Epithelioid Mesothelioma

Epithelioid cells are one of the three main cell types of mesothelioma and the most common. Accounting for nearly 70% of all forms of mesothelioma cancer, Epithelioid malignant mesothelioma has an average life expectancy of 18-24 months.

Epithelioid Mesothelioma
Malignant Epithelial Cells

What is Malignant Epithelioid Mesothelioma?

Epithelioid mesothelioma is a serious and aggressive malignant tumor that can affect various mesothelial structures. Mesothelium is a membrane made up of epithelial cells that cover and protects some of our internal organs such as the lungs (the pleura), the abdominal cavity (the peritoneum) or the heart (the pericardium).

How Common is Malignant Epithelioid Mesothelioma?

Epithelioid mesothelioma is a rare cancer. Most often, it appears in the pleura (pleural mesothelioma). This type of cancer accounts for up to 90% of all mesothelioma cases.  Concerning the cell type, the epithelioid type is the most frequent and include around 70% of the cases. There are other types such as sarcomatoid or biphasic tumors that are more aggressive and fortunately much rarer.

  • The purpose of this article is to expose all the aspects of this pathology, including its statistics, risk factors, symptoms, diagnosis, and evolution. We will also talk about treatment options and the main ways to avoid it.
Cell Characteristics

What are the Characteristics of Epithelioid Mesothelioma?

Epithelioid Mesothelioma Histology

Histologically, epithelial mesothelioma cells have polygonal, ovoid or cuboidal cell shape. This form of mesothelioma is comprised of cells which resemble the normal mesothelial cells in that they are arranged in a trabecular fashion. The occasional presence of signet-ring cells may make it challenging to distinguish this disease from cancers of the lung proper (adenocarcinoma). This is quite different from the histology of sarcomatoid mesothelioma which is characterized by a spindle cell morphology. Biphasic mesothelioma has characteristics of both epithelioid (polygonal, ovoid or cuboidal) and sarcomatoid (spindle) variants depending on the extent in which they are comprised of.

Epithelioid Cell Characteristics
What are the Subtypes of Epithelioid Mesothelioma?
Subtypes

What are the Subtypes of Epithelioid Mesothelioma?

Epithelioid, sarcomatoid and biphasic are the subtypes of Epithelioid mesothelioma. According to the World Health Organization (WHO), these are the 3 different histologic (microscopic) subtypes of this disease. This categorization is relevant and important for 2 reasons.

First, each subtype has a varying prognosis (projected course of the disease).  Second, the subtype of the mesothelioma at diagnosis determines the pharmacotherapeutic and/or surgical treatment. These subtypes are distinguished by a trained histopathologist, with the aid of a microscope and various staining techniques. A CT guided biopsy is utilized to obtain samples of the mesothelioma, with a 60 – 85% diagnostic yield. Occasionally, an open or thoracoscopic pleural biopsy is used for an even higher diagnostic yield.

The sarcomatoid mesotheliomas are comprised of tightly bundled spindle cells. Occasionally, there are malignant cells which are derived from surrounding bone (osteoid), cartilage (chondroid) or muscle (myoid). Sarcomatoid mesotheliomas are extremely rare.

The remaining 25% of mesotheliomas are comprised of biphasic mesotheliomas. The biphasic mesothelioma contains both epithelioid and sarcomatoid components. Specifically, each component comprises about 10% each of the overall microscopic picture, as determined by a histopathologist.

Statistics & Data

Statistics about Malignant Epithelial Mesothelioma

Mesothelioma occurs more frequently in men than women and the risk increases with age, but it can occur in men or women at any age. Incidence rates have increased over the past 20 years, but Epithelial malignancy remains a relatively rare form of epithelioid tissue mutation that leads to mesothelioma.

The incidence of malignant mesothelioma currently reached a level of about 40 cases per 1,000,000 inhabitants in western industrialized nations, depending on the extent of population exposure to asbestos over the past decades.

Statistics about Malignant Epithelial Mesothelioma
malignant mesothelioma epithelioid type
peritoneal epithelial mesothelioma
Risk Factors

What is the Cause of Epithelioid Mesothelioma Cancer?

