Medscape is available in 5 Language Editions – Choose your Edition here.



  • Author: Winston W Tan, MD, FACP; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
Updated: Apr 23, 2014

Practice Essentials

Malignancies involving mesothelial cells that normally line the body cavities, including the pleura (see the image below), peritoneum, pericardium, and testis, are known as malignant mesothelioma. Asbestos, particularly the types of amphibole asbestos known as crocidolite and amosite asbestos, is the principal carcinogen implicated in the pathogenesis of malignant pleural mesothelioma.

Computed tomography scan of a 58-year-old patient Computed tomography scan of a 58-year-old patient with mesothelioma and shortness of breath. This image shows the extensive pleural thickening that is characteristic of mesothelioma, effusion, and reduction in the volume of the affected hemithorax.

Signs and symptoms

Dyspnea and nonpleuritic chest wall pain are the most common presenting symptoms of malignant pleural mesothelioma, with at least 1 of these occurring in 60-90% of patients. Other common accompanying symptoms are as follows:

  • Chest discomfort
  • Pleuritic pain
  • Easy fatigability
  • Fever
  • Sweats
  • Weight loss

On physical examination, findings of pleural effusion are usually noted upon percussion and auscultation. Patients may also be asymptomatic, with evidence of a pleural effusion noted incidentally on physical examination or by chest radiograph.

See Clinical Presentation for more detail.



  • More than 90% of patients with pleural mesothelioma present with pleural effusion that decreases after thoracentesis
  • Typically, the pleural fluid findings are nondiagnostic, with < 1000 leukocytes/μL, few erythrocytes, elevated protein levels, and normal lactate dehydrogenase levels
  • Pleural fluid cytologic findings are diagnostic in only 32% of patients and are suggestive in 56%
  • FISH to distinguish malignant mesothelioma from reactive mesothelial cells in effusions had 79% sensitivity [1]

Thoracoscopically guided biopsy

  • Indicated if mesothelioma is suggested
  • Diagnostic in 98% of cases

Routinely stained biopsy preparations are the most valuable diagnostic tool in malignant mesothelioma. Diagnostic features that distinguish malignant mesothelioma from adenocarcinoma include the following:

  • Negative results for periodic acid-Schiff stain, mucicarmine stain, carcinoembryonic antigen, and Leu M1
  • Positive test results for calretinin, vimentin, and cytokeratin

Serum biomarkers

  • Soluble mesothelin (the current reference biomarker)
  • Megakaryocyte potentiating factor

Chest radiographs

Findings in malignant pleural mesothelioma include one or more of the following:

  • Obliteration of the diaphragm
  • Nodular thickening of the pleura
  • Decreased size of the involved chest
  • Radiolucent, sheetlike encasement of the pleura
  • A loculated effusion (> 50% of patients), with opacification of a major portion of the pleura

See Workup for more detail.


Currently, no therapy is considered standard. Treatment options for the management of malignant mesothelioma include the following:

  • Surgery (reasonable when disease is confined to the pleural space)
  • Chemotherapy [2, 3]
  • Radiation (provides significant palliation of chest pain and chest wall metastasis in 50% of patients)
  • Multimodality treatment

Generally used chemotherapy regimens include the following:

  • Cisplatin – Standard for single-agent therapy
  • Cisplatin/pemetrexed
  • Pemetrexed/gemcitabine – For patients who cannot take cisplatin
  • Single-agent pemetrexed
  • Cisplatin/gemcitabine

See Treatment and Medication for more detail.



Malignancies involving mesothelial cells that normally line the body cavities, including the pleura, peritoneum, pericardium, and testis, are known as malignant mesothelioma. The 3 major histologic types are sarcomatous, epithelial, and mixed. The condition may be localized or diffuse. (See Etiology.)

Primary sites for malignant mesothelioma include the pleura (87%), the peritoneum (5.1%), the pericardium (0.4%), and the right side of the thorax (more so than the left side, by a right-to-left ratio of 1.6:1). (See Etiology, Presentation, and Workup.)

Among patients with malignant pleural mesothelioma, 77% have previously been exposed to asbestos.[4] Diagnosis is difficult because results from fluid analysis of the tumor’s effusion are not usually diagnostic. Death from malignant mesothelioma is usually due to infection or respiratory failure from the progression of the disease. (See Etiology, Presentation, and Workup.)

