Embryonic tumor of the yolk sac. Germ cell tumors in children

Description:

Germ cell tumors develop from a population of pluripotent germ cells. The first germ cells can be found in the endoderm of the yolk sac as early as a 4-week embryo. During embryonic development, primordial germ cells migrate from the endoderm of the yolk sac to the genital ridge in the retroperitoneum. Here, the germ cells develop into gonads, which then descend into the scrotum, forming the testes, or into the pelvis, forming the ovaries. If during the period of this migration, for some unknown reason, a disruption of the normal migration process occurs, the germ cells can linger at any point along their route, where a tumor can subsequently form. Germ cells can most often be found in areas such as the retroperitoneum, mediastinum, pineal region (pineal gland), and sacrococcygeal region. Less commonly, germ cells are retained in the vagina, bladder, liver, and nasopharynx.

Germ cell tumors are an uncommon type of tumor lesion in children. They make up 3-8% of all children and adolescents. Since these tumors can also be benign, their incidence is probably much higher. These tumors are two to three times more common among girls than boys. The mortality rate among girls is three times higher than among boys. After 14 years of age, mortality among males becomes higher, which is due to an increase in the incidence of testicular tumors in adolescent boys.

Symptoms:

The clinical picture of germ cell tumors is extremely diverse and, first of all, is determined by the location of the lesion. The most common locations are the brain (15%), ovaries (26%), coccyx (27%), testicles (18%). Much less often, these tumors are diagnosed in the retroperitoneum, mediastinum, vagina, bladder, stomach, liver, and neck (nasopharynx).

Testicle.
Primary testicular tumors are rare in childhood. Most often they occur before the age of two years and 25% of them are diagnosed at birth. According to histological structure, these are most often either benign teratomas or tumors of the yolk sac. The second peak in the diagnosis of testicular tumors is the puberty period, when the frequency of malignant teratomas increases. Seminomas in children are extremely rare. Painless, rapidly increasing swelling of the testicle is most often noticed by the child's parents. 10% of testicular tumors are combined with hydrocele and other congenital anomalies, especially of the urinary tract. Upon examination, a dense, lumpy tumor is detected, with no signs of inflammation. An increase in alpha-fetoprotein levels before surgery confirms the diagnosis of a tumor containing elements of the yolk sac. Pain in the lumbar region may be symptoms of metastatic lesions of the para-aortic lymph nodes.

Ovaries.
Ovarian tumors often present with abdominal pain. Upon examination, you can detect tumor masses located in the pelvis, and often in the abdominal cavity, increasing the volume of the abdomen due to. These girls often develop fever.

Dysgerminoma is the most common ovarian germ cell tumor, which is mainly diagnosed in the second decade of life, and rarely in young girls. The disease quickly spreads to the second ovary and peritoneum. Tumors of the yolk sac are also more common in girls during puberty. Tumors are usually unilateral and large in size, therefore, rupture of the tumor capsule is a common occurrence. Clinical manifestations of malignant teratomas (teratocarcinomas, embryonal carcinomas) usually have a nonspecific picture with the presence of tumor masses in the pelvis, and menstrual irregularities may be observed. Patients in the prepubertal period may develop a state of pseudopuberty (early puberty). Benign teratomas are usually cystic, can be detected at any age, often give the clinical picture of ovarian torsion with subsequent rupture of the ovarian cyst and the development of diffuse granulomatous.

Vagina.
These are almost always tumors of the yolk sac; all described cases occurred before the age of two years. These tumors usually present with vaginal bleeding or spotting. The tumor arises from the lateral or posterior walls of the vagina and has the appearance of polypoid masses, often pedunculated.

Sacrococcygeal region.
This is the third most common location of germ cell tumors. The incidence of these tumors is 1:40,000 newborns. In 75% of cases, the tumor is diagnosed before two months and is almost always a mature benign teratoma. Clinically, such patients have tumor formations in the perineum or buttocks. Most often these are very large tumors. In some cases, neoplasms have intra-abdominal spread and are diagnosed at an older age. In these cases, the histological picture is most often more malignant, often with elements of a yolk sac tumor. Progressive malignant tumors of the sacrococcygeal region often lead to dysuric symptoms, problems with bowel movements and urination, and neurological symptoms.

Mediastinum.
Germ cell tumors in most cases represent a large tumor, but compression syndrome of the superior vena cava occurs rarely. The histological picture of the tumor is predominantly of mixed origin and has a teratoid component and tumor cells characteristic of a yolk sac tumor. Brain.
Germ cell tumors of the brain account for approximately 2-4% of intracranial neoplasms. In 75% of cases, they are observed in boys, with the exception of the area of the sella turcica, where tumors are favored to be localized in girls. Germinomas form large infiltrating tumors, which are often the source of ventricular and subarachnoid cerebrospinal metastases. may precede other tumor symptoms.

Causes:

Malignant germ cell tumors are very often associated with various genetic abnormalities, such as -telangiectasia, Klinefelter syndrome, etc. These tumors are often combined with other malignant tumors, such as hematological malignancies. Undescended testicles pose a risk for developing testicular tumors.

Patients with germ cell tumors most often have a normal karyotype, but a breakdown in chromosome I is often detected. The genome of the short arm of the first chromosome can be duplicated or lost. Multiple examples of germ cell tumors have been reported in siblings, twins, mothers and daughters.

Differentiation along the embryonic line gives rise to the development of teratomas of varying degrees of maturity. Malignant extraembryonic differentiation leads to the development of choriocarcinomas and yolk sac tumors.

Often, germ cell tumors may contain cells of different germ cell lineages. Thus, teratomas may have a population of yolk sac cells or trophoblasts.

The frequency of each histological tumor type varies with age. Benign or immature teratomas are more common at birth, yolk sac tumors between one and five years of age, dysgerminomas and malignant teratomas are most common in adolescence, and seminomas are more common after 16 years.

The factors causing malignant changes are unknown. Chronic diseases and long-term drug treatment during maternal pregnancy may be associated with an increased incidence of germ cell tumors in children.