Exposure to asbestos causes epithelial cells to mutate which leads to epithelioid mesothelioma, sometimes called asbestos epithelioid mesothelioma. Asbestos is the name given to a group of natural minerals that can be separated into long thin fibers. When a person inhales these fibers, they can reach the smallest airways in the lung and the mesothelium. The fibers thus reach the pleura, where they can eventually cause pleural mesothelioma. If expelled by coughing and then swallowed, asbestos fibers can also infiltrate the peritoneum. This is the most frequent cause of peritoneal mesothelioma.

The link between asbestos and epithelial mesothelioma has been well known for many years. According to the International Agency for Research on Cancer (IARC) and the US National Toxicology Program, all forms of asbestos can cause cancer. Most people with mesothelioma have already been exposed to asbestos (there was an exposition in 75% of the cases).

The risk of epithelial cell mutation that leads to cancer is related to the amount of asbestos to which a person has been exposed and the duration of exposure. Mesothelioma is more likely to occur in a person who was exposed when they were young, for a long time and to a large amount of asbestos.

Asbestos has been widely used in building materials and many industries. People who may come into contact with asbestos at work include the following:

  • Workers in asbestos mines or asbestos removal plants.
  • Construction workers, carpenters, and painters.
  • Electricians.
  • Demolition workers.
  • Workers in the automotive industry, including brake and clutch repairers.

People who live near an asbestos factory are also exposed to this risk. Family members of an exposed worker may also be at risk of this disease because asbestos fibers may remain on the worker’s clothing.

Risk Factors

What is the common Age and Gender of Epithelial Cancer Patients?

This disease affects men much more often than women, probably because men are more likely to be exposed to asbestos in their workplace. Epithelioid histiocyte mutations that lead to mesothelioma occur 15 to 40 years after the person is exposed to asbestos. As a result, mesothelioma is uncommon in people under 50 years of age and its incidence increases with age.

Age and Gender of Epithelial Cancer Patients
Stage 4 Mesothelioma
Carcinogens

Can Other Carcinogens Cause this Disease?

Exposure to erionite, fluoro-edenite, and radiation can lead to the development of Epithelioid mesothelioma. Erionite is recognized as a human carcinogen and is linked to the development of pleural and peritoneal epithelioid cancer. It is a natural mineral substance that belongs to the group of minerals called zeolites (chemically related to asbestos).

Fluoroedenite is a natural mineral that resembles asbestos, with asbestos-like fibers. It is found in the lava that flows on the sides of volcanoes, especially on Mount Etna in Italy. Exposure to this mineral increases the risk of mesothelioma.

Exposure to radiations:

People who have received chest or abdominal radiotherapy for lymphoma, breast cancer or lung cancer are also at increased risk of developing this disease.

  • It should be noted that research shows that there is no link between smoking and a higher risk of mesothelioma.
Symptomology

What Are The Symptoms of Epithelioid Mesothelioma?

Epitheloid mesothelioma usually causes no signs or symptoms in the early stages of the disease. Symptoms occur when the tumor invades surrounding tissues and organs or when fluid accumulates around the lungs (pleural effusion) or in the abdomen (ascites). In most cases, the disease is already advanced at the time of diagnosis (often stage 3 or 4).

If you have already been exposed to asbestos, it is important that you know the symptoms of mesothelioma. Usually, the symptoms of mesothelioma do not appear until 20 to 60 years after exposure to asbestos.

These signs may vary depending on the location of the tumor. Keep in mind that other medical conditions can cause the same symptoms as epithelial mesothelioma (this pathology has a lot of differential diagnostics).

Pleural Epithelioid Mesothelioma Symptoms

  • Chest or lower back pain.
  • Coughing.
  • Shortness of breath (may be caused by pleural effusion).
  • Tiredness.
  • Weight loss.
  • Fever.
  • Perspiration.
  • The difficulty of swallowing.
  • Swelling of the face and arms.

Peritoneal Epithelioid Mesothelioma Symptoms

  • Abdominal pain.
  • Swelling of the abdomen (may be caused by ascites).
  • Nausea and vomiting.
  • Constipation or obstruction of the small intestine or colon.
  • Weight loss.
  • Fever.

