Mesothelioma Diagnosis, Cell Types, Cell Subtypes, Misdiagnosis And Testing Procedures

Diagnosis Of Mesothelioma

Common Mesothelioma Testing Procedures

Imaging Scans: Most people firstly undergo a basic chest X-ray to check for any abnormalities. If an abnormal growth or fluid around the lung is detected, doctors will recommend a more detailed imaging scan such as a PET scan, CT scan or MRI.

Biopsies: If cancer is suspected, doctors will suggest taking a sample of tissue, which is also known as a biopsy. Doctors use this tissue sample to definitively confirm the presence of malignant mesothelioma cells.

Blood Tests: Blood tests might be used but do not confirm the presence of mesothelioma. Researchers are evaluating if blood tests can aid in the early diagnosis of at-risk former asbestos workers.

Staging: An important part of the diagnostic process is determining the cancer’s stage of growth. Doctors use imaging scans and biopsies to assess the growth and spread of mesothelioma tumors. The TNM staging system is the most commonly used system for staging malignant mesothelioma.

Mesothelioma Cell Types

There are three cell types of mesothelioma named for the cancerous cells found in the tumors: Epithelioid, sarcomatoid and biphasic. Some are more common and respond well to treatments. Others are rarer and more resistant to therapies.

• Epithelioid

  These cells are the most responsive to treatment. This type of mesothelioma accounts for 70% of mesothelioma diagnoses. It also leads to improved prognosis and life expectancy.

  Malignant Epithelioid Mesothelioma

  Epithelioid mesothelioma is a cancer subtype caused by asbestos. It is the most common mesothelioma cell type, accounting for 50% to 70% of cases. Symptoms include shortness of breath and chest pain. The median survival rate for epithelioid mesothelioma patients is 18 months.

  Meaning Of Epithelial Mesothelioma?

  Epithelial mesothelioma is the most common of the three cell types of mesothelioma cancer. This tumor cell type involves cuboid cells with low mobility that group together and have visible nuclei. Epithelial and epithelioid both refer to this type of asbestos-related cancer.

  

  More than 50% and up to 70% of mesothelioma cases are epithelioid. Epithelial cells line the portion of the airway known as the bronchus, an area susceptible to asbestos inhalation. The respiratory tract lining consists of pseudostratified columnar ciliated epithelium, which serves as a protective barrier.

  Patients with this tumor cell type live about six months longer than patients with other cancer cell types. It has the best prognosis of the three mesothelioma cell types because it is the most responsive to treatment. Due to this higher response rate, epithelioid cases tend to qualify for more aggressive and effective treatment plans.

  Mesothelioma tumor location has a more significant impact than cell type on the kind of treatments a patient will undergo. However, cell types such as epithelial sarcomatoid or biphasic affect whether patients qualify for specific aggressive therapies.

  Characteristics of Epithelial Cells

  Epithelial mesothelioma cells clump together in groups. Each cell is square, cubed, columnar (long) or squamous (flat) in appearance. The nucleus, the central cellular region that contains genetic material, is noticeably visible in each cell.

  Because epithelioid cells lack mobility and adhere closely together, they are less likely to spread and metastasize than sarcomatoid cells. This characteristic is one of the reasons epithelial mesothelioma has a better prognosis than other cell types.

  Symptoms of Epithelial Cell Mesothelioma

  Mesothelioma symptoms remain the same regardless of the cells that make up tumors. Tumor cell types primarily impact treatment response and growth rate, but they do not influence symptoms. Epithelioid tumor cells do not cause symptoms different from other cell types. As cancer grows and spreads, symptoms appear when organs such as the lungs, heart or kidneys are affected. Initial symptoms of pleural or peritoneal mesothelioma include cough, shortness of breath and lack of appetite. As the disease progresses, more severe symptoms may surface.

  • Shortness of breath
  • Persistent, nonproductive (dry) cough
  • Hoarseness
  • Coughing up blood
  • Low blood oxygen levels
  • Anemia (low iron)
  • Fever
  • Night sweats
  • Weight loss
  • Feeling full, even without eating
  • Lack of appetite and nausea
  • Fatigue and extreme tiredness

  Prognosis for Epithelial Mesothelioma

  According to data published in 2018 from the National Mesothelioma Virtual Bank, the median survival of epithelioid patients is 18 months. This life expectancy measures the time from diagnosis until death. Patients with biphasic cell type have a median survival of 10 months, and life expectancy is seven months for people with sarcomatoid cells.

  Compared with other cell types, patients with epithelioid cells had an improved prognosis of around 200 additional days of survival. This enhanced survival rate can add years to a patient’s life expectancy if they receive an early-stage diagnosis with aggressive treatment.

