Trophoblastic tumor

Introduction to trophoblastic tumor A trophoblastic tumor, also known as "trophoblastic disease", is a tumor formed by the malignant transformation of the embryonic trophoblasts. It was first divided into two types, one benign "hydatidiformmole" and the other malignant called "chorioepithelioma". The chorionic gonadotropin (HCG) produced by trophoblast cells is an ideal tumor marker for trophoblastic tumors, and has special significance for the diagnosis and treatment of such tumors. To prevent malignant transformation after hydatidiform mole, the key now is to do a good job of follow-up work, because early detection, early diagnosis and early treatment can still reduce the harm caused by malignant transformation. basic knowledge The proportion of illness: 0.001% Susceptible people: women Mode of infection: non-infectious Complications: peritonitis sepsis pulmonary embolism nephrotic syndrome splenomegaly

Trophoblastic tumor cause

Malnutrition factors (15%):

The lack of folic acid in experimental animals can cause embryonic death. It is speculated that the lack of folic acid in the mother may be related to the occurrence of trophoblastic tumors, especially during embryonic angiogenesis (13-21 days after conception), such as lack of folic acid and histidine in nutrients. It affects the synthesis of thymine, which leads to the lack of blood vessels in the placental villi and embryonic necrosis. The basic pathological changes of the villi of the hydatidiform mole also conform to this point. From the geographical distribution of the hydatidiform mole, the hydatidiform mole and trophoblastic tumor are high in rice and vegetables. Among the residents of the staple food, because the food is cooked for too long, destroying and losing a lot of protein, vitamins and folic acid, foreign scholars have also confirmed that the serum folic acid activity of patients with trophoblastic disease is very low, and there are also reports of urea in the fetus, creatinine concentration is more obvious than the control group. Elevated, plasma albumin and total protein were significantly reduced, and the above findings were thought to be caused by improper diet and abnormal catabolism.

Viral infection (10%):

It has been reported that hydatidiform moles are associated with viral infections. In the 1950s, Ruyck reported that a filter virus was isolated from hydatidiform moles and choriocarcinoma tissues, called "pro-flocked virus", and that the virus is responsible for nourishment. The cause of cell tumors, but for more than 30 years, no one has confirmed the existence of this virus. In the 1960s, the authors examined the trophoblastic tumor specimens by electron microscopy and saw some inclusion bodies in the cytoplasm, similar to experimental leukemia. The virus particles that were seen, therefore suggesting that trophoblastic tumors are induced by viral viruses, but there are also objections.

Endocrine disorders (5%):

According to the WHO comprehensive report, the incidence of hydatidiform mole in the 15-20 year old group is higher than that in the 20-35 age group, and the risk of developing the disease over 40 years old is increased. The risk of occurrence of hydatidiform mole after pregnancy over 50 years old will be 20 to 35 years old. 200 times, this period is characterized by ovarian function is not completely stable or has gradually declined, so it is associated with whether trophoblastic tumor is closely related to ovarian endocrine function, whether ovarian dysfunction is related to the abnormal egg production, animal experiments prove that pregnancy Early ovariectomy can cause vesicular degeneration of the placenta. Therefore, it is considered that estrogen deficiency may be one of the causes of hydatidiform mole. Clinically, women who have stopped taking oral contraceptives, if they are aborted after a short period of pregnancy, often It can be seen that the villi have vesicular degeneration, suggesting that villus degeneration is associated with ovarian endocrine imbalance.

Racial factors (2%):

Hydatidiform moles are more common in Asian countries, especially in Southeast Asia. Some people think that it may be related to race, but ethnic issues are related to environment, climate, eating habits, water, infectious diseases, animal media and other factors. The incidence of trophoblastic diseases, Orientals (including Japan, China, the Philippines) accounted for 49% of the residents of the area, but accounted for 72% of the number of trophoblastic tumors in the region, while the population of 30% of the population, the incidence At 14%, Hawaiians make up less than 20% of the population, accounting for 9% of the disease.

Cytogenetic abnormal factors (3%):

The cytogenetic study of hydatidiform mole has accumulated a large amount of data, which has important clinical value and theoretical significance for exploring its occurrence. For chromatin and chromosome research, it is found that most of the trophoblasts of hydatidiform mole are positive for chromatin. Chromatin appears in the trophoblasts of day 11 of human embryos and can exist in human life. It shows one of two sex chromosomes in human female mesenchymal cells, which can be stained during division, so at low magnification microscope It can be seen that in 1957, Park-positive chromatin was dominant, and most of the moles were shown as female. Later, many authors have confirmed that although the proportion of positive and negative is different, they are always positive for chromatin. Advantage.

Immunity factor (5%):

Regarding HLA: For pregnant women, the placenta is an unrejected allograft. Embryo and gestational trophoblastic tumors are partly derived from the parental component. Therefore, in theory, it grows in the mother, just like allogeneic transplantation. It causes the immune rejection of the mother, and the embryo is not repelled. The outer layer of the villi has a buffer substance that prevents the graft antigen from entering the mother and thus does not cause the mother lymphocyte reaction. It is known that the normal placenta has lymphocyte antigen (HLA). That is, the cells contained in the intact placenta may all exhibit HLA antigen. As for whether the trophoblast cells express HLA, the opinions are still inconsistent. I do not know which one of the fetal lymphocytes in the trophoblast, villus interstitial cells or interstitial blood vessels, The hydatidiform mole contains specific antibodies against the paternal HLA antigen. Since the villi of the hydatidiform mole lacks interstitial blood vessels, the fetal lymphocytes cause the formation of anti-HLA antibodies, but the villus interstitial can be destroyed directly by the placenta. Contact, it is still possible to cause antibody production, so it is still impossible to conclude whether it is a mole Cultured mesenchymal cells Or immunogenic in the matrix.

