What Are the Different Types of Mesothelioma Cells?

There are three major mesothelioma cell types.

  • Epithelioid: As the most common kind of mesothelioma cell type, it accounts for between 50% and 70% of all mesothelioma cases. Epithelioid is the most responsive to treatment and has a better prognosis than other cell types.
  • Sarcomatoid: This rare type of mesothelioma cell is spindle-shaped and has a poor prognosis.
  • Biphasic: This cell type is a combination of epithelioid and sarcomatoid cells. Treatment options and prognosis depend on the ratio of each cell type present.

These cell types differ based on how they look under a microscope. They also differ in how they grow and form cancerous tumors in the body.

There are many rare cellular subtypes besides the three main mesothelioma cell categories. These are rare variances in histological mesothelioma types.

In addition to cell type, the type of mesothelioma is designated by the location of the tumor. The four types of mesothelioma defined by tumor location are pleural, peritoneal, pericardial and testicular.

Pleural mesothelioma occurs in the chest cavity lining. Peritoneal disease is found in the lining of the abdominal cavity. Pericardial tumors form in the lining around the heart, and testicular mesothelioma occurs in the lining around the testes.

Using tumor location and mesothelioma cell type, doctors can designate key details about a patient’s tumor. For example, a person can have a peritoneal tumor of epithelial cell type or a pleural cancer composed of sarcomatoid cells.

Facts About Mesothelioma Cells

  • Tumors are classified into three main cell types.
  • Epithelial cells are more common and easier to treat.
  • Sarcomatoid cells are rare and harder to treat.
  • Doctors identify the cell type by studying tissue samples of the cancer.

Each cell type responds to treatment in a different way. The cell type also affects prognosis. After a mesothelioma diagnosis, your doctor will study your mesothelioma pathology report. This helps them to understand the details of your cancer cell type.

This information is critical. Mesothelioma testing of the cell type is necessary to develop a useful treatment plan.

A 2021 research study suggests the use of electron microscopy for a more accurate diagnosis of mesothelioma.

What Is Mesothelioma Histology?

Mesothelioma histology is the study of cancerous mesothelial cells.

Histology is a branch of biology that studies cells and tissues. Histopathology is the study of diseased cells. This study falls within the larger field of pathology.

A pathologist uses histology to provide accurate details about your cancer cell type. There are only a small number of mesothelioma pathologists.

These specialists use microscopes to view cells up close. They prepare samples of tissue with chemical stains. The stains make the cells’ features stand out.

Histology also helps prevent misdiagnosis. Studying the cell type helps doctors tell the difference. For example, peritoneal mesothelioma and ovarian cancer can be challenging to distinguish.

Cell Types of Malignant Mesothelioma

Pathologists look for three types of cells. These include epithelial, sarcomatoid and biphasic. Each cell type looks different.

Epithelial cells
A pathology stain showing epithelial mesothelioma cells under a microscope.

Epithelial Cells

These mesothelioma cells are uniform, sharply defined and square to tubular in configuration. They feature prominent nuclei and divide quickly but tend to stick together. This means it takes longer for them to spread throughout the body. The epithelial cell type accounts for more than 50% of all mesothelioma cases and up to 70% of cases.

Treatment: Epithelial cell mesothelioma typically is the most responsive to treatment. This can lead to a better prognosis.

Sarcomatoid Cells

Spindle-shaped sarcomatoid cells lack defining structure and have an irregular configuration. They spread faster than epithelial cells because they don’t tend to stick together as they grow. This rare cell type makes up 10% to 20% of cases.

Treatment: Because sarcomatoid cell mesothelioma is more aggressive and more likely to be diagnosed at an advanced stage than epithelial type, this cancer often has fewer treatment options. It forms less clear-cut tumor boundaries and is harder to treat surgically.

Biphasic mesothelioma cells
A pathology stain showing biphasic mesothelioma cells under a microscope.

Biphasic Cells

Malignant mesothelioma is biphasic when it contains epithelial and sarcomatoid cells. This mixed cell type accounts for 20% to 30% of mesothelioma cases. Each cell type must account for at least 10% of the tumor mass to receive a biphasic diagnosis.

Treatment: Treatment options are better and life expectancy is longer if there are more epithelial cells and fewer sarcomatoid cells. Treatment options can include surgery, chemotherapy and radiation.

Each cell type has different visible traits when seen under a microscope. For example, sarcomatoid cells have long nuclei. Epithelial cells have microvilli. These are microscopic protrusions of the cell. They also have clear structures called organelles within each cell.

Doctors use these features to confirm the diagnosis. They can use this information and cancer staging to estimate prognosis and develop a treatment plan.

Each cell type responds differently to treatment.

