Elsevier

The Lancet

Volume 366, Issue 9483, 30 July–5 August 2005, Pages 397-408
The Lancet

Seminar
Malignant mesothelioma

https://doi.org/10.1016/S0140-6736(05)67025-0Get rights and content

Summary

Malignant mesothelioma is an aggressive, treatment-resistant tumour, which is increasing in frequency throughout the world. Although the main risk factor is asbestos exposure, a virus, simian virus 40 (SV40), could have a role. Mesothelioma has an unusual molecular pathology with loss of tumour suppressor genes being the predominant pattern of lesions, especially the P16INK4A, and P14ARF, and NF2 genes, rather than the more common p53 and Rb tumour suppressor genes. Cytopathology of mesothelioma effusions or fine-needle aspirations are often sufficient to establish a diagnosis, but histopathology is also often required. Patients typically present with breathlessness and chest pain with pleural effusions. Median survival is now 12 months from diagnosis. Palliative chemotherapy is beneficial for mesothelioma patients with high performance status. The role of aggressive surgery remains controversial and growth factor receptor blockade is still unproven. Gene therapy and immunotherapy are used on an experimental basis only. Patterns identified from microarray studies could be useful for diagnosis as well as prognostication.

Introduction

The fact that asbestos can cause cancer is now widely known in western countries, and the public are increasingly familiar with the word mesothelioma, especially since the deaths of some well known individuals with the disease, such as actor Steve McQueen and scientist and author Stephen Jay Gould.1

Why this change in awareness? One reason is that mesothelioma has climbed the league table of male cancers over the past 30 years, and is now roughly as common as cancers of the liver, bone, and bladder, especially in Europe and Australia.2 Its incidence is expected to continue to increase for the next decade or so. Secondly, almost everyone who lives in industrialised areas of the western world has asbestos fibres in their lungs, and many can remember being exposed to asbestos incidentally (eg, carpenters, plumbers, military personnel, school teachers, and students who handled asbestos samples, mats, or blankets; home renovators; and people in many other situations).3 Media interest in asbestos has produced in many of these individuals a level of awareness—even anxiety—about mesothelioma that does not exist for most other sporadic cancers of comparable incidence. These issues, combined with the complex medical–legal aspects of the disease, have led to a lot of interest. For example, a simple Google search of the common cancers at the time of writing identified nearly 3 million webpage results for mesothelioma, second only to breast cancer and substantially more than the number of results for other well known cancers such as lung cancer, leukaemia, lymphoma, and bowel or colon cancer (panel 1).

In this Seminar, we aim to review mesothelioma, highlighting key clinical features plus some controversies, recent developments, and important questions for future research into this disease.

Section snippets

Epidemiology

There are few disease processes for which the distribution and determinants of occurrence in the community are as well known as they are for mesothelioma of the pleura and peritoneum. In fact, mesothelioma owes its entire existence as a disease entity to its relation with asbestos, first recognised by an astute pathologist working in South Africa's Cape Province in the 1950s.4 As an industrial disease, it is one of the most accurately predictable. Of all the outcomes from the production and use

How does asbestos cause mesothelioma?

A single layer of mesothelial cells covers the entire surface of the pleura; these cells aid free movement of the pleural surfaces during respiration by enmeshing lubricating glycoproteins,14, 15 and are readily able to proliferate in response to injury and growth factors.16, 17 At least four plausible explanations have been proposed as to how a mineral fibre such as asbestos causes malignant change in these cells.

First, there is pleural irritation. Good epidemiological evidence shows that the

Clinical presentation

Typically, a patient with mesothelioma presents with a pleural effusion, which is often associated with chest wall pain.59 In fact, mesothelioma should be suspected in any individual with an unexplained pleural effusion associated with chest wall pain. Constitutional symptoms such as weight loss and fatigue can be present, but these generally appear later in the course of disease—the presence of such symptoms at presentation is associated with a poor prognosis.59 Occasionally, patients have no

Diagnosis

Accurate diagnosis of mesothelioma is important for several reasons, not least for clinical management of the patient. Issues of compensation also exist and, because the likelihood of survival a year beyond diagnosis is less than 50%, there may be some urgency to expedite the diagnosis for litigation purposes, especially if the jurisdiction will only accept cases brought on behalf of a living victim.

The most common diagnostic problem is distinguishing mesothelioma from adenocarcinoma,

Management of mesothelioma

In the past few years, there have been several major developments in the management of mesothelioma, especially the development of more effective therapies plus new discoveries that could improve mesothelioma diagnosis and new insights into the pathobiology of the disease.92, 93 These discoveries are producing new approaches to diagnosis and prognostication, such as DNA microarray patterns to predict outcome, and genetic information to develop novel therapies such as gene therapy.

Optimum palliation for mesothelioma (panel 4)

Recurrent pleural effusions are controlled by pleurodesis, usually involving talc instillation, and occasionally surgery. Pain is a major issue for these patients and there are several types of pain in mesothelioma. Invasion of the chest wall can cause localised somatic pain; intercostal nerve invasion or vertebral invasion can cause neuropathic pain; and lung invasion can cause diffuse visceral pain. Also common is dyspnoea due to pleural effusion or more often tumour spread.119

There is no

Prevention of mesothelioma in asbestos-exposed populations

Since the epidemic of mesothelioma began, the notion that the disease could be prevented in high-risk individuals has been suggested. In some highly exposed cohorts the lifetime risk can approach 25%. Since these individuals can be identified by their high exposure, much research has been aimed at identifying possible ways of preventing this disease. The main approach has involved dietary methods. In a study aimed at determining whether vitamin A could be protective,121 daily retinol was

Search strategy and selection criteria

We searched PubMed using the key word “mesothelioma” with the relevant topics—eg, “pathogenesis”, “tumour suppressor genes”, “peritoneal”, “oncogenes”, “angiogenesis”, “SV40”, “cytopathology”, “palliation”, and so on. Fields were limited to publications in English and restricted to the past 15 years. We also reviewed citations from papers from the search. Where possible, primary sources are quoted, but review articles are referenced where pragmatically necessary. References were chosen

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