In some cases, this disease causes serious symptoms related to the advanced evolution of the tumor with signs of distant metastasis:

  • Spinal cord compression: With sensitive or motor deficits as well as disabling back pain.
  • Superior vena cava compression syndrome: Causing ptosis, turgescence of the neck veins, as well as facial edema and intense headaches.
How to Get Diagnosed

How is Epithelioid Mesothelioma Diagnosed?

A Biopsy is the most accurate way to diagnose Epithelioid Mesothelioma. Two positive and Two negative antibodies are required to make a concrete diagnosis of mesothelioma. The International Mesothelioma Panel (IMP) recommends that all patients require at least 1 CK marker, 2 mesothelial markers and 2 carcinoma-related markers in the diagnosis for this disease. The Epithelioid mesothelioma ICD code is C45.9. Because of its insidious evolution, the diagnostic process may be longer than for other forms of cancer. Your doctor will ask you about the symptoms you are experiencing and may give you a physical examination.

CK 5/6 (Cytokeratin 5/6)

CK 5/6 is characteristically expressed by mesothelial cells and is used to distinguish mesothelioma from lung cancer (adenocarcinoma). It is also useful in distinguishing epithelial mesothelioma from non-lung cancer derived tumors which have spread to the pleura (secondary metastasis).

Mesothelial Markers

i) Calretinin
Calretinin is considered to have the greatest specificity for the diagnosis of mesothelioma. This means that a negative calretinin is highly likely to suggest the absence of mesothelioma.
ii) WT1 (Wilms’ Tumour 1 Mutation)
The WT1 gene is responsible for the cellular growth and differentiation of mesothelial cells. The WT1 mutation is highly immunoreactive in epithelioid mesotheliomas but is not very immunoreactive in sarcomatous ones.

Carcinoma-Related Markers

i) CEA (Carcinoembryonic Antigen)
The absence of CEA immunoreactivity is characteristic of mesothelioma and is, therefore, a negative marker for it. Positive immunoreactivity is often seen in the context of lung cancer (adenocarcinoma).
ii) CD15
Most researchers agree that CD15 is not expressed by mesothelioma and is expressed in nearly all lung adenocarcinomas.

Biomarkers

i) SMRP (Soluble Mesothelin-Related Protein)
This is the only FDA-approved mesothelioma biomarker, which is expressed in the mesothelioma. While it is raised in patients with mesothelioma, it is not useful for screening or diagnosis as it is also raised in ovarian, pancreatic and other cancers. It is, however, useful to trend the severity and progress of mesothelioma during treatment.

differential diagnosis for epithelial malignancy
Metastasis of Epithelial Mesothelioma

What if Epithelioid Mesothelioma Spreads?

When this disease moves from the mesothelium to other parts of the body it is called metastasis. Understanding how this form of cancer tends to grow and spread helps your healthcare team plan your treatment and future care.

Pleural Epithelioid Mesothelioma Metastasis

When pleural mesothelioma spreads, it often affects the following structures:

  1. The mediastinum (space in the chest between the lungs).
  2. The esophagus.
  3. Chest muscles and ribs.
  4. The opposite lung.
  5. The diaphragm.
  6. Lymph nodes in the chest.
  7. The liver.
  8. Kidneys and adrenal glands.
  9. Back bones.

Peritoneal Epithelioid Mesothelioma Metastasis

If peritoneal mesothelioma spreads, it often affects the following structures

  1. The pleura.
  2. The liver.
  3. The spleen.
  4. Other organs of the abdomen

It should be noted that peritoneal mesothelioma rarely spreads outside the abdominal cavity.

Survival Rate of Epithelioid Mesothelioma
Life Expectancy

What is the Survival Rate of Epithelioid Mesothelioma?

The survival rate of Epithelioid Mesothelioma after five years is 4% for men and 11% for women (Estimated). One study investigated the utility of examining the degree of epithelioid differentiation in biphasic mesothelioma in 144 patients. The researchers found that the median survival overall was 13 months. In the 100% epithelioid subgroup, the median survival was 20 months. In the 51% to 99% subgroup, the median survival was 12 months. Finally, in the <50% subgroup, the median survival was about 7 months. The conclusion from this study was that the percentage of epithelioid differentiation in biphasic mesothelioma patients is an independent predictor of survival.

Prognosis

What is the Prognosis of Epithelioid Mesothelioma?

