What is Mediastinal Carcinoid Tumors?
Mediastinal carcinoid tumors are essentially a type of cancer known as thymic carcinoid neoplasms. The term ‘carcinoid’ was used historically because these tumors look like carcinoma (a type of cancer), and is often used interchangeably with the term ‘neuroendocrine tumors’ (NETs). These thymic carcinoid tumors are quite rare, originating from the thymus, which is a part of your body’s immune system that sits in front of your heart. Thymic carcinoid tumors are the least common of all NETs.
Contrary to many NETs that come from the digestive system or the lungs, over 80% of thymic neuroendocrine tumors are cancerous and usually show aggressive behavior. In 2015, the World Health Organization (WHO) classified thymic carcinoid tumors into four different categories. These include typical and atypical carcinoids, which are well-defined tumors, and small-cell and large-cell carcinoid tumors which are not well-defined.
What Causes Mediastinal Carcinoid Tumors?
The exact cause of neuroendocrine thymic tumors, which are cancerous tumors that start in the thymus gland, is still not known. These tumors are connected to a condition called ‘Multiple Endocrine Neoplasia type-1’ (MEN-1) in about 25% of the cases. MEN-1 is a disorder that causes tumors in the endocrine glands, which are glands that produce hormones.
There doesn’t seem to be a clear link between these tumors and any harmful substances or environmental factors for cases that occur randomly. However, studies have shown there’s a higher chance of people with MEN-1 who smoke heavily to develop thymic carcinoid, a particular type of thymic tumor.
Risk Factors and Frequency for Mediastinal Carcinoid Tumors
Thymic NETs (neuroendocrine tumors) are very rare. They represent a very small percentage (2% to 5%) of all cancers in the thymus (a small organ in your chest) and only 0.4% of all neuroendocrine cancers, which start in the cells that make hormones.
- Most people diagnosed with thymic NETs are adults, typically around the age of 54.
- They are much more common in males, with a male to female ratio of 3:1.
- In the United States, the estimated number of new cases each year is about 0.2 for every million people.
Signs and Symptoms of Mediastinal Carcinoid Tumors
Thymic NETs, or tumors, start as a mass in the chest’s medial section. These tumors often go unnoticed until they’re in advanced stages, as people either experience no symptoms or show vague and unclear signs. These tumors are aggressive and tend to invade nearby organs. By the time they’re diagnosed, about half of all patients have tumors that have spread to local organs, while 20-30% already have distant metastatic disease. This spread can occur either through the lymphatic system or through blood circulatoin.
People may start to show symptoms of thymic NETs when the tumor compresses local body structures. Some people may not even show any symptoms. The symptoms can vary depending on how far the tumor has spread. Common symptoms include:
- Cough
- Difficulty breathing
- Chest pain
- Hoarseness due to the tumor invading the recurrent laryngeal nerve
About 20% of people with thymic NETs may also present with superior vena cava syndrome, a condition in which the superior vena cava – the major vein carrying blood from the brain and upper body to the heart – is compressed or obstructed, at the time they’re diagnosed.
Testing for Mediastinal Carcinoid Tumors
Thymic Neuroendocrine Tumors (NETs) can be tough to diagnose because often, symptoms are not clear. Therefore, there needs to be a high level of awareness amongst the doctors. Strikingly, sometimes these tumors are discovered while testing for other conditions.
Imaging Studies
For a comprehensive evaluation, doctors generally recommend a type of scan known as a computed tomography (CT) of the chest along with an intravenous (IV) contrast. This is primarily used for assessing the masses present in the front area of the mediastinum, the space between the lungs in the chest. This high level imaging technique using IV contrast not only gives valuable details about the mass’s nature and location, but it can also produce information about the spread of cancer to nearby areas.
A mass that is large, uneven, and often invasive, with signs of internal bleeding or cell death, could be an indication of thymic NETs. Using another type of scan, the magnetic resonance imaging (MRI), doctors can obtain more detailed info about the spread of the tumor to local structures such as big blood vessels, heart structures, or the layer around the heart.
In recent times, doctors are increasingly using imaging based on the somatostatin receptors to diagnose and stage NETs. Thymic NETs, like other NETs, display an overabundance of somatostatin receptors. Therefore, the use of radioactive somatostatin analogs, like the gallium Ga-68 DOTATOC, allows the doctors to spot thymic NETs and differentiate them from other cancers. This whole body scanning can also help identify primary tumors in the thymus as opposed to spreading disease, and it allows for early treatment in advanced cases.
Laboratory Studies
Most thymic NETs cases don’t produce hormones, which limits the use of lab tests. However, in a specific cases, Chromogranin A (CGA) levels, if increased at the time of diagnosis, may help in tracking the disease’s activity, especially for patients with metastatic disease. But due to the test’s lack of sensitivity and specificity, CGA doesn’t work as a diagnostic tool.
In specific cases where there are cancer-related syndromes, such as Cushing’s syndrome, high cortisol levels can be detected in the blood and 24-hour urine cortisol collection. Some other signs such as high calcium and low phosphate levels could be indicative of a disease associated with a high amount of PTHrP, a kind of protein, and these can be used to track disease recurrence.
