Mesothelioma Cells

Cancer specialists can identify important microscopic features of mesothelioma cells through the science of histology. The cell type of mesothelioma plays an important role in determining a patient’s diagnosis, treatment options and prognosis.

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

Histology is a branch of biology that involves the study of cells and tissues. Specialists prepare samples of tissue with chemical stains that make tissue structures and cellular features stand out when viewed under a microscope.

Because mesothelioma histology involves the study of cancerous mesothelial cells, it is considered a branch of histopathology, the study of diseased cells. Histopathology falls within the larger field of pathology.

Specially trained medical doctors, usually board-certified pathologists, examine samples of tumor tissue under a microscope to classify cancer cells by type. Histotechnicians and histopathologists help with tissue staining, which is what makes close-up photos of cells often appear pink and purple.

Mesothelioma Cell Facts

  • Tumors are classified into three main cell types
  • Epithelial cells are more common and easier to treat
  • Sarcomatoid and biphasic cells are rare and harder to treat
  • Doctors identify the cell type through biopsy tissue staining

There are several types of mesothelioma cancer cells. Each cell type responds to treatment differently and affects the individual patient’s prognosis, so an accurate diagnosis of the cancer cell type is essential to developing an effective treatment plan. After a treatment is administered, studying tissue samples can also provide insight on the treatment’s effectiveness.

Histology also helps prevent mesothelioma misdiagnosis. For example, peritoneal mesothelioma and ovarian cancer can be difficult to differentiate without analyzing the cell type through histopathology.

If patients are pursuing legal action against an asbestos company that may have caused their cancer, a misdiagnosis can also negatively affect their chances of obtaining compensation.

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Cell Types of Malignant Mesothelioma

When examining a tumor sample for the presence of mesothelioma, a histopathologist will carefully inspect the sample for three patterns of cellular formation:

Epithelial Cells

Epithelial Cells

Epithelial cells are uniform and sharply defined. They feature prominent nuclei and often form complex branching patterns. They divide quickly but tend to stick together, which means it takes longer for them to spread throughout the body. This cell type characterizes 50 to 70 percent of all mesothelioma cases.

Sarcomatoid Cells

Sarcomatoid Cells

Spindle-shaped sarcomatoid cells typically lack strong characteristics, and because of their looser organization, they spread more easily than epithelial cells. This rare cell type characterizes 10 to 20 percent of cases.

Biphasic Cells

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. The biphasic (mixed) cell type accounts for 20 to 35 percent of mesothelioma cases.

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 organelles.

Doctors use these histological classifications to develop a prognosis and treatment plan for patients. The cell type can account for differences in life expectancy of up to 200 days.

  • Epithelial cells are typically the most responsive to treatment, which often leads to a better prognosis.

  • Sarcomatoid cells are the least responsive to treatment, and some surgeons do not consider sarcomatoid tumors eligible for surgical removal.

  • The biphasic cell type is also considered less responsive to treatment than the epithelial cell type. However, the exact prognosis depends on the ratio of epithelial cells to sarcomatoid cells.

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The characteristics noted in the different cell types are very subtle, which can make the diagnostic process quite challenging. For example, distinguishing mesothelioma cells from adenocarcinoma cells — a cancer that affects glandular tissue — can be a serious challenge for all but the most experienced mesothelioma specialists.

Rare Variances in Histological Mesothelioma Types

Adenomatoid: In this variant of epithelial mesothelioma, sometimes known as glandular or microglandular mesothelioma, cancer cells line small, gland-like structures.

Benign: Benign mesothelioma is not cancerous and is not the result of asbestos exposure.

Cystic: This variant of epithelial mesothelioma is characterized by smooth, thin-walled cysts held together by fragile fibrovascular tissue.

Deciduoid: This variant of epithelial mesothelioma has been diagnosed in just a few dozen cases, and some doctors suspect it may be caused by a hormonal imbalance.

Desmoplastic: In this form of sarcomatoid mesothelioma, more than 50 percent of the tumor is made up of dense, fibrous tissue.