  According to a 2020 study published in Oncology Reports, epithelioid mesothelioma prognosis depends on a protein called CTGF, or connective tissue growth factor. Patients with lower levels of this protein had a better prognosis and more prolonged survival.

  Epithelial cell type allows patients to access more aggressive treatment plans, such as surgery, and innovative clinical trials, especially when treated at a mesothelioma specialty clinic.

Diagnosis Of Epithelial Mesothelioma 

Accurately diagnosing epithelioid mesothelioma requires multiple steps. Many patients experience significant delays between the onset of symptoms and receiving an accurate diagnosis.

When symptoms first appear, such as cough or shortness of breath, they can be vague and prompt general practitioners to order several tests to rule out other illnesses. Eventually, after radiology exams and a biopsy procedure, a mesothelioma specialist can confirm a diagnosis with a tumor cell type.

Challenges

Several obstacles may delay your physician from obtaining a tissue sample. Mesothelioma patients wait approximately three months after symptoms appear before they receive a diagnosis.

Only a tumor biopsy, collected through a procedure such as a thoracoscopy or fine-needle aspiration, leads to accurate identification of epithelioid mesothelioma.

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• Initial symptoms such as cough and fatigue mimic less severe respiratory conditions, according to research in the 2019 Expert Review of Respiratory Medicine.
• Primary care doctors perform in-office exams and tests to rule out common causes of symptoms before referring a patient for more thorough chest scans.
• Even with a referral, X-rays, CT scans or MRI tests can take weeks to schedule.
• Radiological imaging can reveal visual abnormalities, but does not determine the cause of diseased chest areas.
• Once imaging results are available, it may still take several more weeks to schedule an appointment for a biopsy.

One of the most important things you can do to minimize diagnostic delays is to share any history of asbestos exposure with your health care provider.

If your doctor knows you have a history of asbestos exposure, they are more likely to consider mesothelioma or another asbestos-related condition.

Role of Immunotherapy in Diagnosis

Immunohistochemistry is a laboratory test to detect proteins on the surface of cells. These proteins help classify cancer cell types.

Pathologists use immunohistochemistry to identify epithelioid mesothelioma and differentiate it from another type of cancer called adenocarcinoma.

According to the 2018 ASCO pleural mesothelioma treatment guidelines, immunohistochemistry is the recommended test for suspected mesothelioma tumors.

This analysis will confirm the absence or presence of mesothelioma cell markers, leading to the most accurate diagnosis possible.

Your pathology results will show the specific cell type of your cancer. If you don’t have a record of your cell type, be sure to ask your doctor and request a copy of the pathology report for your records.

Epithelial Mesothelioma Cell Subtypes

When a pathologist outlines their report for your treating physician, they provide a wide breadth of information.

These details include the biopsy site where the sample originated, how the surgeon collected the sample, cell characteristics, the distribution of cells in the tissue and an overall diagnosis.

Epithelial cells can vary in many different ways, leading to several additional cellular subtypes within this group. These subtypes can inform your doctor how your cancer might progress and which treatments may be most appropriate.

Tubulopapillary

This subtype of epithelioid mesothelioma is the most common. Most tubulopapillary mesotheliomas contain well-differentiated cells. Doctors without mesothelioma experience can mistake this for adenocarcinoma that has spread to the pleura.

Glandular

Tumors with the glandular pattern are primarily composed of gland-like (acinar) structures. This subtype usually develops in the pleural lining. It may be confused with adenocarcinoma that has spread to the pleura.

Adenomatoid

Adenomatoid mesothelioma, also known as the microglandular cell type, accounts for 6% of pleural mesothelioma cases. These tumor cells appear flat or cube-like with a lining of small gland-like structures.

Adenomatoid cells often combine with other kinds of epithelial cells inside a tumor. Doctors may mistake it for benign adenomatoid tumors or metastatic adenocarcinoma of the pleura.

Solid

The solid subtype has two patterns: Well-differentiated and poorly differentiated.

Solid, well-differentiated epithelial type is more common. It has round cells in nests, cords or sheets.

The poorly differentiated pattern has relatively unorganized cells that are polygonal (having straight sides) to round in appearance.

A pathologist without relevant experience may mistake solid, well-differentiated mesothelioma for benign reactive mesothelial hyperplasia. The poorly differentiated pattern looks like lymphoma and large cell carcinoma.

Deciduoid

Deciduoid mesothelioma is a rare epithelial subtype. This pattern features large round to polygonal cells with sharp borders.

Deciduoid mesothelioma may be mistaken for squamous cell carcinoma, anaplastic large cell lymphoma, gastrointestinal autonomic nerve tumor, pseudotumoral deciduosis, trophoblastic neoplasia and the oxyphilic variant of ovarian clear cell carcinoma.

