DOI: 10.1148/rg.241035058
(Radiographics. 2004;24:105-119.)
© RSNA, 2004
Malignant Pleural Mesothelioma: Evaluation with CT, MR Imaging, and PET1
Zhen J. Wang, MD,
Gautham P. Reddy, MD, MPH,
Michael B. Gotway, MD,
Charles B. Higgins, MD,
David M. Jablons, MD,
Mohan Ramaswamy, MD,
Randall A. Hawkins, MD, PhD and
W. Richard Webb, MD
1 From the Department of Radiology, Box 0628, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA 94143. Presented as an education exhibit at the 2002 RSNA scientific assembly. Received March 10, 2003; revision requested April 10 and received May 23; accepted May 27. All authors have no financial relationships to disclose. Address correspondence to G.P.R. (e-mail: gautham.reddy@radiology.ucsf.edu).
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Abstract
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Imaging plays an essential role in the evaluation of malignant pleural mesothelioma (MPM). Computed tomography is the primary imaging modality used for the diagnosis and staging of MPM. Magnetic resonance (MR) imaging and, more recently, positron emission tomography (PET) have emerged as modalities that can provide additional important diagnostic and prognostic information to help further delineate the extent of disease, especially in surgical candidates. Use of MR imaging performed with different pulse sequences and gadolinium-based contrast material can improve the detection of tumor extension, especially to the chest wall and diaphragm. PET can provide both anatomic and metabolic information, especially in cases of extrathoracic and mediastinal nodal metastasis. Each imaging modality has its advantages and limitations, but their combined use is crucial in determining the most appropriate treatment options for patients with MPM.
© RSNA, 2004
Index Terms: Mesothelioma, 66.3254 • Pleura, CT, 66.1211 • Pleura, MR, 66.1214 • Pleura, neoplasms, 66.3254 • Pleura, PET, 66.12163
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LEARNING OBJECTIVES FOR TEST 4
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After reading this article and taking the test, the reader will be able to:
- Discuss the advantages and limitations of CT, MR imaging, and PET in the diagnosis and staging of MPM.
- Describe key features of MPM at CT, MR imaging, and PET.
- Identify the imaging features of MPM that can help predict tumor resectability.
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Introduction
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Malignant pleural mesothelioma (MPM) is an uncommon neoplasm that arises from the pleura or, rarely, the pericardium or peritoneum. There are approximately 2,000–3,000 new cases diagnosed in the United States every year, the majority of which are associated with prior asbestos exposure (1). Patients frequently present with dyspnea, chest pain, cough, and weight loss. The tumor can invade both visceral and parietal pleura and frequently extends to adjacent structures. The prognosis is poor, with a median survival time of 12 months after diagnosis (2). Several factors have been shown to correlate with reduced survival time: intrathoracic lymph node metastases, distant metastatic disease, and extensive pleural involvement (3).
Various modalities have been used in the treatment of MPM. Radiation therapy alone is gener-ally used for palliation (4). Patients who undergo chemotherapy with a platinum- or doxorubicin-containing regimen have shown limited response without significant change in survival time (5). Aggressive surgical resection (extrapleural pneumonectomy or radical pleurectomy-decortication) used alone has also yielded disappointing results, with a median survival time of less than 1 year (6,7). However, multimodality therapy consisting of surgery followed by chemotherapy and radiation therapy has been shown to prolong survival. Sugarbaker et al (8) studied 183 patients who had undergone extrapleural pneumonectomy followed by adjuvant chemotherapy and radiation therapy and found a median survival time of 19 months at the most recent follow-up. More recently, Lee et al (9) showed a median survival time of 18.1 months for patients who had undergone radical pleurectomy-decortication with aggressive radiation therapy with or without chemotherapy. Proper patient selection is crucial in identifying those most likely to benefit from an aggressive multimodality regimen. Imaging studies, including computed tomography (CT), magnetic resonance (MR) imaging, and positron emission tomography (PET), play an essential role in the staging of disease in patients who are potential surgical candidates.
In this article, we discuss and illustrate the staging and diagnostic evaluation of MPM with CT, MR imaging, and PET.
