Written By: Devin Golden

Biphasic Mesothelioma

Biphasic mesothelioma is a cell type of mesothelioma characterized by a combination of epithelioid and sarcomatoid cells. This cell type is the second most commonly diagnosed, accounting for approximately 30% of mesothelioma cases. A patient’s biphasic mesothelioma prognosis heavily depends on the ratio of epithelioid cells to sarcomatoid cells.

Karen Ritter, RN BSN

Medically Reviewed By

Karen Ritter, RN BSN

Registered Nurse

Karen Ritter, RN BSN

Medically Reviewed By

Karen Ritter, RN BSN

Registered Nurse


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Important Facts About Biphasic Mesothelioma

  • Biphasic mesothelioma is diagnosed when a patient has at least 10% of each of these mesothelioma cell types: epithelioid and sarcomatoid. Biphasic mesothelioma tumors contain a combination of two cell types.
  • Diagnosing biphasic mesothelioma is rare and can be complex as specialists and pathologists must differentiate each cell type and determine the cell ratio. Treatment options vary on a case-by-case basis.
  • Treatment options for biphasic mesothelioma vary depending on the majority cell type and whether the patient’s cancer is pleural or peritoneal.
  • The average survival is 9-10 months for biphasic mesothelioma.

What Is Biphasic Mesothelioma?

Biphasic mesothelioma is a subtype of mesothelioma diagnosed when a combination of epithelioid cells and sarcomatoid cells are found in the patient’s mesothelioma tumors. This cell type accounts for between 20% and 30% of cases.

For mesothelioma to be classified as biphasic, each cell type (epithelioid and sarcomatoid) must account for at least 10% of the cells found in the mesothelioma tumors. If one cell type is less than 10%, then the disease is diagnosed as the majority cell type (either epithelioid or sarcomatoid).

The only cause of biphasic mesothelioma, regardless of the cell type, is asbestos exposure, which often results in irritation to healthy mesothelial cells. This can cause genetic cell mutations and mesothelioma tumor formation. When the cancer-causing asbestos fibers infiltrate the body, the tiny particles become lodged in the mesothelium, which is the thin lining of the lungs, abdomen and heart.

The mesothelium is made up of healthy epithelial cells. When these cells mutate, they become diseased epithelioid or sarcomatoid cells, which results in mesothelioma.

Epithelioid Cell Type
Epithelioid Cell Type

Biphasic Cell Type

Due to the combination of cell types in biphasic mesothelioma, the growth and spread of the cancer can vary along with treatment options. Tumors with a higher epithelioid mesothelioma cell ratio typically grow faster but do not spread as quickly. Tumors with a higher sarcomatoid mesothelioma cell ratio spread faster and are more erratic, meaning they don’t grow in easily identifiable clumps but rather as multiple separate tiny tumors. This characteristic makes biphasic mesothelioma with a higher percentage of sarcomatoid cells more difficult to treat with surgery.

Characteristics of Biphasic Mesothelioma Cells

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Cell Prevalence

Biphasic mesothelioma accounts for 20% to 30% of mesothelioma cases.

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Cell Description

A biphasic diagnosis involves a mixture of the other two mesothelioma cell types. This means the patient's prognosis depends on which cell is more prevalent. More epithelioid cells for the patient equals a better prognosis.

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Cell Behavior

The behavior of a biphasic diagnosis is dependent on the ratio of cells. A mesothelioma with more sarcomatoid cells will spread quicker than a mesothelioma with more epithelioid cells.

What Causes Biphasic Mesothelioma?

Exposure to asbestos is the only cause of mesothelioma. When microscopic asbestos fibers are inhaled or ingested, they can become stuck in the mesothelium lining around the lungs or in the abdominal cavity. If the body is unable to get rid of the toxic fibers, they can cause the cells in the mesothelium to mutate, eventually becoming cancerous.

The human body is made up of four types of cells: epithelial cells, nerve cells, muscle cells and connective tissue cells. Epithelial cells are found in the linings of the lungs, abdomen and heart, which are called the mesothelium.

Biphasic mesothelioma is composed of a combination of epithelioid cells or sarcomatoid cells, which were both once healthy epithelial cells in the mesothelium. Exposure to asbestos can cause these healthy cells to mutate into mesothelioma tumors.

Biphasic mesothelioma is diagnosed when at least 10% of the tumor contains epithelioid and sarcomatoid cells.

