Mesothelioma Pathology

Medical oncologist Dr. Tirrell Johnson explains pathology and the important role it plays in mesothelioma cancer progression.

Pathology, the study of the nature of disease and its causes and effects, plays a significant role in the diagnosis of asbestos cancers. Because each type of cancer has particular characteristics, studying the way cancer behaves in the body and how it affects surrounding body tissues and organs can help doctors provide an accurate diagnosis and develop treatment plans for patients.

Pathology can involve anatomical studies of the appearance of the disease in tissues, the way it progresses, and the study of how the disease affects cells on a microscopic level.

Fast Fact: Pathologists provide crucial information for mesothelioma diagnosis, including the extent of disease progression, surgical resection margins and if the cancer has spread to the lymph nodes.

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Anatomical Pathology

Pathologists note certain physical characteristics of asbestos-related tumors. The majority of these tumors affect the pleura (75 percent) and the peritoneal cavity (10 to 20 percent). Only rarely do they affect the pericardium (1 percent) and tunica vaginalis (less than 1 percent).

One of the most unique pathological features of these diseases is that the cancer forms in the mesothelial cells in the linings of organs and grows in a diffuse pattern. This growth pattern causes the tumors to spread and form tiny nodules across the surface of the outer lining of the lungs (pleura) or abdomen (peritoneum). Localized malignant mesotheliomas are extremely uncommon, though a few cases have been reported. These localized tumors are more easily removed in surgery and therefore have a much better prognosis.

Pathological Characteristics of Disease Progression

Stage I Pathology

Stage I

Cancer is localized. Surgery may be able to remove tumors and prognosis is highest.

Stage II

Cancer has spread beyond point of origin. Surgery may still be an option, but life expectancy is decreased.

Stage II Pathology
Stage III Pathology

Stage III

Cancer has progressed to advanced stage of development. Palliative treatments to ease symptoms may be considered.

Stage IV

Cancer has spread to distant locations. Palliative treatments can improve comfort, but life expectancy is severely decreased.

Stage IV Pathology

In its early stages, diffuse pleural mesothelioma begins as multiple tumor nodules on either or both of the visceral and parietal pleural surfaces. The nodule size ranges from 1 mm to 1 cm. As the disease progresses, the tumors form plaques. Eventually, these tumors can form a rind around the organ, constricting it and interfering with its normal functions. Organ encasement is usually a sign of advanced disease. After tumors begin to encase organs, the visceral and parietal linings in pleural, peritoneal and pericardial mesothelioma typically adhere together.

Pleural cancers often spread to skeletal muscle in the chest wall and may also invade the skin and subcutaneous tissue (deepest layer of skin). Tumors can also invade the hemidiaphragm and spread into the abdominal cavity. When present in the pleural cavity, the tumors can also invade biopsy tracks, surgical incisions and the fissures of the lung. At very late stages, they metastasize into the hilar lymph nodes, which are located in the chest close to where the bronchi enter the lungs.

Fast Fact: Patients are rarely treated for cancer with chemotherapy unless there is a pathological diagnosis.

In advanced peritoneal mesothelioma, the bowel is often encased by tumors, and the liver and spleen may also be encased. Tumors that originate in the pericardium are rare, but the same diffuse spread pattern is also observed and it often infiltrates the muscle tissue of the heart (myocardium).

Cellular Pathology

While the anatomical characteristics of a tumor can help diagnose a type of cancer, most tumors require a pathologist to study the types of cells present in a malignant growth. Using a microscope, pathological studies differentiate mesothelioma cells from other types of cancer and are used to diagnose specific subtypes of the disease through two methods: histology and cytology.

Histopathologic Features

Histology involves the use of tissue samples obtained through a biopsy. Histopathology specifically refers to the study of the cells in diseased tissue. For mesothelioma, actual tissue from tumors is usually obtained through an incisional/core or excisional biopsy.

Histology Stain of Mesothelioma Tissue

Mesothelioma Histology Tissue Stain

This method is the preferred method for diagnosing asbestos cancer because information is comprehensive when using histology. Also, immunohistochemistry “ staining using antibodies “ and other special stains can be applied to tissue samples to reveal more details about a tumor.

Biopsy

  • Thoracotomy
  • Incisional/core biopsy
  • Thoracoscopy

Stain

  • Immunohistochemistry
  • Fluorescent stains to detect genetic abnormalities
  • Standard cell stains (such as hematoxylin and eosin staining)

Study

  • Can detect localized and invasive tumors
  • Required for definitive diagnosis

Medical oncologist Dr. Tirrell Johnson explains the role of pathology in determining malignant cells.