Malignant pleural mesothelioma

Malignant pleural mesothelioma usually begins as discrete plaques and nodules that coalesce to produce a sheetlike neoplasm. Tumor growth usually starts at the lower part of the chest. The tumor may invade the diaphragm and encase the surface of the lung and interlobar fissures.

The tumor may also grow along drainage and thoracotomy tracts. As the disease progresses, it often extends into the pulmonary parenchyma, chest wall, and mediastinum. Malignant pleural mesothelioma may also extend into the esophagus, ribs, vertebra, brachial plexus, and superior vena cava.




Asbestos, particularly the types of amphibole asbestos known as crocidolite and amosite asbestos, is the principal carcinogen implicated in the pathogenesis of malignant pleural mesothelioma. Exposure to chrysotile asbestos is also associated malignant mesothelioma, but at a lower incidence than occurs with the other types. (The rod-shaped amphiboles are more carcinogenic than the chrysotile.)[5]

Approximately 8 million people in the United States have been exposed to asbestos in the workplace. A substantial proportion of patients with malignant pleural mesothelioma were exposed to asbestos in asbestos mills, shipping yards, mines, or their homes. The crocidolite in asbestos is associated with mesothelioma in miners, manufacturers who use asbestos, and heating and construction workers. Family members of workers exposed to asbestos can also be at risk of exposure if asbestos becomes embedded in the workers’ clothing.

The industries associated with asbestos exposure include the following:

  • Mining
  • Ship building involving the use of asbestos
  • Asbestos cement manufacture
  • Ceramics
  • Paper milling
  • Auto parts (asbestos brake lining)
  • Railroad repair
  • Insulation

In Turkey, the use of the fibrous substance erionite (similar to amphibole asbestos) in building construction has led to an epidemic of pulmonary mesothelioma. Environmental exposure to asbestos in areas polluted by the substance may also increase the incidence of mesothelioma.[6]

Alcohol, dietary factors, and tobacco smoke have no effect on the incidence of pleural mesothelioma.

Other sources of mesothelioma

Interleukin-8 has direct growth-potentiating activity in mesothelial cell lines. Malignant mesothelioma has also been linked to therapeutic radiation using thorium dioxide and zeolite, a silicate in the soil.

An etiologic role for simian virus 40 in malignant mesothelioma has been suggested. However, although asbestos exposure alone has been associated with malignant mesothelioma, simian virus 40 alone has not. Thus, some epidemiologic evidence exists that simian virus 40 is a possible cocarcinogen. Its direct role at this point is still controversial.[7]


Most malignant mesotheliomas have complex karyotypes, with extensive aneuploidy and the rearrangement of many chromosomes. Loss of 1 copy of chromosome 22 is the single most common karyotypic change in malignant mesothelioma. Other chromosomal changes commonly observed include deletions in the chromosome arms 1p, 3p, 9p, and 6q. Several changes in the tumor suppressor genes p16 (CDKN2A) and p14 (ARF) and loss of function of neurofibromin-2 (NF2) have also been noted.[8]



Occurrence in the United States

Approximately 3000 cases of malignant mesothelioma are diagnosed annually. In the absence of occupational exposure to asbestos, the incidence is 0.1-0.2 per 100,000 population in both sexes. The risk is increased in polluted areas by 2-10 fold compared with nonpolluted areas. Of patients with malignant mesothelioma in the United States, 80% have been exposed to asbestos.

International occurrence

Incidence of malignant mesothelioma is 0.9 case per 100,000 persons annually. Marked variability exists in the incidence of malignant mesothelioma in different countries. In some countries, the incidence is low even though asbestos exposure is high. The reasons for these differences are not known.

Sex- and age-related demographics

Malignant mesothelioma is more common in men than in women, with a male-to-female ratio of 3:1.[9]

Malignant mesothelioma has a peak incidence 35-45 years after asbestos exposure. Two thirds of cases of malignant mesothelioma develop in the fifth to seventh decade of life.

Malignant mesothelioma also occurs in children; however, these cases are not thought to be associated with asbestos exposure.



Without treatment, malignant mesothelioma is fatal within 4-8 months. With trimodality treatment, some patients have survived 16-19 months. A few have survived as long as 5 years, with rates of 14% for all types and 46% for the epithelial type. However, numbers are small.[10, 11] The tumor recurrence rate is 50% for patients treated with surgery.

Median survival for patients with malignant mesothelioma is 11 months. It is almost always fatal. Median survival based on histologic type is 9.4 months for sarcomatous, 12.5 months for epithelial, and 11 months for mixed. Approximately 15% of patients have an indolent course.

