Mesothelioma Pathology Expertise Matters for Diagnosis
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Dr. Jacques Fontaine: Mesothelioma Pathology Expertise Matters for Diagnosis

Diagnosing mesothelioma is difficult.

Mesothelioma usually presents in the chest with fluid around the lungs.

It presents with pain. It presents with plaques seen on an x-ray or a CT scan. However, there are multiple, much more common reasons to have fluid around the lung or plaques on the chest. They're not necessarily mesothelioma. And that's why a diagnosis of mesothelioma can take months. The best way to diagnose mesothelioma is to actually take a biopsy, a small piece of it, and look at it under a microscope.

And not just look at under a microscope by any pathologist, but pathologist who has an expertise in making that diagnosis. Because even with a good sample of tumor, looking at it under a microscope, it can sometimes be difficult to make that diagnosis.

And it's important not only to know that it's mesothelioma, it's important to know what is the histological subtype. Is it epithelial or is it sarcomatoid or is it a mixture of both called mixed or biphasic? Does that change the type of treatment? But in these days, that's not enough.

We need to know what is the genetic fingerprint of that tumor. What are some of the proteins that are overexpressed on that tumor? What are some of the driver mutations, the genetic alterations on that tumor? Because now we have specific cancer medications for each one of these mutations, for each one of these these proteins.

So it's personalized medicine, individualized treatment for individualized cancers. We can no longer treat all cancers the same way. Just like there's no two people that are identical, there are no two cancers that are identical. The ability to choose the right treatment for the right patient will decrease the likelihood a patient will get side effects, will increase the likelihood that a patient responds to the treatment that the tumor shrinks or the tumor gets cured.

So knowing more about the tumor will allow us to find the right treatment for that tumor.

What Is a Mesothelioma Pathology Report?

A mesothelioma pathology report is the written results of a pathologist examining a sample of your tissue or fluid under a microscope. It is the document that confirms if you have mesothelioma, what type it is and the evidence behind that conclusion.

How a Mesothelioma Pathology Report Is Created

  1. A doctor obtains a tissue biopsy or fluid sample from the area of concern.
  2. The sample is processed in a laboratory and prepared on microscope slides.
  3. A pathologist examines the cells and tissues under a microscope.
  4. Special tests, such as IHC stains, may be performed to help identify the cancer.
  5. The pathologist reviews all findings and writes the final pathology report.

Mesothelioma can be difficult to diagnose because it resembles other cancers or illnesses. Doctors may first examine cells collected from fluid around the lungs or abdomen, a process called cytology. However, fluid samples alone often are not enough to confirm mesothelioma. In most cases, a tissue biopsy is needed so the pathologist can study the cells directly, perform special tests such as immunohistochemistry and issue a final diagnosis. Because additional testing is often required, receiving a final pathology report can take time.

Expert Insight

“Just because your doctor told you that you have fluid around the lung does not necessarily mean you have mesothelioma… Very often you need a surgical biopsy or core biopsy to make sure that you indeed have mesothelioma.”

Dr. Jacques Fontaine , thoracic surgeon, Moffitt Cancer Center

Parts of Your Mesothelioma Pathology Report

Most mesothelioma pathology reports follow the same order. Reading from the top, you’ll see who and what was tested, your clinical history, what the sample looked like to the naked eye, what it looked like under the microscope, the special stains that were run and the final diagnosis. Understanding what each section is designed to tell you can make a complex report much easier to follow.

What Each Section of Your Report Means

Section of the ReportWhat It Tells You
Patient & specimen informationIdentifies you and the specimen (the tissue or fluid sample that was tested), including where in the body it came from.
Clinical historyProvides background information, such as symptoms, imaging findings, or concerns that led to the biopsy.
Gross descriptionDescribes what the sample looked like before it was examined under a microscope.
Microscopic descriptionDescribes what the pathologist saw under the microscope, including cell appearance, growth patterns, and whether the cells were invading nearby tissue.
Special studies / IHCLists special studies used to confirm mesothelioma and rule out other cancers.
Final diagnosisStates the pathologist’s conclusion about what disease is present. 
Pathologist & signatureIdentifies the pathologist who reviewed the case, signed the report, and the institution where the testing was performed.

Patient and Clinical History

The top of the report identifies you, your doctor, the date and the sample that was tested. A specimen is the tissue or fluid sample sent to the laboratory and an accession number is the lab’s tracking number for your case. This section also notes where in the body the specimen came from and restates your clinical history, including symptoms, imaging findings, or asbestos exposure. Seeing “possible mesothelioma” here is normal and does not mean the diagnosis has been confirmed.

