Pediatric germ cell tumors

　　First, Etiology

　　Germ cell tumors can occur at any site where the primitive germ cells normally or ectopically migrate. The migration of normal primitive germ cells often follows the body's central axis, therefore, in addition to originating from the ovary and testis, most germ cell tumors occur in the midline. The etiology is unclear.

　　Second, Pathogenesis

　　1. The origin of germ cell tumors is the undifferentiated, gender-neutral germ cells in the yolk sac area visible in the fourth week of embryonic development. Subsequently, the primitive germ cells migrate from the yolk sac to the posterior mesentery reproductive ridge, under the instruction of sex chromosome information, develop and mature into ovaries or testes, and gradually descend to the pelvic cavity or scrotum. The primitive germ cells can undergo ectopic migration, such as migrating to the pineal gland, mediastinum, posterior mesentery, coccygeal tail, etc. Therefore, germ cell tumors can occur at any site where the primitive germ cells normally or ectopically migrate. In addition to originating from the ovary and testis, most germ cell tumors occur in the midline. The etiology is unclear.

　　2. Histological classification The histological classification of pediatric gonadal and extragonadal germ cell tumors is as follows.

　　(1) Primary ovarian:

　　① Germ cell: asexually reproducing germ cells; yolk sac tumor; teratoma (mature, immature, malignant); embryonal carcinoma; malignant mixed germ cell tumor; polyembryoma; choriocarcinoma; gonadoblastoma.

　　② Non-germ cell: Epithelial tumors; Sex cord-stromal tumors.

　　(2) Primary in the testis:

　　① Germ cell: Endodermal sinus tumor (yolk sac tumor); Teratoma (mature, immature, malignant); Embryonal carcinoma; Germ cell tumor; Other malignant mixed germ cell tumors, spermatocytic tumor, choriocarcinoma.

　　② Non-germ cell: Sex cord-stromal tumors.

　　(3) Extragonadal germ cell tumors: Teratoma (sacrum, mediastinum, retroperitoneum, pineal gland, etc.): +/- yolk sac tumor component; +/- embryonal carcinoma component.

　　3. Pathological characteristics

　　(1) Pathology of germ cell tumors in different sites is consistent: Morphologically, the same type of germ cell tumors have consistent pathological morphological manifestations in both intraglandular and extraglandular sites.

　　(2) Both benign and malignant components: Tumors can contain both benign and malignant components, and the malignant components determine its clinical characteristics. Different parts of the same tumor have different cell components, so multi-level pathological sections are needed to avoid diagnostic errors.

　　The onset site of this disease is more widespread, most commonly seen in the sacrum, testicles, ovaries, pelvis, retroperitoneum, mediastinum, and intracranial region. Different onset sites have different clinical manifestations, often due to palpable masses or enlarged masses causing compression symptoms. When the tumor originates in the sacrum or pelvis and compresses the rectum and urinary tract, changes in defecation and urination habits occur, and the external shape of the sacrum may change or be asymmetrical, often suggesting that there may be a mass in the sacrum. Complications are common among various compression symptoms caused by tumors, ovarian mass torsion can lead to acute abdominal pain, and advanced tumors can cause systemic symptoms such as weight loss, fever, anemia, pleural effusion, and ascites.

　　Germ cell tumors can occur from birth to adolescence, but they are more common in infants and preschool children. The onset site of this disease is more widespread, most commonly seen in the sacrum, testicles, ovaries, pelvis, retroperitoneum, mediastinum, and intracranial region. Different onset sites have different clinical manifestations, often due to palpable masses or enlarged masses causing compression symptoms. When the tumor originates in the sacrum or pelvis and compresses the rectum and urinary tract, changes in defecation and urination habits occur, and the external shape of the sacrum may change or be asymmetrical, often suggesting that there may be a mass in the sacrum. Testicular masses are more easily detected early, with asymmetrical, hard enlargement of the testicles. Retroperitoneal and ovarian masses are asymptomatic in the early stage and are not easily detected, often only being diagnosed when the abdominal circumference increases or a mass is palpated. Ovarian mass torsion can cause acute abdominal pain, and masses originating in the mediastinum can compress blood vessels or trachea, causing superior vena cava syndrome and respiratory tract compression symptoms.

　　Referring to the general prevention methods of tumors, understanding the risk factors of tumors and formulating corresponding prevention and treatment strategies can reduce the risk of tumors. There are two basic clues for preventing the occurrence of tumors, even if tumors have already started to form in the body, they can also help the body improve its resistance. The following strategies are described as follows:

　　1. Avoiding harmful substances (carcinogenic factors) is to help us avoid or minimize contact with harmful substances.

　　2. Improving the body's immune system against tumors can help improve and strengthen the struggle of the body's immune system against tumors.

　　3. The focus of our current tumor prevention and treatment work should first be on and improve those factors closely related to our lives, such as quitting smoking, reasonable diet, regular exercise, and weight loss. Anyone who follows these simple and reasonable lifestyle常识 can reduce the chance of getting cancer.

