Mesothelioma Histology

Cancer specialists can uncover important microscopic features of your disease with the science of histology. These features play an important role in diagnosis, treatment and your life expectancy.

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Histology is a branch of biology and medicine that involves the study of the cells and tissues of animals and plants. Samples of tissue are stained on a slide and observed under a microscope to study the structure and composition of each cell. Because mesothelioma histology involves the study of cancerous mesothelial cells, it is considered a branch of histopathology, which is the study of diseased cells. Trained medical doctors, usually board-certified pathologists, examine the tumor tissue under a microscope and classify cells by type.

Histopathology is within the larger field of pathology, which studies the nature, cause and effect of diseases. Pathologists are highly trained medical professionals who examine tissue samples to get an accurate diagnosis, and they’re assisted by histotechnicians and histopathologists, who help with tissue staining to identify diseased cells.

There are several types of mesothelioma cancer cells. Each cellular type responds to different treatments and affects the individual patient's prognosis, so an accurate diagnosis of cancer cell type is essential to develop an effective treatment plan. After treatment is administered, studying tissue samples can also provide insight on the effectiveness of chemotherapy drugs and other treatments.

Histology also helps prevent mesothelioma misdiagnosis. For example, peritoneal cancer in women and ovarian cancer can be difficult to differentiate without analyzing the cell type through histopathology. If patients are pursuing legal action against an asbestos-producing company that may have caused their cancer, a misdiagnosis can also negatively affect their chances of obtaining compensation.

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Cell Types

Cell Types

When specifically examining a tumor sample for the presence of mesothelioma, a histopathologist will carefully inspect the sample for three types of cells:

Epithelial Cells

Epithelial cells appear most often in these tumors, and this subtype accounts for 50 to 70 percent of all cases. These cells, which are uniform and sharply defined, feature prominent nuclei and often form complex branching patterns.

Sarcomatoid Cells

These spindle-shaped sarcomatoid cells typically lack strong characteristics and occur in approximately 10 to 20 percent of reported cases. While they are the most aggressive cell type, they are also the least common.

Biphasic Cells

Malignant mesothelioma is considered biphasic when both epithelial and sarcomatoid cells are present and each type accounts for at least 10 percent of the tumor's mass. Biphasic (mixed) cells are present in 20 to 35 percent of all mesothelioma cases.

Dr. Fontaine explains how the mesothelioma cell type affects a patient's treatment options.

Doctors use these histological classifications to develop a prognosis and treatment plan for patients. Although the life span associated with mesothelioma can be short, your cell type can account for differences in life expectancy ranging up to 200 days.

Cell Types

Of all subtypes, tumors involving epithelial cells are typically most responsive to treatment, which often leads to a better prognosis. Because sarcomatoid cells are the most resistant to treatment, some surgeons do not consider sarcomatoid tumors eligible for surgery. The biphasic cell type is also considered less responsive to treatment than epithelial.

Diagnosing a patient's specific type of cancer can be challenging for doctors. One common obstacle is differentiating mesothelioma from adenocarcinoma, the most common form of lung cancer among non- smokers.

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Characteristics of Malignant Mesothelioma Cells

Each specific cell type has different visible characteristics. For example, sarcomatoid cells have elongated nuclei, while epithelial cells are most commonly distinguished by the identification of microvilli (microscopic protrusions of a cell) or cell organelle.

The characteristics noted in the different cell types are very subtle. Unfortunately, this can make the diagnosis process quite challenging. Specifically, distinguishing mesothelioma cells from adenocarcinoma cells, a cancer that affects glandular tissue, can be a serious challenge because the cells can appear similar.

Fast Fact: Frozen section fixation is a histology process where a surgically removed tumor is quickly frozen. A slice of the frozen tissue is stained and placed on a slide to determine if a tumor is malignant, usually while the patient is still in surgery.

Rare Variances in Histological Mesothelioma Types

  • Deciduoid Mesothelioma

    A rare variant of epithelial mesothelioma, this cell type has been diagnosed in approximately 45 cases. Roughly half of these cases originate in either the pleura or the peritoneum.

  • Desmoplastic Mesothelioma

    A form of sarcomatoid mesothelioma, the framework of these cells is more than 50 percent collagenized, or made up of fibrous tissue that produces collagen.