Epithelioid mesothelioma life expectancy is around 18 – 24 months on average. To better pinpoint an individual’s life expectancy, many rely on the utilization of nuclear grading. The grading system focalizes on epithelial cells as they are sanctioned to be a great contender due to their well-defined nucleus. The median patient survival for those with a nuclear grade of 1 is approximately 28 months. Individuals may obtain a lower survival rate if their nuclear grade is increased, as grade 2 averages to about 14 months and grade 3 averages to approximately five months.

Prognosis Factors

The following are the main prognostic factors of epithelioid mesothelioma.

Age and gender

People over 60 years of age who are diagnosed with mesothelioma often have a shorter survival time than people with epithelioid mesothelioma at a younger age. In addition, men diagnosed with mesothelioma have a poorer prognosis than women with this pathology.

Advanced stage

The stages play a role in the prognosis of people who will undergo surgery. In general, the prognosis of people with stage 1 or 2 epithelioid mesothelioma is generally quite good. These two stages mean that the tumor hasn’t spread a lot and is still surgically removable.

The prognosis of epithelial mesothelioma that has spread to the lymph nodes or other organs (stage 3 or 4) is often disastrous.

What is the Prognosis of Epithelioid Mesothelioma?
Prognosis Factors at Advanced stage
Prognosis

Prognosis Factors at Advanced stage

High Lacto-dehydrogenase (LDH) levels:

Lacto-dehydrogenase (LDH) is an enzyme found in almost all cells in the body. When cells are damaged or destroyed, they release LDH into the blood. A higher than usual LDH level means that cells or tissues are damaged somewhere in the body. The prognosis of a person with epithelioid mesothelioma with high LDH levels is worse than if the person had normal or low LDH levels.

Weight loss

The prognosis of a person who lost a lot of weight before being diagnosed is often poor.

Chest pain

The prognosis for a person diagnosed with pleural epithelioid mesothelioma and having chest pain is often poor, as this may indicate that the cancer is so advanced that it cannot be removed by surgery.

Concerning the cellular subtype: Fortunately, epithelioid mesothelioma is the most common subtype of mesothelioma and has a better prognosis than sarcomatoid or biphasic types. The sarcomatoid subtype has the least favorable prognosis because it doesn’t respond well to treatment.

Biphasic Mesothelioma Life Expectancy

Biphasic mesothelioma has a life expectancy of 13 months. Biphasic mesothelioma has a worse prognosis than epithelioid variants – studies have shown that the median survival of patients with the epithelioid variant is roughly 55 months, as compared to 13 months for biphasic mesothelioma.

Only a doctor who is familiar with your medical history, the type, stage and characteristics of cancer can review all of this data to arrive at a prognosis.

Treatment Options

What is the Best Epithelioid Mesothelioma Treatment?

Epithelioid mesothelioma treatment options can include surgery, chemotherapy, radiotherapy, and natural/alternative treatments. Your healthcare team will develop a treatment plan specifically for you. This therapeutic plan will be based on your health status and cancer-specific information.

You may be offered one or more of the following treatments for mesothelioma.

Surgery:

If you are able to go through surgery, here are the options available:

  • For pleural mesothelioma:

The following types of curative surgery are used to treat pleural mesothelioma.

An extrapleural pneumonectomy: During this procedure, the parietal and visceral pleura, the lung on the side where the mesothelioma originated, a part of the diaphragm and the lymph nodes in the chest are removed. It is also possible to remove the envelope surrounding the heart (called the pericardium).

A pleurectomy/decortication: During this procedure, the parietal and visceral pleura and tumor are removed, but the lung is not removed.

Palliative surgeries are designed to relieve symptoms such as pain or difficulty breathing, they don’t remove the tumor. The following types of palliative surgery are used to treat pleural mesothelioma.

The most common one is tumor reduction, whereas much of the mesothelioma as possible is removed. Another common palliative surgery is thoracentesis, which is used to extract the fluid surrounding the lungs that hinder normal breathing.

The last palliative surgical option is pleurodesis, the parietal and visceral pleura are sealed together to prevent the accumulation of fluid between them.

In general, it is not possible to operate on people with peritoneal mesothelioma, as this cancer has usually spread too widely to be completely removed. Surgery is often used only to relieve symptoms caused by peritoneal mesothelioma. The only types of surgeries that can be proposed are palliatives like tumor reduction and paracentesis.

