Malignant pleural mesothelioma (MPM) or just “pleural mesothelioma”, is among one of the most aggressive forms of cancer, although rare but is known to be associated with high mortality rates.
Every year there are around 2500 new cases of pleural mesothelioma registered in the United States, out of total about 9000 cases worldwide, as asbestos is prohibited in most parts of the world and completely banned in the European Union since many years ago. Though due to lack of data in many countries, real figures could be much higher. As per World Health Organization estimates, malignant pleural mesothelioma could be responsible for as many as 100,000 fatal outcomes because of cancer each year.
As the name of cancer suggests, it happens on the thin outer lining of the lungs called pleura. It is the most common location of mesothelioma, as almost 70-90% of cases of malignant mesothelioma are pleural. This is much more than the numbers for other types of mesothelioma. It is most frequently diagnosed in the 50-plus age group, though cases in children have been reported.
Causes of Pleural Mesothelioma
Primary and perhaps the only actual cause that has been proven to raise pleural mesothelioma condition is the exposure to asbestos. It is thought that almost 90% of cases of pleural mesothelioma had asbestos exposure sometimes in their life, although pleural mesothelioma may occur even twenty or thirty years after the exposure.
Though there are numerous hypotheses, yet the pathogenesis of pleural mesothelioma due to asbestos exposure is not fully understood. Shipbuilding, construction, military service, and other similar professions where exposure to asbestos is high pose a higher risk of pleural mesothelioma. Other factors that may play a secondary role are exposure to specific viral infections, and genetic predisposition.
Types Of Mesothelioma Found In The Pleura
As pleura is made of a variety of cells, thus mesothelioma may also be different. Around 60-70% of cases of mesothelioma are so-called epithelium mesothelioma, while 10% of the cases belong to a more aggressive form with poorer prognosis called sarcomatoid mesothelium.
Symptoms Of Pleural Mesothelioma
The two most common symptoms of pleural mesothelioma are breathlessness and chest pain. Though frequent, these symptoms are not specific to pleural mesothelioma. Pleural effusion, a condition characterized by an excess of accumulation of fluid in the pleural cavity causing breathlessness and pain is present is 70-80% of the cases. However, pleural effusion may subside either due to therapy or the progression of cancer.
As pleural mesothelioma is a rare disease, it is not uncommon for a specialist to fail to recognize the cause of pleural effusion at the very beginning. As cancer progresses and tumor continues to grow and occupy more space in the pleural cavity, symptoms of breathlessness would become worse, and not respond adequately to the traditional symptomatic therapy.
Unlike inflammatory diseases of the pleura, chest pain associated with pleural mesothelioma is rather dull, some people may just feel immense heaviness in the chest. Typical pain syndrome of pleural inflammation (pleuritis) is often absent. However, as the pleural mesothelioma progresses, so does the inflammatory responses and chest pain. In the later stages, pain may become more widespread as cancer continues to invade the nearby structures. Some of the patients may feel the pain in the ribs. Growing pleural mesothelioma may put pressure on the nerves and thus cause severe intercostal neuropathic pain.
Apart from the specific symptoms of pleural cancer, general signs of the oncological disease like unexplained weight loss, flu-like symptoms, fatigue, lack of appetite, and evening sweating would be present. These are symptoms are caused due to an immune response to the cancer.
Symptoms like cough, bronchitis, tender or visible lymph nodes of the neck, are less frequent with pleural mesothelioma. These symptoms tend to be more commonly associated with either infectious diseases of lungs, or even lung cancer like adenocarcinoma.
As the invasion of tumor in pleural mesothelioma continues, in some cases, depending on the location of pleural mesothelioma in the thoracic cavity, it may cause laryngeal nerve palsy characterized by hoarseness in voice and difficulty in swallowing.
As with many malignant diseases, some of the people may remain symptoms free for long and may be diagnosed with a cancerous lesion in the thoracic cavity just by chance when they had an x-ray or MRI for other reason.
