Diagnostic Considerations

Conditions to consider in the differential diagnosis of malignant mesothelioma include the following:

Non-small cell lung cancer
Oat cell (small cell) lung cancer
Drug-induced pulmonary reactions
Mesothelial hyperplasia
Other primary lung neoplasms or metastatic disease
Pulmonary fibrosis
Pulmonary infection
Reactive airway disease

Differential Diagnoses

Workup

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. [QxMD MEDLINE Link].
Ryan CW, Herndon J, Vogelzang NJ. A review of chemotherapy trials for malignant mesothelioma. Chest. 1998 Jan. 113(1 Suppl):66S-73S. [QxMD MEDLINE Link].
Taub RN, Antman KH. Chemotherapy for malignant mesothelioma. Semin Thorac Cardiovasc Surg. 1997 Oct. 9(4):361-6. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Yang H, Testa JR, Carbone M. Mesothelioma epidemiology, carcinogenesis, and pathogenesis. Curr Treat Options Oncol. 2008 Jun. 9(2-3):147-57. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Carbone M, Adusumilli PS, Alexander HR Jr, et al. Mesothelioma: Scientific clues for prevention, diagnosis, and therapy. CA Cancer J Clin. 2019 Sep. 69 (5):402-429. [QxMD MEDLINE Link]. [Full Text].
Carbone M, Baris YI, Bertino P, Brass B, Comertpay S, Dogan AU, et al. Erionite exposure in North Dakota and Turkish villages with mesothelioma. Proc Natl Acad Sci U S A. 2011 Aug 16. 108 (33):13618-23. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Mazurek JM, Syamlal G, Wood JM, Hendricks SA, Weston A. Malignant Mesothelioma Mortality - United States, 1999-2015. MMWR Morb Mortal Wkly Rep. 2017 Mar 3. 66 (8):214-218. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Malpica A, Sant'Ambrogio S, Deavers MT, Silva EG. Well-differentiated papillary mesothelioma of the female peritoneum: a clinicopathologic study of 26 cases. Am J Surg Pathol. 2012 Jan. 36 (1):117-27. [QxMD MEDLINE Link].
Baas P, Scherpereel A, Nowak AK, Fujimoto N, Peters S, Tsao AS, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021 Jan 30. 397 (10272):375-386. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Zalcman G, Mazieres J, Margery J, et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Apr 2. 387 (10026):1405-14. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Nowak AK, Lesterhuis WJ, Kok PS, Brown C, Hughes BG, Karikios DJ, et al. Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in. Lancet Oncol. 2020 Sep. 21 (9):1213-1223. [QxMD MEDLINE Link].
Forde PM, Anagnostou V, Sun Z, et al. Durvalumab with platinum-pemetrexed for unresectable pleural mesothelioma: survival, genomic and immunologic analyses from the phase 2 PrE0505 trial. Nat Med. 2021 Nov. 27 (11):1910-1920. [QxMD MEDLINE Link]. [Full Text].
Kok PS, et al; Thoracic Oncology Group of Australasia (TOGA) and PrECOG, USA. Protocol of DREAM3R: DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma-a phase 3 randomised trial. BMJ Open. 2022 Jan 25. 12 (1):e057663. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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:
Adusumilli PS, Zauderer MG, Rivière I, et al. A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti-PD-1 Agent Pembrolizumab. Cancer Discov. 2021 Nov. 11 (11):2748-2763. [QxMD MEDLINE Link]. [Full Text].
Placebo Controlled Study of VS-6063 in Subjects With Malignant Pleural Mesothelioma (COMMAND). ClinicalTrials.gov. Available at https://clinicaltrials.gov/ct2/show/NCT01870609. January 30, 2017; Accessed: March 25, 2022.
FDA Approves Drug Combination for Treating Mesothelioma. U.S. Food and Drug Administration. U.S. Food and Drug Administration. 2020 October 2. Available at https://www.fda.gov/news-events/press-announcements/fda-approves-drug-combination-treating-mesothelioma.
Batirel HF, Metintas M, Caglar HB, et al. Trimodality treatment of malignant pleural mesothelioma. J Thorac Oncol. 2008 May. 3(5):499-504. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Taioli E, Wolf AS, Flores RM. Meta-analysis of survival after pleurectomy decortication versus extrapleural pneumonectomy in mesothelioma. Ann Thorac Surg. 2015 Feb. 99 (2):472-80. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Perrot M, Wu L, Wu M, Cho BCJ. Radiotherapy for the treatment of malignant pleural mesothelioma. Lancet Oncol. 2017 Sep. 18 (9):e532-e542. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Simon M, Shochat T, Peled N, Zer A, Kramer MR, Eldan O, et al. Intensity-modulated radiotherapy is a safe and effective treatment for localized malignant pleural mesothelioma. Thorac Cancer. 2018 Nov. 9 (11):1470-1475. [QxMD MEDLINE Link]. [Full Text].
Brooks M. Mesothelioma: Radiation Before Surgery Feasible, Boosts Survival. Medscape Medical News. Available at http://www.medscape.com/viewarticle/819618. Accessed: June 15, 2019.
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. [QxMD MEDLINE Link].
de Perrot M, Feld R, Leighl NB, Hope A, Waddell TK, Keshavjee S, et al. Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2016 Feb. 151 (2):468-73. [QxMD MEDLINE Link].
[Guideline] Woolhouse I, Bishop L, Darlison L, De Fonseka D, Edey A, Edwards J, et al. British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma. Thorax. 2018 Mar. 73 (Suppl 1):i1-i30. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Kindler HL, Ismaila N, Armato SG 3rd, Bueno R, Hesdorffer M, Jahan T, et al. Treatment of Malignant Pleural Mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 May 1. 36 (13):1343-1373. [QxMD MEDLINE Link]. [Full Text].
[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Malignant Pleural Mesothelioma. NCCN.org. Available at https://www.nccn.org/professionals/physician_gls/pdf/mpm.pdf. Version 1.2022 — December 22, 2021; Accessed: March 25, 2022.
[Guideline] Scherpereel A, Opitz I, Berghmans T, et al. ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma. Eur Respir J. 2020 Jun. 55 (6):[QxMD MEDLINE Link]. [Full Text].
Mulcahy N. First Mesothelioma Treatment in 15 Years Approved. Medscape Medical News. May 24, 2019. Available at https://www.webmd.com/lung-cancer/news/20190524/first-mesothelioma-treatment-in-15-years-approved.
NovoTTF™-100L System - H180002. U.S. Food and Drug Administration. Available at https://www.fda.gov/medical-devices/recently-approved-devices/novottftm-100l-system-h180002. May 23, 2019; Accessed: June 15, 2019.
[Guideline] Popat S, Baas P, Faivre-Finn C, Girard N, Nicholson AG, Nowak AK, et al. Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up^☆. Ann Oncol. 2022 Feb. 33 (2):129-142. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Gomez DR, Rimner A, Simone CB 2nd, Cho BCJ, de Perrot M, Adjei AA, et al. The Use of Radiation Therapy for the Treatment of Malignant Pleural Mesothelioma: Expert Opinion from the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation. J Thorac Oncol. 2019 May 21. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].

