The endometrium of the early stage of the proliferation phase of the usual structure. Why does the proliferation process slow down? Changes in the endometrium observed throughout the biphasic menstrual cycle

To find out what a proliferative type of endometrium is, it is necessary to understand how the female body functions. The inner part of the uterus, lined with endometrium, experiences cyclical changes during the entire menstrual period.

The endometrium is a mucous layer covering the inner plane of the uterus, richly supplied with blood vessels and serving to supply the organ with blood.

Purpose and structure of the endometrium

By structure, the endometrium can be divided into two layers: basal and functional.

The peculiarity of the first layer is that it almost does not change and is the basis for the regeneration of the functional layer in the next menstrual period.

It consists of a layer of cells tightly adjacent to one another, connecting tissues (stroma), equipped with glands and a large number of branched blood vessels. In the normal state, its thickness varies from one to one and a half centimeters.

Unlike the basal functional layer, it is constantly undergoing changes. This is due to damage to its integrity as a result of flaking when blood flows out during menstruation, the birth of a child, artificial termination of pregnancy, curettage during diagnostics.

The endometrium is designed to perform several functions, the main of which is to provide the necessary conditions for the onset and successful course of pregnancy, when the number of glands and blood vessels that make up the placenta increases in it. One of the purposes of a child's place is to supply the embryo with nutrients and oxygen. Another function is to prevent the opposite walls of the uterus from sticking together.

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Changes occur monthly in the female body, during which favorable conditions are created for conception and gestation. The period between them is called the menstrual cycle and lasts from 20 to 30 days. The beginning of the cycle is the first day of menstruation.

Any deviations that have arisen during this period indicate the presence of any disturbances in the woman's body. The cycle is divided into three phases:

• proliferation;
• secretion;
• menstruation.

Proliferation - the process of cell reproduction by division, leading to the growth of body tissues. Endometrial proliferation is an increase in mucosal tissue within the uterus as a result of normal cell division. The phenomenon can occur as part of the menstrual cycle, or have a pathological origin.

The duration of the proliferation phase is about 2 weeks. The changes that occur in the endometrium during this period are due to an increase in the amount of the hormone estrogen, which is produced by the maturing follicle. This phase includes three stages: early, middle and late.

The early stage, which lasts from 5 days to 1 week, is characterized by the following: the surface of the endometrium is covered with cylindrical epithelial cells, the glands of the mucous layer resemble straight tubes, in the cross section the outlines of the glands are oval or rounded; the epithelium of the glands is low, the nuclei of the cells are at their base, have an oval shape and intense color. Cells that connect tissues (stroma) are spindle-shaped with large nuclei. The blood arteries are almost not tortuous.

The middle stage, which occurs on the eighth to tenth day, is characterized by the fact that the mucosal plane is covered with high prismatic epithelial cells.

The glands take on a slightly convoluted shape. The nuclei lose their color, increase in size, and are at different levels. A large number of cells obtained by indirect division appear. The stroma becomes loose and edematous.

For the late stage, lasting from 11 to 14 days, it is characteristic that the glands become tortuous, the nuclei of all cells are at different levels. The epithelium is single-layered, but with many rows. In some cells, small vacuoles appear that contain glycogen. Vessels become tortuous. Cell nuclei take on a more rounded shape and greatly increase in size. The stroma is filled.

The secretory phase of the cycle is divided into stages:

• early, lasting from 15 to 18 days of the cycle;
• medium, with the most pronounced secretion, occurring from 20 to 23 days;
• late (extinction of secretion), occurring from 24 to 27 days.

The menstrual phase consists of two periods:

• desquamation occurring from 28 to 2 days of the cycle and occurring if fertilization has not occurred;
• regeneration, lasting from 3 to 4 days and starting until the complete separation of the functional layer of the endometrium, but together with the beginning of the growth of epithelial cells of the proliferation phase.

