Embryonic tumor of the yolk sac. Choriocarcinoma, fetal carcinoma and other testicular tumors

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-old embryo. During embryonic development, the original germ cells migrate from the endoderm of the yolk sac to the genital ridge in the retroperitoneum (Figure 14-1). Here, the sex glands develop from the germ cells, which then descend into the scrotum, forming the testicles, or into the small pelvis, forming the ovaries. If during the period of this migration, for some unknown reason, a violation of the normal migration process occurs, the germ cells can linger at any place 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 often germ cells linger in the area of the vagina, bladder, liver, nasopharynx.

Epidemiology

Germ cell tumors are an uncommon type of neoplastic lesion in children. They make up 3-8% of all malignant tumors in childhood and adolescence. Since these tumors can also be benign, their frequency is probably much higher. These tumors are two to three times more common among girls than boys. Mortality among girls is three times higher than among boys. After 14 years, mortality among males becomes higher, 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's syndrome, etc. These tumors are often combined with other malignant tumors, such as neuroblastoma and hemoblastoses. Undescended testicles pose a risk for the development of 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 may be duplicated or lost. Multiple examples of germ cell tumors have been noted in siblings, twins, mothers and daughters.

Differentiation along the embryonic line gives 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 lineages of germ cell differentiation. Thus, teratomas may have a population of yolk sac cells or trophoblasts.

The frequency of each histological type of tumor 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 of age.

Factors causing malignant changes are unknown. Chronic diseases, long-term drug treatment during pregnancy of the mother may be associated with an increase in the incidence of germ cell tumors in children.

The morphological picture of germ cell tumors is very diverse. Germinomas consist of groups of large neoplastic cells of the same type with a swollen nucleus and light cytoplasm. Tumors of the yolk sac have a very characteristic picture: a mesh stroma, often called a lacy one, in which rosettes of cells containing a-fetoprotein in the cytoplasm are located. 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.

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 localization of the primary tumor: tumors of the yolk sac mainly 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 children (6-14 years old) tumors of the ovaries and pineal region.

Choriocarcinomas are rare but extremely malignant tumors that most commonly occur in the mediastinum and gonads. They may also be congenital.

For dysgerminomas, the typical localization is 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 rare in childhood, most often a combination of elements of embryonic cancer with other types of germ cell tumors, such as teratoma and tumor of the yolk sac, is recorded.

Clinical picture

The clinical picture of germ cell tumors is extremely diverse and, first of all, is determined by the localization 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 retroperitoneal space, mediastinum, vagina, bladder, stomach, liver, neck (nasopharynx) (Table 14-1).

Testicle.
Primary testicular tumors are rare in childhood. Most often they occur before the age of two years and 25% of them are diagnosed already at birth. According to the 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 pubertal period, when the frequency of malignant teratomas increases. Seminomas in children are extremely rare. Painless, rapidly increasing testicular swelling is most often noticed by the child's parents. 10% of testicular tumors are associated with hydrocele and other congenital anomalies, especially of the urinary tract. On examination, a dense, tuberous tumor is found, there are no signs of inflammation. An increase in the level of alpha-fetoprotein 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. On examination, one can detect tumor masses located in the small pelvis, and often in the abdominal cavity, an increase in the volume of the abdomen due to ascites. These girls often develop a fever (Figure 14-3).

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. Yolk sac tumors are also more common in puberty girls. Tumors are usually unilateral, large in size, therefore, rupture of the tumor capsule is a frequent occurrence. Clinical manifestations of malignant teratomas (teratocarcinomas, embryonic carcinomas) usually have a non-specific picture with the presence of tumor masses in the small pelvis, menstrual irregularities may be observed. Patients in the prepubertal period may develop a state of pseudopuberty (early puberty). Benign teratomas - usually cystic, can be detected at any age, often give a clinic of ovarian torsion, followed by rupture of the ovarian cyst and the development of diffuse granulomatous peritonitis.

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 originates from the lateral or posterior walls of the vagina and looks like polypoid masses, often pedunculated.

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

Mediastinum.
Germ cell tumors of the mediastinum in most cases represent a tumor of large size, but the syndrome of compression 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.
Germinogenic brain tumors 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 Turkish saddle, where tumors are favorably localized in girls. Germinomas form large infiltrating tumors, which are often the source of ventricular and subarachnoid cerebrospinal metastases. (See the chapter "Tumors of the CNS"). Diabetes insipidus may precede other symptoms of the tumor.