  • Lymphohistiocytoid Mesothelioma

    This cell type is a rare and often misdiagnosed variant of sarcomatoid mesothelioma that contains histiocyte-like dense lymphocytic infiltrates.

  • Small Cell Mesothelioma

    A rare variant, this cell type occurs when at least 50 percent of desmoplastic cells are formed by small cells.

Additional histological variances include adenoid cystic, tubulopapillary, glandular, histiocytoid, microcystic, macrocystic, signet ring, single file; diffuse, not otherwise specified (NOS), glomeruloid, poorly differentiated (large cell) or pleomorphic, mucin positive, gaucher cell-like, in situ and well-differentiated papillary.

The Histology Process

Before a diagnosis of cell type is made, tissue samples are obtained and prepared for study. Teams made up of surgeons, histotechnicians, histopathologists and other professionals work together to provide a patient's doctor with information.

When testing for mesothelioma, a medical test involving the removal and examination of cells, tissue or fluids from the body, known as a biopsy, is often performed. After the biopsy, the tissue is prepared by specialists called histotechnicians. These scientists process the tissue by preserving it and staining it with a number of special chemicals that will reveal the minute structures of the cells. They also observe the size, shape and anatomical structure of cells, which helps identify the cell type.

How Histotechnicians Prepare a Tissue Sample for Staining

  • Fixing

    Makes the tissue more rigid and allows for easier slicing. The tissue is placed in a chemical like formaldehyde.

  • Sectioning

    Takes place in a machine called a microtome. The microtome can slice extremely thin pieces of the sample.

  • Embedding

    The tissue is embedded in a block of paraffin or plastic resin to make the material easy to cut.

  • Mounting

    After the slices of embedded tissue are smoothed out in a water bath, they are placed on slides and baked to set the paraffin.

After the cancerous tissue is mounted and stained on a slide, the specimen is now ready for study. Then, histopathologists take the slide and view it under a microscope. They can determine what type of cancer may be present by viewing the structure of cells in the tissue.

In addition to staining, histotechnicians may choose to use different techniques for highlighting the details in cells that may be of interest, such as in situ hybridization and immunohistochemistry. In situ hybridization uses the application of fluorescent or radioactive probes to bind DNA and RNA and analyze the genes of a cell. Using this method, scientists can detect genetic abnormalities present in the cells.

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Immunohistochemistry

Immunohistochemistry is based on the principle that antibodies bind to specific antigens and proteins called oncoproteins in human tissue. Different antibodies are applied to tissues on a microscope slide. The tissue samples are then analyzed for specific visual patterns created by the interaction of antibodies and proteins.

Immunohistochemical Staining

Immunohistochemical staining is widely used in the diagnosis of mesothelioma cells and other abnormal cells. However, many medical experts say that immunohistochemistry should be used in context with other diagnostic data. In other words, the results of an immunohistochemistry analysis should not be considered the primary indicator for a mesothelioma diagnosis.

Immunohistochemical Staining
Immunohistochemical Diagnosis

However, other studies have found that immunohistochemical stains improve the accuracy of diagnosis. In one Japanese study, it was estimated that 10 to 15 percent of patients received an inadequate diagnosis. Since many patients require this diagnosis for legal action, the study recommended improving current diagnostic techniques by improving the quality of immunohistochemistry stains.

BerEP4

Two antibodies often used to aid in diagnosis are BerEP4 and vimentin. BerEP4 is helpful in the diagnosis of epithelial mesotheliomas. However, immunohistochemists are still researching the efficacy of BerEP4 as a diagnostic indicator, because this antibody has appeared both in mesotheliomas and other similar tumors.

BerEP4
Vimentin

Like the antibody BerEP4, vimentin helps diagnose mesothelioma, but the protein also appears in other tumors. Because vimentin appears in other malignant tumors, it is not considered a discriminatory marker for mesothelioma, but rather a piece of the diagnostic puzzle.

Additional Resources


Karen Selby is a registered nurse and a Patient Advocate at The Mesothelioma Center. She worked in several subspecialties within nursing before joining Asbestos.com in 2009.

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