Germinoma

Essential Information

Summarize

 

        Germ cell tumors (Germ cell tumors) are a group of tumors that originate from germ cells. These cells, which form during embryonic development, will develop into eggs in females or sperm in males as the body develops normally. In rare cases, germ cells can mistakenly migrate to other parts of the body and form tumors. According to U.S. statistics, about 90% of germ cell tumors occur in the ovaries of women or the testes of men. Additionally, these tumors can also be found in the abdominal cavity, pelvis, mediastinum, and brain.

 

 classify

 

      Based on germ cell and tumor origin location, germ cell tumors can be divided into central nervous system germ cell tumors and extracranial germ cell tumors.

 

1. Central nervous system germ cell tumors

 

      Central nervous system germ cell tumors are tumors that originate from germ cells in the brain or spinal cord. The most common sites for these tumors include the area around the pineal gland and the regions of the brain that contain the pituitary gland and its upper tissues. Occasionally, germ cell tumors can also appear in other parts of the brain. These tumors typically occur in children but can also affect adults. Treatment plans may differ between children and adults.

      Central nervous system germ cell tumors can be classified into different types based on the appearance of tumor cells under a microscope.

      1.1 Germ cell tumours (germinomas)

      Germ cell tumors are the most common germ cell tumors of the central nervous system. Germ cell tumors usually have a good prognosis.

      1.2 Non-germinoma germ cell tumor (NGC)

      Certain non-germ cell tumors of the germ line can secrete hormones. Central nervous system teratomas (CNS teratomas) are a type of non-germ cell tumor that does not secrete hormones. These tumors may contain various tissues, such as hair, muscle, and bone. Based on the degree of cell differentiation observed under a microscope, teratomas can be classified as mature or immature. Some teratomas are a mix of both mature and immature cells.

        Other nongerm cell tumors of the germ line include the following:

 

​ Choriocarcinoma, secreting human chorionic gonadotropin (β-hCG)

Malignant embryonal carcinoma does not secrete hormones

Echocystoma, which secretes the hormone alpha-fetoprotein (AFP)

A germ cell tumor composed of a mixture of various tumor cells

 

Figure 1. Inner brain anatomy

Note: The figure shows the pineal gland, pituitary gland, optic nerve, ventricles (cerebrospinal fluid is shown in blue) and other parts of the brain.

 

2. Extra-cranial germ cell tumors

 

      Extracranial germ cell tumors may be benign or malignant. Extracranial germ cell tumors are commonly found in the following parts of the body: testicles, ovaries, sacrum or coccyx (the bottom of the spine), retroperitoneal cavity (the back wall of the abdomen), mediastinum (the area between the two lungs).

Figure 2. Ectodermal germ cell tumors arising in areas outside the brain (including testis, ovary, sacrum, coccyx, mediastinum and retroperitoneal cavity)

 

 

      2.1 Classification of teratomas of extra-cranial origin (by nature)

 

      Based on their nature, extracranial germ cell tumors are classified into three types: mature teratoma, immature teratoma, and malignant germ cell tumor.

        

      2.1.1 Mature teratomas (Mature Teratomas)

      Mature teratomas are the most common type of extracranial germ cell tumor. These tumors are benign and unlikely to become cancerous. They typically develop in the sacrum or coccyx (the base of the spine) of newborns or in the ovaries of girls just entering puberty. Under a microscope, the cells of mature teratomas closely resemble normal cells. Some mature teratomas secrete enzymes or hormones, which can cause symptoms of the disease.

        

2.1.2 Immature teratomas (Immature Teratomas)

      Immature teratomas are also commonly found in the sacrum or coccyx (the base of the spine) of newborns, or in the ovaries of girls just entering puberty. The cells of immature teratomas appear very different from normal cells under a microscope. These tumors can be malignant (cancerous). They typically contain various tissues, such as hair, muscle tissue, and bone tissue. Based on the amount of immature neural tissue in the tumor, immature teratomas are classified into grades 0 to 3. Tumor grading is independent of the patient's age. High-grade immature teratomas may be associated with yolk sac tumors. Some immature teratomas can secrete enzymes or hormones, leading to disease symptoms.

       

      2.1.3 Malignant germ cell tumors (MGCT)

 

        Malignant germ cell tumors are cancer, mainly two:

 

      (1) Germ cell tumors (Germinomas): These tumors may secrete alkaline phosphatase (ALP, ALKP, ALPase, Alk Phos), lactate dehydrogenase (LDH), human chorionic gonadotropin (hCG) and other hormones. They include the following three types:

 

Dysgerminomas are tumors that form in the ovaries of girls.

Seminomas, which form in the testicles of boys.

A germ cell tumor that occurs in a part of the body other than the ovary or testis.

 

(2) Non-germinoma germ cell tumors (Nongerminomas): include the following four:

 

Ectodermal cystoma, which secretes the hormone alpha-fetoprotein (AFP). It may form in the ovary, testicle, and other parts of the body.

Choriocarcinoma, which secretes human chorionic gonadotropin (β-hCG), may develop in the ovaries, testicles and other parts of the body.

Choriocarcinoma may secrete human chorionic gonadotropin (β-hCG) and/or alpha-fetoprotein (AFP). It may occur in the testis and other parts of the body, but not in the ovary.

A germ cell tumor that is a mixture of malignant germ cell tumors and teratomas. It may occur in the ovaries, testicles, and other parts of the body.

 

      2.2 Classification of extra-cranial germ cell tumors (by location)

 

      According to location, extracranial germ cell tumors in children can be divided into two categories: gonads and extra-gonads.

       

      2.2.1 Gonadal germ cell tumors (GCT)

 

      Gonadal germ cell tumors occur in the testicles of boys or the ovaries of girls.

 

(1) Testicular germ cell tumors (Testicular Germ Cell Tumors): Testicular germ cell tumors are divided into two categories:

 

Seminoma (seminoma)

Non-seminoma (NS)

 

      Spermatocytic tumors secrete human chorionic gonadotropin (β-HCG). Non-spermatocytic tumors are typically larger and can cause clinical symptoms, growing and spreading faster than spermatocytic tumors. Testicular germ cell tumors usually occur in children under 4 years old, or in adolescents and young adult males. Testicular germ cell tumors in adolescents differ from those in young children. Boys over 14 years old with testicular germ cell tumors, although treated at pediatric cancer centers, receive treatment plans similar to those for adults.

