Written By: Devin Golden

Mesothelioma Histology

Mesothelioma histology is a scientific process to diagnose mesothelioma, which is a rare and aggressive cancer caused by asbestos exposure. Through histologic examination, medical experts analyze tissue samples under a microscope to determine the presence of cancerous cells and identify the tumor’s subtype.

Dr. Stephen Williams

Medically Reviewed By

Dr. Stephen Williams

Precision Oncology Scientist

Dr. Stephen Williams

Medically Reviewed By

Dr. Stephen Williams

Precision Oncology Scientist


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What Is Mesothelioma Histology?

Mesothelioma histology, also referred to as mesothelioma histopathology, is the microscopic study of tissue to detect malignant mesothelial cells. This process is part of mesothelioma pathology, which involves examining either tissue or fluid to determine if this cancer exists.

The most notable characteristics of mesothelioma histology are:

  • Studying how mesothelioma cells look and behave under a microscope
  • Most definitive method to diagnose mesothelioma
  • More reliable than testing fluid samples (mesothelioma cytology)
  • Provides a more comprehensive evaluation of tissue cells than cytology
  • Larger tissue samples provide more cells to analyze
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How Is Mesothelioma Histology Performed?

Mesothelioma histology is one of the final steps in the diagnostic process. Histology starts with extracting tissue from the body during a mesothelioma biopsy.

Doctors remove tissue samples from patients due to:

  • Experiencing symptoms of mesothelioma
  • Abnormal imaging tests (X-ray, CT scan, or MRI)
  • Abnormal blood tests (low cell counts, abnormal organ function, inflammation, or tumor markers)

How Are Tissue Samples Collected?

Doctors collect tissue samples for mesothelioma diagnosis through biopsy procedures, which allow medical experts called pathologists to examine tissue cells under a microscope. Because mesothelioma is rare and often difficult to identify, obtaining an adequate tissue sample is essential for an accurate diagnosis.

There are multiple types of mesothelioma biopsy procedures. The specific procedure used depends on where the doctor wants to obtain tissue samples. Mesothelioma biopsy procedures are:

Thoracotomy Icon

Thoracotomy - This surgical procedure opens the chest to access the chest cavity and the thoracic organs. To diagnose pleural mesothelioma, tissue is often removed from the pleura (the lining between the lung and chest wall).

Laparotomy Icon

Laparotomy - This surgical procedure opens the abdomen to access the abdominal cavity and abdominal organs. To diagnose peritoneal mesothelioma, tissue is often taken from the peritoneum (the abdominal lining).

Thoracoscopy Icon

Thoracoscopy - This camera-assisted biopsy removes pleural tissue to diagnose pleural mesothelioma. This type of procedure allows for smaller incisions than a thoracotomy.

Laparoscopy Icon

Laparoscopy - This camera-assisted biopsy removes tissue from the peritoneum to diagnose peritoneal mesothelioma. This type of procedure allows for smaller incisions than a laparotomy.

Mediastinoscopy Icon

Mediastinoscopy - This surgical procedure removes lymph nodes from the mediastinum (the space between the lungs). This procedure is done when lymph nodes in this area are enlarged or if doctors suspect cancer has spread to this location.

How Do Doctors Test Tissue Samples?

After tissue samples are collected, they are sent to a pathology laboratory for analysis. Pathologists examine the tissue cells under a microscope to determine whether mesothelioma is present and identify the tumor’s specific cell type and characteristics.

The histology process includes:

  • Microscopic examination of tissue cell architecture
  • Special staining techniques to confirm mesothelioma and rule out other cancers

Pathology reports summarize the results of mesothelioma histology analysis, where tissue samples are examined microscopically. This evaluation is the standard for diagnosing mesothelioma and determining the tumor’s cell type.

In determining cell type, pathologists look for:

  • Cellular behavior (how cells grow, divide, and interact)
  • Cell appearance under the microscope (size, shape, and organization)
  • Appearance of cell nuclei (including size, shape, and visibility)
  • Growth patterns and overall tissue architecture

Each mesothelioma cell type — epithelioid, sarcomatoid, and biphasic  — has unique characteristics. 

Epithelioid mesothelioma cells are well-defined. They have visible nuclei and tend to clump together. Epithelioid cells grow quickly but metastasize slowly.

Sarcomatoid mesothelioma cells are less defined and difficult to identify. They have an irregular shape with an elongated structure. Sarcomatoid cells spread faster than epithelioid cells but do not clump together.

