What is Mediastinal Nonseminoma?
Germ cell tumors are a type of cancer that starts in the reproductive cells of the testicles or ovaries. Occasionally, these germ cells can also appear in the mediastinum, an area in the middle of the chest, more commonly seen in young males. Around 70% of these tumors are non-seminomas, with the rest being seminomas. Non-seminomas include:
* Embryonal carcinomas
* Yolk sac tumors
* Teratomas
* Choriocarcinomas
The main known risk factor for germ cell tumors outside of the testicles or ovaries, referred to as extragonadal germ cell tumors, is a condition known as Klinefelter syndrome. Most patients with these extragonadal tumors do not have any sign of primary cancer in the scrotum. Often, these tumors in the mediastinum do not cause any symptoms until they grow large and take up space.
What Causes Mediastinal Nonseminoma?
Most germ cell tumors, a type of cancer, are typically found in the reproductive organs. However, these germ cell cancers can also occur in places outside the reproductive organs. These are formed from early forms of germ cells that were in the process of moving to where they usually reside and are called extragonadal germ cell tumors.
Extragonadal germ cell tumors are quite rare, making up only 1 to 5% of all germ cell tumors. They are commonly found in areas like the middle of the chest (mediastinum), the back of the abdomen (retroperitoneal area), the pineal gland (a small endocrine gland in the brain), and the suprasellar area (a part of the brain just above the pituitary gland).
Tumors that appear in the mediastinum, or mid-chest area, are known as mediastinal germ cell tumors, and they’re the most frequent type of extragonadal germ cell tumors.
Risk Factors and Frequency for Mediastinal Nonseminoma
Mediastinal germ cell tumors are pretty rare, making up only 3% to 10% of all tumors found in the area between the lungs (known as the mediastinum), and are more often diagnosed in men. They are categorised, based on their cellular makeup, into seminomatous and non-seminomatous germ cell tumors, similar to how we categorise germ cell tumors that affect the reproductive organs (gonads).
- Common subtypes of mediastinal non-seminomatous germ cell tumors include yolk sac tumor, teratoma, choriocarcinoma, and embryonal carcinoma.
- If a tumor contains multiple different types of cells, it’s called a mixed germ cell tumor and is counted as a non-seminomatous germ cell tumor, even if it contains seminoma cells.
- Mature teratomas are usually not dangerous (benign).
- The yolk sac tumor is the most common form of this subtype, which makes up about 60% of all such cases.
- These tumors are most likely to affect children and young adults, but a few older adults have been diagnosed too.
- There’s also evidence that these tumors can be associated with genetic disorders such as Klinefelter syndrome, or other blood-related cancers like acute myeloid leukemia, mastocytosis, and myelodysplastic syndromes.
Signs and Symptoms of Mediastinal Nonseminoma
The symptoms of mediastinal non-seminomatous germ cell tumors mainly rely on the subtype of the tumor, its size, and how fast it’s growing. Mature teratomas, which grow slowly, can often be diagnosed by accident when the patient is being examined for other conditions. The usual symptoms include:
- Coughing
- Difficulty in breathing, known as dyspnea
- Chest pain
- Fever
- Night sweats
- Weight loss
Sometimes, the tumor can press on important structures like the superior vena cava in the center of the chest. This can lead to additional symptoms such as flushed face and swollen neck veins, a condition known as superior vena cava syndrome. If the tumor compresses the bronchus (the air tubes leading into the lungs), it might result in post-obstructive pneumonia. In cases where the tumor erodes into the bronchus, coughing up blood, or hemoptysis, can be seen.
Testing for Mediastinal Nonseminoma
A thorough physical check-up, including an examination of the genital area is extremely important when these type of tumors are suspected. Certain markers, or signs, of these tumors can be identified in the body using tests that measure alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (b-HCG), and lactate dehydrogenase (LDH). People with benign teratomas, a specific type of tumor, won’t have elevated levels of b-HCG or AFP. However, most patients with non-seminomas, another type of tumor located in the chest area, will show increased levels of AFP and HCG. Tests may also be done to rule out a genetic condition known as Klinefelter syndrome.
When it comes to imaging, these tumors often appear as a mass in the front part of the chest on an x-ray. Teratomas can appear as different forms like bones, calcification, and teeth on an x-ray because they are made up of more than one germ layer. Although a chest x-ray might reveal a large mass in the chest, more detailed imaging like a computed tomography (CT) scan or magnetic resonance imaging (MRI) is necessary to clarify the exact size, shape, and location of the mass. It’s crucial for patients with these types of tumors to undergo a testicular ultrasound as they have a higher risk of having a testicular tumor at the same time.