Media Gallery

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.
The classic description of malignant pleural mesothelioma is a thickening in the pleural space with encasement of the lung by a rindlike visceral pleura. These gross specimens are from an autopsy lung case with diffuse thickening of the pleura causing compression of the underlying lung tissue.
This histologic section stained with hematoxylin and eosin shows papillary structures on the right and a transition to a more solid pattern on the left.
A solid pattern of mesothelioma on the right of this histologic section transitions to a spindle cell morphology on the left of the image in this predominantly sarcomatoid malignant mesothelioma.
Well differentiated papillary mesothelioma is characterized with a single layer of bland cuboidal cells lining fibrovascular cores, as demonstrated in this image.
Immunohistochemistry helps to demonstrate that the atypical mesothelial cells in this reactive proliferation are in fact in one roughly linear layer, an important criterion supporting a benign process.

of 12

Author

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, Division of Hematology/Oncology Education, Chair, Cancer Survivorship Program, Associate Chair, Department of Medicine Faculty Development, Mayo Clinic Florida; Vice President, Florida Society of Clinical Oncology

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

Disclosure: Nothing to disclose.

Chief Editor

Nagla Abdel Karim, MD, PhD Associate Professor of Medicine, Associate Director of Experimental Therapeutics, Division of Hematology/Oncology, University of Cincinnati Cancer Institute, Department of Internal Medicine, University of Cincinnati College of Medicine

Nagla Abdel Karim, MD, PhD is a member of the following medical societies: American Medical Association, American Society of Clinical Oncology, Egyptian American Medical Association, Egyptian Cancer Society, International Association for the Study of Lung Cancer

Disclosure: Nothing to disclose.

Additional Contributors

Alain C Borczuk, MD Professor of Clinical Pathology, Vice Chairman of Anatomic Pathology, Columbia University College of Physicians and Surgeons; Visiting Assistant Professor, Albert Einstein College of Medicine; Attending Pathologist, New York Presbyterian Hospital

Alain C Borczuk, MD is a member of the following medical societies: College of American Pathologists, United States and Canadian Academy of Pathology, Pulmonary Pathology Society, New York Pathological Society

Disclosure: Nothing to disclose.

Acknowledgements

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