In a review of 64 patients undergoing pleurectomy, the overall survival rate was 43%, 28%, and 10% at 1, 2, and 3 years, respectively. The overall median survival with epithelial histology was 21.7 months (n=56 patients); it was 5.8 months for patients with sarcomatous or mixed type mesothelioma (n=28 patients). The causes of morbidity include atrial fibrillation, wound infection, prolonged intubation, pulmonary emboli, myocardial infarction, respiratory failure, deep vein thrombosis, and postoperative bleeding.

In rare cases, malignant mesothelioma manifests as cord compression, brachial plexopathy, Horner syndrome, or superior vena cava syndrome.

Prognostic factors

Based on many clinical factors, 2 separate groups, the Cancer and Leukemia Group B and the European Organization for Research and Treatment of Cancer, identified the following poor prognostic factors[12, 13] :

  • Performance status of 2 or greater
  • Nonepithelial histology
  • Chest pain
  • Age older than 75 years
  • Male sex
  • High platelet count
  • Lactate dehydrogenase greater than 500 IU/L
  • Low hemoglobin
  • High white count
  • Weight loss

Nodal metastasis

The pattern of nodal metastasis is different from that of lung cancer. The mechanism of spread of the disease to the hilar nodes may be through lung invasion and not due to spread directly from the pleura. In a study of 49 patients who underwent surgery, only 7 had no lung invasion and none had positive hilar nodes. In the postpneumonectomy patients, 6 of 14 had positive hilar node and mediastinal nodes.

Contributor Information and Disclosures

Winston W Tan, MD, FACP Associate Professor of Medicine, Mayo Medical School; Consultant and Person-in-Charge of Genitourinary Oncology-Medical Oncology, Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic Jacksonville; Vice Chairman of Education, Division of Hematology/Oncology, Mayo Clinic Florida

Winston W Tan, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Hematology, Texas Medical Association, American Society of Clinical Oncology, Philippine Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, FACP, FRCPC Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD, FACP, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Society of Hematology, Central Society for Clinical and Translational Research, American Society of Clinical Oncology

Disclosure: Nothing to disclose.


Benjamin Movsas, MD Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center

Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, and American Society for Therapeutic Radiology and Oncology

Disclosure: Nothing to disclose.

Michael Perry, MD, MS, MACP Nellie B Smith Chair of Oncology Emeritus, Director, Division of Hematology and Medical Oncology, Deputy Director, Ellis Fischel Cancer Center, University of Missouri-Columbia School of Medicine

Michael Perry, MD, MS, MACP is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, International Association for the Study of Lung Cancer, and Missouri State Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

  1. Savic S, Franco N, Grilli B, Barascud Ade V, Herzog M, Bode B, et al. Fluorescence in situ hybridization in the definitive diagnosis of malignant mesothelioma in effusion cytology. Chest. 2010 Jul. 138(1):137-44. [Medline].

  2. Ryan CW, Herndon J, Vogelzang NJ. A review of chemotherapy trials for malignant mesothelioma. Chest. 1998 Jan. 113(1 Suppl):66S-73S. [Medline].

  3. Taub RN, Antman KH. Chemotherapy for malignant mesothelioma. Semin Thorac Cardiovasc Surg. 1997 Oct. 9(4):361-6. [Medline].

  4. Hodgson JT, Darnton A. The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure. Ann Occup Hyg. 2000 Dec. 44(8):565-601. [Medline].

  5. Yang H, Testa JR, Carbone M. Mesothelioma epidemiology, carcinogenesis, and pathogenesis. Curr Treat Options Oncol. 2008 Jun. 9(2-3):147-57. [Medline]. [Full Text].

  6. Wei B, Jia X, Ye B, Yu J, Zhang B, Zhang X, et al. Impacts of land use on spatial distribution of mortality rates of cancers caused by naturally occurring asbestos. J Expo Sci Environ Epidemiol. 2012 Jul 4. [Medline].

  7. Manfredi JJ, Dong J, Liu WJ, et al. Evidence against a role for SV40 in human mesothelioma. Cancer Res. 2005 Apr 1. 65(7):2602-9. [Medline].

  8. Murthy SS, Testa JR. Asbestos, chromosomal deletions, and tumor suppressor gene alterations in human malignant mesothelioma. J Cell Physiol. 1999 Aug. 180(2):150-7. [Medline].

  9. Ascoli V, Scalzo CC, Facciolo F, et al. Malignant mesothelioma in Rome, Italy 1980-1995. A retrospective study of 79 patients. Tumori. 1996 Nov-Dec. 82(6):526-32. [Medline].