 

      Testicular teratomas and malignant testicular germ cell tumors can occur in children under 11 years old. Malignant testicular germ cell tumors are typically composed of pure yolk sac tumors, also known as yolk sac tumors. These tumors in children share similar characteristics with those in adults, often accompanied by chromosomal abnormalities. The isochromosome of the short arm of chromosome 12 (i12p) is a common marker for these tumors, present in 44% of children with malignant testicular germ cell tumors. Other chromosomal abnormalities include deletions at 1p,4q, and 6q, as well as duplications at 1q,3q, and 20q. In testicular germ cell tumor cases found in adolescents over 11 years old and young adult males, almost all exhibit the isochromosome of the short arm of chromosome 12 (i12p), along with deletions or duplications of chromosomes, resulting in a genome containing more or fewer than 46 chromosomes (aneuploidy).

 

(2) Ovarian germ cell tumors (OGCTs): These tumors are more common in teenage girls and young adult women compared to younger children. Most OGCTs are benign teratomas. However, malignant tumors such as immature teratomas, dysgerminomas, yolk sac tumors, and mixed germ cell tumors can also occur. In patients with malignant OGCTs, an increased copy number of chromosome 12 is often observed in the genome.

 

2.2.2 Extra gonadal extracranial germ cell tumors (EGGCT)

      Extragonadal central germ cell tumors arise in areas of the body other than the brain, testis, and ovary. Most extragonadal central germ cell tumors arise near the midline of the body, including:

 

​ Sacrum (the lower part of the spine, triangular, forms part of the pelvis) ​

Caudal vertebrae (bottom of the spine)

Mediastinum (between the two lungs)

Posterior wall of the abdominal cavity, neck

 

 

 

 

Epidemiological

      In younger children, extragonadal germ cell tumors often appear at birth or in early childhood. Most of these tumors are teratomas located in the sacrum or coccyx. In rare cases, the tumors may exhibit histological features similar to those of malignant yolk sac tumors and may have cytogenetic abnormalities similar to those found in young male testicular tumors.

      In older children, teenagers and young adults, extragonadal extracranial germ cell tumors are more common in the mediastinum.

 

Incidence of extracranial germ cell tumors

 

      Childhood germ cell tumors are rare in children under 15, accounting for about 3% of cancers in this age group. In fetuses and newborns, most extracranial germ cell tumors are benign teratomas located in the midline, including the head and neck, sacrococcygeal region, and retroperitoneal area. The incidence of malignant teratomas in this age group is low, but perinatal tumors have a higher incidence due to the increased risk of fetal hydrops and premature birth. In adolescents aged 15 to 19, extracranial germ cell tumors account for approximately 14% of cancers in this age group.

 

 

Etiology & Risk Factors

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Classification & Staging

 

 clinlcal symptom

 

      Symptoms of tumors vary depending on where they occur.

50. Testicular germ cell tumor: in the early stage, a painless mass can be felt in the scrotum, which is often mistaken for scrotal edema, and may gradually become tender. ​

 

50. Ovarian and abdominal germ cell tumors: common symptoms are abdominal pain or constipation, which become detectable abdominal masses as the tumor grows. ​

 

50. Diaphragmatic germ cell tumor: It is usually not detected until the tumor becomes large enough to compress the trachea or bronchus, causing chest pain, cough, wheezing and other symptoms.

 

50. Sacrococcygeal germ cell tumors are common in infants and young children. These tumors can be visible at birth and are typically surgically removed immediately. However, they may also develop internally, which is often difficult to detect. The tumor can grow for several months before becoming malignant. Symptoms may include constipation, impaired bladder function, and pain.

 

50. Central nervous system germ cell tumors: Most are located in the pineal gland of the brain, but sometimes they can also grow along the spine and may cause neurological symptoms such as diabetes insipidus, nausea, vomiting, drowsiness, headache, etc.

 

 tumor markers

 

      Ectodermal tumors produce alpha-fetoprotein (AFP), while all choriocarcinomas and certain germ cell tumors, such as seminomas and dysgerminomas, and embryonal carcinomas produce β-human chorionic gonadotropin (β-HCG), leading to elevated levels of these substances in the serum. Most malignant pediatric germ cell tumors contain elements of ectodermal tumors, resulting in elevated AFP levels. Continuous monitoring of AFP levels during treatment can help assess the response to therapy. Benign teratomas and immature teratomas may cause slight increases in both AFP and β-HCG levels. It is important to note that the fetal liver produces AFP, and the elevated serum AFP levels in infants under one year old are not associated with tumors.

      The serum half-life of alpha-fetoprotein is 5 to 7 days, and that of β-hCG is 1 to 2 days. For all pediatric patients with malignant germ cell tumors, tumor markers are measured at the end of each chemotherapy cycle. After initial chemotherapy, tumor markers may show a brief increase.

 

Clinical Manifestations 

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Clinical Department

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Examination & Diagnosis

 

      Most germ cell tumors are present as a mass along the midline of the body in the testis or elsewhere. Once a mass is found, doctors often arrange a biopsy of the tumor.

 

      Germ cell tumors are unique solid tumors that secrete serum tumor markers. Elevated levels of alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are very useful indicators for diagnosing and monitoring the treatment response of these tumors. Depending on the tumor's location, imaging techniques such as CT scans, MRI, X-rays, ultrasounds, and bone scans can also be used to diagnose germ cell tumors.

 

Detection and diagnosis of germ cell tumors of central nervous system

 

1. Imaging examination and laboratory tests

 

      Common tests and technical detection methods are as follows:

50. Physical examination and medical history: Use a physical examination to screen for basic health markers, including looking for signs of disease, such as lumps or any visible abnormalities. Also ask about the patient's health habits, medical history and family, and treatments received.

 

50. Neurological examination: A series of questionnaires and tests are used to examine the brain, spinal cord, and nerve function. It assesses a person's mental state, coordination, and ability to walk normally; as well as the condition of muscles, sensory functions, and neurological reflexes. This can also be referred to as a neurological examination or a neurological assessment (neuro/neurologic exam).