The morphological picture of germ cell tumors is very diverse. Germinomas consist of groups of large, uniform neoplastic cells with a swollen nucleus and clear cytoplasm. Tumors of the yolk sac have a very characteristic picture: a reticular stroma, often called lacy, in which there are rosettes of cells containing a-fetoprotein in the cytoplasm. produce human chorionic gonadotropin. Benign, well-differentiated teratomas often have a cystic structure and contain various tissue components, such as bone, cartilage, hair, and glandular structures.

The pathological report for germ cell tumors should include:
-localization of the tumor (organ affiliation);
-histological structure;
-state of the tumor capsule (its integrity);
-characteristics of lymphatic and vascular invasion;
- spread of the tumor to surrounding tissues;
-immunohistochemical study for AFP and HCG.

There is a correlation between the histological structure and the localization of the primary tumor: tumors of the yolk sac predominantly affect the sacrococcygeal region and gonads, and in children under two years of age, tumors of the coccyx and testicles are more often recorded, while in older (6-14 years old) tumors of the ovaries and testicles are more often diagnosed. pineal region.

Choriocarcinomas are rare but extremely malignant tumors that most often arise in the mediastinum and gonads. They can also be congenital.

Typical locations for dysgerminomas are the pineal region and the ovaries. Dysgerminomas account for approximately 20% of all ovarian tumors in girls and 60% of all intracranial germ cell tumors.

Embryonic carcinoma in its “pure form” is rarely found in childhood; most often, a combination of elements of embryonic carcinoma with other types of germ cell tumors, such as teratoma and yolk sac tumor, is recorded.

Treatment:

For treatment the following is prescribed:

If there is a suspicion of a germ cell tumor in the abdominal cavity or pelvis, surgery can be performed to remove the tumor or (in the case of a large tumor) to obtain morphological confirmation of the diagnosis. However, surgical intervention is often used for urgent reasons, for example, in case of torsion of the cyst stalk or rupture of the tumor capsule.

If you suspect an ovarian tumor, you should not limit yourself to a classic transverse gynecological incision. Median is recommended. When opening the abdominal cavity, the lymph nodes of the pelvis and retroperitoneal region are examined, the surface of the liver, the subphrenic space, the greater omentum and the stomach are examined.

In the presence of ascites, a cytological examination of ascitic fluid is necessary. In the absence of ascites, the abdominal cavity and pelvic area should be rinsed and the resulting rinsing water subjected to cytological examination.

If an ovarian tumor is detected, the tumor should be subjected to urgent histological examination, and the ovary should be removed only after confirmation of the malignant nature of the tumor. This practice avoids removing unaffected organs. If there is a massive tumor lesion, non-radical operations should be avoided. In such cases, a preoperative course of chemotherapy is recommended, followed by a “second look” operation. If the tumor is located in one ovary, removing one ovary may be sufficient. If the second ovary is affected, part of the ovary should be preserved if possible.

Recommendations for using the surgical method for ovarian damage:
1. A transverse gynecological incision should not be used.
2. Median laparotomy.
3. In the presence of ascites, a cytological examination is mandatory.
4. In the absence of ascites, rinse the abdominal cavity and pelvic area; cytological examination of rinsing waters.
5. Examination and, if necessary, biopsy:
- lymph nodes of the pelvis and retroperitoneal region;
-surface of the liver, subphrenic space, greater omentum, stomach.

Sacrococcygeal teratomas, most often diagnosed immediately after the birth of a child, must be removed immediately to avoid malignancy of the tumor. The operation must include complete removal of the coccyx. This reduces the likelihood of relapse of the disease. Malignant sacrococcygeal tumors must be treated initially with chemotherapy, followed by surgery to remove any residual tumor.

Surgery for a biopsy for a local tumor in the mediastinum and persistent AFP is not always justified, as it is associated with risk. Therefore, it is recommended to carry out preoperative chemotherapy and, after reducing the size of the tumor, surgical removal.

If the testicle is affected, orchiectomy and high ligation of the spermatic cord are indicated. Retroperitoneal lymphadenectomy is performed only when indicated.
.
Medical therapy has very limited use in the treatment of germ cell tumors. It may be effective in the treatment of ovarian dysgerminoma.

Chemotherapy.
Chemotherapy plays a leading role in the treatment of germ cell tumors. Many chemotherapy drugs are effective for this pathology. For a long time, it was widely used by three cytostatics: vincristine, actinomycin "D" and cyclophosphamide. However, recently, preference has been given to other drugs, on the one hand, new and more effective, on the other hand, having the least number of long-term consequences, and, first of all, reducing the risk of sterilization. The drugs most often used today for germ cell tumors are platinum (in particular, carboplatin), Vepezid and bleomycin.

Chapter 14.

Germ cell tumors develop from a population of pluripotent germ cells. The first germ cells can be found in the endoderm of the yolk sac as early as a 4-week embryo. During embryonic development, primordial germ cells migrate from the endoderm of the yolk sac to the genital ridge in the retroperitoneum (Figure 14-1). Here, the germ cells develop into gonads, which then descend into the scrotum, forming the testes, or into the pelvis, forming the ovaries. If during the period of this migration, for some unknown reason, a disruption of the normal migration process occurs, the germ cells can linger at any point along their route, where a tumor can subsequently form. Germ cells can most often be found in areas such as the retroperitoneum, mediastinum, pineal region (pineal gland), and sacrococcygeal region. Less commonly, germ cells are retained in the vagina, bladder, liver, and nasopharynx.

Epidemiology

Germ cell tumors are an uncommon type of tumor lesion in children. They make up 3-8% of all malignant tumors of childhood and adolescence. Since these tumors can also be benign, their incidence is probably much higher. These tumors are two to three times more common among girls than boys. The mortality rate among girls is three times higher than among boys. After 14 years of age, mortality among males becomes higher, which is due to an increase in the incidence of testicular tumors in adolescent boys.

