Germinogenic tumors

Germogenous tumors are tumors that develop from the primary embryonic cells of the human embryo, from which spermatozoa and oocytes normally form.

[1], [2], [3], [4], [5], [6], [7], [8],

Epidemiology

Germinogenic tumors are considered rare: they account for 3% of all registered malignant tumors of childhood. At the same time, at the first year of life, teratomas and teratoblastomas account for 20% of all newly recorded tumors. Their frequency is 1 case per 26 000-34 000 births. The second peak of morbidity is noted in adolescents aged 15-19 years.

Due to migration of germ cells, germ cell tumors develop not only in the gonads, but also in other organs and tissues of the fetus and child.

[9], [10], [11], [12], [13], [14], [15], [16]

The frequency of germinogenic tumors of various localizations

• The sacrococcygeal region - 42
• Sedation - 7
• The retroperitoneum space is 4
• Eggs - 9
• Ovary - 24
• Pineal area - 6
• Other areas - 6

In this article, only extracranial germinogenic tumors are considered.

Histogenesis of germ cell tumors

Germogenic tumors develop from pluripotent germ cell cells. They arise in the yolk sac endoderm and normally migrate from there along the hindgut towards the urogenital scallop on the posterior abdominal wall where they become part of the developing gonads. Depending on the place of stoppage on the migration path, embryonic germ cells can give rise to tumor growth in one area or another along the midline of the body. Therefore germinogenous tumors are found in various parts of the body, they can have gonadal and extra-localized localization.

Because embryonic cells in the caudal part of the urogenital crest persist longer in the process of embryogenesis than in the head, teratomas and teratoblastomas are more often found in the pelvic, sacrococcygeal, retroperitoneal regions than in the mediastinum, the neck and the intracranial region.

Germinogenic tumors originate from a plurilotent germinogenic cell, so they can consist of all three germinal leaf derivatives. As a consequence, they can contain tissues that are not typical of the anatomical zone in which the growth occurs.

The type of developing tumor depends on the path of migration and the degree of maturity of the ectopic cells.

Histological classification

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

• Germinoma - germinogenous tumors arising in extragonadal regions (pineal region, anterior mediastinum, retroperitoneal space). Neoplasm, histologically identical to germinome, but developing in the testicle, are called seminoma, in the ovaries - disgermin.

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

• Teratomas are embryonic tumors containing the tissues of all three embryonic leaves: 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. The structure of teratomas is divided into cystic and solid.
• Neoplasms of the yolk sac (endodermal sinus) are extragonadal germinogenic tumors that occur in young children in the sacrococcygeal region, and in older ones in the ovaries. Localization in the testicles is characterized by two age faces - in younger children and in adolescents. There may be focal points of the yolk sac tumor in teratoblastomas. Tumors of the yolk sac are classified as highly malignant.
• Embryonic carcinoma (embryonic carcinoma) can be found both in pure form and as a component of teratoblastoma. Localized in the testicles and ovaries. Occurs more often in adolescence.

How are germ cell tumors manifested?

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

• Sacrum and lumbar region - Deformation and enlargement of this area due to neoplasm.
• Sedation - Respiratory disorders when the tumor reaches a large size.
• The retroperitoneal space - Symptoms typical for a given localization.
• Eggs - Enlargement of the testis due to a dense, bumpy formation.
• Ovary - Palpable tumor of the abdominal cavity and small pelvis, with a twisting of the foot of the tumor - pain in the abdomen.
• Pineal region - Focal and general cerebral symptoms.

The sacrococcygeal teratomas are detected, as a rule, at birth and diagnosed without much difficulty. The manifestation of germic testicular tumors 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 young children and adolescents is different: in the younger age group there are new yolk sacs and mature teratomas, while in adolescents - terabloblast and seminoma. In contrast to the well-visualized localization in the testicle, other extracranial germinogenic tumors (mediastinal, abdominal, pelvic) in children appear, as a rule, in the III-IV stage of the process. The manifestation of the disgerminoma of the ovaries occurs in the prepubertal and puberty periods (8-12 years). Germogenic tumor of the mediastinum is revealed in the early period of childhood and in adolescents. At the age of 6 months to 4 years, they are teratoblastomas, yolk sac tumors, embryonic cancer. During adolescence, germinous type predominates among germinogenic mediastinal tumors.

