Germ cell tumors are tumors that occur outside the gonads or germ glands and are formed by the transformation of primitive germ cells or pluripotent germ cells; undifferentiated, sexless embryonic gonads are seen in the yolk sac region during the fourth week of embryonic development, after which the primitive gonads migrate from the yolk sac to the germinal ridge in the posterior peritoneum, where they are regulated by sex chromosome information and mature into ovaries or testes, and descend to the pelvis and scrotum, respectively. During this process, the primordial gonads may also migrate ectopically, such as to the pineal gland, mediastinum, retroperitoneum, and sacrococcygeal region. Since germ cell tumors can occur in any site where the primordial gonads are normal or ectopic, germ cell tumors can occur not only in the ovaries and testes, but also in the extragonadal gonads, mostly located near the midline, such as the pineal gland, sacrococcygeal, mediastinal cavity, and retroperitoneum. Germ cell tumors in children are relatively rare, accounting for about 1% of malignant tumors in children. 58-70% of these tumors originate from extragonadal sources, and their incidence is in order of location: sacrum, retroperitoneum, mediastinum, and pineal gland. Pathology The tissue types of germ cell tumors are complex, for example, asexual cell tumors can occur when the primitive germ cells are undifferentiated, embryonal carcinoma can occur when the germ cells are undifferentiated, and teratoma can be formed if embryonic differentiation occurs; choriocarcinoma and endodermal sinus tumors can occur when the extra-embryonic tissue is differentiated; mesenchymal tumors originate from the ovaries or the sex cords of the testes, and the less common epithelial tumors originate from the epithelium of the corpora cavernosa; moreover, the tumors occur at many sites, and the morphology of various tumors at different sites is similar. The tumors are similar in morphology, but the tissue types and biological characteristics are not the same. Mature teratoma is a benign tumor consisting of differentiated tissues; immature teratoma refers to the immature embryonic tissues in the differentiated mature tissues, mostly neuroglial or neural tube like structures; malignant teratoma refers to the malignant components in the tumor tissues, mainly divided into yolk sac tumor, asexual cell tumor and embryonal carcinoma; according to the degree of tissue maturity and the number of immature tissues, teratoma can be further classified as According to the degree of tissue maturity and immature tissue, teratoma can be further graded (grade). 2.Yolk sac tumor is brittle and soft, gray or gray-yellow mucus-like, often with foci of hemorrhage and necrosis of different sizes. The microscopic structure is complex, with single small cell, little quality, round or ovoid, and inconspicuous nucleoli; or some larger cells with obvious nuclei and nucleoli, like embryonal carcinoma or germ cell tumor arranged in clusters, with different degrees of mitosis, specifically divided into pseudopapillary type, microcystic type, solid type and polycystic yolk type. 3.Germ cell tumor Spermatocytoma has complete envelope, solid, grayish-yellow cut surface, elastic, may be accompanied by hemorrhagic necrosis; microscopically: tumor cells are divided into nests by lymphocyte-impregnated fibrous tissue, large cells, clear cytoplasm cytosol, 1-2 nuclei, large nuclei, often with foreign bodies or Langerhans granuloma, may appear syncytial trophoblast layer, but does not affect the prognosis. 4.Other less common are malignant embryonal carcinoma, choriocarcinoma, polyembryoma, gonadoblastoma, etc. These tumors are highly malignant. Clinical manifestations: The clinical manifestations of patients have different symptoms depending on the location of the tumor: 1. Testicular (testis) germ cell tumor: yolk sac tumor is the most common, and a painless lump can be felt in the scrotum at the beginning, which is often mistaken for scrotal edema, and gradually there may be pressure pain. The chance of malignant testicular tumor in boys with cryptorchidism is 10-50 times higher than that of ordinary boys, so timely treatment should be provided to avoid transformation into testicular tumor. 2.Ovarian (ovary) germ cell tumor: teratoma is the most common, which often causes pain, nausea and vomiting, and sometimes acute abdominal pain due to twisting and rupture of the tumor. 3.Sacrum-coccyx germ cell tumor: It is common in infants and young children, and the tumor is seen in the posterior buttock area at birth, more in girls than boys, mostly benign teratoma. They often present with symptoms such as constipation, bladder function affected, and lower limbs lightly paralyzed. 4.Germ cell tumors of central nervous system: Most of them are located in the pineal body of the brain, sometimes they also grow in the spine, and may cause neurological symptoms, such as enuresis, nausea, vomiting, drowsiness, headache, etc. 5.Mediastinum germ cell tumor: If the tumor compresses the trachea or bronchus, it may cause cough, wheezing, chest pain, coughing up blood and other symptoms. 