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Normal structure of the endometrium

With the help of hysteroscopy (examination of the uterine cavity), it is possible to assess the structure of the glands, assess the degree of occurrence of new blood vessels in the endometrium, and determine the thickness of the cell layer. In different phases of the menstrual period, the results of examinations differ from each other.

Normally, the stratum basalis is 1 to 1.5 cm thick, but may increase to 2 cm at the end of the proliferation phase. His reaction to hormonal influences is weak.

During the first week, the inner mucous surface of the uterus is smooth, painted in a light pink color, with small particles of the non-separated functional layer of the last cycle.

In the second week, there is a thickening of the endometrium of the proliferative type, associated with the active division of healthy cells.

It becomes impossible to see the blood vessels. Due to the uneven thickening of the endometrium, folds appear on the inner walls of the uterus. In the proliferation phase, the back wall and bottom normally have the thickest mucous layer, and the front wall and the lower part of the child's place are the thinnest. The thickness of the functional layer ranges from five to twelve millimeters.

Normally, there should be a complete rejection of the functional layer almost to the basal layer. In reality, complete separation does not occur, only the outer sections are rejected. If there are no clinical violations of the phase of menstruation, then we are talking about an individual norm.

Endometrium is the mucous inner layer of the uterus, which forms optimal conditions for the attachment of the fetal egg and changes its thickness during the menstrual period.

The minimum thickness is observed at the beginning of the cycle, the maximum - in its last days. If fertilization does not occur during the menstrual cycle, there is a detachment of the epithelium and the withdrawal of the unfertilized egg with the menstrual cell.

Speaking in an accessible language, we can say that the endometrium affects the volume of secretions, as well as the frequency and cyclicity of menstruation.

In women, under the influence of negative factors, thinning of the endometrium is possible, which not only negatively affects the attachment of the embryo, but can also lead to infertility.

In gynecology, there are cases of spontaneous miscarriage if the egg was placed on a thin layer. Competent gynecological treatment is enough to eliminate problems that negatively affect conception and the safe course of pregnancy.

Thickening of the endometrial layer (hyperplasia) is characterized by a benign course and may be accompanied by the appearance of polyps. Deviations in the thickness of the endometrium are detected during a gynecological examination and prescribed examinations.

In the absence of symptoms of pathology, as well as infertility, treatment may not be prescribed.

Forms of hyperplasia:

• Simple. Glandular cells predominate, leading to the appearance of polyps. Treatment is with drugs and surgery.
• Atypical. Accompanied by the development of adenomatosis (malignant disease).

menstruation cycle in women

In the female body, changes occur every month that help create optimal conditions for conceiving and bearing a child. The period between them is called the menstrual cycle.

On average, its duration is 20-30 days. The beginning of the cycle is the first day of menstruation.

At the same time, the endometrium is updated and cleansed.

If during the menstrual cycle in women deviations are noted, then this indicates serious disorders in the body. The cycle is divided into several phases:

• proliferation;
• secretion;
• menstruation.

Proliferation refers to the processes of reproduction and division of cells that contribute to the growth of the internal tissues of the body. During the proliferation of the endometrium in the mucous membrane of the uterine cavity, normal cells begin to divide.

Such changes can take place during menstruation or have a pathological origin.

Duration of proliferation averages up to two weeks. In the body of a woman, estrogen begins to increase intensively, which produces an already mature follicle.

This phase can be divided into early, middle and late stages. At an early stage (5-7 days) in the uterine cavity, the surface of the endometrium is covered with epithelial cells that have a cylindrical shape.

In this case, the blood arteries remain unchanged.

Classification of endometrial hyperplasia

According to the histological variant, several types of endometrial hyperplasia are distinguished: glandular, glandular-cystic, atypical (adenomatosis) and focal (endometrial polyps).

Glandular hyperplasia of the endometrium is characterized by the disappearance of the division of the endometrium into functional and basal layers. The border between the myometrium and the endometrium is clearly expressed, an increased number of glands is noted, but their location is uneven, and the shape is not the same.