Pathogenesis

1. Normal villus and trophoblast trophoblasts come from the trophoblast outside the embryo. The trophoblast cells grow rapidly, forming many hairy protrusions on the surface of the embryo sac, called "villi".

The trophoblast begins with only one layer of flat cuboid cells. When the villi are formed, this layer of cells gradually differentiates into two layers. The inner layer and the interstitial contact, formerly known as "Lang Hansi cells", is now called "cytotrophoblast". ", the outer layer and the uterine decidual membrane contact, formerly known as "synthesis cells", is now called "syncytiotrophoblast".

It is further understood that normal trophoblast cells have certain unique biological characteristics that are closer to malignant tumors than normal tissues. The trophoblasts eccentrically invade the endometrium, myometrium and spiral arteries from the part surrounding the embryo sac. Establish a utero placental circulation, trophoblast cells due to invasion of blood vessels, widely spread throughout the normal pregnancy in the blood, mainly to the lungs, disappeared after delivery.

The trophoblast cells covered by chorionic villus are called "flour trophoblasts". The trophoblasts in other parts of the uterus are called "extravital trophoblasts". The extravillous trophoblast cells form a trophoblast cell column, which traverses the villus gap from the base of the villus anchor; Infiltration envelops the basal aponeurosis of the blastocyst, forming a trophoblastic cell shell, which partially evolves into a smooth villus epithelial layer; a spiral artery that invades the placental bed; and an infiltrating muscle layer under the implanted site.

The trophoblast cells are composed of heterogeneous cell populations, and there are three distinct types in morphology:

1 cell trophoblast (CT);

2 syncytiotrophoblasts (ST);

3 intermediate type trophoblasts (IT).

Cytotrophoblasts (CT) consist of uniform, polygonal to ovoid epithelial cells with a single, rounded nucleus, few cytoplasm, transparent or granular, clear cell boundaries, and active nuclear division.

The syncytiotrophoblast (ST) consists of multinucleated, cytoplasmic, double-stained or eosinophilic cells containing vacuoles of varying sizes during the first two weeks of pregnancy, some of which form lacuna, and the syncytiotrophoblasts lack nuclear division. Because it is the most differentiated type of nourishing cells.

Most of the intermediate trophoblasts (IT) are composed of mononuclear cells, which are larger than the cytotrophoblasts, but polynuclear cells are also visible. The intermediate trophoblasts are round or polygonal, and can be fusiform outside the villi, and the cytoplasm is clear. Rich, double-stained or eosinophilic, the nucleus is round and leafy, oval, irregular chromatin distribution, nuclear division is rare, intermediate trophoblasts and cytotrophoblasts, syncytiotrophoblasts have some common characteristics, but in Light microscopy, ultrastructure, biochemistry and functional characteristics are distinct from cytotrophoblasts and syncytiotrophoblasts.

The villus trophoblast is mainly a cytotrophoblast and a syncytiotrophoblast. The intermediate trophoblast is an independent trophoblast cell type that covers the morphological and functional characteristics of the above two cells, and is a major component of the extravillous trophoblast.

The three trophoblasts have different light microscopy, ultrastructural and immunohistochemical features.

When the villi are formed, another cell that is freed in the embryo sac, called "extraembryonic mesoderm", also rapidly develops into the villi, forming the mid-axis or interstitial of the villi, thereby producing tissues such as blood vessels in the villi.

The pathological examination of the villus section showed that the outer layer of the villi was unclear between the trophoblast cells, containing multiple nuclei, the nuclear chromosome was thick and deep, the cytoplasmic eosinophilic was strong, and it was pink-purple-brown, and the inner cell trophoblastic nucleus was present. Round or oval, fine chromatin, clear cell boundaries, thick and transparent cytoplasm, weak basophilic, fusiform or astrocyte in the interstitial space of villi scattered in some sticky substances (called Wharton colloid) In the middle, some cell-like, nucleated vacuoles of round cells, called "Hofbour cells", which are phagocytic cells, whose function is still unclear, may be related to immunity or endocrine. Related, small blood vessels can also be seen in the villus interstitial, and there are nucleated red blood cells in the fetal blood in the lumen. Between the villi and the villi, a cluster of trophoblast cells can be seen, which is called "trophoblastic cell mass".

There are three main functions of syncytiotrophoblasts:

1 is to absorb nutrients from the mother body and discharge the waste to the mother;

2 is to select, degrade or synthesize the absorbed material to meet the needs of the embryo;

3 can produce a variety of glycoprotein hormones and sex hormones, cell trophoblasts do not have such functions, it is generally considered to be the stem cells that produce syncytiotrophoblasts, the cell trophoblasts divide many times, but the daughter cells do not separate to form a syncytiotrophoblast Nuclear fission is often seen in cytotrophoblasts.

