Radiologic Assessment of Mesothelioma

Imaging plays an essential role in the diagnosis, staging, and clinical management of patients with mesothelioma. X-ray imaging techniques [chest radiography and computed tomography (CT)], magnetic resonance imaging (MRI), and positron emission tomography (PET) have all been used to evaluate this disease, although the relative importance of these imaging modalities has changed over time. Our understanding of mesothelioma has been advanced through radiologic examination, and nearly every mesothelioma patient makes numerous trips to the radiology department during the course of treatment. Imaging studies define the morphology and extent of mesothelioma, tumor perfusion, tumor physiology, the presence of mediastinal or chest wall involvement, and the presence of concomitant disease. The image acquisition device (i.e., the hardware) is only one component of the radiologic examination; software tools for the subsequent visualization and postprocessing of the acquired image data are required to extract useful information from the image pixels and to fully exploit the wealth of information contained within the image. This chapter describes the imaging modalities that have been employed for the evaluation of mesothelioma and emphasizes the role of CT in the important task of tumor thickness measurement for the assessment of tumor progression
or response to therapy.

Imaging Modalities for mesothelioma

Radiography
Chest radiography continues to rank as the most common radiologic procedure performed in the United States. Consequently, initial detection of mesothelioma in a patient is likely to result from a radiographic chest examination. The two-dimensional radiographic projection of mesothelioma with its complex three-dimensional morphology, however, provides neither a sensitive nor a specific diagnosis, and a follow-up study with another imaging modality is almost always indicated. The ability to diagnose mesothelioma on chest radiography usually occurs at later, more advanced stages of the disease when tumor burden is greater.
Initial radiographic signs of mesothelioma include a unilateral pleural abnormality with an associated ipsilateral pleural effusion, ipsilateral shift of the mediastinum, and unilateral lung volume loss due to encasement of the lung by the tumor as the below image:

Posteroanterior chest radiograph in an 83-year-old man shows “mesothelioma “ diffusely involving the pleura on the right (arrow) accompanied by volume loss of the right hemithorax. Signs of other asbestos-related disease are usually absent, and the typical finding of diffuse lobulated pleural thickening is indistinguishable from pleural metastases .

At later stages of the disease, radiography may demonstrate thickening of interlobular septa, rib or vertebral body destruction, lymph node metastases, and metastatic pulmonary nodules Contralateral pleural abnormalities, when present, are typically the result of benign asbestos-related disease rather than metastases since mesothelioma generally spreads by contiguous growth; nevertheless, hematogenous spread of mesothelioma may be observed on imaging studies See image below:

Enhanced CT of the chest in a 41-year-old man at the level of the right pulmonary artery shows left-sided pleural thickening with volume loss accompanied by rib crowding and ipsilateral shift of the mediastinum. Numerous sharply circumscribed nodules bilaterally, consistent with hematogenous metastases, are also evident. Pleural thickening involves the left major fissure, which indicates involvement of the visceral pleura.

and was present in 44 of 66 autopsy cases in one series Radiography plays a role in the posttherapy follow-up of patients. For example, patients who undergo extrapleural pneumonectomy may be monitored for complications and recurrence with chest radiography once the affected hemithorax has opacified.

Findings such as mediastinal shift, a new air–fluid level in the affected hemithorax, or nodules in the contralateral lung would indicate that a CT scan is warranted to differentiate between recurrent disease, infection, or a postsurgery complication.

FIG A. A 70-year-old man with prior surgery on the right, which consisted of resection and placement of a synthetic patch (curvilinear bright density just internal to the rib cage). This enhanced computed tomography (CT) scan demonstrates recurrence of disease after surgery as a 22 ¥ 18-mm soft tissue density in the lower right anterior chest wall (arrow). More often, however, CT is being used as the sole imaging modality for routine posttherapy follow-up.

Computed Tomography
The imaging modality with the greatest impact on the current evaluation of mesothelioma is CT. The transaxial images generated by CT overcome the superposition of anatomic and pathologic structures that limits the two-dimensional projection images acquired by radiography.
Accordingly, the spatial extent and radiologic characteristics of mesothelioma tumor may be more clearly appreciated with CT. The radiologic manifestation of pleural response to a variety of diseases falls into three broad categories: pleural effusion, pleural thickening, and pleural calcification Computed tomography is especially capable of demonstrating such pleural responses. The particular CT findings of mesothelioma, however, are not pathognomonic; a variety of benign and malignant diseases (including metastatic disease, tuberculous pleurisy, empyema, and asbestos-related advanced pleural abnormalities) can have similar characteristics on CT.

