Written By: Devin Golden
Biphasic Mesothelioma
Biphasic mesothelioma is one of the three cell types of mesothelioma. This specific type of mesothelioma is characterized by a combination of two distinct cell types: epithelioid cells and sarcomatoid cells. Among all mesothelioma cases, biphasic mesothelioma accounts for approximately 30% of mesothelioma cases in the United States.
Medically Reviewed By
Dr. Stephen Williams
Precision Oncology Scientist
Medically Reviewed By
Dr. Stephen Williams
Precision Oncology Scientist
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Important Facts About Biphasic Mesothelioma
- Biphasic mesothelioma is diagnosed when a patient’s tumor contains at least 10% of both epithelioid mesothelioma cells and sarcomatoid mesothelioma cells.
- Diagnosing biphasic mesothelioma is rare and can be complex as specialists and pathologists must differentiate each cell type and assess their ratio within the tumor.
- Treatment options for biphasic mesothelioma vary depending on the majority cell type of the patient’s tumor and/or whether the patient’s cancer is pleural or peritoneal.
- The average survival is 9-10 months for biphasic mesothelioma. However, outcomes can vary significantly based on the cell type ratio, location of cancer, and patient’s overall health.
What Is Biphasic Mesothelioma?
Biphasic mesothelioma is one of the three primary cell types of mesothelioma, a rare and aggressive cancer often linked to asbestos exposure. This specific form is characterized by a combination of two distinct cell types: epithelioid cells and sarcomatoid cells.
Epithelioid cells are more structured and uniform, often associated with better prognosis due to their responsiveness to treatment, while sarcomatoid cells are more irregular and aggressive, typically linked to poorer outcomes. The coexistence of these two cell types within the same tumor makes biphasic mesothelioma unique and more challenging to treat.
Among all mesothelioma cases, biphasic mesothelioma is the second most commonly diagnosed cell type, accounting for approximately 30% of cases. Diagnosis typically requires a biopsy and a thorough pathological analysis to identify the proportions and distribution of each cell type, as these factors can influence treatment decisions and prognosis. Understanding the unique characteristics of biphasic mesothelioma is essential for developing personalized treatment plans and improving patient outcomes.
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
Cell Prevalence
Biphasic mesothelioma accounts for ~30% of mesothelioma cases.
Cell Description
Biphasic mesothelioma does not have a specific cell description since it is a combination of epithelioid and sarcomatoid cells. Epithelioid cells have a clearly defined, elongated egg-shape, while sarcomatoid cells are spindle-shaped, long and narrow. The patient’s prognosis depends on which cell is more prevalent. Patients with tumors more abundant with epithelioid cell types have a better overall prognosis.
Cell Behavior
The behavior of biphasic mesothelioma is dependent on the ratio of epithelioid cells to sarcomatoid cells. Epithelioid cells grow quickly, but the cells stick to each other and spread slowly, while sarcomatoid cells multiply rapidly through nearby tissues. A mesothelioma tumor with more sarcomatoid cells will spread quicker than a mesothelioma tumor with more epithelioid cells.
What Causes Biphasic Mesothelioma?
This condition is most commonly associated with prolonged asbestos exposure and can affect the lining of the lungs (pleura) or the abdomen (peritoneum). 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 rid the toxic fibers, they can cause the cells in the mesothelium to undergo genetic mutations, becoming cancerous.
Mesothelial cells make up the thin linings around the lungs, inside the chest wall and the abdominal cavity, called the mesothelium.
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.
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
The most common symptoms of biphasic mesothelioma include shortness of breath, difficulty swallowing, nausea and coughing. However, these symptoms will vary from patient to patient. Not all patients will experience each symptom. A major factor influencing which symptoms a patient experiences is dependent on whether the disease forms near the lungs (pleural mesothelioma) or the abdominal cavity (peritoneal mesothelioma).
