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Differential diagnosis of mesothelioma

By Michael Bartlett

Posted on May 05th, 2020

Mesothelioma, a rare and aggressive cancer, which develops on the outer lining of the lungs, is quite prevalent among people with a history of asbestos exposure. However, it is often misdiagnosed, so seeking a second opinion is strongly advised.

As a rare and aggressive cancer affecting the outer lining of the lungs, the heart, the abdomen, or the testicles, mesothelioma is diagnosed in approximately 3,000 people in the United States every year. The only known cause of mesothelioma, regardless of the area of the body where it occurs, is asbestos exposure, particularly occupational and military asbestos exposure. The average age of diagnosis for mesothelioma is 72 and the disease occurs mostly in men, as they made up the majority of industrial workers and military personnel during the last century. Because it is so rare, diagnosing mesothelioma may be challenging for medical professionals who do not specialize in diseases caused by asbestos exposure. Furthermore, the symptoms of mesothelioma often mimic the signs of more common and less serious diseases, such as pneumonia or bronchitis, so misdiagnosis happens quite often when it comes to mesothelioma. A clinical diagnosis is assigned based solely on the symptoms and medical history of the patient, whereas a differential diagnosis is made by using specific diagnosis tools, such as a chest X-ray, a CT scan, a biopsy, or blood tests. Therefore, because mesothelioma often resembles other diseases, receiving a differential diagnosis is essential for being prescribed appropriate and effective treatment.

What is the differential diagnosis of mesothelioma?

Mesothelioma is a form of cancer whose only known cause is asbestos exposure. The disease affects the lining of various organs in the body, which is medically known as the mesothelium, hence the name of this cancer. Exposure to asbestos occurs when a person inhales or ingests asbestos fibers from the air, which subsequently travel through the bloodstream and attach themselves to the lining of the following organs: the lungs, the heart, the abdomen, and the testicles. Consequently, there are 4 types of mesothelioma: pleural, pericardial, peritoneal, and testicular.

The diagnosis rate of mesothelioma increased after 1950, as more and more people with a history of asbestos exposure began developing it. It is worthy of note that it may take 20 to 50 years for mesothelioma to develop since it has a long latency period. During the latency period, the asbestos fibers in the body gradually cause inflammation and tissue scarring to the lining of the organs, giving way to the growth of malignant tumors, which develop later. Because the symptoms of mesothelioma are often very similar to those of more common diseases, this cancer is frequently misdiagnosed. Misdiagnosis occurs particularly when the physician assigns a clinical diagnosis, which is one based solely on the symptoms and medical history of the patient. A differential diagnosis, however, takes into consideration multiple essential aspects, including the result of various tests, which are effective in diagnosing mesothelioma, such as a chest X-ray, a CT scan, blood tests, and a biopsy.

When mesothelioma is suspected in a patient, differential diagnosis is crucial, as a wrong diagnosis can easily be assigned if the patient does not undergo a series of medical exams and tests. For instance, the symptoms of pleural mesothelioma mimic those of lung cancer, which is a completely different disease and requires specific treatment, and thereby, misdiagnosis may happen if the patient receives only a clinical diagnosis. Similarly, the symptoms of peritoneal mesothelioma resemble those of irritable bowel syndrome, hernia, and ulcerative colitis, which are more common conditions. Therefore, if peritoneal mesothelioma is not taken into consideration in the case of a person with a history of asbestos exposure, they are bound to receive a wrong diagnosis and, implicitly, a wrong treatment. This is why a differential diagnosis is important when it comes to mesothelioma.

Accounting for the majority of cases, pleural mesothelioma develops on the outer lining of the lungs and is the result of the inhalation of asbestos fibers. It was discovered that prolonged exposure to asbestos, as well as a high concentration of asbestos fibers on the lining of the lungs, are more likely to result in mesothelioma. Thereby, if one was heavily exposed to asbestos for an extended period they have significantly more chances to receive a pleural mesothelioma diagnosis.