Well-Differentiated Papillary Mesothelioma

This cell type grows slowly and features small bumps or protrusions lined by a single layer of thin cells. This type of mesothelioma is primarily benign and responds well to surgery. It occurs mainly in younger and older adult women with peritoneal mesothelioma.

Treatment Options Of Epithelial Mesothelioma 

Patients have a better chance of improving life expectancy when they seek out specialized mesothelioma care and treatments tailored to their diagnosis. The first step in finding the best mesothelioma treatment is to seek the advice of an expert physician.

Of the three mesothelioma types, epithelial responds best to treatment. Patients diagnosed with the epithelial variant tend to have more treatment and clinical trial options, such as immunotherapy and radiation therapy.

Early-stage epithelioid mesothelioma is treated aggressively with a combination of surgery, chemotherapy and radiation therapy. According to a 2019 report in The Annals of Thoracic Surgery, combination therapy resulted in significantly better outcomes for patients with epithelial malignant pleural mesothelioma.

As cancer progresses it has a higher chance of spreading and metastasizing to other areas, making surgery less beneficial. Late-stage cases respond better to chemotherapy, immunotherapy and Tumor Treating Fields therapy.

Frequently Asked Questions (F.A.Q) About Epithelial Mesothelioma

Question: How does a mesothelioma cell type affect my prognosis and treatment?

Answer: Patients with the epithelioid cell type have the most mesothelioma treatment options because their cell type responds the best to all forms of treatment. Epithelioid patients also live an average of 200 days longer than patients with other cell types.

Question: How do I find a doctor who treats epithelial mesothelioma?

Answer: Most oncologists are not trained to treat epithelioid mesothelioma. Mesothelioma doctors have trained for years to specialize in the treatment of this cancer. Our Patient Advocates can help you find a top doctor who treats epithelial mesothelioma.

 

• Sarcomatoid

  Cells of this type are least responsive to treatment. Patients with these cell types have poorer diagnoses and shorter life expectancies. This mesothelioma type accounts for 10% of all cases.

Sarcomatoid Mesothelioma

Sarcomatoid mesothelioma is an aggressive form of cancer caused by asbestos exposure. It is rare, accounting for 10%-20% of mesothelioma cases. Sarcomatous cells are resistant to treatment due to their spindle shape.

Meaning Of Sarcomatoid Mesothelioma

Sarcomatoid mesothelioma is the rarest and most challenging to treat variant of the disease’s three primary tumor cell types. Compared to epithelial and biphasic mesothelioma, it is also the most aggressive and resistant to treatment. Inhaling asbestos fibers causes mutations in mesothelial cells that can develop into sarcomatoid mesothelioma.

The term sarcomatoid is the general classification for sarcomatous, spindle or diffuse malignant fibrous mesothelioma. Sarcomatoid tumors can merge to form a sheet-like, fibrous mass on the pleural membrane.

Treating the spindle cell variant is more challenging than other types of mesothelioma because the tumor cells are resistant to therapy and quickly spread or metastasize to new areas.

Tumors with this cell type appear fibrous and diffuse throughout the pleura, the term for the pleural membrane surrounding the lungs and lining the chest cavity.

Facts About Sarcomatoid Mesothelioma

The characteristics of sarcomatoid cells make this variant of mesothelioma especially difficult to treat. Pathologists who specialize in mesothelioma are able to identify some of these rare cellular features when viewing tissue samples under a microscope.

• Spindle cells appear long, oval and spindle-shaped.
• The center, or nucleus, of sarcomatoid cells is often enlarged and elongated. Some cells may have more than one nucleus.
• Nearly all sarcomatoid mesotheliomas are pleural. There are fewer than 30 documented cases of sarcomatoid peritoneal mesothelioma.

Rare Sarcomatoid Mesothelioma Cell Subtypes

Epithelial, biphasic and sarcomatoid are the three major cell types of mesothelioma tumors. Within each variant, cells may have different characteristics that pathologists further classify into subtypes. There are three rare sarcomatoid mesothelioma cell subtypes.

Transitional Mesothelioma: This variant tends to grow and spread in ways similar to other sarcomatoid mesotheliomas. It has fat, spindle-shaped cells, which helps pathologists differentiate it from other cells.

Lymphohistiocytoid Mesothelioma: These tumors contain inflammatory and immune cells. The lymphohistiocytoid variant makes up less than 1% of all mesotheliomas. Some patients with this cancer have a better-than-average life expectancy.

Desmoplastic Mesothelioma: This sarcomatoid subtype is one of the most difficult to diagnose. Half or more of the tumor shows no discernible pattern of growth. Desmoplastic type accounts for approximately 5% of all mesotheliomas.

