Use of imaging in the management of malignant pleural mesothelioma

doi:10.1016/j.crad.2005.05.015

Clinical Radiology

Volume 60, Issue 12, December 2005, Pages 1237-1247

https://doi.org/10.1016/j.crad.2005.05.015 Get rights and content

Malignant pleural mesothelioma (MPM) is an increasingly prevalent tumour. The death rate associated with MPM is predicted to peak in the next 10 years, although radiologists and clinicians will be encountering cases for the next few decades. Contrast-enhanced CT is an established technique for evaluating suspected malignant pleural disease, but MPM can be reliably diagnosed only by histological sampling. However, even with adequate sampling and the use of immunocytochemistry, histological diagnosis is known to be difficult; definitive diagnosis may involve a combination of clinical presentation, radiological and histological appearances. Percutaneous biopsy is a promising technique for sampling the pleura. In view of its pattern of growth, MPM is a challenging disease to image by any method, and it behaves quite differently from lung cancer. This review aims to highlight the practical aspects of assessing malignant pleural mesothelioma.

Introduction

Malignant pleural mesothelioma (MPM) currently accounts for 1700 deaths per year in the UK, but is forecast to peak at 1950 to 2450 deaths per year between 2011 and 2015. Although the peak of the epidemic may last for 10 to 15 years, the tail may last until 2050.1, 2 MPM is predicted to become one of the more common cancers, with a higher mortality than melanoma, uterine or cervical cancer.¹ Men born in the late 1940s are predicted to be at the highest risk of dying from MPM³ and, although rare in the first 10 to 15 years after exposure to asbestos, the risk of mesothelioma increases thereafter with time.4, 5 MPM has a high association with asbestos exposure,⁵ but there is no relevant history in up to 20% of cases.⁶ MPM should be considered in all cases of unilateral pleural abnormalities and chest pain, and in cases of chest pain with a history of asbestos exposure.

The biological behaviour of MPM is very different to that seen in lung cancer, and there are many difficulties in diagnosis, staging and assessment of response. There are a number of ongoing or planned trials in the UK. Surgery may have a role in a limited number of cases, and preoperative assessment holds further challenges. We present a review of the radiological techniques involved in the management of MPM.

Section snippets

Pleural anatomy and lymph node drainage

The anatomy of the pleura is complex and is not always appreciated.⁷ The inferior margins of the pleura in the posterior costodiaphragmatic recesses of the hemithorax extend considerably lower than the corresponding border of the lung, to the level of the 12th dorsal vertebra. The diaphragm extends more inferiorly, and the right crus arises from the anterolateral surfaces of the bodies and intervertebral discs of the upper three lumbar vertebrae. In cases of established mesothelioma being

Chest radiograph

A plain chest radiograph is usually the first imaging investigation to be performed, and here the appearances of MPM range from normal in early disease to complete opacification of a hemithorax. These findings depend on the differing amounts of pleural thickening and fluid. A review of 4710 cases⁹ showed that a pleural effusion is usually present on the initial radiograph. The mediastinum can be central or it can be displaced towards or away from the affected hemithorax. The pleural thickening

Image-guided biopsy

Pleural fluid cytology has a low sensitivity (26% to 32%) for diagnosis of MPM,23, 24 and reliable pathological diagnosis requires histological sampling. Historically, the standard technique for pleural biopsy has been to use a reverse-bevelled needle such as the Abrams' needle. Even in experienced hands, Abrams' biopsy has a sensitivity of only 55%,²⁶ probably because of the patchy distribution of MPM and its predilection for the basal and diaphragmatic pleural surfaces.

Image-guided pleural

Positron emission tomography

F-18 fluorodeoxyglucose positron emission tomography (FDG PET) may be a useful problem-solving tool in differentiating benign from malignant pleural disease, with a sensitivity for detecting malignancy of 96.8% and a specificity of 88.5% in 63 cases³² (Fig. 5), and appears to confirm malignant pleural disease which cannot be identified at CT. In a prospective study, Kramer et al.³³ studied 32 patients, 19 with malignant and 13 with benign disease, and found that FDG PET had a high negative

Staging and resectability

The TNM staging system proposed by the International Mesothelioma Interest Group is used for patients with potentially resectable disease.⁴³ Emphasis is placed on criteria for determining the extent of local tumour and lymph node involvement, both of which affect overall survival. Patients with T1 to T3 disease are potential surgical candidates but may not necessarily be cured. The staging system was designed as a surgical tool, and may not be completely applicable to imaging. In practical

Radical surgery

Extrapleural pneumonectomy entails removal of the lung and all the parietal pleura, pericardium and diaphragm on the affected side. It usually forms part of trimodality treatment, combined with preoperative and postoperative chemotherapy and radiotherapy. In selected patients, 5-year survival can reach nearly 50%.⁴⁹ A large prospective trial over the next 8 years, the Mesothelioma and Radical Surgery (MARS) trial, aims to determine whether radical surgery alters prognosis. Results will

Conclusions

MPM is a disease with an increasing incidence, and radiologists and clinicians will be seeing patients with the disease well into the 21st century. MPM behaves quite differently from lung cancer, and there are many difficulties in TNM staging and assessing response to chemotherapy. There is a need for a more practical, radiology-friendly staging system, as the majority of patients do not undergo radical surgery. CT-PET may hold the key to more accurate assessment, by providing further

References (58)