Pathological anatomical diagnosis of the state of the endometrium by biopsies / Pryanishnikov V.A., Topchieva O.I. ; under. ed. prof. OK. Khmelnitsky. - Leningrad.

Diagnosis by biopsy of the endometrium often presents great difficulties due to the fact that the same very similar microscopic picture of the endometrium can be due to various reasons (O.I. Topchieva 1968). In addition, the endometrial tissue is distinguished by an exceptional variety of morphological structures, depending on the level of steroid hormones secreted by the ovaries in normal conditions and under pathological conditions associated with endocrine regulation disorders.

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PATHOLOGICAL AND ANATOMICAL DIAGNOSIS OF ENDOMETRIUM CONDITIONS BY BIOPSY

Accurate microscopic diagnosis of endometrial scrapings is of great importance for the daily work of an obstetrician-gynecologist. Biopsies (scrapings) of the endometrium make up a significant part of the material sent by obstetric and gynecological hospitals for microscopic examination.

Diagnosis by endometrial biopsies often presents great difficulties due to the fact that the same very similar microscopic picture of the endometrium can be due to various reasons (O. I. Topchieva 1968). In addition, endometrial tissue is characterized by an exceptional variety of morphological structures, depending on the level of steroid hormones secreted by the ovaries in normal and pathological conditions associated with endocrine regulation.

Experience shows that a responsible and complex diagnosis of changes in the endometrium by scrapings is complete only if there is close contact in the work between the pathologist and the gynecologist.

The use of histochemical methods, along with classical morphological research methods, significantly expands the possibilities of pathoanatomical diagnostics and includes such histochemical reactions as a reaction to glycogen, alkaline and acid phosphatases, monoamine oxidase, etc. The use of these reactions makes it possible to more accurately assess the degree of imbalance of estrogens and progestogens in the body women, and also makes it possible to determine the degree and nature of endometrial hormone sensitivity in hyperplastic processes and tumors, which is of great importance when choosing methods for treating these diseases.

METHOD OF OBTAINING AND PREPARATION OF MATERIAL FOR STUDY

Important for the correct microscopic diagnosis of endometrial scrapings is the observance of a number of conditions when collecting material.

The first condition is the correct determination of the time that is most favorable for the production of scraping. There are the following indications for scraping:

• a) in case of sterility with suspected insufficiency of the corpus luteum or anovulatory cycle - scraping is taken 2-3 days before menstruation;
• b) with menorrhagia, when delayed rejection of the endometrial mucosa is suspected; depending on the duration of bleeding, scraping is taken 5-10 days after the onset of menstruation;
• c) in case of dysfunctional uterine bleeding such as metrorrhagic scrapings should be taken immediately after the onset of bleeding.

The second condition is the technically correct curettage of the uterine cavity. The "accuracy" of the pathologist's answer depends largely on how the endometrial scraping is taken. If small, fragmented pieces of tissue are received for research, then it is extremely difficult or even impossible to restore the structure of the endometrium. This can be eliminated with the correct work of curettage, the purpose of which is to obtain as large as possible, non-crushed strips of tissue of the uterine mucosa. This is achieved by the fact that after passing the curette along the wall of the uterus, it must be removed from the cervical canal each time, and the resulting mucosal tissue is carefully folded onto gauze. In the event that the curette is not removed every time, then the mucous membrane separated from the uterine wall is crushed with repeated movements of the curette and part of it remains in the uterine cavity.

Complete diagnostic curettage of the uterus is performed after the expansion of the cervical canal to the 10th number of the Hegar dilator. Usually curettage is carried out separately: first, the cervical canal, and then the uterine cavity. The material is placed in the fixative liquid in two separate jars, marked where it came from.

