What are the other Names for this Condition? (Also known as/Synonyms)

• Tubulopapillary Epithelioid Mesothelioma
• Tubulopapillary Type of Malignant Mesothelioma

What is Malignant Tubulopapillary Epithelioid Mesothelioma? (Definition/Background Information)

• A malignant mesothelioma is a malignancy of the mesothelial cells (membrane lining the various body cavities). They are known to mostly arise in the pleura and peritoneum, and rarely, in the pericardium, the tunica vaginalis of testis, and ovary
• Based on the cell type or histology, the tumor is classified into the following types:
  • Malignant epithelial mesothelioma
  • Malignant sarcomatoid mesothelioma
  • Malignant biphasic mesothelioma
• Malignant Tubulopapillary Epithelioid Mesothelioma is a rare histological variant of malignant epithelial mesothelioma. The tumor is diagnosed under a microscope, on examination of the cancer cells by a pathologist
• As the name suggest, the tumor consists of a combination of tubules and papillary architecture of cells; psammoma bodies may also be noted. The tubulopapillary subtype can be confused with adenocarcinoma spreading to the lungs, pleural cavity, or pericardium
• Malignant Tubulopapillary Epithelioid Mesothelioma may be associated with asbestos exposure (inhalation or swallowing of asbestos dust or fibers), certain surgical procedures, and radiation treatment to cancers in the chest or abdominal region. The cause of formation of the tumor is not well-established
• The signs and symptoms depend upon the location of the tumor. Small-sized tumors during the initial stages may remain asymptomatic. Large-sized tumors can cause pain, obstructive symptoms, fatigue, and weight loss. The complications of Malignant Tubulopapillary Epithelioid Mesothelioma include tumor metastasis to various regions and recurrence following its surgical removal
• The treatment of Malignant Tubulopapillary Epithelioid Mesothelioma is undertaken through surgery. However, since it is generally difficult to remove the entire tumor, chemotherapy and/or radiation therapy may be proposed. The prognosis is generally poor due to organ dysfunction, local invasion, and metastasis of the malignancy to various body sites

Who gets Malignant Tubulopapillary Epithelioid Mesothelioma? (Age and Sex Distribution)

• Malignant Tubulopapillary Epithelioid Mesothelioma is a rare histological subtype of epithelial type of malignant mesothelioma
• Even though the tumor may occur in children and young adults, a majority are found in older adults
• Both males and females are affected, although males are at a higher risk by virtue of their occupation
• No racial or ethnic group preference is generally noted

What are the Risk Factors for Malignant Tubulopapillary Epithelioid Mesothelioma? (Predisposing Factors)

Currently, no definitive risk factors are noted for the development of Malignant Tubulopapillary Epithelioid Mesothelioma. But it may be associated with the following factors:

• Association with asbestos/fiberglass exposure is strongly noted; the tumors may often develop many years after exposure to these substances. Workers exposed to asbestos include the following and those involved in occupations such as:
  • Manufacturing of industrial products containing asbestos such as paints, insulation, floor tiles, ceiling, etc.
  • Construction workers, home builders
  • Electricians
  • Firefighters
  • Demolition workers
  • Military personnel
  • Those working in chemical plant manufacturing facilities, refineries, power plants, etc.
  • Shipyard workers
• Secondary asbestos exposure (inhalation) during the job, when one may be exposed being in the vicinity. The environmental asbestos exposure can occur in a variety of ways
• Iatrogenic tumors: Some tumors have been reported to form following medical treatment for angina pectoris; for tumors affecting the pericardium
• Chronic smoking
• Radiation therapy for a variety of cancers: In rare cases, treatment for breast or abdominal cancer using radiation therapy is also known to cause the formation of malignant mesothelioma
• Exposure to eronite, a type of naturally-occurring mineral fiber, in some parts of the world (e.g. Turkey)
• Family history of mesothelioma: Mutations in BAP1 gene that can run in some families can increase the risk for malignant mesothelioma. The gene mutation can also cause an increased risk for a variety of cancers, such as ocular melanoma, clear cell renal cell carcinoma, liver cancer including intrahepatic cholangiocarcinoma, melanoma of skin, etc. in such individuals
• In experimental animal models, simian virus 40 (SV40, which is generally found in monkeys and humans) has been shown to cause malignant mesothelioma. However, whether SV40 causes mesothelioma in humans is not yet definitely established

Note:

• The adverse health effect caused by smoking and exposure to asbestos may act as a combination factor in some individuals and result in a much amplified risk for mesothelioma
• In some cases, no association to any of the above factors may be identified

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Malignant Tubulopapillary Epithelioid Mesothelioma? (Etiology)

The exact cause and mechanism of formation of Malignant Tubulopapillary Epithelioid Mesothelioma is unknown. However, the tumor formation seems to be influenced by exposure to certain carcinogenic substances (such as asbestos fibers), radiation therapy for cancer, and medical procedures.

