What is Germ Cell Seminoma?
Germ cell tumors (GCT) are a type of cancer that originates from early “seed” cells and typically grows in the reproductive organs, i.e., the testicles for men and ovaries for women. However, these tumors can also uncommonly develop in other parts of the body like the front part of the chest cavity (anterior mediastinum), the pineal gland in the brain and other parts of the brain. There are two main types of GTC: seminomas and non-seminomas.
Seminomas usually have a good chance of recovery, while non-seminomas are more likely to spread (metastasize) to other parts of the body. In some cases, a tumor might contain two or more different GCT types, which is referred to as a mixed germ cell tumor. Furthermore, a small number (1-3%) of all GTC cases, called “extragonadal germ cell tumors” (EGGCT), appear outside of the reproductive organs without any primary tumor in those organs. Around 60% of these EGGCT are seminomas.
They can appear in midline locations of the body like the front part of the chest cavity (anterior mediastinum), the central nervous system (including the brain) and the retroperitoneum (the space in the abdominal cavity behind the abdominal lining). If a seminoma is found in the retroperitoneum, it is generally assumed to be a metastasis from a primary seminoma in the reproductive organs, unless proven otherwise. Within the central nervous system, the pineal gland and regions above the sella turcica (a saddle-shaped area in the skull base) are more often affected.
A seminoma appearing in the brain is called a germinoma, and it makes up about two-thirds of all brain GCT cases. Germinomas can be pure (only containing seminoma cells) or mixed (containing other non-germinoma GCT types). The remaining one third of brain GCT cases are non-germinomas, which include different types of non-seminomas like embryonal carcinoma, yolk sac tumor, choriocarcinomas, teratomas, and mixed tumors (with more than one type of abnormal cells).
Rarely, GCT can form in paraventricular regions of basal ganglia and thalamus (parts of the brain). Very rarely, germinomas can appear in two places (the pineal gland and the region above the sella turcica) at the same time, which is referred to as a bifocal germinoma. Germinomas are more common in young teens and are typically diagnosed during their second decade of life. However, the chances of recovering from a germinoma are quite high, with a 5-year survival rate greater than 90%, as this type of tumor is highly responsive to radiation therapy.
What Causes Germ Cell Seminoma?
The root cause of EGGCT, which are tumors that start in cells that are going to become sperm or eggs, isn’t completely known yet. Two main ideas have been suggested about how these tumors start, but there isn’t enough clinical evidence to be certain about either explanation yet.
The first theory is that during the embryo’s development, cell migration doesn’t go as planned. This means that primal germ cells (early stage cells which eventually develop into sperm or eggs) end up in different parts of the body along the midline instead of where they were supposed to be.
The second theory suggests that germ cells, which are initially developing in the reproductive organs, somehow migrate backwards to other places, and that’s where the tumors form.
Certain tests, like Fluorescence in situ hybridization (FISH), found that an untypical form of chromosome 12 (named isochromosome 12p) is often seen in a type of cancer called testicular seminoma.
Advancements in gene sequencing technology have managed to identify several gene changes that play a part in the development of these brain tumors. Particularly, germinomas, one kind of these tumors, have been linked with a positive, abnormal change in the gene c-KIT, which makes a protein vital for cell growth and division. Notably, some other findings include mutations in proteins named KRAS and NRAS which control the c-Kit receptor pathway. Furthermore, germinomas were found to have less methylation (a chemical process that can control gene activity), a feature they share with the primal germ cells, suggesting they come from the same origin.
Risk Factors and Frequency for Germ Cell Seminoma
Primary intracranial germ cell tumors (GCTs) are rare, making up less than 5% of all brain and nervous system tumors. They are even more uncommon in adults, accounting for 0.4% to 1% of all brain tumors. The occurrence of these tumors varies depending on location and race, being more common in Asians.
- GCTs represent less than 5% of all brain and nervous system tumors.
- In adults, they constitute between 0.4% and 1% of all brain tumors.
- The rate of occurrence is higher in Asians compared to other races, with an incidence rate of 0.136 per 100,000 people.
- In the United States, the incidence rate is 0.10 per 100,000 person-years.
- The largest portion of GCTs, about 65%, is germinoma.
- Most individuals are diagnosed between the ages of 10 and 12, although a substantial number are diagnosed before the age of 20.
