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Malignant Mesothelioma Cancer

  • 9 minutes, 13 seconds
  • Oncology
  • 2020-07-05

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Malignant mesothelioma is a rare but highly aggressive cancer that arises from the surface of mesothelial cells of the pleural, peritoneal and pericardial surfaces. The mesothelium is a membrane or layer of tissue that lines and protects body cavities.

When the mesothelium covers internal organs it's known as visceral mesothelium and when it lines the body walls its known as parietal mesothelium.

Mesothelioma is, therefore, cancer that develops in this lining membrane that comes about due to the uncontrolled division of the mesothelial cells and invasion to the nearby tissues.

  • Mesothelioma can arise from the pleura is known as pleural mesothelioma),
  • From the peritoneum is termed as peritoneal mesothelioma,
  • Pericardial mesothelioma from the pericardium
  • Testicular mesothelioma from tunica vaginalis covering the testis.

Approximately 3,000 new cases of mesothelioma reported each year in the United States. Out of these, 80% occur as pleural mesothelioma making pleural mesothelioma is the most common form.

Mesothelioma usually presents 20 to 50 years after exposure to asbestos with the median age being 60 years. Malignant mesothelioma occurs five times more common in males than in females.

The duration of exposure and diagnosis known as latency period depends greatly on the occupation of the individual. It is shorter in dock workers and insulators and longer in maritime workers, ship workers and domestic exposures to asbestos.

Causes of malignant mesothelioma

Malignant mesothelioma accounts for less than 1% of cancers).

Exposure to asbestos fibres is the primary cause, although 50% of patients have no history of exposure.

The risk is greatest with blue asbestos (crocidolite) then brown asbestos (amosite) and least with white asbestos (chrysolite).

In 60–83% of human malignant mesotheliomas the cells contain and express simian 40 viruses (SV40) DNA, suggesting it is a possible co-factor.

SV40 is an oncogenic polyomavirus in human cells and its infection leads to inactivation of tumour suppressor genes p53 and the retinoblastoma gene (Rb).

The exposure to asbestos fibres can produce reactive oxygen species that react with hydrogen peroxide and superoxide to form hydroxyl radicals, which can then induce DNA damage.

Epidemiology and pathogenesis

The incidence of malignant mesothelioma has been steadily increasing despite awareness and a lifetime risk is estimated to be around 0.5 – 1%.

Malignant mesothelioma was originally described by occupational health doctors who were working in the asbestos factories in the East End of London during the last periods of WW1.

The development of mesothelioma is generally related to asbestos exposure, but this is not always the case.

Risk has been estimated to be linearly proportional to the duration of exposure. However, it may not only occur in the asbestos worker but also among his/her family members who have been exposed to the asbestos fibres from the clothing.

Most patients with mesothelioma who were diagnosed between the age of 20 and 40 years report household or neighbourhood exposure to asbestos during childhood.

Although asbestos exposure is the major known cause of mesothelioma, children who present with the disease generally have no apparent asbestos exposure.

There are no specific chromosomal changes associated with the development of mesothelioma, but there are a host of abnormalities that may occur, which are entirely non - specific.

Different asbestos fibres have been identified to have different properties and abilities to cause cancer.

The most carcinogenic type being the needle-shaped blue (crocidolite) and brown (amosite) asbestos and the lesser being the commoner corkscrew-shaped white asbestos (chrysotile).

In the United States, mesothelioma is a disease of Caucasian men reflecting the population of asbestos workers in the 1960s and early 1970s.

 Signs and symptoms of malignant mesothelioma

Mesothelial cancers take their origins in the pleura or peritoneum.

Patients present with pleural effusions or ascites.

Majority of about 90% present with intrathoracic symptoms, such as cough, non-pleuritic chest wall pain and dyspnea.

Discordant chest wall expansion and palpable chest wall mass.

When it has involved the mediastinal pleural it can produce cardiac arrhythmias or dysphagia, but these are rare.

Fever of unknown origin, night sweats, anorexia and weight loss are most frequent nonspecific symptoms;

Thrombocytosis, disseminated intravascular coagulation, thrombophlebitis and haemolytic anaemia can also occur.

On examination, most patients have dullness at one lung base and a unilateral pleural effusion is seen on a plain chest X-ray. Findings on a chest x-ray may be incidental in asymptomatic patients with a pleural effusion.

Most of these lesions are right-sided lesions and fewer than 5% of the patients have bilateral involvement at the time of diagnosis.

Malignant mesothelioma spreads predominantly by local invasion of the lung on the involved side, extending to the interlobular septa, fissures, adjacent organs in the mediastinum and chest wall. This tumour can also track along the drainage sites

Thoracic lymph nodes invasion is seen in up to 70% of patients and haematogenous metastases are documented to liver and lung, and less commonly to the kidney, adrenal and, rarely, bone.

Diagnosis and Investigations

The diagnosis of mesothelioma may be suspected from a chest X-ray. On a chest X-ray mesothelioma appears as a thickened, nodular, irregular pleural-based mass, that covers the pleural surface. Pleural plaques may be visible in some patients due to previous exposure to asbestos.

plaural thickening in malignant mesothelioma

The tumour usually encompasses the involved lung but can be seen bilaterally in 5% cases. Chest wall, diaphragmatic and mediastinal invasion may be seen in advanced cases.

There is a moderate to large pleural effusion on the affected side.

CT scanning will show the extent of the pleural or peritoneal tumour.