On CT, mesothelioma is characterized by a circumferential, lobulated soft tissue mass that often involves the interlobar fissures and the mediastinal pleura of a hemithorax.

Enhanced CT in a 70-year-old man demonstrates left-sided irregular, nodular pleural thickening greater than 1 cm, characteristic of mesothelioma. Focal nodular thickening of the left major fissure is also seen (white arrow). Also of note is a small subpleural nodule (likely metastatic disease) posteriorly on the right (black arrow).

bilateral disease is rare Pleural effusions, see below image:

Enhanced CT in an 83-year-old man with malignant mesothelioma shows a large right-sided pleural effusion with underlying compressive atelectasis.

and nodular pleural thickening, especially in the lower thoracic zone, are typical CT findings in mesothelioma patients A tendency for right-sided disease has been observed Intravenous iodinated contrast administered intravenously is typically used to identify mediastinal lymph node enlargement and to determine the relation of lesions to adjacent vascular structures. a recognized shortcoming of CT, however, is its limited sensitivity for hilar lymph node involvement. Although pleural plaques are a common CT finding in mesothelioma, this reflects the role of asbestos exposure in the pathogenesis of both lesions; the possible preneoplastic nature of such plaques has not been proven In a series of 50 patients, Ng et al observed that 76% of the initial CT scans demonstrated pleural effusions, of which the majority were considered “small” (i.e., they occupied less than one third of the hemithorax). Pleural thickening was observed in 94% of cases, of which 72% was nodular, 50% showed a lower zone predominance, and 47% exceeded 1cm .

Superior mediastinal pleural thickening was observed in 70% of cases, diaphragmatic crural thickening was demonstrated in 84% of cases, and thickening of the pleural surfaces of the interlobar fissures was present in 84% of cases Kawashima and Libshitz report similar findings. In their series of CT scans from 50 mesothelioma patients, 74% of cases demonstrated pleural effusions (of which approximately half occupied less than one third of the hemithorax), 86% of cases demonstrated thickening of the pleural surfaces of the interlobar fissures, and pleural thickening of various extent, thickness, and nodularity was observed in 92% of cases. Focal pleural masses (ranging from 7 to 18cm in maximum diameter) were observed in 8% of cases; half of these cases demonstrated chest wall invasion Fig A Above.

The volumetric extent of disease may be more clearly appreciated with CT than with chest radiography. The CT findings depicting the impact of mesothelioma on the affected hemithorax volume are varied. In response to volume loss of the ipsilateral hemithorax, for example, ipsilateral mediastinal shift may occur Alternatively, tumor encasement of the ipsilateral lung may result in ipsilateral volume loss without mediastinal shift (referred to as the “fixed mediastinum”). Ipsilateral volume loss may also be demonstrated on CT by narrowed
intercostal spaces [so-called rib crowding (10)] and ipsilateral hemidiaphragm elevation.

led rib crowding and ipsilateral hemidiaphragm elevation. Substantial pleural effusion or pleural thickening, however, may cause contralateral mediastinal shift with a corresponding increase in ipsilateral hemithorax volume. The CT section in Figure below.

Fig B. Enhanced CT in a 56-year-old woman shows right-sided irregular, nodular thickening of the pleura with rib crowding and contralateral shift of the mediastinum. Involvement of the anterior chest wall and subcutaneous
tissue is also seen (arrow).

represents a hybrid of these mechanisms: ipsilateral volume loss with rib crowding combined with contralateral shift of the mediastinum. Ng et a observed ipsilateral volume loss in 27% of cases, of which 68% demonstrated ipsilateral mediastinal shift; ipsilateral volume increase was observed in 10% of cases, of which 57% demonstrated contralateral mediastinal shift. It is interesting to note that the volume of the affected hemithorax was not substantially altered in 63% of cases at initial CT Kawashima and Libshitz observed ipsilateral volume loss in 42% of cases, of which approximately half demonstrated ipsilateral mediastinal shift; contralateral mediastinal shift (due to a large effusion or a combination of effusion and mass) was observed in 14% of cases. Neither change in hemithorax volume nor shift of the mediastinum were observed in 44% of cases. Yilmaz et al (10) also noted ipsilateral volume loss with (9% of cases) and without (22% of cases) ipsilateral mediastinal shift, contralateral mediastinal shift due to a large effusion or a combination of effusion and mass (26% of cases), and no change in mediastinal position or affected hemithorax volume (43% of cases)

Although primary pericardial mesothelioma is rare, pericardial invasion of pleural mesothelioma is demonstrated at CT by pericardial thickening with potential concomitant pericardial effusion.

