What Are Germ Cell Tumors?

Germ cell tumors are tumors that occur in or outside the gonads and are formed by the transformation of primitive germ cells or pluripotent germ cells; undifferentiated, sexless embryonic gonads can be seen in the yolk sac region at the 4th week of embryo development. The gonads migrate from the yolk sac to the genital spine of the retroperitoneum. They are regulated and developed by the sex chromosome information to mature into ovaries or testes, and descend to the pelvic cavity and scrotum. To the pineal gland, mediastinum, posterior peritoneum, palate tail and so on. Because germ cell tumors can occur in any place where the primitive gonads are normal or ectopic, the germ cell tumors can occur in the ovaries and testes, and can also occur outside the gonads (extragonadal), and are mostly located near the midline. Such as pineal gland, zygomatic coccyx, mediastinal cavity, posterior abdominal cavity, etc. Germ cell tumors in children are relatively rare, accounting for about 1% of childhood malignancies, of which 58-70% originate from outside the gonads, and the incidence rate by site is: sacrum, retroperitoneum, mediastinum, and pineal gland.

Germ cell tumor

Germ cell tumors are tumors that occur in or outside the gonads and are formed by the transformation of primitive germ cells or pluripotent germ cells; undifferentiated, sexless embryonic gonads can be seen in the yolk sac region at the 4th week of embryo development. The gonads migrate from the yolk sac to the genital spine of the retroperitoneum. They are regulated and developed by the sex chromosome information to mature into ovaries or testes, and descend to the pelvic cavity and scrotum. To the pineal gland, mediastinum, posterior peritoneum, palate tail and so on. Because germ cell tumors can occur in any place where the primitive gonads are normal or ectopic, the germ cell tumors can occur in the ovaries and testes, and can also occur outside the gonads (extragonadal), and are mostly located near the midline. Such as pineal gland, zygomatic coccyx, mediastinal cavity, posterior abdominal cavity, etc. Germ cell tumors in children are relatively rare, accounting for about 1% of childhood malignancies, of which 58-70% originate from outside the gonads, and the incidence rate by site is: sacrum, retroperitoneum, mediastinum, and pineal gland.

pathology

Germ cell tumors have complex tissue types. For example, asexual cell tumors can occur when primordial germ cells are undifferentiated, embryo cancers can occur when undifferentiated germ cells, and teratomas can form if embryonic differentiation occurs; choriocarcinoma can occur in extraembryonic tissue differentiation Endodermal sinus tumors; interstitial tumors originated from ovarian or testicular sex cords, and less common epithelial tumors originate from body cavity epithelium; and there are many tumor sites, and the tumor types in different parts are similar, but the tissue type and biology The characteristics are different. Each tumor has both benign and malignant components. Malignant components determine biological behavior. According to the tissue source of the tumor, germ cell tumors can be divided into the following categories:

Teratoma

Divided into mature teratoma, immature teratoma and malignant teratoma according to pathological type. Mature teratomas are benign tumors composed of differentiated tissues. Immature teratomas refer to mature mature tissues containing immature embryonic tissues, mostly glial or neural tube-like structures. Malignant teratomas It means that the tumor tissue contains malignant components, which are mainly divided into yolk sac tumor, asexual cell tumor and embryonic cancer; according to the degree of tissue maturity and the number of immature tissues, teratomas can be further graded (grade).

2. yolk sac tumor

Tumors are brittle and soft, grayish or grayish-yellow, and often have bleeding and necrosis of varying sizes. The structure under the microscope is complex, showing a single small cell, less plasm, round or oval, and the nucleoli is not obvious; or some larger cells with obvious nucleus and nucleoli, such as embryonic cancer or germ cell tumor Arranged in groups, the degree of mitosis varies, and they are specifically divided into pseudo-papillary, microcapsule, solid, and polycystic yolk.

Germ cell tumor

Seminoma has a complete envelope, solid, cut to gray-yellow, elastic, and may be accompanied by hemorrhage and necrosis; under the microscope: tumor cells are divided into nests by fibrous tissue impregnated with lymphocytes, with large cells and cytoplasmic cells The membrane is clear, the nucleus is 1-2, the nucleus is large, there are often foreign bodies or Langerhans granulomas, and trophozoite can appear, but the prognosis is not affected.

