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Biphasic Mesothelioma

Biphasic mesothelioma, also referred to as mixed mesothelioma, is the second most common cell type, accounting for 15% – 20% of malignant pleural mesothelioma cases.

As with all forms of mesothelioma, the biphasic cell type is caused primarily by asbestos exposure. While epithelioid and sarcomatoid are separate mesothelioma cell types, biphasic mesothelioma is a combination of the two, meaning tumors contain both epithelial and sarcomatoid cells. Symptoms, treatment and prognosis can all vary depending on which of the two cell types is dominant. On average, patients survive one year.

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Biphasic Cell Structure

Biphasic tumors consist of the two other mesothelioma cell types, and structure will vary depending on which cell is more prominent. Epithelioid cells have a well-defined shape and nucleus, and are found in uniform and organized arrangements. Sarcomatoid cells are typically oval or oblong in shape, and the nucleus is not as easily recognizable.

Though biphasic tumors have a mixture of both cell types, the two kinds of cells are typically not found in the same location and form differentiated arrangements in different areas of the tumor. For instance, epithelial cells may cluster together in the pleura (lung lining), whereas sarcomatoid cells don’t typically stay together and are faster to spread, so might be found in the chest cavity or elsewhere. The extent of metastasis or spreading may also depend on which cell type is dominant. Epithelial cells will likely spread minimally and locally, while sarcomatoid cells may spread locally and distantly.

Diagnosing Biphasic Mesothelioma

As with all forms of malignant mesothelioma cancer, symptoms may not appear for decades after asbestos exposure. In instances of biphasic mesothelioma, recognizing symptoms can be even more difficult as they will vary depending on the location of the tumor and the percentage of each cell type in the tumor. Other factors, such as overall health, age, and pre-existing conditions can also affect the breadth and intensity of cancer symptoms.

Common Symptoms of Biphasic Mesothelioma
  • Shortness of breath
  • Chest pain
  • Tightness in the chest
  • Fluid buildup in the lungs or abdomen
  • Weight loss
  • Fever and/or night sweats

Biphasic mesothelioma is typically pleural-based, meaning it is located in the linings of the lungs, though there have been some peritoneal mesothelioma cases. Malignant pleural mesothelioma is extremely aggressive and can cause an array of bothersome symptoms, not limited to those listed above.

A proper mesothelioma diagnosis will begin with imaging tests, including x-rays and CT scans, to find any visible tumors or excess fluid in the chest cavity or abdomen. Doctors may also sometimes perform blood tests to identify specific biomarkers that can help differentiate mesothelioma from other cancers and conditions.

The most important step for an accurate diagnosis is a biopsy, a fluid or tissue sample that is analyzed under a microscope. Since biphasic mesothelioma has a combination of cell types, often in different regions of the tumor, multiple biopsies may be needed to recognize the two types of cells. Studies have found that even with multiple biopsies, an accurate biphasic mesothelioma is challenging. Research indicates at least 20 – 50% of biphasic mesothelioma cases were originally diagnosed as epithelioid. One study noted the accuracy of initial diagnosis was dependent on the type of biopsy:

For a biphasic mesothelioma diagnosis, there has to be at least 10% of epithelial or sarcomatoid cells in the tumor.

Biphasic Mesothelioma Prognosis

Biphasic mesothelioma can lead to a wide variance in prognosis for individual cases, largely dependent on the percentage of each cell type present in the tumors. Epithelial cells are typically more responsive to treatment and don’t metastasize as quickly as the sarcomatoid type. As such, patients with predominantly epithelial cells will have a better prognosis. Other factors, like stage of the disease and a patient’s overall health, can also impact an individual’s life expectancy.

Resources for Biphasic Mesothelioma Patients

Overall, epithelioid mesothelioma patients typically survive one to two years, while sarcomatoid mesothelioma patients have an average survival of six months. Studies have suggested an average prognosis of one year for biphasic mesothelioma, though researchers have noted survival times ranging from six months to five years or longer.

Treatment Options for Biphasic Mesothelioma

Surgery, chemotherapy, and radiation are three common modes of treatment for all forms of mesothelioma. Patients with the biphasic cell type may sometimes be more limited in treatment options, should sarcomatoid cells be most predominant. In those instances, a mesothelioma specialist may recommend palliative care as the best treatment option to relieve symptoms, like pleural effusion, and improve comfort.

Surgery, like an extrapleural pneumonectomy, may be a viable option for biphasic mesothelioma patients with predominantly epithelial cells and an earlier diagnosis. One of the most successful treatments for peritoneal mesothelioma is combination cytoreductive surgery with intraoperative heated chemotherapy (HIPEC), which has led to a five-year survival rate of at least 50%. Previously, doctors believed this treatment wouldn’t be an option for biphasic mesothelioma because of the potential distant metastasis of sarcomatoid cancer cells. A recent clinical trial explored the treatment for 34 biphasic peritoneal mesothelioma patients. The study found five-year survival rates from 41.6% with near complete resection to 50.2% for patients who experienced complete surgical resection.

Chemotherapy and radiation therapy are also often part of a multimodal mesothelioma treatment plan, but doctors have seen mixed results with biphasic mesothelioma. Both therapies are largely ineffective for sarcomatoid cells, though have shown some success in extending life expectancy for epithelioid mesothelioma. Immunotherapy treatments have been shown to be active in patients with mesothelioma who have already received chemotherapy, and are becoming a standard treatment option for many patients with mesothelioma.

Patients and their loved ones may also explore potential clinical trials focused on improving treatments for biphasic mesothelioma, which may further extend life expectancy.

Author: Linda Molinari

Editor in Chief, Mesothelioma Cancer Alliance

Linda Molinari

Reviewer: Dr. James Stevenson

Medical Reviewer and Thoracic Medical Oncologist

Dr. James Stevenson

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Scherpereel A, Mazieres J, et al. Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma(IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial. Lancet Oncology. February 2019;20(2):239-253. doi: 10.1016/S1470-2045(18)30765-4

Votanopoulos KI, Sugarbaker P, et al. 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. March 2018; 25(3):667-673. doi: 10.1245/s10434-017-6293-5

Wu D, Hiroshima K, et al. Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma. Annals of Diagnostic Pathology. February 2017; 26:31-37. doi: 10.1016/j.anndiagpath.2016.10.010

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