Mesothelioma Pathology

This pathological information is gained through a combination of the two different types of mesothelioma pathology, histopathology and cytology. Mesothelioma histopathology examines groups of cells gained from a tissue biopsy. Histopathology is the largest specialty within pathology.

Mesothelioma cytology examines single cells, often through analysis of bodily fluids. For mesothelioma patients, this fluid most commonly is either pleural effusion in pleural malignant mesothelioma patients or peritoneal effusion for those with mesothelioma of the peritoneum.

Histopathology and Mesothelioma

Histopathology, a subset of mesothelioma histology, is used to diagnose the cancer quickly and more accurately than other traditional diagnostic processes. This increased speed in accurate diagnosis can create better outcomes for patients as they are more immediately treated.

According to one study, approximately 10 – 15% of mesothelioma patients receive an inaccurate diagnosis, which can diminish their odds of a positive outcome. Appropriately using mesothelioma histopathology may help to lower this statistic, improve the efficacy of patient treatment and increase survival rates.

By looking at the detailed structures of the cancerous cells under a microscope, histopathologists can ascertain identifying characteristics of the patient’s cancer. To better visualize the cell parts, pathologists employ immunohistochemistry practices.

Immunohistochemistry to Diagnose Mesothelioma

The pathologist’s job is made easier through the use of immunohistochemistry. During this process, cells are stained so that cancerous tissue is more easily identified. Immunohistochemistry works by selecting particular proteins (antigens) in the tissue sample and seeing what antibodies bind to them under a microscope. In the case of mesothelioma immunohistochemistry, the most commonly used stain is pan-cytokeratin, which is often referred to as keratin.

Keratin is the stain of choice because, in most cases, all mesothelioma tumors react to the stain, which increases its efficacy. The only tumors that have been found to be resistant to the stain are sarcomatoid mesothelioma. This resistance may result in false negatives and delay diagnosis.

In rare instances, false negatives may also arise in the case of epithelioid mesothelioma cells. Studies have found that in some cases of mesothelioma showing pleural thickening, or thickening of the lung linings caused by scar tissue, the epithelioid cells remain undetected when stained. In these cases, other tests should be completed to rule out other forms of cancer. The negative response to the stain can lead to misdiagnoses, which complicates treatment plans and determining prognosis.

Other stains that may be used in these instances include:

• Calretinin
• Podoplanin
• WT1
• Other mesothelial markers

Due to the intricate nature of immunohistochemical studies and results indicated from the use of cell staining alone, biomarkers are often included by the pathologist to identify malignant mesothelial proliferations. These immunohistochemical markers differentiate between mesothelioma cell types and rule out other forms of disease, allowing pathologists to make an accurate diagnosis.

However, there is currently no single biomarker that can accurately distinguish the different mesothelioma cell types. The present standard is to test and identify a bevy of biomarkers, which should have either a positive or negative result to indicate mesothelioma. When combined appropriately, the biomarkers are able to accurately detect the cancer. The biomarkers used vary according to the laboratory and the initial signs that a patient is presenting with.

Mesothelioma Cell Types Identified Through Histopathology

Using the above histopathology practices, including immunohistochemistry and biomarkers, pathologists can identify a tumor’s mesothelioma cell type. There are three main categories that mesothelioma cells are split into:

• Epithelioid
• Sarcomatoid
• Biphasic

Knowing which of the three main forms of mesothelioma cells are present can enable a patient’s care team to make differential diagnoses. A differential diagnosis is a process by which doctors are able to differentiate between diseases that present with similar symptoms.

Mesothelioma presents with common symptoms, which without the use of histopathology may be misdiagnosed as more common illnesses. For example, mesothelioma can be misdiagnosed as the flu, a common cold or lung cancer.

Making a differential diagnosis within the mesothelioma cell types is important because the cells metastasize differently and react to treatment differently.

Histopathology becomes even more important when the cells do not fall neatly into one of the three main mesothelioma cell types. These rare mesothelioma cell subtypes require additional care to best understand how they’re reacting in order to most effectively treat the cancer. Imaging scans are often used to properly identify these rarer cells.

Mesothelioma Cytology: Looking at Single Cells

Mesothelioma cytology is a useful tool that enables analysis without necessitating a tissue biopsy. By forgoing a tissue biopsy, there is less risk of morbidity of the patient. However, there is still a small risk of tumor cell seeding (microscopic spreading of cancer due to cells moving during a biopsy) during cytologic procedures.

Instead of a tissue biopsy, cytology analyzes bodily fluids to diagnose a patient with a specific form of cancer. In the case of mesothelioma, the fluid is commonly from a pleural or peritoneal effusion.

Diagnosing malignant mesothelioma through cytology is a two-step process:

1. Confirming that the effusion is malignant
2. Confirming that the cancerous cells began from mesothelial cells

As a comparable diagnostic tool, cytology can be used instead of histopathology to diagnose mesothelioma. However, there are times when it is necessary to confirm a cytologic diagnosis with histopathology to ensure accuracy. In these cases, immunohistochemistry is the most common means of confirming a cytologic mesothelioma diagnosis.

When the results from the cytologic analysis of fluid are inconclusive, a tissue analysis should be completed to ensure accurate results. This is frequently the case with mesothelioma that is predominantly sarcomatoid cell type or when there is blood in the effusion fluid.

Importance of Accurate Mesothelioma Pathological Analysis

Pathology is an important diagnostic tool for all types of diseases because it enables prompt and effective treatment options. Doctors use the insight from pathology reports to create the most impactful treatment plan possible.

The prognosis for mesothelioma patients is dependent on the stage at which the cancer is diagnosed and when interventions can begin. Including pathology at the onset of symptoms can ensure an expedited diagnosis of malignant mesothelioma.

According to researchers, pathology, including cytology, can accurately diagnose mesothelioma 99% of the time, when used on the appropriate patients. For those patients whose case did not fulfill all criteria for mesothelioma, the sensitivity falls to approximately 50%. Sensitivity can be improved when doctors use the pathology reports as just one piece of a broader diagnostic process. The process should include looking at many aspects of the patient through:

• Pathology
• Imaging test
• Physical exam
• Medical/work history
• Discussing any previous asbestos exposure

Patients should discuss with their healthcare team if they would benefit from adding pathology to the diagnostic testing being completed on their case.