Histogenesis

Malignant germ cell tumors are very often associated with various genetic abnormalities, such as ataxia-telangiectasia, Klinefelter syndrome, etc. These tumors are often combined with other malignant tumors, such as neuroblastoma and hematological malignancies. Undescended testicles pose a risk for developing testicular tumors.

Often, germ cell tumors may contain cells of different germ cell lineages. Thus, teratomas may have a population of yolk sac cells or trophoblasts.

The morphological picture of germ cell tumors is very diverse. Germinomas consist of groups of large, uniform neoplastic cells with a swollen nucleus and clear cytoplasm. Tumors of the yolk sac have a very characteristic picture: a reticular stroma, often called lacy, in which there are rosettes of cells containing a-fetoprotein in the cytoplasm. Trophoblastic tumors produce human chorionic gonadotropin. Benign, well-differentiated teratomas often have a cystic structure and contain various tissue components, such as bone, cartilage, hair, and glandular structures.

Choriocarcinomas are rare but extremely malignant tumors that most often arise in the mediastinum and gonads. They can also be congenital.

Typical locations for dysgerminomas are the pineal region and the ovaries. Dysgerminomas account for approximately 20% of all ovarian tumors in girls and 60% of all intracranial germ cell tumors.

Embryonic carcinoma in its “pure form” is rarely found in childhood; most often, a combination of elements of embryonic cancer with other types of germ cell tumors, such as teratoma and yolk sac tumor, is recorded.

Clinical picture

Testicle.
Primary testicular tumors are rare in childhood. Most often they occur before the age of two years and 25% of them are diagnosed at birth. According to histological structure, these are most often either benign teratomas or tumors of the yolk sac. The second peak in the diagnosis of testicular tumors is the puberty period, when the frequency of malignant teratomas increases. Seminomas in children are extremely rare. Painless, rapidly increasing swelling of the testicle is most often noticed by the child's parents. 10% of testicular tumors are combined with hydrocele and other congenital anomalies, especially of the urinary tract. Upon examination, a dense, lumpy tumor is detected, with no signs of inflammation. An increase in alpha-fetoprotein levels before surgery confirms the diagnosis of a tumor containing elements of the yolk sac. Pain in the lumbar region may be symptoms of metastatic lesions of the para-aortic lymph nodes.

Ovaries.
Ovarian tumors often present with abdominal pain. Upon examination, you can detect tumor masses located in the pelvis, and often in the abdominal cavity, an increase in the volume of the abdomen due to ascites. These girls often develop fever (Figure 14-3).

Vagina.
These are almost always tumors of the yolk sac; all described cases occurred before the age of two years. These tumors usually present with vaginal bleeding or spotting. The tumor arises from the lateral or posterior walls of the vagina and has the appearance of polypoid masses, often pedunculated.

Sacrococcygeal region.
This is the third most common location of germ cell tumors. The incidence of these tumors is 1:40,000 newborns. In 75% of cases, the tumor is diagnosed before two months and is almost always a mature benign teratoma. Clinically, such patients have tumor formations in the perineum or buttocks. Most often these are very large tumors (Figure 14-4). In some cases, neoplasms have intra-abdominal spread and are diagnosed at an older age. In these cases, the histological picture is most often more malignant, often with elements of a yolk sac tumor. Progressive malignant tumors of the sacrococcygeal region often lead to dysuric symptoms, problems with bowel movements and urination, and neurological symptoms.

Mediastinum.
Mediastinal germ cell tumors in most cases are large tumors, but superior vena cava compression syndrome occurs rarely. The histological picture of the tumor is predominantly of mixed origin and has a teratoid component and tumor cells characteristic of a yolk sac tumor. Brain.
Germ cell tumors of the brain account for approximately 2-4% of intracranial neoplasms. In 75% of cases, they are observed in boys, with the exception of the area of the sella turcica, where tumors are favored to be localized in girls. Germinomas form large infiltrating tumors, which are often the source of ventricular and subarachnoid cerebrospinal metastases (see the chapter “CNS Tumors”). Diabetes insipidus may precede other tumor symptoms.

Diagnostics

The initial examination reveals the location of the primary tumor, the extent of spread of the tumor process and the presence of distant metastases.

Chest X-ray is a mandatory research method to establish a diagnosis in the case of primary mediastinal lesions, and is also indicated for identifying metastatic lesions of the lungs, which is very common.

Currently, CT has practically become the leading diagnostic method for any tumor location. Germ cell tumors are no exception. CT is extremely useful in the differential diagnosis of mediastinal lymphomas. This is the most sensitive method for detecting metastatic lesions of lung tissue, especially micrometastases. CT is indicated when ovarian lesions are detected. When the ovaries are involved, CT clearly demonstrates damage to the ovary itself, and also reveals the spread of the process to surrounding tissues. For sacrococcygeal tumors, CT helps determine the spread of the process to the soft tissues of the pelvis and reveals damage to bone structures, although traditional X-ray examination of the sacrum and coccyx is also very useful and more convenient for monitoring. X-ray examination with the introduction of a contrast agent is very often necessary to determine the position of the bladder, ureters, and rectum in relation to the tumor.

CT and MRI of the brain are necessary to identify germ cell tumors of the pineal gland.

Ultrasound is a very useful examination method for quickly and easily diagnosing the primary lesion and for monitoring the effect of treatment. Ultrasound is a more convenient method, since CT often requires anesthesia to conduct the study.
Tumor markers.

Germ cell tumors, especially those of extraembryonic origin, produce markers that can be detected by radioimmunoassay and are commonly used in monitoring to judge response to treatment.

Tumors with a trophoblastic component can produce HCG, while neoplasms with yolk sac elements can produce AFP derivatives. The largest amount of AFP is synthesized in the early fetal period of life and the highest level of AFP is determined at 12-14 weeks of the fetal period. The AFP content drops by birth, but its synthesis continues during the first year of life, progressively falling by 6-12 months. life. Blood levels of AFP and HCG should be determined before surgery and chemotherapy. After treatment (surgery and chemotherapy), in case of complete tumor removal or tumor regression after chemotherapy, their level drops, half after 24-36 hours for HCG and after 6-9 days for AFP. An insufficiently rapid drop in indicators is a sign of the activity of the tumor process or the insensitivity of the tumor to the therapy. Determination of glycoproteins in cerebrospinal fluid may be useful for diagnosing patients with CNS tumors.