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Staging
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The new staging system from the International Mesothelioma Interest Group is a TNM (tumor-node-metastasis) system that was initially developed to categorize like cases into homogeneous prognostic groups to aid in evaluating new treatment options (Tables 1–3) (3,10). This staging system emphasizes criteria used to determine the extent of local tumor and lymph node involvement, both of which factors have been shown to be related to the overall survival rate in MPM (3,11). With locally advanced tumors, it is important to distinguish between T3 (potentially resectable) and T4 (technically unresectable) disease. This distinction guides the choice of treatment options and implies significant differences in survival. The presence of N3 nodal disease or distant metastasis also precludes surgery. Although surgical staging is often required in patients with potentially resectable lesions, CT, MR imaging, and PET can aid in choosing whether to treat MPM surgically, medically, or both.
CT is usually the primary imaging modality used for disease staging in patients who are being considered for resection. CT is readily available and provides a significant amount of anatomic information. The results can be used to preclude surgery in patients with obviously unresectable tumors (eg, diffuse extension of tumor into the chest wall, mediastinum, or peritoneum or distant metastasis). MR imaging or PET can then be used as the final preoperative radiologic examination to complement CT, particularly in questionable cases. MR imaging with use of different pulse sequences and gadolinium-based contrast material can improve the detection of tumor extension, especially to the chest wall and diaphragm. PET is useful for the detection of nodal involvement and occult metastasis. Correlation of all imaging findings is essential in directing exploration to areas of possible invasion and selecting those patients who may benefit from aggressive therapy.
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Diagnostic Evaluation
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Computed Tomography
CT is the primary imaging modality used for the evaluation of MPM. Key CT findings that suggest MPM include unilateral pleural effusion (Fig 1), nodular pleural thickening (Figs 2–4), and interlobar fissure thickening (Fig 5). Growth typically leads to tumoral encasement of the lung with a rindlike appearance (Fig 3). Calcified pleural plaques are found at CT in approximately 20% of patients with MPM and may become engulfed by the pri-mary tumor, causing the tumor to mimic calcified MPM (Fig 6) (12). There is also frequent contraction of the affected hemithorax with associated ipsilateral mediastinal shift, narrowed intercostal spaces, and elevation of the ipsilateral hemidiaphragm (Figs 3, 7).
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Figure 1a. Pleural effusion in a 70-year-old man with a history of asbestos exposure and known left-sided MPM. Axial contrast material-enhanced CT scans obtained at different levels show unilateral pleural effusion (P) with extensive calcified pleural plaques (arrows).
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Figure 1b. Pleural effusion in a 70-year-old man with a history of asbestos exposure and known left-sided MPM. Axial contrast material-enhanced CT scans obtained at different levels show unilateral pleural effusion (P) with extensive calcified pleural plaques (arrows).
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Figure 3. Pleural thickening in a 51-year-old man with MPM. Axial contrast-enhanced CT scan shows circumferential and nodular left-sided pleural thickening (arrows). The tumor encases the contracted left hemithorax, having a rindlike appearance.
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Figure 4. Pleural thickening in a 63-year-old man with MPM who had undergone an Eloesser flap procedure for mesothelioma. Axial contrast-enhanced CT scan shows circumferential right-sided pleural thickening (arrowheads). Note also the large chest wall defect (arrow) from the Eloesser flap procedure.
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Figure 5. Interlobar fissure involvement in an 82-year-old man with MPM and a history of pleurodesis. Axial nonenhanced CT scan shows right-sided pleural thickening and a pleural mass that extends into the right major fissure (arrows).
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Figure 6a. Calcified pleural mass in a 55-year-old woman with MPM. Axial nonenhanced CT scans obtained at different levels show multiple calcified subpleural and pleura-based masses (arrow). The masses represent either plaques that have been engulfed by the primary tumor or calcified MPM.
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Figure 6b. Calcified pleural mass in a 55-year-old woman with MPM. Axial nonenhanced CT scans obtained at different levels show multiple calcified subpleural and pleura-based masses (arrow). The masses represent either plaques that have been engulfed by the primary tumor or calcified MPM.
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Figure 7. Hemithoracic contraction in a 68-year-old man with a history of MPM. Axial contrast-enhanced CT scan shows a severely contracted left hemithorax and ipsilateral mediastinal shift.
