Mesothelioma Pathology

Pathology, the study of the nature of disease and its causes and effects, plays a significant role in the diagnosis of asbestos cancers. Because each type of cancer has particular characteristics, studying the way cancer behaves in the body and how it affects surrounding body tissues and organs can help doctors provide an accurate diagnosis and develop treatment plans for patients.

Pathology can involve anatomical studies of the appearance of the disease in tissues, the way it progresses, and the study of how the disease affects cells on a microscopic level.

Fast Fact: Pathologists provide crucial information for mesothelioma diagnosis, including the extent of disease progression, surgical resection margins and if the cancer has spread to the lymph nodes.

Anatomical Pathology

Pathologists note certain physical characteristics of asbestos-related tumors. The majority of these tumors affect the pleura (75 percent) and the peritoneal cavity (10 to 20 percent). Only rarely do they affect the pericardium (1 percent) and tunica vaginalis (less than 1 percent).
One of the most unique pathological features of these diseases is that the cancer forms in the mesothelial cells in the linings of organs and grows in a diffuse pattern. This growth pattern causes the tumors to spread and form tiny nodules across the surface of the outer lining of the lungs (pleura) or abdomen (peritoneum). Localized malignant mesotheliomas are extremely uncommon, though a few cases have been reported. These localized tumors are more easily removed in surgery and therefore have a much better prognosis.

Pathological Characteristics of Disease Progression

Stage I

Cancer is localized. Surgery may be able to remove tumors and prognosis is highest.

Stage II

Cancer has spread beyond point of origin. Surgery may still be an option, but life expectancy is decreased.

Stage III

Cancer has progressed to advanced stage of development. Palliative treatments to ease symptoms may be considered.

Stage IV

Cancer has spread to distant locations. Palliative treatments can improve comfort, but life expectancy is severely decreased.

In its early stages, diffuse pleural mesothelioma begins as multiple tumor nodules on either or both of the visceral and parietal pleural surfaces. The nodule size ranges from 1 mm to 1 cm. As the disease progresses, the tumors form plaques. Eventually, these tumors can form a rind around the organ, constricting it and interfering with its normal functions. Organ encasement is usually a sign of advanced disease. After tumors begin to encase organs, the visceral and parietal linings in pleural, peritoneal and pericardial mesothelioma typically adhere together.
Pleural cancers often spread to skeletal muscle in the chest wall and may also invade the skin and subcutaneous tissue (deepest layer of skin). Tumors can also invade the hemidiaphragm and spread into the abdominal cavity. When present in the pleural cavity, the tumors can also invade biopsy tracks, surgical incisions and the fissures of the lung. At very late stages, they metastasize into the hilar lymph nodes, which are located in the chest close to where the bronchi enter the lungs.

Fast Fact: Patients are rarely treated for cancer with chemotherapy unless there is a pathological diagnosis.

In advanced peritoneal mesothelioma, the bowel is often encased by tumors, and the liver and spleen may also be encased. Tumors that originate in the pericardium are rare, but the same diffuse spread pattern is also observed and it often infiltrates the muscle tissue of the heart (myocardium).

Cellular Pathology

While the anatomical characteristics of a tumor can help diagnose a type of cancer, most tumors require a pathologist to study the types of cells present in a malignant growth. Using a microscope, pathological studies differentiate mesothelioma cells from other types of cancer and are used to diagnose specific subtypes of the disease through two methods: histology and cytology.

Histopathologic Features

Histology involves the use of tissue samples obtained through a biopsy. Histopathology specifically refers to the study of the cells in diseased tissue. For mesothelioma, actual tissue from tumors is usually obtained through an incisional/core or excisional biopsy.

Mesothelioma Histology Tissue Stain

This method is the preferred method for diagnosing asbestos cancer because information is comprehensive when using histology. Also, immunohistochemistry “ staining using antibodies “ and other special stains can be applied to tissue samples to reveal more details about a tumor.

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Mesothelioma Imaging Scans

Doctors use imaging scans, such as X-rays, CT scans, MRIs and others, as noninvasive tools that help detect tumors in the body when a patient experiences symptoms usually associated with an asbestos-related disease like mesothelioma.

