What Is Biphasic Mesothelioma?
Malignant mesothelioma is categorized into different histological subtypes based on the appearance and behavior of the cancer cells under a microscope. These subtypes help doctors understand how the disease is likely to progress and which treatments may work best. Learn more about histology and its relation to cancer.
Biphasic mesothelioma is one of the three main subtypes of mesothelioma, alongside epithelioid and sarcomatoid mesothelioma. It is characterized by the presence of both epithelioid and sarcomatoid cells within the same tumor. The proportion of these two cell types can vary significantly, which directly impacts the behavior of the disease and its response to treatment.
Where Is Biphasic Mesothelioma Found?
Biphasic mesothelioma can develop in any of the serosal linings of the body, including the pleura (the thin membrane surrounding the lungs), the peritoneum (the lining of the abdominal cavity), the pericardium (the lining around the heart), and the tunica vaginalis (the lining of the testes). The pleura is the most common site for biphasic mesothelioma, as it is for other mesothelioma subtypes, due to the tendency of asbestos fibers to lodge in the pleural lining after inhalation.
How Does Biphasic Mesothelioma Behave Compared to Other Cell Types?
Biphasic mesothelioma exhibits a combination of behaviors seen in epithelioid and sarcomatoid mesothelioma, depending on the ratio of the two cell types. Tumors with a higher proportion of epithelioid cells tend to grow more slowly and respond better to treatment, while those with a higher proportion of sarcomatoid cells are more aggressive and resistant to therapy.
Growth and Spread: Biphasic mesothelioma can exhibit both localized and invasive growth patterns. The sarcomatoid component often drives more aggressive behavior, leading to faster spread to distant tissues.
Treatment Responsiveness: The response to treatment varies widely. Tumors with a higher percentage of epithelioid cells are more likely to respond to surgery, chemotherapy, and radiation, while those with predominantly sarcomatoid cells are less responsive.
Prognosis: The prognosis for biphasic mesothelioma is generally intermediate between epithelioid and sarcomatoid mesothelioma. Patients with a higher proportion of epithelioid cells tend to have better outcomes, while those with more sarcomatoid cells face a poorer prognosis.
What Percentage of Cases Does Biphasic Mesothelioma Represent?
Biphasic mesothelioma accounts for approximately 20% to 35% of all mesothelioma cases, making it the second most common subtype after epithelioid mesothelioma. The variability in cell composition within biphasic tumors makes it a particularly complex subtype to study and treat.
Additional Pertinent Information
The diagnosis of biphasic mesothelioma requires careful examination of tumor samples to identify both epithelioid and sarcomatoid cells. This can be challenging, as small biopsy samples may not capture the full diversity of cell types within the tumor. Pathologists often rely on advanced diagnostic techniques, such as immunohistochemical staining and electron microscopy, to confirm the diagnosis.
Early and accurate diagnosis is critical for biphasic mesothelioma, as it allows doctors to tailor treatment plans based on the tumor's cell composition. For example, patients with a higher proportion of epithelioid cells may benefit from more aggressive treatment approaches, while those with predominantly sarcomatoid cells may require palliative care to manage symptoms and improve quality of life.
How Biphasic Mesothelioma Differs from Other Types
Biphasic mesothelioma is distinct from the other two main mesothelioma subtypes—epithelioid and sarcomatoid—in several key ways, including its cellular structure, growth behavior, treatment responsiveness, and overall prognosis. These differences are critical for diagnosis, treatment planning, and understanding patient outcomes.
Structure of Cells Under a Microscope
Under a microscope, biphasic mesothelioma contains a mix of epithelioid and sarcomatoid cells:
Epithelioid Cells: These cells are cube-shaped or columnar and form organized structures such as tubules, papillae, or solid sheets. They resemble normal epithelial cells and are more responsive to treatment.
Sarcomatoid Cells: These cells are spindle-shaped, elongated, and less organized. They resemble cells found in connective tissue and are more aggressive and resistant to treatment.
The proportion of these two cell types can vary widely, even within the same tumor, making biphasic mesothelioma more complex to diagnose and treat.
Growth Rate and Pattern
Biphasic mesothelioma exhibits a combination of growth behaviors:
Tumors with a higher proportion of epithelioid cells tend to grow more slowly and spread locally before advancing to distant tissues.
Tumors with a higher proportion of sarcomatoid cells are more invasive and spread rapidly to distant organs.
