Mesothelioma overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]
Overview
Mesothelioma is a rare, highly aggressive cancer which arises from the mesothelial cells which form the lining of the pleural, and less frequently the peritoneal, pericardial, and tunica vaginalis cavities.[1][2] Mesothelioma is a form of cancer that is most commonly caused by exposure to asbestos.[3]
Historical Perspective
Wagner et al. were the first to discover the association between asbestos exposure and development of mesothelioma.[4]
Classification
Mesothelioma may be classified into several subtypes based on the location (pleural, peritoneal, pericardial, cystic/multicystic, and tunica vaginalis testis), histology (epithelial, sarcomatoid, and biphasic), and potential to spread (benign and malignant).[5][6]
Pathophysiology
Asbestos causes DNA damage directly by mechanically interfering with the segregation of chromosomes during mitosis and indirectly by inducing mesothelial cells and macrophages, to release mutagenic reactive oxygen and nitrogen species.[4] Asbestos fibres have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favor the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences. Genes involved in the pathogenesis of mesothelioma include BAP1, CDKN2A, WT1, NF2, and TP53.[4][7][8][9][10][11][12] On gross pathology, pleural mesothelioma is characterized by discrete plaques and nodules that coalesce to produce a sheet-like tumor, with the pleural surface seeding of malignant mesothelioma cells.[13] Based on the histology, mesothelioma may be classified into 3 subtypes: epithelial, sarcomatoid, and biphagic.[5] Mesothelioma is demonstrated by positivity to tumor markers, such as calretinin, epithelial membrane antigen, cytokeratin, and mesothelin.[14][15]
Causes
Common causes of mesothelioma include asbestos-fibre exposure, erionite-fibre exposure, Simian virus 40, and radiation exposure.[16]
Differentiating Mesothelioma from other Diseases
Mesothelioma must be differentiated from pleural effusion, lung cancer, pulmonary tuberculosis, peritoneal tuberculosis, pseudomyxoma peritonei, constrictive pericarditis, ovarian cystadenoma, and mesothelial hyperplasia of the testis.[17][18][19][20][21][22][23]
Epidemiology and Demographics
Mesothelioma is a rare disease which accounts for 5-28% of all malignancies that involve the pleura.[13] The incidence of mesothelioma is estimated to be 3,000 cases annually.[1] The incidence of pleural mesothelioma is approximately 1 per 100,000 individuals in the United States.[24] Males are more commonly affected with mesothelioma than females. The male to female ratio is approximately 3 to 1.[13] The incidence of mesothelioma increases with age; the median age at diagnosis for pleural mesothelioma and peritoneal mesothelioma are 74 years and 68 years, respectively.[4] There is no racial predilection to mesothelioma.[13]
Risk Factors
The most potent risk factor in the development of mesothelioma is asbestos exopsure. Other risk factors include erionite-fibre exposure, Simian virus 40, and radiation exposure.[25]
Screening
There is insufficient evidence to recommend routine screening for mesothelioma.
Natural History, Complications and Prognosis
If left untreated, mesothelioma may progress to develop dyspnea, dysphagia, pleural effusion, thrombophlebitis, constrictive pericarditis, recurrent hydrocele, and metastases, depending on the site involved.[26][27][28][29][30][31][32] Complications of mesothelioma include pleural effusion, spinal cord compression, Horner's syndrome, superior vena cava syndrome, hyperviscocity syndrome, pericardial effusion, cardiac tamponade, heart failure, ascites, and recurrent hydrocele.[27][28][29][30][31][33][32] The prognosis of mesothelioma depends on the cell subtype.[26]
Diagnosis
Staging
According to the Union for International Cancer Control staging system, there are four stages of pleural mesothelioma based on the primary tumor, lymph nodes, and metastasis: stage I (IA, IB), stage II, stage III, and stage IV.[34] There is no established staging system for peritoneal mesothelioma.
