pleural or peritoneal surfaces; this condition is usually associated with occupational exposure to asbestos. Wagner et al connected asbestos to mesothelioma in a classic 1960 study of 33 patients with mesothelioma who were exposed to asbestos in a mining area in South Africa's North Western Cape Province.1 Of the 33 patients, 32 had been exposed to crocidolite, the most carcinogenic type of asbestos.
An image of mesothelioma is shown below:
Magnetic resonance image (MRI) in a 72-year-old Veterans Administration patient with left-sided mesothelioma. Note that the MRI well delineates the soft tissues and, in particular, the thoracoabdominal interface at the diaphragm.
Asbestos mining and production peaked from the 1930s-1960s, and asbestos was used in a variety of products ranging from construction supplies to brake linings. During World War II, hundreds of thousands of civilian and military workers, through their occupations, were exposed to asbestos. Production slowed dramatically in the 1970s as the health risks of asbestos became known. Governmental restrictions were placed on its use, and alternative materials became available. Despite these changes, asbestos continues to be used in the manufacture of some fire safety products.
The clinical latency period between asbestos exposure and mesothelioma development is 35-40 years, and as a result, the number of mesothelioma patients has continued to rise despite decreased asbestos production.
Recent studies
Yildirim et al examined the efficacy of using 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) and computed tomography (CT) scanning together to differentiate malignant mesothelioma from asbestos-related benign pleural disease. In a study of 31 patients (17 with malignant mesotheliomas, 9 with benign asbestos pleurisies, 5 with diffuse pleural fibrosis), the authors found that FDG PET/CT scanning accurately detected malignant lesions in 15 of the 17 patients with these neoplasms and that the combined modalities had a sensitivity of 88.2%, specificity of 92.9%, and overall accuracy of 90.3%. In addition, benign pleural disease was correctly detected in 13 of 14 patients.2
In a study of 55 patients, Mavi et al examined the usefulness of dual time-point FDG PET scanning in the differentiation of malignant mesothelioma from benign pleural disease. The authors found that at the second time point, FDG uptake in malignant lesions had increased over that at the first time point, while in benign lesions, uptake at the second time point had generally remained stable or decreased. The authors concluded that dual time-point FDG PET scanning seems to be an accurate means of differentiating malignant from benign pleural disease.3 Evidence from a similar study by Yamamoto et al also suggested that dual time-point FDG is useful for differentiating malignant pleural mesothelioma from benign pleural lesions.4
Pathophysiology
The 2 subgroups of asbestos are termed amphiboles and serpentines. Amphiboles are long needlelike fibers with high length-to-diameter ratios and are resistant to dissolution. These fibers remain in the tissues for years. Crocidolite is the amphibole most available commercially and is strongly associated with mesothelioma.
Serpentines have a corkscrew shape and are more soluble. Chrysotile, the lone serpentine, accounts for 80-90% of commercial asbestos used in the United States and Canada. Chrysotile is less toxic than crocidolite because of its smaller length-to-diameter ratio, increased tissue solubility, and tendency to deposit in the central airways. Chrysotile that has been contaminated with tremolite (a noncommercial amphibole) has been suggested as the only occupational cause of mesothelioma, although this is not accepted universally. The mechanism by which asbestos fibers cause mesothelioma is not well understood. One possible explanation is that malignant transformation of cells follows a foreign-body reaction that is caused by the insoluble fibers.
The "families" of asbestos fibers are as follows:
- Serpentine - Chrysotile
- Amphibole - Crocidolite (strongly associated with mesothelioma), amosite, anthophyllite, tremolite, actinolite
The 3 primary pathologic types of mesothelioma are epithelioid, sarcomatoid, and biphasic. Patients with epithelioid mesothelioma (55-65%) have a slightly better median survival time. Pathologically, the epithelioid subtype can appear similar to adenocarcinoma. Special staining and immunohistochemical and ultrastructural analysis are necessary to differentiate the 2 diseases. Sarcomatoid mesotheliomas (10-15%) are similar in appearance to true sarcomas. Biphasic mesothelioma (20-35%) has both epithelioid and sarcomatoid features.