  • Epithelial cells typically are the most responsive to treatment, which often leads to a better prognosis.
  • Sarcomatoid cells are the least responsive to treatment. Some mesothelioma specialists do not consider sarcomatoid tumors eligible for surgical removal.
  • Biphasic cell type contains some sarcomatoid cells and also may be considered less treatment responsive than epithelial cell type. The exact prognosis depends on the ratio of epithelial to sarcomatoid cells. More epithelial and fewer sarcomatoid is associated with a better prognosis.

The appearance of the different cell types is subtle. Only the most experienced pathologists can tell the difference. This can make a diagnosis quite tricky. For example, discerning mesothelioma cells from adenocarcinoma cells can be a challenge.

Rare Variances in Histological Mesothelioma Types

Some rare mesothelioma cells can be histologically classified with more detail than the three major cell classifications of epithelial, sarcomatoid and biphasic.

Adenomatoid

In this variant of epithelial mesothelioma, the cells line small, gland-like structures. This type is also called glandular or microglandular mesothelioma.

Benign

Benign mesothelioma is neither cancerous nor the result of asbestos exposure.

Cystic

This type has smooth, thin-walled cysts held together by fragile fibrovascular tissue. It is a subtype of epithelial mesothelioma.

Deciduoid

The term deciduoid reflects this unusual epithelial cell subtype’s histological resemblance to cell changes occurring in early pregnancy. It most commonly affects young women.

Desmoplastic

In this form of sarcomatoid mesothelioma, more than 50% of the tumor is made of dense, fibrous tissue.

Heterologous

Tumors of heterologous cell type contain bodily tissues different from the tissues in which they form. Only a handful of cases are documented in the medical literature.

Lymphohistiocytoid

This subtype of sarcomatoid mesothelioma is often misdiagnosed. It is made up of a dense bundle of inflammatory and immune cells.

Papillary

This variant of epithelial mesothelioma resembles healthy cells that grow and multiply at a slow rate. It does not typically spread to other parts of the body.

Small Cell

This type occurs when a large proportion of a mesothelioma tumor comprises small cells that grow in a pattern similar to small-cell carcinoma.

The Histology Process

The histology process starts with the surgeon who takes the biopsy. A technician transfers the tissue from the biopsy onto a slide for a microscope. The pathologist then works to identify cancer cells.

Histology Process

Histology Steps to Determine Mesothelioma Cell Type

A surgeon removes tumor tissue during a biopsy. In the lab, a technician fixes, embeds, sections and mounts the cells on a slide. Then, chemical stains reveal the appearance of the cells for a pathologist to identify.

Quick Fact:
“Frozen section fixation” is used to diagnose cancer during surgery. Small sections of the tumor are removed and quickly frozen while the patient is still in surgery. A slice of the frozen tissue is then stained and placed on a slide for a rapid assessment by a pathologist to determine if a tumor is malignant.

Once the technician mounts and stains the biopsy cells on a slide, the sample is ready to view under a microscope. The pathologist notes the cells’ size, shape and structure to identify the tumor’s cell type.

Additional Lab Processes to Support Histology Cell Studies

Pathologists use other techniques to learn more about cells. These techniques include in situ hybridization and immunohistochemistry.

In situ hybridization

In situ hybridization uses fluorescent or radioactive probes to bind DNA and RNA. Using this method, scientists can analyze the genes of a cell. They can also detect genetic abnormalities.

Immunohistochemistry

Immunohistochemistry is based on the principle that antibodies bind to specific antigens. Antibodies also bind to cancer cell proteins called oncoproteins.

Different antibodies are applied to tissues on a microscope slide depending on the suspected cancer type. Visual patterns are created by the interaction of antibodies and oncoproteins. These patterns help pathologists diagnose mesothelioma.

Common Immunohistochemical Markers for Mesothelioma

  • Cytokeratin 5 and 6
  • Calretinin
  • WT-1 protein
  • Podoplanin (D2-40)

Immunohistochemistry is regularly used in conjunction with other diagnostic procedures, including mesothelioma histology, to provide the most accurate diagnosis of mesothelioma.

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Why Is Mesothelioma Pathology Important?

The results of pathology and cytology testing play a major role in confirming a mesothelioma diagnosis. This helps doctors determine the best treatment plans.  

The pathology report is the most crucial component in a mesothelioma diagnosis. It provides the definitive cancer diagnosis, describing the specific types of cells found in a patient’s tumors.  

Doctors tend to recommend more aggressive treatment for patients with epithelial cells because they typically respond better to treatment than patients with sarcomatoid cells. Doctors also consider other factors when developing treatment plans. These factors include the stage of the cancer’s progression and the patient’s age, gender and overall health.