In the past, only cytotrophoblasts were considered to be potentially malignant. Now, understanding the syncytiotrophoblasts is also very erosive. When pregnant eggs enter the decidua, it is often seen that the syncytiotrophoblasts are at the forefront, and the cell bodies become narrow and long, and they are squeezed into the intimal cells. And can phagocytose other cells or tissue fragments.

2. Gestational trophoblastic disease histological classification WHO's scientific group on gestational trophoblastic diseases and the International Society of Obstetrics and Gynecologists have revised the classification table (the terminology in parentheses is the previous name, which has been deprecated):

Hydatidiform mole (bubble block): complete hydatidiform mole; partial hydatidiform mole (transitional mole)

Aggressive hydatidiform mole (destructive choriocarcinoma)

Choriocarcinoma (chorionic epithelial cancer)

Placental site trophoblastic tumor (trophoblastic pseudotumor)

Epithelioid trophoblastic tumor

Mixed trophoblastic disease

Exaggerated placental site

Placental site nodule and plague

Unclassified trophoblastic disease

(1) Pathology of hydatidiform mole: hydatidiform mole is a benign villus lesion, confined to the uterus. It is characterized by edema changes in the villi, and each branch of the villus becomes a small blisters with fluffy hairs connected to each other. For example, immature grapes, hence the name, also known as blister-like blocks, the size of the blisters is small, small as rice grains, large diameter of 1 ~ 2cm.

Hydatidiform mole can be divided into complete hydatidiform mole and partial hydatidiform mole. Complete hydatidiform mole is all placental villi degeneration, swelling is grape-like without normal villi, no embryo, umbilical cord, amniotic membrane and other fetal appendages; partial hydatidiform mole Part of the placenta is degenerated, the swelling is grape-like, the diameter is generally less than 5mm, even up to 20mm, sometimes the pregnancy can last until the middle, some of the normal villi are visible, may be accompanied by embryos or fetus, umbilical cord and / or amniotic membrane.

The microscopic characteristics of hydatidiform mole are: interstitial edema and swelling; interstitial blood vessels are sparse or disappear; trophoblast cells have different degrees of hyperplasia, and proliferating trophoblasts are all type 3 trophoblasts (cytotrophoblasts, syncytiotrophoblasts, Intermediate trophoblasts, composed in different proportions, atypical manifestations of trophoblasts are nuclear enlargement, pleomorphism and chromatin too deep.

According to the degree of trophoblastic proliferation and differentiation, the moles are divided into 3 levels:

1 trophoblastic mild hyperplasia (including no hyperplasia): Most of the villi are covered with thin layer of trophoblast cells, often two layers. When degraded, only one layer of syncytial cells remains. The cytotrophoblasts disappear or remain small, and a few nourishing cell clusters are seen between the villi. , no poor differentiation or poorly differentiated, slightly enlarged nucleus, slightly darker chromatin.

2 trophoblasts moderately proliferating villus interstitial trophoblast cell clusters, large areas of hypertrophic trophoblast cell clusters (more than 20 layers), with mild or moderately poor differentiation, larger nuclei, deeper chromatin, nuclear atypia Obviously, nuclear division is visible.

3 trophoblasts are highly proliferating, and the area of hypertrophic trophoblasts often exceeds the entire area of the villi. The cells are lightly and highly differentiated, with abnormal nucleus or tumor giant cells, and nucleoli are obvious, and nuclear division is easier to find.

In histopathology, the most important of both complete and partial hydatidiform moles is the functional circulation of partial hydatidiform villi. The main evidence is that there are red blood cells in the villi, and the proportion of nucleated red blood cells is the same as normal. The distinction.

Regarding the degree of cell trophoblast and syncytiotrophoblast proliferation in hydatidiform mole, the relationship between the proportion of the two cells and malignant transformation, the relationship between the size of the blisters and the relationship between malignant transformation, etc., the Beijing Union Medical College Hospital conducted a special study. It is difficult to see the degree of cell proliferation and differentiation through pathological section and follow-up results. There is a relationship between the two kinds of cells and the malignant transformation. The proportion of the two cells is not related to the malignant transformation; the vesicle vesicles may be beginning to have edema and degeneration, the trophoblastic hyperplasia is strong, and it is easy to invade the sinus of the uterine wall, so the chance of malignant transformation is higher.

Another pathological change of hydatidiform mole is ovarian luteinized cyst, which is a long-term stimulation of a large number of chorionic gonadotropin (HCG), which causes granulosa cells and ovarian follicular cells to undergo flavination. The ovarian luteinized cyst is often bilateral. Small cysts can only be seen under the microscope, while large ones have large or larger heads, smooth appearance, multi-atrial, thin wall, and can gradually shrink after the discharge of hydatidiform moles (sometimes temporarily increased). 2 to 3 months gradually return to normal, but there are also those that last for half a year or longer. The cystic fluid of the luteinized cyst is often pale yellow, and a large amount of HCG is stored, so that the blood or urine HCG often does not turn immediately after the hydatidiform mole is discharged. Yin, cysts are also prone to torsional rupture, stimulating the peritoneum to produce symptoms and ascites.