G. Hillerdal
Malignant mesothelioma 1982: Review of 4710 published cases
Br J Dis Chest
(1983)
Z.C. Traill et al.
Thoracic computed tomography in patients with suspected malignant pleural effusions
Clin Radiol
(2001)
M. Metintas et al.
Computed tomography features in malignant pleural mesothelioma and other commonly seen pleural diseases
Eur J Radiol
(2002)
C.S. Ng et al.
Malignant pleural mesothelioma: The spectrum of manifestations on CT in 70 cases
Clin Radiol
(1999)
C. Boutin et al.
Prevention of malignant seeding after invasive diagnostic procedures in patients with pleural mesothelioma
Chest
(1995)
E.M. Marom et al.
The role of imaging in malignant pleural mesothelioma
Semin Oncol
(2002)
G. Hillerdal
Staging and evaluating responses in malignant pleural mesothelioma
Lung Cancer
(2004)
A.A. Renshaw et al.
The role of cytologic evaluation of pleural fluid in the diagnosis of malignant mesothelioma
Chest
(1997)
N.A. Maskell et al.
Standard pleural biopsy versus CT-guided cutting needle biopsy for diagnosis of malignant disease in pleural effusions: A randomised controlled trial
Lancet
(2003)
R.F. Adams et al.
Percutaneous image-guided cutting needle biopsy of the pleura in the diagnosis of malignant mesothelioma
Chest
(2001)

B. Duysinx et al.

Evaluation of pleural disease with 18-fluorodeoxyglucose positron emission tomography imaging

Chest

(2004)

F. Benard et al.

Metabolic imaging of malignant pleural mesothelioma with fluorodeoxyglucose positron emission tomography

Chest

(1998)

B.H. Kwek et al.

Fluorodeoxyglucose positron emission tomography and CT after talc pleurodesis

Chest

(2004)

J. Hierholzer et al.

MRI and CT in the differential diagnosis of pleural disease

Chest

(2000)

V.W. Rusch et al.

The role of computed tomography scanning in the initial assessment and follow-up of malignant pleural mesothelioma

J Thorac Cardiovasc Surg

(1988)

D.J. Sugarbaker et al.

Resection margins, extrapleural nodal status and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: Results in 183 patients

J Thorac Cardiovasc Surg

(1999)

F. Monetti et al.

Inadequacy of the new response evaluation criteria in solid tumours (RECIST) in patients with malignant pleural mesothelioma: Report of four cases

Lung Cancer

(2004)

R.J. Van Klaveren et al.

Inadequacy of the RECIST criteria for response evaluation in patients with malignant pleural mesothelioma

Lung Cancer

(2004)

M.J. Byrne et al.

Modified RECIST criteria for assessment of response in malignant pleural mesothelioma

Ann Oncol

(2004)

Mesothelioma mortality in Great Britain: Estimating the future burden

(2003)

From cancer research UK statistics, mortality; 2002. http://www.cancerresearchuk.org/aboutcancer/statistics/mortality?...

J. Peto et al.

The European mesothelioma epidemic

Br J Cancer

(1999)

J. Peto et al.

Mesothelioma mortality in asbestos workers: Implications for models of carcinogenesis and risk assessment

Br J Cancer

(1982)

D.H. Yates et al.

Malignant mesothelioma in south east England: Clinicopathological experience in 272 cases

Thorax

(1997)

A.R. Gibbs

Role of asbestos and other fibres in the development of diffuse malignant mesothelioma

Thorax

(1990)

Williams PL, editor. Gray's anatomy. 38th ed. London: Churchill Livingstone; 1995; p. 1625–6, 1662–4,...

A. Sharma et al.

Patterns of lymphadenopathy in thoracic malignancies

RadioGraphics

(2004)

Statement on malignant mesothelioma in the United Kingdom

Thorax

(2001)

F. Herth

Diagnosis and staging of mesothelioma transthoracic ultrasound

Lung Cancer

(2000)

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71% (41/58) patients had PM. Pleural thickening was <10 mm in 49/58 (84%). ECE sensitivity was 83% (95% CI 61–94%), specificity 83% (95% CI 68–91%), positive predictive value 68% (95% CI 47–84%), negative predictive value 92% (78–97%). ECE performance was similar or superior to subjective CT and MRI. MSIG correlated with MVD (r = 0.4258, p = .02).
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However, benign pleural reaction may resemble malignancy, as the pleura can react to disparate pathologic processes in a similar way, namely thickening and effusions (8). Although magnetic resonance (MR) imaging is not routinely used as the first-line modality in patients with MPM (9,10), it is particularly useful in staging and evaluating regions of possible chest wall or diaphragmatic invasion suspected on CT, or as an alternative imaging modality in patients in whom iodinated contrast material is contraindicated (11). Radiomics describes the process of extraction and quantification of a large number of shape and texture metrics that may not be perceptible to human vision (12).
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ReviewUse of imaging in the management of malignant pleural mesothelioma

Introduction

Section snippets

Pleural anatomy and lymph node drainage

Chest radiograph

Image-guided biopsy

Positron emission tomography

Staging and resectability

Radical surgery

Conclusions

Br J Dis Chest

Clin Radiol

Eur J Radiol

Clin Radiol

Chest

Semin Oncol

Lung Cancer

Chest

Lancet

Chest

Chest

Chest

Chest

Chest

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Lung Cancer

Lung Cancer

Ann Oncol

Mesothelioma mortality in Great Britain: Estimating the future burden

The European mesothelioma epidemic

Br J Cancer

Mesothelioma mortality in asbestos workers: Implications for models of carcinogenesis and risk assessment

Br J Cancer

Malignant mesothelioma in south east England: Clinicopathological experience in 272 cases

Thorax

Role of asbestos and other fibres in the development of diffuse malignant mesothelioma

Thorax

Patterns of lymphadenopathy in thoracic malignancies

RadioGraphics

Statement on malignant mesothelioma in the United Kingdom

Thorax

Diagnosis and staging of mesothelioma transthoracic ultrasound

Lung Cancer

Review
Use of imaging in the management of malignant pleural mesothelioma