Written By: Devin Golden

Biphasic Mesothelioma Diagnosis

A diagnosis of biphasic mesothelioma means your mesothelioma tumor is composed of both epithelioid and sarcomatoid cells. Getting a diagnosis of mesothelioma and determining the cell type are important steps in your journey to fighting this rare cancer.

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 Diagnosis

  • A diagnosis of biphasic mesothelioma means the patient’s mesothelioma tumors consist of at least 10% of epithelioid cells and 10% of sarcomatoid cells.
  • The diagnostic process begins with patients reporting their symptoms to a doctor and undergoing imaging tests. The final step of the process is getting a tissue biopsy to confirm that there are mesothelioma tumors in the patient’s body.
  • Doctors stain the tissue cells from the biopsy to determine if mesothelioma is present and, if so, which mesothelioma cell type makes up the tumors.

How is Biphasic Mesothelioma Diagnosed?

A medical diagnosis is confirmation of a disease or other condition that explains a person’s symptoms. The process of receiving a mesothelioma diagnosis – regardless of whether it’s biphasic mesothelioma or another cell type – involves imaging tests and eventually a biopsy to test tissue samples for the presence of cancerous cells.

Imagining tests may include X-rays, CT scans or MRIs. If the imaging tests detect a mass, doctors will perform a biopsy and extract a sample of tissue from the chest or abdominal cavity – wherever the mass was found – and send it to a laboratory to be examined under a microscope. Specialists examine the biopsy tissue sample under a microscope to determine which cell type is present.

There are three mesothelioma cell types: epithelioid; sarcomatoid; and biphasic. Biphasic mesothelioma is not an actual cell but rather a combination of epithelioid cells and sarcomatoid cells. Biphasic mesothelioma is diagnosed in approximately 20%-30% of all mesothelioma cases.

How to Determine the Cell Type of Mesothelioma

Doctors determine the mesothelioma cell type by studying tissue samples under a microscope. This process is called pathology, which is the microscopic study of tissue or fluid samples for the presence of cancer.

These tests are conducted by pathologists, who examine the appearance of cells. Pathologists identify the cell type based on:

  • Behavior
  • Size and shape
  • Nuclei
  • Pattern of the sample

Staining for Biphasic Mesothelioma

Pathologists conduct tests on tissue samples by staining tissue cells, which is a process called immunohistochemistry.

The pathologists stain the tissue cells to see if specific cancer proteins react to indicate the presence of mesothelioma. Epithelioid cells and sarcomatoid cells can have different proteins, so this staining process is a method of determining the cell type.

Biphasic mesothelioma is not an individual type of cancer cell but rather a combination of two types of mesothelioma cancer cells: epithelioid cells and sarcomatoid cells. Therefore, there is no one specific stain for biphasic mesothelioma.

Staining for this biphasic cell type involves getting positive reactions for antigens (markers) on the surface of epithelioid cells and sarcomatoid cells.

Epithelioid mesothelioma immunohistochemical antigens (markers):

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

Sarcomatoid mesothelioma immunohistochemical antigens (markers):

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

Doctors can also look at the appearance of the cells as an identifier for whether they are epithelioid cells or sarcomatoid cells. The two cell types differ in their appearance:

  • Epithelioid cells have a well-defined shape and easily visible nuclei. The cells seem to clump together, making them easier to identify.
  • Sarcomatoid cells have a long, narrow and oval shape. The cells either have no clearly defined nuclei or multiple elongated nuclei. Sarcomatoid cells do not clump together, often spreading in a disconnected manner.

Steps of a Biphasic Mesothelioma Diagnosis

Regardless of the mesothelioma cell type, there is a specific process patients should follow to receive an accurate diagnosis. The steps are below:

  • The patient notices symptoms and meets with a doctor.
  • 2
  • Imaging tests, such as an X-ray, CT scan or MRI scan, are performed to see if there are any signs of mesothelioma (such as an unexplained mass or thickening in the thoracic cavity or abdomen) or another condition.
  • 3
  • If these tests show signs of mesothelioma, the doctor will recommend a biopsy to test tissue for the presence of mesothelioma cells.
  • 4
  • The tissue samples from the biopsy are sent to a pathology lab for a microscopic evaluation and undergo a staining process to detect proteins unique to mesothelioma tumor cells.
  • 5
  • After the tissue samples are examined and the staining process is complete, specialists can determine the cell type (epithelioid, sarcomatoid or biphasic) if mesothelioma is present.

