Malignant mesothelioma

Other Names: Mesothelioma, malignant Malignant mesothelioma is a form of cancer that develops in the thin layer of tissue that surrounds the lungs, chest wall, or abdomen. Mesothelioma is an aggressive and deadly form of cancer. Mesothelioma treatments are available, but for many people with mesothelioma, a cure isn't possible.

CXR demonstrating a mesothelioma

Doctors divide mesothelioma into different types based on what part of the mesothelium is affected. Mesothelioma most often affects the tissue that surrounds the lungs (pleura). This type is called pleural mesothelioma. Other, rarer types of mesothelioma affect tissue in the abdomen (peritoneal mesothelioma), around the heart and around the testicles. Common features include abdominal bloating, abdominal pain, chest pain, coughing, fatigue, shortness of breath, and/or weight loss.

Cause

It isn't clear what causes the initial genetic mutations that lead to mesothelioma, though researchers have identified factors that may increase the risk. Malignant mesothelioma is thought to be caused by long-term exposure to asbestos (a fire-resistant material that was once commonly found in insulation; ceiling and roof vinyls; cement; and automotive brake materials). Most people appear to be diagnosed with the condition approximately 30 years after being in contact with the asbestos.

Risk factors

Asbestos exposureBold: The primary risk factor for mesothelioma Most mesotheliomas are thought to be related to asbestos exposure. Asbestos is a mineral that's found naturally in the environment. Asbestos fibers are strong and resistant to heat, making them useful in a wide variety of applications, such as in insulation, brakes, shingles, flooring and many other products.

When asbestos is broken up, such as during the mining process or when removing asbestos insulation, dust may be created. If the dust is inhaled or swallowed, the asbestos fibers will settle in the lungs or in the stomach, where they can cause irritation that may lead to mesothelioma. Exactly how this happens isn't understood. It can take 20 to 60 years or more for mesothelioma to develop after asbestos exposure.

Most people with asbestos exposure never develop mesothelioma. This indicates that other factors may be involved in determining whether someone gets mesothelioma. For instance, you could inherit a predisposition to cancer or some other condition could increase your risk.

Factors that may increase the risk of mesothelioma include:

Personal history of asbestos exposure If you've been directly exposed to asbestos fibers at work or at home, your risk of mesothelioma is greatly increased. Living with someone who works with asbestos People who are exposed to asbestos may carry the fibers home on their skin and clothing. Exposure to these stray fibers over many years can put others in the home at risk of mesothelioma. People who work with high levels of asbestos can reduce the risk of bringing home asbestos fibers by showering and changing clothes before leaving work. A family history of mesothelioma If your parent, sibling or child has mesothelioma, you may have an increased risk of this disease. Radiation therapy to the chest. If you had radiation therapy for cancer in your chest, you might have an increased risk of mesothelioma.

Symptoms

Signs and symptoms of mesothelioma vary depending on where the cancer occurs.

Pleural mesothelioma, which affects the tissue that surrounds the lungs, causes signs and symptoms that may include:

• Chest pain
• Painful coughing
• Shortness of breath
• Unusual lumps of tissue under the skin on your chest
• Unexplained weight loss

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

• Abdominal pain
• Abdominal swelling
• Nausea
• Unexplained weight loss

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

Pericardial mesothelioma, which affects tissue that surrounds the heart, can cause signs and symptoms such as breathing difficulty and chest pains.

Mesothelioma of tunica vaginalis, which affects tissue surrounding the testicles, may be first detected as swelling or a mass on a testicle.

Diagnosis

Micrographs showing conventionally-stained mesothelioma in a core biopsy (higher magnifications on right).

Diagnosis of mesothelioma can be suspected with imaging but is confirmed with biopsy. It must be clinically and histologically differentiated from other pleural and pulmonary malignancies, including reactive pleural disease, primary lung carcinoma, pleural metastases of other cancers, and other primary pleural cancers. Primary pericardial mesothelioma is often diagnosed after it has metastasized to lymph nodes or the lungs.

Imaging

Diagnosing mesothelioma is often difficult because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray and often lung function tests. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma.

A CT (or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytopathology if this fluid is aspirated with a syringe. For pleural fluid, this is done by thoracentesis or tube thoracostomy (chest tube); for ascites, with paracentesis or ascitic drain; and for pericardial effusion with pericardiocentesis. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g., tuberculosis, heart failure). However, with primary pericardial mesothelioma, pericardial fluid may not contain malignant cells and a tissue biopsy is more useful in diagnosis. Using conventional cytology diagnosis of malignant mesothelioma is difficult, but immunohistochemistry has greatly enhanced the accuracy of cytology.

Biopsy

Generally, a biopsy is needed to confirm a diagnosis of malignant mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy.

In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples. Alternatively, the chest surgeon might directly open the chest (thoracotomy). If the cancer is in the abdomen, the doctor may perform a laparoscopy.

To obtain tissue for examination, the doctor makes a small incision in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, an open surgical procedure may be necessary.

Immunochemistry

Immunohistochemical studies play an important role for the pathologist in differentiating malignant mesothelioma from neoplastic mimics, such as breast or lung cancer that has metastasized to the pleura. There are numerous tests and panels available, but no single test is perfect for distinguishing mesothelioma from carcinoma or even benign versus malignant. The positive markers indicate that mesothelioma is present; if other markers are positive it may indicate another type of cancer, such as breast or lung adenocarcinoma. Calretinin is a particularly important marker in distinguishing mesothelioma from metastatic breast or lung cancer.

Differential diagnosis

• Metastatic adenocarcinoma
• Pleural sarcoma
• Synovial sarcoma
• Thymoma
• Metastatic clear cell renal cell carcinoma
• Metastatic osteosarcoma

Treatment

Unfortunately, there is generally no cure for malignant mesothelioma unless it is diagnosed at an early stage and can be surgically removed. If surgery is not an option, chemotherapy and/or radiation therapy may still be recommended to help alleviate some of the associated symptoms.

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Pemetrexed disodium (Brand name: Alimta)Treatment of patients with malignant pleural mesothelioma whose disease is either unresectable or who are otherwise not candidates for curative surgery.

NIH genetic and rare disease info

• NIH info on Malignant mesothelioma

Malignant mesothelioma is a rare disease.

Malignant mesothelioma Resources
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