Heterologous: Tumors of this variant are peculiar because they contain bodily tissues different from the tissues in which they form.

Lymphohistiocytoid: This often misdiagnosed variant of sarcomatoid mesothelioma is made up of a dense bundle of inflammatory and immune cells.

Papillary: This variant of epithelial mesothelioma is practically benign in many cases, resembling healthy cells that grow and multiply at a slow rate.

Small Cell: Occurs when a large proportion of a mesothelioma tumor is made up of small cells that grow in a pattern similar to small-cell carcinoma.

The Histology Process

When diagnosing mesothelioma, a team of surgeons, histotechnicians, histopathologists and other professionals work together to provide the patient’s doctor with information.

Histology Process

After a surgeon removes a sample of tumor tissue through a biopsy procedure, the sample is prepared by a histotechnician. This scientist processes the tissue by preserving it and staining it with a number of special chemicals that reveal the minute structures of the cells.

How Histotechnicians Prepare a Tissue Sample for Staining

  1. Fixing: The tissue is preserved with a chemical such as formaldehyde.

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

  3. Sectioning: A machine called a microtome slices extremely thin pieces of the sample.

  4. Mounting: The slices of embedded tissue are smoothed out in a water bath and then placed on slides and baked.

Quick Fact

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

After the cancerous tissue is mounted and stained on a slide, the specimen is now ready for histopathologists to view under a microscope. They observe the size, shape and anatomical structure of the cells to identify the tumor’s cell type.

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

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 depending on what type of cancer is suspected. The tissue samples are then analyzed for specific visual patterns created by the interaction of antibodies and oncoproteins.

Common Immunohistochemical Markers for Mesothelioma

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

Immunohistochemical staining is widely used in the diagnosis of mesothelioma cells and other abnormal cells. This technique improves the accuracy of diagnosis when used in context with other diagnostic data.

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Karen Selby, RN and Patient Advocate at The Mesothelioma Center

Karen Selby joined Asbestos.com in 2009. She is a registered nurse with a background in oncology and thoracic surgery and was the director of a tissue bank before becoming a Patient Advocate at The Mesothelioma Center. Karen has assisted surgeons with thoracic surgeries such as lung resections, lung transplants, pneumonectomies, pleurectomies and wedge resections. She is also a member of the Academy of Oncology Nurse & Patient Navigators.

Sources
  1. National Cancer Institute. (2016, October 14). Malignant Mesothelioma Treatment (PDQ)–Health Professional Version. Retrieved from https://www.cancer.gov/types/mesothelioma/hp/mesothelioma-treatment-pdq#section/all
  2. Betta, P.-G. et al. (2012). Immunohistochemistry and Molecular Diagnostics of Pleural Malignant Mesothelioma. Retrieved from http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2010-0604-ra
  3. Galateau-Salle, F. (2010). Pathology of Malignant Mesothelioma. London: Springer-Verlag.
  4. Kouki, I. (2008, March). Pathology of mesothelioma. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698271/
  5. Dodson, R., and Hammar, S. (2006). Asbestos: Risk Assessment, Epidemiology, and Health Effects. Boca Raton: Taylor & Francis.
  6. Rice University Institute of Biosciences and Bioengineering. (2005, April 13). Histology and Immunohistochemistry. Retrieved from http://www-bioc.rice.edu/bios576/immuno/immuno.html
  7. Pass, H., Vogelzang, N., and Carbone, M. (2005). Malignant Mesothelioma: Advances in Pathogenesis, Diagnosis, and Transitional Therapies. New York: Springer.
  8. Khalidi, H., Medieros, L., and Battifora, H. (2000, May). Lymphohistiocytoid mesothelioma: An often misdiagnosed variant of sarcomatoid malignant mesothelioma. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10800396
  9. American Cancer Society. (n.d.). Malignant mesothelioma. Retrieved from https://www.cancer.org/cancer/malignant-mesothelioma.html

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