Diagnostics

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

Chest X-ray is an obligatory method of research, which allows to establish a diagnosis in case of primary mediastinal lesion, and is also indicated for the detection of metastatic lung disease, which is very common.

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

CT and MRI of the brain are needed to detect a germ cell tumor of the pineal gland.

Ultrasound is a very useful imaging modality for quick and easy diagnosis of a primary lesion and for monitoring the effect of treatment. Ultrasound is a more convenient method, since CT often requires anesthesia for 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, neoplasms with elements of the yolk sac are derivatives of AFP. 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 content of AFP falls 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 prior to surgery and chemotherapy. After treatment (surgery and CT), in the case of complete removal of the tumor or regression of the tumor after chemotherapy, their level drops, and by 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 the cerebrospinal fluid may be useful for the diagnosis of patients with a CNS tumor.

Staging.

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

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

Treatment.

Operative method of treatment.

If a germ cell tumor is suspected in the abdominal cavity or in the small 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 indications, for example, in case of torsion of the cyst stem or rupture of the tumor capsule.

If you suspect an ovarian tumor, you should not be limited to the classic transverse gynecological incision. A median laparotomy is recommended. When opening the abdominal cavity, the lymph nodes of the small pelvis and retroperitoneal region are examined, the surface of the liver, subdiaphragmatic space, greater omentum and 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 washed and the resulting lavage should be subjected to cytological examination.

If an ovarian tumor is detected, the tumor should be subjected to urgent histological examination, removal of the ovary only after confirmation of the malignant nature of the tumor. This practice avoids the removal of 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 localized in one ovary, removal of one ovary may be sufficient. If the second ovary is affected, if possible, part of the ovary should be preserved.

Recommendations when using the surgical method for ovarian lesions:
1. Do not use a transverse gynecological incision.
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 washing waters.
5. Examination and, if necessary, biopsy:
- lymph nodes of the small 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, should be removed immediately to avoid malignancy of the tumor. The operation must include the complete removal of the coccyx. This reduces the likelihood of recurrence of the disease. Malignant sacrococcygeal tumors should be treated first with chemotherapy, followed by surgery to remove the residual tumor.

Surgical intervention for the purpose of biopsy in case of a local tumor in the mediastinum and persistence of AFP is not always justified, as it is associated with risk. Therefore, it is recommended to perform preoperative chemotherapy and, after reducing the size of the tumor, surgical removal of it.

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 dysgerminomas.

Chemotherapy

The leading role in the treatment of germ cell tumors belongs to chemotherapy. Many chemotherapy drugs are effective in this pathology. For a long time, polychemotherapy with three cytostatics was widely used: vincristine, actinomycin "D" and cyclophosphamide. However, in recent years, 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 effects, and, first of all, reducing the risk of sterilization. Platinum preparations (in particular, carboplatin), vepezid and bleomycin are currently used most often for germ cell tumors.

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

In past treatment of yolk sac tumors did not inspire optimism. Kurman and Norris reported no long-term survival in 17 stage I patients who received additional RT or a single alkylating agent (dactinomycin or methotrexate). In 1979, Gallion presented a review of the literature, which indicated that only 27% of 96 patients with stage I disease survived 2 years. The tumor is insensitive to RT, although positive dynamics may be observed at the beginning of its implementation. Surgical treatment is considered optimal, but one operation is ineffective and leads to a cure extremely rarely.

In the past there have been optimistic reports of long-term remissions in some patients who received multicomponent chemotherapy (XT) after surgery. In their study, GOG used VAC chemotherapy (XT) to treat 24 patients with pure yolk sac tumors after total resection and 7 after partial resection. Of the total number of patients (31), 15 failed, including 11 (46%) of 24 cases with complete resection of the tumor.

15 patients with mixed germ cell neoplasms containing elements of a yolk sac tumor received chemotherapy (XT) according to the VAC scheme, in 8 (53%) it was ineffective. Subsequently, GOG experts conducted 6-9 cycles of chemotherapy (XT) according to the VAC regimen in 48 patients with completely resected stage I-III yolk sac tumors. At a median follow-up of 4 years, 35 (73%) patients had no signs of disease. Recently, 21 patients with similar tumors were treated with bleomycin, etoposide, and cisplatin (VER). The first 9 patients had no signs of the disease.