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MPM is locally aggressive, with frequent invasion of the chest wall, mediastinum, and dia-phragm. Chest wall involvement may manifest as obliteration of extrapleural fat planes, invasion of intercostal muscles, displacement of ribs, or bone destruction (Figs 8, 9). However, irregularity of the interface between the chest wall and the tumor is not a reliable predictor of chest wall invasion (13). Occasionally, MPM can extend into the chest wall via needle biopsy tracks, surgical scars, and chest tube tracts (14). Direct extension of the tumor into vascular structures and mediastinal organs including the heart, esophagus, and trachea may occur (Fig 10). There is usually obliteration of surrounding fat planes, and the presence of a soft-tissue mass that surrounds more than 50% of the circumference of a vascular structure is strong evidence of invasion (13). MPM may invade the pericardium and can be seen at CT as nodular pericardial thickening or pericardial effusion. Transdiaphragmatic extension of MPM is suggested by a soft-tissue mass that encases the hemidiaphragm (Fig 11) (13). In contrast, a clear fat plane between the diaphragm and adjacent abdominal organs and a smooth diaphragmatic contour indicate that the tumor is limited to the thorax (13).
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Figure 8. Chest wall invasion in a 65-year-old man with a history of MPM. Axial nonenhanced CT scan shows a large left-sided pleural mass with involvement of the chest wall (*). Note the extension of the tumor into the extrapleural fat plane.
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Figure 9. Chest wall invasion in a 60-year-old man with a history of asbestos exposure and MPM. Axial contrast-enhanced CT scan shows diffuse chest wall involvement by the tumor (arrows). Obliteration of extrapleural fat planes and invasion of intercostal muscles are also seen. Such diffuse chest wall involvement is classified as T4 disease (unresectable).
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Figure 10a. Mediastinal invasion in a 65-year-old woman with MPM. Axial contrast-enhanced CT scans show nodular tumor extension into the mediastinum, with a soft-tissue mass behind the trachea (* in a), esophagus (arrowheads in b), and left atrium (arrows in c). Such diffuse mediastinal involvement is classified as T4 disease (unresectable).
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Figure 10b. Mediastinal invasion in a 65-year-old woman with MPM. Axial contrast-enhanced CT scans show nodular tumor extension into the mediastinum, with a soft-tissue mass behind the trachea (* in a), esophagus (arrowheads in b), and left atrium (arrows in c). Such diffuse mediastinal involvement is classified as T4 disease (unresectable).
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Figure 10c. Mediastinal invasion in a 65-year-old woman with MPM. Axial contrast-enhanced CT scans show nodular tumor extension into the mediastinum, with a soft-tissue mass behind the trachea (* in a), esophagus (arrowheads in b), and left atrium (arrows in c). Such diffuse mediastinal involvement is classified as T4 disease (unresectable).
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Figure 11a. Transdiaphragmatic extension in a 65-year-old woman with a history of MPM. Axial contrast-enhanced CT scans obtained at different levels show a soft-tissue mass that encases the diaphragm (* in a) and liver (arrows in b). Transdiaphragmatic extension makes this a T4 tumor (unresectable).
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Figure 11b. Transdiaphragmatic extension in a 65-year-old woman with a history of MPM. Axial contrast-enhanced CT scans obtained at different levels show a soft-tissue mass that encases the diaphragm (* in a) and liver (arrows in b). Transdiaphragmatic extension makes this a T4 tumor (unresectable).
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Pulmonary metastases of MPM manifesting as nodules and masses and, rarely, diffuse miliary nodules may be identified at CT (Figs 12, 13). Chest CT may also rarely demonstrate extrathoracic spread of MPM (eg, direct hepatic invasion, retroperitoneal extension, retrocrural adenopathy) (Fig 14) (15).
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Figure 12. Pulmonary metastases in a 68-year-old man with MPM. Axial high-resolution chest CT scan shows extensive septal thickening and perilymphatic nodules (arrows), findings that are consistent with lymphangitic tumor spread. The presence of pulmonary metastases makes this a stage IV tumor (unresectable).
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Figure 13. Pulmonary metastases in a 72-year-old man with MPM. Axial high-resolution chest CT scan shows multiple pulmonary nodules (circled), findings that are consistent with hematogenous tumor spread and represent stage IV disease (unresectable). Note also the right apical pneumothorax (*).
