Mesothelioma Histology

Accurate diagnosis is particularly important for a complex disease like mesothelioma that can be challenging to identify, even by the experts. It’s not uncommon for mesothelioma to be confused with other forms of cancer. Histology helps reduce the chances of misdiagnosis.

Written and Fact-Checked by: Mesothelioma Hope Team

What Is Histology?

“Histology is the study of microscopic disease cells and is a subspecialty of pathology, the study of disease.”

Histology is one of the oldest forms of disease diagnosis, with the first incarnations of today’s methods developed in the mid-1880s. Despite its age, clinical histology is a reliable diagnostic process used to accurately identify many types of cancers, including mesothelioma.

Many mesothelioma specialists favor histology over any other form of diagnosis, including cytology, because it’s the most effective and accurate means of diagnosing cancer.

Mesothelioma histology involves two steps:

  1. Doctors perform a tissue biopsy on a patient to collect tissue samples.
  2. The tissue samples are sent to a laboratory where an experienced pathologist will review the samples and look for epithelioid, sarcomatoid, or biphasic mesothelioma cells.

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Histology Process For Diagnosis Mesothelioma

Histology samples collected from a biopsy are placed into a container with a preservative and then sent to the pathology lab for examination.

The first test performed by a pathologist is a gross examination, which means the tissue sample is reviewed without the use of any tools. The pathologist will take a look at the specimen with their naked eye and record their observations. In some cases, a photo is taken as well.

Pathologists perform a gross examination to determine whether a sample looks cancerous and to determine which parts of the sample should undergo further examination.

Mesothelioma samples are typically small, allowing pathologists to review the entire specimen at once. The sample is placed into a container called a cassette where it will be processed for a few hours, before being placed in a hot paraffin wax mold. The wax is then left to cool and harden.

Once the wax form is solid throughout, an instrument called a microtome is used to slice the tissue into extremely thin slices. It’s then placed on a glass slide and dipped into dyes, coloring the cells, so they are easier to see.

Pathologists consider numerous factors when looking for mesothelioma cells, including cell shape, size, composition, and general behavior.

Finally, the pathologist can look at the biopsied tissue under a microscope. Mesothelioma specialists recommend electron microscopes for this process, which use electron beams to create highly detailed images magnified too much stronger resolutions than traditional light microscopes.

Frozen Section Exam

In some cases, histologists will review a tissue sample during the middle of a patient’s surgery to help surgeons make instant decisions. This form of biopsy processing is called a frozen section exam, and it usually takes 10 to 20 minutes.

Instead of using wax, the tissue is placed into a specially developed solution that encases the tissue and forms an ice cube. Next, the cube is sliced into thin sections, dipped into several staining dyes, and then reviewed under a microscope.

A frozen section exam is not as accurate or clear as the traditional histology process, but it’s often adequate to enable surgeons to make fast decisions. The most frequent uses of a frozen section exam are to identify whether a specific mass is malignant or benign and to determine whether a surgeon has removed enough of the tissue to catch all cancer.

Looking for Mesothelioma Cells

Pathologists are looking for three types of cells when using histology to identify mesothelioma:

  1. Epitheliod: The most common mesothelioma cell type.
  2. Sarcomatoid: A Highly aggressive form of mesothelioma.
  3. Biphasic: Combination of epithelioid and sarcomatoid cells.

The presence of any of these cells will result in a mesothelioma diagnosis, although the pathologist will also have to determine whether the cells are malignant or benign.

Epithelioid Cells

Epithelioid cells are by far the most common type of mesothelioma cell. This is a good thing, considering that epithelioid mesothelioma is the easiest of the types to treat, and typically coincides with the best prognosis. Epithelioid cells are well defined with a single nucleus and tend to clump together into large masses.

Sarcomatoid Cells

Sarcomatoid cells are the rarest form of mesothelioma and are recognized by pathologists by their spindly appearance and multiple nuclei. Sarcomatoid cells don’t tend to clump together in the same way that epithelioid cells do, making their masses smaller and allowing cancer to spread faster. Sarcomatoid cells tend to be linked to the worst patient prognosis.

Biphasic Cells

Biphasic cells are a mix of both epithelioid and sarcomatoid cells. Their appearance is determined by the percentage of each cell type present. Patient prognosis is greatly influenced by this percentage, with outcomes becoming more favorable with higher concentrations of epithelioid cells. Biphasic mesothelioma is the next most common form of the disease after epithelioid.

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Procedures Used To Collect Histology Samples

The two most common procedures used to collect biopsy samples in patients who may have mesothelioma are a needle biopsy and a thoracoscopy, although other procedures may be used. In some cases, histology samples may also be collected during major surgeries, including pleurectomy decortication (P/D) or extrapleural pneumonectomy (EPP), to further identify a specific cell subtype, or contribute to a tissue bank or mesothelioma research project.

Fine Needle Biopsy

A fine needle biopsy is a common procedure used to diagnose mesothelioma after other tests have indicated that cancer cells may be present. Although some patients find needles intimidating, the procedure has minimal risk and is one of the simplest histological means of testing for mesothelioma.

A needle biopsy is a fairly simple procedure and is usually performed in under an hour. Many biopsies use a general anesthetic to numb the patient, while others will require heavy sedation or general anesthesia. The doctor will discuss the plan before the procedure to ensure the patient knows what to expect.


A thoracoscopy, also known as a thoracic biopsy or a video-assisted thoracic surgery (VATS) biopsy, is a surgical procedure used to take biopsy samples from the lungs of people suspected to have mesothelioma or other forms of lung cancer. It’s a fairly advanced diagnostic procedure and is typically only performed after other diagnostic tests have indicated a likely cancer diagnosis.

Surgeons performing a thoracoscopy will make three small incisions into a patient, which are for the camera and tools used throughout the procedure. Because the entire biopsy is performed through these three little holes, thoracoscopy is considered a minimally invasive surgery. Minimally invasive surgeries tend to be lower risk, have fewer complications, and allow faster recovery times than more traditional forms of surgery.

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Challenges of Histology

Misdiagnosis Update

Although histology is one of the most effective ways of identifying and diagnosing mesothelioma, misdiagnosis does occur. Mesothelioma is a challenging type of disease to identify, and even the most experienced pathologists can misidentify the cells.

Mesothelioma is rare and its behavior and appearance often mimic other cancers. Also, the three mesothelioma cell types each present differently, adding another layer of difficulty in determining an accurate diagnosis. And finally, although most mesothelioma cells are malignant, there are recorded cases of patients with benign mesothelioma cells. Histologists have to feel confident in their observations and work through all of these factors before they can make a mesothelioma diagnosis.

Patients who think their cancer was misdiagnosed should reach out to a mesothelioma specialist. If you’ve been diagnosed with mesothelioma, talk to one of our Medical Experts now to learn more about getting a second opinion on your diagnosis.

Mesothelioma Hope was founded by a team of passionate health advocates to educate people about this aggressive form of cancer. Mesothelioma affects thousands of people each year. Our team works tirelessly to give hope to those impacted by mesothelioma. Learn more about operating principles and our Editorial Guidelines.

4 References
  1. Archives of Pathology. “Guidelines for Pathologic Diagnosis of Malignant Mesothelioma.” Retrieved from Accessed on January 12, 2018.

  2. Johns Hopkins Medicine. “Lung Biopsy.” Retrieved from,P07750. Accessed on January 13, 2018.

  3. American Cancer Society. “What happens to biopsy and cytology specimens?” Retrieved from Accessed on January 13, 2018.

  4. Journal of Histotechnology. “A Short History of Histopathology Technique.” Retrieved from Accessed on January 14, 2018.

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