What is Mediastinal Germ Cell Tumors?
Germ cell tumors are a type of cancer, which most often occur outside of the gonads (sexual/reproductive organs) in the front part of the space between the lungs, known as the anterior mediastinum. This location accounts for about 50 to 70% of all cases. It’s quite rare to find these tumors in the back part of this space, or the posterior mediastinum. The main types of these are primary mediastinal and gonadal germ cell tumors, which have a lot in common in terms of their characteristics, including particular genetic features. There is a known link between mediastinal germ cell tumors and Klinefelter syndrome, a genetic condition, and various blood cancers.
There are three main types of germ cell tumors: teratomas, other non-seminomatous tumors, and seminomas. Each type has different implications for what kind of treatment is needed and what the outcome might be.
Most of the time, these tumors are found by chance when someone has an imaging scan for another reason. When they are first diagnosed, between 20 and 40% of patients don’t have any symptoms. If they do have symptoms, these are usually caused by enlargement of the space where the tumor is located and pressure on surrounding structures. This can lead to common symptoms such as chest pain, cough, difficulty breathing, fever, night sweats, and weight loss. The symptoms experienced can depend on the size of the tumor and its type.
Once diagnosed, the treatment will usually involve either surgery to remove the tumor or chemotherapy based on a drug called cisplatin, followed by surgery, depending on the type of the tumor.
What Causes Mediastinal Germ Cell Tumors?
Germ cell tumors are a type of cancer that usually develop in the testicles in men, and very rarely in the ovaries in women. It’s not common, but they can also originate from places in the middle of the body like the area around the heart (mediastinum), the back of the abdomen (retroperitoneum), or near the brain (pineal or suprasellar areas).
The exact cause of this type of cancer, especially when it’s found outside of the sex organs, is not fully understood yet. There are, however, a few competing theories.
One of the theories relates to how the testicles develop in the body during pregnancy. The cells that will become the testicles (primordial germ cells) start in one place and have to move to another place in the body. The main theory is that sometimes these cells get stuck during their journey, and this can later cause a tumor to form in the area around the heart.
The other theory suggests that cells that have already gotten to the place they’re supposed to be (the sex organs) start moving backwards and this also leads to tumor formation. This idea is supported by some genetic research, however, it doesn’t explain all the observed biological differences in these tumors.
Risk Factors and Frequency for Mediastinal Germ Cell Tumors
Germ cell tumors in the mediastinum are quite rare, only accounting for 15% of all tumors in that area. They are the most common type of germ cell tumors found outside the reproductive organs, but they only represent about 1% to 3% of all germ cell cancers. These tumors primarily occur in men (97% of cases) and in younger patients, with an average age of 31. It’s also worth mentioning that these tumors are often linked with Klinefelter syndrome, particularly the non-seminomatous variants.
- Germ cell tumors in the mediastinum are rare, making up only 15% of all tumors in that area.
- They account for approximately 1% to 3% of all germ cell cancers.
- These most often occur in men, with 97% of cases affecting males.
- The average age of patients with this type of tumor is 31.
- These mediastinal germ cell tumors are often associated with Klinefelter syndrome, especially the non-seminomatous variants.
Signs and Symptoms of Mediastinal Germ Cell Tumors
Mediastinal germ cell tumors are a type of tumor that can be discovered by chance during medical imaging. While these tumors might not show any symptoms, larger ones can cause discomfort or complications by putting pressure on or blocking surrounding structures. In rare instances, these tumors can become infected. Some of these tumors may also contain digestive enzymes. Sometimes, these tumors can rupture on their own, leading to inflammation around the nearby organs.
The complications can be severe if the tumor ruptures into the space around the lungs (pleural space) or the heart (pericardial space). If a tumor blocks the airways (bronchial obstruction), it can result in conditions like post-obstructive pneumonia or bleeding from the lungs (hemoptysis) if erosion occurs.
Non-seminomatous mediastinal germ cell tumors have a higher likelihood of causing symptoms and can spread to the lymph nodes, unlike seminomas and teratomas. Symptoms associated with these tumors can include weight loss, fever, cough, shortness of breath, and chest pain. In serious cases, these tumors may also cause superior vena cava syndrome, a severe condition where the large vein carrying blood from the upper body to the heart is squeezed.