FIG D Enhanced CT scan at the level of the dome of the right hemidiaphragm in a 62-year-old woman demonstrates malignant mesothelioma involving the pericardium overlying the left ventricle (arrow). Widespread involvement of the pleura and parenchyma on the left is also seen.

It should be noted, however, that distinction between mediastinal pleural disease alone and associated pericardial disease is difficult on CT Some investigators suggest that pericardial involvement should be considered likely when involvement of the mediastinal pleura is bulky or extensive at CT leura is bulky or extensive at CT .
CT findings are often used in the differential diagnosis of diffuse pleural disease to distinguish between benign pleural disease and mesothelioma (or other malignant pleural disease). The presence of a pleural rind, involvement of the mediastinal pleura, pleural nodularity, and pleural thickening in excess of 1cm have all been associated specifically with malignant pleural disease and are all well depicted on CT. Moreover, invasion of the chest wall or mediastinum the as above image FIG A and FIG D. displacement or destruction of ribs or vertebral bodies in below image:

transdiaphragmatic growth image in below:

and lymph node metastases in below:

are other CT-based indicators of malignancy, although MRI may have advantages over CT with regard to some of these indicators. In a series of 74 patients with diffuse pleural disease, Leung et al observed that among the 71 patients with pleural thickening on CT, four CT findings—presence of a pleural rind, nodular pleural thickening, parietal pleural thickening greater than 1cm, and mediastinal pleural involvement—were significantly more common in patients with malignant pleural disease than in patients with benign pleural disease. The three patients without pleural thickening demonstrated unilateral pleural effusions, the sole indicator of pleural malignancy in these patients; thus, the authors conclude that absence of pleural thickening does not preclude a malignant diagnosis. The CT findings in mesothelioma patients were the same as the CT findings in patients with metastatic pleural disease, and the CT findings that distinguished mesothelioma from benign pleural disease were essentially the same as those that distinguished malignant pleural disease from
benign pleural disease (7). Pleural calcifications were observed to be indicative of a benign process, since none of the mesothelioma patients in this series demonstrated pleural calcifications. Although benign pleural disease in general may present unilaterally, unilateral pleural disease within asbestos-exposed patients was highly specific for malignant disease generally and suggestive of mesothelioma in articular

Computed tomography has also been shown to differentiate between esothelioma and other malignant pleural disease, although this task as generally been considered a more difficult radiologic challenge. In  series of 215 patients (99 with mesothelioma, 39 with metastatic leural disease, and 77 with benign pleural disease), Metintas et al (8) sed multivariate analysis to show that (1) the presence of a pleural ind, (2) mediastinal pleural involvement, and (3) pleural thickness reater than 1cm were independent findings both for differentiating
mesothelioma from metastatic pleural disease and for differentiating alignant pleural disease (i.e., mesothelioma and metastatic pleural isease) from benign pleural disease. The first two findings were also
useful for the differentiation of mesothelioma from benign pleural isease. Nodular pleural thickening was common among the CT scans f mesothelioma patients, and although it was found to be an independent finding for the differentiation of mesothelioma or malignant leural disease from benign pleural disease, nodular pleural thickening could not be used to differentiate mesothelioma from metastatic leural disease .
Another important aspect of CT is its ability to depict ancillary findings in the lungs that typically accompany mesothelioma and are associated with prior asbestos exposure. These findings include ipsilateral telectasis [observed in 74% of cases in the 70-patient series of Ng et al, rounded atelectasis [observed in 9% of cases in this series, nd lung nodules [observed in 11% of cases. A CT finding of compressive atelectasis secondary to a large pleural effusion in a mesothelioma patient is shown in Figure below:

omputed tomography has become a valuable tool for biopsy guidance. Closed pleural needle biopsy may be used in lieu of more invasive procedures (e.g., thoracoscopy or thoracotomy) to obtain pleural issue or fluid samples for histopathologic diagnosis. In the absence of T guidance, however, the sensitivity of closed pleural needle biopsy or the diagnosis of mesothelioma has been limited due to a typically mall sample size and an inability to visualize the source of the cquired sample within the patient. The addition of CT guidance to the biopsy procedure greatly reduces these limitations. In a eries of 30 patients, Metintas et al correctly diagnosed mesothelioma in 83% of cases by use of CT-guided closed pleural needle biopsy,  figure that represents a substantial improvement in efficiency relative o the same biopsy procedure performed without CT.

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