　　4. Enhancing the body's immune system to resist tumors: The most important thing to improve immune system function is diet, exercise, and controlling stress. A healthy lifestyle choice can help us stay away from cancer. Maintaining a good emotional state and appropriate physical exercise can keep the body's immune system in the best state, which is also beneficial for preventing tumors and other diseases. In addition, some studies have shown that appropriate exercise not only strengthens the human immune system but also reduces the incidence of colon cancer by increasing the peristalsis of the human intestinal system. Here we mainly understand some issues about diet in the prevention of tumor occurrence.

　　5. Human epidemiological studies and animal experiments show that vitamin A plays an important role in reducing the risk of cancer. Vitamin A supports normal mucous membranes and vision, and it directly or indirectly participates in the function of most tissues in the body. Vitamin A exists in animal tissues such as liver, whole eggs, and whole milk, and in plants it exists in the form of beta-carotene and carotenoids, which can be converted into vitamin A in the human body. Overconsumption of vitamin A can cause adverse reactions in the body, while beta-carotene and carotenoids do not have this phenomenon. An increase in low vitamin A content in the blood increases the risk of malignant tumors. Studies have shown that those with low levels of vitamin A intake in the blood are more likely to develop lung cancer, and for smokers, those with low levels of vitamin A intake in the blood have twice the risk of developing lung cancer. Vitamin A and its mixtures can help clear free radicals in the body (free radicals can cause damage to genetic material), and secondly, they can stimulate the immune system and help differentiate cells in the body, forming ordered tissues (while the characteristic of tumors is disorderly). Some theories suggest that vitamin A can help reverse the mutated cells that are early attacked by carcinogens and become normal growing cells.

　　6. Some studies suggest that simply supplementing beta-carotene drugs does not reduce the risk of cancer, on the contrary, it slightly increases the incidence of lung cancer. However, when beta-carotene is combined with vitamin C, E, and other anti-toxin substances, its protective effect becomes evident. The reason is that when it is consumed itself, it can also increase the free radicals in the body. In addition, there are interactions between different vitamins. Studies in humans and mice have shown that the application of beta-carotene can reduce the level of vitamin E in the body by 40%. A relatively safe strategy is to eat different foods to maintain the balance of vitamins to resist the invasion of cancer, because some protective factors have not been discovered yet.

　　7. Vitamin C and E are another type of antitumor substance, which can prevent the harm of carcinogens in food such as nitrosamines. Vitamin C can protect sperm from genetic damage and reduce the risk of leukemia, kidney cancer, and brain tumor in offspring. Vitamin E can reduce the risk of skin cancer. Vitamin E has antitumor effects like vitamin C and is a scavenger for antitoxins and free radicals. The combined use of vitamin A, C, and E has a better protective effect on the body against toxins than their single use.

　　Currently, the research on phytochemicals has attracted widespread attention. Phytochemicals are chemical substances found in plants, including vitamins and other substances found in plants. Thousands of chemical components have been found in plants, many of which have anticancer effects. The protective mechanism of these chemical substances not only reduces the activity of carcinogens but also enhances the body's immunity to resist the invasion of carcinogens. Most plants provide antioxidant activity that exceeds the protective effect of simple vitamin A, C, and E. For example, a cup of kale contains only 50mg of vitamin C and 13U of vitamin E, but its antioxidant activity is equivalent to 800mg of vitamin C and 1100U of vitamin E, indicating that the antioxidant effect of antioxidants in fruits and vegetables is much stronger than that of vitamins we know. There is no doubt that natural plant products will help in the future cancer prevention work.

　　First, Laboratory examination

　　1. Blood

　　The levels of chorionic gonadotropin, alpha-fetoprotein, and carcinoembryonic antigen in the patient's blood may be elevated. They can return to normal after surgery, but will increase again if there is recurrence or metastasis. Foreign reports show that in 11 cases of germinoma, all patients had increased chorionic gonadotropin or alpha-fetoprotein in their blood. Therefore, most scholars believe that patients with elevated chorionic gonadotropin or alpha-fetoprotein before surgery have poor prognosis.

　　2. Cerebrospinal fluid

　　Most patients have increased pressure, and some patients have mild to moderate increase in cerebrospinal fluid protein content. Cerebrospinal fluid can significantly increase chorionic gonadotropin or alpha-fetoprotein. Cerebrospinal fluid cytology examination may sometimes find tumor cells. In 70% of cases, there may be squamous cells in the cerebrospinal fluid, but it does not necessarily mean the occurrence of spinal cord metastasis.

　　Second, Imaging examination

　　1. Skull X-ray

　　Signs of increased intracranial pressure can be displayed. 40% to 60% of patients may have pineal gland abnormal calcification, especially when calcification occurs in children aged 10 to 15, with calcification spots larger than 1cm in diameter and calcification shifting downward and backward, which are strong evidence for the diagnosis of germinoma.