6. Retroperitoneal (retroperitoneum) germ cell tumor: If the tumor presses on the intestine or urinary tract, it may cause pain, intestinal obstruction, constipation, etc. 7. Other: germ cell tumors may also invade the vagina and uterus, causing abnormal vaginal bleeding. A small number of teratomas may occur in the throat, mouth, eye sockets, cervical spine and other parts of the body, which may cause obstruction of the respiratory tract. Common tests for germ cell tumors: 1. Complete history taking and physical examination for evaluation. 2. 2. Tumor marker examination: Some germ cell tumors secrete special fetoprotein (α-fetoprotein, AFP) and human chorionic gonadotropin (β-HCG), which can be used as a reference for diagnosis and treatment, and is also one of the important tests for follow-up after completion of treatment. AFP is the earliest plasma-bound protein in fetal life, produced in the yolk sac in early embryonic life, and later by hepatocytes and the digestive tract. Elevated AFP is an important guide for the diagnosis of most malignant germ cell tumors, but because of the large variation in AFP plasma concentration in children within 1 year of age, changes in AFP concentration in infants younger than 8 months of age do not indicate residual or recurrent tumors; human The human chorionic gonadotropin (β-HCG) is a glycoprotein that is synthesized by placental syncytial trophoblast cells during pregnancy to maintain luteal activity, and the serum is determined to have an antigen-specific β fragment. It is common in seminomatous cell tumor or anaplastic cell tumor, and embryonal carcinoma is occasionally seen; lactate dehydrogenase (LDH) is a glycolytic enzyme related to the growth and regression of various solid tumors, and has a certain relationship with tumor runners, which helps to assess the feasibility of surgical treatment. 3.Chest X-ray: to confirm whether there is lung metastasis. 4.Ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI): to confirm the location and size of the tumor, as well as the presence of surrounding tissue invasion, lymph node metastasis and metastasis to the liver, lung and even the central nervous system. 5.Bone scan: to confirm whether there is bone metastasis. 6.Pathological biopsy: surgically remove the tumor to confirm the pathological tissue. In recent years, with the development of effective chemotherapy drugs, surgical treatment has made great progress, especially in choosing the timing of surgery and improving the rate of surgical resection, and reflexology is also an important treatment tool for certain types of childhood germ cell tumors. In addition, reflexology is also an important treatment tool for certain types of germ cell tumors in children. If effective chemotherapy is feasible, progressive malignant tumors should not be removed at the cost of important vital organs, but should be partially excised or biopsied first to determine the tissue type and guide the selection of chemotherapy regimen, and after the implementation of effective chemotherapy (rapid reduction of the tumor and histological maturation to teratoma), then elective surgery can be performed. The best therapeutic effect can be achieved by secondary surgery. Many chemotherapeutic drugs can be used in the treatment of pediatric germ cell tumors, such as actinomycin D, vincristine, bleomycin, cisplatin and etoposide, but the mechanism of action and the degree of sensitivity of each drug are different. At present, various chemotherapy regimens are based on the combination of cisplatin. The standard PEB regimen is 5 days, once every 3-4 weeks, for 4-6 courses, with cisplatin 20 mg/m2 intravenously; for children younger than 1 year old, the regimen is given by kilogram of body weight: bleomycin 0.5 mg/kg, etoposide 3 mg/kg, cisplatin 0.7 mg/kg. The latest study of the British Pediatric Cancer Research Group confirmed that the 3-day PEB regimen is safe and feasible for germ cell tumors with good prognosis, with a 5-year survival rate of 93.2% and a tumor-free survival rate of 87.8%. Radiation therapy is mainly used to treat germ cell tumors (germinoma) or tumors located in the brain, and has better efficacy; staging, recurrence and metastasis of germ cell tumors The degree of invasion of germ cell tumors can help physicians to decide the treatment plan and understand the prognosis. Generally speaking, germ cell tumors that are confined to the primary site without invasion of large blood vessels and can be completely removed are stage I. If the tumor has metastasized to the liver, lung, bone and other parts of the body at the time of onset, it is called stage IV. Germ cell tumors are prone to recurrence because the few remaining cancer cells after treatment are difficult to be detected in various examinations, and the symptoms will only appear again when these cancer cells have proliferated to a considerable extent. Does germ cell tumor affect reproductive function? Generally speaking, chemotherapy does not affect reproductive function, but the degree of impact on reproductive function varies with each individual’s tumor site and the severity of treatment. Teratoma is a tumor derived from germ cells with 2-3 germ layers differentiation, most of them (about 90-95%) are benign, a few are malignant, mostly seen in adolescents. In order of location, they are sacrococcygeal, gonadal (ovarian and testicular), retroperitoneal