Epithelioid mesothelioma is a serious and aggressive malignant tumor that can affect various mesothelial structures. Mesothelium is a membrane made up of epithelial cells that cover and protects some of our internal organs such as the lungs (the pleura), the abdominal cavity (the peritoneum) or the heart (the pericardium).

How Common is Malignant Epithelioid Mesothelioma?

Epithelioid mesothelioma is a rare cancer. Most often, it appears in the pleura (pleural mesothelioma). This type of cancer accounts for up to 90% of all mesothelioma cases.  Concerning the cell type, the epithelioid type is the most frequent and include around 70% of the cases. There are other types such as sarcomatoid or biphasic tumors that are more aggressive and fortunately much rarer.

• The purpose of this article is to expose all the aspects of this pathology, including its statistics, risk factors, symptoms, diagnosis, and evolution. We will also talk about treatment options and the main ways to avoid it.

Epithelioid Mesothelioma Histology

Histologically, epithelial mesothelioma cells have polygonal, ovoid or cuboidal cell shape. This form of mesothelioma is comprised of cells which resemble the normal mesothelial cells in that they are arranged in a trabecular fashion. The occasional presence of signet-ring cells may make it challenging to distinguish this disease from cancers of the lung proper (adenocarcinoma). This is quite different from the histology of sarcomatoid mesothelioma which is characterized by a spindle cell morphology. Biphasic mesothelioma has characteristics of both epithelioid (polygonal, ovoid or cuboidal) and sarcomatoid (spindle) variants depending on the extent in which they are comprised of.

Epithelioid, sarcomatoid and biphasic are the subtypes of Epithelioid mesothelioma. According to the World Health Organization (WHO), these are the 3 different histologic (microscopic) subtypes of this disease. This categorization is relevant and important for 2 reasons.

First, each subtype has a varying prognosis (projected course of the disease).  Second, the subtype of the mesothelioma at diagnosis determines the pharmacotherapeutic and/or surgical treatment. These subtypes are distinguished by a trained histopathologist, with the aid of a microscope and various staining techniques. A CT guided biopsy is utilized to obtain samples of the mesothelioma, with a 60 – 85% diagnostic yield. Occasionally, an open or thoracoscopic pleural biopsy is used for an even higher diagnostic yield.

The sarcomatoid mesotheliomas are comprised of tightly bundled spindle cells. Occasionally, there are malignant cells which are derived from surrounding bone (osteoid), cartilage (chondroid) or muscle (myoid). Sarcomatoid mesotheliomas are extremely rare.

The remaining 25% of mesotheliomas are comprised of biphasic mesotheliomas. The biphasic mesothelioma contains both epithelioid and sarcomatoid components. Specifically, each component comprises about 10% each of the overall microscopic picture, as determined by a histopathologist.

This disease affects men much more often than women, probably because men are more likely to be exposed to asbestos in their workplace. Epithelioid histiocyte mutations that lead to mesothelioma occur 15 to 40 years after the person is exposed to asbestos. As a result, mesothelioma is uncommon in people under 50 years of age and its incidence increases with age.

A Biopsy is the most accurate way to diagnose Epithelioid Mesothelioma. Two positive and Two negative antibodies are required to make a concrete diagnosis of mesothelioma. The International Mesothelioma Panel (IMP) recommends that all patients require at least 1 CK marker, 2 mesothelial markers and 2 carcinoma-related markers in the diagnosis for this disease. The Epithelioid mesothelioma ICD code is C45.9. Because of its insidious evolution, the diagnostic process may be longer than for other forms of cancer. Your doctor will ask you about the symptoms you are experiencing and may give you a physical examination.

CK 5/6 (Cytokeratin 5/6)

CK 5/6 is characteristically expressed by mesothelial cells and is used to distinguish mesothelioma from lung cancer (adenocarcinoma). It is also useful in distinguishing epithelial mesothelioma from non-lung cancer derived tumors which have spread to the pleura (secondary metastasis).

Mesothelial Markers

i) Calretinin
Calretinin is considered to have the greatest specificity for the diagnosis of mesothelioma. This means that a negative calretinin is highly likely to suggest the absence of mesothelioma.
ii) WT1 (Wilms’ Tumour 1 Mutation)
The WT1 gene is responsible for the cellular growth and differentiation of mesothelial cells. The WT1 mutation is highly immunoreactive in epithelioid mesotheliomas but is not very immunoreactive in sarcomatous ones.

Carcinoma-Related Markers

i) CEA (Carcinoembryonic Antigen)
The absence of CEA immunoreactivity is characteristic of mesothelioma and is, therefore, a negative marker for it. Positive immunoreactivity is often seen in the context of lung cancer (adenocarcinoma).
ii) CD15
Most researchers agree that CD15 is not expressed by mesothelioma and is expressed in nearly all lung adenocarcinomas.

Biomarkers

i) SMRP (Soluble Mesothelin-Related Protein)
This is the only FDA-approved mesothelioma biomarker, which is expressed in the mesothelioma. While it is raised in patients with mesothelioma, it is not useful for screening or diagnosis as it is also raised in ovarian, pancreatic and other cancers. It is, however, useful to trend the severity and progress of mesothelioma during treatment.

Epithelioid mesothelioma treatment options can include surgery, chemotherapy, radiotherapy, and natural/alternative treatments. Your healthcare team will develop a treatment plan specifically for you. This therapeutic plan will be based on your health status and cancer-specific information.

You may be offered one or more of the following treatments for mesothelioma.

Surgery:

If you are able to go through surgery, here are the options available:

• For pleural mesothelioma:

The following types of curative surgery are used to treat pleural mesothelioma.

An extrapleural pneumonectomy: During this procedure, the parietal and visceral pleura, the lung on the side where the mesothelioma originated, a part of the diaphragm and the lymph nodes in the chest are removed. It is also possible to remove the envelope surrounding the heart (called the pericardium).

A pleurectomy/decortication: During this procedure, the parietal and visceral pleura and tumor are removed, but the lung is not removed.

Palliative surgeries are designed to relieve symptoms such as pain or difficulty breathing, they don’t remove the tumor. The following types of palliative surgery are used to treat pleural mesothelioma.

The most common one is tumor reduction, whereas much of the mesothelioma as possible is removed. Another common palliative surgery is thoracentesis, which is used to extract the fluid surrounding the lungs that hinder normal breathing.

The last palliative surgical option is pleurodesis, the parietal and visceral pleura are sealed together to prevent the accumulation of fluid between them.

• Peritoneal mesothelioma

In general, it is not possible to operate on people with peritoneal mesothelioma, as this cancer has usually spread too widely to be completely removed. Surgery is often used only to relieve symptoms caused by peritoneal mesothelioma. The only types of surgeries that can be proposed are palliatives like tumor reduction and paracentesis.

External radiotherapy can be used to treat pleural mesothelioma. After an extra-pleural pneumonectomy, radiotherapy can be administered to the side of the chest from which a lung has been removed.
Radiation therapy is not indicated after a pleurectomy because it could damage the lung tissues. Radiation therapy can also be used to relieve symptoms caused by pleural mesothelioma, such as back pain in bone metastasis.