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Figure 14a. Hepatic metastases in a 73-year-old man with a history of MPM. (a) Axial contrast-enhanced chest CT scan shows a nodular right-sided posterior pleural mass with associated calcification (arrow), a finding that is consistent with the patient’s known history of mesothelioma. (b, c) Axial contrast-enhanced abdominal CT scans obtained at different levels show a large, hypovascular liver mass (M) with central necrosis (b) and calcification (arrows in c).
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Figure 14b. Hepatic metastases in a 73-year-old man with a history of MPM. (a) Axial contrast-enhanced chest CT scan shows a nodular right-sided posterior pleural mass with associated calcification (arrow), a finding that is consistent with the patient’s known history of mesothelioma. (b, c) Axial contrast-enhanced abdominal CT scans obtained at different levels show a large, hypovascular liver mass (M) with central necrosis (b) and calcification (arrows in c).
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Figure 14c. Hepatic metastases in a 73-year-old man with a history of MPM. (a) Axial contrast-enhanced chest CT scan shows a nodular right-sided posterior pleural mass with associated calcification (arrow), a finding that is consistent with the patient’s known history of mesothelioma. (b, c) Axial contrast-enhanced abdominal CT scans obtained at different levels show a large, hypovascular liver mass (M) with central necrosis (b) and calcification (arrows in c).
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Metastasis to the hilar and mediastinal lymph nodes is present at autopsy in approximately 40%–45% of patients with MPM (Fig 15) (16). Although CT is the most commonly used modality for the evaluation of lymph node groups, its accuracy remains suboptimal because enlarged nodes alone do not prove nodal involvement (17). CT can also lead to underestimation of the extent of disease in early chest wall involvement and peritoneal studding (10,18). Despite these limitations, CT remains the imaging study of choice for initial evaluation of patients with MPM. Furthermore, multi–detector row CT with multiplanar reformatting capability may potentially improve the accuracy of tumor detection. Three-dimensional reconstruction of CT data has been shown to be useful in the staging of neck and lung cancer (19,20). Although MPM staging with CT and multiplanar reformatting has not been studied extensively, it is conceivable that volumetric CT technique can improve the visualization of tumor extent, especially in regions such as the diaphragm that may be difficult to assess with axial imaging.
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Figure 15a. Mediastinal lymphadenopathy in a patient with MPM. Axial contrast-enhanced CT scans obtained at different levels show lymphadenopathy in low right paratracheal (a) and left retrobronchial (b) locations (arrows).
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Figure 15b. Mediastinal lymphadenopathy in a patient with MPM. Axial contrast-enhanced CT scans obtained at different levels show lymphadenopathy in low right paratracheal (a) and left retrobronchial (b) locations (arrows).
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MR Imaging
In patients with potentially resectable disease, MR imaging can provide additional staging information. Use of different pulse sequences and gadolinium-based contrast material can help differentiate between tumor and normal tissue. Relative to adjacent chest wall muscle, MPM is typically iso- or slightly hyperintense on T1-weighted images and moderately hyperintense on T2-weighted images. MPM enhances with use of gadolinium-based contrast material. The excellent contrast resolution of MR imaging can allow improved detection of tumor extension, especially to the chest wall and diaphragm, and better prediction of overall resectability (Fig 16). Anatomic and morphologic MR imaging features similar to those seen at CT are used to establish local invasion of MPM. Loss of normal fat planes, extension into mediastinal fat, and tumoral encasement of more than 50% of the circumference of a medi-astinal structure are some of the MR imaging features that suggest tumor extension.
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Figure 16a. MR imaging evaluation of MPM in a 63-year-old man. (a, b) Coronal (a) and contrast-enhanced fat-saturated (b) T1-weighted MR images show a large, enhancing right apical mass (M) with invasion of the chest wall (arrows in a). An enhancing right major fissure is also seen (arrowheads in b). (c, d) Sagittal T1-weighted (c) and coronal T2-weighted (d) MR images show the mass (M) with involvement of the diaphragmatic pleura (arrows). However, there is no invasion of the diaphragmatic muscle itself, which is visualized as an intact black line above the liver (arrowheads).