The patients received 3 courses VER-XT within 9 weeks. According to Gershenson et al., 18 (69%) of 26 patients with clear yolk sac tumors after VAC chemotherapy (XT) showed no signs of disease. Gallion et al. reported 17 (68%) of 25 patients with stage I disease who survived 2 years or more after VAC treatment. Sessa et al. treated 13 patients with yolk sac tumors, 12 of whom underwent unilateral oophorectomy. All received chemotherapy (XT) according to the VBP regimen and lived for 20 months. up to 6 years old. 3 patients were diagnosed with relapses, the treatment of which was completed successfully.

This experience is important because 9 patients were IIb or higher stage of the disease. Chemotherapy regimens (XT) are presented in the table below.

Schwartz et al. at stage I of the disease, the VAC regimen was used, and at stages II-IV, VBP was preferred. Of the 15 patients, 12 survived and showed no signs of illness. According to the authors, after the normalization of the AFP titer, at least one more course of chemotherapy (XT) is necessary. Now this provision has become the standard in many cancer centers. One relapse was successfully treated with the PEP regimen. In 2 cases of unsuccessful treatment of VAC, the VBP regimen also did not save the lives of patients. GOG experts analyzed the results of the VBP regimen in stage III and IV disease and in recurrent malignant germ cell tumors, in many cases with a known and measurable tumor volume after surgical treatment. For yolk sac tumors, long-term survival was observed in 16 (55%) of 29 patients.

Scheme VBP gave a significant number of persistent complete responses, even in patients after previous chemotherapy (XT). However, this scheme causes a large number of side effects. Although second-look laparotomy was included in this protocol, it was not performed in all patients (for various reasons). Smith et al. reported 3 cases of resistance to methotrexate, actinomycin D, and cyclophosphamide (MAC), as well as to the VBP regimen; complete responses have been documented in patients treated with regimens containing etoposide and cisplatin. All patients had no signs of the disease for 4 years or more. According to Williams, in disseminated germ cell tumors, primarily testicular, the BEP regimen was more effective with less neuromuscular toxicity than VBP.

Williams also reported on the GOG study of adjuvant postoperative (XT) BEP in 93 patients with malignant ovarian germ cell tumors: 42 had immature teratomas, 25 had yolk sac tumors, and 24 had mixed germ cell tumors. At the time of publication of the report, 91 of 93 patients were disease-free after 3 courses of XT on the BEP regimen with a median follow-up of 39 months. One patient after 22 months after treatment, acute myelomonocytic leukemia developed, the second after 69 months. diagnosed with lymphoma.

Dimopoulos reported similar findings from the Hellenic Cooperative Oncology Group. 40 patients with tumors that did not include dysgerminomas received treatment according to the BEP or VBP scheme. With a mean follow-up of 39 months. in 5 patients the disease progressed and they died, but only 1 of them received VER.

In Japan Fujita observed 41 cases of pure and mixed tumors of the yolk sac during a long period of observation (1965-1992); 21 patients underwent unilateral oophorectomy. More radical surgical interventions did not increase survival. Survival did not differ between VAC and VBP. All patients with stage 1 disease treated with VAC or PBV after surgery survived with no signs of relapse.

Definition in serum AFP- a valuable diagnostic tool for yolk sac tumors, it can be considered as an ideal tumor marker. AFP allows you to control the results of treatment, to detect metastases and relapses. As noted earlier, many researchers use AFP values as a criterion for determining the number of chemotherapy (XT) cycles required for a particular patient. In many cases, only 3 or 4 cycles of chemotherapy (XT) were needed to achieve long-term remission.

After organ-preserving operations and chemotherapy(XT) had a significant number of successful pregnancies. However, Curtin reported 2 patients with normal AFP levels but a positive second-look laparotomy, although these cases should now be considered exceptions. According to publications, relapses in the retroperitoneal lymph nodes can also occur in the absence of intraperitoneal metastases.

Germ cell tumors are typical neoplasms of childhood. Their source is the primary sex cell, i.e. these tumors are malformations of the primary germ cell. During the development of the embryo, germ cells migrate to the genital ridge, and if this process is disturbed, the germ cells can linger at any stage of their journey, and in the future there is a chance of tumor formation.

Tumors of this type account for up to 7% of all tumors in children and adolescents. 2-4% - in children under 15 years old and about 14% in adolescents from 15 to 19 years old. The probability of falling ill in adolescent boys under 20 is slightly higher than in girls - 12 cases versus 11.1 per million. According to some reports, the pathological course of pregnancy and smoking in the mother increase the risk of germ cell tumors in the child.