Symptoms of metastatic lesions depend on the localization and degree of development of the metastatic process and do not have specific signs in comparison with other malignant neoplasms. Tumor symptom complex can develop with teratoblastome in the case of massive decaying neoplasms.

Classification (clinical staging)

The POG / CCSG research team uses separate postoperative staging systems for neoplasm of testicles, ovaries and extragonadal neoplasms of germinogenic nature.

I. Germinogenous testicular tumors.

• Stage I - the neoplasm is limited to the testicle, completely removed as a result of high inguinal or overhung oropharyngectomy. There are no clinical, radiological and histological signs of the spread of the tumor beyond the limits of the organ. The content of tumor markers studied with regard to half-life (alpha-fetoprotein-5 days, beta-hCG-16 hours), is not increased. In patients with normal or unknown initial values of oncomarkers, retroperitoneal lymph nodes are not affected.
• II stage - performed transkrtalny orchiectomy. Microscopically determine the presence of a neoplasm in the scrotum or high in the spermatic cord (less than 5 cm from its proximal end). The retroperitoneal lymph nodes are affected by a tumor (sizes less than 2 cm) and / or elevated values of the oncomarker content (taking into account the half-life).
• III stage - lesion of the neoplasm of retroperitoneal lymph nodes (the size is more than 2 cm), but there is no lesion by the tumor of the abdominal cavity organs and the spread of the tumor beyond the abdominal cavity.
• IV stage - distant metastases, including the liver.

II. Germinogenic tumors of the ovaries.

• I stage - the tumor is confined to the ovary (ovaries), lavage water from the peritoneum does not contain malignant cells. There are no clinical, radiologic or histological signs of the spread of the neoplasm beyond the ovaries (the presence of peritoneal gliomatosis is not considered the basis for a change in stage I to a higher one). The content of tumor markers is not increased in view of the time of their half-life.
• II stage - microscopically define a tumor lesion of lymph nodes (sizes less than 2 cm), lavage water from the peritoneum does not contain malignant cells (the presence of gliomatosis of the peritoneum is not considered the basis for changing the II stage to a higher one). The content of markers of the neoplasm is not increased in view of the time of their half-life.
• III stage - lymph nodes are affected by a tumor (the size is more than 2 cm). After surgery, a massive tumor or a biopsy was performed. Tumor lesions of adjacent organs (eg, epiploon, intestine, bladder), lavage water from the peritoneum contain malignant cells. The content of markers of the neoplasm may be normal or elevated.
• IV stage - distant metastases, including the liver.

III. Vnegonadnye germinogennye tumor.

• Stage I - complete removal of neoplasm with any of its localization, localization in the sacrococcygeal region carried out removal of the coccyx, histologically resected within healthy tissues. The content of tumor markers is normal or increased (but decreases with the time of their half-life). Regional lymph nodes are not affected.
• II stage - the malignant cells are microscopically determined by the line of resection, the lymph nodes are not affected, the contents of the tumor markers are normal or increased.
• III stage - after the operation there was a massive neoplasm or only a biopsy was performed. The retroperitoneal lymph nodes may be affected or not affected by the tumor. The content of tumor markers is normal or increased.
• IV stage - distant metastases, including the liver.

[17], [18]

How are germ cell tumors recognized?

Diagnosis of the primary focus in germinogenic tumors includes ultrasound, radiography. PCT and / or MRI. Ultrasound Doppler angioscanning. Diagnosis of possible metastases includes chest X-ray. Ultrasound of the abdominal cavity and regional zones, study of myelograms. To exclude the neoformation of a neurogenic nature in the localization of neoplasm in the mediastinum, retroperitoneal space, the prescalar region, the excretion of catecholamines and their metabolites should be investigated.

Germinogenic tumors of the sacrococcygeal region require detection (in case of its presence) of the presacral component of the neoplasm. This requires a rectal examination and careful evaluation of ultrasound and RVT or MRI data.