Staging.

Staging of germ cell tumors presents significant difficulties due to the wide variety of tumor locations. Currently, there is no unified stage classification of germ cell tumors.

It should be noted that for intracranial germ cell tumors two features are of great importance: the size of the primary tumor and the involvement of central structures. For all other locations, the most important prognostic factor is the volume of the tumor lesion. This feature forms the basis for the currently most commonly used stage classification (Table 14-2).

Treatment.

Surgical method of treatment.

If you suspect an ovarian tumor, you should not limit yourself to a classic transverse gynecological incision. Midline laparotomy is recommended. When opening the abdominal cavity, the lymph nodes of the pelvis and retroperitoneal region are examined, the surface of the liver, the subphrenic space, the greater omentum and the stomach are examined.

If the testicle is affected, orchiectomy and high ligation of the spermatic cord are indicated. Retroperitoneal lymphadenectomy is performed only when indicated.

Radiation therapy

Medical therapy has very limited use in the treatment of germ cell tumors. It may be effective in the treatment of ovarian dysgerminoma.

Chemotherapy

Chemotherapy plays a leading role in the treatment of germ cell tumors. Many chemotherapy drugs are effective for this pathology. For a long time, polychemotherapy with three cytostatics was widely used: vincristine, actinomycin "D" and cyclophosphamide. However, recently, preference has been given to other drugs, on the one hand, new and more effective, on the other hand, having the least number of long-term consequences, and, first of all, reducing the risk of sterilization. The drugs most often used today for germ cell tumors are platinum (in particular, carboplatin), Vepezid and bleomycin.

Since the spectrum of germ cell tumors is extremely diverse, it is impossible to propose a single treatment regimen. Each location and histological variant of the tumor requires its own approach to treatment and a reasonable combination of surgical, radiation and chemotherapy methods

The most common germ cell tumor in boys under 5 years of age.

Testicular choriocarcinoma (chorionepithelioma) - a malignant tumor of the testicles from germ cells with extra-embryonic differentiation, the structure resembles a tumor arising from the placenta tissue of a pregnant woman. Consists of mononuclear cells with clear cytoplasm (resemble cytotrophoblast cells) and giant cells (resemble syncytiotrophoblast structures).

Macroscopically small painless compaction with foci of necrosis and hemorrhages on the incision. Larger choriocarcinomas are less common.

Microscopically syncytiotrophoblast is represented by giant cells of irregular shape with highly vacuolated cytoplasm. The cytotrophoblast is formed by polygonal cells with round hyperchromic nuclei and a small volume of cytoplasm. The tumor is extremely invasive, grows blood vessels, resulting in areas of hemorrhage. In some cases, hemorrhagic necrosis is so severe that it can be quite difficult to identify living tumor cells, and testicular choriocarcinoma is replaced by scar tissue. Testicular choricarcinoma, consisting only of cytotrophoblast and syncytiotrophoblast, is rare; more often the tumor is found as a component of mixed germ cell tumors.

Mixed germ cell tumors.

Almost half of testicular germ cell tumors consist of more than one type of transformed germ cells and are classified as mixed germ cell tumors. There are more than a dozen possible combinations of different types of tumor cells.

The most common are the following: 1) teratoma and embryonal cancer (teratocarcinoma); 2) teratoma, embryonal carcinoma and seminoma; 3) embryonal cancer and seminoma. Such combinations may contain
and yolk sac tumor components. Teratocarcinoma is detected in 20% of cases (more often than embryonal cancer) after the development of metastases.

In some cases, a painless testicular tumor is mistakenly diagnosed as epididymitis or orchitis. Sometimes the first symptoms of the disease are caused by metastases. Possible ureteral obstruction(manifestation of lesions of the para-aortic lymph nodes). You can also watch stomach ache or pulmonary symptoms caused by multiple metastatic nodes.

Tumor markers. The presence of characteristic products of tumor germ cells in the blood helps in the diagnosis, treatment and prognosis of the disease. The content of tumor markers in the blood decreases after orchiectomy (resection of the testicle) and increases again with re-growth of the tumor.

Metastasis. Tumor tissue from transformed germ cells grows into the appendage and metastasizes to regional lymph nodes and lungs. Choriocarcinoma, unlike other germ cell tumors, immediately disseminates hematogenously into the lungs. In order of decreasing frequency, metastases are found in the retroperitoneal lymph nodes, lungs, liver, and mediastinal lymph nodes. Distant metastases are usually detected in the first 2 years after diagnosis and surgical treatment. Metastases of nonseminoma germ cell tumors treated with chemotherapy after orchiectomy are represented by teratoma components.

Tumors from stromal cells and seminiferous tubules.

Primary tumor growth from Sertoli cells, Leydig cells and granulosa cells accounts for 5% of all testicular tumors. There are tumors from one type of cell or mixed - from Sertoli cells and Leydig cells.

T u m o r i s c l e t o c l e d i g a .

A rare neoplasm (about 2% of all testicular tumors), developing from interstitial Leydig cells. The disease is detected in boys over 4 years of age and in men from 30 to 60 years of age. Functionally active cells synthesize androgens and/or estrogens, the level of which in the blood may be increased. The activity of tumor cells in boys during the prepubertal period leads to premature physical and sexual development. In some cases, on the contrary, feminization and gynecomastia are found in men.

A rather dangerous disease is a tumor of the yolk sac. Children under three years of age are at particular risk. Much less often, the neoplasm appears in adults and develops together with other germ cell type tumors. This malignant neoplasm is localized in the testicles in men and ovaries in women. It can also spread to the epididymis or spermatic cord. In addition, in women, it is clinically characterized by enlargement of the ovary in a very short period of time, which can pose a serious threat to overall health.