4. Other

Rarely, it includes malignant embryonic carcinoma, choriocarcinoma, polyembryoma, gonadoblastoma, etc. These tumors are highly malignant.

Clinical manifestations:

The clinical manifestations of patients have different symptoms depending on where the tumor occurs:

1. Testis germ cell tumors: Yolk sac tumors are most common. Painless masses can be felt on the scrotum in the early stage. They are often mistaken for scrotal edema, which may gradually cause tenderness, which may easily be transferred to the posterior abdominal lymph nodes, The liver, lungs, bones and other parts may be complicated by other symptoms. Cryptochidism is 10-50 times more common in boys than in normal boys, so they should be treated promptly to prevent them from turning into testicular tumors.

2. Ovary germ cell tumors: Teratomas are the most common, and pain, nausea, and vomiting often occur. Sometimes the tumors are twisted or ruptured, causing acute abdominal pain.

3. Sacrum-coccyx germ cell tumor: It is common in infants and young children. The tumor is longer than the posterior gluteal region at birth, and there are more girls than boys. They are benign teratomas. Symptoms such as constipation, affected bladder function, and paresis in the lower limbs often occur.

4. Central nervous system germ cell tumor: most of the pineal body in the brain, sometimes longer than the spine, may cause neurological symptoms such as diabetes insipidus, nausea, vomiting, drowsiness, headache Wait.

5. Mediastinum germ cell tumor: If the tumor compresses the trachea or bronchus, it may cause symptoms such as cough, wheezing, chest pain, and hemoptysis.

6. Retroperitoneum (retroperitoneum) germ cell tumor: The tumor may compress the intestine or urinary tract, causing pain, intestinal obstruction, constipation, etc.

7. Other: Germ cell tumors may also invade the vagina, uterus and other parts, causing abnormal vaginal bleeding. A small number of teratomas occur in the throat, mouth, eye socket, cervical spine, etc., and may cause respiratory tract obstruction.

Common tests for germ cell tumors:

1. Complete medical history collection and physical examination evaluation.

2. Tumor marker examination: Some germ cell tumors secrete special fetal protein (-fetoprotein, AFP) and human chorionic gonadotropin (-HCG), which can be used for diagnosis and treatment. Reference basis is also one of the important examinations after the completion of treatment.

AFP is the earliest plasma-binding protein that appears in the fetus. It is produced in the yolk sac early in the embryo, and then produced by hepatocytes and the digestive tract. AFP elevation is important for the diagnosis of most malignant germ cell tumors. AFP plasma concentration changes greatly, so for infants younger than 8 months, the change in AFP concentration cannot indicate the residual or recurrence of the tumor;

-human chorionic gonadotropin (-HCG) is a glycoprotein that is synthesized by placental syncytiotrophoblast cells during pregnancy to maintain luteal activity. Serum is measured with antigen-specific fragments. Germ cell tumors The patient was accompanied by an increase in serum -HCG, suggesting that there are two types of cell clones, one is a syncytiotrophoblast, such as chorionic carcinoma, and the other is a syncytiotrophoblast giant cell, which is common in seminoma or asexual tumor Occasional embryonic cancer;

Lactate dehydrogenase (LDH) is a glycolytic enzyme that is involved in the growth and regression of various solid tumors. It has a certain relationship with tumor charms and helps evaluate the feasibility of surgical treatment.

3. Chest X-ray: confirm if there is lung metastasis.

4. Ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI): confirm the tumor site, size, and presence of surrounding tissue invasion, lymph node metastasis, and liver, lung, and even central nervous system metastases.

5. Bone scan: confirm whether there is bone metastasis.

6. Pathological examination: surgically remove the tumor to confirm the pathological tissue.

treatment

The treatment of children's germ cell tumors needs to be different according to tissue type, tumor origin, age, and clinical stage. Individual comprehensive treatment programs are needed. In recent years, with the continuous development of effective chemotherapy drugs, surgical treatment, especially in the selection of surgery Significant progress has been made in timing and increasing the rate of surgical resection. In addition, reflex therapy is also an important treatment for some types of childhood germ cell tumors.