Biopsy
After examining the CT chest imaging and determining the characteristics of the mass and its invasiveness, doctors decide whether tissue biopsy or mass resection due to suspected cancer is needed. For small, enclosed masses, surgical removal of the tumor is generally attempted. However, for larger masses with unclear boundaries, a tissue biopsy is recommended before attempting surgical removal, to clarify the possibility of requiring chemotherapy.
Most biopsies are done through a CT guided core needle biopsy, which usually identifies a thymic NET. However, in situations where there may not be enough tumor cells for a conclusive diagnosis, or the tumor location doesn’t allow for a CT guided approach, other procedures such as endoscopic or transbronchial ultrasound-guided fine needle biopsy might be preferred. These techniques are also preferred if the disease has spread to the mediastinal lymph nodes.
If all else fails, a surgical approach might be warranted. Depending on the tumor’s location, either an anterior mediastinotomy for cases where the mass invades towards the anterior chest wall, or a video-assisted thoracoscopic (VATS) approach if the mass has invaded towards either side of the chest is chosen. The VATS approach is also useful if there are concerns about possible lung metastases.
Treatment Options for Mediastinal Carcinoid Tumors
There aren’t any official guidelines for treating thymic NETs (neuroendocrine tumors of the thymus gland), as the data we have is based mainly on case studies rather than large, controlled trials. The recommended treatment is complete surgical resection, which involves removing all of the anterior mediastinal compartment (the front part of the area between the lungs), including the lymph nodes located there. However, many thymic NETs are too large to be removed at the time of diagnosis.
We don’t yet fully understand the role of therapies that are used before surgery, such as chemo or radiation therapy. When the disease stays local or affects only a limited area, surgical removal is usually the best option. But even then, it’s not always possible to remove all of the tumor on a microscopic level, and there’s a high chance the disease could return. If total resection is completed, chemo and radiation therapy may be used afterwards to control any remaining disease. Options for this treatment could include cisplatin or carboplatin plus etoposide, which are recommended for patients with moderately or poorly distinguished diseases. However, the evidence supporting this approach is limited.
When the disease returns or spreads to other areas of the body, the tumor should be removed surgically if possible. If the disease cannot be surgically removed or if it has metastasized (spread to other areas), then systemic therapy (treatment to the entire body) is preferred. If the tumor shows expression of somatostatin receptors (proteins that bind somatostatin, a hormone that regulates endocrine system), somatostatin analogs could be chosen. In such rare cases, octreotide and lanreotide are considered reasonable options.
Chemotherapy regimen involving carboplatin and etoposide is used for medium to poorly differentiated tumors. These recommendations are based on the treatment guidelines for poorly distinguished NETs of the digestive tract and lungs. Other therapies, like everolimus, which have shown survival benefits in patients with advanced lung and gastrointestinal NETs, are also considered a therapeutic option for thymic NETs, as they are thought to work similarly.
Lastly, the role of radiation therapy in treating recurrent or metastatic disease is primarily to alleviate symptoms and improve the quality of life, rather than to cure the disease.
What else can Mediastinal Carcinoid Tumors be?
These are various types of diseases related to the thymus, a small organ in your chest. They include:
- Thymic carcinoma
- Thymoma
- Paraganglioma
- Lymphoma
- Germ cell tumors
What to expect with Mediastinal Carcinoid Tumors
The chances of recovery from thymic neuroendocrine tumors (NETs), a type of cancer, depend on several factors. These factors include the stage and size of the tumor, whether it can be removed by surgery, histologic grade (a measure of how abnormal the cancer cells look under a microscope), and the proliferation index (how quickly the cancer cells are growing).
Generally, these tumors found in the thymus gland (an organ in your chest) have a worse prognosis than the same type of tumors found in the digestive system or the lungs. This is due to the aggressive nature of thymic NETs, which tend to spread or come back in the same area. Furthermore, these tumors are often detected very late, making them harder to treat effectively.
In a study analyzing cancer data, the overall survival time for patients with localized disease (cancer that has not spread beyond the thymus) was found to be nearly 110 months. This greatly contrasts with patients whose cancer had spread to nearby regions or other parts of the body, as they had survival times of just 59 and 35 months respectively.
Possible Complications When Diagnosed with Mediastinal Carcinoid Tumors
Some complications related to the disease are carcinoid or paraneoplastic syndromes, such as Cushing’s syndrome or humoral hypercalcemia of malignancy, which is an elevated calcium level in the blood due to cancer. There can also be complications related to treatment or intervention, specifically after a thymectomy, or surgical removal of the thymus. These include possible injury to the phrenic and recurrent laryngeal nerves, infection at the site of surgery, mediastinitis which is an infection in the space between the lungs, and wound dehiscence, which is a surgical complication where the wound ruptures along a surgical incision.
Here’s a simplified list:
- Carcinoid or paraneoplastic syndromes, like Cushing’s syndrome or humoral hypercalcemia of malignancy
- Complications after a thymectomy:
- Injury to the phrenic and recurrent laryngeal nerves
- Infection at the site of surgery
- Mediastinitis, an infection in the space between the lungs
- Wound dehiscence, a surgical complication where the wound ruptures along a surgical incision
Preventing Mediastinal Carcinoid Tumors
The only factor related to the environment that has been linked with thymic NETs, a type of tumor in the thymus gland, is heavy smoking, especially in patients with MEN-1. MEN-1 is a rare disorder that increases the risk of tumors in the glands of the endocrine system. Because of this association, it is strongly suggested that these individuals stop smoking.