Immediately after the hydatidiform mole is removed, the uterus is removed. In the pathological section, scattered corpus callosum in the decidua and superficial muscle layer are often seen, and mixed with different amounts of inflammatory cells. This condition is also seen in normal uterus sections after normal delivery and abortion. It is generally believed that this is not a malignant manifestation. It is a reaction of the placenta. It is called "syncytial endometritis", but it must be sliced. It is true that no trophoblastic cells can erode the deep muscles. It is distinguished from trophoblastic tumors in the placenta.

Partial hydatidiform mole is different from complete hydatidiform mole, its water swelling is focal; the formation of the pool is less obvious, and more limited, the chorionic villus often has a fan-shaped contour, different from the round shape of the complete mole. In the swollen form, the interstitial fibrosis of some hydatidiform moles often fibrosis, which is different from the interstitial edema and the formation of the pool of complete hydatidiform moles. The capillaries of the villi in some hydatidiform moles often contain nucleated red blood cells. The trophoblasts coated with villi often have only mild focal hyperplasia. The cell type is composed of cytotrophoblasts and syncytiotrophoblasts. Intermediate trophoblast cells are sometimes seen. Some hydatidiform moles often have triploid karyotypes, typically 69. , XXY, occasionally 69, XXX, at least 69,XYY, a normal egg and two meiotic sperm fertilization, often appear fetal and fetal membranes, but need to be carefully examined to find out, because the general fetus died very early ( In the 8th to 9th week of menstruation, if part of the hydatidiform mole is extended to the second trimester, it can be combined with placental hypertrophy, large area, excessive amniotic fluid, fetal malformation and so on.

Partial hydatidiform moles develop a lower risk of persistent trophoblastic disease than complete moles.

(2) Invasive hydatidiform mole (malignant hydatidiform mole) Pathology: Aggressive hydatidiform mole is a blister-like block in which the hydatid villi appear in the myometrium or its blood vessels. The villi are usually swollen, but not as complete as in the uterine cavity. The size of the hydatidiform mole is so large that the degree of trophoblastic hyperplasia is uncertain. Because of the conservative treatment of the drug, the uterus specimen is often not obtained, so the invasiveness to the muscular layer or blood vessel is not seen, but the fetus in the lesion found outside the uterus Block fluff is also evidence of invasiveness of the fetus. In the uterus, the invasion often manifests as the occurrence of block villi in the blood vessels, rather than invading adjacent tissues. The diagnosis of invasive hydatidiform moles cannot be based on curettage. Even if the muscle layer fragments are occasionally scraped, the villi containing the invasive block can not show the deep muscle layer infiltration.

The pathological feature of the invasive hydatidiform mole is that the hydatidiform mole invades the myometrium or other tissues, and the degree of invasion ranges from a few millimeters to a deep serosal surface. If the erosion part reaches the serosal surface, the surface of the uterus has a purple-blue knot. Section, the cut surface can be seen in the myometrium, there are defects, or contain different amounts of grape-like tissue and clots, blister-like tissue, hemorrhage, clots and necrotic tissue indefinitely, microscopically visible villus structure or shadow, nourishing cells are different Degree of hyperplasia.

Erosive hydatidiform moles are also prone to lung or vaginal metastasis, occasional brain metastasis, metastasis of liver and spleen and other organs. Pathological findings of metastases are similar to those of primary uterine lesions, as well as vesicular tissue, hemorrhagic necrosis, etc. The fluff structure or shadow can be seen under the microscope.

In some cases, the primary lesion is erosive hydatidiform mole, and the metastatic lesion has been consistent with the pathological findings of the villus, or the primary tumor is choriocarcinoma and the metastatic lesion is still seen in the pathological path of erosive hydatidiform mole, as long as the lesion is in any part. If you still see the villi, you should still be diagnosed as an aggressive mole.

(3) choriocarcinoma: an invasive tumor consisting of two types of trophoblasts, lacking a villus structure. Carcinoma can occur in any form of pregnancy and pregnancy, characterized by cell clumps invading adjacent tissues and invading the vascular lumen. Usually the tumor is dilated, eccentrically growing, often accompanied by extensive hemorrhage and necrosis. The living tumor cells only exist at the interface of the muscle layer, forming a thin layer around the central hemorrhage and necrosis, and the vascular invasion is obvious. There is no intrinsic interstitial blood vessel. The typical growth mode is to reproduce the formation of trophoblasts before villus, but other growth modes may occur. Different types of trophoblast types can occur in different proportions, but in most cases, there are clear The cytotrophoblasts and syncytiotrophoblasts are present in the tumor area in the form of a combination of intermediate trophoblasts and syncytiotrophoblasts.

No trophoblasts in the curettage specimens, especially small specimens, may be difficult to diagnose. The emphasis should be on the tendency of hemorrhage and necrosis of choriocarcinoma to make the diagnosis characteristics unclear. On the other hand, the trophoblasts in early pregnancy are abnormal. Therefore, it is easy to suspect choriocarcinoma, and it is necessary to diagnose choriocarcinoma in the curettage specimen, which is only suitable for placental site trophoblastic tumor (PSTT).