Signs And Symptoms of Sarcomatoid Mesothelioma

Because sarcomatoid mesothelioma is almost exclusively found in the pleural membrane, most patients experience nonspecific respiratory symptoms such as cough and shortness of breath. Common symptoms include:

• Shortness of breath
• Prolonged hoarseness
• Persistent cough
• Coughing up blood
• Low blood oxygen levels
• Anemia (low iron)
• Weight loss and weakness
• Chest pain or abdominal fullness
• Lack of appetite, anorexia and nausea
• Fatigue and extreme tiredness

Patients also commonly experience chest pain prior to diagnosis. As the disease progresses, symptoms become more serious. It’s important to speak with a specialist about any history of first or possible secondhand asbestos exposure and symptoms as early as possible.

Diagnosis of Sarcomatoid Mesothelioma

Mesothelioma is unfortunately often misdiagnosed because signs of the disease mimic other, less severe conditions.

A 2018 study described a new approach for a more accurate sarcomatoid malignant mesothelioma diagnosis. Tests for the BAP1 and MTAP genes were 100% accurate for distinguishing sarcomatoid mesothelioma from fibrous pleuritis.

However, since genetic testing for mesothelioma requires further clinical trials before widespread adoption, most doctors still favor traditional diagnostic methods.

Misdiagnosis Of Sarcomatoid Mesothelioma

Physicians inexperienced with sarcomatoid mesothelioma tend to misdiagnose the disease as other types of thoracic or lung cancer.

Seeking a second opinion from a mesothelioma specialty team is essential for sarcomatoid patients because this group will include pathologists skilled in this diagnosis.

Imaging Scans: As part of the initial diagnostic procedure, doctors rule out causes of ongoing symptoms using physical exams and in-office testing. Then, they will order imaging studies such as X-rays, CT scans or MRIs. These tests reveal abnormalities in the chest, but they do not show specific details such as cell type.

Biopsies: If your imaging studies suggest cancer, your doctor will refer you for a biopsy where a surgeon collects a small tumor sample for analysis and identification under a microscope. Depending on the type of biopsy, physicians can obtain tumor tissue samples using a needle under CT scan guidance or in an outpatient procedure with anesthesia.

Surgeons often use thoracoscopy or video-assisted thoracic surgery procedures to biopsy mesothelioma. These techniques result in high-quality tissue samples that can increase the chances of an accurate diagnosis.

Immunohistochemistry: Specific tests called immunohistochemistry reveal the cancer cell type and stage from a biopsy. Immunohistochemistry involves staining the cells using antibodies that attach to antigens on the tumor. This method indicates to pathologists whether the cancer is benign or malignant. These protein markers include calretinin, podoplanin, D2-40 and pan-cytokeratin.

Prognosis for Sarcomatoid Mesothelioma

Each patient’s prognosis differs based on the stage and location of the cancer and overall patient health. The median survival for patients with sarcomatoid tumors is typically less than six months without treatment. However, an early diagnosis and newer therapies available in clinical trials have allowed patients to live for a year or longer.

Sarcomatoid cells are notoriously resistant to treatment because of their fibrous nature. Current treatments, however, have helped several patients with the lymphohistiocytoid cell subtype survive for up to four years, and one documented patient remained alive without symptoms 12 years after his diagnosis.

It’s important to note that doctors use past data to make prognosis estimates. As treatment options improve and newer, cutting-edge therapies are employed, prognosis typically improves as well. Current survival rate statistics don’t take this most recent data into account.

Clinical trials offer the best chance at improving prognosis and are available at specialized centers. Patients interested in the newest available therapies should seek treatment at a specialty mesothelioma treatment facility.

Sarcomatoid Mesothelioma Treatment Options

The best mesothelioma treatment options for the sarcomatoid cell type include immunotherapy, chemotherapy, targeted therapy and radiation therapy. Patients should seek care from a mesothelioma specialist because sarcomatoid mesothelioma is harder to treat than the epithelioid or biphasic cell types.

Surgeons generally do not operate on patients with this type of mesothelioma because sarcomatoid cancer cells tend to return within a few months of the procedure.

There is currently no cure for sarcomatoid or any other variant of mesothelioma. Treatment can improve cancer symptoms, extend survival and increase quality of life for many patients.

Immunotherapy: Nivolumab and ipilimumab, also known by the brand names Opdivo and Yervoy, are part of an FDA-approved immunotherapy combination for mesothelioma, including the sarcomatoid cell type.

This drug combination has improved the median overall survival of patients by four months compared to those receiving chemotherapy. It became the new first-line treatment for inoperable mesothelioma in 2020.

Chemotherapy: If immunotherapy stops working, the standard chemotherapy for treating pleural sarcomatoid mesothelioma is a combination of pemetrexed (Alimta) plus cisplatin or carboplatin. This treatment regimen is also the standard chemotherapy for patients with any cell type of malignant pleural mesothelioma.