Because the symptoms of mesothelioma match those of other diseases, mesothelioma can be difficult to diagnose and locate. The tumors may show up in any part of thin layer that surrounds the organs. They can even be found between organs. For this reason, it is important to use advanced imaging technology to assist with proper diagnosis.
A cancer doctor begins a patient examination with a thorough review of the patient's medical history. As the diagnosis process continues, there may be several tools used simultaneously to get the most accurate results. Along with blood tests and other examinations, a medical professional may use one or more noninvasive body scans to detect any abnormalities.

X-rays

The most basic imaging scan is an X-ray. This scan is limited, but may be able to detect damage or abnormalities in the body. One of the biggest drawbacks of an X-ray is that it can only produce a flat, two-dimensional image. When an X-ray is taken, electromagnetic radiation is sent through the body with a photographic film on the other side. The way the waves, or rays, behave will change as they pass through the body, creating a representative image.

• Only flat, two-dimensional images
• Most common imaging technique
• Radiation level not harmful

Tumors

On standard X-rays, healthy lungs appear black. When a tumor is present on the pleura, doctors will see a wispy white area that indicates tumor growth. Tumors can also distort the normal shape of the lungs, which can be detected on the radiograph. A tumor-encased lung appears compressed and can show an elevated diaphragm.

Radiation

One single chest X-ray exposes patients to the same amount of radiation they would naturally encounter over a period of 10 days. This exposure generally does not cause any serious side effects. However, patients are encouraged to hold on to copies of their results to avoid the need for unnecessary duplicate tests over their lifetime.

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Mesothelioma Latency Period

The typical mesothelioma latency period is 20 to 50 years, with recent studies finding a median of 30 to 45 years. Under normal circumstances, the shortest possible latency period is 10 to 15 years, while the longest is more than 50 years. The time period depends on a number of factors such as the duration and intensity of asbestos exposure, as well as the patient’s gender and the type of mesothelioma. Because of this long time span, most of those who are diagnosed with mesothelioma and other asbestos-related disease are in their 60s or 70. Those diagnoses come after symptoms of the disease — a persistent cough or difficulty breathing — become nagging or debilitating.
Studies show that lower exposure levels and shorter durations of exposure can lead to longer latency periods. Conversely, individuals with high levels of exposure for long periods of time have significantly shorter latency periods.

The latency period typically continues until later stages of the disease, when symptoms finally begin and a doctor can diagnose the patient. For most illnesses, a latency period begins when an individual is exposed to a virus or other illness-inducing entity and ends when the person first begins experiencing symptoms. Although some experts use this definition for mesothelioma latency period, most agree this asbestos-related cancer is considered latent until it is actually diagnosed.

This is because symptoms of mesothelioma can actually arise before a patient has the cancer. Asbestosis, a non-cancerous illness caused by asbestos, has many of the same symptoms and is often a precursor to mesothelioma. So a patient suffering from asbestosis could have mesothelioma-like symptoms such as a persistent cough and chest pain before the cancer manifests itself.
At these later stages, the cancer is more difficult to treat and the patient generally has a shorter life expectancy. But a prompt diagnosis followed by immediate treatment can lead to an improved prognosis.

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Blood Tests and Biomarkers

While imaging tests and tissue biopsies are the most common methods for diagnosing mesothelioma, blood tests can also help doctors identify the disease. These blood tests look for certain indicators of disease, known as biomarkers, in a patient's blood.

Although the broadest definition of biomarker also includes the measurement of physiological and anatomical criteria, for mesothelioma blood tests the term refers to measuring the levels of biological molecules associated with the disease, such as specific proteins or genes. If these biomarkers are detected in the blood in abnormally high concentrations, it may suggest a diagnosis.

Diagnostic sensitivity of three different blood-based biomarkers

In addition to their diagnostic benefits, biomarkers can also be used to predict the progression and aggressiveness of a patient's mesothelioma. This can affect a patient's prognosis and help doctors identify the patients who will respond best to certain treatments.

The MESOMARK assay is the most well-known blood test for mesothelioma. This FDA-approved test was the world's first blood serum-based test sensitive for the disease. The MESOMARK kit scans a patient's blood for levels of soluble mesothelin-related peptide (SMRP), a protein released into the blood by the cancerous cells of this illness.

Other blood tests can scan a patient's blood for the biomarkers osteopontin and megakaryocyte potentiating factor (MPF). However, these tests are less readily available, and doctors still do not consider them accurate enough to replace histology as the gold standard for diagnosis.
While the term “tumor marker” is often used interchangeably with biomarker, the definitions of these two terms are slightly different. Tumor markers are substances found in or expressed by the actual tumor, while biomarkers are not necessarily expressed by tumor cells.