Cell changes caused by the malignant cells can also be seen in histology stains. Pathologists can get more information on the tumor by studying gland formation, connective tissue, blood vessels and membranes. This information is unavailable in cytology stains.

Using histology, pathologists classify mesothelioma cells into three general types based on cellular patterns from tumor tissue observed under a microscope: epithelioid, sarcomatoid or biphasic (mixed). Epithelioid cells are polygonal, cuboidal or oval in shape and can often mimic noncancerous mesothelial cells. Sarcomatoid mesotheliomas are spindle shaped and mixed cells types contain characteristics of both epithelioid and sarcomatoid cell types. Aside from these major cell types, there are a number of variants including deciduoid, desmoplastic, lymphohistiocytoid and small cell mesothelioma.

The histologic features of peritoneal cancer are similar to primary pleural tumors, but the biphasic cell type is less common which is important to note since this cell type has a poor prognosis. The well-differentiated papillary mesothelioma cell subtype is more frequently seen in the peritoneum versus the pleura. These cells are smooth contoured and lack nucleoli. This cell type also has an excellent prognosis, though it has a tendency to reoccur.

Immunohistochemistry is a type of staining technique used by histopathologists. This technique uses antibodies applied to tissue samples on a slide. Pathologists can then observe the characteristics of cellular proteins as they react to the antibodies. The International Mesothelioma Interest Group (IMIG) states that a definitive diagnosis of asbestos cancer must include immunohistochemical stains. One highly useful stain is an antibody called pancytokeratin. This stain will almost always be positive in asbestos-related tumors and is highly reliable for diagnosis. However, because most of these stains lack some accuracy as single stains, doctors use an entire panel of antibodies made up of epithelial markers and mesothelial markers.

Immunohistochemistry stains can be used in cytology, although the methods for preparation of cell smears differ from those in histology that use actual tissue samples. Generally, immunohistochemistry is more reliable when used in histology than cytology.

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Cytologic Features

Cytology uses cells from fluids or surface scrapings without actual tissue samples. Pathologists can gather pleural fluid from a patient suspected of having pleural cancer through fine needle aspiration. This method is less expensive and test results are available within minutes. However, cytology cannot differentiate between a tumor in situ “ a tumor that has not yet invaded surrounding tissues “ and an invasive tumor. Often histology is still needed to confirm a diagnosis.

Cytology Fluid Stain of Mesothelioma Tissue

Cytology Pleural Mesothelioma Fluid Stain

Biopsy

  • Cell scrapings
  • Fine needle aspiration (FNA)
  • Fluid (pleural fluid or blood)

Stain

  • Immunohistochemistry is not as easily applied

  • Standard cell stains (such as hematoxlyin and eosin staining)

Study

  • Faster results
  • Less expensive
  • Histology tissue sample still needed to confirm diagnosis

The exact role of cytology in the primary diagnosis of asbestos cancer is still debated by the medical community. The International Mesothelioma Interest Group (IMIG) recommends that cytologic suspicion of the disease be supported by tissue confirmation and radiologic and clinical data.

Though some cytologic features of mesothelioma may be shared with benign mesothelioma cells, useful features include the presence of:

  • Relatively large cell balls made up of more than 50 cells with berrylike or knobby contours
  • Prominent macronucleoli (not present in all malignant mesotheliomas)
  • Nuclear atypia (abnormal nuclei)

Additional Resources

  1. Inai, K. (2008). Pathology of mesothelioma. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698271/
  2. Allen, T. C., Cagle, P. T., Churg, A. M., Colby T. V., Gibbs, A. R., Hammar, S. P., Corson, JK. M., ….& Wick, M. R. (2005). Localized malignant mesothelioma. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15958850/
  3. Baldi, A. (Ed.). (2008). Mesothelioma from bench side to clinic. New York: Nova Science Publishers, Inc.
  4. Husain, A. N., Colby T. V., Ordonez, N. G., Krausz, T., Borczuk, A., Cagle, P. T., Chirieac, L. R.,….& Wick, M.R. (2009). Guidelines for pathologic diagnosis of malignant mesothelioma: A consensus statement from the International Mesothelioma Interest Group. Retrieved from http://www.archivesofpathology.org/doi/full/10.1043/1543-2165-133.8.1317
  5. Marchevsky, A. M. (2008). Application of immunohistochemistry to the diagnosis of malignant mesothelioma. Retrieved from http://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165%282008%29132%5B397%3AAOITTD%5D2.0.CO%3B2
  6. Fowler, L. J., & Lachar, W. A. (2008). Application of immunochemistry to cytology. Retrieved from http://rpatologiahfmp.org/descargas/articulos/ApImmunohistochemistryCytology.pdf

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