Diagnosis

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-raylung 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 cytology if this fluid is aspirated with a syringe. For pleural fluid this is done by a pleural tap or chest drain, in ascites with an paracentesis or ascitic drain and in a 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). and often

If cytology is positive or a plaque is regarded as suspicious, a biopsy is needed to confirm a diagnosis of mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a histopathologist. 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.

If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small opening in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.

Typical immunohistochemistry results

Positive	Negative
EMA (epithelial membrane antigen)	CEA (carcinoembryonic antigen)
WT1 (Wilms' tumour 1)	B72.3
Calretinin	MOC-3 1
Mesothelin-1	CD15
Cytokeratin 5/6	Ber-EP4
HBME-1 (human mesothelial cell 1)	TTF-1 (thyroid transcription factor-1)

Signs and symptoms

Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space are often symptoms of pleural mesothelioma.

Symptoms of peritoneal mesothelioma include weight loss and cachexia, abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.

These symptoms may be caused by mesothelioma or by other, less serious conditions.

Mesothelioma that affects the pleura can cause these signs and symptoms:

• chest wall pain
• pleural effusion, or fluid surrounding the lung
• shortness of breath
• wheezing, hoarseness, or cough

In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread, to other parts of the body.

Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:

• abdominal pain
• ascites, or an abnormal buildup of fluid in the abdomen
• a mass in the abdomen
• problems with bowel function
• weight loss

In severe cases of the disease, the following signs and symptoms may be present:

• blood clots in the veins, which may cause thrombophlebitis
• disseminated intravascular coagulation, a disorder causing severe bleeding in many body organs
• jaundice, or yellowing of the eyes and skin
• low blood sugar level
• pleural effusion
• pulmonary emboli, or blood clots in the arteries of the lungs
• severe ascites

A mesothelioma does not usually spread to the bone, brain, or adrenal glands. Pleural tumors are usually found only on one side of the lungs.

Causes of mesothelioma

Up to 9 out of 10 cases of mesothelioma are caused by exposure to asbestos. Asbestos is a natural mineral, mined from rock found in many countries. It is made up of tiny fibres that are as strong as steel but can be woven like cotton and are highly resistant to heat and chemicals.

Before the 1980s, asbestos was imported to the UK in large quantities. It was used in construction, ship-building and in household appliances. When asbestos is disturbed or damaged, it releases tiny fibres that can be breathed into the lungs and cause inflammation, a build-up of scar tissue (fibrosis) and sometimes cancer.

During the 1960s the first definite link between mesothelioma and asbestos was made. Asbestos is now known to be the most common cause of the disease.

Asbestos was very widely used in insulation materials, such as amosite insulation board, and building materials, including asbestos cement. Asbestos fibres are very fine and if they are breathed in they can make their way into the smallest airways of the lung, so they cannot be breathed or coughed out. Once the fibres are in the lungs the body’s defence mechanism tries to break them down and remove them, which leads to inflammation in the lung tissue.

The asbestos fibres can also penetrate through the lung tissue to settle in the pleura (the membrane around the lung). Over many years they can cause mesothelioma or other lung diseases to develop.

The asbestos fibres can also be swallowed, and some of the fibres can stick in the digestive system. They can then move into the membrane that lines the abdomen (the peritoneum), where they cause inflammation.

The people likely to have been exposed to asbestos include:

• construction workers
• plumbers
• electricians
• boilermakers
• shipbuilders
• demolition workers
• people who lived near to asbestos factories
• people who worked in places where asbestos was present.

Family members of people who worked with asbestos and brought the dust home on their clothes have sometimes developed mesothelioma.

There are three types of asbestos: blue, brown and white. Blue and brown asbestos, are most commonly linked with mesothelioma. They are now very rarely used and cannot be imported into the UK. Originally, white asbestos was not thought to be dangerous but recent studies have now shown that it is also harmful.

Mesothelioma does not usually develop until 10–60 years after exposure to asbestos and for this reason it is often difficult to discover the exact cause.

In the 1980s, imports of blue and brown asbestos into the UK were stopped and in 1999 the importation and use of all asbestos was banned. However, as mesothelioma develops so slowly, it is estimated that by 2015 approximately 3000 people will be diagnosed with mesothelioma each year. The number of people who develop mesothelioma will then start to reduce each year.

Occasionally, mesothelioma develops in people who have never been exposed to asbestos. The other causes of the disease are not fully understood, but in rare cases the development of mesothelioma has been linked to exposure to radiation.

Currently a research study is taking place to try to find out more about the causes of mesothelioma. It is called the National Study of Occupation and Lung Diseases. Your doctor may invite you to take part in the study, and if you agree you will be asked to fill in a short questionnaire and have a telephone discussion for about an hour with a researcher.

Research has not found any evidence that smoking increases a person’s risk of developing mesothelioma. It is also thought that exposure to other building materials such as fibreglass does not increase the risk.

Mesothelioma is not contagious and cannot be passed on to other people. It is not caused by inherited faulty genes and so family members do not have an increased risk of developing it, unless they have been in contact with asbestos.

Peritoneal mesothelioma

The lining of the abdomen is known as the peritoneum. It also has two layers: the inner (visceral) layer, which is next to the abdominal organs; and the outer (parietal) layer, which lines the abdominal wall.

If the mesothelioma is in the peritoneum it is called peritoneal mesothelioma and causes thickening of the membranes surrounding the abdominal organs and a collection of fluid in the abdomen. The collection of fluid is called ascites and causes swelling of the abdomen.

A diagram of the side view of the abdomen showing the peritoneum

Pleural mesothelioma

Pleural mesothelioma

The pleura has two layers: the inner (visceral) layer, which is next to the lung; and the outer (parietal) layer, which lines the chest wall. The two layers of the pleura are usually in contact and slide over each other as we breathe. The membranes produce fluid, which allows them to slide over each other easily.

When a mesothelioma develops in the pleura (pleural mesothelioma), the delicate membranes thicken and may press inwards on the lung. Fluid may also collect between the two layers of the pleura: this is known as a pleural effusion.

A diagram showing the structure of the lungs and pleura