Stages of Biphasic Mesothelioma

After receiving a biphasic mesothelioma diagnosis, patients will learn from their doctor which stage their cancer is in at that time. Most types of cancer have four stages: stage 1, stage 2, stage 3 and stage 4. Doctors determine the stage of mesothelioma by testing the size of the tumors and how far the disease has spread.

The stage of mesothelioma changes and progresses. For instance, a patient in stage 1 or 2 at the time of their diagnosis can advance to stage 3 or stage 4 quickly. The progression of the cancer heavily depends on where the cancer forms and the majority cell type.

The 4 Stages of Biphasic Pleural Mesothelioma

There are four stages of pleural mesothelioma (regardless of the cell type):

  • Stage 1 – The earliest stage is defined by tumors localized to the pleura, which is the thin lining of the lungs and where pleural mesothelioma originally forms.
  • Stage 2 – This stage is characterized by tumors in the pleura on one side of the chest with possible disease found in the diaphragm or lung tissue on the same side.
  • Stage 3 – This is the first advanced stage, with tumors spreading beyond the pleura and to the nearby lung, the chest wall, the diaphragm and the mediastinum (the space between your lungs).
  • Stage 4 – The most advanced stage is characterized by tumors found throughout the thoracic cavity and in other areas of the body (such as the abdominal cavity or spinal cord).

Using PCI to Stage Biphasic Peritoneal Mesothelioma

Mesothelioma doctors use a system called the peritoneal cancer index (PCI) to determine the stage of peritoneal mesothelioma.

The system divides the abdomen into 13 sections, and each section receives a score from 0-3 depending on how much cancer is in each section. The scores are added up for a total PCI score, which correlates to one of the four stages used for most cancers: 

  • Stage 1 – PCI score between 1 and 10
  • Stage 2 – PCI score between 11 and 20
  • Stage 3 – PCI score between 21 and 30
  • Stage 4 – PCI score between 31 and higher

Frequently Asked Questions About Biphasic Mesothelioma Diagnosis

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What Do Biphasic Mesothelioma Cells Look Like?

There is not one specific cell called “biphasic mesothelioma.” It is a combination of epithelioid cells and sarcomatoid cells. Therefore, there is no definitive look or appearance of a biphasic mesothelioma cell except that it’s a mixture of both epithelioid cells and sarcomatoid cells.

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How is Biphasic Mesothelioma Diagnosed?

Biphasic mesothelioma is diagnosed by conducting a biopsy where tissue is removed from the chest or abdominal cavity, whichever area doctors suspect mesothelioma may exist and based on the patient’s symptoms. After removing the tissue samples, the medical team sends the tissue to a laboratory for microscopic review.

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How Often is Biphasic Mesothelioma Diagnosed?

Biphasic mesothelioma accounts for 20%-30% of all mesothelioma cases. It’s the second most common type of mesothelioma cell type. Since there are approximately 2,500 new cases of mesothelioma diagnosed in the U.S. each year, biphasic mesothelioma is diagnosed approximately 500-750 times each year.

Sources & Author

  1. Guidelines for Pathologic Diagnosis of Malignant Mesothelioma. Archives of Pathology and Laboratory Medicine. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/28686500/. Accessed: 10/04/19.
  2. Immunohistochemistry. National Cancer Institute. Retrieved from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/immunohistochemistry. Accessed: 10/04/19.
  3. Malignant Mesothelioma Stages. American Cancer Society. Retrieved from: https://www.cancer.org/cancer/types/malignant-mesothelioma/detection-diagnosis-staging/staging.html. Accessed: 05/04/2023.
  4. 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.
Devin Golden

About the Writer, Devin Golden

Devin Golden is a 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.