Gross and Microscopic Descriptions

The gross description explains what the sample looked like to the naked eye, including its size, color and texture. The microscopic description explains what the pathologist saw under the microscope, including cell shapes, growth patterns and whether the cells are invading nearby tissue. This is also where much of the evidence for the mesothelioma cell type appears, as epithelioid and sarcomatoid cells look different under the microscope.

Special Studies

This section lists the stains and molecular tests used to confirm the cancer’s identity. These findings help pathologists determine whether the cells are mesothelioma or another type of cancer. Markers expected to be positive in mesothelioma, such as calretinin or cytokeratin 5/6, help confirm it, while markers expected to be negative help rule out other cancers. Some specialized tests, including IHC markers, are performed to confirm the cancer type.

Pathologist Information and Signature

This section names the pathologist who signed the report and the institution where the testing was performed. It is also where you can see whether the diagnosis was made by a mesothelioma-experienced pathologist or a general community pathologist. If the diagnosis was made outside a specialty center, many patients choose to have their slides and tissue reviewed by a mesothelioma specialist for additional confirmation.

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Understanding Your Final Mesothelioma Diagnosis

The final mesothelioma diagnosis is the one line that states what you have. For mesothelioma, it usually names the site that confirms “malignant mesothelioma” and gives the cell type, such as epithelioid. Everything else on the pathology report is the evidence behind this conclusion.

Mesothelioma Diagnosis Example

  • Left pleura → The site where the cancer was found.
  • Malignant mesothelioma → The confirmed diagnosis. “Malignant” means cancerous.
  • Epithelioid type → The mesothelioma cell type, which can help guide treatment decisions.

The diagnosis line tells you what the cancer is, not how far it has spread. Information about mesothelioma staging is determined separately and usually comes from imaging studies and your care team.

Thoracic Surgeon Dr. Andrea Wolf says, “The patient needs to have the correct cancer diagnosis… a primary cancer of the pleura is very different than a cancer from some other organ that has gone to that lining… and is treated very differently.” An accurate mesothelioma diagnosis can help patients seek proper treatment as soon as possible.

Your Mesothelioma Cell Type

Mesothelioma has three cell types: epithelioid, sarcomatoid, and biphasic (also called mixed). Your cell type appears in the final diagnosis and helps your doctors choose treatment.

Types of Mesothelioma Cells

  • Epithelioid mesothelioma: The most common cell type. Patients with epithelioid mesothelioma generally respond best to treatment.
  • Sarcomatoid mesothelioma: A less common cell type that tends to be more aggressive.
  • Biphasic (mixed) mesothelioma: A combination of epithelioid and sarcomatoid cells within the same tumor.

Pathologists also use a simple rule when classifying mesothelioma. If more than about 90% of the tumor is made up of one cell type, it is usually called a “pure” epithelioid or sarcomatoid mesothelioma. If there is a meaningful mix of both cell types, it is classified as biphasic. Your cell type helps guide treatment decisions, but it is only one factor your care team considers when discussing treatment options.

Expert Insight

“If there’s more than ninety percent of one cell type, it is referred to as pure of that cell type… But if there is a representation for both cell types, that’s called biphasic or mixed cell.”

Andrea Wolf
Dr. Andrea Wolf , thoracic surgeon & mesothelioma researcher

What Your IHC Markers Mean

Immunohistochemistry markers are a set of stains pathologists use to confirm mesothelioma and tell it apart from other cancers. Your report shows some markers as positive and others as negative. The pattern is what confirms the diagnosis. Some markers are expected to light up in mesothelioma (positive), while others are run specifically to rule out other cancers.

Calretinin and cytokeratin are specific markers you may see on your IHC results. If listed as positive, they may confirm the presence of mesothelioma when examined with other markers. The individual markers do not confirm a mesothelioma diagnosis, but are instead interpreted together.

Common IHC Markers

MarkerTypical Result in Mesothelioma*What It’s Helping Show
CalretininOften positiveMay support a diagnosis of mesothelioma when interpreted with other markers.
Cytokeratin 5/6Often positiveMay support a diagnosis of mesothelioma when interpreted with other markers.
WT-1Often positiveMay support a diagnosis of mesothelioma when interpreted with other markers.
D2-40 (Podoplanin)Often positiveMay support a diagnosis of mesothelioma when interpreted with other markers.
BAP1Loss may support mesotheliomaHelps distinguish malignant mesothelioma from some noncancerous conditions.
MTAPLoss may support mesotheliomaCan provide additional evidence supporting mesothelioma.
TTF-1Usually negativeHelps rule out many lung cancers.
Ber-EP4, Claudin-4, MOC-31Usually negativeHelp rule out other types of carcinoma.