Germinogenic tumors are divided into gonadal, which develop inside the gonads, and extragonadal. There are two peaks in the incidence of germ cell tumors: the first - up to 2 years of tumors of the sacrococcygeal region (74% are girls) and the second - 8-12 years for girls and 11-14 years for boys with lesions of the gonads.

The most common symptoms of the disease are an increase in the size of the affected organ and pain. There may be complaints of difficulty urinating, intestinal obstruction, the appearance of clinical signs of compression of the mediastinal organs or CNS damage.

The most common localizations of germ cell tumors:

cross-coccygeal region;
ovary;
testicle;
epiphysis;
retroperitoneal space;
mediastinum.

Tumors are extremely diverse in their morphological structure, clinical course and prognosis, they can be both benign and malignant.

Morphological classification of germ cell tumors:

Dysgerminoma (seminoma);
Teratoma mature and immature;
Tumor of the yolk sac;
Choriocarcinoma;
Embryonic cancer;
germinoma;
Mixed germ cell tumor.

Diagnostics

If a child develops symptoms, we recommend a comprehensive diagnosis at the Oncology Research Institute. Depending on the indications, the doctor may prescribe the following tests and studies:

laboratory tests: complete blood count, general urinalysis, biochemical blood test, AFP, coagulogram;
instrumental studies: chest x-ray, abdominal ultrasound, ultrasound of the affected area, CT of the chest and abdomen, MRI of the affected area, osteoscintigraphy, myeloscintigraphy;
invasive examinations: puncture, bone marrow trepanbiopsy, lumbar puncture (according to indications); tumor biopsy.

Treatment

Treatment of children with germ cell tumors is to remove the tumor and conduct chemotherapy. The sequence of surgery and chemotherapy depends on the location of the tumor. As a rule, the defeat of the gonads dictates the removal of the tumor at the first stage with chemotherapy in the postoperative period. If a CT or MRI scan shows clear infiltration into the surrounding tissue or metastases, the first therapeutic step is chemotherapy.

Most extragonadal germ cell tumors are of considerable size, and their removal is accompanied by an increased risk of opening the tumor capsule. In these cases, patients are given chemotherapy to reduce the risk of tumor recurrence. Radiation therapy is rarely used and has limited indications.

Ideally, the goals of treatment are to achieve recovery and maintain menstrual and reproductive function in patients.

Forecast

Overall survival for germ cell tumors is:

at stage I 95%
at stage II - 80%
at stage III - 70%
at IV - 55%.

The prognosis for patients with germ cell tumors is affected by the histological structure, the level of tumor markers, and the prevalence of the process. Unfavorable factors are late diagnosis, large tumor size, tumor rupture, chemoresistance, and relapse of the disease.

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

In this article, only extracranial germ cell tumors are considered.

Histogenesis of germ cell tumors

Germ cell tumors develop from pluripotent germ cells. They originate in the endoderm of the yolk sac and normally migrate from there along the hindgut towards the urogenital crest on the posterior abdominal wall, where they become part of the developing gonads. Depending on the place of stopping on the way of migration, 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 in the process of embryogenesis the germ cells in the caudal part of the urogenital crest persist longer than in the head, teratomas and teratoblastomas are more common in the pelvic area, sacrococcygeal region, retroperitoneal space than in the mediastinum, in the neck and intracranial region.

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

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

Histological classification

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

Germinomas are germ cell tumors that occur in extragonadal areas (pineal region, anterior mediastinum, retroperitoneal space). A neoplasm, histologically identical to a germinoma, but developing in the testis, is called seminoma, in the ovaries - dysgerminoma.

Germinogenic 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 occur in the sacrococcygeal region, mediastinum, ovaries and are divided into mature teratomas (benign variant), immature teratomas (intermediate variant) and malignant tumors - teratoblastomas. According to the structure, teratomas are divided into cystic and solid.
Neoplasms of the yolk sac (endodermal sinus) - extragonadal germ cell tumors that occur in young children in the sacrococcygeal region, in older children - in the ovaries. For localization in the testicles, two age faces are characteristic - in younger children and in adolescents. There may be foci of a yolk sac tumor 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?

Germinogenic tumors manifest themselves in different ways. Their symptoms depend on the location of the neoplasm.