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Figure 16b. MR imaging evaluation of MPM in a 63-year-old man. (a, b) Coronal (a) and contrast-enhanced fat-saturated (b) T1-weighted MR images show a large, enhancing right apical mass (M) with invasion of the chest wall (arrows in a). An enhancing right major fissure is also seen (arrowheads in b). (c, d) Sagittal T1-weighted (c) and coronal T2-weighted (d) MR images show the mass (M) with involvement of the diaphragmatic pleura (arrows). However, there is no invasion of the diaphragmatic muscle itself, which is visualized as an intact black line above the liver (arrowheads).
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Figure 16c. MR imaging evaluation of MPM in a 63-year-old man. (a, b) Coronal (a) and contrast-enhanced fat-saturated (b) T1-weighted MR images show a large, enhancing right apical mass (M) with invasion of the chest wall (arrows in a). An enhancing right major fissure is also seen (arrowheads in b). (c, d) Sagittal T1-weighted (c) and coronal T2-weighted (d) MR images show the mass (M) with involvement of the diaphragmatic pleura (arrows). However, there is no invasion of the diaphragmatic muscle itself, which is visualized as an intact black line above the liver (arrowheads).
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Figure 16d. MR imaging evaluation of MPM in a 63-year-old man. (a, b) Coronal (a) and contrast-enhanced fat-saturated (b) T1-weighted MR images show a large, enhancing right apical mass (M) with invasion of the chest wall (arrows in a). An enhancing right major fissure is also seen (arrowheads in b). (c, d) Sagittal T1-weighted (c) and coronal T2-weighted (d) MR images show the mass (M) with involvement of the diaphragmatic pleura (arrows). However, there is no invasion of the diaphragmatic muscle itself, which is visualized as an intact black line above the liver (arrowheads).
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A recent study showed that MR imaging is superior to CT in revealing two types of invasive growth of MPM: invasion of the diaphragm and invasion of endothoracic fascia or a single chest wall focus (21). MR imaging is most useful in evaluating patients with questionable areas of local tumor extension at CT or in whom intravenous administration of iodinated contrast material is contraindicated.
Positron Emission Tomography
In PET, the positron-emitting radionuclides of several biologically fundamental elements are used to obtain quantitative tomographic images. The use of 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) PET for the diagnosis of MPM has been described recently (22). The elevated glucose metabolism of tumor cells helps identify malignancy at PET. The standardized uptake value, which is a semiquantitative measure of the metabolic activity of a lesion, is significantly higher in MPM than in benign pleural diseases such as in-flammatory pleuritis and asbestos-related pleural thickening (22,23). Because it can provide both anatomic and metabolic information about a lesion, PET is useful in the staging and preoperative evaluation of MPM (Figs 17–21). Studies have demonstrated that PET has increased accuracy in the detection of mediastinal nodal metastases (22). In a recent study of 18 patients with MPM, identification of occult extrathoracic metastases at PET was used as the basis for excluding two patients from surgery (24).
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Figure 17a. Preoperative PET evaluation in a 78-year-old man with biopsy-proved MPM. (a) Axial contrast-enhanced CT scan shows circumferential nodular left-sided pleural thickening (arrows). (b, c) Axial (b) and coronal (c) PET scans show diffusely increased FDG uptake in the pleura of the left hemithorax (arrows), a finding that correlates well with the CT finding.
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Figure 17b. Preoperative PET evaluation in a 78-year-old man with biopsy-proved MPM. (a) Axial contrast-enhanced CT scan shows circumferential nodular left-sided pleural thickening (arrows). (b, c) Axial (b) and coronal (c) PET scans show diffusely increased FDG uptake in the pleura of the left hemithorax (arrows), a finding that correlates well with the CT finding.
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Figure 17c. Preoperative PET evaluation in a 78-year-old man with biopsy-proved MPM. (a) Axial contrast-enhanced CT scan shows circumferential nodular left-sided pleural thickening (arrows). (b, c) Axial (b) and coronal (c) PET scans show diffusely increased FDG uptake in the pleura of the left hemithorax (arrows), a finding that correlates well with the CT finding.
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Figure 18. PET evaluation in a 65-year-old woman with MPM. Sagittal PET scan shows increased FDG uptake in the entire left pleural space with involvement of the left major fissure (arrow).