Targeted Therapy: AZD8186 is an experimental targeted therapy drug that is effective with some cancers when combined with other targeted drugs or chemotherapy. Research in mice suggests a combination of AZD8186 and the targeted drug selumetinib may be successful in patients with sarcomatoid malignant mesothelioma.

Radiation Therapy: Radiation therapy is not considered curative for mesothelioma, but for patients with painful tumors penetrating the chest wall it can reduce pain and improve quality of life.

Surgery: A 2020 study published in Translational Lung Cancer Research confirms surgeons do not operate on patients with sarcomatoid mesothelioma because sarcomatoid tumors recur quickly after surgery.

Sarcomatoid tumors are rigid, and they often spread over large areas and into the chest wall, which makes it challenging to remove all cancerous cells through surgery. Similarly, in the abdomen, peritoneal mesothelioma tumors can grow into or encase the soft internal organs.

Sarcomatoid cancer cells tend to return quickly, even after extensive surgery, because it is harder to remove sarcomatoid tumors compared to epithelioid tumors. Patients with epithelioid tumors may live for years after surgery, where sarcomatoid patients tend to live for only a few months. Surgeons do not consider a few months enough of a survival benefit to justify the risks of surgery.

Frequently Asked Questions (F.A.Q) About Sarcomatoid Mesothelioma

• Biphasic

  This is a combination of epithelioid and sarcomatoid cells. It’s less responsive to treatment. Prognosis and life expectancy depend on the ratio of both cell types. It accounts for 30% to 40% of cases.

Biphasic Mesothelioma

Biphasic mesothelioma is a cancer caused by asbestos exposure. Malignant biphasic tumors contain a combination of epithelioid and sarcomatoid cells. Symptoms of biphasic mesothelioma can include a dry cough, shortness of breath and pleural effusion. Biphasic mesothelioma is sometimes known as mixed mesothelioma.

Meaning Of Biphasic Mesothelioma

Mesothelioma is known as biphasic when tumors contain a combination of epithelial and sarcomatoid cells. Like all other cell types of mesothelioma, asbestos exposure is the leading cause of the disease.

The life expectancy of patients with biphasic mesothelioma varies because prognosis depends on the ratio of epithelial and sarcomatoid cells.

The larger the percentage of sarcomatoid cells, the poorer the prognosis. This cell type is more common among pleural patients than peritoneal patients.

Biphasic is the second most common mesothelioma cell type.

• Epithelial mesothelioma, also known as epithelioid, is the most common and the easiest to treat.
• The sarcomatoid cell type accounts for 10% to 20% of cases and is more resistant to treatment.
• Prognosis and life expectancy for biphasic mesothelioma depends on the ratio of epithelial and sarcomatoid cells.

Understanding the characteristics and diagnosis of this type of mesothelioma can help you make informed treatment decisions with your doctor. The study of these cells is known as mesothelioma histology.

Features of Biphasic Mesothelioma

In biphasic mesothelioma cases, epithelioid cells and sarcomatoid cells can exist close together. They can also appear within separate areas of a tumor.

Areas of epithelial cells, usually composed of solid and tubopapillary cells (which are epithelial subtypes), are found scattered among sarcomatoid cells. The proportion of epithelial and sarcomatoid cells can vary greatly.

Cell Behavior and Prevalence

Incidence rates show nearly 30% of pleural mesothelioma tumors and 25% of peritoneal tumors are biphasic.

However, many pathologists believe the cell prevalence of biphasic mesothelioma would be higher if more areas of mesothelioma tumors were sampled and analyzed. Pathologists are experts in the field of pathology, which is the study of diseased tissue to diagnose conditions such as cancer. The pathologist is the doctor who reviews biopsies.

The cell behavior of a biphasic mesothelioma depends on which cell type is more prevalent.

Diagnosis Of the Biphasic Cell Type

The biphasic cell type can be difficult to detect and diagnose.

However, a 2021 clinical research study discovered that membranous HEG1 staining had a specificity of 92.3% in distinguishing biphasic mesotheliomas from all carcinomas and 98.7% in distinguishing biphasic mesotheliomas from pulmonary carcinomas.

Mesothelioma cell types are important to detect because some clinical trials and treatments target specific cell types.

The characteristics of your cell type do not affect your symptoms. However, they may affect your life expectancy, according to a 2017 study published in Lung Cancer International.

On average, epithelial mesothelioma patients survive 200 days longer than the other types.

During a key diagnostic test called a biopsy, doctors may collect only a small sample of tissue to study in the lab.

Taking samples from just one location offers a limited view of the type and amount of mesothelioma cells involved.

Doctors can make a more accurate mesothelioma diagnosis by taking tissue samples from several parts of the tumor. Determining the specific cell type is important to the diagnostic process because it can affect your treatment options and prognosis.