The presence of these tumors can sometimes be mistaken for other conditions such as retrosternal thyroid tumors, lymphomas, and thymic tumors. Therefore, additional tests are recommended to examine lactate dehydrogenase (LDH) and thyroid-stimulating hormone (TSH) levels in the blood. A biopsy, or a sample of the tissue, is needed to definitively diagnose the condition and plan the following steps. However, there can be complications associated with biopsy such as seeding, where cancer cells can spread during the biopsy process. So, if clinical examination and elevated marker levels suggest the presence of tumors, a biopsy might not be necessary.
Treatment Options for Mediastinal Nonseminoma
Mediastinal non-seminomatous germ cell tumors aren’t common and are considered high-risk. Because they’re so rare, there isn’t a standardized system for determining their stage or how advanced they are. Treatment strategies for these types of tumors are mainly informed by their specific characteristics or histology. The strategies are based on small case studies, retrospective data, single-center studies, and information from similar types of tumors found in the gonads (testicles or ovaries). The main treatment options currently being evaluated are chemotherapy and surgery.
Teratomas, a specific type of germ cell tumor, usually do not respond to chemotherapy. Thus, surgical removal is the best treatment option for these benign tumors. In contrast, the majority of malignant or cancerous mediastinal non-seminomatous germ cell tumors, except mature teratomas, are primarily treated with a combination of different chemotherapy drugs, including cisplatin, followed by surgery to remove any remaining tumors. This approach was found to be effective in a study comparing two combinations of chemotherapy drugs in patients with advanced germ cell tumors.
Sometimes, one combination of drugs might be preferred over another to help prevent potential lung toxicity and the potential need for additional surgery after chemotherapy. There’s also evidence that a treatment sequence of chemotherapy followed by a procedure known as autologous stem cell transplantation (where a patient’s own stem cells are used to help their body recover from high-dose chemotherapy) might improve a patient’s chance of survival. It’s also important to monitor certain proteins called tumor markers in the blood to assess how well the chemotherapy is working.
Surgical removal of leftover tumor mass is typically recommended to improve overall outcomes. This is true even for patients whose tumor markers remain high after chemotherapy if they are surgically operable. If a viable tumor remains after surgery, more chemotherapy is generally advised. In contrast to seminomas (another type of germ cell tumor), radiation therapy is not typically part of the treatment plan for non-seminomatous germ cell tumors. If the remaining mass after chemotherapy is larger than 3 cm, surgery is recommended. If the mass is a dead lesion or mature teratoma, no further chemotherapy is usually needed.
What else can Mediastinal Nonseminoma be?
These are some conditions that may present similar symptoms to each other:
- Thymoma
- Lymphoma
- Tuberculosis
- Sarcoma
- Neurogenic tumors
- Myasthenia gravis
What to expect with Mediastinal Nonseminoma
The chances of getting better from this disease depend on several factors:
Firstly, the type of cancer cells involved: Seminomas, a specific kind of testicular cancer, generally have a higher chance of successful treatment compared to non-seminomas.
Next, the location of the cancer also matters. Those that are found in the scrotum or an area behind the abdomen called the retroperitoneum, typically have a better outlook compared to those in the brain or in an area inside the chest called the mediastinum.
Furthermore, the higher the initial levels of B HCG and AFP (specific substances in the body that increase when cancer is present), the worse the outlook typically is.
After chemotherapy, the survival chance of seminomas located in the mediastinum is generally higher than non-seminomas. However, germ cell tumors (a different type of cancer) in the mediastinum tend to be more resistant to chemotherapy. These can also affect breathing and some patients may even develop a blood cancer. Patients who have seminomas in the mediastinum and whose disease has spread to other parts of the body generally have the worst survival rates.
Possible Complications When Diagnosed with Mediastinal Nonseminoma
- Development of blood cancer
- Difficulty breathing
- Complications related to chemotherapy
- Radiation treatment related complications such as expedited heart disease
Recovery from Mediastinal Nonseminoma
It’s important for patients to have regular check-ups in the long term since it’s not unusual for the condition to return after some time. For kids who have undergone radiation treatment, it’s possible to experience a decrease in intellectual ability and develop hearing issues.