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Figure 19. PET evaluation of metastatic disease in a 73-year-old man with known MPM. Sagittal PET scan shows a single focus of increased FDG uptake in the superficial aspect of the left middle to lower portion of the neck (arrow). Biopsy results confirmed MPM metastases to the skin.
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Figure 20a. PET evaluation of metastatic disease in a 71-year-old man with known MPM. Coronal PET scans obtained at different levels show increased FDG uptake in the left supraclavicular (a) and right mediastinal (b) regions (arrows), a finding that is consistent with nodal metastases. Involvement of contralateral mediastinal lymph nodes or of ipsilateral or contralateral supraclavicular lymph nodes is classified as stage IV disease (unresectable).
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Figure 20b. PET evaluation of metastatic disease in a 71-year-old man with known MPM. Coronal PET scans obtained at different levels show increased FDG uptake in the left supraclavicular (a) and right mediastinal (b) regions (arrows), a finding that is consistent with nodal metastases. Involvement of contralateral mediastinal lymph nodes or of ipsilateral or contralateral supraclavicular lymph nodes is classified as stage IV disease (unresectable).
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Figure 21. PET evaluation of metastatic disease in a 61-year-old woman with known MPM. Axial PET scan shows increased FDG uptake in the left inferolateral chest wall (arrows), a finding that is consistent with tumor invasion.
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In addition to its role in diagnosis and staging, FDG PET has several other advantages in the management of MPM. Patients with MPM may have diffuse pleural thickening but only focal areas of malignancy. Areas of pleural thickening may not necessarily correspond to areas of high metabolic activity, and the most appropriate biopsy site may not be apparent from CT findings. Because FDG PET can provide information about metabolically active areas when findings are correlated with anatomic imaging information, it may be used to help determine the most appropriate biopsy site for obtaining positive results (25). Moreover, PET may help predict prognosis in patients with MPM. A recent study showed that MPM with higher FDG uptake is associated with significantly shorter survival time (26). This infor-mation may be clinically useful in determining whether to pursue an aggressive therapeutic approach based on the biologic features of the tumor.
Although PET has increased sensitivity in the detection of malignant lesions, it also has inferior spatial resolution and should be used in conjunction with an anatomic imaging study such as CT. Coregistration techniques that involve the fusion of CT and PET scans can provide more accurate identification of abnormalities seen at the two modalities.
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Tissue Diagnosis
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A histologic diagnosis is required once MPM is suspected radiologically. Neither cytologic analysis of pleural fluid nor needle aspiration biopsy of a pleural mass is diagnostic because it is extremely difficult to distinguish between cells of MPM, metastatic adenocarcinoma, and severe atypia (2,14,27). In contrast, CT-guided core needle biopsy has been shown to improve diagnostic accuracy. In a study by Metintas et al (28), the diagnosis of MPM was made with CT-guided pleural needle biopsy in 83.3% of cases. The remaining cases were diagnosed at thoracoscopy, thoracotomy, or excisional biopsy of the chest wall mass. As mentioned earlier, FDG PET in combination with CT may further improve diagnostic accuracy by directing the surgeon to sites most likely to yield positive biopsy results.
Thoracoscopy or thoracotomy is sometimes necessary, especially when a large core of tissue is needed. Video-assisted thoracoscopic surgery has been shown to have a diagnostic rate of 98% (29). Thoracoscopic evaluation may also allow more accurate staging of MPM compared with noninvasive methods such as CT and MR imaging. However, video-assisted thoracoscopic surgery causes postprocedural chest wall seeding in up to one-half of patients (29). Local postoperative radiation therapy can prevent such seeding (29). In contrast, seeding caused by imaging-guided biopsy is seen in no more than 22% of patients (28).
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Conclusions
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Radiologic studies play an important role in the evaluation of MPM. CT is the most widely used initial imaging modality for the diagnosis and staging of MPM. MR imaging and, more recently, PET have proved helpful in further delin-eating the extent of disease, especially in surgical candidates. Each imaging modality has its advantages and limitations, but in combination they are crucial in determining the most appropriate treatment options for patients with MPM.
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Footnotes
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Abbreviations: FDG = 2-[fluorine-18]fluoro-2-deoxy-D-glucose,
MPM = malignant pleural mesothelioma
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References
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LEARNING OBJECTIVES FOR TEST...