　　2. Radionuclide scanning

　　Continuous brain scintigraphy with radionuclides, in most cases, radionuclides can be seen to accumulate in the tumor, with a diameter greater than 1.5 cm.

　　3. CT scanning

　　(1) CT scanning can accurately determine its size, location, and surrounding relationships. Plain CT shows density similar to or slightly higher than that of brain gray matter, and the incidence of calcification in pineal region germ cell tumors is much higher than that in sellar region germ cell tumors. During the growth process of pineal region germ cell tumors, calcified pineal glands (in the form of bullets) may be surrounded by them, so the calcified 'bullets' may be within the tumor or at the periphery of the tumor, often on the side or rear, and occasionally may be pushed to the front. The tumor shape is round, irregular, or butterfly-shaped, and the latter has characteristic value in the diagnosis of germ cell tumors. The calcification rate of the pineal gland in normal people is about 40%, while the calcification rate of the pineal gland in patients with germ cell tumors is nearly 100%; suprasellar germ cell tumors can be without calcification or with fine calcification.

　　(2) Enhanced CT: When lesions are found during CT plain scanning, immediate injection of contrast agent should be performed for CT enhancement scanning. It is characterized by moderate to marked uniform enhancement, with a few cases showing uneven enhancement, which can show smaller cystic changes. Therefore, in children or adolescents, if a slightly high-density mass in the pineal region is found on CT, and there is uniform enhancement after injection (a few cases may be uneven), and if there is bullet-shaped calcification, it strongly suggests a germ cell tumor. Suprasellar germ cell tumors are located in the median infundibulum and (or) the pituitary entering the sella, and it is not uncommon to invade the neurohypophysis. Suprasellar germ cell tumors can be round or lobulated, similar to the pineal region in CT plain scan and enhancement, but some scholars point out that calcification rarely occurs in this region of germ cell tumors. In addition to the aforementioned 'solitary' tumors, the most typical case of 'multifocal' germ cell tumors is the simultaneous discovery of 2 or 3 germ cell tumors during CT examination. CT examination is of great value for germ cell tumors, especially providing important information on calcification of the tumor and brain ventricle expansion or displacement. Different subtypes of germ cell tumors have their unique manifestations, and sometimes, combined with clinical findings, even a qualitative diagnosis of the tumor can be made.

　　4. MRI examination

　　MRI is suitable for showing small germ cell tumors above the sella (diameter

　　1. What foods are good for children with germ cell tumors

　　It is advisable to maintain a light diet, eat more vegetables and fruits, reasonably match the diet, and pay attention to sufficient nutrition.

　　2. What foods should children with germ cell tumors not eat

　　Avoid smoking, drinking, spicy and pungent foods. Avoid greasy, smoking, and drinking. Avoid eating cold foods.

　　First, the treatment of germ cell tumors

　　1. Being a group of diseases with significant differences in age, pathological histological type, and primary site, corresponding treatment measures should be provided individually during the diagnosis and treatment process. In recent years, due to the progress of chemotherapy, new suggestions have been proposed for the indications, timing, and extent of resection for surgery. The application of radiotherapy in germ cell tumors has not yet been established.

　　2. Surgery For localized tumors and benign tumors such as benign teratomas, surgery is the main treatment method. When it is estimated that the tumor cannot be completely resected or resection may damage important life-supporting tissue structures, consideration should be given to only performing a biopsy. After confirming the diagnosis, chemotherapy should be performed first to reduce the tumor burden and create conditions for surgery. The radical surgery should be performed after the mass has significantly shrunk and can be basically completely resected. For those who have not been completely resected in the first operation and still have residual lesions after chemotherapy, a second operation may be considered.

　　3. Chemotherapy For pediatric malignant germ cell tumors that cannot be completely resected by surgery, the prognosis was very poor in the past. In recent years, due to the intervention of effective chemotherapy, the prognosis has improved significantly. Single-agent effective drugs include actinomycin D (regeneratin), vincristine, bleomycin, doxorubicin (adriamycin), cisplatin, etoposide (VP-16), etc. Other newer drugs such as carboplatin and ifosfamide are also effective. Clinically, combined chemotherapy is mainly used, with vincristine as the basis and adding other effective chemotherapy drugs, combined with surgery to further improve the disease-free survival rate. The addition of cisplatin recently has significantly increased the cure rate. The commonly used combined chemotherapy regimens are shown in the table.

　　4. Radiotherapy The status of radiotherapy in the treatment of germ cell tumors is not yet determined.

　　Secondly, the prognosis depends on the pathological type of the tumor

　　It depends on the early or late discovery and whether there is metastasis. For example, testicular dysgerminoma: the age of the child is closely related to the prognosis, the younger the age, the higher the survival rate. Radical orchiectomy can be performed within 1 year of age, and 95% can be cured. Combined chemotherapy regimens are used. The recent efficacy can reach 100%, and the long-term survival rate is increasing after active treatment of lung metastasis cases. The overall survival rate is above 60% to 80%.