  10. Sugarbaker DJ, Garcia JP, Richards WG, et al. Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma. Results in 120 consecutive patients. Ann Surg. 1996 Sep. 224(3):288-94; discussion 294-6. [Medline].

  11. Huncharek M, Kelsey K, Mark EJ, et al. Treatment and survival in diffuse malignant pleural mesothelioma; a study of 83 cases from the Massachusetts General Hospital. Anticancer Res. 1996 May-Jun. 16(3A):1265-8. [Medline].

  12. Curran D, Sahmoud T, Therasse P, van Meerbeeck J, Postmus PE, Giaccone G. Prognostic factors in patients with pleural mesothelioma: the European Organization for Research and Treatment of Cancer experience. J Clin Oncol. 1998 Jan. 16(1):145-52. [Medline].

  13. Herndon JE, Green MR, Chahinian AP, et al. Factors predictive of survival among 337 patients with mesothelioma treated between 1984 and 1994 by the Cancer and Leukemia Group B. Chest. 1998 Mar. 113(3):723-31. [Medline].

  14. Betta PG, Andrion A, Donna A, et al. Malignant mesothelioma of the pleura. The reproducibility of the immunohistological diagnosis. Pathol Res Pract. 1997. 193(11-12):759-65. [Medline].

  15. Hollevoet K, Nackaerts K, Thimpont J, Germonpré P, Bosquée L, De Vuyst P, et al. Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma. Am J Respir Crit Care Med. 2010 Mar 15. 181(6):620-5. [Medline].

  16. Renshaw AA, Dean BR, Antman KH, et al. The role of cytologic evaluation of pleural fluid in the diagnosis of malignant mesothelioma. Chest. 1997 Jan. 111(1):106-9. [Medline].

  17. Orengo AM, Spoletini L, Procopio A, et al. Establishment of four new mesothelioma cell lines: characterization by ultrastructural and immunophenotypic analysis. Eur Respir J. 1999 Mar. 13(3):527-34. [Medline].

  18. Wang ZJ, Reddy GP, Gotway MB, et al. Malignant pleural mesothelioma: evaluation with CT, MR imaging, and PET. Radiographics. 2004 Jan-Feb. 24(1):105-19. [Medline].

  19. Benard F, Sterman D, Smith RJ, et al. Prognostic value of FDG PET imaging in malignant pleural mesothelioma. J Nucl Med. 1999 Aug. 40(8):1241-5. [Medline].

  20. Rice DC, Stevens CW, Correa AM, Vaporciyan AA, Tsao A, Forster KM, et al. Outcomes after extrapleural pneumonectomy and intensity-modulated radiation therapy for malignant pleural mesothelioma. Ann Thorac Surg. 2007 Nov. 84(5):1685-92; discussion 1692-3. [Medline].

  21. Brooks M. Mesothelioma: Radiation Before Surgery Feasible, Boosts Survival. Medscape Medical News. Available at Accessed: January 27, 2014.

  22. Cho BC, Feld R, Leighl N, Opitz I, Anraku M, Tsao MS, et al. A Feasibility Study Evaluating Surgery for Mesothelioma After Radiation Therapy: The "SMART" Approach for Resectable Malignant Pleural Mesothelioma. J Thorac Oncol. 2014 Jan 17. [Medline].

  23. Dowell JE, Dunphy FR, Taub RN, et al. A multicenter phase II study of cisplatin, pemetrexed, and bevacizumab in patients with advanced malignant mesothelioma. Lung Cancer. 2012 Jul 4. [Medline].

  24. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15. 21(14):2636-44. [Medline].

  25. Santoro A, O'Brien ME, Stahel RA, et al. Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaïve patients with malignant pleural mesothelioma: results of the International Expanded Access Program. J Thorac Oncol. 2008 Jul. 3(7):756-63. [Medline].

  26. Simon GR, Verschraegen CF, Janne PA, et al. Pemetrexed plus gemcitabine as first-line chemotherapy for patients with peritoneal mesothelioma: final report of a phase II trial. J Clin Oncol. 2008 Jul 20. 26(21):3567-72. [Medline].

  27. Taylor P, Castagneto B, Dark G, et al. Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. J Thorac Oncol. 2008 Jul. 3(7):764-71. [Medline].

  28. Byrne MJ, Davidson JA, Musk AW, et al. Cisplatin and gemcitabine treatment for malignant mesothelioma: a phase II study. J Clin Oncol. 1999 Jan. 17(1):25-30. [Medline].