Germinogenic tumors differ in that it is possible before assessing the degree of malignancy with the help of the Abelev-Tatarin reaction - the study of the concentration of the alpha-fetoprotein protein in the blood serum. This protein normally synthesizes the cells of the yolk sac, the liver and (in a small number) the gastrointestinal tract of the fetus. The biological role of alpha-fetoprotein is that, by penetrating the placenta into the blood of a pregnant woman, it inhibits the immunological reaction of rejection of the fetus by the mother organism. Protein alpha-fetoprotein begins to be synthesized in the early stages of intrauterine development. Its maximum content reaches the period of pregnancy 12-14 above, descending to the level of an adult to the age of 6-12 months of postnatal life. Malignant germinogenic tumors are able to synthesize a-fetoprotein, so the study of Abelev-Tatarinov's reaction makes it possible to assess the degree of malignancy of the tumor. At the age of a child under 3 years with a severe condition, making any surgical intervention undesirable, even in the volume of a biopsy, a high titer of alpha-fetoprotein may serve as the basis for the beginning of antitumor treatment without morphological verification of the diagnosis. When determining the dynamics of the content of alpha-fetoproten in serum, the half-life of this protein and the dependence of this index on age should be taken into account.

In the diagnosis of teratoblastoma and other germ cell tumors, other cancer markers, the cancer embryonic antigen (CEA), play an important role. Beta-human chorionic gonadotropin (beta-hCG) and placental alkaline phosphatea. An increase in the latter is due to the presence of syncytiotrophoblast formation in the tissue. The half-life of beta-hCG is 16 hours (in children up to a year - 24-36 hours).

In a small part of cases, a teratoblastoma course is possible without increasing the content of alpha-fetoprotein and other oncomarkers. On the other hand, an increase in the content of alpha-fetoprotein does not necessarily indicate the presence of a germinogenic tumor. This indicator also increases in malignant neoplasms of the liver.

Mandatory and additional studies in patients with suspected germ cell tumors

Compulsory 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, phosphoric-calcium metabolism)
• Coagulogram
• Ultrasound of the affected area
• Ultrasound of the abdominal cavity and retroperitoneal space
• RCC (MRI) area of lesion
• Radiography of the chest cavity in five projections (straight, two side, two oblique)
• Research of oncomarkers
• Examination of catecholamine excretion
• Bone puncture from two points
• ECG
• Echocardiography
• Audiogram
• In children older than 3 years and with normal and questionable values of alpha-fetoprotein or beta-hCG
• The final stage is biopsy of the neoplasm (or complete removal) for the verification of the cytologic diagnosis. It is advisable to make prints from a biopsy for a cytological study

[19], [20], [21],

Additional diagnostic tests

• If there is a suspicion of lung metastasis - the chest wall of the thoracic cavity
• If there is a suspicion of a metastasis, and the brain - EchoEG and RKT of the brain
• Ultrasound color duplex angioscanning of the affected area

[22], [23], [24]

How are germinogenic tumors treated?

Treatment of benign germinogenic tumors - surgical, malignant - combined and complex. Apply radiation therapy and course chemotherapy with the use of drugs of platinum, ifosfamide, etoposide. With disgerminomas, chemoradiotherapy is administered initially in unresectable neoplasms and after surgery - in II-IV postoperative stages. In other histological variants of malignant germinogenic tumors (for example, yolk sac tumor, choriocarcinoma, embryonic cancer), treatment at all stages consists of a surgical operation and postoperative chemotherapy.

When a resectable neoplasm is identified, the first stage of treatment is performed by a radical operation. In the case of non-resectability of the primary tumor should be limited to biopsy. Radical surgery is performed after neoadjuvant chemotherapy and the acquisition of signs of resectability on its background. In cases of neoplasm in children under 3 years of age and undesirability of the operation, even in the volume of biopsy due to the severity of the patient's condition, a high titer of alpha-fetoprotein or B-hCG serves as a basis for abandoning the diagnostic operation and initiating chemotherapy without morphological confirmation of the diagnosis.

