Diagnosing Mesothelioma By Cytology

Pathologists can diagnose mesothelioma by examining fluid samples for mesothelioma cells. If an oncologist or specialist suspects mesothelioma or other forms of cancer, he or she may request the procedure to confirm the diagnosis. Cytology is often one of the first tests used in the diagnosis of mesothelioma after imaging tests reveal the possibility of cancer.

Written and Fact-Checked by: Mesothelioma Hope Team

What Is Cytology?

Cytology or fluid biopsy is a pathology specialty, which studies disease by looking at the appearance and behavior of cells in bodily fluids.

Cytopathology was first recognized as a specialty field by the American Board of Examination in 1989, and it has become a respected means of diagnosing disease and cancer, including mesothelioma.

The fluids tested for mesothelioma come from the pleural space between the lung and chest or the heart sac, as this is where mesothelioma and other cancer cells often accumulate. The location of the cells collected determines whether the procedure is called a thoracentesis or pericardiocentesis.

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Difference Between Cytology and Histology

Some experts have criticized cytology as less effective than histology, questioning whether it should be used for mesothelioma diagnosis. However, more recent research has determined the two diagnostic procedures to be complementary: cytology is less invasive and therefore recommended as the first test for mesothelioma, with biopsy recommended if the cytology results are inconclusive.

In fact, cytology is often the preferred method of diagnosing mesothelioma because it’s:

  • Easier to obtain
  • Relatively comfortable
  • Has low complication risk
  • Less expensive
  • Faster results

Cytology and histology are both forms of pathology, and they follow a similar process. Both require samples to be collected and then sent to a lab so that a pathologist can review the cells. The main difference between cytology and histology is the type of biopsy that is performed.

Histology uses tumors and tissue samples, which are typically comprised of cells clumped together. By contrast, cytology uses fluid samples. While fluids contain cells too, they aren’t as concentrated as they are in tumor samples, which can make them more challenging to identify. If the cell sample size isn’t large enough, a definitive diagnosis can’t be obtained.

Mesothelioma specialists tend to have the best results when drawing cytology samples, as they know exactly which parts of the body are most likely to collect mesothelioma cells. Patients who suspect a mesothelioma diagnosis should, therefore, seek out the help and expertise of a qualified mesothelioma specialist.

Cytology Process for Diagnosing Mesothelioma

The cytology process used in diagnosing mesothelioma is fairly straightforward, and test results are often available within one to two days of collection.

Once sample cells are collected from a patient, they are sent to a laboratory for review. A cytologist will review the fluid and take note of the cells, identifying their characteristics and eventually diagnosing the cell types.

Cytologists place fluid samples onto slides, called smears, and then use a collection of dyes to help reveal the cells contained within the smear. They will then examine the smear under a microscope, looking at the composition of the cells, and also noting how the cells interact with the various dyes.

Cytologists are typically looking at the cell’s shape and size, and will also compare samples to existing reference slides or databases. This process can take hours but being able to compare live cells helps cytologists determine whether a patient has mesothelioma.

Cytology is often preferred as the first line of diagnostic testing, but additional tests may be needed to confirm a mesothelioma diagnosis. If a cytologist suspects mesothelioma, doctors will typically order a tissue biopsy to corroborate the diagnosis.

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Looking for Mesothelioma Cells

There are three types of mesothelioma cells that can be diagnosed:

  1. Epitheliod: The most common mesothelioma cell type.
  2. Sarcomatoid: A Highly aggressive form of mesothelioma.
  3. Biphasic: Combination of epithelioid and sarcomatoid cells.

These cell types are what determine the overall type of diagnosis and directly impact a patient’s prognosis and treatment options.

Mesothelioma Cells Update

Each cell type has its own characteristics and looks quite different from one another. Even the way they clump together differs between the types of cells. Fortunately, many cytologists are familiar with the contrasting characteristics of mesothelioma and can still make an accurate diagnosis.

Epithelioid Cells

The most common mesothelioma cell type, epithelioid cells are recognized by cytologists because of their uniform and defined appearance. They contain a single nucleus and tend to grow slower than other cancerous cell types. While epithelial cells multiply quickly, they have a tendency to lump together, which makes their overall tumor growth relatively slow. Patients diagnosed with epithelioid mesothelioma tend to have the best prognosis.