Surgical treatment

Surgical resection is preferred for benign tumors, and any localized malignant tumors should be completely removed as much as possible. When effective chemotherapy is feasible, advanced malignant tumors do not come at the cost of resection of vital vital organs. Partial resection or biopsy should be taken first to determine the tissue. The type, guides the choice of chemotherapy regimen, and after the effective chemotherapy is implemented (the tumor shrinks rapidly and histologically matures into a teratoma), the second surgery can be selected to achieve the best treatment effect.

Chemotherapy

Many chemotherapy drugs can be used to treat germ cell tumors in children, such as actinomycin D, vincristine, bleomycin, cisplatin, and etoposide, but the mechanism of action and sensitivity of each drug are different. Therefore, the principles of chemotherapy for children's germ cell tumors are consistent with the principles of other malignant tumors, and they must follow the principle of joint and sequential; combined use can play a synergistic effect of drugs and can effectively reduce the generation of drug resistance. At present, various The chemotherapy regimens are based on the combination of cisplatin. The chemotherapeutic schemes for children's germ cell tumors currently use the PEB standard scheme of the Children's Tumor Collaboration Group and the Children's Cancer Collaboration Group; the standard PEB regimen is 5 days, once every 3-4 weeks, a total of 4-6 courses, 20 mg of cisplatin / m, intravenous drip; those younger than 1 year of age were administered according to kg of body weight: bleomycin 0.5 mg / kg, etoposide 3 mg / kg, and cisplatin 0.7 mg / kg. The latest research from the British Pediatric Cancer Research Group confirms that 3-day PEB 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%.

3. Radiotherapy

Radiation therapy is mainly used to treat germinoma or tumors located in the brain, with better efficacy;

Staging, recurrence and metastasis of germ cell tumors

The degree of germ cell tumor invasion can help physicians decide on treatment plans and understand the prognosis. Germ cell tumors have different staging methods depending on the site of occurrence. Generally speaking, they are limited to the primary site and do not invade the large blood vessels. This is the first stage. If the tumor has metastasized to the liver, lungs, bones, etc. at the time of onset, it is called the fourth stage.

Germ cell tumors are prone to relapse, because the few cancer cells remaining after treatment are difficult to find in various examinations. The symptoms will not reappear until these cancer cells have proliferated to a considerable degree, even if the surgery is very successful Long-term follow-up is also required, and regular serology, ultrasound, and imaging examinations are performed to achieve early detection and early treatment.

Will germ cell tumors affect fertility? In general, chemotherapy does not affect reproductive function, but each person's tumor site and treatment severity are different, and the degree of influence on reproductive function is also different.

Several common germ cell tumors:

Teratoma

Teratomas are tumors derived from germ cells with 2-3 germ layers. Most (about 90-95%) are benign, and a few are malignant. They are more common in adolescents, and 50% of childhood ovarian tumors are teratomas. According to the site of the disease, they are: the tail of the palate, gonads (ovary and testis), retroperitoneum and mediastinum; benign cystic teratoma, also known as mature teratoma, is the most common ovarian tumor one. To the naked eye, most of them are single large sacs filled with sebaceous matter, which are mixed with different amounts of hair. The sac wall often has one or several nodular protrusions, and the surface of the nodule has hair. The skin, fat, cartilage, bone and other structures can be seen on the section, and about 1/3 of the teeth can be seen. Under the microscope, it is composed of tissues or organ-like structures derived from two germ layers or three germ layers that are mature and differentiated. The most common are mature and differentiated skin tissues and their appendages, adipose tissue, and smooth muscle. Rarely, there are respiratory mucosa, bone, cartilage, nerve tissue, gastrointestinal tract, and thyroid tissue. A few benign teratomas can also present. Solid, but completely composed of mature tissue, about 1% of benign teratoma can be malignant, most of which are squamous epithelial components and become squamous cell carcinoma. Immature teratoma occurs mostly in young women, children and adolescents under 25 years of age. Macroscopically, tumors are generally large in size, and are mainly solid. Among them, cysts of various sizes can be seen, often with hemorrhage and necrosis. Microscopically, the tumor contains mature and immature 2-3 germ layers. Common are immature neural tissues that form chrysanthemum-like neural tube-like or diffuse pieces of neuroepithelium, immature cartilage or embryonic mesenchymal tissue. Malignant teratoma tumor tissue contains more immature tissue, the higher the degree of malignancy, the more likely it is to relapse or the pelvic and abdominal implants are metastasized after surgery, and the prognosis is poor.