and mediastinal; benign cystic teratoma, also known as mature teratoma, is one of the most common tumors of the ovary. It is a single large bursa filled with sebaceous material and mixed with a variable number of hairs, often with one or several nodular projections on the bursal wall and hairs on the surface of the nodules). Skin, fat, cartilage, bone and other structures were visible in the section, and about 1/3 of the teeth were visible. Microscopically, it consists of differentiated mature tissue or organ-like structures of two or three germ layers origin. The most common ones are differentiated mature skin tissue and its appendages, adipose tissue and smooth muscle, less common ones are respiratory mucosa, bone, cartilage, nerve tissue, gastrointestinal tract and thyroid tissue, etc. A few benign teratomas can also be solid, but they are composed entirely of mature tissue. About 1% of benign teratomas can become malignant, mostly the squamous epithelial component malignantly changes into squamous cell carcinoma. Immature teratoma occurs mostly in young women, children and adolescents under 25 years of age. To the naked eye, the tumor is usually large and predominantly solid, in which sacs of varying sizes are visible, often with hemorrhagic necrosis. Microscopically, the tumor contains both mature and immature 2-3 germ layer differentiated components. It is common to find immature neural tissue forming chrysalis clusters neural tube like or diffuse patches of neuroepithelium, immature cartilage or embryonic mesenchymal tissue. The more immature tissues contained in malignant teratoma tumor, the higher the malignancy, and the more prone to recurrence or pelvic or abdominal implantation and metastasis after surgery, with poor prognosis. If immature teratoma cannot be removed surgically, some of them may need chemotherapy. Very few teratomas may turn malignant and become malignant germ cell tumors or other malignant tumors in the future. Before 1959, it was called mesonephric tumor, but now it is recognized that its occurrence is not related to mesonephric and endodermal sinus, but its basic histological features are similar to the differentiation of yolk sac in embryonic development, so it is a tumor with extraembryonic yolk sac differentiation from germ cells. The most common site is the sacrococcygeal spine, followed by the testes and ovaries, and the majority of patients have elevated α-FP in their sera. There are 10 types of microscopic structures: (1) microcystic structures with flattened or cuboidal epithelium; (2) endodermal sinus-like structures with tumor cells surrounding thick-walled blood vessels in the form of disorganized papillae with balloon-like structures outside the papillae; (3) solid structures with infantile embryonic solid epithelial masses; (4) glandular follicle or duct-like structures; (5) polycystic yolk tumors. (5) polycystic yolk sac-like structures; (6) mesenchymal sparse mucus-like; (7) papillary; (8) macrocapsular; (9) hepatic-like structures, resembling hepatocellular carcinoma; and (10) primitive endoderm, resembling intestinal-type epithelial differentiation. A mixture of these 10 structures exists, often with 2-3 structures as the main components. Microscopically, there is also a more specific component, namely proteinous vesicles showing drop-like red staining and PAS positivity in conventional HE sections. Immunohistochemistry shows positive vesicles and intraepithelial α-FP. Immunohistochemistry is important in the diagnosis and differential diagnosis. In addition to positive α-FP, immunohistochemistry may also be positive for EMA and α-1 chymotrypsin (α-l-ACT). Endodermal sinus tumors are common in adolescents and have a poor prognosis, with a 3-year survival rate of only 13%. Patients with testicular yolk cysts who are younger than 1 year old and have not metastasized can usually have their testicles surgically removed; children older than 1 year old have a poor prognosis and must be treated with chemotherapy and radiation. Ovarian yolk cyst tumors usually grow quickly and are prone to metastasis, so in addition to removal of the affected fallopian tubes and ovaries, chemotherapy or radiation therapy is required. Germ cell tumors, also known as anaplastic cell tumors or seminoma, are the most common malignant germ cell tumors that occur in the ovaries and central nervous system of children, and are derived from multipotential, undifferentiated germ cells. It is a solid, spherical gyrus-shaped tumor. The cut surface is soft, homogeneous, and grayish-yellow in color. Microscopically, the histology of asexual cell tumors is similar to that of testicular spermatocytes. The tumors consist of morphologically uniform tumor cells that resemble primitive germ cells. The nuclei are large and round with prominent nucleoli. The tumor cell mass is separated into lobules by a thin layer of mesenchyme. The interstitium is often infiltrated with lymphocytes. A tuberculosis-like granulomatous reaction may also be present, which helps in the diagnosis. Asexual cell tumors are more sensitive to radiotherapy and have a 5-year survival rate of more than 70%. In a few cases, the tumor may have a trophoblastic component or endodermal sinus tumor differentiation, and the prognosis is poor.