Statistics show that asymptomatic cases have a better prognosis, as in most such cases pleural mesothelioma grows slowly. This means that the condition can be at an early stage, far from stage 4, where there is an improved survival rate.
Taking into consideration the fact that asbestos exposure is the most prominent culprit in pleural mesothelioma, anyone who had asbestos exposure, age above 40, and symptoms of pleural effusion may need to make sure that these symptoms are not due to malignant pleural mesothelioma.
CONSIDER EARLY DIAGNOSIS IF YOU ARE ABOVE 40 AND HAD FREQUENT ASBESTOS EXPOSURE. YOU CAN DETECT PLEURAL MESOTHELIOMA AT AN EARLY STAGE, HAVE A BETTER PROGNOSIS AND AN IMPROVED SURVIVAL RATE
Diagnosis of Pleural Mesothelioma
Considering the rarity of pleural mesothelioma, regular screening has no place in the diagnostics even in those with a proven history of asbestos exposure.
Pleural mesothelioma is challenging to diagnose in the early stages due to lack of symptoms. Imaging of chest by X-ray, CT-scan, and MRI are not only among the most valuable methods but due to better availability remain the methods of choices for initial diagnosis of most conditions of the chest.
If the doctor is unsure and does not want to use any invasive method, the second step would be a blood test for various markers of mesothelioma. However, the problem with the biomarkers is the lower accuracy and dependency.
Thus in the high-risk groups, or in groups where imaging and biomarkers seem to indicate the presence of pleural mesothelioma, a specialist may opt for the most precise diagnostic method for any type of cancer, and that is a histological examination. That is taking a small piece of tumor through the guided needle and examining it under the microscope. It would not only confirm the diagnosis but is also able to help in the differential diagnosis. The exact choice of method of biopsy would vary on the availability of specific technique in the hospital, and the location of the lesion.
Staging Of The Cancer
Once the diagnosis has been confirmed, doctors would have to stage the cancer, as prognosis and treatment are dependent on it. Doctors would use the so-called TNM classification for staging cancer. Where T is about the size of the tumor, N gives information about the involvement of the lymph nodes, and M would tell how widespread the metastasis is, lower numbers indicate better prognosis, while higher figures are associated with reduced survival.
For the sake of simplicity, doctors may inform the average of TNM, thus merely stating whether cancer is in stage 1 or 4 or anything in between. Stage 1 has a good prognosis as it indicates that pleural mesothelioma is located in the thoracic cavity and has not spread, while stage 4 is worst as it says that tumor has spread to the nearby organs and lymph nodes.
Challenges In Diagnosis of Pleural Mesothelioma
Pleural mesothelioma is considered to be difficult to diagnose for the number of reasons. It is not a single type of tumor, instead of a name for various, dissimilar kinds of cancers that have similarities to many other types of malignant tumors.
Though pleural mesothelioma has three main subtypes (epithelial, sarcomatoid and biphasic), but all these three types have many subtypes. Above all, pleura is one of the most common sites for cancers originating in other parts of the body. Thus it is not uncommon to confuse them with pleural mesothelioma.
Treatment of Pleural Mesothelioma
Multimodal treatment is the method of choice; it would be a combination of surgery, radiation therapy, and use of anti-cancer drugs. The strategy of treatment that is deployed in a particular patient would be decided by taking into consideration the age and stage of pleural mesothelioma. Thus in the case of stage 4, surgical resection may not be practicable, and the doctor may treat with a combination of radiotherapy and medical drugs.
Surgical Treatment For Pleural Mesothelioma
In most of the young patients in the early stages of cancer, a surgical procedure would be done at the earliest. It is useful in stage 1 and 2, though may not be of much use in stage 3 when the cancer has already spread.
In stage 1 surgeons may use a less invasive method by removing just a part of pleura along with the tumor, but in other cases, they may decide to remove more of the surrounding tissues, part of the lungs, and diaphragm. The scope of the surgery would also depend on the location of the cancer.