Epithelial cells line the thin membrane just outside of the lung cavity, abdominal cavity and heart
Epithelial cells line the thin membrane just outside of the lung cavity, abdominal cavity and heart

Mesothelial cells make up the thin linings around the lungs, inside the chest wall and the abdominal cavity, called the mesothelium.

Epithelial cells can transform into sarcomatoid cells when they become cancerous
Epithelial cells can transform into sarcomatoid cells when they become cancerous

Asbestos fibers can remain in the body for more than a decade, causing inflammation and cell damage. Genetic changes can occur in the mesothelial cells resulting in the development of the rare cancer, mesothelioma.

When mesenchymal cells become cancerous, they are called sarcomas
When mesenchymal cells become cancerous, they are called sarcomas

Epithelioid cells form tubular or cubic patterns while sarcomatoid cells are tightly packed spindle shaped. Biphasic mesothelioma will present with a combination of both cell types, each contributing more than 10% of the malignant cells.

Biphasic Mesothelioma Symptoms

Biphasic mesothelioma symptoms resemble those of epithelioid mesothelioma and sarcomatoid mesothelioma. Symptoms are dependent on where the disease forms, whether it’s pleural mesothelioma or peritoneal mesothelioma.

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Biphasic pleural mesothelioma symptoms include:

  • Shortness of breath
  • Chest or lower back pain
  • Coughing
  • Difficulty swallowing
  • Pleural effusions (fluid in and around the lungs)
  • Abdominal pain
  • Nausea
  • Vomiting
  • Constipation
  • Digestive issues
  • Ascites (fluid in the abdomen)

Biphasic Mesothelioma Diagnosis

Biphasic mesothelioma can be complicated to diagnose due to the combination of cells present in the tumors. Specialists will often need to conduct multiple diagnostic tests in order to determine the ratio of epithelioid cells to sarcomatoid cells and determine a final diagnosis.

The diagnositic process for biphasic mesothelioma begins with a biopsy. Doctors will extract tissue from the affected area and analyze the tissue sample under a microscope. For instance, a patient with biphasic pleural mesothelioma will undergo a biopsy taken from the lining of the lungs. In cases of biphasic peritoneal mesothelioma, a biopsy will be taken from the lining of the abdomen.

After the tissue biopsy, doctors will examine the tissue samples for the presence of cancer cells. Once cancer is detected, the tissue sample is analyzed using immunohistochemistry to help identify the type of cancer.

Immunohistochemistry is a diagnostic technique that helps pathologists identify the type and subtype of cancer by locating tumor markers on the surface of cancer cells. Antibodies (proteins) are used to bind with antigens (markers) found on the cell surface.

Antigens are like locks on the surface of cells and the antibodies are like keys that can locate and connect to these antigens. When the antibodies bind to the antigens, a colored dye is activated indicating the presence of a certain type of cell that may help determine the exact type of cancer.

Since biphasic mesothelioma is characterized by a combination of epithelioid and sarcomatoid cells, pathologists are looking for a number of immunohistochemical markers. The final cell type diagnosis heavily depends on the ratio of epithelioid cells to sarcomatoid cells.

Epithelioid mesothelioma immunohistochemical antigens (markers) include:

  • Calretinin
  • Cytokeratin 5 or 5/6
  • Wilms' tumor-I antigen (WT1)
  • Podoplanin (D2-40)

Sarcomatoid mesothelioma immunohistochemical antigens (markers) include:

  • Podoplanin (D2-40)
  • Pancytokeratin
  • Calretinin
  • GLUT1
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Second Opinions

Mesothelioma is a rare, aggressive and complex cancer that requires a deep understanding to identify, diagnose, and treat. Patients diagnosed with mesothelioma, especially those with rare cell types like biphasic, should seek a second opinion from a mesothelioma specialist.

Mesothelioma specialists dedicate their entire careers to gaining more knowledge on mesothelioma and how to effectively treat it. Finding a mesothelioma specialist to review diagnostic tests and determine the best possible treatment plan often makes a difference in the patient’s outcome.

A second opinion from a mesothelioma specialist can significantly improve your chances of survival. Oncologists and surgeons do not typically possess the experience required to create the best treatment plan, as some mesothelioma treatment options are only offered through clinical trials and not yet FDA-approved.

Due to the rarity of mesothelioma, it is sometimes necessary to get a second opinion from a specialized pathology lab to receive a definitive diagnosis. For instance, Johns Hopkins Medicine offers a specific pathology lab dedicated to providing second opinions for diagnostic purposes.

