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Mesothelioma Pathology

Pathologists examine a patient’s cells to accurately diagnose mesothelioma and help develop the most favorable treatment plan.

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Key Points

  • 1

    Pathology uses cellular inspection to differentiate cancerous cells from healthy tissue.

  • 2

    Mesothelioma pathology enables accurate diagnosis.

  • 3

    Pathology can be used to stage mesothelioma and detect metastasis.

  • 4

    The practice of pathology can be broken into histopathology and cytology.

Mesothelioma pathology is an important aspect of reaching an accurate diagnosis. Pathology, including histopathology and cytology analyses, helps doctors determine the mesothelioma cell type, stage and how the cancer is expected to progress. Biopsies are the only way to definitively diagnose mesothelioma, and it is important that samples are studied by an experienced pathologist to achieve an accurate diagnosis.

How Mesothelioma Pathology Is Used to Serve Patients

Pathology is used by medical professionals to glean various identifying factors about a patient’s cancer on the cellular level. A pathology report details the level of mutation within the cancer cells, the rate at which the cancer is growing, if metastasis has occurred and the stage of the cancer.

Facts Included in a Pathology Report
Histologic Grade

The severity of the mutation of the cells. Low grade means the mesothelioma cells are quite similar to healthy tissue, which has a more favorable prognosis compared to high-grade mesothelioma cells.

Mitotic Rate

The rate at which the cancer cells are dividing. This number is ascertained by counting the dividing cells within the biopsy sample. A low mitotic rate often equates to improved prognosis for patients.

Lymph Node Involvement

Denotes if the cancer has invaded the lymph nodes. If the cancer has spread to the lymph nodes, there is an enhanced risk of metastasis,  making the mesothelioma more difficult to treat.


Cancer staging involves analyzing how much cancer is in a patient’s body and where it is within the body. Accurate staging of the cancer is an important aspect of determining a treatment plan.

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.

Mesothelioma Histopathology
  • Studying diseased cells under a microscope
  • Analysis of a small piece of tissue gained from a traditional biopsy
  • Widely used for differential diagnoses
Mesothelioma Cytology
  • Studying a single mesothelial cell under a microscope
  • Cells often are taken from bodily fluids
  • Less risk of serious complications with only mild side effects

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.

Researchers recommend that whatever panel, or biomarker assay, is used have at least an 80% sensitivity rate in control testing to ensure the accuracy of results.

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:

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.

Mesothelioma Cell Types
Epithelioid Cell Type
  • Most common mesothelioma cell type
  • Appears cuboidal under the microscope
  • Rare subtypes:  tubulopapillary, deciduoid, small cell type and papillary mesothelioma.
  • Epithelioid pleural mesothelioma differential diagnoses:  mesothelial hyperplasia, lung adenocarcinoma and renal cell carcinoma
  • Epithelioid peritoneal mesothelioma differential diagnoses: ovarian serous papillary adenocarcinoma or peritoneal serous carcinoma
Sarcomatoid Cell Type
  • Least common mesothelioma cell type
  • Rare subtype: Desmoplastic mesothelioma
  • Sarcomatoid mesothelioma differential diagnoses: sarcoma of the pleura, peritoneum, intestine, chest wall and lungs
  • Sarcomatoid pleural mesothelioma is most difficult to differentiate from sarcomatoid carcinoma, also called spindle cell carcinoma or pleomorphic carcinoma
Biphasic Cell Type
  • Second most common mesothelioma cell type
  • A combination of the epitheliod and sarcomatoid types
  • Most common among patients with mesothelioma of the peritoneum and pericardium
  • Biphasic pleural mesothelioma differential diagnoses: carcinosarcoma, pulmonary blastoma in the lung and biphasic synovial sarcoma
  • Biphasic peritoneal mesothelioma differential diagnoses: carcinosarcoma of the ovaries

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.

Ways to Confirm a Cytologic Diagnosis
  • Biomarker analysis
  • Electron microscopy
  • Immunohistochemistry
  • Molecular biology

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.