Epithelioid mesothelioma treatments
Chemotherapy
Conventional Cancer Treatment

Chemotherapy

Most people with mesothelioma receive chemotherapy. In the presence of pleural mesothelioma, chemotherapy is used after surgery; if surgery cannot be performed, it can also be used as the primary treatment.

The most common chemotherapeutic combinations used to treat pleural mesothelioma are:

  • Cisplatin and pemetrexed.
  • Cisplatin and raltitrexed.
  • Cisplatin and gemcitabine.

In the presence of peritoneal mesothelioma, chemotherapy is a regional treatment and is administered directly into the peritoneal cavity. The most common chemotherapeutic agents used as intra-peritoneal chemotherapy to treat epithelioid peritoneal mesothelioma are Cisplatin, Mitomycin and Doxorubicin.

 

Conventional Cancer Treatment

Radiotherapy

External radiotherapy can be used to treat pleural mesothelioma. After an extra-pleural pneumonectomy, radiotherapy can be administered to the side of the chest from which a lung has been removed.
Radiation therapy is not indicated after a pleurectomy because it could damage the lung tissues. Radiation therapy can also be used to relieve symptoms caused by pleural mesothelioma, such as back pain in bone metastasis.

Radiology
Epithelial Mesothelioma Support

Supportive Care for People with Epithelioid Mesothelioma Cancer

Supportive care helps to overcome the physical, emotional and spiritual effects caused by epithelioid mesothelioma. They are an important component of the care provided to people with this disease. Many programs and services are available to meet the needs and improve the quality of life of these individuals and their families, either before or after treatment is completed. A person who has been treated for an epithelioid mesothelioma may be concerned about the following:

Pleural effusion refers to an accumulation of fluid around the lungs. This fluid can exert pressure on the lungs, making it difficult to breathe. Pleural effusion commonly occurs in the presence of pleural epithelioid mesothelioma, but it can also be caused by peritoneal mesothelioma.
Symptoms of pleural effusion include shortness of breath, coughing, feeling of heaviness in the chest and anxiety of not being able to breathe.
If you have pleural effusion, your health care team will monitor you closely and suggest ways to treat it. A needle could be used to remove fluid from the chest (thoracentesis) or surgery to seal the pleura together (pleurodesis) to prevent further accumulation of fluid.

Ascites is an accumulation of fluid in the abdomen. It causes swelling of the abdomen, which can cause discomfort or pain. It can also cause nausea and shortness of breath. Ascites occurs in most people with peritoneal epithelioid mesothelioma.
If you have ascites, your healthcare team may suggest ways to treat it. It is common for the liquid to accumulate again after it has been removed. More than one treatment may, therefore, be necessary. A needle could be used to remove fluid from the abdomen (paracentesis). Chemotherapeutic agents may also be administered directly into your abdomen through a small tube (catheter).

Many people with advanced epithelioid mesothelioma have loss of appetite, which can lead to weight loss and poor nutrition. Severe weight loss can lead to loss of muscle mass (cachexia).

It is important that you try to maintain your weight, even if you don’t want to eat. Adequate nutrition helps your body fight disease and cope with the effects of cancer treatment. There are some popular diets that mesothelioma patients should avoid. Your healthcare team can suggest ways to help you treat loss of appetite.

Fatigue is a generalized lack of energy. This is a very common symptom in people with mesothelioma. Fatigue in epithelioid mesothelioma patients is multifactorial and can be caused by the disease itself, its treatments or a loss of appetite.
Your healthcare team can suggest ways to help you treat fatigue. These will vary depending on the cause of fatigue. It’s also advisable to get enough sleep, organize your activities to reduce fatigue and eat a healthy diet.

Pain is common in people with epithelioid mesothelioma. It can occur when cancer grows and puts pressure on other organs or nerves. The intensity of pain often increases as the cancer progresses.
Cancer pain can have physical and emotional repercussions. It may interfere with healing and cause fatigue, loss of appetite and sleep disorders. In addition, coping with pain requires energy, at a time when you need it to fight the disease and carry out your usual daily activities.
For most people who experience pain related to cancer or its treatments, it can be controlled. Your healthcare team can help you find ways to prevent, treat or relieve it (these include both a pharmaceutical and psychological approach).