What is a yolk sac tumor and why is it dangerous?

A tumor of the yolk sac, or as it is also called in medicine “tumor of the endodermal sinus,” is a malignant formation, gray or yellow-gray in color. It develops from particles of the yolk sac and has a soft, elastic consistency. It is the third most common among.

Its rapid growth poses a particular danger. Untimely diagnosed pathology develops over a short period and leads to the formation of cysts and degeneration of tumor areas. The development of such events leads to the death of the patient in the absence of timely treatment.

Exact causes of development and who is at risk

Due to a failure in the process of movement and retention of embryonic cells, active growth of the tumor begins. Risk factors for such developments are:

Chemicals and their effects on the fetus in the womb.
Genetic predisposition. Often the pathology accompanies Klinefelter syndrome (an extra X chromosome in boys). Boys whose fathers suffered from this phenomenon are more susceptible to developing cancer than others.
The testicles did not descend into the scrotum. The pathology in medicine is called cryptorchidism. The temperature in the peritoneum is higher than in the cavity into which these organs should descend. This contributes to the development of oncology.
Age 20-34 years. The neoplasm can occur at different age periods, but infancy and the above-mentioned age are in a special risk zone.
HIV infection.
Congenital pathologies of the testicles, kidneys or male reproductive organ.
Race and Ethics. Statistics show that white people are disproportionately affected by this type of cancer. But there is no scientific basis for this fact yet.

The exact causes of the disease have not yet been fully studied.

How to independently recognize a yolk sac tumor by its early signs?

Often such tumors are diagnosed after a complete examination of the patient. But a person is able to recognize the presence of a malignant tumor by the following signs:

torsion of the leg can create acute pain in the abdominal area, reminiscent of an exacerbation of appendicitis;
a painless volumetric roundness can be felt in the abdomen or pelvis;
Women may not have periods. In this case, pathology may develop against the background of gonadal dyskinesia. Doctors refer the patient for a karyotype study.

When analyzed, almost every patient has an increased level of AFP in the serum (a very important tumor marker).

What does an advanced clinical picture look like?

A tumor of the yolk sac poses a threat to human life. Metastases tend to grow and multiply very quickly, which often leads to the death of patients due to ignoring the disease or late diagnosis. The formation, in the absence of necessary treatment, can metastasize lymphogenously to the lymph nodes of the peritoneum, and hematogenously to other organs: liver, lungs and others. Such a development of events without the necessary treatment leads to irreversible consequences.

What is included in the diagnosis?

Most often, a neoplasm of this type is diagnosed at the age of 16-18 years. When a yolk sac tumor is detected, a number of diagnostic procedures are carried out, as with any other germ cell formation:

Anamnesis collection: examination and interview of the patient.
General analysis of urine and blood.
Ultrasound of the peritoneum.
Chest X-ray.
MRI of the affected area.
Electrocardiogram and echocardiogram.
Coagulogram and audiogram.
Biochemical blood test.
Boipsia.

If the lungs are suspected, an MRI of these organs and a separate EchoCG of the brain are performed.

A very important and indicative study is the determination of AFP in serum. Using the analysis, you can monitor the treatment process, its result, as well as identify metastases and the possibility of relapse. Doctors often use this method to determine the number of courses of chemotherapy required for a particular patient.

Non-surgical treatment and its feasibility

When a yolk sac tumor is diagnosed, surgery is immediately prescribed, since the formation is malignant and can actively spread, affecting other human organs.

Afterwards, for several years, monitoring is carried out using a chest x-ray and analysis of AFP levels. An increase in the latter indicator threatens a relapse of the pathology. In these cases, chemotherapy or radiation therapy is performed. Previously, doctors tried to treat patients with various medications, but the results did not live up to expectations. Until now, unfortunately, no miracle cure for such a malignant tumor has been invented.

What medications are used to treat yolk sac tumor?

In the past, treatment of the tumor was carried out through radiation therapy or taking an alkylating drug such as Methotrexate or Dactinomycin. But the result was not very positive: only 27% of patients managed to live at least another couple of years. Later, it was revealed that such a tumor was not sensitive to radiation, although the presence of positive dynamics at first may be confusing.

Chemotherapy, as mentioned above, is effective only after surgery. As a result of complete removal of stage 1-3 tumors, chemotherapy according to the VAC regimen for 6-9 courses in 78% of patients resulted in complete absence of signs of the disease. In the recent past, treatment was carried out with Bleomycin, Etoposide, and Cisplatin. Of the 21 people, 9 patients did not have the disease. Statistics noted by GOG experts.

Surgical treatment and its possible consequences

Surgical treatment is used at any stage of development of a yolk sac tumor. In medicine, the operation is called radical orchiectomy - complete removal of the organ down to the level of the deep inguinal ring. If there is pathology in the inguinal lymph nodes, they are also eliminated through a modified radical retroperitoneal lymphadenectomy.

After surgery, AFP levels return to normal after five days. Otherwise, incomplete removal of the formation or the presence of metastases is assumed. In most cases, surgery is successful. To consolidate the results, chemotherapy is often carried out according to an individually prescribed program for each person.

What happens if the yolk sac tumor is not treated and what are the consequences?

As a result of the fact that metastases radiate to the liver, kidneys and brain, it is unlikely to be able to avoid death in the absence of special treatment. Moreover, age and gender do not play any particular role. Therefore, it is very important to consult a doctor at the first signs of the disease and follow all recommendations, carry out all procedures and not refuse surgical treatment! The patient's life expectancy directly depends on this.

Prognosis and how long do such patients live?

In general, the prognosis at the first stage of pathology is favorable. When a malignant tumor is diagnosed at the first stage of its progression, treatment is successful in 95% of cases.

Children under 2 years of age have a greater chance of full recovery than people of other age categories. The reason for this is the combination of formation with other germ cell tumors in older people. With a disseminated process, survival rate is only 50%, even if surgery and chemotherapy are performed.