- The tumors are more frequent in males compared to females.
- The most commonly affected areas by the tumor are the pineal gland and the region above and below the pituitary gland.
- Although less frequent, other regions such as the thalamus, basal ganglia, and ventricles can also be affected.
- Tumor locations can also vary by sex, with tumors in the pineal region being more common in males and non-pineal tumors showing a slight female predominance.
Signs and Symptoms of Germ Cell Seminoma
The symptoms of brain tumors largely depend on their size and location. If the tumor affects the suprasellar region – the area above the pituitary gland – it can disrupt the functioning of the hypothalamus or pituitary, leading to an imbalance of hormones. Symptoms might include excessive thirst and urination due to a condition known as diabetes insipidus, as well as growth delays, adrenal insufficiency, thyroid-related issues, and abnormal puberty. Vision problems occur when the tumor extends towards the back and starts pressing against the optic chiasm. However, these symptoms can be quite mild, leading to potential delays in diagnosis.
Tumors in the pineal region of the brain often lead to symptoms associated with increased pressure inside the skull, such as headaches, nausea, vomiting and optic disc swelling which is visible during an eye exam (papilledema). This increase in pressure can be caused by a blockage that results in fluid buildup, known as obstructive hydrocephalus. Issues related to eye movement and vision, including double vision and Parinaud syndrome (characterized by upward gaze paralysis, loss of light perception, loss of eye convergence, and involuntary eye movements called nystagmus), may be present.
It’s essential to conduct a thorough physical analysis, especially looking for changes in vision and neurological function. In adolescents and adults, primary and secondary sexual traits should be checked. In young children, potential growth disruptions should be examined closely.
- Excessive thirst and urination (indicative of diabetes insipidus)
- Growth delays or abnormal puberty
- Adrenal insufficiency
- Thyroid-related issues
- Vision problems
- Headaches, nausea, and vomiting (indicative of increased skull pressure)
- Optic disc swelling (papilledema)
- Double vision and/or Parinaud syndrome
Testing for Germ Cell Seminoma
If your doctor suspects you have a germinoma—a type of tumor—they will need to run several tests.
One of the most important tests is a type of medical imaging called an MRI scan. This scan can spot germinomas due to the specific way they appear on the images. They look like a uniform lump that varies in color depending and can be either the same intensity or less intense on T1 and the same or more intense on T2 weighted images. In more advanced cases, germinomas may appear uneven or partially filled with fluid and may invade the nearby brain tissue. While an MRI is the preferred method, a CT scan can also be used to detect germinomas. However, just seeing a mass on an MRI or CT scan does not confirm it’s a germinoma, and further testing will need to be done.
Your doctor may also test your levels of certain tumor-related proteins, called oncoproteins, in your blood and cerebrospinal fluid (CSF – the fluid that surrounds your brain and spinal cord). For germinomas, these proteins—specifically alpha-fetoprotein (AFP) and beta-HCG—remain normal. However, beta-HCG may be slightly elevated if the germinoma contains a type of cells called syncytiotrophoblast cells, but the levels will still be less than 50 IU/ml.
Analyzing your cerebrospinal fluid (CSF) is a very important part of testing. If cancer cells are found in your CSF, it may indicate that cancer has spread, or metastasized, to other parts of your body.
Another test that might be conducted is a biopsy, which is a procedure where a doctor removes a small piece of the suspected tumor for examination under a microscope.
Except for imaging and fluid analysis, a technique called immunohistochemistry (IHC) is also used. IHC helps to detect specific proteins (markers) on the cells of the suspected tumor. Germinomas show specific marker “c-kit (CD117)”, and the test can also look for Oct 3/4, PLAP, and D2-40 markers.
While biopsy can help in identifying the tumor, sometimes, especially in mixed GCT, due to limited tissue availability, biopsy might not give a clear result. Thus, a thorough correlation is required between imaging results, tumor markers, and biopsy for correct identification of a germinoma. Doctors are well-equipped to handle these complex evaluations and will ensure accurate diagnosis.
Treatment Options for Germ Cell Seminoma
Germinoma is a type of cancer with a high survival rate. It responds very well to radiation and chemotherapy treatments, with survival rates over 90% within five years. The typical treatment plan usually involves radiation to the whole brain and spinal cord, or chemotherapy combined with a lower dose of radiation.