History and Symptoms
When evaluating a patient for mesothelioma, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review. Other specific areas of focus include a history of any exposure to asbestos or radiation.[16] Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Symptoms of mesothelioma include chest pain, shortness of breath, cough, abdominal pain, palpitation, hemoptysis, and swelling in the legs.[35]
Physical Examination
Common physical examination findings of mesothelioma include dullness on percussion and decreased breath sounds on ausculatation of the lung, ascites, abdominal mass, hemoptysis, pedal edema, and murmurs.[35]
Laboratory Findings
Laboratory findings consistent with the diagnosis of mesothelioma include abnormal pleural fluid analysis (decreased pleural pH and pleural fluid/serum glucose ratio).[36]
Chest X Ray
Chest x-rays are of limited utility and are non-specific in a case of mesothelioma, demonstrating a pleural opacity which may extend around and encase the lung.[37]
CT
Chest CT scan may be diagnostic of mesothelioma. CT is the most commonly used modality for the assessment of mesothelioma and is able to stage the disease accurately in majority of the patients.[38]
MRI
MRI, although not routinely used, may have a role in refining the staging and better delineating the extent of the disease in surgical candidates especially with regard to chest wall and diaphragmatic invasion. Findings on MRI include iso- to slightly hyperintense on T1-weighted images and iso- to hyperintense on T2-weighted images. There is enhancement on contrast administration.[38]
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Summary of Treatment for Pleural Mesothelioma
Summary of Treatment for Peritoneal Mesothelioma
Primary Prevention
Secondary Prevention
References
- ↑ 1.0 1.1 Philip A. Rascoe, Xiaobo X. Cao and W. Roy Smythe (2012). Molecular Pathogenesis of Malignant Pleural Mesothelioma, Mesotheliomas - Synonyms and Definition, Epidemiology, Etiology, Pathogenesis, Cyto-Histopathological Features, Clinic, Diagnosis, Treatment, Prognosis, Dr Alexander Zubritsky (Ed.), ISBN: 978-953-307-845-8, InTech, Available from: http://www.intechopen.com/books/mesotheliomas-synonyms-and-definition-epidemiology-etiology-pathogenesis-cyto-histopathological-features-clinic-diagnosis-treatment-prognosis/molecular-pathogenesis-of-malignant-pleural-mesothelioma
- ↑ Mesothelioma. Wikipedia 2016. https://en.wikipedia.org/wiki/Mesothelioma. Accessed on February 3, 2016
- ↑ "Mesothelioma risks and causes : Cancer Research UK : CancerHelp UK". Cancerhelp.org.uk. 2010-06-23. Retrieved 2010-08-20.
- ↑ 4.0 4.1 4.2 4.3 Thomas, Anish; Chen, Yuanbin; Yu, Tinghui; Gill, Ammara; Prasad, Vinay (2015). "Distinctive clinical characteristics of malignant mesothelioma in young patients". Oncotarget. 6 (18): 16766–16773. doi:10.18632/oncotarget.4414. ISSN 1949-2553.
- ↑ 5.0 5.1 Mesothelioma. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/mesothelioma. Accessed on February 8, 2016
- ↑ What is mesothelioma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/mesothelioma/mesothelioma/?region=on. Accessed on February 8, 2016
- ↑ Ladanyi M (2005). "Implications of P16/CDKN2A deletion in pleural mesotheliomas". Lung Cancer. 49 Suppl 1: S95–8. doi:10.1016/j.lungcan.2005.03.017. PMID 15950811.
- ↑ Kumar-Singh S, Segers K, Rodeck U, Backhovens H, Bogers J, Weyler J; et al. (1997). "WT1 mutation in malignant mesothelioma and WT1 immunoreactivity in relation to p53 and growth factor receptor expression, cell-type transition, and prognosis". J Pathol. 181 (1): 67–74. doi:10.1002/(SICI)1096-9896(199701)181:1<67::AID-PATH723>3.0.CO;2-Z. PMID 9072005.
- ↑ Ladanyi M, Zauderer MG, Krug LM, Ito T, McMillan R, Bott M; et al. (2012). "New strategies in pleural mesothelioma: BAP1 and NF2 as novel targets for therapeutic development and risk assessment". Clin Cancer Res. 18 (17): 4485–90. doi:10.1158/1078-0432.CCR-11-2375. PMC 3432735. PMID 22825583.
- ↑ Andujar P, Pairon JC, Renier A, Descatha A, Hysi I, Abd-Alsamad I; et al. (2013). "Differential mutation profiles and similar intronic TP53 polymorphisms in asbestos-related lung cancer and pleural mesothelioma". Mutagenesis. 28 (3): 323–31. doi:10.1093/mutage/get008. PMID 23435014.
- ↑ Opitz I, Soltermann A, Abaecherli M, Hinterberger M, Probst-Hensch N, Stahel R; et al. (2008). "PTEN expression is a strong predictor of survival in mesothelioma patients". Eur J Cardiothorac Surg. 33 (3): 502–6. doi:10.1016/j.ejcts.2007.09.045. PMID 18248818.
- ↑ Murakami H, Mizuno T, Taniguchi T, Fujii M, Ishiguro F, Fukui T; et al. (2011). "LATS2 is a tumor suppressor gene of malignant mesothelioma". Cancer Res. 71 (3): 873–83. doi:10.1158/0008-5472.CAN-10-2164. PMID 21245096.