Prevention Of Misdiagnosis

Doctors use advanced tests such as immunohistochemistry to distinguish biphasic mesothelioma from other diseases that are easily confused with this cancer. This technique can detect certain proteins, revealing the specific type of abnormal cells.

Fact:

The diagnostic process can be harder for biphasic patients since epithelioid and sarcomatoid cells must be detected.

With this information, doctors can rule out common misdiagnoses, including cancers such as synovial sarcoma and carcinosarcoma.

A 2011 study published in the Journal of Thoracic Oncology found the biphasic type can be misdiagnosed after a biopsy. A total of 83 patients in the study were confirmed to have this type of pleural cancer after undergoing an extensive surgical procedure called an extrapleural pneumonectomy.

However, only 26% of those patients had been originally diagnosed with this subtype. The authors explained biphasic mesothelioma can be more accurately diagnosed following surgery.

The initial diagnostic methods included thoracoscopy, thoracotomy, computerized tomography and other biopsy methods.

Biphasic Mesothelioma Treatment Options

Patients with the biphasic mesothelioma cell type may not be considered for an aggressive treatment plan as would patients with the epithelioid type.

The reason is that biphasic carries a slightly poorer prognosis than epithelioid. However, treatment is not completely based on cell type.

Most patients undergo one or more of these common therapies:

• Surgery
• Chemotherapy
• Radiation

Treatment may depend more on the stage and location of the tumor than the cell type involved.

Clinical trials are testing new drugs and therapies specifically for mesothelioma patients with sarcomatoid or biphasic tumors.

For example, a phase II/III clinical trial is investigating an anti-cancer enzyme on sarcomatoid and biphasic mesothelioma tumors. Known as ADI-PEG 20 (pegylated arginine deiminase), the enzyme significantly improved survival of sarcomatoid patients in its phase I trial.

Prognosis and Life Expectancy Of Biphasic

The prognosis for biphasic mesothelioma varies depending on the ratio of epithelial and sarcomatoid cells present in each case.

Fact:

The more epithelial cells you have in a biphasic mix, the better your prognosis may be. How much better may amount to only a few months depending on the case.

In one study involving 85 pleural mesothelioma patients with a variety of cellular subtypes, people with the biphasic cell type had an average survival of about 15 months. Those with the epithelial subtype displayed the highest average survival — more than 22 months.

The researchers observed slightly better survival among biphasic patients whose tumors had mostly epithelial cells, compared to those with mostly sarcomatoid cells.

While the survival advantage was only 16 days, sarcomatoid cells are less responsive to treatment than epithelial cells. As a result, biphasic patients with a lower number of sarcomatoid cells tend to see better results from treatment.

In another study, researchers observed the survival of 255 mesothelioma patients. Seventeen of the patients were diagnosed with desmoplastic mesothelioma, which is a cell subtype of sarcomatoid mesothelioma. Of those 17 patients, 11 had pure sarcomatoid tumors while six had biphasic tumors. Patients with pure sarcomatoid tumors survived 5.8 months and patients with biphasic tumors survived 6.8 months.

Epithelial cells in the biphasic tumors likely contributed to the one-month survival advantage observed in the biphasic patients.

The poorer prognosis may partially be influenced by PD-L1 levels. In a 2019 study published in Clinical Lung Cancer, pleural mesothelioma patients with sarcomatoid and biphasic cells had higher levels of PD-L1, which is associated with shorter survival.

Another factor contributing to the poorer prognosis of biphasic mesothelioma is that sarcomatoid cells tend to spread faster than epithelial cells.

Biphasic tumors with a high ratio of sarcomatoid cells may spread quicker and result in shorter life expectancy.

Methods Of Mesothelioma Diagnosis

Depending on the patient’s symptoms, doctors will order different tests to narrow down the cause. In some cases, imaging tests for another illness may reveal mesothelioma. In other cases, a known history of asbestos exposure may require a tissue sample, known as a biopsy.

There is no clear path to a mesothelioma cancer diagnosis for every patient.

Providing your doctor with a comprehensive work history is essential to the diagnostic process. Doctors are unlikely to suspect the disease unless a patient describes a job where asbestos exposure may have occurred. Usually, mesothelioma symptoms develop 20 to 50 years after the initial asbestos exposure.

Doctors diagnose more than 3,000 cases of mesothelioma every year. However, because mesothelioma is a rare disease with similar symptoms to more common and less severe conditions, doctors sometimes confuse it for a different illness or another type of cancer.

Initial misdiagnosis is common for mesothelioma patients. Doctors often misdiagnose pleural mesothelioma as pneumonia or lung cancer. Peritoneal mesothelioma can appear similar to more common abdominal cancers. A mesothelioma specialist makes an accurate diagnosis by using imaging scans, biopsy results and other tests.