 

50. Visual field examination: This test assesses a person's visual field, the entire area they can see. It measures central vision (the extent of the area visible when looking straight ahead) and peripheral vision (the size of the area visible in other directions when looking straight ahead). The test is conducted with the eyes separated, and the patient must cover the untested eye.

 

50. Magnetic Resonance Imaging (MRI): This examination uses magnets, radio waves, and computers to create detailed images of the brain and spinal cord. The patient receives an intravenous injection of a substance called gadolinium. Gadolinium accumulates around cancer cells, making them appear brighter in the images. This procedure is also known as Nuclear Magnetic Resonance Imaging (Nuclear MRI).

 

50. Lumbar puncture (lumbap puncture) is a procedure to collect cerebrospinal fluid (CSF) from the spine. The needle is inserted between two vertebrae, passing through the spinal cord and collecting a sample of CSF fluid. The collected CSF sample is then examined under a microscope for signs of tumor cells. The sample is also tested for protein and glucose levels. Elevated protein levels or low glucose levels may indicate the presence of a tumor. This procedure is also known as a lumbar puncture or spinal tap.

​

Figure 1. Lumbar puncture (LP)

 

Note: The patient lies on the operating table in a curled position. After a small area of the lower back is anesthetized, a long and thin spinal needle is inserted into the lower part of the spine to draw cerebrospinal fluid (CSF, as shown in blue). The fluid may be sent to the lab for testing.

        

50. Tumor Marker Tests: These tests involve analyzing blood or cerebrospinal fluid (CSF) samples to measure the levels of chemicals released by organs, tissues, or tumor cells into the bloodstream and cerebrospinal fluid. Elevated levels of certain substances in the blood can indicate specific types of cancer, known as tumor markers. Alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (β-hCG) are two common tumor markers used for diagnosing specific CNS germ cell tumors.

 

50. Blood biochemistry: Tests for chemicals in blood samples to measure how much chemicals are released into the blood by body organs and tissues. Abnormal levels of substances in blood samples (higher or lower than normal) may be a sign of disease.

 

50. Blood hormone studies (Blood hormone studies): Blood samples are examined to measure the amount of hormones released into the blood by organs and tissues in the body to check hormone levels produced by the pituitary gland and other glands. Higher or lower than normal hormone levels may be a sign of disease in the organ or tissue that produces the hormone.

 

2. Biopsy (biopsy) to confirm the diagnosis of germ cell tumor of the central nervous system

 

      If a doctor suspects your child may have a germ cell tumor of the central nervous system, a biopsy might be performed to confirm the diagnosis. For brain tumors, a biopsy involves removing a small piece of tissue from the skull using a needle. Sometimes, the sampling needle is guided by a computer to ensure accurate tissue sampling. After the biopsy sample is taken, a pathologist will examine it under a microscope for cancer cells. If cancer cells are found, the doctor may remove as much of the tumor as possible during the same surgery. After the biopsy, the skull that was removed is usually replaced.

 

      Sometimes a diagnosis can be made based on imaging results and tumor marker tests, without the need for a biopsy.

 

      Immunohistochemical testing can be performed on the tissue samples removed: this involves using antibodies to detect specific antigens in the tissue. Antibodies are typically labeled with radioactive substances or dyes, which makes the tissue appear brighter under a microscope. This type of test can help differentiate between different types of brain tumors.

Figure 2. Craniotomy (an incision is made in the skull and a piece of bone removed to show part of the brain)

 

Detection and diagnosis of extracranial germ cell tumors

 

1. Imaging and blood tests

 

        The following tests and technical detection methods may be used for diagnosis:

 

50. Physical examination and medical history: Check for any swelling, bulge, or pain in the testicles.
50. Serum tumor marker tests: Most malignant germ cell tumors release tumor markers. The following markers are used to detect extracranial germ cell tumors: alpha-fetoprotein (AFP) and β-human chorionic gonadotropin (β-hCG). For testicular germ cell tumors, the concentration of tumor markers in the blood helps determine whether the tumor is a seminoma (a type of malignant tumor that is sensitive to radiotherapy) or a non-seminoma.
50. Blood biochemistry
50. Chest X-ray
50. CT scan (CAT scan)
50. MRI (magnetic resonance imaging)
50. Ultrasound examination (B-mode ultrasound)

 

 

2. Biopsy

 

      Cells or tissues are removed (from the body) so that a pathologist can examine them under a microscope for signs of cancer. In some cases, during a biopsy, the tumor is removed and the biopsy is completed.

      The following tests may be performed on the tissue samples removed:

 

50. Cytogenetic analysis: Laboratory analysis of cells in tissue samples under a microscope to look for certain changes in chromosomes.
50. Immunohistochemistry: This type of test may be used to distinguish between different types of cancer.

 

3. Possible tests after diagnosis

 

        After a child is diagnosed with extracranial germ cell tumor, the following tests are used to check whether cancer cells have spread from the primary site to nearby areas or other parts of the body:

 

50. MRI (magnetic resonance imaging)
50. CT scan (CAT scan)
50. Bone scan: A detection method to check for rapidly dividing cells, such as tumor cells, in the bone. Very small doses of radioactive material are injected into a vein and passed through the blood. The radioactive material accumulates in the cancerous bone and is detected by a scanner.
50. Percutaneous thoracentesis: A needle is used to remove fluid from the space between the lining of the chest cavity and the lungs, which is examined under a microscope by a pathologist for cancer cells.
50. Puncture: A needle is used to remove fluid from the space between the lining of the abdominal cavity and the abdominal organs, which is examined under a microscope by a pathologist for cancer cells.

 

Clinical Management

 

      There are two main treatments for germ cell tumors: surgical removal of the tumor tissue and chemotherapy to kill any remaining tumor cells.

 

1. Surgical treatment

 

      The location of the tumor can influence whether surgery is necessary or the likelihood of surgical treatment. If possible, the preferred approach is to attempt to remove the entire tumor. A complete surgical removal is sufficient for treating most teratomas and immature teratomas. Surgery can also treat some malignant germ cell tumors of the testes and ovaries. For testicular germ cell tumors, successful surgery may eliminate the need for additional chemotherapy. If the disease has not spread to the lymph nodes and the tumor marker levels return to normal after surgery, further chemotherapy is unnecessary. For older boys, a biopsy of the abdominal lymph nodes may be required to determine if the disease has spread.