On gross pathologic examination, mesothelioma is a grayish, lobulated pleural tumor that usually spreads by direct extension into adjacent structures such as the lungs, mediastinum, and chest wall. Peritoneal mesothelioma usually occurs as a direct extension of pleural disease across the diaphragm, but the peritoneum can be the primary site of disease.
Two of the most common mesothelioma staging systems are the Butchart system5 and the tumor, node, metastases (TNM)-based system (see the table below) that was introduced by the International Mesothelioma Interest Group.6
The Butchart staging system for malignant pleural mesothelioma is as follows5 :
- Stage I - Tumor confined to the ipsilateral pleura, lung, or pericardium
- Stage II - Tumor invades the chest wall or mediastinal structures or metastasizes to the thoracic lymph nodes
- Stage III - Tumor penetrates the diaphragm to involve the peritoneum or metastasizes to the extrathoracic lymph nodes
- Stage IV - Distant blood-borne metastases
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Table
| Stage | Location |
| T1a | Ipsilateral parietal pleura only (including mediastinal and diaphragmatic pleura), without visceral pleura involvement |
| T1b | Ipsilateral parietal pleura (including mediastinal and diaphragmatic pleura), with scattered foci of visceral pleural involvement |
| T2 | Ipsilateral pleural surface has at least 1 of the following:
|
| T3 | Locally advanced but resectable tumor; each ipsilateral pleural surface has at least 1 of the following:
|
| T4 | Locally advanced, technically unresectable tumor; each ipsilateral pleural surface has at least 1 of the following:
|
| NX | Regional lymph nodes not assessable |
| N0 | No regional lymph nodes metastases |
| N1 | Metastases in the ipsilateral bronchopulmonary or hilar lymph nodes |
| N2 | Metastases in the subcarinal or ipsilateral mediastinal lymph nodes, including the ipsilateral internal mammary nodes |
| N3 | Metastases in the contralateral mediastinal, contralateral internal mammary, and the ipsilateral or contralateral supraclavicular lymph nodes |
| MX | Distant metastases not assessable |
| M0 | No distant metastases |
| M1 | Distant metastases present |
| Stage | Location |
| T1a | Ipsilateral parietal pleura only (including mediastinal and diaphragmatic pleura), without visceral pleura involvement |
| T1b | Ipsilateral parietal pleura (including mediastinal and diaphragmatic pleura), with scattered foci of visceral pleural involvement |
| T2 | Ipsilateral pleural surface has at least 1 of the following:
|
| T3 | Locally advanced but resectable tumor; each ipsilateral pleural surface has at least 1 of the following:
|
| T4 | Locally advanced, technically unresectable tumor; each ipsilateral pleural surface has at least 1 of the following:
|
| NX | Regional lymph nodes not assessable |
| N0 | No regional lymph nodes metastases |
| N1 | Metastases in the ipsilateral bronchopulmonary or hilar lymph nodes |
| N2 | Metastases in the subcarinal or ipsilateral mediastinal lymph nodes, including the ipsilateral internal mammary nodes |
| N3 | Metastases in the contralateral mediastinal, contralateral internal mammary, and the ipsilateral or contralateral supraclavicular lymph nodes |
| MX | Distant metastases not assessable |
| M0 | No distant metastases |
| M1 | Distant metastases present |
Frequency
United States
Annually, approximately 1.0-1.1 in 100,000 people present with mesothelioma.8 The incidence rate of mesothelioma is highest in the Pacific and Mid-Atlantic states and may be related to the location of industries such as shipyards.9,10
International
The incidence rate of mesothelioma varies greatly among nations and is difficult to document in countries without mesothelioma registries. Crude incidence rates are highest in Australia, Belgium, and Great Britain (about 30 cases per million annually).11 The incidence rates of mesothelioma tend to be high in industrialized countries where asbestos was widely used; however, for unknown reasons, the incidence rates have also been reported to be low in some countries where there was wide use of asbestos.11
Mortality/Morbidity
Malignant mesothelioma is usually fatal. Death generally occurs within 18 months of symptom onset.
Race
No racial predisposition is recognized.