Radiation Therapy For Pleural Mesothelioma
It involves killing the cancer tissues with the help of radiation given by various methods. It is deployed after the surgery, though in some cases it may be used before the surgery.
Radiation therapy would be used in most cases, and even if it will not cure the condition altogether, it may play a significant role in shrinking the tumor. It should be understood that radiation therapy is not just about cancer treatment, as it may also help in symptomatic relief. In some selected cases, radiation may be used to treat neuropathic pain.
Chemotherapy or Treatment With Medical Drugs
Whether early stage or advanced, operable or non-operable, chemotherapy would help in the majority of cases in prolonging the survival. In most cases, doctors would start chemotherapy treatment by combining pemetrexed or raltitrexed with cisplatin.
This combination mentioned is the first line of treatment recommended in the United States and the European Union by most authorities in the field. The combination has been shown to be better in prolonging survival as compared to monotherapy in the trial, although it may also mean more unwanted effects. Some people are not able to tolerate cisplatin either due to age or genetic makeup, in those cases, a specialist may use another drug called carboplatin.
Right until now, the combination mentioned above has remained the most effective treatment, and no other drug or combination has shown better results, although many drugs are being investigated.
Many drugs like Defactinib, Gemcitabine, and others are being investigated for their role in maintenance therapy after primary chemotherapy and other treatments.
At present, there are many second-line therapies under investigation and may help in some instances. Thus patients are encouraged to learn more about ongoing clinical trials and to participate in them.
When it comes to personalized medicine, it may help in some instances as no two tumors are similar because of a genetic difference in the patients. The exact nature of cancer can be understood after extensive molecular analysis.
Thus in some instances, a specialist may be able to offer personalized drug therapy, as an example, mutation of NF2 is sensitive to another group of anticancer drugs.
Considering the high mortality, palliative care is another critical aspect. Many modern medical strategies may help to tackle symptoms better.
Pleural Mesothelioma Prognosis
At present long-term survival in this condition can be regarded as poor even after the so-called successful treatment.
In this condition, doctors would call the treatment successful if they have given all the treatment as per protocol and the tumor did not progress for next 90 days, and there were no severe toxic effects of therapy. However, the so-called successful treatment does not indicate the cure.
By 2020, 70-80% cases of would survive after a year of diagnosis, but after ten years less than 5% men would survive, with prognosis for women being much better and having a 10-year survival rate as high as up to 15%.
Pleural mesothelioma is a difficult to treat cancer that has a high mortality rate, though things are changing fast and for better. Prognosis is quite complicated by the difficulties in diagnosis and late identification of this condition. In the near future, it is entirely possible that more precise biomarkers may help to diagnose early or even predict this condition.
A recent clinical trial with bevacizumab, a product called Avastin, has raised the hopes of better survival rates. In the future, personalized medical solutions may also change the way that this condition is treated.
- van Zandwijk N, Clarke C, Henderson D, et al. Guidelines for the diagnosis and treatment of malignant pleural mesothelioma. J Thorac Dis. 2013;5(6): E254-E307. DOI:10.3978/j.issn.2072-1439.2013.11.28.
- Scharf JB, Lees GM, Sergi CM. Malignant pleural mesothelioma in a child. Journal of Pediatric Surgery Case Reports. 2015;3(10):440-443. DOI:10.1016/j.epsc.2015.09.002.
- Bibby AC, Tsim S, Kanellakis N, et al. Malignant pleural mesothelioma: an update on the investigation, diagnosis, and treatment. European Respiratory Review. 2016;25(142):472-486. doi:10.1183/16000617.0063-2016.
- Baas P, Fennell D, Kerr K, Van Schil P, Haas R, Peters S. Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Annals of oncology. 2015;26(suppl_5):v31-v39.
- Patz EF, Shaffer K, Piwnica-Worms DR, et al. Malignant pleural mesothelioma: the value of CT and MR imaging in predicting resectability. American Journal of Roentgenology. 1992;159(5):961-966. DOI:10.2214/ajr.159.5.1414807.