 

2. Chemotherapy

 

      Chemotherapy has been successfully applied to the treatment of certain germ cell tumors. The standard chemotherapy regimen currently involves a four-course PEB regimen, which includes cisplatin (Cisplatin, P), etoposide (Etoposide, E), and bleomycin (Bleomycin, B). Carboplatin and ifosfamide are sometimes used as well.

      Boys with testicular tumors may require close monitoring without chemotherapy after a complete surgical removal. If the tumor marker levels do not return to normal or rise during the follow-up period, chemotherapy can be very effective. This is sometimes referred to as salvage chemotherapy, as it can address any remaining tumors that were not completely removed after surgery.

 

Treatment of germ cell tumors of the central nervous system

 

1. Radiotherapy

 

      External beam radiotherapy is used to treat germ cell tumors of the central nervous system (CNS) in children. This therapy involves using an external machine to deliver radioactive material to cancer cells. Stereotactic radiosurgery, a form of external beam radiotherapy, uses a head frame attached to the skull to keep the head stable. A single high-dose dose of radioactive material is directly targeted at the brain tumor, minimizing damage to surrounding healthy tissue. It is used to treat first-time diagnosed teratomas. Stereotactic radiotherapy is also known as radiosurgery. This procedure does not involve open surgery.

      Radiation therapy to the brain may affect a child's growth and development. Some specific ways of giving radiation therapy may reduce damage to healthy brain tissue. For children younger than 3 years of age, chemotherapy can be used instead of radiation therapy, which can delay or reduce the use of radiation therapy.

 

2. Chemotherapy

 

      Chemotherapy involves using chemical drugs to kill cancer cells or prevent their division, thereby inhibiting the growth of cancer cells. There are two types of chemotherapy: systemic and local. Systemic chemotherapy involves administering drugs orally, intravenously, or into the muscles, which then enter the bloodstream and reach cancer cells throughout the body. Local chemotherapy typically involves applying drugs directly to the skin or injecting them into the cerebrospinal fluid, organs, or body cavities (such as the abdomen), where they primarily target and kill cancer cells in specific areas.

      The specific chemotherapy depends on the type of cancer being treated.

 

3. Surgery

 

      Whether surgery can remove the tumor depends on its location in the brain. Surgical removal of the tumor may result in severe and long-term side effects. Surgery can be used to remove teratomas and recurrent germ cell tumors. Even if all visible tumors are removed during surgery, some patients still need radiation or chemotherapy to reduce the risk of tumor recurrence.

 

4. High-dose chemotherapy combined with stem cell transplantation

 

      High-dose chemotherapy combined with stem cell transplantation involves first administering a high dose of chemotherapy, followed by the replacement of blood cells damaged by tumor treatment. Stem cells (immature blood cells) are extracted from the patient's or donor's blood or bone marrow and stored in a cryopreservation facility. After completing chemotherapy, the stored stem cells are thawed and infused back into the patient. These reinfused stem cells will help restore the patient's blood cell count.

 

5. Targeted therapy and other treatments in clinical trials

 

      Targeted therapy is a treatment that uses drugs or other substances to attack cancer cells. Targeted therapy usually causes less damage to normal cells than chemotherapy or radiation therapy. Clinical trials are currently underway to use targeted therapy in children with recurrent CNS germ cell tumors.

 

6. Common treatment methods for different types of central nervous system tumors

 

      6.1 First-visit germ cell tumors (germinomas)

 

        The treatment of primary germ cell tumors of the reproductive system may include the following:

 

50. ​ Radiotherapy to the brain tumor and ventricles (including fluid cavity). The dose of radioactive material given to the tumor is higher than that around the tumor.
50. For younger children, chemotherapy is followed by radiotherapy.
50. First, participate in a clinical trial of chemotherapy, and then have lower doses of radiation based on the effectiveness of the chemotherapy.

 

      6.2 Non-germinomas of germ cell origin at first diagnosis (non-germ cell tumours)

 

        The optimal treatment for non-germinomas in the first diagnosis is not yet known. The treatment of choriocarcinoma (carcinoma of the corpus choriaceum), embryonal carcinoma (embryonal carcinoma), yolk sac tumor (yolk sac tumor) or mixed germ cell tumor may include the following:

 

50. Chemotherapy is followed by radiotherapy. If there is still residual tumor tissue after treatment, a second operation may be needed to check whether the residue is cancer. If the tumor marker level is normal and the mass continues to grow, as much of the mass as possible should be removed to identify the tumor cells.
50. High-dose chemotherapy combined with the patient's own stem cells.
50. First, participate in a clinical trial of chemotherapy, and then have lower doses of radiation based on the effectiveness of the chemotherapy.

 

      6.3 Recurrent central nervous system germ cell tumors in children

 

        The treatment of recurrent central nervous system germ cell tumors in children may include the following:

 

50.  surgical operation 。
50. Radiation therapy is given to the tumor or the entire brain and spinal cord.
50. Chemotherapy followed by radiotherapy.
50. High-dose chemotherapy combined with patient autologous stem cell rescue.
50. Participate in clinical trials of new therapies.
50. Participate in clinical trials to test the genes of patients' tumor samples and conduct targeted therapy based on the genotype of patients.

 

Treatment of extracranial germ cell tumors

 

1. Traditional therapies

 

1.1 Surgery

 

      Common surgical options include:

 

50. Routine resection: tissue or local/total organ resection.
50. Radical inguinal orchiectomy: an incision is made in the groin and one or both testicles are removed.
50. Unilateral salpingo-oophorectomy: removal of one ovary and fallopian tube.
50.       

       1.2 Observation

 

      Observation involves closely monitoring the patient's physical condition without initiating any treatment until symptoms appear or change. For certain patients, such as those with mature teratomas, some immature teratomas, and tumors within the sex glands, if the tumor tissue is completely removed through surgery, additional treatment may not be necessary. However, the patient's condition must be closely monitored, and any specific signs or symptoms should be promptly addressed.