Biphasic mesothelioma is defined by the presence of both epithelioid and sarcomatoid cells within the same tumor. Pathologists may see areas of epithelioid and sarcomatoid cells clearly separated and other times when the two cell types are intermingled.

Immunohistochemistry in Mesothelioma Histology

Immunohistochemistry is an integral part of mesothelioma histology. Tissue samples are analyzed for specific protein markers associated with mesothelioma tumors. This technique, along with the pathologist’s microscopic examination of the cells, helps strengthen diagnostic accuracy.

Tissue staining is required for immunohistochemical testing. This involves introducing a foreign substance to the tissue samples. The foreign substance is an antibody that reacts with mesothelioma cells. The reaction reveals the presence of cancer.

No single antibody can definitively identify mesothelioma through immunohistochemical staining. For that reason, pathologists use multiple antibody tests to establish a diagnosis.

Staining is also used to determine which mesothelioma cell type is present in the tumors. Mesothelioma cells respond differently to specific antibodies used in staining. The most common stains used to identify pleural mesothelioma are:

  • CalretininStrongly associated with mesothelial cells; positive in most cases of epithelioid mesothelioma
  • Cytokeratin 5 or 5/6Expressed in a high percentage of mesothelioma tumors; distinguishes mesothelioma from adenocarcinoma
  • Wilms’ tumor-I antigen (WT1)Commonly expressed in pleural mesothelioma and epithelioid cell type
  • Podoplanin (D2-40)Highly sensitive mesothelial marker; frequently positive in pleural mesothelioma

Pathologists typically require at least two positive mesothelial markers before confirming a diagnosis. For sarcomatoid mesothelioma, AE1/AE3 and CAM5.2 stains are often used to identify the cancer cells.

Mesothelioma Histology Accuracy and Seeking the Help of a Specialist

Mesothelioma histology is more reliable than cytology for diagnosing this disease. Tissue samples often provide a greater number of intact tumor cells for analysis, while fluid samples may yield scattered or damaged cells.

One study published on UpToDate compared the accuracy of tissue biopsies and fluid samples:

  • Camera-assisted tissue biopsies were 98% accurate in diagnosing mesothelioma.
  • Fluid biopsies were only 26% accurate in diagnosing mesothelioma.

Mesothelioma misdiagnosis is common due to vague symptoms often associated with other illnesses. Mesothelioma is a rare cancer, and many pathologists do not have the knowledge and experience needed to identify mesothelioma cells during their microscopic analysis.

If you believe you may have mesothelioma, you should see a specialist. They work with pathologists who have experience detecting this cancer and performing mesothelioma histology. We can help you connect with some of the top mesothelioma specialists to begin the diagnostic process.

Sources & Author

  1. What Is Histopathology? VeryWellHealth. Retrieved from: https://www.verywellhealth.com/histopathology-2252152. Accessed: 05/06/2020.
  2. Tests for Malignant Mesothelioma. American Cancer Society. Retrieved from: https://www.cancer.org/cancer/malignant-mesothelioma/detection-diagnosis-staging/how-diagnosed.html. Accessed: 05/05/2020.
  3. Types of biopsies used to look for cancer. American Cancer Society. Retrieved from: https://www.cancer.org/treatment/understanding-your-diagnosis/tests/testing-biopsy-and-cytology-specimens-for-cancer/biopsy-types.html. Accessed: 05/05/2020.
  4. Diffuse Malignant Mesothelioma. Pathology Outlines. Retrieved from: http://www.pathologyoutlines.com/topic/pleuramesothelioma.html/. Accessed: 09/4/18.
  5. Guidelines for Pathologic Diagnosis of Malignant Mesothelioma. International Mesothelioma Interest Group. Retrieved from: https://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2017-0124-RA. Accessed: 10/04/19.
  6. Presentation, initial evaluation, and prognosis of malignant pleural mesothelioma. UpToDate. Retrieved from: https://www.uptodate.com/contents/presentation-initial-evaluation-and-prognosis-of-malignant-pleural-mesothelioma?topicRef=4625&source=see_link. Accessed: 03/19/19.
  7. The immunohistochemical characterization of sarcomatoid malignant mesothelioma of the pleura. American Journal of Cancer Research. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180102/. Accessed: 06/01/2020.
Devin Golden

About the Writer, Devin Golden

Devin Golden is the senior content writer for Mesothelioma Guide. He produces mesothelioma-related content on various mediums, including the Mesothelioma Guide website and social media channels. Devin's objective is to translate complex information regarding mesothelioma into informative, easily absorbable content to help patients and their loved ones.