- ↑ 13.0 13.1 13.2 13.3 Mesothelioma. CGMH.ORG 2016. https://www1.cgmh.org.tw/intr/intr5/c6700/OBGYN/f/web/Mesothelioma/index.htm. Accessed on February 15, 2016
- ↑ Pathology of mesothelioma. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/mesothelioma. Accessed on February 10, 2016
- ↑ Immunohistochemistry of mesothelioma. Wikipedia 2016. https://en.wikipedia.org/wiki/Mesothelioma. Accessed on February 12, 2016
- ↑ 16.0 16.1 Risk factors for mesothelioma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/mesothelioma/risks/?region=on. Accessed on February 8, 2016
- ↑ Differential diagnosis of mesothelioma. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/mesothelioma. Accessed on February 12, 2016
- ↑ Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/pleural-tumours. Accessed on February 12, 2016
- ↑ Differential diagnosis of peritoneal mesothelioma. Dr Alexandra Stanislavsky et al. Radiopaedia 2016. http://radiopaedia.org/articles/peritoneal-mesothelioma. Accessed on February 12, 2016
- ↑ Primary peritoneal neoplasms. Dr Praveen Jha and Radswiki et al. Radiopaedia 2016. http://radiopaedia.org/articles/primary-peritoneal-neoplasms. Accessed on February 12, 2016
- ↑ Seek a Second Opinion to Avoid Misdiagnosis of Pericardial Mesothelioma. Asbestos.com 2016. http://www.asbestos.com/mesothelioma/pericardial.php. Accessed on February 12, 2016
- ↑ Differential diagnosis of multicystic mesothelioma. Dr Aditya Shetty and Dr Yuranga Weerakkody et al. Raiopaedia 2016. http://radiopaedia.org/articles/multicystic-mesothelioma. Accessed on February 12, 2016
- ↑ Chekol, Seble S; Sun, Chen-Chin (2012). "Malignant Mesothelioma of the Tunica Vaginalis Testis: Diagnostic Studies and Differential Diagnosis". Archives of Pathology & Laboratory Medicine. 136 (1): 113–117. doi:10.5858/arpa.2010-0550-RS. ISSN 0003-9985.
- ↑ Saint-Pierre, Mathieu D.; Pease, Christopher; Mithoowani, Hamid; Zhang, Tinghua; Nicholas, Garth A.; Laurie, Scott A.; Wheatley-Price, Paul (2015). "Malignant Pleural Mesothelioma Outcomes in the Era of Combined Platinum and Folate Antimetabolite Chemotherapy". Lung Cancer International. 2015: 1–7. doi:10.1155/2015/590148. ISSN 2090-3197.
- ↑ Mesothelioma. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al.Radiopaedia 2016. http://radiopaedia.org/articles/mesothelioma. Accessed on 13th January, 2016
- ↑ 26.0 26.1 Survival statistics for mesothelioma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/mesothelioma/prognosis-and-survival/survival-statistics/?region=on. Accessed on February 10, 2016
- ↑ 27.0 27.1 Complications of mesothelioma. Mayo clinic 2016. http://www.mayoclinic.org/diseases-conditions/mesothelioma/basics/complications/con-20026157. Accessed on February 13, 2016
- ↑ 28.0 28.1 Mensi C, Termine L, Garberi A, Meroni S, Levi D, Balzarini L; et al. (2012). "Spinal cord compression: an unusual presentation of malignant pleural mesothelioma. A case report and review of the literature". Tumori. 98 (4): e92–7. doi:10.1700/1146.12651. PMID 23052177.
- ↑ 29.0 29.1 Minami T, Matsumoto K, Aizawa H, Nakano H, Sugio K, Nakashima Y; et al. (1999). "[Horner's syndrome in a patient with diffuse malignant pleural mesothelioma]". Nihon Kokyuki Gakkai Zasshi. 37 (4): 287–90. PMID 10390966.
- ↑ 30.0 30.1 Ragalie GF, Varkey B, Choi H (1983). "Malignant pleural mesothelioma presenting as superior vena cava syndrome". Can Med Assoc J. 128 (6): 689–91, 740. PMC 1875200. PMID 6825037.
- ↑ 31.0 31.1 Clinical presentation of peritoneal mesothelioma. Dr Alexandra Stanislavsky et al. Radiopaedia 2016. http://radiopaedia.org/articles/peritoneal-mesothelioma. Accessed on February 13, 2016
- ↑ 32.0 32.1 Clinical presentation of tunica vaginalis testis mesothelioma. Dr Matt A. Morgan and Dr Dalia Ibrahim et al. Radiopaedia 2016. http://radiopaedia.org/articles/tunica-vaginalis-testis-mesothelioma. Accessed on February 13, 2016
- ↑ Complications of pericardial mesothelioma. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/pericardial-mesothelioma. Accessed on February 13, 2016
- ↑ Stages of pleural mesothelioma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/mesothelioma/staging/?region=on. Accessed on February 6, 2016
- ↑ 35.0 35.1 Signs and symptoms of mesothelioma. Wikipedia 2016. https://en.wikipedia.org/wiki/Mesothelioma. Accessed on February 16, 2016
- ↑ Gottehrer A, Taryle DA, Reed CE, Sahn SA (1991). "Pleural fluid analysis in malignant mesothelioma. Prognostic implications". Chest. 100 (4): 1003–6. PMID 1914546.
- ↑ Mesothelioma. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/mesothelioma. Accessed on 13th January, 2016
- ↑ 38.0 38.1 Radiographic findings of mesothelioma. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/mesothelioma. Accessed on February 8, 2015