      For children with extracranial germ cell tumors, observation includes regular physical examination, imaging examination and tumor marker detection.

      

      1.3 Chemotherapy

      Chemotherapy is a common treatment for malignant tumors, using drugs to kill cells or inhibit their growth, thereby controlling the spread of tumor cells. Systemic chemotherapy involves administering drugs orally or through injection into muscles or veins, allowing them to enter the bloodstream and reach the entire body. Local chemotherapy involves injecting drugs directly into the cerebrospinal fluid, specific organs, or body cavities (such as the abdominal cavity), where they act locally.

      The chemotherapy regimen depends on the type and stage of the cancer being treated. Commonly used chemotherapy drugs for malignant extracranial germ cell tumors in children include cisplatin, etoposide, and bleomycin. The specific chemotherapy regimen is determined by the type and stage of the cancer. Mature teratomas and immature teratomas may respond poorly to chemotherapy.

 

2. New therapies

 

      Some treatments under clinical trial:

      

      2.1 High-dose chemotherapy combined with stem cell transplantation

 

      Healthy blood stem cells (immature blood cells) are taken from the patient's or donor's blood or bone marrow and cryopreserved. After the completion of intensive chemotherapy, the stored stem cells are thawed and infused back into the patient. These reinfused stem cells restore the body's hematopoietic function.

       

      2.2, heat therapy

 

      Therapeutic heat involves heating tissues above normal body temperature to destroy or kill cancer cells and make them more sensitive to radiation or certain anticancer drugs.

       

        2.3 Radiotherapy

      Radiation therapy is a cancer treatment that uses high-energy X-rays or other types of radiation to kill cancer cells or prevent their growth. The decision to use radiation therapy depends on the type of cancer and whether it has recurred. Research is currently underway to use external beam radiation therapy to treat recurrent extracranial germ cell tumors in children.

     

      Targeted therapy

      The use of drugs or other substances to attack specific cancer cells is usually less damaging to normal cells than chemotherapy or radiotherapy, and research is under way into the use of targeted therapy for recurrent extracranial germ cell tumors.

 

3. Common treatment methods for different types of extracranial germ cell tumors

 

      3.1, teratoma

 

        Teratomas are most commonly found in the sacrococcygeal region of newborns and young children, as well as in the ovaries of adolescent girls. They are rarely seen in the testicular area of boys under 4 years old or in the mediastinum of adolescents. The primary treatment for teratomas is surgery. Depending on the tumor's location, surgery can usually remove the teratoma completely.

      3.1.1, mature teratoma

 

      The tumor is surgically removed, followed by observation and monitoring. For mature teratomas in the sacrococcygeal region, complete removal of the coccyx can significantly reduce the risk of recurrence. Postoperative follow-up examinations and alpha-fetoprotein testing are conducted. Sometimes, malignant cells may be present in mature teratomas. Teratomas with malignant cells may require a different treatment approach.

      3.1.2 Immature teratoma

      (1) Treatment of immature teratomas located outside the sacrum or coccyx:

 

50. Stage I: tumor resection and continued observation.
50. II to IV: tumor resection surgery is performed, combined with chemotherapy, it is not clear whether chemotherapy can prolong the life of patients. ​

 

      (2) Treatment of immature teratomas located in the sacrum or coccyx:

 

50. The sacrum and coccyx were removed (sacrospinalysis) and continued to be observed. ​

 

      Sometimes mature or immature teratomas also have malignant cells, and teratomas and malignant cells may require special treatment. In addition, patients should adhere to at least 3 years of routine follow-up examination, including imaging detection and alpha-fetoprotein tumor marker detection.

 

      3.2 Germ cell malignant tumors

      

      3.2.1 Malignant germ cell tumor of the testis

 

      Testicular germ cell tumors in children almost exclusively occur in boys under the age of 4. The diagnostic method should be carefully selected, and a scrotal biopsy may lead to inguinal lymph node metastasis. Radical inguinal orchiectomy and initial high ligation of the spermatic cord are better options.

      The disease can be staged using CT or MRI, as well as tumor marker levels. The surgical plan is typically determined by the patient's age and the location of the tumor. All malignant testicular germ cell tumors should be surgically removed. If there is a risk of damaging nearby tissues, the testicle may be removed first for diagnostic purposes. Surgery will then be performed on patients who still have residual tumor tissue after chemotherapy post-surgery.

        

      The treatment of testicular malignant germ cell tumor is as follows:

        

      (1) Male under 15 years of age:

 

50. Stage I tumor, radical orchiectomy was performed and the patient was closely monitored.
50. For stage II to IV tumors, radical orchiectomy and combined chemotherapy are performed; if there is residual tumor after chemotherapy, a second operation is required.

        

      (2) Male 15 years and over:

 

      The approach to treating malignant germ cell tumors of the testis in men 15 years and older varies, and surgery may also involve the removal of lymph nodes from the abdomen.

 

       Phase 0:

50. Radiation therapy, observation or surgical removal of the testicle.

 

      Phase I:

50. Seminoma: The testicle is surgically removed and then monitored. Some patients may need chemotherapy.
50. Non-seminoma: The testis is surgically removed (and possibly abdominal lymph nodes removed at the same time), and some patients require chemotherapy followed by long-term follow-up.

 

      Phase II:

50. Seminoma less than 5 cm: orchiectomy (possibly with simultaneous removal of abdominal lymph nodes), radiotherapy to the abdomen and pelvic lymph nodes, combined with chemotherapy.
50. Seminoma larger than 5 cm: The testis is surgically removed, chemotherapy or radiotherapy to the abdominal and pelvic lymph nodes, followed by a long-term follow-up.
50. Non-seminoma: the testis is surgically removed (lymph nodes may be removed at the same time), followed by chemotherapy and long-term follow-up.
50. For cancer that is spreading or threatening life, chemotherapy is followed by surgery to remove the testicle.

