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Mesothelioma Pathology

Pathology is the study of how a disease develops and spreads. Mesothelioma cytology and histology are two aspects of this area of research, focusing specifically on the cell types and how they function. These specialties work together to ensure the most accurate diagnosis and help create the best treatment plan.

Mesothelioma pathology focuses on understanding how mesothelial cells form, spread and interact in the body. Pathologists study normal and diseased tissue samples to make an accurate diagnosis. Since mesothelioma is often mistaken for other diseases and cancers, these cellular studies are vital in properly detecting mesothelioma before it becomes more advanced. It is important that biopsies be reviewed by an experienced mesothelioma pathologist.

Diagnostic Methods
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Mesothelioma Histology: Understanding Cell Types

Mesothelioma histology is the study of the function and structure of anatomy, including tissues and cells. Another subset of this field, called histopathology, looks specifically at the microstructure of diseased cells and tissues, which is what a pathologist will focus on when studying a tissue sample to make a diagnosis. Examining the diseased tissue and tumor cells is the only way to make a definitive diagnosis of malignant mesothelioma.

The histopathology process will generally begin by taking a biopsy, which is most often a tissue sample. The sample will be prepared and stained for viewing under the microscope to observe the cells present, including their size, shape and cell type.

This process will also entail a process known as immunohistochemistry, which is a staining technique that uses specific antibodies to selectively image antigens or proteins in the tissue sample, like cytokeratin, WT-1 protein or other mesothelial markers. The antibodies will bind to the selected antigens, which can then be seen under the microscope. Finding diagnostic markers like calretinin, WT-1, D2-40 or mesothelin are important in achieving a proper diagnosis. Researchers note the immunohistochemical study is highly reliable for cancer diagnosis, including mesothelioma.

In general, histopathologists look for three typical cell types for a mesothelioma diagnosis:

Epithelioid Mesothelioma

Normal, healthy epithelial cells form the lining of our organs and skin. After asbestos exposure, the cells may change genetically and become cancerous. Cells of the epithelioid type are elongated with visible nuclei, known to cluster together in groups and spread more slowly through the body.

Sarcomatoid Mesothelioma

Sarcomatoid cells generally form in the pleural cavity and visceral pleura, often being confused for healthy cells. These cells also have an elongated nucleus or multiple nuclei, but are spindle shaped. The spindle cells are known to grow and spread quickly, since they don’t typically group into clusters.


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Biphasic Mesothelioma

Biphasic mesothelioma is defined as a combination of epithelial and sarcomatoid cells. Whichever cell type is more dominant will determine how the cells form and spread in the body. Biphasic cells are more commonly associated with peritoneal mesothelioma or pericardial mesothelioma.

Each of these mesothelioma cell types also have more rare subtypes that may be present, which can make it more difficult for mesothelioma specialists to properly diagnose the disease. While the more standard cell types can easily be mistaken for other types of cancer like lung adenocarcinoma, renal cell carcinoma, or synovial sarcoma, these rare types are even more difficult to confirm by differential diagnosis.

Rare Mesothelioma Cell Types

Rare mesothelioma cell types can be deivided into the following two subcategories:

Epithelioid Cell Subtypes

  • Adenoid mesothelioma
  • Small cell mesothelioma
  • Cystic mesothelioma
  • Papillary mesothelioma
  • Deciduoid mesothelioma

Sarcomatoid Cell Subtypes

  • Lymphohistiocytoid mesothelioma
  • Desmoplastic mesothelioma
  • Heterologous mesothelioma
  • Osteosarcomatous mesothelioma
  • Chondrosarcomatous mesothelioma

Determining the cell type is one of the most important prognostic factors, especially with the additional insight that mesothelioma cytology can provide.

Mesothelioma Cytology: A Look at How the Cancer Will Advance

Mesothelioma cytology or cytopathology goes hand-in-hand with histology. While the histological determination will focus more on the cell type, the cytology research will dive deeper into how these cells are forming, interacting, and spreading in the body. Some more recognized practices of cytology at work are preventive tests or screenings, like the Pap test.

To conduct cytology research, doctors will first take a fluid biopsy. Pleural effusions, for instance, may occur in malignant pleural mesothelioma patients, where fluid builds up in the lungs. Pathologists may take samples of this liquid, which can then be used to study mesothelioma cytology. Other types of mesothelioma can also result in fluid build ups near the chest wall or in the abdomen, which can also be biopsied for testing.

Common Cytologic Features

  • Shape and size of cancerous cells’ formations
  • Cytomegaly – enlargement of cells
  • Nuclear pleomorphism – variability in size, shape, and staining of nuclei in cells
  • The N/C ratio of nucleus to cytoplasm – a high ratio suggests malignancy

Overall, when observing the cytology of malignant mesothelioma and other cancers, researchers tend to focus on certain microscopic features of the structure and function of the cells.

With a better understanding of these and other characteristics, researchers may ultimately be able to decipher how the cancer may spread and react to treatment. This knowledge could someday enable doctors to make a more personalized treatment plan for each individual, which will have a higher likelihood of improving a patient’s prognosis.

Next Steps After Mesothelioma Pathology

After pathologists can go through the histology and cytology processes and other types of testing, patients can feel more confident that they are receiving an accurate diagnosis. Once doctors can differentiate these cancerous cells from other forms of cancer and disease, they will be able to determine the appropriate treatment plan, while also keeping other factors like the patient’s age, gender, and overall health in consideration.

All of these factors together will ensure even patients who are diagnosed with advanced stage mesothelioma know all their treatment options and have the best opportunity to improve quality of life and extend life expectancy.

Researchers also believe understanding more about these cancer cells and genetic mutations of cancer are crucial for the development of new diagnostic tests and treatments, and likely the best way to get closer to finding a cure.

Author: Linda Molinari

Editor in Chief, Mesothelioma Cancer Alliance

Linda Molinari

Reviewer: Dr. James Stevenson

Medical Reviewer and Thoracic Medical Oncologist

Dr. James Stevenson

Betta P, Magnani C, et al. Immunohistochemistry and Molecular Diagnostics of Pleural Malignant Mesothelioma. Archives of Pathology & Laboratory Medicine. 2012 March; 136:253–261. doi: 10.5858/ arpa.2010-0604-RA

Blum W, Schwaller B. Calretinin is essential for mesothelioma cell growth/survival in vitro: A potential new target for malignant mesothelioma therapy? International Journal of Cancer. 133(9):2077–2088. doi: 10.1002/ijc.28218.

Cagle P, Churg A. Differential diagnosis of benign and malignant mesothelial proliferations on pleural biopsies. Archives of Pathology & Laboratory Medicine. 2005 Nov;129(11):1421-7. doi:10.1043/1543-2165

Husain A, Colby T, et al. Guidelines for Pathologic Diagnosis of Malignant Mesothelioma: A Consensus Statement from the International Mesothelioma Interest Group. Archives of Pathology & Laboratory Medicine. 2009 August; 133(8).

Kouki I. Pathology of mesothelioma. Environmental Health and Preventive Medicine. 2008 March; 13(2): 60–64. doi: 10.1007/s12199-007-0017-6

Marchevsky A. Application of immunohistochemistry to the diagnosis of malignant mesothelioma. Archives of Pathology & Laboratory Medicine. 2008 Mar;132(3):397-401. doi: 10.1043/1543-2165

Mangano W, Cagle PT, Churg A, et al. The Diagnosis of Desmoplastic Malignant Mesothelioma and Its Distinction from Fibrous Pleurisy. Anatomic Pathology. 1998;110:191-199.

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