Biphasic Mesothelioma

Key Points

  • Biphasic mesothelioma tumors contain a combination of epithelioid and sarcomatoid cell types.
  • One of the two cell types often makes up the majority of the tumor.
  • Small amounts of biopsy tissue may not reveal both cell types and lead to misdiagnosis.
  • The cancer’s aggressiveness and response to treatment and prognosis differs according to which cell type is dominant.
  • Median survival generally ranges from 10 to 15 months after diagnosis.

Biphasic mesothelioma, also known as mixed mesothelioma, is one of the three major cell types. The biphasic tumor contains a mixture of epithelioid and sarcomatoid malignant cells, the other two major mesothelioma cell types. It is the second most common cell type of mesothelioma, comprising 20 to 40% of all mesothelioma cases.

Biphasic Mesothelioma Cell Characteristics

In biphasic mesothelioma, the epithelioid and sarcomatoid cells can either exist close together, or more often, in separate areas of the tumor.

The growth characteristics and behavior of biphasic mesothelioma vary according to the ratio of the two cell types.

  • When there are more epithelioid cells than sarcomatoid cells, the tumor is more likely to spread locally.
  • When there is a majority of sarcomatoid cells, local and distant metastases are more common.

Like all forms of mesothelioma, the extent and severity of symptoms associated with biphasic mesothelioma will vary with the degree of cancer advancement, and often include shortness of breath, chest pain or tightness, weight loss, and fever. Those patients whose tumors contain large proportions of sarcomatoid cells may also develop pain and breathing restrictions associated with tumor spread to the other side of the chest, as well as symptoms from metastases to local or more distant sites.

Diagnosis Requires The Presence of Both Cell Types

The diagnosis of biphasic mesothelioma is more common in pleural mesothelioma patients. A biphasic diagnosis requires both epithelioid and sarcomatoid cells in at least 10% of the tumor. When a radiological evaluation and/or laboratory test identifies mesothelioma in the chest, tumor tissue is then evaluated. A sample of the tumor is usually obtained with a biopsy. A biopsy is usually performed prior to surgery since the decision to perform radical surgery is influenced by cell type and, in the case of biphasic mesothelioma, the relative proportions of epithelioid and sarcomatoid malignant cells.

The selected method must also take into consideration the accuracy of the biopsy-based diagnosis. This is particularly important for patients with biphasic mesothelioma since preoperative biopsies usually provide rather small amounts of tumor tissue for testing and the epithelioid and sarcomatoid elements often grow in different parts of the tumor. As a result, the sample obtained may not be representative of the overall tumor makeup, leading to misdiagnosis. For example:

  • Around 20 to 50% of patients with biphasic mesothelioma are initially classified as epithelioid.
  • It is reported that as many as 44% of patients with an initial diagnoses of either biphasic or sarcomatoid had a final diagnosis of epithelioid cell type.

Such inaccuracies can have serious consequences, especially if a patient with epithelioid mesothelioma fails to undergo radical surgery because the tumor was initially classified as biphasic or sarcomatoid. In a recent report, a preoperative needle biopsy classified the cell type correctly only 44% of the time. Thoracotomy was the most accurate, correctly classifying cell type in 83% of cases, followed by thoracoscopy at 74%.

To prevent misdiagnosis, doctors use an advanced test known as immunohistochemistry, which can detect certain proteins in cells.

Treatment Success and Response Varies

Patients with biphasic mesothelioma usually have a poorer prognosis and may not be considered for as aggressive a treatment plan as other cell types. However, a number of other factors determine treatment options, and patients may be treated with any or all of the usual mainstays of trimodal therapy:

However, the effectiveness of trimodal treatment for biphasic mesothelioma varies considerably. Responses to therapy and outcomes are strongly affected by the relative amounts of epithelioid and sarcomatoid cells in a given case. Those with biphasic tumors where the epithelioid component predominates would be expected to have a more favorable response to treatment compared to those with sarcomatoid predominance.