In the presence of bleeding, especially in women who are in the menopause or menopause, it is necessary to scrape out the tubal corners of the uterus with a small curette, remembering that it is in these areas that polyposis growths of the endometrium can be localized, in which areas of malignancy are most common.

If a large amount of tissue is removed from the uterus during curettage, then it is necessary to send the entire material to the laboratory, and not part of it.

Tsugi or the so-called dashed scrapings are taken in cases where it is necessary to determine the reaction of the uterine mucosa in response to the secretion of hormones by the ovaries, to monitor the results of hormone therapy, to determine the causes of a woman's sterility. To obtain trains, a small curette is used without first expanding the cervical canal. When taking a train, it is necessary to hold the curette to the very bottom of the uterus so that the mucous membrane gets into the strip of dashed scraping from top to bottom, i.e., lining all parts of the uterus. To obtain the correct answer from the histologist for the train, as a rule, it is enough to have 1-2 strips of the endometrium.

The train technique should in no case be used in the presence of uterine bleeding, since in such cases it is necessary to have endometrium from the surface of all walls of the uterus for examination.

Aspiration biopsy- Obtaining pieces of endometrial tissue by suction from the uterine cavity, can be recommended for mass preventive examinations of women in order to identify precancerous conditions and endometrial cancer in “high-risk groups”. At the same time, I do not allow negative results of aspiration biopsy! to reject with confidence the initial forms of asymptomatic cancer. In this regard, if cancer of the uterine body is suspected, the most reliable and only indicated diagnostic method remains [complete curettage of the uterine cavity (V. A. Mandelstam, 1970).

After performing a biopsy, the doctor sending the material for examination must fill out accompanying direction l about our proposed form.

The direction should indicate:

• a) the duration of the menstrual cycle characteristic of this woman (21-28, or 31-day cycle);
• b) the date of the onset of bleeding (on the date of the expected menstruation, ahead of time or late). In the presence of menopause or amenorrhea, it is necessary to indicate its duration.

Information about:

• a) the constitutional type of the patient (obesity is often accompanied by pathological changes in the endometrium),
• b) endocrine disorders (diabetes, changes in the function of the thyroid gland and adrenal cortex),
• c) Has the patient been subjected to hormonal therapy, about what, with what hormone and in what dosage?
• d) whether methods of hormonal contraception were used, the duration of the use of contraceptives.

Histological processing 6-iopsium material includes fixation in 10% neutral formalin solution, followed by dehydration and paraffin embedding. You can also use the accelerated method of pouring into paraffin according to G.A. Merkulov with fixation in formalin, heated to 37°C in a thermostat V within 1-2 hours.

In everyday work, you can limit yourself to staining preparations with hematoxylin-eosin, according to Van Gieson, mucicarmine or alcian oitaim.

For a finer diagnosis of the state of the endometrium, especially when addressing issues of the cause of sterility associated with inferior ovarian function, as well as to determine the hormone sensitivity of the endometrium in hyperplastic processes and tumors, it is necessary to use histochemical methods that allow detecting glycogen, assessing the activity of acid, alkaline phosphatases and a number of other enzymes.

cryostat sections, obtained from non-fixed endometrial tissue frozen at liquid nitrogen temperature (-196°C) can be used not only for examination using conventional histological staining methods (hematoxylin-eosin, etc.), but also for determining the glycogen content and enzyme activity in morphological structures uterine mucosa.

To conduct histological and histochemical studies from endometrial biopsies on cryostat sections, the pathoanatomical laboratory must be equipped with the following equipment: MK-25 cryostat, liquid nitrogen or carbon dioxide (“dry ice”), Dewar vessels (or household thermos), PH-meter, refrigerator at +4°C, thermostat or water bath. To obtain cryostat sections, you can use the method developed by V.A. Pryanishnikov and colleagues (1974).