A congenital teratoid tumor of the sacrococcygeal region should be removed as early as possible. It should be borne in mind that this tumor can have two components: sacrococcygeal, removed from the crotch access, and presacral, removed from laparotomic access. Thus, in such cases, surgery is required from combined abdominal and perineal access. The unselected and unsuccessful presacral component becomes a source of recurrent growth, while in the case of an initially benign neoplasm it can be malignant with the development of a relapse of a malignant nature. Before the beginning of the operation, to avoid injury to the rectum to control its position, a tube is inserted into it. It is necessary to perform resection of the coccyx, and with widespread lesions - sacrum. During the operation, you should consider the variant of the tumor (cystic, solid). In the first case, it is necessary to avoid opening the cystic cavities.

When the morphological data on the benign nature of the process are obtained after the removal of the sacrococcygeal tumor, the tumor is regarded as a mature terato, and this treatment is terminated. The picture of malignancy in histological preparations becomes the basis to the diagnosis of teratoblastoma. Which requires chemoradiation treatment. In immature teratomas after surgery, patients are left under observation, chemotherapy is performed only in the diagnosis of tumor recurrence.

Ovarian germ cell tumors, like other neoplasms of the retroperitoneal space, are removed from laparotomic access. Salpingo-ovariectomy with a tumor is performed. With unilateral ovarian damage, along with its removal, a biopsy of the opposite ovary should be performed. Also, when ovarian tumor is removed, resection of the large omentum (the latter due to the mechanism of contact metastasis can be affected by metastases) and perform biopsy of retroperitoneal lymph nodes. The presence of ascites fluid is an indication to its cytological study. Bilateral tumor lesion is an indication for the removal of both ovaries.

A feature of ovarian teratomas is the possibility of colonization of the peritoneum with tumor cells (the so-called gliomatosis of the peritoneum). Glythomatosis of the peritoneum is possible in the form of a microscopic or macroscopic lesion. In cases of detection of gliomatosis of the peritoneum, the appointment of postoperative chemotherapy is advisable.

Germogenic tumor of the mediastinum

When the tumor is localized in the mediastinum, thoracotomy is performed. In some cases, with localization options, sternotomy is possible.

Germic Tumor Tumors

In case of a tumor lesion, the testicles are given an orhofunkulectomy from the inguinal access with a high bandage of the spermatic cord. Removal or biopsy of retroperitoneal lymph nodes is performed (from laparotomy access), as a second-look operation, after carrying out programmed chemotherapy according to indications.

If the pulmonary metastases that exist before the treatment start are preserved on radiographs and computer tomograms and are recognized as resectable. Their surgical removal is necessary.

What is the prognosis of germ cell tumors?

Malignant extracranial germ cell tumors before the use of effective chemotherapy had an extremely unfavorable prognosis. With the use of chemotherapy, a 5-year survival rate of 60-90% was achieved. The prognosis depends on the histological variant, age, localization and prevalence of the neoplasm, and also on the initial level of the tumor markers. For teratomas of the sacrococcygeal region, the prognosis is better in patients up to 2 months. With mediastinal ther- apy, 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 with unfavorable (embryonic carcinoma, yolk sac tumor, choriocarcinoma) have a better prognosis. The prognosis is worse with a higher level of oncomarkers before the start of treatment compared with patients with a lower level.

Non-germogenic tumors of sexual glands

Non-germogenic tumors of sexual glands in childhood are rare, nevertheless they are met in children. In this type of pathology, differential diagnostics with neoplasms such as germ cell tumors and appropriate treatment is necessary.

Sertiolioma (a sustenocytoma, an androblastoma) is usually benign. Identify at any age, but more often in young boys. Clinically, sertolioma is manifested by tumor formation of the testicle. The neoplasm consists of the stenocytes forming the tubular structures.

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

A benign ovarian cyst is 50% of all ovarian tumors. Cysts can be detected with occasional ultrasound. As well as with laparotomy. Performed on the "acute abdomen" with torsion or torsion cysts. Such patients are obliged to study oncomarkers before and after the operation.

Other ovarian tumors are extremely rare. Granulosceletal tumors (tecomas) are benign tumors that have a stromal origin. The tumor is manifested by premature sexual development. Cystadenocarcinoma is distinguishable from other tumors only histologically. In a few cases, a primary manifestation of non-Hodgkin's malignant ovarian lymphoma is described.

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