Pathologists at Johns Hopkins can help determine a definitive diagnosis by analyzing pathology slides which can then help mesothelioma specialists provide an effective treatment plan for each individual patient. Receiving a second opinion from an experienced specialist is crucial in fighting mesothelioma.

To get in touch with a mesothelioma specialist for a second opinion, use our free Doctor Match program.

Biphasic Mesothelioma Treatment Options

Biphasic mesothelioma treatment options vary depending on where the cancer forms and which cell type is most prevalent. Surgery, chemotherapy, immunotherapy and radiation are common treatment options for mesothelioma patients.

Emerging treatment options, such as gene therapy, oncolytic virus therapy and others, may also be suggested by mesothelioma specialists. Patients interested in these new therapies must enroll in clinical trials to receive the treatments, as they are not yet FDA-approved for mesothelioma.

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Biphasic Mesothelioma Surgery

Biphasic mesothelioma can be treated with three surgical procedures, depending on where the cancer forms. Patients with biphasic pleural mesothelioma have two options: extrapleural pneumonectomy and pleurectomy with decortication. Patients with biphasic peritoneal mesothelioma only have one surgical option: cytoreduction with heated intraperitoneal chemotherapy (HIPEC).

Extrapleural pneumonectomy (EPP) for biphasic pleural mesothelioma removes the affected inner pleural lining of the lung (visceral pleura), the outer pleural lining of the chest wall (parietal pleura), the entire diseased lung, and potentially part of the diaphragm and the lining around the heart (pericardium).

Pleurectomy with decortication (P/D) for biphasic pleural mesothelioma removes the affected inner pleural lining of the lung (visceral pleura) and outer pleural lining (parietal pleura). An extended version of P/D, sometimes called a “radical pleurectomy”, may also remove part or all of the diaphragm and pericardium, if diseased tissue is present.

Cytoreduction with heated intraperitoneal chemotherapy (HIPEC) is the surgical option to treat biphasic peritoneal mesothelioma. It is an aggressive, two-part surgery beginning with cytoreduction (debulking) and removes all visible mesothelioma tumors in the abdomen. The surgeon then removes the peritoneum (lining inside the abdominal cavity), which is where peritoneal mesothelioma forms.

Many times it is necessary to remove part of the intestines or other affected abdominal organs. Once all the visible tumors are removed, the doctor will administer heated chemotherapy directly into the abdominal cavity.

Chemotherapy, Immunotherapy, Radiation, and Emerging Treatment Methods Icon

Chemotherapy, Immunotherapy, Radiation, and Emerging Treatment Methods

Aside from surgery, mesothelioma can be treated with chemotherapy, immunotherapy, radiation and other emerging treatments. These methods are often recommended in conjunction with surgery, but are a first line option when the patient is not eligible for surgery.

With many mesothelioma clinical trials in progress, researchers are developing innovative ways to treat biphasic mesothelioma with oncolytic virus therapy, gene therapy and other emerging treatment methods. The newest research recommendations state that biphasic mesothelioma patients should not be excluded from participating in clinical trials, which could promote the development of effective treatment options for all mesothelioma cell types.

Where mesothelioma forms is the greatest contributing factor for determining the treatment methods available to the patient. For instance, biphasic peritoneal mesothelioma patients should not receive radiation therapy. This type of mesothelioma forms in the abdomen, and the radiation beams can cause significant damage to vital abdominal organs, resulting in further health issues. However, biphasic pleural mesothelioma patients may receive radiation therapy, if recommended by their doctor.

Chemotherapy is a commonly used treatment method for all types of mesothelioma. There are two FDA-approved chemotherapy drugs for mesothelioma treatment, pemetrexed and cisplatin.

Immunotherapy is a treatment option growing in use and acceptance by mesothelioma specialists. The FDA has approved three immunotherapy drugs for the treatment of pleural mesothelioma: Opdivo, Yervoy and Keytruda. Immunotherapy is being tested in clinical trials for peritoneal mesothelioma treatment.

Multimodal treatment is commonly used to describe an effective approach to mesothelioma treatment, as it combines multiple therapies or treatment methods to improve effectiveness. Specialists often recommend using chemotherapy before or after surgery, or chemotherapy followed by radiation.

Prognosis for Biphasic Mesothelioma

A patient’s biphasic mesothelioma prognosis is dependent on the ratio of epithelioid cells to sarcomatoid cells. Patients with biphasic mesothelioma largely composed of epithelioid cells tend to have a better prognosis than those with mostly sarcomatoid cells.