Pleural mesothelioma symptoms include:
- Shortness of breath
- Chest or lower back pain
- Coughing
- Difficulty swallowing
- Pleural effusions (fluid in and around the lungs)
Peritoneal mesothelioma symptoms include:
- Abdominal pain
- Nausea
- Vomiting
- Constipation
- Digestive issues
- Ascites (fluid in the abdomen)
Biphasic Mesothelioma Diagnosis
The process for a biphasic mesothelioma diagnosis begins with a biopsy, an essential procedure in which doctors extract tissue from the areas suspected of being affected by cancer. This step is critical for confirming the presence of mesothelioma and identifying the specific cell type.
In cases of biphasic pleural mesothelioma, a biopsy is typically taken from the pleura, the lining surrounding the lungs. For patients with biphasic abdominal mesothelioma (peritoneal mesothelioma), the biopsy sample is obtained from the peritoneum, the abdominal lining. These tissue samples form the foundation for an in-depth analysis of the cancerous cells.
After the tissue biopsy, the extracted sample undergoes microscopic examination to detect the presence of cancer cells. If cancer is confirmed, further analysis is conducted using immunohistochemistry, a diagnostic method that helps determine the cancer type and/or subtype(s).
In the context of diseases like mesothelioma, immunohistochemistry can be used to identify specific cancer markers that distinguish between different cell types (e.g., epithelioid cells versus sarcomatoid cells). This allows for a more accurate diagnosis and understanding of the tumor, guiding precise treatment decisions.
The sensitivity and specificity of immunohistochemistry make it an indispensable tool in both basic research and clinical diagnostics, enabling pathologists to pinpoint exact cell types, tumor subtypes, and specific molecular markers that are essential for treatment planning and prognosis.
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
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 include surgery, chemotherapy, immunotherapy and radiation.
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.
Biphasic Mesothelioma Surgery
Biphasic mesothelioma surgery can eliminate tumors from the patient’s body. 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
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.
Mesothelioma 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.
Mesothelioma 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
The prognosis for biphasic mesothelioma is approximately one year following diagnosis.
A patient’s biphasic mesothelioma prognosis is dependent on the ratio of epithelioid cells to sarcomatoid cells. Patients with biphasic mesothelioma mostly 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.
Aside from the prevalence of epithelioid or sarcomatoid cells, the site of the patient’s mesothelioma can affect their 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 study 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 several cases of patients with biphasic mesothelioma 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
What Is Biphasic Mesothelioma?
Biphasic mesothelioma is one of three cell types of mesothelioma. It is defined as a mesothelioma tumor consisting of both epithelioid cells and sarcomatoid cells. For a case to be diagnosed as biphasic mesothelioma, tumors must contain at least 10% of both epithelioid cells and sarcomatoid cells.
How Common is Biphasic Mesothelioma?
Biphasic mesothelioma accounts for ~30% of all diagnosed mesothelioma cases in the United States. It can occur in both pleural mesothelioma and peritoneal mesothelioma, although it is diagnosed more in pleural mesothelioma cases.
How Long Do People with Biphasic Mesothelioma Live?
Patients with biphasic mesothelioma usually live 9-10 months on average following their 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.
How is Biphasic Mesothelioma Treated?
The standard of care for biphasic mesothelioma is surgery, chemotherapy, immunotherapy and/or radiation. The treatment plan depends on the patient’s specific diagnosis, such as where the tumors are in their body, the ratio of epithelioid cells to sarcomatoid cells, and their overall health. If the cancer is mostly epithelioid cells and the cancer is in early stages, then doctors may find it easier to remove using mesothelioma surgery.
Sources & Author
- About Malignant Mesothelioma. American Cancer Society. Retrieved from: https://www.cancer.org/content/dam/CRC/PDF/Public/8733.00.pdf. Accessed: 3/2/18.
- Malignant Pleural Mesothelioma. Edited by Kenneth O’Byrne and Valerie Rusch. Oxford University Press. 2006.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
