Malignant mesothelioma (often shortened as mesothelioma) is a rare form of malignancy caused by exposure to asbestos - naturally occurring fiber-like minerals that have unique heat-resistant properties. During the first half of the twentieth century, this disease has risen from obscurity to become a major occupational and public health problem in the end of twentieth and the beginning of twenty-first century.
The link between asbestos exposure and subsequent development of mesothelioma was definitely established in 1960, and to date it represents the most important occupational malignancy (apart from lung cancer) among industrial workers. Even though the mineral is rarely used today in most industrialized countries, its use is still widespread in developing nations.
There is a prolonged time interval (also called latency) between the first inhalation of asbestos and the diagnosis of mesothelioma, generally in the range of 20 to 40 years. A myriad of different therapies have been tried in the past 50 years – including surgery, radiotherapy, chemotherapy, immunotherapy and, more recently, targeted therapy.
Types of mesothelioma
Mesothelial cells, which are a primary target in this disease, represent one layer of specialized, pavement-like cells that line the body's internal cavities and most organs. Although a cell layer formed by these cells (called mesothelium) provides protective and non-adhesive surface, it also has a role in transport of cells and fluids across the surface of the body wall and organs.
Malignant change in mesothelial cells and mesothelium results in malignant mesothelioma – an aggressive tumor mainly of the pleural, but also the peritoneal and pericardial spaces. Although the condition is closely associated with exposure to asbestos, there are other factors that have a role in its pathogenesis, including certain genetic traits and even a viral agent SV40 (Simian virus 40).
Malignant mesothelioma can be divided into three different types: epitheloid, sarcomatoid and a mixture of both types (also called biphasic type). Most mesotheliomas (50-70%) are epitheloid, with cube-shaped and uniform cells. Sarcomatoid mesothelioma has its roots in supportive tissue (i.e. bone, cartilage or muscles) and occurs in 7-20% of cases. Mixed or biphasic type is found in 20-35% of cases with quite a dismal prognosis.
Disease course, management and prognosis
Malignant pleural mesothelioma is most commonly presented with dyspnea and nonpleuritic chest wall pain, with at least one of them occurring in 60-90% of the patients. Those cardinal symptoms can be associated with constitutional symptoms as well, especially weight loss, malaise and occasional night sweats.
Frequent presenting radiologic findings include effusion, pleural masses and pleural thickening. Computed tomography (CT) is more sensitive for determining the extent of the pleural abnormalities and involvement of adjacent structures. The pleural aspirate is an exudate with reduced glucose and pH levels. The diagnosis is confirmed with a biopsy and microscopic examination.
Life expectancy for diagnosed malignant pleural mesothelioma is usually poor, with median survival varying between 8 and 12 months (irrespective of the histologic type). After the introduction of cytoreductive surgery followed by intraperitoneal hyperthermic perfusion, a significant prolongation in the median survival has been achieved for malignant peritoneal mesothelioma, with almost half the patients alive at 5 years.
As new agents are being explored for the disease, new combinations of therapies being tried and novel biomarkers identified, there is a reasonable expectation that the median survival rate in mesothelioma patients will increase in the years to come. Nevertheless, it continues to be a very serious disease with poor prognosis and low survival rates.
- Smith DD. The History of Mesothelioma. In: Pass HI, Vogelzang NJ, Carbone M. Malignant Mesothelioma: Pathogenesis, Diagnosis, and Translational Therapies. Springer Science & Business Media, 2006; pp. 3-20.
- Galateau-Sallé F. Pathology of Malignant Mesothelioma. Springer Science & Business Media, 2010; pp. 1-39.