Aggressive treatment of patients with mixed mesothelioma may reduce or eliminate epithelioid cells, but the sarcomatoid component is largely unaffected. As such, palliative care may be the best course for those patients with a large proportion of sarcomatoid cells. Palliative therapy may include radiation therapy to reduce tumor size, along with other measures to improve breathing and provide comfort and pain control. Limited surgical procedures such as pleurodesis or drainage of pleural effusions may also be considered if likely to provide greater patient comfort or relieve labored or painful breathing.

Prognosis Depends on Ratio of Cell Types

Studies show biphasic median survival is better than the sarcomatoid cell type, but worse compared to epithelioid tumors. In a study comparing the three, median survival was 11-15 months for biphasic mesothelioma. In the study, patients with more epithelial cells survived longer, but only by 16 days. Sarcomatoid cells are less responsive to treatment than epithelial cells. The more epithelial cells in a biphasic diagnosis, the better the prognosis may be, but only marginally, depending on the particular case.

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Sources & About the Writer [+]
  • 1 Attanoos, R. L. and A. R. Gibbs (2008). "The comparative accuracy of different pleural biopsy techniques in the diagnosis of malignant mesothelioma." Histopathology 53(3): 340-344.
  • 2 Balduyck, B., et al. (2010). "Therapeutic surgery for nonepithelioid malignant pleural mesothelioma: is it really worthwhile?" Ann Thorac Surg 89(3): 907-911
  • 3 Ceresoli, G. L., et al. (2001). "Therapeutic outcome according to histologic cell type in 121 patients with malignant pleural mesothelioma." Lung Cancer 34(2): 279-287.
  • 4 Galetta, D., et al. (2015). "Sarcomatoid mesothelioma: future advances in diagnosis, biomolecular assessment, and therapeutic options in a poor-outcome disease." Tumori: 0.
  • 5 Kao, S. C., et al. (2011). "Accuracy of diagnostic biopsy for the histological cell type of malignant pleural mesothelioma." J Thorac Oncol 6(3): 602-605.
  • 6 Klebe, S., et al. (2010). "Sarcomatoid mesothelioma: a clinical-pathologic correlation of 326 cases." Mod Pathol 23(3): 470-479.
  • 7 Linton, A., et al. (2014). "Factors associated with survival in a large series of patients with malignant pleural mesothelioma in New South Wales." Br J Cancer 111(9): 1860-1869.
  • 8 Mansfield, A. S., et al. (2014). "Systematic review of response rates of sarcomatoid malignant pleural mesotheliomas in clinical trials." Lung Cancer 86(2): 133-136.
  • 9 Meyerhoff, R. R., et al. (2015). "Impact of mesothelioma histologic cell type on outcomes in the Surveillance, Epidemiology, and End Results database." J Surg Res 196(1): 23-32.
  • 10 Neragi-Miandoab, S., et al. (2008). "Morbidity, mortality, mean survival, and the impact of histology on survival after pleurectomy in 64 patients with malignant pleural mesothelioma." Int J Surg 6(4): 293-297.  Retrieved from
  • 11 Taioli, E., et al. (2015). "Determinants of Survival in Malignant Pleural Mesothelioma: A Surveillance, Epidemiology, and End Results (SEER) Study of 14,228 Patients." PLoS One 10(12): e0145039.
  • 12 Viti, A., et al. (2015). "Biologic therapy and gene therapy in the multimodality treatment of malignant pleural mesothelioma." Ann Transl Med 3(17): 248.
  • 13 Wong, R. M., et al. (2014). "Immunotherapy for malignant pleural mesothelioma. Current status and future prospects." Am J Respir Cell Mol Biol 50(5): 870-875.
  • About The Writer Photo of Dan Heil Dan Heil

    Dan is a contributing writer for The Mesothelioma + Asbestos Awareness Center. He hopes to help educate on everything related to a mesothelioma diagnosis and answer any questions patients or family members may have.