• Mesotheliomas have been shown to have a variety of different genetic mutations
• Long-term exposure to asbestos:
  • Asbestos is a silicate mineral with a fibrous structure. Due to its high heat resistance, it is used as a versatile insulating material in several industries including construction, firefighting, automobile industry, etc. However, it is harmful to humans and is recognized as a hazardous material
  • It is researched that when the asbestos particles get into the body (part/site), they irritate the body tissue causing genetic damage. The entry into the human body may be through inhalation of asbestos dust particles or by inadvertently swallowing small-sized asbestos fibers
  • Generally it takes years to develop mesothelioma; around 10-50 years following exposure to asbestos or asbestos products
• In general, it is known that cancers form when normal, healthy cells begin transforming into abnormal cells - these cancer cells grow and divide uncontrollably (and lose their ability to die), resulting in the formation of a mass or a tumor
• The transformation of normally healthy cells into cancerous cells may be the result of genetic mutations. Mutations allow the cancer cells to grow and multiply uncontrollably to form new cancer cells
• These tumors can invade nearby tissues and adjoining body organs, and even metastasize and spread to other regions of the body

What are the Signs and Symptoms of Malignant Tubulopapillary Epithelioid Mesothelioma?

The signs and symptoms of Malignant Tubulopapillary Epithelioid Mesothelioma depend upon the location of the tumor. These may include:

• The presence of large-sized tumors that are nodular in appearance
• Most of the tumors are seen around the chest region affecting the pleura or pericardium
• Reports of the tumor at other sites, such as the peritoneum, are highly infrequent
• Low-grade fever and profuse sweating
• Tiredness or fatigue
• With respect to lung mesothelioma, right side lung involvement is more common than the left side (in a 3:2 ratio, per some study reports). In majority of cases, only one side is involved; the involvement of both sides simultaneously is very uncommon
• Tumors in the pleura or pericardium can lead to:
  • Shortness of breath or rapid breathing
  • Pleural or pericardial effusion; an abnormal collection of fluid within the pleura/pericardium
  • Chest pain or discomfort, such as feelings of heaviness/fullness of the chest
  • Intermittent cough
  • Tumors in the heart or lung can spread and obstruct major blood vessels or airways
• Fainting or feeling faint, dizziness
• Swelling in the lower legs
• Weight loss

There are no signs and symptoms during the initial stages of tumor growth and development. Also, small-sized tumors usually do not cause any symptoms. But, occasionally they may become painful, if the surrounding structures are compressed.

How is Malignant Tubulopapillary Epithelioid Mesothelioma Diagnosed?

The following tools may be used towards establishing a diagnosis of Malignant Tubulopapillary Epithelioid Mesothelioma:

• Complete evaluation of family (medical) history, along with a thorough physical examination
• X-ray of the affected region
• CT or CAT scan with contrast of the affected region may show the presence of a mass. This radiological procedure creates detailed 3-dimensional images of structures inside the body
• MRI scans of the affected region: Magnetic resonance imaging (MRI) uses a magnetic field to create high-quality pictures of certain parts of the body, such as tissues, muscles, nerves, and bones. These high-quality pictures may reveal the presence of the tumor
• Whole-body PET scan, bone scan of affected region to check for tumor metastasis. This helps with the staging of the tumor

Although the above modalities can be used to make an initial diagnosis, a tissue biopsy of the tumor is necessary to make a definitive diagnosis to begin treatment. The tissue for diagnosis can be procured in multiple different ways which include:

• Fine needle aspiration (FNA) biopsy of the tumor: A FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the tumor. Hence, a FNA biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy is preferred
• Core biopsy of the tumor
• Open biopsy of the tumor

Tissue biopsy of the tumor:

• A biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
• Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
• Sometimes, the pathologist may perform additional studies, which may include immunohistochemical stains, electron microscopy, and molecular studies to assist in the diagnosis

Note:

• It is rare to find a tumor that has purely one subtype. Often, there is a mixture of more than one cell type. The predominant pattern determines the histological subtype of the tumor
• Due to the rarity of these tumors, the diagnosis of this malignancy can be missed. It can even cause diagnostic challenges during a frozen section biopsy
• Tubulopapillary Type of Malignant Mesothelioma is often diagnostically confused with adenocarcinoma spreading to the chest and affecting the lungs, pleural cavity, or heart (pericardium)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Malignant Tubulopapillary Epithelioid Mesothelioma?