Have a Mesothelioma Specialist Read Your Case

Mesothelioma is rare and difficult to diagnose. One of the most valuable things you can do is have a pathologist who specializes in mesothelioma re-review your case, including the actual slides and tissue, not just the written report. Because mesothelioma can resemble other cancers under the microscope, specialist review can help reduce the risk of a mesothelioma misdiagnosis and ensure you receive the most appropriate treatment.

Information on Your Pathology Report

  • Who reads it: Check the pathologist’s name and institution on your report. If your diagnosis was made at a community hospital or general pathology laboratory, that is not a red flag. However, it is often a good reason to seek confirmation from a specialist pathologist with experience diagnosing mesothelioma.
  • Slides, not just the report: A second opinion involves reviewing the original pathology materials, including the glass slides and tissue block, not simply reading the written report. A specialty center can re-examine the original slides and tissue to confirm the diagnosis.
  • How to request it: You do not need to arrange the transfer yourself. A mesothelioma specialist or someone who can talk to a Patient Advocate can usually help coordinate the transfer of slides and tissue for review. Most insurance plans cover second-opinion consultations, although coverage varies by policy.

Confirm who signed your pathology report and where it was performed. Ask whether a mesothelioma specialist has reviewed the case and request a pathology second opinion if one has not already been obtained. Use a doctor-matching service to find a doctor or mesothelioma specialist.

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What Your Mesothelioma Pathology Report Doesn’t Tell You

Your pathology report confirms what the cancer is, but it usually does not tell you how far it has spread, what your outlook is or your full molecular or genetic profile. Those answers come from other tests and often arrive separately.

What Your Pathology Report Doesn’t Tell You

  • Staging: Describes how far the cancer has spread. This information typically comes from imaging studies, surgical findings and your care team’s overall evaluation, not from the pathology report alone.
  • Prognosis and life expectancy: Depend on many factors, including your stage, cell type, overall health, and response to treatment.
  • Eligibility for treatments or clinical trials: Molecular or genomic testing may be performed after the diagnosis is confirmed. These tests can identify genetic changes that may help determine eligibility for certain treatments or clinical trials.

A confirmed mesothelioma diagnosis is an important milestone, but it is only one part of the information your care team uses to understand your disease and recommend treatment. A pathology report establishes a plan for your medical team on the optimal treatments and course of action to take.

Questions to Ask Your Doctor About Your Mesothelioma Pathology Report

A pathology report provides important but limited information about your mesothelioma case. Asking your doctor questions on key terms and meanings of the report can help determine your next steps.

Questions for Your Next Appointment

  1. Can you walk me through my final diagnosis line?
  2. What is my cell type, and what does it mean for my treatment options?
  3. Who read my case (a general pathologist or a mesothelioma specialist) and should I get a second opinion from a specialty center?
  4. Are any of my results still pending, including molecular or genetic testing that could affect my treatment options or eligibility for clinical trials?
  5. Based on my pathology report, what are my next steps and who do I call with questions?

A pathology report aids in navigating treatment and medical plans after a mesothelioma diagnosis. Your doctor and medical team are there for support and guidance throughout your treatment.

Common Questions About Your Mesothelioma Pathology Report

What is the most important part of a mesothelioma pathology report?

The most important part of a mesothelioma pathology report is the final diagnosis line, which names the cancer and usually defines the cell type. Everything else on the report is the evidence supporting that conclusion. The diagnosis line tells you whether the pathologist found mesothelioma and whether it is epithelioid, sarcomatoid or biphasic. Supporting findings, including microscopic features and IHC results, help confirm that diagnosis.

What do epithelioid, sarcomatoid and biphasic mean in my report?

They are the three mesothelioma cell types. Epithelioid is the most common and generally responds best to treatment, sarcomatoid is more aggressive and biphasic (also called mixed) contains both cell types. Pathologists classify a tumor as “pure” epithelioid or sarcomatoid when more than about 90% of the cells are one type. If there is a meaningful mix of both cell types, the tumor is classified as biphasic.

What do positive and negative IHC markers mean?

Pathologists run a panel of immunohistochemistry stains and dyes to look for traces of cancer. Positive markers confirm traces of mesothelioma while negative markers rule out other illnesses. The whole pattern of IHC results matter, not just one marker.

Can mesothelioma be diagnosed without a biopsy?

Generally no. Imaging, blood tests and fluid analysis can suggest mesothelioma, but a biopsy examined under a microscope is almost always required to confirm it. A tissue sample allows the pathologist to evaluate the cells directly and perform additional testing.

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