The choriocarcinoma is a hyperplasia of trophoblasts and a large invasion of the myometrium and blood vessels, accompanied by obvious and extensive hemorrhagic necrosis, often accompanied by distant metastasis. Pregnancy choriocarcinoma begins in the uterus, and the uterus is irregularly enlarged and soft. The surface can be seen with blue-purple nodular protuberances. The uterus and lesions are seen in the uterus. The local part is dark red, accompanied by hemorrhage, necrosis and infection. The tissue is soft and brittle. If there are multiple courses of chemotherapy before surgery, the uterine lesions are limited. The boundary between the lesion and the surrounding area is clear, and the cut surface is degraded brown or yellowish white. Microscopically, there are trophoblast cells with hyperplasia and poor differentiation, arranged in a sheet shape, invading the uterus tissue, the tumor tissue is disorderly arranged, no fluff structure, hyperplasia The trophoblast cells are 2 to 3 times larger than the normal trophoblast cells, and have obvious nucleoli. When the choriocarcinoma tissue invades the blood vessels or normal tissues, the forefront is a cluster of syncytial cells that become elongated and extend into the tissue or Cell gap, and cause bleeding and necrosis, after the cell mass is cytotrophoblast, different choriocarcinoma cases, the proportion of tissue of the two cells is different.

The research on the histology of choriocarcinoma is also increasing, and it is also beneficial to understand the occurrence, development and immunity of tumors.

The incidence of metastasis of choriocarcinoma cases is high, and there are three main types of metastasis:

1 partial venous embolization, embolization through the uterine vein, vaginal vein or other pelvic vein retrograde embolization;

2 blood line distant transfer;

3 lymphatic metastasis, but less common, it is reported today that malignant trophoblastic tumors can transfer various organs of the human body with blood, and all parts, except for hair and nail cancer, can be transferred to the fetus.

(4) Placental site trophoblastic tumor:

1 Gross morphology: The trophoblastic tumors in the placenta are diverse. They are characterized by unclear masses or well-defined nodules in the muscle wall, with or without protruding into the endometrial cavity. The lesions are brown or yellow. Focal necrosis, but usually lack of obvious bleeding, intrauterine tumors are polypoid, nodular, or diffuse infiltration of the uterine wall to thicken the uterine wall and no lumps in the uterine cavity, most of the cases have undergone curettage, so the resection The uterus is not easy to see the tumor remains, but in many specimens, a solid mass can be seen. The uterine cavity is polypoid, sometimes filling the entire uterine cavity, or implanted in the myometrium, or even the uterine wall. In the muscular layer, it can also be infiltrated and infiltrated, and it can also be diffusely infiltrated. The former uterus can be limited, the uterus is irregular, the latter has uniformity of the uterus, and the cut surface can be seen as white or yellow tissue, soft and has small bleeding. Foci, but no choriocarcinoma-like diffuse hemorrhage.

2 microscopic examination: the tumor is mainly composed of intermediate type trophoblast cells. Therefore, the tumor cells are more complex in shape, round, polygonal or fusiform, rich in cytoplasm and heterogeneous, and the former two are like decidua. Cells, but the cytoplasm is more alkaline; the latter is sometimes difficult to identify with smooth muscle cells, but the cytoplasmic eosin is lighter, even the cytoplasm contains large vacuoles, most of the tumor cells are mononuclear, a few visible multinuclei, nuclear The size, shape and dyeing can be varied. Some of the nuclei are small and round, pale and nucleoli. Others are large and distorted, can be deeply stained, and mitotic figures are rare. In the cell-rich area, 50 high-power fields are continuous. The mitotic figures are counted in the range of 1 to 5/10 high-definition fields, with an average of 2/10 high-power fields. The heterogeneous mitotic figures are rarely found, and the tumor cells can be individually dispersed or small in the form of cords or patches to individual muscle fibers. Or interstitial infiltration or diffuse hyperplasia between muscle fiber bundles, smooth muscle fibers are mostly intact, some may be mildly degenerated, visible small focal hemorrhage, no extensive hemorrhage and large coagulative necrosis, regardless of curettage specimen or whole uterus In the inner membrane and muscle layer, the invasion of tumor cells can be seen, especially the characteristic infiltration of the muscular layer. The infiltrating muscle layer is only about 0.5cm shallow, and the deep can involve the whole muscle layer directly to the serosa, scattered Tumor cell infiltration can occur in areas far from the main lesion.

There may also be varying degrees of vascular invasion, often involving small to moderate movements, veins, and infiltration of vascular endothelial cells by tumor cells. The most common feature is the presence of abundant eosinophilic extracellular fibroids, which can invade or cross the blood vessels individually. In the wall, a single scattered or agglomerated invading cell appears in the lumen of the blood vessel. The invading cell can not only erect the vascular endothelial cells, but also replace the endothelial cells, sometimes even partially or the entire blood vessel wall is invaded by cells or red-stained fiber-like Substituted by matter.

The endometrium showed a decidual-like reaction, and a small number of Arias-stella phenomena were observed. No trophoblastic villus structure or degenerative shadow was observed, and ovarian cysts were seen in the ovary.

The characteristics of 3 placental site trophoblastic tumors are as follows:

A. Single-mode intermediate trophoblastic hyperplasia, forming a tumor, which is polypoid convex to the uterine cavity, infiltrating between the muscle bundles, or to the serosa and parametrial tissue.

B. The morphology of tumor cells is diverse, round or fusiform, cytoplasmic eosinophilic, and tumor cells infiltrating vascular types are more common.