Diagnosing a tumor in the early stages is treated less aggressively. As a result, there are much fewer side effects.

Malignant yolk sac tumor It is quite rare and can be successfully cured, so do not despair. Seek help from good doctors. They will do everything possible to ensure that the patient continues to live a full life for a long time. If you ignore the disease, then the outcome can be disastrous.

Sacrococcygeal region - 42
Mediastinum - 7
Retroperitoneal space - 4
Testicle - 9
Ovary - 24
Pineal gland area - 6
Other areas - 6

This article discusses only extracranial germ cell tumors.

Histogenesis of germ cell tumors

Germ cell tumors develop from pluripotent germ cells. They arise in the endoderm of the yolk sac and normally migrate from there along the hindgut towards the urogenital ridge on the posterior abdominal wall, where they become part of the developing gonads. Depending on where they stop along the migration path, embryonic germ cells can give rise to tumor growth in one or another area along the midline of the body. Therefore, germ cell tumors are found in various parts of the body; they can have gonadal and extragonadal localizations.

Due to the fact that during embryogenesis, germ cells in the caudal part of the urogenital ridge persist for a longer time compared to the head, teratomas and teratoblastomas are more often found in the pelvic region, sacrococcygeal region, retroperitoneal space than in the mediastinum, neck and intracranial region.

Germ cell tumors originate from a plurilotent germ cell and can therefore consist of derivatives of all three germ layers. As a result, they may contain tissues that are not typical for the anatomical area in which the tumor occurs.

The type of tumor that develops depends on the route of migration and the degree of maturity of the ectopic cells.

Histological classification

Histologically, germ cell tumors are divided into germinomas and non-germ cell tumors. The latter include teratomas, yolk sac neoplasms, embryonal cancer, choriocarcinoma, and mixed germ cell tumors.

Germinomas are germ cell tumors that arise in extragonadal areas (pineal region, anterior mediastinum, retroperitoneal space). Neoplasms histologically identical to germinoma, but developing in the testicle, are called seminomas; in the ovaries, dysgerminomas.

Germ cell tumors are divided into secreting (alpha-fetoprotein, beta-chorionic gonadotropin) and non-secreting.

Teratomas are embryonic tumors containing tissues of all three germ layers: ectoderm, endoderm and mesoderm. They arise in the sacrococcygeal region, mediastinum, ovaries and are divided into mature teratomas (benign variant), immature teratomas (intermediate variant) and malignant tumors - teratoblastomas. Based on their structure, teratomas are divided into cystic and solid.
Neoplasms of the yolk sac (endodermal sinus) are extragonadal germ cell tumors that occur in the sacrococcygeal region in young children and in the ovaries in older children. Localization in the testicles is characterized by two age groups - in younger children and in adolescents. Foci of yolk sac tumor may be present in teratoblastomas. Yolk sac tumors are classified as highly malignant.
Embryonic cancer (embryonic carcinoma) can be found both in its pure form and as a component of teratoblastoma. Localized in the testicles and ovaries. Occurs more often in adolescence.

How do germ cell tumors manifest?

Germ cell tumors present in different ways. Their symptoms depend on the location of the tumor.

Sacrolumbar region - Deformation and enlargement of this area due to neoplasm.
Mediastinum - Respiratory disorders when the tumor reaches a large size.
Retroperitoneal space - Symptoms characteristic of this location.
Testicle - Enlargement of the testicle due to a dense tuberous formation.
Ovary - Palpable tumor of the abdominal cavity and small pelvis, with torsion of the tumor stalk - abdominal pain.
Pineal gland area - Focal and cerebral symptoms.

Sacrococcygeal teratomas are usually detected at birth and diagnosed without much difficulty. The manifestation of germ cell tumors of the testicles has two peaks of incidence: before 4 years of age (most cases) and in the period over 14-15 years. At the same time, the biology in early childhood and adolescence is different: in the younger age group, neoplasms of the yolk sac and mature teratomas are encountered, while in adolescents - teratoblastoma and seminoma. In contrast to the well-visualized localization in the testicle, other extracranial germ cell tumors (mediastinal, abdominal, pelvic) in children appear, as a rule, at stages III-IV of the process. Manifestation of ovarian dysgerminoma occurs in the prepubertal and pubertal periods (8-12 years). Germ cell tumors of the mediastinum are detected in early childhood and in adolescents. Moreover, at the age of 6 months to 4 years, they are represented by teratoblastomas, yolk sac tumors, and embryonal cancer. In adolescence, among germ cell tumors of the mediastinum, the germ cell type predominates.

Symptoms of metastatic lesions depend on the location and degree of development of the metastatic process and do not have specific signs compared to other malignant neoplasms. A tumor symptom complex can develop with teratoblastoma in the case of massive disintegrating neoplasms.

Classification (clinical staging)

The POG/CCSG study group uses separate postoperative staging systems for testicular, ovarian, and extragonadal germ cell neoplasms.

I. Testicular germ cell tumors.

Stage I - the tumor is limited to the testicle, completely removed as a result of a high inguinal or transscrotal orchofuniculectomy. There are no clinical, radiological or histological signs of the tumor spreading beyond the organ. The content of tumor markers studied taking into account the half-life (alpha-fetoprotein - 5 days, beta-hCG - 16 hours) was not increased. In patients with normal or unknown initial tumor marker values, the retroperitoneal lymph nodes are not affected.
Stage II - transscrotal orchiectomy was performed. The presence of a neoplasm in the scrotum or high in the spermatic cord (less than 5 cm from its proximal end) is determined microscopically. Retroperitoneal lymph nodes are affected by a tumor (size less than 2 cm) and/or increased values of tumor markers (taking into account half-life).
Stage III - neoplasm damage to the retroperitoneal lymph nodes (size more than 2 cm), but there is no tumor damage to the abdominal organs or tumor spread beyond the abdominal cavity.