Testing for Mediastinal Germ Cell Tumors
If you visited your doctor with signs that suggest a condition called mediastinal germ cell tumors, you will need to have a detailed physical examination. Your examination will pay extra attention to your reproductive organs. As a part of this physical examination, your doctor may use sound waves to create a picture of the internal structures of your testicles (testicular ultrasound). This is done to check if there are any additional tumors.
This suspicion of a mediastinal germ cell tumor often comes after an X-ray of your chest reveals a lump, or mass, in your anterior mediastinum (the area in the front part of the space between your lungs). You might also visit your doctor if you have symptoms caused by this lump.
To get a better understanding of the size, location, and borders of the tumor, your doctor may order a Computed Tomography (CT) scan or Magnetic Resonance Imaging (MRI). Also, specific molecules in your blood – alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (B-hCG), and lactate dehydrogenase (LDH) – may be high in cases of mediastinal germ cell tumors, and therefore will be checked in your blood. If your B-hCG levels in the blood are over 1,000 U/L, and/or if there is an increase in your AFP, it helps support the diagnosis of mediastinal germ cell tumors.
Mediastinal germ cell tumors can come in different forms – Teratomas, Seminomatous Tumors, and Non-seminomatous Tumors.
In the case of teratomas, they’re usually found in or near the thymus gland, which is located in the front part of the space between your lungs. Test results typically do not show an increase in specific blood molecules in benign (non-cancerous) masses. The tumor will contain cells that resemble at least two of the three types of cells found in an embryo. It is not uncommon for these tumors to contain teeth or bone.
If your doctor suspects seminomatous tumors, these usually look like a lobulated surface (like a rough surface with rounded projections) with areas of tissue death and bleeding. The cells have a clear border filled with clear cytoplasm that contains glycogen and would respond to a particular type of test called the periodic acid-Schiff (PAS) reaction.
On the other hand, non-seminomatous mediastinal germ cell tumors could include a variety of subtypes, and they account for the most malignant forms of mediastinal germ cell tumors. Among these, the most common is the yolk sac tumor, which makes up about 60% of cases. These tumors appear as soft gray-white masses with areas of tissue death and bleeding. They also show unique, kidney-shaped structures that look like tiny blood vessels.
All this detailed information, or factors, and findings are used by your doctor to make a final diagnosis to guide your treatment plan.
Treatment Options for Mediastinal Germ Cell Tumors
Mediastinal germ cell tumors, tumors that develop in the area of the chest that separates the lungs, are rare but are treated similarly to gonadal germ cell tumors, which develop in the reproductive glands. Mediastinal germ cell tumors can be classified into different risk categories. “Poor risk” represents an advanced form of the disease. Teratomas, a type of germ cell tumor, and seminomatous (relating to or resembling semen or a seminiferous epithelium) mediastinal germ cell tumors are considered good or intermediate risk based on their markers and any evidence of the cancer spreading.
Benign mature teratomas don’t respond to chemotherapy, so doctors usually take a surgical route when symptoms are present. The operation may involve creating a surgical incision along the middle of the chest (median sternotomy) or in the upper back (posterolateral thoracotomy). If the surgery doesn’t completely remove the tumor to avoid disturbing vital bodily structures, there’s typically no need for further radiotherapy or chemotherapy because these tumors don’t usually invade outside the mediastinum, the part of the chest cavity where the tumor resides.
The treatment for seminomatous mediastinal germ cell tumors consists primarily of a chemotherapy treatment plan with bleomycin, etoposide, and cisplatin, depending on the risk category of the tumor.
In the case of the “poor risk” tumors, treatment often involves chemotherapy first, followed by surgical removal of any remaining tissue. Initial treatments for this type of tumor involved a combination of bleomycin, etoposide, and cisplatin. With this plan, harmful lung issues were observed that complicated patients’ conditions, especially considering they might need extensive chest surgery afterward.
Due to these potential complications, bleomycin has been replaced with ifosfamide in certain situations. When areas of the tumor persist after chemotherapy, additional surgery is needed since leftover germ cell tissue can lead to the development of further teratomas. Repeat surgeries can result in improved survival rates in the long term, while radiation therapy is considered for patients with leftover tumor tissue near essential organs.
The role of high-dose chemotherapy followed by replacing of your own cells through stem cell therapy needs more research. However, it could be considered for patients with advanced disease or cases of an early return of the cancer. Relapse after treatment is possible, and further rounds of chemotherapy could be warranted. Regardless of the type of chemotherapy used, cure rates in the setting of salvage therapy, a further line of treatment when the initial regimen fails, range from 5% to 10% on average.