Sacro-lumbar region - Deformation and enlargement of this region due to neoplasm.
Mediastinum - Respiratory disorders when the tumor reaches a large size.
Retroperitoneal space - Symptoms characteristic of this localization.
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 pedicle of the tumor - pain in the abdomen.
Area of the pineal gland - 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 peak incidence: up to 4 years (most cases) and in the period older than 14-15 years. At the same time, biology in younger children and adolescents is different: in the younger age group, neoplasms of the yolk sac and mature teratomas are found, while in adolescents - teratoblastoma and seminomas. In contrast to the well visualized localization in the testis, other extracranial germ cell tumors (mediastinal, abdominal, small pelvis) in children appear, as a rule, at stage III-IV of the process. The 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. At the same time, at the age of 6 months to 4 years, they are represented by teratoblastomas, tumors of the yolk sac, embryonic cancer. In adolescence, the germinoma type predominates among germ cell tumors of the mediastinum.

Symptoms of a metastatic lesion 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 decaying neoplasms.

Classification (clinical staging)

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

I. Germinogenic tumors of the testis.

Stage I - the neoplasm is limited to the testicle, removed completely as a result of a high inguinal or transscrotal orchiofuniculectomy. There are no clinical, radiological and histological signs of the spread of the neoplasm outside 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 values of tumor markers, the retroperitoneal lymph nodes are not affected.
Stage II - performed transscrotal orchiectomy. Microscopically, the presence of a neoplasm in the scrotum or high in the spermatic cord (less than 5 cm from its proximal end) is determined. The retroperitoneal lymph nodes are affected by a tumor (less than 2 cm in size) and / or elevated levels of tumor markers (taking into account the half-life).
Stage III - defeat of the neoplasm of the retroperitoneal lymph nodes (sizes more than 2 cm), but there is no tumor damage to the abdominal organs and the spread of the tumor outside the abdominal cavity.

II. Germinogenic 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 the spread of the neoplasm beyond the ovaries (the presence of peritoneal gliomatosis is not considered a basis for changing stage I to a higher one). The content of tumor markers is not increased taking into account their half-life.
Stage II - a tumor lesion of the lymph nodes is microscopically determined (dimensions less than 2 cm), lavage water from the peritoneum does not contain malignant cells (the presence of peritoneal gliomatosis is not considered a basis for changing stage II to a higher one). The content of neoplasm markers is not increased taking into account their half-life.
Stage III - lymph nodes are affected by a tumor (sizes more than 2 cm). After the operation, a massive tumor remained or only a biopsy was performed. Tumor lesion of adjacent organs (for example, omentum, intestines, bladder), lavage water from the peritoneum contains malignant cells. The content of neoplasm markers can be normal or elevated.
Stage IV - distant metastases, including the liver.

III. Extragonadal germ cell tumors.

Stage I - complete removal of the neoplasm in any of its localization, with localization in the sacrococcygeal region, the coccyx was removed, histologically resection within healthy tissues. The content of tumor markers is normal or elevated (but decreases taking into account their half-life). Regional lymph nodes are not affected.
Stage II - microscopically determine malignant cells 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 neoplasm remained or only a biopsy was performed. Retroperitoneal lymph nodes may or may not be affected by the tumor. The content of tumor markers is normal or elevated.
Stage IV - distant metastases, including the liver.

How are germ cell tumors recognized?

Diagnosis of the primary focus in germ cell tumors includes ultrasound, radiography. CT and/or MRI. ultrasonic doppler angioscanning. Diagnosis of possible metastases includes chest x-ray. Ultrasound of the abdominal cavity and regional zones, myelogram examination. Excretion of catecholamines and their metabolites should be investigated to exclude neoplasms of a neurogenic nature in the localization of the neoplasm in the mediastinum, retroperitoneal space, presacral region.

Germinogenic tumors of the sacrococcygeal region require the identification (if any) of the presacral component of the neoplasm. This requires a rectal examination and a careful assessment of ultrasound and CT or MRI data.