II. Germ cell tumors of the ovaries.

Stage I - the tumor is limited to the ovary (ovaries), lavage water from the peritoneum does not contain malignant cells. There are no clinical, radiological or histological signs of tumor spread beyond the ovaries (the presence of peritoneal gliomatosis is not considered a basis for changing stage I to a higher stage). The content of tumor markers is not increased taking into account their half-life.
Stage II - tumor lesions of the lymph nodes are determined microscopically (size less than 2 cm), lavage water from the peritoneum does not contain malignant cells (the presence of peritoneal gliomatosis is not considered a reason to change stage II to a higher stage). The content of tumor markers is not increased taking into account their half-life.
Stage III - lymph nodes are affected by a tumor (size more than 2 cm). After the operation, a massive tumor remained or only a biopsy was performed. Tumor damage to adjacent organs (for example, omentum, intestines, bladder), lavage water from the peritoneum contains malignant cells. The content of neoplasm markers may be normal or elevated.
Stage IV - distant metastases, including the liver.

III. Extragonadal germ cell tumors.

Stage I - complete removal of the tumor at any localization; if localized in the sacrococcygeal region, the coccyx was removed, histologically resection was carried out within healthy tissue. The content of tumor markers is normal or increased (but decreases taking into account their half-life). Regional lymph nodes are not affected.
Stage II - malignant cells are microscopically determined along the resection line, the lymph nodes are not affected, the content of tumor markers is normal or increased.
Stage III - after the operation a massive tumor remains or only a biopsy is performed. Retroperitoneal lymph nodes may or may not be affected by the tumor. The content of tumor markers is normal or increased.
Stage IV - distant metastases, including the liver.

How are germ cell tumors recognized?

Diagnosis of the primary focus for germ cell tumors includes ultrasound and radiography. CT and/or MRI. Doppler ultrasound angioscanning. Diagnosis of possible metastases includes chest x-ray. Ultrasound of the abdominal cavity and regional areas, myelogram study. To exclude a neoplasm of a neurogenic nature when the tumor is localized in the mediastinum, retroperitoneum, or presacral region, the excretion of catecholamines and their metabolites should be examined.

Germ cell tumors of the sacrococcygeal region require identification (if present) of the presacral component of the tumor. This requires a rectal examination and careful assessment of ultrasound and X-ray CT or MRI data.

Germ cell tumors are different in that it is possible, before receiving a histological conclusion, to assess the degree of malignancy using the Abelev-Tatarin reaction - a study of the concentration of alpha-fetoprotein protein in the blood serum. This protein is normally synthesized by the cells of the yolk sac, liver and (in small quantities) the gastrointestinal tract of the fetus. The biological role of alpha-fetoprotein is that, penetrating through the placenta into the blood of a pregnant woman, it inhibits the immunological reaction of fetal rejection by the mother's body. The protein alpha-fetoprotein begins to be synthesized in the early stages of fetal development. Its content reaches its maximum at gestational age 12-14 nad, dropping to the adult level by the age of 6-12 months of postnatal life. Malignant germ cell tumors are capable of synthesizing α-fetoprotein, so the study of the Abelev-Tatarinov reaction allows one to assess the degree of malignancy of the neoplasm. In a child under 3 years of age with a severe condition that makes any surgical intervention undesirable, even a biopsy, a high titer of alpha-fetoprotein can serve as a basis for starting antitumor treatment without morphological verification of the diagnosis. When determining the dynamics of alpha-fetoproten content in blood serum, the half-life of this protein and the dependence of this indicator on age should be taken into account.

In the diagnosis of teratoblastoma and other germ cell tumors, other tumor markers - cancer embryonic antigen (CEA) - also play an important role. Beta-human chorionic gonadotropin (beta-hCG) and placental alkaline phosphate. An increase in the latter indicator is associated with the presence of syncytiotrophoblasts in the neoplasm tissue. The half-life of beta-hCG is 16 hours (in children under one year old - 24-36 hours).

In a minority of cases, teratoblastoma may progress without an increase in the content of alpha-fetoprotein and other tumor markers. On the other hand, an increase in alpha-fetoprotein levels does not necessarily indicate the presence of a germ cell tumor. This indicator also increases with malignant liver tumors.

Mandatory and additional studies in patients with suspected germ cell tumors

Mandatory diagnostic tests

Complete physical examination with assessment of local status
Clinical blood test
Clinical urine analysis
Biochemical blood test (electrolytes, total protein, liver function tests, creatinine, urea, lactate dehydrogenase, alkaline phosphatase, phosphorus-calcium metabolism)
Coagulogram
Ultrasound of the affected area
Ultrasound of the abdominal cavity and retroperitoneal space
CT (MRI) of the affected area
X-ray of the chest organs in five projections (direct, two lateral, two oblique)
Tumor marker research
Catecholamine excretion study
Two-point bone marrow puncture
EchoCG
Audiogram
In children over 3 years of age and with normal and questionable alpha-fetoprotein or beta-hCG values
The final stage is a biopsy of the tumor (or complete removal) to verify the cytological diagnosis. It is advisable to make impressions from the biopsy specimen for cytological examination

Additional diagnostic tests

If metastases to the lungs are suspected - RCT of the chest organs
If metastases are suspected in the brain - EchoEG and CT scan of the brain
Ultrasound color duplex angioscanning of the affected area

How are germ cell tumors treated?

Treatment of benign germ cell tumors is surgical, malignant - combined and complex. Radiation therapy and a course of chemotherapy using platinum, ifosfamide, and etoposide are used. For dysgerminomas, chemoradiotherapy is prescribed initially for unresectable tumors and after surgery - for postoperative stages II-IV. For other histological variants of malignant germ cell tumors (for example, yolk sac tumor, choriocarcinoma, embryonal cancer), treatment for all stages consists of surgery and postoperative chemotherapy.