Steps Taken In Mesothelioma Diagnosis

Not every patient will need all these tests, but the process from symptoms to a final diagnosis is generally similar for most mesothelioma patients.

The symptoms of mesothelioma are vague, and seeking a diagnosis is often a multistep process. Coughing and shortness of breath are signs of pleural mesothelioma, while abdominal pain or digestive issues may signify peritoneal disease.

Patients with a known history of asbestos exposure are likely to receive a quicker referral to a mesothelioma specialist from the primary care physician. Accurately reporting your medical history, work history and symptoms to your doctor are essential in receiving mesothelioma tests that will lead to a diagnosis.

General physicians and oncologists are responsible for confirming a diagnosis before starting treatment for a disease. Treatment for mesothelioma cannot begin until radiology and biopsy results have solidified an accurate diagnosis.

Tests for Mesothelioma

The first step toward getting tested and diagnosed for mesothelioma involves speaking with your primary doctor about your symptoms, health history and asbestos exposure.

If you have symptoms of mesothelioma, your doctor will conduct a physical exam to check for any unusual signs. Mesothelioma testing commonly includes imaging scans, such as MRI and CT scans, to identify malignant tumors. A biopsy, such as pleural aspiration or thoracoscopy, is the only definitive way to confirm a mesothelioma diagnosis.

Doctors also use mesothelioma blood tests to measure treatment response.

Physical Exam and Medical History

Mesothelioma is rare and difficult to diagnose. The more details your doctor has about your medical history, symptoms and asbestos exposure, the more informed they will be when ordering mesothelioma tests.

During a physical exam, your provider may use specific tools or devices to look for signs of disease throughout the body.

Imaging Tests

Radiologists use imaging tests to reveal the location and size of mesothelioma tumors. These scans are precise and detailed enough to determine the extent and stage of cancer, such as whether it has entered lymph nodes or other organs. The “gold standard” for mesothelioma imaging is a combination PET-CT scan with contrast dye.

Scans that use contrast dye, such as PET or MRI, involve oral contrast that the patient drinks before the exam or IV contrast injected through a vein. Imaging tests are painless, and many take only minutes. An MRI can take 30 to 90 minutes and may cause anxiety in some patients due to the small space and loud noise.

X-Rays

X-rays use radiation to produce basic images of areas within the body that show various densities, such as tumors or fluid. During an X-ray, the technician instructs the patient to hold a position and then takes several pictures. Contrast dye may or may not be involved.

Doctors use X-ray results to identify mesothelioma signs such as fluid buildup. This can include pleural effusion in the chest, pericardial effusion surrounding the heart or peritoneal effusion in the abdomen.

CT Scans

Computerized axial tomography, or CAT scans, use computer software to integrate hundreds of fine X-ray images into highly defined pictures. These images of internal structures are much more precise than regular X-rays but also require more radiation.

The process is like undergoing an X-ray but utilizes a much larger machine, and contrast may or may not be necessary for patients. The improved detail of a CT scan helps doctors identify smaller areas of tissue affected by cancer, making it easier to evaluate the cancer stage.

MRIs 

Magnetic resonance imaging, or MRI, uses electromagnetic technology instead of radiation. MRIs generate precise images that are especially useful when looking at bone, nerve and brain tissue. This kind of scan helps doctors visualize which types of tissues are affected by mesothelioma and whether metastasis or spreading has occurred.

The MRI patient lies on their back inside a narrow tube while a large magnet rotates inside the device. The process takes an average of 30 to 90 minutes, and contrast dye is optional. For patients with claustrophobia or anxiety, doctors may prescribe a one-time anti-anxiety medication.

PET-CT

Positron emission tomography, or PET, involves an intravenous dose of a unique radioactive glucose dye, making inflamed cells light up during CT scans. As cells metabolize or eat the glucose due to infection or rapid growth, they cause inflammation, a sign of cancer that appears in detail on a PET-CT.

For the patient, the process is identical to a CT scan. For doctors, the improved contrast identifies areas within a tumor with the highest density of new growth. This information tells physicians how quickly the cancer is growing and where to target treatment.

Mesothelioma Blood Tests and Biomarkers

Some blood tests, such as MESOMARK and SOMAmer, can detect signs of mesothelioma. However, mesothelioma blood tests, biomarkers and immunohistochemical markers are not accurate enough to confirm a diagnosis alone. Doctors use these tests to rule out other disorders and monitor response to treatment.

Blood tests work by detecting mesothelin, a protein found in healthy patients, which circulates at higher blood levels when mesothelioma is present. For example, the FDA-approved MESOMARK test can detect soluble mesothelin-related peptides known as SMRPs.