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Mesothelioma Biopsy

During this procedure, a surgeon removes a tissue or fluid sample for analysis. A pathologist then views the sample’s cells under a microscope, which reveals their features, activity and interactions. Biopsies can also prove when cancer is not the correct diagnosis.

Analyzing biopsied cells is a highly accurate method for diagnosing mesothelioma.

Various methods for biopsy exist, including techniques that use needles, bronchoscopes and surgery to obtain samples. Depending on the invasiveness of the method used, local or general anesthesia may be required.
The type and location of a patient’s tumor dictates which procedure should be performed. Peritoneal mesothelioma patients commonly undergo a fine-needle aspiration biopsy, while a thoracoscopic biopsy is more effective for patients with pleural mesothelioma. Because 75 percent of all asbestos cancer cases involve the protective layer of the lungs, the majority of patients undergo thoracoscopies.

Thoracoscopy

A VATS biopsy requires only one small incision at either of the locations pictured above.

Thoracoscopic biopsy has a remarkable track record of accurate diagnoses. Also known as open pleural biopsy, this procedure allows doctors to see into the pleural space and retrieve multiple tissue samples. Most treatment centers offer video-assisted thoracoscopic surgery (VATS), which uses a camera and various small tools to collect samples.
Several studies reported that a thoracoscopy can make an accurate diagnosis in up to 98 percent of asbestos cancer patients. Direct examination of the pleura may also help with determining cancer stage and the patient's prognosis.
In a 2008 postmortem study of 45 malignant mesothelioma patients, researchers compared the accuracy of several biopsy techniques, including open pleural biopsy, closed needle biopsy and computer tomography (CT)-guided biopsy. The open pleural procedure displayed the highest diagnostic accuracy, confirming a diagnosis in 95 percent of patients with the disease.

Other Types

Although thoracoscopy yields superior results compared with other techniques, the procedure may not always be possible because of the tumor’s location and other complications. Other biopsies that doctors use to diagnose mesothelioma include:

• Fine-Needle Aspiration -- A quick and safe procedure, fine-needle aspiration (FNA) biopsies use a long, hollow needle to remove up to 10,000 sample cells for testing. This procedure is preferred for its ability to access hard-to-reach areas without the need for anesthesia. FNA biopsies of a pleural or peritoneal effusion can diagnose mesothelioma with an accuracy of up to 84 percent.
• Thoracentesis -- This procedure uses a hollow needle to extract fluid and air from the space between the lungs and pleura. While it is commonly used to remove excess fluid that causes pain and weakens lung function, thoracentesis can also be used to obtain fluid samples for analysis.
• Thoracotomy -- A thoracotomy is a type of invasive surgery used to access the lungs, heart, aorta, diaphragm and trachea. For mesothelioma patients, a segmentectomy, or wedge resection, is the preferred type of thoracotomy since it leaves most of the affected lung intact. During the surgery, a wedge-shaped piece of the lung is removed to be tested by a pathologist for cancer.
• Endoscopic Biopsy --An endoscopic biopsy is one of the most common biopsy techniques. This procedure uses an instrument called an endoscope that allows the surgeon to see into the area being sampled. Small forceps attached to the endoscope are used to collect slivers of tissue from a potentially cancerous tumor.
• Incisional (Core) Biopsy-- During an incisional biopsy, only a small section of suspicious tissue growth is removed. This is a common procedure when the tumor is easily accessible. Unfortunately, mesothelioma tumors typically do not develop in easy-to-reach locations.
• Excisional Biopsy -- In an excisional biopsy, the entire lesion is removed rather than a small tissue sample. This procedure can eliminate the need for a second removal surgery if testing shows the tumor is malignant.

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Mesothelioma Diagnosis

There is no clear path to a mesothelioma diagnosis for every patient. Because the disease is so rare and has such common symptoms, doctors sometimes confuse it for a less-serious illness or a different type of cancer.
Pinpointing the disease involves several procedures, including X-rays, CT scans, MRIs, biopsies and PET scans. Each of these tests is performed by a different medical professional, and most people get their diagnosis within two or three months from the time they notice their symptoms.
Diagnosing the cancer in its earliest stages supports a wider range of treatment possibilities that could extend your life expectancy. So it's important you start looking for a mesothelioma expert.

What Steps Lead to a Mesothelioma Diagnosis?