What else can Mediastinal Germ Cell Tumors be?
The following are potential medical conditions that could be diagnosed:
- Lymphoma
- Thymoma
- Thymic carcinoma
- Sarcoma
- Tuberculosis
- Mediastinal goiter
- Thymolipoma
Surgical Treatment of Mediastinal Germ Cell Tumors
Mature teratoma-type mediastinal germ cell tumors are typically treated with initial surgery, especially when there aren’t any severe risk factors present, like high tumor markers. Tumor markers are substances, usually proteins, that the body produces in response to cancer growth. These are used by doctors to help evaluate how serious a cancer case is or how well treatment is working.
On the other hand, seminomatous germ cell tumors are highly responsive to chemotherapy, which means they can often be treated effectively without surgery. Chemotherapy is a type of cancer treatment that uses drugs to kill cancer cells.
However, even when patients undergo chemotherapy, surgery might be required to remove any residual disease. This is considered the standard healthcare practice. The timing of the surgery is decided depending on the normalization of tumor markers, and when the disease is only present in one site. This means that if the tumor markers return to normal and the cancer is only found in one area, then it’s time for the surgery to remove any lingering disease after chemotherapy.
What to expect with Mediastinal Germ Cell Tumors
Certain factors can affect the prognosis or outcome of germ cell tumors, a form of cancer that often affects the testicles or ovaries. These negative factors include non-seminomatous germ cell tumors (a more aggressive type of germ cell cancer), older age, the spread of the cancer to the lungs, and increased levels of specific tumor markers – proteins (AFP, B-hCG, LDH) found in the blood that often increase when cancer is present.
Patients with seminomatous germ cell tumors– a less aggressive type of germ cell cancer– in the area between the lungs (mediastinum) have a 5-year survival rate between 72% and 100%. In contrast, patients with non-seminomatous germ cell tumors have a 5-year survival rate between 48% and 65%.
The best outcomes for non-seminomatous cancers were seen in younger patients (under 29 years of age) with normal levels of the tumor marker B-hCG. If the cancer has spread to other organs besides the lungs (nonpulmonary visceral metastasis), the prognosis is typically poorer.
However, in seminomatous tumors that have not spread to the lungs, the 5-year survival rate is more than 90%.
According to a recent update from a group of international experts (the International Germ Cell Cancer Collaborative Group), patients with seminomatous mediastinal germ cell tumors who have levels of the enzyme LDH that are more than 1.5 times higher than normal typically have worse outcomes.
Possible Complications When Diagnosed with Mediastinal Germ Cell Tumors
Mediastinal germ cell tumors, a type of disease, can spread to nearby structures during its progression. These tumors typically migrate to other parts, such as the bone, lungs, liver, and lymph nodes located in the chest area.
During the treatment process, there is a risk of complications related to chemotherapy. After surgical procedures, patients might experience various complications like pyothorax (a condition where pus accumulates in the chest), injury to the phrenic nerve (a very important nerve that controls the diaphragm), and profuse bleeding. These are all potential issues that can emerge when managing mediastinal germ cell tumors.
Common Complications:
- Spread of disease to nearby structures (such as bones, lungs, liver, and chest lymph nodes)
- Chemotherapy-related complications
- Post-surgical complications like pyothorax
- Phrenic nerve injury
- Excessive blood loss
Preventing Mediastinal Germ Cell Tumors
Mediastinal germ cell tumors are believed to form due to irregular movement of germ cells while a baby develops in the womb. These tumors are most commonly found in younger males. Germ cells are early-stage cells that will later become sperm in the testicles or eggs in the ovaries. “Embryogenesis” is the process by which an embryo forms and develops.
Specific tests that detect certain biological markers (AFP, B-hCG, LDH) are necessary for patients who have a mass located in the front part of their mediastinum (the area in the middle of the chest that separates the lungs), even if they don’t have any symptoms. The mediastinum contains the heart, large blood vessels, windpipe, and some glands.
Patients with this type of tumor also need to be checked for signs of Klinefelter syndrome, a genetic condition sometimes associated with these tumors. This is done through a cytogenetic analysis – a test that examines the number and structure of a person’s chromosomes. Klinefelter syndrome is a condition where males have an extra ‘X’ chromosome.
Spotting these symptoms early and starting treatment can lead to improved chances of beating the disease.