Treatment Responsiveness
The treatment responsiveness of biphasic mesothelioma depends on the ratio of epithelioid to sarcomatoid cells:
Tumors with more epithelioid cells are more likely to respond to surgery, chemotherapy, and radiation.
Tumors with more sarcomatoid cells are less responsive to treatment and may require palliative care to manage symptoms.
Prognosis Comparison
The prognosis for biphasic mesothelioma is intermediate between epithelioid and sarcomatoid mesothelioma:
Patients with a higher proportion of epithelioid cells tend to have better outcomes, with median survival times ranging from 12 to 16 months.
Patients with predominantly sarcomatoid cells have a poorer prognosis, with median survival times of 6 to 12 months.
Additional Pertinent Information
The variability in cell composition within biphasic mesothelioma highlights the importance of accurate diagnosis. Pathologists use advanced techniques, such as immunohistochemical staining and molecular testing, to differentiate biphasic mesothelioma from other subtypes and malignancies. This distinction is crucial for determining the most effective treatment plan and providing patients with a realistic understanding of their prognosis.
In summary, biphasic mesothelioma is a complex and variable subtype of mesothelioma that combines features of both epithelioid and sarcomatoid mesothelioma. Its behavior, treatment responsiveness, and prognosis depend on the proportion of each cell type, making accurate diagnosis and tailored treatment essential for improving patient outcomes.
How Doctors Identify the Biphasic Subtype
Accurately identifying the biphasic subtype of mesothelioma is critical for determining the best treatment options and providing an accurate prognosis. Diagnosis involves a combination of biopsy, histological examination, and immunohistochemical testing. Expert pathology is essential, as misclassification can lead to inappropriate treatment and poorer outcomes.
Biopsy and Histology (Microscopic Review)
The first step in identifying the biphasic subtype is obtaining a tissue sample through a biopsy. There are several methods for collecting biopsy samples, including:
Thoracoscopic biopsy: A minimally invasive procedure where a camera and instruments are inserted into the chest to collect tissue.
CT-guided needle biopsy: A needle is guided by imaging to collect tissue from the affected area.
Open surgical biopsy: A more invasive procedure used when other methods fail to provide sufficient tissue.
Once the tissue is collected, it is examined under a microscope by a pathologist. Biphasic mesothelioma is characterized by the presence of both epithelioid and sarcomatoid components within the same tumor. According to the World Health Organization (WHO), at least 10% of each component must be present to classify the tumor as biphasic. The epithelioid areas often form organized structures, while the sarcomatoid areas consist of spindle-shaped cells. This dual morphology can make diagnosis challenging, requiring further testing.
Immunohistochemical Markers
To confirm the diagnosis and differentiate biphasic mesothelioma from other cancers, pathologists use immunohistochemical (IHC) staining. This technique involves applying antibodies to the tissue sample to detect specific proteins expressed by mesothelioma cells. Key markers for biphasic mesothelioma include:
Calretinin: A highly sensitive and specific marker for mesothelioma, positive in both epithelioid and sarcomatoid components.
WT-1 (Wilms Tumor-1): Strongly expressed in mesothelioma, including biphasic cases, but not in most other cancers.
Cytokeratin 5/6: Commonly expressed in mesothelioma and helps distinguish it from other malignancies.
D2-40 (podoplanin): Often positive in mesothelioma and aids in differentiation from other cancers.
Thrombomodulin: Frequently expressed in mesothelioma and used as part of a diagnostic panel.
In contrast, markers such as CEA (carcinoembryonic antigen), MOC-31, and Ber-EP4 are typically negative in mesothelioma but positive in adenocarcinoma. This helps pathologists rule out other cancers that may mimic mesothelioma.
The use of a panel of markers, rather than relying on a single test, is critical for accurate diagnosis. Pathologists often use a combination of positive and negative markers to confirm the biphasic subtype and exclude other possibilities.
Why Expert Pathology Matters
Diagnosing mesothelioma, particularly the biphasic subtype, is challenging and requires specialized expertise. Misclassification is a significant concern, as biphasic mesothelioma can resemble other cancers or even benign conditions. Studies have shown that general pathologists may misdiagnose mesothelioma in a significant number of cases, leading to inappropriate treatment.
Expert pathologists with experience in mesothelioma use advanced techniques, such as IHC staining and molecular testing, to ensure an accurate diagnosis. They are also more likely to recognize subtle differences in cell structure and staining patterns that distinguish mesothelioma from other diseases. In some cases, a second opinion from a mesothelioma specialist is necessary to confirm the diagnosis.