There are three steps to the mesothelioma diagnosis:

• 

  Symptoms Begin to Show

  Patient detects symptoms, which general start to appear 20-50 years after exposure. These symptoms often mimic those of other diseases.
  
• 

  Patient Consults Primary Care Physician

  The primary care physician discusses symptoms with patient. These doctors perform preliminary tests. If cancer is suspected, they refer patient to an oncologist.
  
• 

  Oncologist Makes Final Diagnosis

  The oncologist conducts a variety of tests based on the patient's health. Tests may include imaging scans, blood tests and biopsies to positively confirm a mesothelioma diagnosis..
  If you find yourself in this situation, doctors will start the diagnostic process by asking about your medical history and by performing some standard physical exams. They should ask if you recall any personal past exposure to asbestos.
  Providing your doctor with a comprehensive work history can hasten an early diagnosis. Because mesothelioma is a rare cancer with nonspecific symptoms, doctors are unlikely to suspect the disease unless a patient describes a former job where asbestos exposures may have occurred.
  By recognizing that they worked in a high risk industry, such as asbestos mining, construction or shipbuilding, patients can express concerns that their symptoms may be asbestos-related.
  Next, doctors will order imaging tests to identify any abnormal growths. If those show a suspicious mass that looks like mesothelioma, doctors will request a biopsy to confirm the diagnosis. They will take fluid or tissue samples during the biopsy.
  During this process, you'll see several doctors. Patients usually visit a general practitioner, pulmonologist, radiologist, surgeon, pathologist and an oncologist. If any of these doctors suspect mesothelioma or another asbestos disease, that's a sign for any patient to get a second opinion from a mesothelioma specialist, an expert who has experience staging the cancer and treating people who have it.
  
  

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Mesothelioma

The cancer usually affects the thin, protective membrane surrounding the lungs, heart or abdominal cavity. Doctors diagnose an estimated 3,000 cases a year in the United States, and the majority of those are traced to job-related asbestos exposure.
Although asbestos use declined dramatically in recent decades in this country, the incidence of malignant mesothelioma remains steady. That difference can be traced to the distinct latency period linked to the cancer. The disease can take anywhere from 20 to 50 years after exposure to asbestos before it shows obvious symptoms and an oncologist can make a definitive diagnosis. While no cure for the disease exists and the prognosis is typically poor, researchers made significant progress in recent years in understanding the cancer and developing new treatment options and alternative therapies.

How Asbestos Causes Cancer

Mesothelioma typically develops after exposure to asbestos in the workplace – in industrial settings, shipyards, auto repair shops, old houses, schools and public buildings. While it usually takes long-term exposure to put someone at risk, short-term and one-time exposures are also known to cause mesothelioma cancer.

70-80% of all mesothelioma cases are caused by asbestos exposure at work

Asbestos inhalation occurs

Fibers lodge in mesothelial tissue

Fibers cause cellular damage, resulting in tumor growth

Dr. Fontaine explains what mesothelioma is.

Microscopic asbestos fibers are breathed in or swallowed, and the human body has difficulty destroying or getting rid of them. Over decades, fibers cause biological changes that result in inflammation, scarring and genetic damage. The most susceptible area to these fibers is the lining of the lungs, called the pleura, although fibers also can become trapped in the lining of the abdominal cavity (peritoneum). Once fibers cause biological damage, the stage is set for the decades-long latency period for the development of malignant mesothelioma.

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Mesothelioma & Asbestos Lawyers

Successful asbestos ligation requires an attorney who understands the many facets of the case, from how people get exposed to asbestos to the state-by-state regulations about filing lawsuits, to the fragile nature of many clients. Often, people who inquire about an asbestos-related claim are people who are also coping with mesothelioma cancer and all the health issues that go along with treatment.
Choosing a lawyer to represent you in depositions and in legal filings can be as important to your family's future as selecting the right doctor. If were you exposed to asbestos and you got sick as a result, you have a right to stake a claim for compensation.
The dangers and toxicity of asbestos were well-known in the 1930s, yet corporations continued using it extensively through much of the 20th century. They willingly put profits ahead of the health and well-being of employees and the public. An experienced asbestos lawyer will know how to hold those corporations responsible.

Tips When Looking For an Asbestos Litigation Specialist

You should consider several things when you start to evaluate the hiring of an attorney. You want to find someone with whom you feel comfortable talking because you will be discussing intimate details about your health and about where you used to work. Although your lawyer likely will know all the right questions to ask you, good communication is essential.

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