Between 70% and 75% of mesothelioma cases affect the lungs. The majority of patients are eligible for treatment with chemotherapy and radiotherapy and some of them may also benefit from immunotherapy. When it is discovered in stage 1, the prognosis is approximately 3 years, whereas if it is found in stage 4, the life expectancy is only 12 months. Pleural mesothelioma is usually diagnosed in people older than 75.

The most common symptoms of pleural mesothelioma are the following:

  • chest pain
  • a dry cough
  • shortness of breath
  • fatigue
  • unintentional weight loss
  • fever
  • night sweats
  • wheezing
  • muscle weakness

When it comes to diagnosing pleural mesothelioma, it is crucial to take into considerations other diseases which are similar to mesothelioma, such as non-small cell lung cancer, drug-induced pulmonary reactions, small cell lung cancer, mesothelial hyperplasia, other primary lung neoplasms or metastatic disease, pulmonary fibrosis, asbestosis, pulmonary infection, reactive airway disease, pleural effusion, and pleural thickening. Therefore, only by undergoing a chest X-ray, a CT scan, a series of blood tests and a biopsy, which is the most effective diagnostic tool in determining with certainty whether mesothelioma is present on your lungs, the patient will receive a correct diagnosis.

It is important to know that epithelioid mesothelioma cells may have a similar appearance to those of squamous cell carcinoma, as they have approximately the same form. For this reason, further medical investigations are necessary to differentiate between the two cancers. If mesothelioma occurs in a person, the malignant tumors will usually appear on the surface of both lungs, and asbestos fibers will be found inside of the cancerous growths.

As a rare type of mesothelioma, approximately 200 cases of pericardial mesothelioma are diagnosed annually in the country. Pericardial mesothelioma develops on the outer lining of the heart, which is medically known as the pericardium, and is even more aggressive than pleural mesothelioma, as people who have this diagnosis have a life expectancy ranging between 6 weeks to 15 months. A considerable number of pericardial mesothelioma patients qualify for surgery to remove the malignant tumors. The one-year survival rate for this mesothelioma type is 51%.

When asbestos fibers reach the lining of the heart through the bloodstream, they become embedded in the tissue, slowly causing inflammation and scarring, which will, over time, turn into malignant tumors. According to a study published in the Journal of Clinical Oncology in 2017, approximately 60% of pericardial mesothelioma cases occur in men. Treatment options for this mesothelioma type include surgery, chemotherapy, and, in rare cases, radiotherapy. However, a significant number of patients receive palliative care, as their disease is discovered at a very advanced stage when nothing can be done to remove or shrink the tumor.

Surgery is the most frequently used treatment for pericardial mesothelioma, as 46% of patients undergo it, whereas 37% of patients receive chemotherapy. The reason why only 8% of people who suffer from pericardial mesothelioma undergo radiotherapy is because it is dangerous to apply this treatment to the heart. Approximately 25% of individuals who receive a pericardial mesothelioma diagnosis are not eligible for any form of treatment since their cancer is very advanced. Thereby, they only receive palliative care to make their last months as bearable as possible. It is noteworthy that, because of the proximity of the disease to the heart, people may experience severe symptoms during the early stages of the disease.

The symptoms of pericardial mesothelioma include:

  • heart palpitations
  • irregular heartbeat
  • difficulty breathing
  • heart murmurs
  • a dry cough
  • fever
  • night sweats
  • fatigue
  • chest pain

Pericardial mesothelioma may be mistaken, in the absence of a differential diagnosis, for pericardial effusion, pericardial thickening, heart disease, heart failure, or discreet pericardial mass. Nevertheless, mesothelioma is the most common malignant disease which occurs on the pericardium, so it poses less difficulty to medical professionals when it comes to assigning a correct diagnosis. It is essential for radiologists to know that the presentation of pericardial mesothelioma on X-rays is non-specific and it may thereby be incidentally noted on radiological studies for investigation of non-related symptoms. A biopsy is also necessary in this case, as it can tell with certainty which type of cells is present within the pericardial mesothelioma tumor, as well as a CT scan, which can reveal the stage of cancer.

