You are in: eMedicine Specialties > Radiology > CHEST Mesothelioma, MalignantArticle Last Updated: Aug 15, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Elizabeth K Dee, MD, Consulting Staff, Department of Radiology, Denver Health Medical Center Elizabeth K Dee is a member of the following medical societies: American Medical Association and Radiological Society of North America Coauthor(s): Kavita Garg, MD, Professor, Department of Radiology, University of Colorado Health Sciences Center Editors: Judith K Amorosa, MD, FACR, Clinical Professor and Program Director, Department of Radiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School; Consulting Staff, Department of Radiology, Robert Wood Johnson University Hospital; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; W Richard Webb, MD, Chief of Thoracic Imaging, Professor, Department of Radiology, University of California at San Francisco; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Eugene C Lin, MD, Consulting Staff, Department of Radiology, Virginia Mason Medical Center Author and Editor Disclosure Synonyms and related keywords: malignant pleural mesothelioma, MPM, diffuse mesothelioma, asbestos exposure, Butchart staging system INTRODUCTIONSection 2 of 11
  BackgroundMesothelioma 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. 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. PathophysiologyThe 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:
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 system2 and the tumor, node, metastases (TNM)-based system (see Table) that was introduced by the International Mesothelioma Interest Group.3 The Butchart staging system for malignant pleural mesothelioma is as follows2:
TNM Staging System for Malignant Pleural Mesothelioma3
FrequencyUnited StatesAnnually, approximately 1.0-1.1 in 100,000 people present with mesothelioma.4 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.5 InternationalThe 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).6 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.6 Mortality/MorbidityMalignant mesothelioma is usually fatal. Death generally occurs within 18 months of symptom onset. RaceNo racial predisposition is recognized. SexThe 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.4 AgeMesothelioma is most commonly diagnosed at age 50-70 years, with the greatest incidence rates at age 65 and older in both sexes.4 Clinical DetailsMesothelioma 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:
Other symptoms include the following:
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:
The most common signs of peritoneal mesothelioma include the following:
Adams et al also described decreased chest excursion (15%), palpable lymph nodes (12%), and a palpable liver (9%).7 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.8 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.9 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). 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.10 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
Limitations of TechniquesChest 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.11 Neither CT scanning nor MRI provides an unequivocal diagnosis of mesothelioma; tissue biopsy is required for the definitive diagnosis. DIFFERENTIALSSection 3 of 11
Asbestos-Related Disease Congestive Heart Failure Empyema Localized Fibrous Tumor of the Pleura Lung, Metastases Renal Cell Carcinoma Other Problems to Be ConsideredAdenocarcinoma (lung, breast, ovarian, gastric) RADIOGRAPHSection 4 of 11
FindingsThe most common mesothelioma finding on radiographs is unilateral, concentric, plaquelike, or nodular pleural thickening. Pleural effusions are common and may obscure the presence of the underlying pleural thickening. The tumor frequently extends into the fissures, which become thickened and irregular in contour. A slight right-sided predominance is observed, possibly because of a larger pleural surface area. The tumor can rigidly encase the lung, causing compression of lung parenchyma, diaphragm elevation, intercostal space narrowing, and mediastinal shift toward the tumor. Calcified pleural plaques are present in 20% of patients with mesothelioma and are usually related to the previous asbestos exposure. Lung nodules and hilar masses usually result from direct mesothelioma tumor extension into the lung parenchyma and mediastinal structures, such as lymph nodes, the pericardium, and the heart. Mechanical distortion of the hemithorax, chest wall masses, periosteal rib reaction, or rib destruction by the tumor are signs of advanced disease. Although usually unilateral, direct extension of the tumor across the mediastinum into the contralateral hemithorax does occur. Degree of ConfidenceAlthough a definite diagnosis cannot be made on the basis of plain film findings, new unilateral pleural thickening or effusion in a patient who has a history of exposure to asbestos is highly suggestive of mesothelioma. CT SCANSection 5 of 11
FindingsCT scan findings are similar to those of plain films but are seen better and in more detail. Furthermore, pleural thickening and effusion can be distinguished with CT scanning. Nodular pleural thickening, pleural thickening greater than 1 cm, involvement of the mediastinal pleural surface, and concentric pleural thickening are all highly suggestive of malignant pleural disease, either mesothelioma or metastases. The tumor extent along the pleural surfaces and into the mediastinum, diaphragm, or chest wall can be evaluated much better with CT scanning than plain radiography. Chest wall invasion manifests as obliteration of fat planes or chest wall nodules. Diaphragmatic invasion, ascites, and omental caking are common CT scan findings of peritoneal mesothelioma. False Positives/NegativesBenign pleural plaques or pleural thickening from asbestos exposure may mimic the appearance of nodular pleural thickening in patients with mesothelioma. MRISection 6 of 11
FindingsMRI produces images in multiple planes and is superior to CT scanning in demonstrating solitary foci of chest wall invasion, endothoracic fascial involvement, and diaphragmatic invasion. Mesothelioma images on MRI demonstrate minimally increased T1 signals relative to the chest wall musculature and moderately increased signals on T2-weighted images or T1-weighted images that have been obtained following injection of gadolinium. Fibrous pleural plaques are usually isointense or less intense relative to muscle. Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. Degree of ConfidenceInflammatory pleural disease may mimic the increased MRI signal intensity of mesothelioma. ULTRASOUNDSection 7 of 11
FindingsUltrasonography can demonstrate pleural thickening or effusions in patients with mesothelioma. This modality can be used as a guide for biopsy, but it is not typically used for assessment of the disease extent in patients with mesothelioma. NUCLEAR MEDICINESection 8 of 11
FindingsIf surgical resection of the tumor is a possibility, a quantitative ventilation-perfusion scan helps in assessing the function of the contralateral lung. PET scanning has been used, although not routinely, to evaluate mesothelioma and may help preoperatively by documenting the extent of lymph node involvement or distant metastases. False Positives/NegativesPleural inflammation can also reveal increased uptake on PET scanning. INTERVENTIONSection 9 of 11
Percutaneous catheter drainage and pleurodesis may be used for treatment of pleural effusions secondary to mesothelioma. Medical/Legal Pitfalls
MULTIMEDIASection 10 of 11
REFERENCESSection 11 of 11
Mesothelioma, Malignant excerpt Article Last Updated: Aug 15, 2007 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