According to a 2018 study published in Clinical Lung Cancer, the average survival time for patients with biphasic mesothelioma was 9.5 months following their diagnosis. Patients who underwent surgery extended their survival time by nearly six months.

In another study, researchers found that biphasic mesothelioma patients whose tumors were made up of more than 50% sarcomatoid cells have an average prognosis of 6.6 months. Patients whose tumors include more than 50% epithelioid cells had a prognosis of 11.8 months.

Aside from the prevalence of epithelioid or sarcomatoid cells, where the patient’s mesothelioma forms can affect a patient’s prognosis. A study published in the Annals of Surgical Oncology evaluated the effects of cytoreductive surgery with HIPEC on biphasic peritoneal mesothelioma patients. The median survival time was 6.8 years following complete resection of peritoneal mesothelioma tumors, and the 5-year survival rate was 50%.

Another report published in the Annals of Surgical Oncology observed survival times for biphasic pleural mesothelioma patients after surgery compared with no operation. The median overall survival for the patients who underwent surgery was 15.8 months compared to 9.3 months for patients who had no operation.

There have been cases of biphasic mesothelioma patients living longer than the average survival rate. Receiving mesothelioma treatment from a specialist is the most effective way to improve your prognosis.

Frequently Asked Questions About Biphasic Mesothelioma

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What Does Biphasic Mesothelioma Mean?

Biphasic mesothelioma is a combination of both epithelioid cells and sarcomatoid cells, which are two cell types often present in mesothelioma tumors. For a case to be diagnosed as biphasic mesothelioma, it must consist of at least 10% of both types of cells.

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How Common is Biphasic Mesothelioma?

Biphasic mesothelioma accounts for between 20% and 30% of all mesothelioma cases. It can occur in both pleural mesothelioma and peritoneal mesothelioma, although it is diagnosed more in pleural mesothelioma cases.

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How Long Do People with Biphasic Mesothelioma Live?

The average life expectancy for biphasic mesothelioma is 9-10 months following diagnosis. Surgery can extend a patient’s life by months or even years. The prognosis also depends on whether the cancer consists of more epithelioid cells or more sarcomatoid cells.

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How is Biphasic Mesothelioma Treated?

Treatment for biphasic mesothelioma depends on which cell type makes up the majority of the tumor cells. If the cancer is mostly epithelioid cells, then doctors may find it easier to remove using mesothelioma surgery. If the patient’s biphasic mesothelioma is made up mostly of sarcomatoid cells, surgery is more difficult and complicated. Doctors may opt for chemotherapy or immunotherapy as a first line treatment option to extend the patient’s life.

Sources & Author

  1. About Malignant Mesothelioma. American Cancer Society. Retrieved from: https://www.cancer.org/content/dam/CRC/PDF/Public/8733.00.pdf. Accessed: 3/2/18.
  2. Malignant Pleural Mesothelioma. Edited by Kenneth O’Byrne and Valerie Rusch. Oxford University Press. 2006.
  3. Survival results in biphasic malignant pleural mesothelioma patients: A multicentric analysis. Journal of Thoracic and Cardiovascular Surgery. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/31590954. Accessed: 10/22/19.
  4. Is Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Justified for Biphasic Variants of Peritoneal Mesothelioma? Outcomes from the Peritoneal Surface Oncology Group International Registry. Annals of Surgical Oncology. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/29260418?dopt=Abstract. Accessed: 10/22/19.
  5. Is There a Role for Cancer-Directed Surgery in Early-Stage Sarcomatoid or Biphasic Mesothelioma? Annals of Thoracic Surgery. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/30278171. Accessed: 10/23/19.
  6. Survival by Histologic Subtype of Malignant Pleural Mesothelioma and the Impact of Surgical Resection on Overall Survival. Clinical Lung Cancer. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/30224273. Accessed: 10/23/19.
  7. Application of Immunohistochemistry in Diagnosis and Management of Malignant Mesothelioma. National Library of Medicine. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082260/. Accessed: 08/21/2023.
  8. Clinical Significance of Histologic Subtyping of Malignant Pleural Mesothelioma. National Library of Medicine. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354152/. Accessed: 08/22/2023.
Devin Golden

About the Writer, Devin Golden

Devin Golden is the senior content writer for Mesothelioma Guide. He produces mesothelioma-related content on various mediums, including the Mesothelioma Guide website and social media channels. Devin's objective is to translate complex information regarding mesothelioma into informative, easily absorbable content to help patients and their loved ones.