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Mesothelioma

Malignant Pleural Mesothelioma

Mesothelioma

Malignant mesothelioma is a type of cancer.

That is occurs in the thin layer of tissue that covering the majority of your internal organs that is called mesothelium.

Introduction of Mesothelioma

Mesothelioma is an uncommon neoplasm arising from the mesothelial cells lining the pleura.

Rarely, pleural mesothelioma is localized, benign, and readily resectable for cure. A variant of localized pleural mesothelioma is a fibrous tumor of the pleura that probably arises from a different layer of cells in the pleura, and it also is usually completely resectable. For the purposes of this review, only the more common and aggressive diffuse malignant pleural mesothelioma (MPM) will be discussed. MPM is usually associated with history of chronic asbestos exposure. Despite its relatively rare incidence, there is a great interest in this disease as it has spawned many legal battles and consequently has led to the elimination of asbestos in all the industrial sectors, particularly in shipping and construction.

Mesothelioma

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Incidence of Mesothelioma

In the United States, MPM occurs in approximately 2,500 persons per year, with nearly 200 individuals diagnosed in Florida annually, and 19% are women. Almost 72,000 cases are expected to occur in the United States in the next 20 years.

In Western Europe, 5,000 patients die of the disease each year. Worldwide, the incidence is increasing and it is expected to peak in the year 2020. Nevertheless, most physicians will encounter MPM only a few times in their careers. Historically, the untreated median survival has only been 6 months, which explains the palliative approach taken by the oncologists treating patients with MPM.

Malignant mesothelioma was first recognized in 1870, but the link between asbestos and MPM was not discovered until 1960 in South Africa when the first convincing evidence of a link between malignant mesothelioma and both occupational and incidental asbestos exposure was reported.

It was not until the second half of the 20th century that mesotheliomas and lung cancer were considered separate entities. Due to the extraordinary fire-resistant properties of asbestos, this substance was widely used in the United States and Europe in an uncontrolled fashion, mostly in the shipbuilding and construction industries, between the 1940s and 1979 when the US government curtailed its use.

During that time, an estimated 40% of the entire workforce, or about 27 million individuals, were exposed to asbestos. Although its industrial use was largely eliminated, asbestos is still present in countless buildings where it was commonly used as insulation and a fire retardant.

Manmade and natural disasters that destroy these building could therefore still expose millions to asbestos. An estimated 10 million New Yorkers were possibly exposed to this carcinogen during the World Trade Center disaster on September 11, 2001, where dust laden with asbestos filled the air.

Mesothelioma

Symptoms of Mesothelioma

Pleural mesothelioma that is affecting the tissue that surrounding the lungs, symptoms and causes signs that may include:

1. Chest pain

2. Painful coughing

3. Shortness of breath

4. Unusual lumps of tissue under the skin on your chest

5. Unexplained weight loss

Peritoneal mesothelioma which occuring in tissue in the abdomen, symptoms and causes signs that may include:

1. Abdominal pain

2. Abdominal swelling

3. Nausea

4. Unexplained weight loss

Other forms of mesothelioma

symptoms and Signs of all other types of mesothelioma are unclear, since these forms of the disease are very very rare.

Mesothelioma

Diagnosis of Mesothelioma

The physical examination and chest radiographs will demonstrate a large pleural effusion in 80% to 95% of patients with MPM. Conversely, 10% to 29% have little or no fluid.

As the disease advances, there tends to be less pleural fluid present. Initially, the fluid is free flowing and layers out on decubitus chest radiographs, which may be similar in appearance to the effusion seen in heart failure, early empyema, and other benign causes.

Later, as MPM progresses, the effusion becomes loculated. Localized chest pain and a palpable chest wall mass indicate chest wall invasion and unresectability.

Computed chest tomography (CT) with contrast is a much more sensitive examination. CT scans will show the pleural effusion, the size of the lymph nodes in the hilum and mediastinum, and the presence of pleural masses, especially as the tumor tends to form a rind of tissue that encases the lung and often extending into the fissures and along the mediastinal pleura and diaphragm.

Although chest wall invasion and transdiaphragmatic spread of tumor may be visible or suspected on chest CT scans,magnetic resonance imaging(MRI) of the chest with contrast, which includes coronal and sagittal views, is more sensitive in illustrating this and is especially important when a potentially
curative surgery is being considered for the patient.illustrates some of the findings typically seen on imaging studies in MPM.