C. Biological behavior may be benign, potentially malignant, malignant, less mitotic is benign, mitosis 5 / HPF is mostly malignant, 1 ~ 4 / HPF is potentially malignant.

4 Ultrastructure: The trophoblastic tumor of the placenta is composed of trophoblasts and fibroblasts. The former has a cell diameter of 20-30 m. The cells are large and the nucleus is obvious. There is a layer of non-cellular structural material around the cells. The cells are uneven and sometimes surface. There are microvilli protrusions, mainly intermediate trophoblasts, a single round nucleus surrounded by intermediate microfilaments, nucleolus network, cytoplasm containing many free ribosomes, glycogen and lipid droplets, rows of rough surface The endoplasmic reticulum is associated with dilated vesicles; it contains flocculent material, well-developed Golgi and layered mitochondria.

The nucleus contains a large number of autosomes, sometimes the nucleolus is obvious, there are many microfilaments around the nucleus, or the microfilaments are bundled into bundles, like elastic fibers, and the rough endoplasmic reticulum, mitochondria, ribosomes, vacuoles, Organelles such as lipid droplets, in which the rough endoplasmic reticulum is most prominent, and the Golgi apparatus is poorly developed. Generally, there are many microfilaments in monocytes, while the organelles in multinucleated cells are abundant, and the granules are also visible in the cytoplasm. Adjacent mononuclear, multinucleated cells are abundant.

5 Immunohistochemistry: Immunohistochemistry of trophoblastic tumors in placenta, confirmed that HCG, HPL, and typical cases of HCG and HPL were more positive in tumor cells, suggesting that HPL is a more sensitive tumor marker of placental trophoblastic tumors. Identification of tumor development is significant, cell morphology and strong HPL and weak HCG immune response form strongly support PSTT is a mesenchymal trophoblastic tumor.

The Obstetrics and Gynecology Hospital affiliated to Zhejiang Medical University used SP and ABC methods for epithelial membrane antigen (EMA), keratin, pregnancy specific globulin (SP1) and placental alkaline phosphatase (PLAP). ), human placental lactogen (HPL), human chorionic gonadotropin (HCG), prolactin (PRL) actin and vimentin, 9 antibody markers, positive staining sites, EMA Positive for cell membrane, Ker, SPl, PLAP, HPL, HCG, PRL are cytoplasm positive, EMA, Ker, HPL are positive, Act, Vim are negative, SP1, PLAP, HCG, PRL positive and negative, the above immune group Chemotherapy is a simple and easy method for diagnosing trophoblastic tumors in the placenta. It can assist clinical and light histological features to diagnose this disease. The main characteristic change is that HPL is stronger than HCG, EMA, Ker, and no Vim. Act expression, from immunohistochemical studies suggest that the disease is derived from trophoblastic tumors, but unlike choriocarcinoma and aggressive hydatidiform moles, serum HPL is more sensitive than HCG in the monitoring of this disease.

6 Cell proliferation kinetics: The relationship between cell proliferation and pathological clinical features of trophoblastic tumors in placenta was explored from the perspective of cell proliferation, and the nature of PSST was explored from another perspective. The main content was the nucleus split count in 50 consecutive high power fields. The nucleolar organizer region of nucleolar organizer region (AgNORs) staining and flow cytometric DNA analysis and comparison with hydatidiform mole and choriocarcinoma showed that the number of mitotic divisions of trophoblastic tumors in the placenta was 1.3/10HPF, while hydatidiform mole and choriocarcinoma were 0.8/10HPF and 2.2/10HPF, the number of AgNORs in PSTT was (2.70±0.055) cells/cell, while the hydatidiform mole and choriocarcinoma were (1.96±0.38) cells/(4.50±0.73) cells/cell, placenta site. The DNA index (DI) of trophoblastic tumor is 1.10, which is nearly diploid, and the proliferation index (PI) is 26.6%. All of the above indicate that the trophoblastic tumor of placenta has lower cell proliferative capacity, and its benign clinical course and non-malignant The pathological features may be related to the diploid DNA and low cell proliferative capacity of trophoblastic tumors in the placenta. It also explains that PSTT is mostly benign compared with choriocarcinoma, and the prognosis is good. Although pathologically, there are muscle infiltration and the like. It appears to be malignant, but lacks hemorrhagic necrosis and vascular destruction.

Light microscopy, immunochemical methods and ultrastructural studies have shown that PSTT cells are similar to normal placenta cells, and the infiltrating cells are similar to the normal placental trophoblasts, especially in the primary chorionic trophoblasts of the early placenta, supporting lesions. Originated from the idea of nourishing cells.

3. Ultrastructure of trophoblastic tumors After the 1960s, foreign studies on the ultrastructure of trophoblastic tumors were carried out, but in a few reports, the description of ultrastructure was inconsistent. The reason may be the trophoblast itself. Morphological variation, different site or observer error, but most researchers believe that hydatidiform cells of hydatidiform mole, choriocarcinoma and normal early villus are similar in ultrastructure.

(1) Cellular nourishment (tumor) cells: Each cell has a clear plasma membrane, which is wavy on one side of the basal layer, and has short and few cell processes and desmosomes on one side of the syncytium cell layer. The thickness of the basal layer is consistent, no more than 100nm; there is no basal layer between the cytotrophoblasts in the erosive hydatidiform mole or choriocarcinoma, the endoplasmic reticulum is rare, the Golgi complex is not well developed, the nucleus is larger than normal, and the nucleus is uniform. In the case of aggressive hydatidiform mole or choriocarcinoma, the shape of the nucleus is irregular and the density is uneven.