Peritoneal mesothelioma occurs on the outer lining of the abdomen, also known as the peritoneum. It is responsible for 10% to 20% of mesothelioma cases, namely 600 people diagnosed every year in the United States. Asbestos fibers, once inhaled or ingested, can easily reach the peritoneum through the bloodstream, as they are microscopic, and gradually produce inflammation and tissue scarring. Surprisingly, the prognosis of peritoneal mesothelioma is better than that of pleural mesothelioma. Accordingly, 52% of people who undergo surgery and heated chemotherapy (HIPEC) live 5 years or more following their diagnosis. The one-year survival rate for peritoneal mesothelioma is 92%, regardless of the treatment approach. Immunotherapy is also a beneficial treatment for people who struggle with peritoneal mesothelioma and can be administered during a clinical trial.

Some of the most common symptoms of peritoneal mesothelioma are:

  • abdominal distension
  • swelling around the abdomen
  • abdominal pain
  • constipation
  • diarrhea
  • nausea
  • vomiting
  • night sweats
  • unexplained weight loss
  • fatigue
  • anemia
  • a feeling of fullness

Since peritoneal mesothelioma can easily be mistaken for irritable bowel syndrome, hernia, ovarian cancer or ulcerative colitis, a differential diagnosis is crucial. Because of the symptoms peritoneal mesothelioma presents, the disease can easily be misdiagnosed if only a clinical diagnosis is assigned. Therefore, a differential diagnosis is superior to clinical diagnosis in the case of peritoneal mesothelioma. The patient must undergo a series of medical tests, such as a CT scan, blood tests and a biopsy, which will reveal the type of cells present in the malignant tumor and confirm or deny the occurrence of peritoneal mesothelioma.

Immunohistochemistry may be very useful when it comes to diagnosing peritoneal mesothelioma, as it can selectively identify antigens in the cells of a tumor and subsequently determine whether the patient has peritoneal mesothelioma. The immunohistochemistry markers which are positive when peritoneal mesothelioma is occurring include calretinin and mesothelin. Furthermore, the immunohistochemistry markers which are typically used to differentiate carcinoma from mesothelioma are estrogen receptor, carcinoembryonic antigen, and progesterone receptor. Consequently, immunohistochemistry is a very useful and effective diagnostic tool for peritoneal mesothelioma and differentiating it from another form of cancer.

As the rarest type of mesothelioma, testicular mesothelioma develops in the tunica vaginalis, commonly known as the outer lining of the testicles. Less than 100 people in the United States are diagnosed with testicular mesothelioma every year, which represents 1% of all mesothelioma cases. The average life expectancy following diagnosis is 2 years. Treatment for testicular mesothelioma includes surgery and chemotherapy. Unfortunately, approximately 93% of people with testicular mesothelioma experience a reoccurrence of their cancer within the next 5 years of their first diagnosis.

The most frequently experienced symptoms of testicular mesothelioma are the following:

  • swelling in the scrotum
  • a lump or mass in the testicles
  • testicular pain

As testicular mesothelioma can easily be misdiagnosed as a hernia or testicular cancer, differential diagnosis is very important. Oftentimes, testicular mesothelioma is diagnosed during or after surgery. However, a biopsy can reveal whether the patient has testicular cancer or testicular mesothelioma. A buildup of fluid in the scrotum is the main symptom of testicular mesothelioma. Nevertheless, it is also the most common symptom encountered by urologists, as more than half of patients experienced it within a 2019 study. For this reason, a clinical diagnosis is not enough, as the symptom may be one of testicular mesothelioma. A differential diagnosis is necessary to determine whether the patient suffers from testicular mesothelioma or another condition. If the patient has a history of asbestos exposure, the medical professional who examines them needs to take testicular mesothelioma into consideration when assigning a diagnosis.