 

        Phase III:

50. Seminoma: the testis is surgically removed, and chemotherapy is performed after surgery. If there is still tumor residue after chemotherapy, monitoring can be selected. If the tumor does not grow, no treatment will be carried out, or the tumor larger than 3 cm can be selected for surgical resection, or the tumor detected by PET can be selected for resection.
50. Non-seminoma: the testis is surgically removed and chemotherapy is administered after surgery. Chemotherapy is performed first, followed by surgical removal of the testis and other residual tumors. If the tumor is not completely removed after surgery, chemotherapy can be performed again. Clinical trials of chemotherapy can also be selected.

        

      3.2.2 Ovarian malignant germ cell tumor

 

      Most ovarian tumors in children and adolescents originate from germ cells. Ovarian germ cell tumors are rare in young girls, but the incidence begins to rise around the age of 8 or 9 and continues to increase throughout adulthood. Pediatric malignant ovarian germ cell tumors can be categorized into germ cell tumors (seminomas) and non-germ cell malignant tumors (e.g., yolk sac cancer, mixed germ cell tumors, choriocarcinoma, and embryonal carcinoma).

 

      (1) Sex cell tumor

 

50. Stage I teratomas: surgery (unilateral salpingo-oophorectomy) was performed and continued observation; if the tumor recurred, combined chemotherapy could be performed.
50. Stage II to IV dysgerminoma: surgery (unilateral salpingo-oophorectomy) is performed and continued observation is made. Combined chemotherapy can be used to reduce the volume of the tumor, on which basis surgery (unilateral salpingo-oophorectomy) is performed.

 

      (2) Non-reproductive germ cell tumor

 

50. Stage I non-germinoma: continue to be observed after surgery. It is also possible to undergo combined chemotherapy after surgery. ​
50. Stage II to IV non-germ cell tumors: combined chemotherapy after surgery; if there is residual tumor, a second operation can be performed. Combined chemotherapy after biopsy to reduce the volume of tumor; sometimes this regimen can also be used when cancer is diagnosed but cannot be operated on.

    

        3.3 Malignant extragonadal extracranial germ cell tumor

 

        The treatment of malignant extragonadal extracranial germ cell tumor depends not only on the stage of the disease, but also on the location of the disease.

 

      3.3.1 Tumors located in the sacrum or coccyx: chemotherapy can be used to shrink the volume of the tumor, followed by surgery to remove the sacrum and coccyx (the bottom end of the spine).

 

      3.3.2 Tumors located in the mediastinum: combined chemotherapy can be used to reduce its volume, followed by surgical removal.

 

      3.3.3 Tumors located in the abdomen: biopsy can be performed first, followed by combined chemotherapy to reduce its volume and surgical removal.

 

      3.3.4 Head and neck tumors: surgical clearance can be performed first, followed by combined chemotherapy.

 

      3.3.5 Tumors in other parts: surgery can be performed first, followed by combined chemotherapy.

 

      3.4 Recurrent malignant extracranial germ cell tumors in children

 

      3.4.1 Factors affecting the treatment plan:

 

        There is no standard treatment for recurrent malignant extracranial germ cell tumors in children, and the specific regimen depends on the following factors:

 

      (1) The treatment used at the time of cancer diagnosis.

      (2) Changes in the tumor after the first treatment.

        

      3.4.2 Treatment method:

 

        The treatment is usually part of a clinical trial and includes the following:

 

50.  surgical operation

 

50. Postoperative combined chemotherapy is typically used for the treatment of most extracranial germ cell tumors, including immature teratomas, malignant testicular germ cell tumors, and malignant ovarian germ cell tumors. This strategy involves surgically removing any tumors that have recurred in the sacrum or coccyx (the base of the spine). If the sacrum or coccyx was not removed at the time of cancer diagnosis, this method can still be used for treatment. Preoperative chemotherapy can help reduce the tumor size, and if any residual cancer is present postoperatively, additional chemotherapy may be necessary.

 

50. Combination chemotherapy. Used to treat stage I testicular malignant germ cell tumors and stage I ovarian dysgerminomas.

 

50. High-dose chemotherapy and stem cell transplantation

 

50. For cancer with brain metastasis, surgery can be performed after radiotherapy to remove the brain tumor.

 

50. Targeted therapy: Certain genetic changes are examined in a patient's tumor sample, and the type of targeted therapy depends on the type of genetic change.

 

      Tip:

      The treatment information provided by Sunflower children is for reference only and cannot replace the advice of doctors and other medical personnel, nor can it replace the doctor's face-to-face consultation. If you have specific questions about disease, treatment plan, diagnosis or clinical symptoms, please seek help from professional medical personnel.

Research on new advances in treatment

 

        Doctors and researchers are still studying germ cell tumors to understand how to prevent them, how to treat them most effectively, and how to provide the best diagnostic methods for patients. Current clinical trials are seeking significant breakthroughs in several areas. Please communicate more with your child's primary doctor to choose the most suitable diagnostic and treatment options for your child.

 

1. New drug development

 

      Scientists are working on new drugs that can better control tumor growth. These include:

 

      1.1 Targeted drugs

 

      Recent studies have identified specific genes, proteins, and other unique factors associated with germ cell tumors in the central nervous system. Researchers are developing targeted therapies that target these tumor-related factors. These factors are likely to directly influence the growth and survival of tumors. Therefore, targeted therapy can inhibit the growth and spread of tumor cells. Additionally, because it specifically targets tumor cells, its impact on normal human cells is relatively limited.

 

      1.2 Immunotherapy

 

      Immunotherapy, also known as biological therapy, primarily works by stimulating the body's natural immune system to fight tumors. This therapy uses either the body's own immune materials or targeted, highly effective antibodies and immune cells produced in laboratories to boost the patient's immune response. Researchers are currently exploring ways to more effectively and safely apply these new therapies to combat germ cell tumors of the central nervous system.

 

      1.3 Improve imaging technology

 

        Imaging techniques help doctors pinpoint the location of tumors. This is crucial to reducing damage to normal tissue during treatment.

 

50. Functional magnetic resonance imaging (fMRI) can identify the brain regions that control language, hearing, vision, touch, and movement. The exact location of these functional areas varies among different patients. Therefore, fMRI can assist doctors in more accurately locating these areas, thus allowing for safer surgical planning. ​

 

50. Image-guided stereotactic brain positioning helps doctors visualize their operations using 3D images of the brain and tumors. With the help of special software, the images can guide doctors to more accurately locate tumors. Thanks to this technology, tumors that were once considered inoperable have been successfully removed.
50. Magnetic resonance imaging (MRS) and positron emission tomography (PET) can also be used to assess the metabolic activity of tumors. Clinical trials are currently being conducted to see if these techniques can help doctors predict tumor growth levels and metastasis risk.