Pleural thickening more than 1 cm is seen in92% cases, thickening which extends into the interlobular fissure, pleural effusions and pleural calcifications.

pleural thickening

Missing pleural thickening does not exclude mesothelioma since the only finding might be pleural effusion.

Also on a CT imaging, one can differentiate benign from malignant pleural thickening, but may not distinguish primary from metastatic malignancy.

Three main imagine modalities, computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI), are used to evaluate patients with newly diagnosed mesothelioma

The next step in the investigatory process is to carry out a pleural or peritoneal biopsy.

Multiple biopsies are usually required to make the diagnosis. The diagnostic procedure of choice is a thoracoscopic biopsy.

Sometimes a pleural biopsy may not be sufficient to obtain diagnostic material. This may necessitate video-assisted thoracic screening.

Pulmonary function tests may indicate a restrictive lung pattern from the encasement of the lung.

Cytology assessment of the pleural fluid is of limited value in mesothelioma, due to high false-negative results. This means that even with a positive result, many patients still require a biopsy.

A percutaneous needle biopsy of the pleura or peritoneum is done under local anaesthetic to obtain a tissue sample but is diagnostic in only 60% of patients with mesothelioma.

The remainder requires an open biopsy, which is more reliable and provides a larger tissue specimen for assessment. Talc pleurodesis with pleural stripping can be performed at the same time as the VAT biopsy.

The pathologic evaluation of malignant mesothelioma can be challenging and the disease can sometimes be confused pathologically with adenocarcinoma of the lung

It should be noted that tumour seeding may occur along the needle tract of a biopsy and local radiotherapy to the biopsy site may prevent nodule growth.

Two serum markers, osteopontin and soluble mesothelin-related (SMR) proteins, are potential diagnostic markers in mesothelioma.

Staging of mesothelioma

There are multiple staging systems that have been described for pleural mesothelioma while there is no staging system for peritoneal mesothelioma.

The goal of staging is to stratify prognosis and to identify patients that are potential candidates for surgery

Stage 1

Tumour involving the right or left pleura and may have spread to the lung, pericardium, or diaphragm on the same side.

Lymph nodes are not involved.

Stage II

Tumour has spread from the pleura on one side to nearby lymph nodes next to the lung on the same side. It may have spread into the lung, pericardium, or diaphragm on the same side

Stage III

Tumour is invading the chest wall, muscle, ribs, heart, oesophagus, or other organs in the chest on the same side with or without spread to lymph nodes on the same side as the primary tumour.

Stage IV

Tumour involving lymph nodes in the chest on the side opposite the primary tumour, or extends to the pleura or lung on the opposite side, or directly extends into organs in the abdominal cavity or neck. Any distant metastases are included in this stage.


There is no standard therapeutic approach for malignant mesothelioma.

Majority of patients with mesothelioma present with an incurable disease.

Treatment approaches to mesothelioma vary significantly and range from palliative care to chemotherapy to aggressive surgical approaches based on the patient’s age, comorbid medical conditions and performance status

Malignant mesothelioma is poorly responsive to chemotherapy making it generally ineffective, with response rates in the order of less than 10%. Although palliation can be achieved with systemic chemotherapy using carboplatin (cisplatin) and pemetrexed.

Analgesics are administered for chest pain, antibiotics for any infection and cough suppressants to relieve cough as palliative measures.

Like the above measures, the approach to surgery and systemic treatments is usually palliative, as a cure is unlikely unless patients present with localized disease that is resected.

Occasionally patients have operable stage 1 disease with tumour confined to the ipsilateral pleural space, when either decortication (pleurectomy) or extrapleural pneumonectomy may be performed followed by adjuvant radiotherapy

Radiation therapy may be helpful in controlling pain and is often given to pleural biopsy track sites to prevent the tumour from growing down these channels.

Multiple pleurodeses are often required, with installation into the pleural cavities of materials such as talc, tetracycline and bleomycin.

Mesothelioma patients have high circulating levels of vascular endothelial growth factor (VEGF), and mesothelioma tissue stains strongly positively for VEGF receptor 3. Due to this reason, these patients have been treated with antibodies to VEGF, such as bevacizumab, and with angiogenesis inhibitors, such as thalidomide.

Agents such as thalidomide have led to disease stabilization in patients with progressive mesothelioma.


The prognosis for patients with mesothelioma is poor. The 5-year survival for mesothelioma is 5%, with survival ranging from 6 to 18 months.

The disease course even when untreated can be highly variable. Therefore a number of prognostic systems have been developed in order to identify patients subsets with different prognoses.

The two main prognostic systems are the Cancer and Leukemia Group B (CALGB) prognostic groups and the European Organization for Research and Treatment of Cancer (EORTC) prognostic factors and prognostic scores.

Patients with sarcomatoid mesothelioma, those with poor performance status and those who present with chest pain (indicative of disease invasion into the chest wall) are ones with a poor prognosis

Mesothelioma is a very debilitating kind of cancer with limited hope for new therapeutic strategies. The one true hope is in the reduction of risk to workers, and little compensation for those currently suffering as a result of the global epidemic.

Possibly the most important aspect of the care of patients with mesothelioma is to ensure that the appropriate compensatory mechanisms are put in place.

In the UK, industrial compensation is usually arranged for patients by their union officers and involves an examination of the tumour by a pathology panel. These patients are eligible for a lump-sum payment in addition to their other benefit entitlements and they should be directed to appropriate advice.


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