Sex
The incidence rate of mesothelioma is much lower in women than in men, probably because fewer women than men worked outside the home in the mid-20th century; therefore, they were less exposed to asbestos. Between 4- to 6-fold more men than women are affected by mesothelioma.8
Age
Mesothelioma is most commonly diagnosed at age 50-70 years, with the greatest incidence rates at age 65 and older in both sexes.8
Presentation
Mesothelioma usually appears 35-40 years after asbestos exposure. The onset of symptoms is insidious, and patients often experience symptoms for 4-6 months before the diagnosis is made. The most common symptoms are as follows:
- Recent onset of shortness of breath (31%)
- Recent increase in shortness of breath (30%)
- Chest pain (43%)
Other symptoms include the following:
- Cough (35%)
- Weight loss (23%)
- Weakness (18%)
- Increased sputum production (18%)
The most common findings on physical examination (79%) are signs of pleural effusion (eg, dullness to percussion, decreased breath sounds).
Patients with peritoneal involvement experience symptoms as follows:
- Abdominal pain (60%)
- Anorexia (27%)
- Weakness (12%)
- Nausea (11%)
The most common signs of peritoneal mesothelioma include the following:
- Abdominal distention (56%)
- Ascites (37%)
- Weight loss (38%)
- Abdominal mass (11%)
Adams et al also described decreased chest excursion (15%), palpable lymph nodes (12%), and a palpable liver (9%).12
The primary risk factor for mesothelioma is asbestos exposure. Occupations with the highest risk of such exposure include insulation work, asbestos production, the heating trades, shipyard work, and construction. In some patients, no specific asbestos exposure can be found; frequently, these patients have worked in a job where the exposure was not recognized.
An interesting example of unrecognized asbestos exposure was a factory in Nottingham, England, where women manufactured gas masks during World War II using asbestos that was imported from Australia. Not until 1965, when the first patient from the factory was diagnosed with mesothelioma, did an astute doctor begin to suspect the etiology of her disease. By 1996, of the 1200 women, 67 were diagnosed with malignant mesothelioma.
Other predisposing factors include sharing households with asbestos workers and living near asbestos mines and factories. Nevertheless, mesothelioma without asbestos exposure does occur. In a study of 80 children with mesothelioma, only 2 were known to have been exposed to asbestos.13
Although industrial asbestos exposure accounts for most instances of mesothelioma, reports indicate that another environmental mineral fiber is also implicated as a risk factor for this tumor. Nearly 50% of deaths in 3 Turkish villages in central Cappadocia, where a mineral fiber termed erionite was found in the rocks, resulted from mesothelioma.14
Interestingly, there is no association between smoking and mesothelioma.
The diagnosis of mesothelioma should be made with care. A clinical history of asbestos exposure and radiologic findings that are consistent with mesothelioma warrant inclusion of mesothelioma in the differential diagnosis, but it is important to stress that a diagnosis of mesothelioma cannot be made exclusively with imaging studies. Other more common diseases such as benign asbestos-related pleural disease and metastatic adenocarcinoma can look radiographically identical to mesothelioma. Biopsy with special staining and immunohistochemical and ultrastructural analysis are absolutely essential for the accurate diagnosis of mesothelioma.
Mesothelioma is very difficult to treat; the treatment is usually surgical, although other treatment options such as chemotherapy and radiotherapy are used. The 2 primary surgical interventions are pleurectomy and extrapleural pneumonectomy (EPP).15
Pleurectomy is usually a palliative procedure to relieve chest wall pain and prevent recurrent pleural effusions by stripping off the visceral and parietal pleura. Extensive debulking is possible, but incomplete resection is often seen along the diaphragmatic and mediastinal pleura.
EPP is an en bloc resection of the parietal and mediastinal pleura, lung, hemidiaphragm, and ipsilateral pericardium to remove all gross disease. EPP is indicated for stage I tumors without involvement of the mediastinal lymph nodes. No difference in overall long-term survival is seen between pleurectomy and EPP, but the disease-free survival period is improved with pleurectomy. EPP is a technically demanding surgery with significant morbidity.
The surgical complications of pleurectomy and EPP include pneumonia, bronchopleural fistulae, bronchial leaks, empyema, chylothorax, respiratory insufficiency, myocardial infarction, congestive heart failure, hemorrhage, cardiac volvulus, subcutaneous emphysema, incomplete tumor removal, and vocal cord paralysis.