Positron emission tomography (PET) may offer some additional information in the staging of MPM since it reliably detects contralateral chest involvement and extrathoracic metastases such as supraclavicular nodal disease.

In some cases, it maymay be difficult to differentiate the primary tumor from N2 mediastinal lymph node involvement because of their close anatomic proximity.Pleural fluid cytology may yield a definitive diagnosis of MPM in 20% to 33% of patients by checkup the patient.

A blind core needle biopsy of the pleura modestly improves the yield in subject. A CT-guided core needle biopsy of one of the pleural masses is more sensitive (87%) in making a diagnosis. Diagnostic accuracy of greater than 95% is possible using video-assisted thoracoscopy (VATS), which allows directed pleural biopsy and drainage of the effusion after breaking up loculations.

Intrapleural talc,which yields the highest pleurodesis rate in MPM, can then be instilled to prevent reaccumulation of the effusion. One disadvantage of VATS in mesothelioma is the possible seeding of tumor along the surgical incisions and chest tube tracts, which ultimately results in tumor growth in the chest wall in up to 20% of patients.

In addition to standard histology, special immunohistochemical stains of the biopsy tissue may be necessary to make a definitive diagnosis of MPM because ofits histomorphologic similarities to adenocarcinoma.

Mesothelioma is characterized by staining for calretinin 88% and vimentin in 50%of patients. However, adenocarcinoma usually lacks these markers and instead stains positive for carcinoembryonic antigen (84%),CD15(77%) and Ber-EP-4 (82%).

A complete array of immunostains must be performed to make a reliable diagnosis.Electron microscopy, although more costly, may be needed in equivocal cases to make the distinction between the two neoplasms.Adequate tumor tissue not only allows a definitive diagnosis but also helps to determine which of the histologic subtypes is present.

Epithelial mesothelioma is the most common, is found in approximately 50% of cases, and has the best prognosis. The more aggressive sarcomatoid type is seenin 16%, and the mixed type is seen in 34%.Recently, investigators in Australia have discovered a new serum marker called soluble mesothelin-related protein (SMRP) in 84% of patients with mesothelioma.

This protein, which is detected with a simple blood test, may offer not only a useful diagnostic test for MPM, but also a means of monitoring treatment responses. It could also be a method for screening at risk individuals. SMRP is elevated in only 2% of patients with other pleural diseases.

A Commercial SMRP tumor marker assay test kit should be available soon.In a recently published study,serum osteopontin levels were found to be significantly higher in patients with pleural mesothelioma than in patients with exposure to asbestos or those patients who have fibrosis alone. Samples of pleural mesothelioma Immunohistochemical analysis revealed osteopontin staining of the tumor cells in 36 of 38.

This indicates that osteopontin levels may help us in the near future in early diagnoses of patients who have a known history of asbestos exposure.

Despite the ready availability of multiple diagnostic techniques with this neoplasm, a definitive diagnosis of MPM is often delayed due to a low clinical suspicion for this disease.

Hence the clinician must have a high index of suspicion, especially in a patient with a history of asbestos exposure who has a pleural effusion or atypical non cardiac chest pain to ensure that a timely diagnosis is made.

Mesothelioma

Treatment of Mesothelioma

Since none reliably results in cure MPM does not have one widely accepted treatment modality. Moreover, there is a striking lack of randomized, clinical trials comparing treatment regimens in this disease, due in part to the relatively low incidence of this neoplasm. Clinical series generally are either at best phase II trials of one treatment regimen or retrospective reviews of a small number of patients treated over a long period of time. Despite these shortcomings, significant improvements in therapy for MPM offer a ray of hope in this aggressive malignancy.

Conclusions

Malignant mesothelioma continues to be a difficult disease to treat. Maintaining a high index of suspicion may result in an earlier diagnosis and a more successful treatment outcome. The overall outlook for the treatment of this disease has improved with the emergence of newer therapies. Several new agents are currently under active investigation and hold promise to further improve treatment outcomes. Results of currently ongoing clinical trials are anxiously awaited. In fact, survival for patients with MPM is now generally greater than for patients with advanced non-small cell lung cancer. As with any rare disease, referral of the patient to a center with extensive experience and expertise in this disease is recommended to enhance the probability of accruing such patients to clinical trials.

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