Mesothelioma cell types

As previously mentioned, there are 3 types of cells, which occur in mesothelioma tumors. Treatment highly depends on the type of malignant cells, so determining it with accuracy is crucial for a good prognosis. The incidence of these types of cells varies by the location of the mesothelioma in the body. Below is more information about each mesothelioma cell type:

  • Epithelioid mesothelioma cells. When epithelioid cells occur in a mesothelioma tumor, the patient usually has a good response to treatment. Epithelioid cells are present in 70% to 80% of mesothelioma tumors. People who have epithelioid mesothelioma have a life expectancy of 12 to 24 months. This type of mesothelioma tends to be less aggressive. Furthermore, epithelioid cells exist in 50% of individuals who have pleural mesothelioma and in 75% of people with peritoneal mesothelioma. However, epithelioid cells can also be present in pericardial mesothelioma, although rarely. This type of cell can present in multiple forms, such as cubed, columnar, or squamous.
  • Sarcomatoid mesothelioma cells. As the least common type of mesothelioma cells, sarcomatoid cells are found in 10% to 20% of mesothelioma tumors. They are very aggressive and usually do not respond well to treatment. There are 3 types of sarcomatoid mesothelioma: sarcomatous, spindle, or diffuse malignant fibrous. Approximately 20% of pleural mesothelioma tumors contain sarcomatoid cells, whereas only 1% of peritoneal mesothelioma tumors have it. The average prognosis for sarcomatoid mesothelioma is 6 months. These cells have a spindle, oval shape, and multiple nuclei in some of them. Sarcomatoid mesothelioma also tends to spread faster to adjacent organs and tissues than epithelioid mesothelioma.
  • Biphasic mesothelioma cells. When both epithelioid and sarcomatoid cells are present in a tumor, biphasic mesothelioma is diagnosed. Depending on the number of each cell, biphasic mesothelioma may respond to treatment in more or less favorable ways. For instance, if more epithelioid cells exist, the prognosis is more favorable, as these cells respond better to treatment than the other. However, if more sarcomatoid cells are inside the tumor, mesothelioma will not respond very well to treatment, as they are very aggressive and difficult to remove.

However, there are other types of mesothelioma cells, which are found very rarely in people who struggle with this disease, such as:

  • adenomatoid mesothelioma
  • cystic mesothelioma
  • papillary mesothelioma

Mesothelioma patients and their family members are eligible for compensation

If you have a mesothelioma diagnosis, you have the right to seek financial compensation for your physical and emotional distress, as the only cause of mesothelioma is occupational or military asbestos exposure.

Please contact our attorneys as soon as you receive your diagnosis, as asbestos exposure cases have a statute of limitations of 3 years from the moment of diagnosis in the majority of states. Our lawyers, who have been pursuing compensation for people who struggle with mesothelioma for the last 30 years, will expedite your claim, which will be filed with the asbestos trust funds of the companies responsible with the manufacturing of the hazardous products you were exposed to, as well as with the VA if you are a veteran who was exposed to asbestos during military service.

Your involvement in the legal process will be minimal, as we only need your employment or military records and your medical records to use as proof of asbestos exposure and of related diagnosis. Because mesothelioma is a very aggressive cancer, we prioritize clients with this diagnosis, as it is the most serious disease which can develop as a consequence of asbestos exposure.

In the regrettable case of wrongful death, the remaining family members of the mesothelioma patient are also entitled to file a claim on the behalf of the person who passed away. However, the statute of limitations for wrongful death caused by asbestos exposure is 2 years in most states from the moment of death, so we strongly advise you to take legal action immediately. Our attorneys will thoroughly review your case and file a claim with the asbestos trust funds and with the VA, is the deceased person was a veteran, and you will receive the compensation you deserve within the shortest time possible. Nevertheless, even if the mesothelioma patient is alive, family members can help with the legal process by reaching out to us and by subsequently sending the necessary documents to our law firm.