Biphasic Mesothelioma

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Biphasic mesothelioma is a mixture of epithelioid and sarcomatoid cells. For a tumor to be diagnosed as biphasic, each cell type must make up at least 10% of it. This is most common in pleural mesothelioma cases. A higher percentage of sarcomatoid cells indicates a more aggressive cancer.

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Patient Advocate Karen Selby explains biphasic mesothelioma.
Patient Advocate Karen Selby explains biphasic mesothelioma.

What Is Biphasic Mesothelioma?

Malignant biphasic mesothelioma is the second most common cell type of the disease. Like all other cell types of mesothelioma, asbestos exposure is the leading cause of the disease.

The life expectancy of patients with this form of cancer varies because prognosis depends on the ratio of epithelial and sarcomatoid cells.

The larger the percentage of sarcomatoid cells, the poorer the prognosis. This cell type is more common among pleural patients than peritoneal patients.

Understanding the characteristics and diagnosis of this type of mesothelioma can help you make informed treatment decisions with your doctor.

Characteristics of Biphasic Mesothelioma

In biphasic mesothelioma cases, epithelioid cells and sarcomatoid cells can exist close together. They can also appear within separate areas of a tumor.

Areas of epithelial cells, usually composed of solid and tubopapillary cells (which are epithelial subtypes), are found scattered among sarcomatoid cells. The proportion of epithelial and sarcomatoid cells can vary greatly.

Incidence rates show nearly 30% of pleural mesothelioma tumors are biphasic. However, many pathologists believe the incidence of biphasic mesothelioma would be higher if more areas of mesothelioma tumors were sampled and analyzed. Pathologists are experts in the field of pathology, which is the study of diseased tissue to diagnose conditions such as cancer.

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Diagnosing the Biphasic Cell Type

The biphasic cell type can be difficult to detect and diagnose.

Mesothelioma cell types are important to detect because some clinical trials and treatments target specific cell types.

The characteristics of your cell type do not affect your symptoms. However, they may affect your life expectancy. On average, epithelial mesothelioma patients survive 200 days longer than the other types.

During a key diagnostic test called a biopsy, doctors may collect only a small sample of tissue to study in the lab.

Taking samples from just one location offers a limited view of the type and amount of mesothelioma cells involved.

Doctors can make a more accurate diagnosis by taking tissue samples from several parts of the tumor. Determining the specific cell type is important to the diagnostic process because it can affect your treatment options and prognosis.

Preventing a Misdiagnosis

Doctors use advanced tests such as immunohistochemistry to distinguish biphasic mesothelioma from other diseases that are easily confused with this cancer. This technique can detect certain proteins, revealing the specific type of abnormal cells.

Quick Fact:

The diagnostic process can be harder for biphasic patients since epithelioid and sarcomatoid cells must be detected.

With this information, doctors can rule out common misdiagnoses, including cancers such as synovial sarcoma and carcinosarcoma.

A 2011 study published in the Journal of Thoracic Oncology found the biphasic type can be misdiagnosed after a biopsy. A total of 83 patients in the study were confirmed to have this type of pleural cancer after undergoing an extensive surgical procedure called an extrapleural pneumonectomy.

However, only 26% of those patients had been originally diagnosed with this subtype. The authors explained biphasic mesothelioma can be more accurately diagnosed following surgery.

The initial diagnostic methods included thoracoscopy, thoracotomy, computerized tomography and other biopsy methods.

Biphasic Mesothelioma Treatment

Patients with the biphasic mesothelioma cell type may not be considered for an aggressive treatment plan as would patients with the epithelioid type.

The reason is that biphasic carries a slightly poorer prognosis than epithelioid. However, treatment is not completely based on cell type.

Most patients undergo one or more of these common therapies:

  • Surgery
  • Chemotherapy
  • Radiation

Treatment may depend more on the stage and location of the tumor than the cell type involved.

Clinical trials are testing new drugs and therapies specifically for mesothelioma patients with sarcomatoid or biphasic tumors.