Additional Considerations
Full-thickness biopsy samples: Providing pathologists with full-thickness tissue samples is crucial, as superficial samples may only show reactive changes rather than malignant cells.
Histological subtyping: Identifying the biphasic subtype is important because it has a worse prognosis compared to the epithelioid subtype but better than the sarcomatoid subtype.
Necropsy findings: In rare cases, the diagnosis may only be confirmed post-mortem, as some tumors are difficult to classify during a patient’s lifetime.
How The Biphasic Subtype Affects Treatment Decisions
Which Treatments Typically Work Best
The biphasic subtype of mesothelioma presents unique challenges in treatment due to its mixed histology. While it generally has a worse prognosis than the epithelioid subtype, it may respond better to treatment than the sarcomatoid subtype. Multimodal treatment approaches, which often include a combination of surgery, chemotherapy, and radiation therapy, are typically employed. However, the response to treatment can vary depending on the proportion of epithelioid and sarcomatoid components.
Surgery: Patients with a higher proportion of epithelioid cells may be eligible for aggressive surgical interventions, such as extrapleural pneumonectomy or pleurectomy/decortication. However, the presence of significant sarcomatoid components may limit surgical options due to the more invasive nature of these cells.
Chemotherapy: Standard chemotherapy regimens, such as pemetrexed and cisplatin, are often used. The response may be less favorable compared to the epithelioid subtype but better than the sarcomatoid subtype.
Radiation Therapy: Radiation may be used as part of a multimodal approach or for palliative care to manage symptoms.
Eligibility for Surgery or HIPEC
Patients with biphasic mesothelioma may be eligible for cytoreductive surgery combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in cases of peritoneal mesothelioma. However, eligibility depends on the proportion of sarcomatoid components, as these are associated with more aggressive disease and poorer outcomes. Patients with a higher proportion of epithelioid cells are more likely to benefit from these intensive treatments.
Use of Immunotherapy for Aggressive Types
Immunotherapy is being explored as a treatment option for biphasic mesothelioma, particularly in cases with a significant sarcomatoid component. Agents such as immune checkpoint inhibitors (e.g., nivolumab and ipilimumab) have shown promise in clinical trials for mesothelioma, including the biphasic subtype. Immunotherapy may be considered as part of a multimodal approach or for patients who are not candidates for surgery.
Notes About Subtype-Specific Clinical Trials
Clinical trials focusing on the biphasic subtype have provided valuable insights into treatment strategies. For example:
Trials have demonstrated that patients with biphasic histology may benefit from tailored multimodal therapies, depending on the proportion of epithelioid and sarcomatoid components.
Research into gene therapy and immunotherapy is ongoing, with some studies exploring the use of these treatments as neoadjuvant (pre-surgery) or adjuvant (post-surgery) options to improve outcomes.
Subtype-specific trials have also highlighted the importance of early diagnosis and tailored treatment plans, emphasizing the need for further research to optimize therapy timing and combinations.
Conclusion
The identification of the biphasic subtype of mesothelioma relies on a combination of biopsy, histological examination, and immunohistochemical testing. Key markers such as calretinin and WT-1 play a vital role in confirming the diagnosis. Expert pathology is essential to avoid misclassification, which can lead to inappropriate treatment and worse outcomes. By ensuring an accurate diagnosis, doctors can provide patients with the most effective treatment options and a clearer understanding of their prognosis.
The biphasic subtype significantly influences treatment decisions, with a preference for multimodal approaches, eligibility for aggressive surgical options like HIPEC (in select cases), and ongoing exploration of immunotherapy and clinical trials to refine and improve outcomes.
Prognosis for Biphasic Mesothelioma
Median Survival Time
Biphasic mesothelioma, which contains both epithelioid and sarcomatoid cell types, has a prognosis that falls between the epithelioid and sarcomatoid subtypes. Studies indicate that the median survival for patients with biphasic mesothelioma ranges from 6 to 12 months, depending on factors such as the proportion of sarcomatoid cells, stage at diagnosis, treatment approach, and overall health. This is shorter than the median survival for epithelioid mesothelioma (12 to 30 months) but better than that of sarcomatoid mesothelioma (4 to 12 months).