The SOMAmer test can detect more than 1,000 proteins in blood serum. These proteins may have diagnostic value in identifying mesothelioma. Another test known as Human MPF measures a protein called megakaryocyte potentiation factor. These tests have different rates of accuracy judged by sensitivity and specificity.

In testing, the SOMAmer mesothelioma blood test correctly diagnosed 90% of patients. This sensitivity is important because for a blood test to be practical, it must accurately predict disease reliably.

Mesothelioma blood tests also undergo specificity testing. For example, MESOMARK accurately predicted that 92% of healthy patients did not have mesothelioma. Unfortunately, these results are not high enough for blood tests to definitively predict or diagnose mesothelioma. However, research is ongoing to develop blood tests with higher sensitivity and specificity.

Mesothelioma Biopsies

Biopsies are the only way to confirm a mesothelioma diagnosis. These tissue samples inform doctors of cancer cell type and stage, helping them develop a more precise treatment plan. The most accurate biopsy technique for mesothelioma is called a thoracoscopy. The process differs for each type of biopsy, but doctors provide anesthesia to reduce pain.

Approximately 98% of biopsies are definitive in diagnosing mesothelioma. The type of biopsy depends on cancer location and patient tolerance. Although less accurate, the surgeon may perform a fine needle aspiration or liquid biopsy, also known as a cytology test, for tumor tissue that is difficult to biopsy.

In a cytology test, the doctor removes fluid from the suspected tumor site. A pathologist then looks at the liquid under a microscope to search for cancer cells. For solid tissue samples, a doctor removes a piece of the suspected tumor during a biopsy. Then, a pathologist looks at it under a microscope to determine cancer cell type and characteristics.

Thoracoscopy

Patients are under general anesthesia during a thoracoscopy. The surgeon inserts a small camera between the ribs to examine the appearance of the chest cavity. The scoped camera, called a thoracoscope, also suctions out excess fluid and collects small tissue samples as biopsies.

Thoracoscopies are the most accurate mesothelioma biopsy because they collect solid tissue samples directly from the primary tumor. Patients are asleep during the 45- to 90-minute procedure, and recovery takes about two weeks. The main risk with thoracoscopy is pneumonia.

Mediastinoscopy

Doctors perform a mediastinoscopy to determine if cancer is present in the central chest region, called the mediastinum. The patient is under general anesthesia during the procedure. The surgeon inserts a tiny camera at the base of the neck to obtain biopsies of the lymph nodes around the windpipe.

Like thoracoscopy, the scope device allows the surgeon to visually examine the area while removing excess fluid and collecting biopsy samples. Doctors use these samples to determine cancer stage based on the cancer’s extent within the lymph nodes. Greater lymph node involvement indicates a higher likelihood of metastasis.

Thoracentesis

Thoracentesis requires only local anesthesia and is less invasive than thoracoscopy or mediastinoscopy. Doctors perform this procedure using an ultrasound probe for guidance, and the process takes roughly 15 minutes.

The physician inserts a small needle between the ribs in the back or side to remove pleural fluid buildup around the lungs. Thoracentesis helps diagnose the cause of pleural effusions, but biopsy samples from this technique are of lower quality.

Fine-Needle Aspiration

Like thoracentesis, fine-needle aspiration involves a small needle inserted between the ribs. However, compared to thoracentesis, the objective of FNA is to sample or biopsy tumors while the patient is in the CT scan machine.

While not as accurate as a solid tissue biopsy, FNA can rule out other illnesses and confirm a mesothelioma diagnosis along with positive radiology imaging such as a PET-CT scan.

Endobronchial Ultrasound-Guided Biopsy

In a 2016 study, researchers used endobronchial ultrasound to guide biopsies and diagnose pleural mesothelioma when other biopsy techniques couldn’t obtain a tumor sample. This method uses a bronchoscope to examine the bronchi, the airways in the upper respiratory tract.

Doctors combine transbronchial needle aspiration with endobronchial ultrasound to obtain tissue samples from the thoracic region. The process is similar to fine-needle aspiration, and the biopsies have a high level of diagnostic accuracy.

Preparation Of Mesothelioma Diagnostic Appointments

Preparing for a mesothelioma test such as a biopsy or imaging scan involves several steps, depending on the procedure. Your provider will detail dietary restrictions leading up to the day of your diagnostic appointment.

You should also verify how and when to check your results. Some results, such as a mesothelioma biopsy, may take one to two weeks, whereas blood test results may be available immediately.

Preparation Of A Biopsy

Timeline Leading Up to a Diagnosis

The diagnostic process is different for everyone depending on health status, asbestos exposure history and more. A potential diagnostic timeline can help explain how long it may take to receive a diagnosis after experiencing the first symptoms of mesothelioma.

Not everyone goes through the same diagnostic steps, or even in the same order. However, once you receive a mesothelioma diagnosis, this timeline can help you understand your treatment plan.