Mature teratomas are usually removed by surgery. If immature teratomas cannot be completely removed, some may require chemotherapy. Very few teratomas may undergo malignant transformation and become malignant germ cells in the future. Tumors or other malignancies, it is still recommended to follow up regularly.

2. yolk sac tumor

Before 1959, it was called mesangial tumor. It is now recognized that its occurrence has nothing to do with the mesonephros and endoderm sinus. The basic histological characteristics are similar to the differentiation of the yolk sac during embryonic development, so it is derived from germ cells. Tumors with characteristics of yolk sac differentiation outside the embryo are the most common in childhood malignant germ cell tumors. The most commonly occurring site is the sacrococcygeal vertebrae, followed by the testis and ovaries. In most clinical patients, -FP levels in serum high.

Yolk sac tumors grow faster, the cystic structure is more pronounced, and the hemorrhage and necrosis are more widespread. There are a variety of structures under the microscope, which can have the following 10 structures: microcystic structure with sac covered flat or cubic epithelium; endodermal sinus Structure, tumor cells around the thick-walled blood vessels, showing a polar disorder of the papillary shape, outside the nipple is a balloon-like structure; solid structure, juvenile embryonic solid epithelial cluster-like structure; acinar or glandular tube-like structure; Polycystic yolk sac-like structure; interstitial loose mucus-like; papillary; large cystic; liver-like structure, like liver cancer; primitive endoderm, like intestinal epithelial differentiation. These 10 structures are mixed, often with 2-3 structures as the main component. There is also a more special component under the microscope, which is a drop of red staining and PAS-positive protein bodies in conventional HE sections. Immunohistochemistry showed positive -FP in corpuscle and intraepithelium. Immunohistochemistry has important significance in diagnosis and differential diagnosis. In addition to -FP positive immunohistochemistry, EMA and -1 chymotrypsin (-l-ACT) can also be positive. Endodermal sinus tumors are more common in adolescents with a poor prognosis, with a 3-year survival rate of only 13%.

Testicular yolk sac tumor patients, if younger than 1 year old, and no metastasis, usually remove the testis surgically; if the child is older than 1 year, the prognosis is poor, you must add chemotherapy and radiation therapy. Ovarian yolk sac tumor usually grows quickly and is easy to metastasize. In addition to the removal of the affected fallopian tube and ovary, chemotherapy or radiation therapy is required.

Germ cell tumor

Germ cell tumor, also known as asexual cell tumor or seminoma, is the most common malignant germ cell tumor that occurs in children's ovary and central nervous system. It originates from pluripotent, undifferentiated germ cells. The macroscopic view is a substantially spherical brain gyrus. The cut surface is soft, homogeneous and grayish yellow. Microscopically, the tissue structure of asexual cell tumors is similar to that of testicular seminoma. The tumor is composed of tumor cells that are similar in shape to primitive germ cells. Most of the tumor cells are large round, rich in cytoplasm, clear in state, and contain more sugar. original. The nuclear circle has prominent nucleoli. Tumor cell clusters are separated into thin leaflets by a thin layer of stroma. Lymphocyte infiltration is often associated with stroma. And can have tuberculosis-like granulomatous reaction, which is helpful for diagnosis.

Asexual cell tumors are more sensitive to radiotherapy, and the 5-year survival rate is more than 70%. A few cases of tumors can be combined with trophoblast cell components or endodermal sinus tumor differentiation, and the prognosis is poor.