Germinogenic tumors differ in that it is possible, before obtaining a histological conclusion, to assess the degree of malignancy using the Abeleva-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 a small amount) the gastrointestinal tract of the fetus. The biological role of alpha-fetoprotein is that, penetrating the placenta into the blood of a pregnant woman, it inhibits the immunological reaction of rejection of the fetus by the mother's body. Protein alpha-fetoprotein begins to be synthesized in the early stages of intrauterine development. Its maximum content becomes at a gestational age of 12-14 years above, dropping to the level of an adult by the age of 6-12 months of postnatal life. Malignant germ cell tumors are capable of synthesizing α-fetoprotein, therefore, the study of the Abelev-Tartarinov reaction makes it possible to assess the degree of malignancy of the neoplasm. In a child under 3 years of age, in a serious condition that makes any surgical intervention undesirable, even in the amount of 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 the content of alpha-fetoproten in the blood serum, one should take into account the half-life of this protein and the dependence of this indicator on age.

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

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

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 analysis of urine
Biochemical blood test (electrolytes, total protein, liver 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 cavity in five projections (direct, two lateral, two oblique)
Study of tumor markers
Excretion study of catecholamines
Bone marrow puncture from two points
echocardiography
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 neoplasm (or complete removal) to verify the cytological diagnosis. It is advisable to make prints from a biopsy for cytological examination

Additional diagnostic tests

If metastases to the lungs are suspected - CT scan of the chest cavity
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 - surgical, malignant - combined and complex. Apply radiation therapy and course chemotherapy using platinum drugs, ifosfamide, etoposide. With dysgerminomas, the appointment of chemoradiotherapy is performed initially for unresectable neoplasms and after surgery - at II-IV postoperative stages. For other histological variants of malignant germ cell tumors (eg, yolk sac tumor, choriocarcinoma, fetal cancer), treatment for all stages consists of surgery and postoperative chemotherapy.

If a resectable neoplasm is detected, the first stage of treatment is a radical operation. If the primary tumor is unresectable, a biopsy should be limited. Radical surgery is performed after neoadjuvant chemotherapy and the tumor acquires signs of resectability against its background. In cases of detection of a neoplasm in children under 3 years of age and the undesirability of surgery even in the amount of a biopsy due to the severity of the patient's condition, a high titer of alpha-fetoprotein or V-hCG serves as a basis for refusing a diagnostic operation 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 access, and presacral, removed from the laparotomy access. Thus, in such cases, surgery from a combined abdominoperineal 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, its malignancy with the development of a malignant recurrence is possible. Before starting the operation, in order 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 the operation, the variant of the tumor (cystic, solid) should be taken into account. In the first case, opening of cystic cavities should be avoided.

Upon receipt after removal of the sacrococcygeal tumor, morphological data on the benign nature of the process, the tumor is regarded as a mature teratoma, and the treatment is completed. The picture of malignancy in histological preparations becomes the basis for the diagnosis of teratoblastoma. requiring chemoradiotherapy. In immature teratomas after surgery, patients are left under observation, chemotherapy is carried out only in the diagnosis of recurrence of the neoplasm.

Ovarian germ cell tumors, like other neoplasms of the retroperitoneal space, are removed from the laparotomy access. A salpingo-oophorectomy with a tumor is performed. With a unilateral ovarian lesion, 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). Gliomatosis of the peritoneum is possible in the form of a microscopic or macroscopic lesion. In cases of detection of peritoneal gliomatosis, it is advisable to prescribe postoperative chemotherapy.

Germinogenic tumors of the mediastinum

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

Testicular germ cell tumors

With a tumor lesion of the testicle, an orchiofuniculectomy is performed from the inguinal access with a high ligation of the spermatic cord. Removal or biopsy of the retroperitoneal lymph nodes is performed (from laparotomy access) as a second-look operation after program chemotherapy according to indications.

If the pulmonary metastases that were present before the start of treatment persist on radiographs and computed tomograms and are recognized as resectable. they need to be surgically removed.

What is the prognosis for germ cell tumors?

Malignant extracranial germ cell tumors before the use of effective chemotherapy had an extremely unfavorable prognosis. With chemotherapy, a 5-year survival rate of 60-90% has been achieved. The prognosis depends on the histological variant, age, localization and prevalence of the neoplasm, as well as on the initial level of tumor markers. With teratomas of the sacrococcygeal region, the prognosis is better in patients up to 2 months. With mediastinal teratomas, the prognosis is better in patients under 15 years of age. Favorable histological germ cell tumors (terminomas, teratomas without tumor tissue foci of unfavorable histological variants) compared to 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 in childhood are rare, however, they are found in children. With this type of pathology, differential diagnosis with such neoplasms as germ cell tumors, as well as appropriate treatment, is necessary.