  29. Favaretto AG, Aversa SM, Paccagnella A, et al. Gemcitabine combined with carboplatin in patients with malignant pleural mesothelioma: a multicentric phase II study. Cancer. 2003 Jun 1. 97(11):2791-7. [Medline].

  30. Pavlakis N, Vogelzang NJ. Ranpirnase--an antitumour ribonuclease: its potential role in malignant mesothelioma. Expert Opin Biol Ther. 2006 Apr. 6(4):391-9. [Medline].

  31. Mikulski SM, Costanzi JJ, Vogelzang NJ, McCachren S, Taub RN, Chun H. Phase II trial of a single weekly intravenous dose of ranpirnase in patients with unresectable malignant mesothelioma. J Clin Oncol. 2002 Jan 1. 20(1):274-81. [Medline].

  32. Betta PG, Bottero G, Pavesi M. Apoptosis and Related Proteins BCL-2and BAX in Malignant Mesothelioma of the Pleura. Presented at: American Society of Clinical Oncology 35th Annual Meeting. Atlanta, Ga: 1999. Vol 18:

  33. Verastem, Inc. (press release) Verastem Receives Orphan Drug Designation from the U.S. FDA for Defactinib in Mesothelioma. Available at Accessed: July 24, 2013.

  34. Batirel HF, Metintas M, Caglar HB, et al. Trimodality treatment of malignant pleural mesothelioma. J Thorac Oncol. 2008 May. 3(5):499-504. [Medline].

  35. Nakas A, Trousse DS, Martin-Ucar AE, Waller DA. Open lung-sparing surgery for malignant pleural mesothelioma: the benefits of a radical approach within multimodality therapy. Eur J Cardiothorac Surg. 2008 Oct. 34(4):886-91. [Medline].

  36. Neragi-Miandoab S, Richards WG, Sugarbaker DJ. Morbidity, mortality, mean survival, and the impact of histology on survival after pleurectomy in 64 patients with malignant pleural mesothelioma. Int J Surg. 2008 Aug. 6(4):293-7. [Medline].

  37. Cao C, Yan TD, Bannon PG, McCaughan BC. Summary of prognostic factors and patient selection for extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma. Ann Surg Oncol. 2011 Oct. 18(10):2973-9. [Medline].

  38. Hughes A, Calvert P, Azzabi A, et al. Phase I clinical and pharmacokinetic study of pemetrexed and carboplatin in patients with malignant pleural mesothelioma. J Clin Oncol. 2002 Aug 15. 20(16):3533-44. [Medline].

  39. Husain AN, Mirza MK, Gibbs A, et al. How useful is GLUT-1 in differentiating mesothelial hyperplasia and fibrosing pleuritis from epithelioid and sarcomatoid mesotheliomas? An international collaborative study. Lung Cancer. 2013 Dec 30. [Medline].

  40. Reuters Staff. GLUT-1 aids in differentiating mesothelioma from reactive mesothelial lesions. Reuters Health Information. February 3, 2014. Available at Accessed: February 10, 2014.

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.
Chest radiograph of a 58-year-old patient with mesothelioma and shortness of breath. This image reveals diffuse, left-sided pleural thickening, a pleural effusion, and ipsilateral volume loss.
Computed tomography scan of a 58-year-old patient with mesothelioma and shortness of breath. This image shows the extensive pleural thickening that is characteristic of mesothelioma, effusion, and reduction in the volume of the affected hemithorax.
Computed tomography scan of the chest. This image demonstrates mesothelioma that extends into the chest wall. Note the concentric left pleural thickening, pleural effusion, reduction in volume of the left hemithorax, and the tumor nodules within the chest wall.
Magnetic resonance imaging (MRI) scan in a 72-year-old Veterans Administration patient with left-sided mesothelioma. Note that the MRI scan well delineates the soft tissues and, in particular, the thoracoabdominal interface at the diaphragm.
Computed tomography (CT) scan in a male Veterans Administration patient with a history of asbestos exposure and an enlarging abdominal girth. This upper CT scan slice reveals the calcified pleural plaques along the diaphragmatic surface that are associated with asbestos exposure. Ascites is seen lateral to the liver. Aspiration of the ascitic fluid demonstrated mesothelioma.
The soft-tissue window setting of this chest computed tomography (CT) scan shows the envelope-like mass along the pleural surface surrounding the lung. This was a mesothelioma.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.