 

      1.4 Improve radiotherapy technology

 

Researchers are experimenting with new radiotherapy techniques for specific tumors. These methods will create detailed 3D maps of the brain and tumor, allowing doctors to precisely target the tumor tissue while minimizing damage to surrounding healthy tissue. This technology will help reduce the total radiation dose received by patients, thereby decreasing long-term adverse effects.

 

      1.5 Palliative care

 

Some clinical trials are trying to find better palliative care to reduce symptoms and side effects of treatment, thereby improving the quality of life of patients.

 

 

Prognosis

 

      The cure rate for children with germ cell tumors of the reproductive system is 90%. For other types of brain germ cell tumors, radiotherapy can control the condition in 40 to 60 percent of children. If chemotherapy is added, the overall 10-year survival rate is between 70 and 80 percent.

        

      Several factors can affect the survival of patients with germ cell tumors:

 

50. Location: The likelihood of successful treatment varies depending on the tumor's location. Germ cell tumors within the gonads generally have a better prognosis compared to those outside the gonads (extragonadal). Mediastinal germ cell tumors, which are often small and hard to detect, are less responsive to treatment and thus more challenging to treat.

 

50. Cell characteristics: benign teratomas have a very good prognosis after surgery.

 

50. Tumor markers: The decline rate of markers such as alpha-fetoprotein (AFP) and human chorionic gonadotropin (β-hCG) after surgery or chemotherapy is recognized as one of the prognostic factors.

 

50. Stage: Patients with metastasis have a worse prognosis. For stage 1 and 2 disease ​: 90%; for stage 3 disease: 87%; for stage 4 disease: 82%.

 

50. Age at diagnosis: Older patients (or generally, those diagnosed after puberty) have a worse treatment outcome than younger patients. ​

 

50. Complete removal of the tumor often saves patients from the disease.

              ​

1. Prognosis of mature teratoma ​

 

        Mature teratomas generally have a good prognosis. Studies show that patients who undergo complete surgical removal of the tumor have a 6-year recurrence-free survival rate of 96%, while those with incomplete resection have a 55% recurrence rate. After surgery, it is important to follow up and continuously monitor alpha-fetoprotein levels to detect any recurrence early. The recurrence rate for benign tumors is reported to be between 10-21%, with nearly half of these recurrences being malignant, typically occurring within three years after surgery.

       

2. Malignant teratoma with immature prognosis ​

 

      The prognosis after surgery for immature teratoma in stage I is good, with a 3-year event-free survival rate of 97.8% for ovarian tumors, 100% for testicular tumors, and 80% for extragonadal tumors. The 5-year time-free survival rate for stage I and II patients can reach 92%, and for stage III and IV patients, it is 52%.

       

3. Prognosis of malignant germ cell tumor of testis ​

 

       Factors that favor a favorable prognosis for testicular malignant germ cell tumors include age less than 11 at onset, pure yolk sac tumor, and primary tumor not infiltrating the lymphatic vessels.

 

50. Patients in phase I achieved an 82% 6-year event-free survival rate with surgery alone, and a 100% 6-year survival rate for those who relapsed after chemotherapy. ​
50. In a study of stage II patients, the 4-year event-free survival rate after surgery and chemotherapy was about 80% in the under-11 group and about 50% in the over-11 group, but the 4-year survival rate was 100% with follow-up and timely treatment.
50. The 6-year survival rate for patients in stages III and IV younger than 15 years of age was 100% (stage III) and 94% (stage IV) after surgery and chemotherapy.

 

4. Prognosis of malignant ovarian germ cell tumors

 

      According to the study, the survival rate of patients with ovarian malignant germ cell tumors who receive surgery and chemotherapy can reach 95%. The long-term disease-free survival rate of patients with stage IV ovarian tumors over 11 years old at the time of onset is 67%.

       

5. Prognosis of extracranial germ cell tumors of the gonads in children

      Extragonadal germ cell tumors in children are a relatively poor prognosis category. The event-free survival rate of patients with stage III and IV extragonadal germ cell tumors younger than 11 years of age is 85%, and the long-term disease-free survival rate of patients with stage III and IV extragonadal germ cell tumors older than 11 years of age is about 40%.

       

6. Prognosis of malignant sacrococcygeal tumor ​

 

      Malignant sacrococcygeal tumors are often graded high at diagnosis, but if they can be completely removed by surgery, the survival rate can be as high as 90%, and if they cannot be removed and visible remnants remain, the survival rate may be only 40%.

 

Follow-up & Review

 

      For children who successfully complete treatment, daily follow-up includes regular medical history and physical exams, evaluation of serum tumor markers (β-hCG, AFP, and/or LDH), and radiological studies. Understanding the details of previous medical history (including chemotherapy, radiotherapy, and surgery) is critical for future health.

 

      For germ cell tumors, the potential late effects after treatment depend on the type of treatment received, the age at which your child was treated, and many other factors. Some treatments for childhood cancers can increase the risk of developing a second cancer. High doses of alkylating agents, such as cyclophosphamide or nitrogen mustard; etoposide or teniposide; and anthracyclines like doxorubicin or daunorubicin, can increase the risk of developing a second leukemia. Radiation therapy for childhood cancers can also increase the risk of developing a second solid tumor in adulthood. Common sites of these tumors include the skin, breast, central nervous system (brain and spinal cord), thyroid, and bones. Unlike leukemia, a second solid tumor is most likely to develop more than 10 years after treatment. Giving high-dose and extensive radiation therapy to young children increases their risk of developing a second solid tumor.

 

      Although most delayed side effects are not life-threatening, they can have a very negative impact on children's health and quality of life. Delayed side effects can be controlled through regular follow-up after treatment and the development of good living habits, so it is important to communicate with your child's doctor about possible side effects of treatment in a timely manner.

         

      For more information on delayed side effects, see long-term effects of childhood cancer treatment.