Radiotherapy is usually palliative or adjunctive to surgery. Because mesothelioma is resistant to radiation, a dose of 4000 cGy is usually required to achieve adequate palliation. Brachytherapy (intrapleural implantation of radioactive isotopes) delivers high-dose radiation locally to the pleural space and is used for recurrent pleural effusions or diffuse miliary seeding of the pleura. Postoperative radiation therapy can prevent recurrence within chest wall incision sites. Complications of radiotherapy include nausea and vomiting, radiation hepatitis, esophagitis, myelitis, myocarditis, and pneumonitis with deterioration of pulmonary function.
Response of mesotheliomas to chemotherapy has been disappointing. Comparison of chemotherapy regimens has been difficult because of the relative rarity of the disease. Doxorubicin, one of the more commonly used single agents, has had response rates of 0-16%.
Several new therapies are undergoing evaluation for the treatment of mesothelioma. Immunotherapy has shown promise, particularly in patients with stage I disease. In one study, 38.4% of patients with stage IA disease demonstrated complete response after intrapleural administration of γ -interferon.16
Photodynamic therapy is also an adjuvant treatment under investigation. A light-activated photosensitizing drug is instilled intrapleurally and is excited by light of a certain wavelength to produce oxygen-free radicals that cause tumor necrosis.
Preferred Examination
- Chest radiography is the initial screening examination.
- CT scanning is preferred for staging the tumor.
- Magnetic resonance imaging (MRI) complements CT scanning in some patients. MRI provides better delineation of soft tissues (better soft-tissue contrast) and allows imaging in the sagittal and coronal planes.17
- PET scanning may also be useful in delineating the extent of tumor or metastases.18 A PET scan of a patient with mesothelioma is shown below.
Positron emission tomography (PET) scan in a male patient with known mesothelioma. Although PET scanning is not standard for the evaluation of mesothelioma, this image illustrates the extent of the disease into the mediastinum and peritoneum.
Limitations of Techniques
Chest radiography has limited usefulness. The radiographic findings of mesothelioma are nonspecific and observed in other diseases, including metastatic carcinoma, lymphoma, and benign asbestos disease. Small malignant pleural effusions may not be observed on standard radiographs. Alternatively, large pleural effusions can obscure pleural thickening or masses; therefore, disease extent is frequently underestimated in radiographs.
CT scanning provides more and better information than plain radiography with regard to tumor characteristics and extent. Although MRI is superior to CT scanning in some areas, this advantage did not change the surgical treatment in a 1999 study by Heelan et al.19 Neither CT scanning nor MRI provides an unequivocal diagnosis of mesothelioma; tissue biopsy is required for the definitive diagnosis.
Differential Diagnoses
Asbestos-Related Disease
Congestive Heart Failure
Empyema
Localized Fibrous Tumor of the Pleura
Lung, Metastases
Renal Cell Carcinoma
Other Problems to Be Considered
Adenocarcinoma (lung, breast, ovarian, gastric)
Lymphoma
Thymoma
Leukemia
Myeloma
Renal cell carcinoma
Asbestos-related benign pleural disease
Infection (tuberculosis, fungal, bacterial)
Tuberculous pleural thickening
More on Mesothelioma, Malignant |
 Overview: Mesothelioma, Malignant |
| Imaging: Mesothelioma, Malignant |
| Follow-up: Mesothelioma, Malignant |
| Multimedia: Mesothelioma, Malignant |
| References |
| Further Reading |
| Next Page » |
References
Wagner JC, Sleggs CA, Marchand P. Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Ind Med. Oct 1960;17:260-71. [Medline].
Yildirim H, Metintas M, Entok E, Ak G, Ak I, Dundar E, et al. Clinical Value of Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography in Differentiation of Malignant Mesothelioma from Asbestos-Related Benign Pleural Disease: An Observational Pilot Study. J Thorac Oncol. Oct 28 2009;[Medline].
Mavi A, Basu S, Cermik TF, Urhan M, Bathaii M, Thiruvenkatasamy D, et al. Potential of dual time point FDG-PET imaging in differentiating malignant from benign pleural disease. Mol Imaging Biol. Sep-Oct 2009;11(5):369-78. [Medline].