Lifestyle Changes

Impact of living with Advanced Epithelioid Mesothelioma Cancer

Psychological impact

Many people with mesothelioma are diagnosed at an advanced cancer stage. Advanced cancer stage refers to a cancer that is unlikely to heal. It is therefore essential to treat the psychological effects linked to this diagnosis and not focus only on the organic and therapeutic aspects of this disease.

Financial worries

One of the best decisions someone with this form of mesothelioma can do is to work with a mesothelioma lawyer. People with this form of mesothelioma can have financial worries because of their illness. Mesothelioma lawyers help workers (and their families) with compensation to help with expenses. The basis for financial compensation typically stems from the companies or company that exposed you or your loved ones to asbestos in the workplace (professional exposure). In any case, ask your doctor or health insurance about these programs and services.

How to reduce the risks of Epithelioid Mesothelioma?

You can reduce your risks of epithelial mesothelioma by adopting these following behaviors:

Avoid exposure to asbestos

Try to avoid any exposure to asbestos. If you workplace causes an exposure, take appropriate safety measures to limit it. Use all protective equipment provided by your employer, and follow recommended occupational health and safety procedures.

Spread Awareness

Spreading awareness concerning this disease will help preventing it. This effort also leads to an earlier diagnosis and therefore to a better prognosis.

Consult your doctor in case of persistent symptoms

If you suffer from a persistent symptom, do not hesitate to consult your doctor, especially if you have been exposed to asbestos. This will also lead to earlier diagnosis and better prognosis.

Conclusion

To conclude, malignant epithelioid mesothelioma is a serious tumor that grows insidiously. At the moment of the diagnosis, the tumor has usually spread a lot and the prognosis is often very bad. It’s therefore essential to learn about this pathology to reduce its risk and to increase the chances of an early diagnosis for at-risk individuals.

References

  1. – Environmental asbestos exposure and risk of mesothelioma. Annals of translational medicine Journal.
    Annals of translational medicine Journal
  2. Malignant mesothelioma. National Center for Biotechnology Information (NCBI).
    National Center for Biotechnology Information (NCBI)
  3. Malignant peritoneal mesothelioma: a review. Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  4. Malignant pleural mesothelioma: Current and future perspectives. Journal of Thoracic diseases.
  5. Malignant Mesothelioma: Facts, Myths, and Hypotheses. Journal of Cellular Physiology.
  6. Malignant pleural mesothelioma: an epidemiological perspective. (Epithelioid mesothelioma pathology outlines). Annual of cardiothoracic surgery.
  7. New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma. Frontiers in Oncology Journal.
  8. Advances in the diagnosis, treatment, and prognosis of malignant pleural mesothelioma. Annals of translational medicine Journal.
  9. Thomas, A., et al., Distinctive clinical characteristics of malignant mesothelioma in young patients. Oncotarget, 2015. 6(18): p. 16766-16773. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599306/
  10. Rossini, M., et al., New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma. Frontiers in oncology, 2018. 8: p. 91-91. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891579
  11. Kim, J., S. Bhagwandin, and D.M. Labow, Malignant peritoneal mesothelioma: a review. Annals of translational medicine, 2017. 5(11): p. 236-236. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497105/
  12. Bononi, A., et al., Latest developments in our understanding of the pathogenesis of mesothelioma and the design of targeted therapies. Expert review of respiratory medicine, 2015. 9(5): p. 633-654. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887271/
  13. Moore, A.J., R.J. Parker, and J. Wiggins, Malignant mesothelioma. Orphanet journal of rare diseases, 2008. 3: p. 34-34. https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-3-34
  14. Liu, S., et al., Diffuse mesothelioma of the peritoneum: correlation between histological and clinical parameters and survival in 73 patients. Pathology, 2014. 46(7): p. 604-9. https://www.ncbi.nlm.nih.gov/pubmed/25393250
  15. Vigneswaran, W.T., et al., Amount of Epithelioid Differentiation Is a Predictor of Survival in Malignant Pleural Mesothelioma. Ann Thorac Surg, 2017. 103(3): p. 962-966. https://www.ncbi.nlm.nih.gov/pubmed/27765170