(2) Transitional (intermediate) nourishment (tumor) cells: Most of the proliferating trophoblasts in hydatidiform mole and choriocarcinoma are transitional cells. Under electron microscope, cell size, morphology, electron density and organelle composition are all between Between the two trophoblasts, the plasma membrane and desmosome still exist, but the organelles are abundant, the endoplasmic reticulum is often arranged in parallel, the Golgi complex is well developed, and the mitochondria are larger.

(3) Synergistic nourishment (tumor) cells: When the intermediate cells gradually transition to typical syncytial cells, the nuclear and cytoplasmic ratio of the cells gradually decreases, and the cell surface has characteristic microvilli, and the syncytial cells have no desmosome, but are rich. A large number of round or oval-shaped endoplasmic reticulum, in the less mature cells, the endoplasmic reticulum is arranged in a parallel tubular shape, or densely integrated into a plate-like shape. In the mature cells, the endoplasm is saclike, and the number of mitochondria is increased. In erosive hydatidiform mole and choriocarcinoma, mitochondria have edema and rich basophilic particles, often clustered around the Golgi complex and mitochondria. The nucleus of the choriocarcinoma is irregularly jagged or lobulated, and the nucleoli density is different.

(4) Atrophic and degraded trophoblasts: In the degraded areas, the syncytial cell layer becomes thinner, the microvilli become pure or disappear, the mitochondrial matrix first degenerates, and then the mitochondrial ridge degenerates, the endoplasmic reticulum expands, and finally becomes fragments and disappears. Secretory granules and apical secretory droplets become insignificant, and phagocytic red blood cells and other cellular debris are visible in the cytoplasm.

(5) Terminally differentiated trophoblast cells: characterized by uniformity of cytoplasm, lack of well-differentiated rough endoplasmic reticulum and Golgi complex, mitochondria are sparse, elliptical, nucleus oval, transparent and large. Overall close to cell trophoblasts.

Ultrastructural observations and studies have contributed to the study of the biochemical characteristics of trophoblastic diseases, immunological behavior, tumorigenesis and development, confirming some speculations under light microscopy, and correcting some previous errors, which can be summarized as :

The speculation that 1 syncytial cells are derived from cytotrophoblasts was confirmed by electron microscopy.

2 It is proved that HCG is mainly secreted by syncytiotrophoblasts. Because it contains a large number of rough endoplasmic reticulum and Golgi complex, it is closely related to secretory function and synthetic exogenous protein. The two subunits of HCG are on the rough endoplasmic reticulum. Synthetic.

3 Immunological characteristics: The fibrinous substance present between the trophoblast and the maternal aponeurosis may form a barrier, and the speculation that the placenta tissue survives the mother's exclusion is confirmed by electron microscopy, revealing some of the nourishing cells. Immunological characteristics.

4 According to the different ultrastructure, such as tissue composition, cell structure and phagocytic activity to distinguish between hydatidiform mole and malignant trophoblastic tumor.

5 studies on the causes of trophoblastic tumors.

4. Trophoblastic tumors Other pathological studies of trophoblastic tumors Other pathological studies are also involved in many fields, including basic and clinical applications, which are beneficial for exploring the occurrence and development of trophoblastic tumors, as well as combining clinical diagnosis and treatment.

(1) Uterine vascular architecture research of trophoblastic tumors: trophoblastic tumors originate from the trophoblasts of placental villi, which have different characteristics from other solid tumors of human beings. They do not have inherent blood vessels, but rely on invasion and destruction. Nutrition has been obtained from adjacent blood vessels. For this reason, domestic and foreign scholars have carried out basic and clinical research on blood vessels. However, the research on uterine blood vessels of trophoblastic tumors has been limited to imaging (angiography, color Doppler blood vessels). Indirect observation of resistance index, pulse index, etc., but with certain limitations, can not directly, accurately and comprehensively display the vascular structure of the entire uterus, and can not observe the tiny blood vessels in depth, Wan Xiaoyun et al (1993) Using the vascular casting method, combined with scanning electron microscopy to observe the uterine vascular cast and in-depth study of complex three-dimensional structures including tiny blood vessels, the uterine vascular architecture of gestational trophoblastic tumors has changed compared with the normal uterus, mainly:

1 The vascular level disappeared and went to disorder. The uterine wall of the gestational trophoblastic tumor disappeared in the vascular wall, and the middle and the vertical were disappeared. The blood vessels around the lesion were often centered on the lesion and arranged in a radial pattern.

2 The number of blood vessels, morphological changes, the number of small blood vessels increased, and the branches were numerous and disordered. Under scanning electron microscopy, the small arteries were directly excited by the anterior capillary artery, and the initial part of the latter was narrowed and narrowed. The surface of the surface is still visible with a spherical bulge, and the diameter of the uterine wall is thickened. There are various forms of venous dilatation and swelling such as a spherical shape, and the anastomosis between the veins is very rich.