Yamamoto Y, Kameyama R, Togami T, Kimura N, Ishikawa S, Yamamoto Y, et al. Dual time point FDG PET for evaluation of malignant pleural mesothelioma. Nucl Med Commun. Jan 2009;30(1):25-9. [Medline].
Butchart EG, Ashcroft T, Barnsley WC, Holden MP. Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients. Thorax. Feb 1976;31(1):15-24. [Medline].
Rusch VW. A proposed new international TNM staging system for malignant pleural mesothelioma. From the International Mesothelioma Interest Group. Chest. Oct 1995;108(4):1122-8. [Medline]. [Full Text].
Rusch VW, Crowley J, Giroux DJ, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. Jul 2007;2(7):603-12. [Medline].
National Cancer Institute, National Institutes of Health. SEER Cancer Statistics Review, 1975-2004. Surveillance, Epidemiology, and End Results. Available at http://seer.cancer.gov/faststats/sites.php?stat=Incidence&site=Mesothelioma&x=16&y=18. Accessed August 13, 2007.
Bang KM, Pinheiro GA, Wood JM, Syamlal G. Malignant mesothelioma mortality in the United States, 1999-2001. Int J Occup Environ Health. Jan-Mar 2006;12(1):9-15. [Medline].
Matanoski GM, Tonascia JA, Correa-Villaseñor A, et al. Cancer risks and low-level radiation in U. S. shipyard workers. J Radiat Res (Tokyo). Aug 10 2007;epub ahead of print. [Medline]. [Full Text].
Bianchi C, Bianchi T. Malignant mesothelioma: global incidence and relationship with asbestos. Ind Health. Jun 2007;45(3):379-87. [Medline]. [Full Text].
Adams VI, Unni KK, Muhm JR, et al. Diffuse malignant mesothelioma of pleura. Diagnosis and survival in 92 cases. Cancer. Oct 1 1986;58(7):1540-51. [Medline].
Fraire AE, Cooper S, Greenberg SD, Buffler P, Langston C. Mesothelioma of childhood. Cancer. Aug 15 1988;62(4):838-47. [Medline].
Carbone M, Emri S, Dogan AU, et al. A mesothelioma epidemic in Cappadocia: scientific developments and unexpected social outcomes. Nat Rev Cancer. Feb 2007;7(2):147-54. [Medline].
Ceresoli GL, Gridelli C, Santoro A. Multidisciplinary treatment of malignant pleural mesothelioma. Oncologist. Jul 2007;12(7):850-63. [Medline]. [Full Text].
Boutin C, Nussbaum E, Monnet I, et al. Intrapleural treatment with recombinant gamma-interferon in early stage malignant pleural mesothelioma. Cancer. Nov 1 1994;74(9):2460-7. [Medline].
Wilcox BE, Subramaniam RM, Peller PJ, Aughenbaugh GL, Nichols Iii FC, Aubry MC, et al. Utility of integrated computed tomography-positron emission tomography for selection of operable malignant pleural mesothelioma. Clin Lung Cancer. Jul 2009;10(4):244-8. [Medline].
Gill RR, Gerbaudo VH, Sugarbaker DJ, Hatabu H. Current trends in radiologic management of malignant pleural mesothelioma. Semin Thorac Cardiovasc Surg. Summer 2009;21(2):111-20. [Medline].
Heelan RT, Rusch VW, Begg CB, et al. Staging of malignant pleural mesothelioma: comparison of CT and MR imaging. AJR Am J Roentgenol. Apr 1999;172(4):1039-47. [Medline]. [Full Text].
Chaisaowong K, Aach T, Jäger P, et al. Computer-assisted diagnosis for early stage pleural mesothelioma: towards automated detection and quantitative assessment of pleural thickening from thoracic CT images. Methods Inf Med. 2007;46(3):324-31. [Medline].
Antman KH. Current concepts: malignant mesothelioma. N Engl J Med. Jul 24 1980;303(4):200-2. [Medline].
Bonn D. Asbestos--the legacy lives on. Lancet. Apr 17 1999;353(9161):1336. [Medline].
Boutin C, Schlesser M, Frenay C, Astoul P. Malignant pleural mesothelioma. Eur Respir J. Oct 1998;12(4):972-81. [Medline]. [Full Text].
