6 Min Read
Last Updated: 05/22/2024
Fact Checked

Written by Karen Selby, RN | Medically Reviewed By Dr. Andrea Wolf | Edited By Walter Pacheco

Facts About Biphasic Mesothelioma
  • Combination of epithelioid and sarcomatoid mesothelioma cells.
  • Epithelial mesothelioma, also known as epithelioid, is the most common and the easiest to treat.
  • The sarcomatoid cell type accounts for 10% to 20% of cases and is more resistant to treatment.
  • Prognosis and life expectancy for biphasic mesothelioma depends on the ratio of epithelial and sarcomatoid cells.

What Is Biphasic Mesothelioma?

Biphasic mesothelioma is a cell type that contains a combination of epithelial and sarcomatoid cells. Like all other cell types of mesothelioma, asbestos exposure is the leading cause of the disease.

The life expectancy of patients with biphasic mesothelioma varies because prognosis depends on the ratio of epithelial and sarcomatoid cells. A 2021 clinical trial of the immunotherapy drugs Opdivo (nivolumab) and Yervoy (ipilimumab) reported a median survival of 18.1 months for biphasic patients.

The most impressive advancement for checkpoint blockade has been the demonstration that for people with sarcomatoid and biphasic mesothelioma, we can double survival with the combination of ipilimumab and nivolumab.

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

Understanding the characteristics and diagnosis of this type of mesothelioma can help you make informed treatment decisions with your doctor. The study of these cells is known as mesothelioma histology.

Characteristics of Biphasic Mesothelioma

Biphasic mesothelioma cells
Biphasic mesothelioma cells under a microscope.

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 scattered among sarcomatoid cells. The proportion of epithelial and sarcomatoid cells can vary greatly.

Incidence rates show nearly 30% of pleural mesothelioma tumors and 25% of peritoneal tumors are biphasic.

However, many experts believe the cell prevalence of biphasic mesothelioma would be higher if more areas of mesothelioma tumors were sampled and analyzed. How biphasic mesothelioma responds to treatment depends on which type is more prevalent.

Diagnosing the Biphasic Cell Type

During a critical diagnostic test called a biopsy, doctors may collect only a small tissue sample to study in the lab. Taking samples from just one location offers a limited view of the type and amount of mesothelioma cells involved. The biphasic cell type can be challenging to detect and diagnose for this reason.

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

A 2021 clinical research study discovered that membranous HEG1 staining had a specificity of 92.3% in distinguishing biphasic mesotheliomas from all carcinomas and 98.7% in distinguishing biphasic mesotheliomas from pulmonary carcinomas.

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

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. This information allows doctors to rule out common misdiagnoses, including cancers such as synovial sarcoma and carcinosarcoma.

If there’s more than 90% of one cell type, it is referred to as pure of that cell type. So somebody with more than 90% epithelioid cell type under the microscope is considered epithelial. But if there is a representation for both cell types, that’s called biphasic or mixed cell.

A 2011 study published in the Journal of Thoracic Oncology found the biphasic type can be misdiagnosed after a biopsy. Over 80 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 diagnosed initially with this subtype. The authors explained biphasic mesothelioma could 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 those with the epithelioid type.

The reason is that biphasic carries a slightly poorer prognosis than epithelioid. However, treatment is not entirely based on cell type. Treatment may depend more on the stage and location of the tumor than the cell type involved.

Treatment of Biphasic Mesothelioma

  • Chemotherapy: Biphasic cases with more epithelial cells respond better to chemotherapy.
  • Immunotherapy: Pleural cases live at least 18 months with immunotherapy, but the treatment isn’t approved for peritoneal cases yet.
  • Radiation: Patients undergoing multimodal therapy have a lower risk of local recurrence with radiation.
  • Surgery: Early-stage cases benefit the most from surgery.

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

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

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Biphasic Prognosis and Life Expectancy

The prognosis for biphasic mesothelioma varies depending on each case’s ratio of epithelial and sarcomatoid cells. 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.

Research On Biphasic Mesothelioma Survival
  • Clinical Lung Cancer: PD-L1 levels may partially influence the poorer prognosis. In a 2019 study, pleural mesothelioma patients with sarcomatoid and biphasic cells had higher levels of PD-L1, associated with shorter survival.
  • Journal of Clinical Pathology: This study reported that 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.
  • Lung Cancer International: This study reported that cell type affects your life expectancy. On average, epithelial mesothelioma patients survive 200 days longer than patients with biphasic or sarcomatoid cells.
  • Science Reports: A 2021 phase III trial of the immunotherapy drugs Opdivo and Yervoy reported that patients with the sarcomatoid or biphasic cell type had a median survival of 18.1 months compared to just 8.8 months for those on standard chemotherapy.

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 quickly and result in shorter life expectancy.

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