Sarcomatoid Cells

Sarcomatoid cells are spindly in shape, with fibrous-looking groups of cells. They sometimes have more than one nucleus and don’t form large clumps in the same manner as epithelioid cells; instead, sarcomatoid cell groups tend to be smaller nodules, spreading through the body with greater mobility. Because of its ability to spread rapidly, sarcomatoid mesothelioma is a highly aggressive form and tends to have the worst prognosis.

Biphasic Cells

Biphasic cells are a combination of epithelioid cells and sarcomatoid cells. Mesothelioma patients are actually more likely to have biphasic cells than just sarcomatoid cells, making it the second most common type of mesothelioma. The prognosis of the patient typically depends on the percentage of epithelioid cells versus sarcomatoid cells, with higher concentrations of epithelioid cells having the best outcomes.

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Procedures Used To Collect Cytology Samples

Cytology studies fluid samples, which are first collected from a patient. Doctors usually collect fluid samples with a needle through one of two procedures, depending on the location of the fluid within the patient’s body.


Thoracentesis is the procedure used to collect fluid from the lungs and can help diagnose pleural and peritoneal mesothelioma. Thoracentesis specifically targets the open space between a patient’s chest and the lining of their lungs, where people naturally build up about four tablespoons of lung fluid. For most patients, the procedure is a quick one and only takes 10 to 15 minutes. However, if a lot of fluid has built up and caused a pleural effusion, the thoracentesis procedure can take longer.


A pericardiocentesis is the procedure used to collect fluid samples from the sac around a patient’s heart and may be used to diagnose pericardial mesothelioma. During a pericardiocentesis, a needle is placed into the space between the two thin layers outside the heart, where fluid naturally exists. A pericardiocentesis may also be used to remove any extra fluid that has built up between these layers, called pericardial effusion. The pericardiocentesis procedure takes approximately one hour.

Challenges of Cytology

Pathology has advanced significantly over the past couple of decades, but there are still challenges when using cells to identify mesothelioma. Because cells mutate in different ways, and at different rates, even the same types of mesothelioma cells can look very different between patients. Cytologists have to learn what various stages of mutation look like and have a strong understanding of the variation between cells.

In addition, cytologists have to differentiate between many types of cancer that all have similar-looking cells. Malignant mesothelioma and adenocarcinoma are two different forms of cancer that present similarly in patients and can be confused by cytopathologists. While cytologists are getting better at diagnosing mesothelioma, there are still margins of error and misdiagnosis does occasionally occur. Patients who suspect a misdiagnosis should request a second opinion or a histology test.

Did you know? Patients diagnosed with mesothelioma are often eligible for financial compensation. Talk to our Patient Advocates today to find out more.

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Mesothelioma Hope was founded by a team of passionate health advocates to educate people about this aggressive form of cancer. Mesothelioma affects thousands of people each year. Our team works tirelessly to give hope to those impacted by mesothelioma. Learn more about operating principles and our Editorial Guidelines.

5 References
  1. Acta Cytologica. “Guidelines for the Cytopathologic Diagnosis of Epithelioid and Mixed-Type Malignant Mesothelioma.” Retrieved from https://www.karger.com/Article/FullText/377697. Accessed on January 10, 2018.

  2. American Cancer Society. “Types of cytology tests used to look for cancer.” Retrieved from https://www.cancer.org/treatment/understanding-your-diagnosis/tests/testing-biopsy-and-cytology-specimens-for-cancer/cytology-types.html. Accessed on January 10, 2018.

  3. American Cancer Society. “What happens to biopsy and cytology specimens?” Retrieved from https://www.cancer.org/treatment/understanding-your-diagnosis/tests/testing-biopsy-and-cytology-specimens-for-cancer/what-happens-to-specimens.html. Accessed on January 14, 2018.

  4. Johns Hopkins Medicine. “Thoracentesis.” Retrieved from https://www.hopkinsmedicine.org/healthlibrary/test_procedures/pulmonary/thoracentesis_92,P07761. Accessed on January 10, 2018.

  5. Johns Hopkins Medicine. “Pericardiocentesis.” Retrieved from https://www.hopkinsmedicine.org/healthlibrary/test_procedures/cardiovascular/pericardiocentesis_135,361. Accessed on January 10, 2018.

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