When it comes to radiation treatment, initially, the complete brain and spinal cord would receive radiation, followed by targeted radiation to the cancerous tumor. However, this method led to substantial side effects. The current method involves radiation to the entire brain (instead of the spinal cord) followed by targeted radiation, leading to fewer chances of the cancer returning.
With chemotherapy, we are able to reduce the amount of radiation, thereby lessening harmful effects on the body. Chemotherapy using platinum-based drugs before radiation has proven to be quite effective. However, using only chemotherapy is linked with a higher chance of the cancer returning.
In situations where the germinoma has spread, as indicated by MRI scans or tests of the cerebrospinal fluid (the fluid surrounding the brain and spinal cord), a combination of full brain and spinal cord radiation coupled with targeted radiation works best.
As for surgery, its role in treating germinoma is unclear due to the risk of damaging surrounding brain structures. Typically, surgery is reserved for obtaining a sample of the tumor for diagnosis or relieving pressure caused by excess fluid buildup in the brain. In some cases, surgeons may conduct a second surgery to remove any tumor that did not respond to the standard treatment, but this is more common in patients with other types of germ cell tumors.
What else can Germ Cell Seminoma be?
Diagnosing the type of brain tumor depends on where it is located.
For a tumor in the pineal gland (a gland in the brain), doctors look to rule out specific types of tumors. These include:
- pineocytoma
- pineoblastoma
- papillary tumor of the pineal region
For a tumor located in the sellar/suprasellar region (area near the pituitary gland), the potential diagnosis could be:
- pituitary adenoma/carcinoma
- craniopharyngioma
- meningioma
Differentiating between a germinoma (a certain type of tumor) from non-germinomatous germ cell tumors, particularly mixed ones, is essential because of their different treatments and how they affect overall health. Imaging techniques alone cannot make this distinction, so a biopsy is needed for a final diagnosis. Although germinoma and mature teratoma can have normal levels of certain proteins (called AFP and Beta-HCG), increased levels of AFP can rule out a germinoma. If there is an elevated beta-HCG, it could mean that the tumor is composed of specific cells (multinucleated syncytiotrophoblastic cells) and this could potentially trigger early puberty.
Surgical Treatment of Germ Cell Seminoma
Surgery doesn’t usually have a major part to play in treating germinoma, a type of tumor. Its primary use is for taking a sample of the tumor for diagnostic purposes or for treating a condition called hydrocephalus, which is a buildup of fluid in the brain.
What to expect with Germ Cell Seminoma
Germinoma is a type of cancer that usually has a positive reaction to treatment. In fact, more than 90% of patients live for at least five years after being diagnosed with this disease. However, it’s important to continue regular check-ups, as there is a risk that the cancer could come back even after 10 to 15 years of being in remission.
Possible Complications When Diagnosed with Germ Cell Seminoma
Some people have experienced complications due to treatment. Radiation therapy can lead to issues like impaired brain functions, vision problems, underactivity of the pituitary gland, and risk of stroke. There’s also an elevated chance of developing secondary brain cancers like gliomas and meningiomas. On the other hand, chemotherapy can cause side effects that are concerning for patients’ health, such as low blood cell count, ear damage, and hair loss.
Common Side Effects From Treatment:
- Impaired brain functions
- Vision issues
- Underactivity of the pituitary gland
- Stroke
- Secondary brain cancers, such as gliomas and meningiomas
- Low blood cell count
- Ear Damage
- Hair loss
Preventing Germ Cell Seminoma
No one knows exactly what causes germinoma, a type of cancer, so currently we don’t recommend specific screenings for everyone. The good news is, although germinoma is a cancerous growth, it has a high survival rate.
Germinomas that form in the suprasellar region (the area around the pituitary gland in your brain), can develop very slowly, and often, their symptoms may go unnoticed for a while. It’s important not to ignore subtle signs like failure to grow at a normal rate, a decrease in school performance, feeling tired often, changes in sleep patterns, or delayed puberty. If you notice any signs or symptoms related to hormone irregularities, for instance, needing to pee very often (polyuria) and feeling extremely thirsty (polydipsia), it’s vital to seek medical advice.