3 uterine wall arteriovenous anastomosis exists, the number is small, but there is a rich arteriovenous anastomosis in the lesions of the uterine wall of the drug-resistant patients. The uterine vascular architecture changes in the chemotherapy regimen of 1 or 2 courses are consistent with those without chemotherapy.

(2) Detection of argyrophilic protein in nucleolar organizer region: In recent years, research on nucleolar arginine protein (AgNORs) in tumor cells has increased, and the distribution of Ag-NOR in trophoblastic disease (tumor) cells, morphology Changes and effects of chemotherapy on AgNOR, exploration of AgNORs determination in the diagnosis and prognosis of trophoblastic diseases (tumor) have also been reported, the number of AgNOR particles in the trophoblastic nucleus of the hydatidiform mole and the average number of AgNOR in each nucleus compared with the aggressive hydatidiform mole and velvet Carcinoma was significantly lower, and choriocarcinoma was the highest; AgNORs had no correlation with the ratio of two trophoblasts, and was positively correlated with the degree of hypertrophy of trophoblasts. The high rate of Ag-NOR was also high, and AgNOR was also significantly decreased after chemotherapy. Because the nucleolar organizer regions (NORs) are located in specific parts of certain chromosomes, the main reason for the number and structural changes of NORs is enhanced transcriptional activity, polyploidy carrying NORs chromosomes, and related differentiation of tumor cells. Trophoblastic tumors are The main feature of trophoblastic proliferation is that not only the cell proliferation is active, but also the chromosomal aberration rate is increased, so AgNORs can reflect Change management and genetic aspects.

(3) Detection of interleukin-6 in gestational trophoblast tissue: interleukin-6 (IL-6) plays a role in tumorigenesis, development, and tumor immunity. In vitro experiments have shown that IL-6 has tumors. Double action, it promotes proliferation and growth of some tumors, but has obvious inhibitory effect on other tumor cells. IL-6 is also involved in tumor invasion and metastasis, apoptosis, and response to chemotherapy drugs. Immunohistochemical method (SP method) found that gestational cells in early pregnancy, hydatidiform mole, invading and choriocarcinoma can secrete IL-6, and IL-6 positive granules are localized in trophoblastic cytoplasm, but nucleus and cells The membrane is not stained, and most of them are located in syncytiotrophoblasts. Positive reactions are also observed in a few cell trophoblasts, and interstitial cells are not stained.

In early gestational villus trophoblast cells and hydatidiform mole tissues, IL-6 was moderately and strongly positive, 92.8% and 91.6%, respectively, while there was no strong positive expression in the invasive hydatidiform mole tissue, and the medium intensity positive was 23%. For weak positive and negative, there was no strong positive expression in choriocarcinoma, moderate positive was 17%, and the rest were also weak positive and negative, so IL-6 in invasive and choriocarcinoma tissues was significantly lower than hydatidiform mole, malignant trophoblast The expression of IL-6 in tumors is significantly weakened, suggesting that IL-6 plays a role in the development of gestational trophoblastic tumors. IL-6 may inhibit the growth and proliferation of malignant trophoblast cells together with some cytokines in an autocrine manner.IL-6IL-6

(4)(300nmol/L)JARDNADNA180200bpDNAFeulgenJARJAR

5.nm23H(PCNA)P(P-gp)S(GST-)p21

nm23H1

PCNAPC-NAPCNA(P<0.05)

P-gPP-gpP-gpP-gpP-gp

GST-GST-GST-

p21(P<0.001)p21

(matrix metalloproteinaseMMP)(tissue inhibitor of metalloprateinaseTIMP)MMPMMPTIMPTIMPMMP

(1994)

(Mel-CAM);;Cathepsin D;DNA

()

1.

2.19891619404352.2%197619827%

3.15%>40HCGHCGHCGHCG

4.

;

;

;

(acute pulmonary embolization);

(acuteo Dnpulmonale)

1. (benignmole);

(1)68(4)

10%20HCG

(2)(50%)45AB(810)

(lutinizcng cyct of ovany)

(3)(fetus papyraceus)

(4)HCGHCG(residualmole)

(5)HCG3(persistent mole)HCG14.5%40

(6)

(7)(repeat molerecurrent mole)2%4%103.7%3372453342

(8)3()

2.

25%

(1)HCGXCT

HCG()1()

(2)

1. (HCG)HCGHCGHCG-(FSH)(LH)(TSH)--HCGHCGHCG

2. HCG(HPL)(SP)5(PP5)A(PAPPA)HCG

3.

4.(FCM)DNADNA1000DNAG1DNA(DI)DI 1DI 1.5DI

5.(PCR) FisherDNA(PCR)DNA3

6.(FISH)(FISH)1712132112DNA

7.

8.B BBHCG

9.X XX

10. (CT)XCT

11.(MRI) (magnetic resonance imagingMRI)10MRI310mm010mm

12. (PET) (positron emission tomographyPET)2111(11C)13(13N)15(15O)18(18F)PETPET

13.

Diagnostic criteria

1.;5

43%;;;;;;HCG

2.HCG8;

3.HCG11

1954NovakNovak(ghost villi)

4.

(1)

(2)

(3)

(4)HPLHCG

PSTTPSTT

Differential diagnosis

()

1.300()()

2.1701696273720.51

3()

()()()

The material in this site is intended to be of general informational use and is not intended to constitute medical advice, probable diagnosis, or recommended treatments.