How Prognosis Changes with Stage/Anatomical Location
The stage of the disease and its anatomical location significantly impact the prognosis for biphasic mesothelioma:
Early-Stage Disease (Stage I or II): In early stages, the prognosis for biphasic mesothelioma is better than in advanced stages but remains limited. Median survival may range from 12 to 16 months, particularly if the proportion of epithelioid cells is higher and aggressive treatment is pursued.
Advanced-Stage Disease (Stage III or IV): For late-stage biphasic mesothelioma, median survival typically falls to 6–10 months due to the aggressive nature of the sarcomatoid component and the disease's resistance to treatment.
Anatomical Location: Pleural mesothelioma (affecting the lining of the lungs) is the most common form of biphasic mesothelioma and generally has a better prognosis compared to peritoneal mesothelioma (affecting the abdominal lining). However, outcomes are still poor, particularly when the sarcomatoid component is predominant.
Factors That Influence Outcomes
Several factors influence the prognosis for patients with biphasic mesothelioma:
Proportion of Sarcomatoid Cells: A higher percentage of sarcomatoid cells within the tumor is associated with a worse prognosis, as sarcomatoid cells are more aggressive and resistant to treatment.
Treatment Center: Outcomes are often better at specialized mesothelioma treatment centers with access to clinical trials and advanced therapies.
Overall Health and Performance Status: Patients with good overall health and a high performance status may tolerate treatments better, but the mixed nature of biphasic mesothelioma limits the impact of these factors.
Age: Younger patients may have slightly better outcomes, but the prognosis remains poor overall.
Treatment Approach: Multimodal therapy, including surgery, chemotherapy, and radiation, may improve outcomes in some cases, particularly when the epithelioid component is dominant. However, the sarcomatoid component often limits the effectiveness of these treatments.
Histological Confirmation: Accurate diagnosis of the biphasic subtype and assessment of the proportion of sarcomatoid versus epithelioid cells are crucial for setting realistic expectations and tailoring treatment plans.
Summary
In summary, the prognosis for biphasic mesothelioma is poor, with median survival times ranging from 6 to 12 months. The mixed nature of this subtype, particularly the presence of sarcomatoid cells, contributes to its aggressive behavior and resistance to standard treatments. Continued research and innovation in treatment strategies are essential to improve outcomes for patients with biphasic mesothelioma.
Legal and Compensation Considerations for Biphasic Mesothelioma
A diagnosis of biphasic mesothelioma qualifies individuals for legal compensation through asbestos lawsuits, bankruptcy trust claims, and government benefits. Like all forms of mesothelioma, biphasic cases are almost always caused by asbestos exposure, whether through work, secondary contact, or contaminated products.
Why the Biphasic Subtype Matters in Legal Claims:
The mixed nature of biphasic tumors can affect treatment strategy, costs, and life expectancy
Diagnostic complexity may delay recognition, making expert legal and medical guidance even more critical
The prognosis varies—cases with more epithelioid cells may qualify for more aggressive (and expensive) treatments, increasing claim value
Because biphasic mesothelioma blends characteristics of both epithelioid and sarcomatoid cell types, legal strategy often depends on the histological ratio and the patient's treatment trajectory.
Our firm has helped thousands of mesothelioma clients—including many with biphasic diagnoses—recover compensation for:
Medical bills and specialized treatment
Lost wages and future earnings
Home care and long-term support
Pain and suffering
Funeral costs (in wrongful death cases)
👉 Learn more about mesothelioma lawsuits and legal options
📞 Or call 833-4-ASBESTOS for a free consultation.
Frequently Asked Questions About Biphasic Mesothelioma
Q: What does "biphasic" mean in mesothelioma?
A: Biphasic mesothelioma contains both epithelioid and sarcomatoid cells. The behavior of the cancer depends on the dominant cell type—more epithelioid usually means slower growth and better treatment options, while more sarcomatoid means a more aggressive disease.
Q: Does having biphasic mesothelioma affect legal eligibility?
A: No. If you have a confirmed diagnosis and a history of asbestos exposure, you’re eligible to pursue compensation—regardless of cell subtype.
Q: Can biphasic mesothelioma be treated successfully?
A: It depends on the ratio of cell types, stage of the disease, and the patient’s overall health. Cases with more epithelioid cells may respond better to surgery and chemotherapy. In general, biphasic mesothelioma has an intermediate prognosis between the other two subtypes.
Q: What if my loved one passed away before being diagnosed?
A: Family members may still file wrongful death lawsuits or trust fund claims on behalf of a loved one. Our team can help determine what documentation is needed and guide you through the process.