Complications due to Malignant Tubulopapillary Epithelioid Mesothelioma are dependent upon the site of the tumor and could include the following:

• Pleural tumors may result in:
  • Large tumors can obstruct the bronchus (airways) and other adjoining organs/structures
  • Severely impaired lung function
• Pericardial tumors may result in:
  • Congestive heart failure, depending on the location of the tumor in the heart
  • Cardiac tamponade due to fluid around the pericardium, which can lead to low blood pressure, fatigue, anxiety, rapid breathing, and fainting
  • Increased risk for thromboembolism (blood clot obstructing a blood vessel) 
• Large tumors can compress adjoining organs and structures and impair their function
• Metastasis of the tumor to other sites in the body such as to the lymph nodes
• Recurrence of the tumor after surgery, when the entire tumor is not removed
• Blood loss during invasive treatment methods may be heavy
• Damage of vital nerves, blood vessels, and surrounding structures during surgery
• Side effects from chemotherapy (toxicity), radiation therapy (radiation fibrosis)

How is Malignant Tubulopapillary Epithelioid Mesothelioma Treated?

In general, Tubulopapillary Type of Malignant Mesothelioma is a highly-aggressive cancer and the treatment can be challenging. A multidisciplinary approach with a team of healthcare specialists and experts from various medical fields may be necessary to treat the cancer at a healthcare institution that has the experience and expertise in dealing with such high-grade cancers.

The treatment measures for Malignant Tubulopapillary Epithelioid Mesothelioma may include a combination of the following:

• Surgery: Complete excision where possible is attempted; though, it is difficult for the tumor to be removed completely. Even though it may not be curative, it can aid in the diagnosis and relieve obstructive symptoms
• Radiation therapy and/or chemotherapy
• Immunotherapy: It is a newer method of treatment that has shown promising results in some individuals. The healthcare provider will determine if immunotherapy is to be employed in treating the tumor
• Embolization (clotting the vessels in the tumor) may be used to provide temporary relief from the symptoms and reduce blood loss during a surgical procedure
• Organ transplantation (such as lung or heart) may be undertaken in some cases; when no distant metastasis has occurred and the primary tumor, which cannot be surgically removed, is confined to the organ site
• Follow-up care with regular screening and check-ups are important

How can Malignant Tubulopapillary Epithelioid Mesothelioma be Prevented?

Current medical research has not established a method of preventing the formation of Malignant Tubulopapillary Epithelioid Mesothelioma. However, the following factors may be considered to reduce the risk of cancer development:

• Avoid or stop smoking: Individuals, who are smokers or have a prior history of the condition or suffer from other lung diseases, should regularly follow-up with their primary care physician to ensure that their lung functions are normal
• Reducing exposure to known causative agents such as asbestos and asbestos products
• Early detection of exposure to asbestos dust particles can help avoid further exposure
• Wearing appropriate respirators and masks while performing jobs that involve dust, chemicals, and metals
• While working in industry, maintain a clean work area that is dust-free. Also, regularly shower and change clothes after industrial work
• Ensure that industrial safety regulations for exposure to hazardous materials is adhered to at workplaces
• Ensure that the industries strictly comply with implementation of prevalent statutory codes on occupational safety measures, especially with respect to workplace exposure
• Undertake routine screening of individuals working in environment where exposure to asbestos is evident
• Government regulations have decreased or even eliminated the use of asbestos through increased safety measures and through the usage of substitute products (instead of asbestos)
• It is recommended that regular screening be undertaken for mesothelioma, if any of the following tumors are observed:
  • Clear cell renal cell carcinoma
  • Intrahepatic cholangiocarcinoma (a type of liver cancer)
  • Cutaneous melanoma
  • Uveal or ocular melanoma

Due to its high metastasizing potential and recurrence rate, regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory for those who have already been treated for this tumor.

What is the Prognosis of Malignant Tubulopapillary Epithelioid Mesothelioma? (Outcomes/Resolutions)

• The prognosis of Malignant Tubulopapillary Epithelioid Mesothelioma is generally poor. Death mostly occurs due to spread of cancer, large size of tumor, or severely affected function of the affected organ
• Nevertheless, the prognosis depends on a combination of factors, such as:
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • Grade of the tumor: It is considered as a helpful parameter in predicting the prognosis
  • Cell growth rate of the cancer (its ki-67 value): The ki-67 value is based on a protein found in cells that is a good indicator of how fast the tumor cells are growing. The ki-67 value is determined by a pathologist and is usually mentioned in the pathology report
  • Response to treatment and medical therapy: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
  • The size of the tumor and the extent of its invasion: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Stage of cancer per FIGO (or TNM): With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Individuals with bulky disease have a poorer prognosis
  • Involvement of the regional lymph nodes, which can adversely affect the prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical respectability of the tumor (meaning, if the tumor can be removed completely)
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
  • Progression of the condition makes the outcome worse

Additional and Relevant Useful Information for Malignant Tubulopapillary Epithelioid Mesothelioma:

Malignant epithelial mesothelioma is the most common histological type of malignant mesothelioma. It can occur in all 5 body sites, though the most frequent location is the pleura (in the lungs).