When a resectable tumor is identified, the first stage of treatment is radical surgery. If the primary tumor is unresectable, biopsy should be used. Radical surgery is performed after neoadjuvant chemotherapy and the tumor has acquired signs of resectability. In cases where a neoplasm is detected in children under 3 years of age and surgery is undesirable even in the scope of a biopsy due to the severity of the patient’s condition, a high titer of alpha-fetoprotein or B-hCG serves as a basis for refusing diagnostic surgery and starting chemotherapy without morphological confirmation of the diagnosis.

Congenital teratoid tumor of the sacrococcygeal region should be removed as early as possible. It must be borne in mind that this neoplasm can have two components: sacrococcygeal, removed from the perineal approach, and presacral, removed from laparotomy. Thus, in such cases, surgery from a combined abdominal-perineal approach is necessary. An undetected and unremoved presacral component becomes a source of recurrent growth, while in the case of an initially benign variant of the neoplasm, it may become malignant with the development of a malignant relapse. Before the operation, to avoid injury to the rectum, a tube is inserted into it to control its position. It is imperative to resect the coccyx, and in case of widespread lesions, the sacrum. During surgery, the type of tumor (cystic, solid) should be taken into account. In the first case, opening the cystic cavities should be avoided.

Upon receipt of morphological data about the benign nature of the process after removal of the sacrococcygeal tumor, the tumor is regarded as a mature teratoma, and treatment is completed. The picture of malignancy in histological preparations becomes the basis for the diagnosis of teratoblastoma. which requires chemoradiation treatment. For immature teratomas, patients are left under observation after surgery; chemotherapy is administered only if a relapse of the tumor is diagnosed.

Ovarian germ cell tumors, like other neoplasms of the retroperitoneal space, are removed through laparotomy. A salpingo-oophorectomy with the tumor is performed. If the ovary is unilaterally affected, along with its removal, a biopsy of the opposite ovary should be performed. Also, when removing an ovarian tumor, it is necessary to resect the greater omentum (the latter, due to the mechanism of contact metastasis, can be affected by metastases) and perform a biopsy of the retroperitoneal lymph nodes. The presence of ascitic fluid is an indication for its cytological examination. Bilateral tumor lesion is an indication for removal of both ovaries.

A feature of ovarian teratomas is the possibility of seeding the peritoneum with tumor cells (the so-called peritoneal gliomatosis). Peritoneal gliomatosis can occur as a microscopic or macroscopic lesion. In cases of peritoneal gliomatosis, it is advisable to prescribe postoperative chemotherapy.

Mediastinal germ cell tumors

If the tumor is localized in the mediastinum, a thoracotomy is performed. In some cases, with variants of localization, sternotomy is possible.

Testicular germ cell tumors

In case of tumor lesions of the testicle, orchofuniculectomy is performed from the inguinal approach with high ligation of the spermatic cord. Removal or biopsy of retroperitoneal lymph nodes is carried out (from laparotomy access) as a second-look operation, after program chemotherapy according to indications.

If the pulmonary metastases present before the start of treatment persist on radiographs and computed tomograms and are considered resectable. their surgical removal is necessary.

What is the prognosis for germ cell tumors?

Before the use of effective chemotherapy, malignant extracranial germ cell tumors had an extremely unfavorable prognosis. When using chemotherapy, a 5-year survival rate of 60-90% was achieved. The prognosis depends on the histological variant, age, location and extent of the tumor, as well as on the initial level of tumor markers. For teratomas of the sacrococcygeal region, the prognosis is better in patients under 2 months of age. For mediastinal teratomas, the prognosis is better in patients under 15 years of age. Favorable histological germ cell tumors (terminomas, teratomas without foci of tumor tissue of unfavorable histological variants) compared with unfavorable ones (embryonic carcinoma, yolk sac tumor, choriocarcinoma) have a better prognosis. The prognosis is worse with higher levels of tumor markers before treatment compared with patients with lower levels.

Non-germinogenic tumors of the gonads

Non-germinogenic tumors of the gonads are rare in childhood; however, they are found in children. With this type of pathology, differential diagnosis with neoplasms such as germ cell tumors is necessary, as well as appropriate treatment.

Sertolioma (sustenocytoma, androblastoma) is usually benign. It is detected at any age, but more often in infant boys. Clinically, sertolioma manifests itself as a tumor formation of the testicle. The neoplasm consists of sutenocytes forming tubular structures.

Leydigoma (interstitial cell tumor) originates from glandulocytes. usually benign. Occurs in boys aged 4 to 9 years. As a result of hypersecretion of testosterone and some other hormones, affected boys begin premature sexual development. Histologically, the neoplasm is indistinguishable from ectopic adrenal cortex tissue. In both cases, an inguinal orchofuniculectomy is performed (as an option, orchiectomy from the scrotal access).

Benign ovarian cysts account for 50% of all ovarian tumors. Cysts can be detected by random ultrasound. as well as during laparotomy. performed for an “acute abdomen” with torsion or torsion of the cyst. For such patients, it is necessary to study tumor markers before and after surgery.

Other ovarian tumors are extremely rare. Granulosa cell tumors (thecomas) are benign neoplasms of stromal origin. The tumor is manifested by premature sexual development. Cystadenocarcinoma is distinguishable from other tumors only histologically. In isolated cases, the primary manifestation of malignant non-Hodgkin's lymphoma of the ovary has been described.

Gonadoblastomas are detected in patients with gonadal dysgenesis (true hermaphroditism). 80% of patients have a female phenotype with signs of virilization. The remaining 25% of patients have a male phenotype with signs of cryptorchidism, hypospadias and/or the presence of internal female genital organs (uterus, fallopian tubes or their rudiments). Histological examination reveals a combination of germ cells and elements of immature granulosa, Sertoli or Leydig cells. These neoplasms must be surgically removed along with the stroke gonads due to the high risk of malignancy of the latter. To establish the true gender of the patient, a cytogenetic karyotype study is performed.

It is important to know!

Germ cell tumors originate from pluripotent germ cells. Impaired differentiation of these cells leads to the development of embryonal carcinoma and teratoma (embryonic lineage of differentiation) or choriocarcinoma and yolk sac tumor (extraembryonic lineage of differentiation).