1. Follow-up treatment and follow-up of germ cell tumors of the central nervous system

 

      Most children with central nervous system germ cell tumors also have endocrine disorders, including diabetes insipidus and panhypopituitarism. In most cases, even if the tumor is controlled, these endocrine disorders are permanent and patients require continuous hormone replacement therapy in subsequent treatment.

       

      To control possible complications and recurrence, children treated for CNS germ cell tumors should be regularly reviewed annually to screen for recurrence and manage the side effects of subsequent treatment. Typical review items generally include physical examination, laboratory tests, and imaging scans.

      

      For children whose cancer affects the pituitary gland, follow-up visits should include testing blood hormone levels. If the hormone levels are low, replacement hormone therapy should be administered. If higher levels of tumor markers (alpha-fetoprotein or β-human chorionic gonadotropin) are detected during follow-up, blood tumor marker levels should also be checked. If tumor marker levels rise after initial treatment, it may indicate a recurrence of the tumor.

       

      In addition, the child's subsequent treatment may also include regular speech and physical therapy rehabilitation.

 

2. Follow-up treatment and follow-up of extra-cranial germ cell tumors

 

      The American Cancer Research Center has the following follow-up recommendations for the prognosis of extracranial germ cell tumors.

 

      2.1 If tumor markers are elevated at the time of diagnosis, doctors can monitor after treatment:

 

50. AFP and β-hCG: For the first 6 months, AFP and β-hCG levels were monitored monthly (the highest risk period), and then every 3 months for a total of 2 years (3 years for sacrococcygeal teratoma).

 

50. Imaging examination:

          -MRI/CT at the end of treatment.

          -Imaging of the site of tumor occurrence: every 3 months in the first year and every 6 months in the second year. Precocious cell tumors and dysgerminomas may recur over a longer period, so follow-up time may need to be extended.

          -Annual chest X-ray examination.

       

      2.2 Tumor markers are normal at diagnosis and can be monitored after treatment:

 

50. Imaging: Ultrasound or CT/MRI was performed every 3 months for 2 years. Then, it was tested once a year for 5 years. ​

 

 

Daily Care

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Cutting-edge therapeutic and clinical Trials

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References

 data source ：

1. https://www.childrensoncologygroup.org/index.php/germcelltumors

2. http://www.cancer.gov/types/extracranial-germ-cell/patient/germ-cell-treatment-pdq

3. http://www.cancer.gov/types/brain/patient/child-cns-germ-cell-treatment-

 

 data source ：

1. http://www.cancer.gov/types/extracranial-germ-cell/patient/germ-cell-treatment-pdq

2. http://www.cancer.gov/types/brain/patient/child-cns-germ-cell-treatment-pdq#section/_1

 

 reference material ：

1. http://www.cancer.gov/types/extracranial-germ-cell/hp/germ-cell-treatment-pdq#link/_588_toc

2. https://www.childrensoncologygroup.org

3. https://www.stjude.org/disease/germ-cell-tumors-solid-tumor.html

4. https://www.stjude.org/disease/germ-cell-tumors-brain.htm

 

 reference material ：

1. https://www.childrensoncologygroup.org/index.php/in-treatment-with-germ-cell-tumors

2. http://www.cancer.gov/types/brain/patient/child-cns-germ-cell-treatment-pdq#section/_100

3. http://www.cancer.gov/types/extracranial-germ-cell/patient/germ-cell-treatment-pdq#section/_159

 

 reference documentation ：

1. Wessalowski, R., et al. Regional deep hyperthermia for salvage treatment of children and adolescents with refractory or recurrent non-testicular malignant germ-cell tumours: an open-label, non-randomised, single-institution, phase 2 study. Lancet Oncology, 2013. 14(9): p. 843-852.

2. de Wit, R., et al. Randomized Phase III Study Comparing Paclitaxel-Bleomycin, Etoposide, and Cisplatin (BEP) to Standard BEP in Intermediate-Prognosis Germ-Cell Cancer: Intergroup Study EORTC 30983. Journal of Clinical Oncology, 2012. 30(8): p. 792-799.

3. Albany, C., et al. Randomized, Double-Blind, Placebo-Controlled, Phase III Cross-Over Study Evaluating the Oral Neurokinin-1 Antagonist Aprepitant in Combination With a 5HT3 Receptor Antagonist and Dexamethasone in Patients With Germ Cell Tumors Receiving 5-Day Cisplatin Combination Chemotherapy Regimens: A Hoosier Oncology Group Study. Journal of Clinical Oncology, 2012. 30(32): p. 3998-4003.

4. Lorch, A., et al. Conventional-Dose Versus High-Dose Chemotherapy As First Salvage Treatment in Male Patients With Metastatic Germ Cell Tumors: Evidence From a Large International Database. Journal of Clinical Oncology, 2011. 29(16): p. 2178-2184.

5. Feldman, D.R., et al. Presence of Somatic Mutations within PIK3CA, AKT, RAS, and FGFR3 but not BRAF in Cisplatin-Resistant Germ Cell Tumors. Clinical Cancer Research, 2014. 20(14): p. 3712-3720.

6. Dieckmann, K.P., et al. MicroRNAs miR-371-3 in serum as diagnostic tools in the management of testicular germ cell tumours. British Journal of Cancer, 2012. 107(10): p. 1754-1760.

7. Murray, M.J., et al. Identification of MicroRNAs From the miR-371 similar to 373 and miR-302 Clusters as Potential Serum Biomarkers of Malignant Germ Cell Tumors. American Journal of Clinical Pathology, 2011. 135(1): p. 119-125.

8. Kanetsky, P.A., et al. A second independent locus within DMRT1 is associated with testicular germ cell tumor susceptibility. Human Molecular Genetics, 2011. 20(15): p. 3109-3117.

9. Kratz, C.P., et al. Variants in or near KITLG, BAK1, DMRT1, and TERT-CLPTM1L predispose to familial testicular germ cell tumour. J Med Genet, 2011. 48(7): p. 473-6.

10. Chung, C.C., et al. Meta-analysis identifies four new loci associated with testicular germ cell tumor. Nat Genet, 2013. 45(6): p. 680-5.

 

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