Flores RM, Akhurst T, Gonen M, et al. Positron emission tomography predicts survival in malignant pleural mesothelioma. J Thorac Cardiovasc Surg. Oct 2006;132(4):763-8. [Medline].
Giesel FL, Bischoff H, von Tengg-Kobligk H, et al. Dynamic contrast-enhanced MRI of malignant pleural mesothelioma: a feasibility study of noninvasive assessment, therapeutic follow-up, and possible predictor of improved outcome. Chest. Jun 2006;129(6):1570-6. [Medline]. [Full Text].
Harpole DH, Liptay MJ, DeCamp MM Jr, et al. Prospective analysis of pneumonectomy: risk factors for major morbidity and cardiac dysrhythmias. Ann Thorac Surg. Mar 1996;61(3):977-82. [Medline].
McDonald AD, McDonald JC. Malignant mesothelioma in North America. Cancer. Oct 1 1980;46(7):1650-6. [Medline].
Miller BH, Rosado-de-Christenson ML, Mason AC, et al. From the archives of the AFIP. Malignant pleural mesothelioma: radiologic-pathologic correlation. Radiographics. May 1996;16(3):613-44. [Medline]. [Full Text].
Patz EF Jr, Rusch VW, Heelan R. The proposed new international TNM staging system for malignant pleural mesothelioma: application to imaging. AJR Am J Roentgenol. Feb 1996;166(2):323-7. [Medline]. [Full Text].
Patz EF Jr, Shaffer K, Piwnica-Worms DR, et al. Malignant pleural mesothelioma: value of CT and MR imaging in predicting resectability. AJR Am J Roentgenol. Nov 1992;159(5):961-6. [Medline]. [Full Text].
Price B. Analysis of current trends in United States mesothelioma incidence. Am J Epidemiol. Feb 1 1997;145(3):211-8. [Medline]. [Full Text].
Quint LE. PET: other thoracic malignancies. Cancer Imaging. 2006;6:S82-8. [Medline].
Ribak J, Lilis R, Suzuki Y, Penner L, Selikoff IJ. Malignant mesothelioma in a cohort of asbestos insulation workers: clinical presentation, diagnosis, and causes of death. Br J Ind Med. Mar 1988;45(3):182-7. [Medline].
Rusch VW, Piantadosi S, Holmes EC. The role of extrapleural pneumonectomy in malignant pleural mesothelioma. A Lung Cancer Study Group trial. J Thorac Cardiovasc Surg. Jul 1991;102(1):1-9. [Medline].
Sterman DH, Kaiser LR, Albelda SM. Advances in the treatment of malignant pleural mesothelioma. Chest. Aug 1999;116(2):504-20. [Medline]. [Full Text].
Sterman DH, Recio A, Carroll RG, et al. A phase I clinical trial of single-dose intrapleural IFN-{beta} gene transfer for malignant pleural mesothelioma and metastatic pleural effusions: high rate of antitumor immune responses. Clin Cancer Res. Aug 1 2007;13(15):4456-66. [Medline].
Further Reading
Related eMedicine topics
Mesothelioma
Asbestos-Related Disease
Asbestosis
Clinical guidelines
Pemetrexed for the treatment of malignant pleural mesothelioma. National Institute for Health and Clinical Excellence (NICE) - National Government Agency [Non-U.S.]. 2008 Jan. 28 pages. NGC:006979
Clinical trials
Pemetrexed (ALIMTA) Plus Cisplatin Followed by Surgery and Radiation Therapy for Mesothelioma
Video-Assisted Surgery or Talc Pleurodesis in Treating Patients With Malignant Mesothelioma
Extrapleural Pneumonectomy /Pleurectomy Decortication, IHOC Cisplatin and Gemcitabine With Amifostine and Sodium Thiosulfate Cytoprotection for Resectable Malignant Pleural Mesothelioma
Keywords
malignant mesothelioma, asbestos, mesothelioma, mesothelioma cancer, asbestos cancer mesothelioma, mesothelioma asbestos, pleural mesothelioma, asbestos exposure, malignant pleural mesothelioma, amphibole, chrysotile, crocidolite, chrysotile asbestos, asbestos disease, mesothelioma lung cancer, amphiboles, diffuse mesothelioma