Sertolioma (sustenocytoma, androblastoma) is usually benign. It occurs at any age but is more common in infants. Clinically, sertolioma is manifested by a tumor formation of the testicle. The neoplasm consists of sustenocytes forming tubular structures.

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

Benign ovarian cyst accounts for 50% of all ovarian tumors. Cysts can be detected by accidental ultrasound. as well as laparotomy. performed for "acute abdomen" with torsion or torsion of the cyst. Such patients are required 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 non-Hodgkin's malignant ovarian lymphoma 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 vestiges). Histological examination reveals a combination of germ cells and elements of immature granulosa, Sertoli or Leydig cells. These neoplasms must be removed surgically along with stroke gonads due to the high risk of malignancy of the latter. To establish the true gender of the patient, a cytogenetic study of the karyotype is performed.

It is important to know!

Germ cell tumors originate from pluripotent germ cells. Violation of the differentiation of these cells leads to the emergence of embryonic carcinoma and teratoma (embryonic line of differentiation) or choriocarcinoma and tumor of the yolk sac (extraembryonic differentiation pathway).

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-old embryo. During embryonic development, the original germ cells migrate from the endoderm of the yolk sac to the genital ridge in the retroperitoneum. Here, the sex glands develop from the germ cells, which then descend into the scrotum, forming the testicles, or into the small pelvis, forming the ovaries. If during the period of this migration, for some unknown reason, a violation of the normal migration process occurs, the germ cells can linger at any place 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 often germ cells linger in the area of the vagina, bladder, liver, nasopharynx.

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

Symptoms:

Testicle.
Primary testicular tumors are rare in childhood. Most often they occur before the age of two years and 25% of them are diagnosed already at birth. According to the 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 pubertal period, when the frequency of malignant teratomas increases. Seminomas in children are extremely rare. Painless, rapidly increasing testicular swelling is most often noticed by the child's parents. 10% of testicular tumors are associated with hydrocele and other congenital anomalies, especially of the urinary tract. On examination, a dense, tuberous tumor is found, there are no signs of inflammation. An increase in the level of alpha-fetoprotein 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. On examination, it is possible to detect tumor masses located in the small pelvis, and often in the abdominal cavity, an increase in the volume of the abdomen due to. These girls often have a fever.

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 originates from the lateral or posterior walls of the vagina and looks like polypoid masses, often pedunculated.

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

Mediastinum.
Germinogenous in most cases represent a tumor of large size, however, the syndrome of compression 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.
Germinogenic brain tumors 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 Turkish saddle, where tumors are favorably localized in girls. Germinomas form large infiltrating tumors, which are often the source of ventricular and subarachnoid cerebrospinal metastases. may precede other symptoms of the tumor.

Causes of occurrence:

Malignant germ cell tumors are very often associated with various genetic abnormalities, such as -telangiectasia, Klinefelter's syndrome, etc. These tumors are often combined with other malignant tumors, such as hemoblastoses. Undescended testicles pose a risk for the development of testicular tumors.

Often, germ cell tumors may contain cells of different lineages of germ cell differentiation. 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 neoplastic cells of the same type with a swollen nucleus and light cytoplasm. Tumors of the yolk sac have a very characteristic picture: a mesh stroma, often called a lacy one, in which rosettes of cells containing a-fetoprotein in the cytoplasm are located. produce 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 commonly occur in the mediastinum and gonads. They may also be congenital.

Embryonic carcinoma in its "pure form" is rare in childhood, most often a combination of elements of embryonic with other types of germ cell tumors, such as teratoma and tumor of the yolk sac, is recorded.

Treatment:

For treatment appoint:

If you suspect an ovarian tumor, you should not be limited to the classic transverse gynecological incision. Medium is recommended. When opening the abdominal cavity, the lymph nodes of the small pelvis and retroperitoneal region are examined, the surface of the liver, subdiaphragmatic space, greater omentum and 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.
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Medical therapy has very limited use in the treatment of germ cell tumors. It may be effective in the treatment of ovarian dysgerminomas.

Chemotherapy.
The leading role in the treatment of germ cell tumors belongs to chemotherapy. Many chemotherapy drugs are effective in this pathology. For a long time it was widely used by three cytostatics: vincristine, actinomycin "D" and cyclophosphamide. However, in recent years, 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 effects, and, first of all, reducing the risk of sterilization. Platinum preparations (in particular, carboplatin), vepezid and bleomycin are currently used most often for germ cell tumors.