For example, a phase II/III clinical trial is investigating an anti-cancer enzyme on sarcomatoid and biphasic mesothelioma tumors. Known as ADI-PEG 20 (pegylated arginine deiminase), the enzyme significantly improved survival of sarcomatoid patients in its phase I trial.

Prognosis and Life Expectancy

The prognosis for patients with biphasic mesothelioma varies depending on the ratio of epithelial and sarcomatoid cells present in each case.

Quick Fact:

The more epithelial cells you have in a biphasic mix, the better your prognosis may be. How much better may amount to only a few months depending on the case.

In one study involving 85 pleural mesothelioma patients with a variety of cellular subtypes, people with the biphasic cell type had an average survival of about 15 months. Those with the epithelial subtype displayed the highest average survival — more than 22 months.

The researchers observed slightly better survival among biphasic patients whose tumors had mostly epithelial cells, compared to those with mostly sarcomatoid cells.

While the survival advantage was only 16 days, sarcomatoid cells are less responsive to treatment than epithelial cells. As a result, biphasic patients with a lower number of sarcomatoid cells tend to see better results from treatment.

In another study, researchers observed the survival of 255 mesothelioma patients. Seventeen of the patients were diagnosed with desmoplastic mesothelioma, which is a cell subtype of sarcomatoid mesothelioma. Of those 17 patients, 11 had pure sarcomatoid tumors while six had biphasic tumors. Patients with pure sarcomatoid tumors survived 5.8 months and patients with biphasic tumors survived 6.8 months.

Epithelial cells in the biphasic tumors likely contributed to the one-month survival advantage observed in the biphasic patients.

The poorer prognosis may partially be influenced by PD-L1 levels. In a 2019 study published in Clinical Lung Cancer, pleural mesothelioma patients with sarcomatoid and biphasic cells had higher levels of PD-L1, which is associated with shorter survival.

Another factor contributing to the poorer prognosis of biphasic mesothelioma is that sarcomatoid cells tend to spread faster than epithelial cells.

Biphasic tumors with a high ratio of sarcomatoid cells may spread quicker and result in shorter life expectancy.

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Registered Nurse and Patient Advocate

Karen Selby joined Asbestos.com in 2009. She is a registered nurse with a background in oncology and thoracic surgery and was the regional director of a tissue bank before becoming a Patient Advocate at The Mesothelioma Center. Karen has assisted surgeons with thoracic surgeries such as lung resections, lung transplants, pneumonectomies, pleurectomies and wedge resections. She is also a member of the Academy of Oncology Nurse & Patient Navigators.

Walter Pacheco, Managing Editor at Asbestos.com
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8 Cited Article Sources

  1. Brosseau, S. et al. (2019). Shorter Survival in Malignant Pleural Mesothelioma Patients With High PD-L1 Expression Associated With Sarcomatoid or Biphasic Histology Subtype: A Series of 214 Cases From the Bio-MAPS Cohort.
    Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/31279641
  2. American Cancer Society. (2018, November 16). About Malignant Mesothelioma. :
    Retrieved from: https://www.cancer.org/cancer/malignant-mesothelioma/about/malignant-mesothelioma.html
  3. Kao, S.C. et al. (2011). Accuracy of Diagnostic Biopsy for the Histological Subtype of Malignant Pleural Mesothelioma.
    Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/21266919
  4. Dodson, R. & Hammar, S. Asbestos: Risk Assessment, Epidemiology, and Health Effects. Taylor & Francis: Boca Raton, 2006.
  5. Galateau-Salle, F. Pathology of Malignant Mesothelioma. Springer-Verlag London Limited: London, 2006.
  6. Pass, I., Vogelzang, N. & Carbone, M. Malignant Mesothelioma: Advances in Pathogenesis, Diagnosis, and Transitional Therapies. Springer: New York, 2005.
  7. Trupiano, J.K. et al. (2004). Diffuse Malignant Mesothelioma of the Peritoneum and Pleura, analysis of markers.
    Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/14976533
  8. Bruce, W., Robinson, A. & Chahinian, P. Mesothelioma. Informa Health Care, 2002.
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Last Modified July 25, 2019

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