Malignant Mesothelioma Imaging 

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.

A positron emission tomography (PET) scan of mesothelioma is provided below.

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. The most common findings on physical examination (79%) are signs of pleural effusion (eg, dullness to percussion, decreased breath sounds).

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. 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).^[2]

Preferred examination

Chest radiography is the initial screening examination, while computed tomography (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.^[3]

PET scanning may also be useful in delineating the extent of tumor or metastases.^[4]

Limitations of techniques

Chest radiography has limited usefulness. The radiographic findings of mesothelioma are nonspecific and are 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 study by Heelan et al.^[5]

Neither CT scanning nor MRI provides an unequivocal diagnosis of mesothelioma; tissue biopsy is required for the definitive diagnosis.

The most common mesothelioma finding on radiographs is unilateral, concentric, plaquelike, or nodular pleural thickening (as seen in the images below). 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 confidence

Although 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 scan findings (examples of which are shown in the images below) are similar to those of plain films but are seen better and in more detail.^{[6, 7]} 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 with 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/negatives

Benign pleural plaques or pleural thickening from asbestos exposure may mimic the appearance of nodular pleural thickening in patients with mesothelioma (see the image below).

MRI produces images (an example is of which is shown below) in multiple planes and is superior to CT scanning in demonstrating solitary foci of chest wall invasion, endothoracic fascial involvement, and diaphragmatic invasion.^{[8, 7]} 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. Inflammatory pleural disease may mimic the increased MRI signal intensity of mesothelioma.

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). 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.

NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.

Ultrasonography 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 to assess the extent of disease in patients with mesothelioma.

If 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.^{[3, 4, 9, 10, 11, 12]}

Yildirim et al examined the efficacy of using 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) PET and 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.^[9]

A study by Mavi et al concluded that dual time-point FDG PET scanning seems to be an accurate means of differentiating malignant mesothelioma from benign pleural disease. In the study, which involved 55 patients, 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 had decreased.^[10]

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.^[11]

False positives/negatives

Pleural inflammation can also reveal increased uptake on PET scanning.