According to this method, the following stages of preparation of cryostat sections are distinguished:

1. Pieces of the endometrium (without prior washing with water and without fixation) are placed on a strip of filter paper moistened with water and gently immersed in liquid nitrogen for 3-5 seconds.
2. Filter paper with pieces of endometrium frozen in nitrogen is transferred to the cryostat chamber (-20°C) and carefully frozen to the microtome block holder with a few drops of water.
3. Sections 10 µm thick obtained in the cryostat are mounted in the cryostat chamber on cooled glass slides or coverslips.
4. The straightening of the sections is carried out by melting the sections, which is achieved by touching a warm finger to the lower surface of the glass.
5. Glass with thawed sections is quickly removed from the cryostat chamber (do not allow the sections to freeze again), dried in air, and fixed in 2% solution of glutaraldehyde (or vapor form) or in a mixture of formaldehyde - alcohol - acetic acid - chloroform in a ratio of 2: 6 :1:1.
6. Fixed media are stained with hematoxylin-eosin, dehydrated, cleared, and mounted in polystyrene or balm. The choice of the level of the studied histological structure of the endometrium is made on temporary preparations (non-fixed cryostat sections) stained with toluidine blue or methylene blue and enclosed in a drop of water. Their production takes 1-2 minutes.

For histochemical determination of the content and localization of glycogen, air-dried cryostat sections are fixed in acetone cooled to +4°C for 5 minutes, dried in air, and stained according to the McManus method (Pearce 1962).

To identify hydrolytic enzymes (acid and alkaline phosphatase), cryostat sections are used, fixed in 2% chilled to a temperature of +4°C. neutral formalin solution for 20-30 minutes. After fixation, the sections are rinsed in water and immersed in an incubation solution to detect acid or alkaline phosphatase activity. Acid phosphatase is determined by the method of Bark and Anderson (1963), and alkaline phosphatase is determined by the method of Burston (Burston, 1965). Sections may be counterstained with hematoxylin prior to imaging. It is necessary to store drugs in a dark place.

CHANGES IN THE ENDOMETRIUM OBSERVED DURING THE TWO-PHASE MENSTRUAL CYCLE

The mucous membrane of the uterus, lining its various parts - the body, isthmus and neck - has typical histological and functional features in each of these departments.

The endometrium of the body of the uterus consists of two layers: basal, deeper, located directly on the myometrium and superficial-functional.

Basal the layer contains a few narrow glands lined with a cylindrical single-row epithelium, the cells of which have oval nuclei that are intensely stained with hematoxylin. The response of the tissue of the basal layer to hormonal influences is weak and inconsistent.

From the tissue of the basal layer, the functional layer is regenerated after various violations of its integrity: rejection in the menstrual phase of the cycle, with dysfunctional bleeding, after abortion, childbirth, and also after curettage.

Functional the layer is a tissue with a special, biologically determined high sensitivity to sex steroid hormones - estrogens and gestagens, under the influence of which its structure and function change.

The height of the functional layer in mature women varies depending on the phase of the menstrual cycle: about 1 mm at the beginning of the proliferation phase and up to 8 mm in the secretion phase at the end of the 3rd week of the cycle. In this period, in the functional layer, the deep, spongy layer, where the glands are located more closely, and the superficial-compact layer, in which the cytogenic stroma predominates, are most clearly marked.

The basis of cyclic changes in the morphological picture of the endometrium observed during the menstrual cycle is the ability of sex steroids-estrogens to cause characteristic changes in the structure and behavior of the tissue of the mucous membrane of the uterine body.

So, estrogens stimulate the proliferation of cells of the glands and stroma, promote regenerative processes, have a vasodilating effect and increase the permeability of endometrial capillaries.

Progesterone has an effect on the endometrium only after prior exposure to estrogens. Under these conditions, gestagens (progesterone) cause: a) secretory changes in the glands, b) decidual reaction of stromal cells, c) development of spiral vessels in the functional layer of the endometrium.

The above morphological features were taken as the basis for the morphological division of the menstrual cycle into phases and stages.

According to modern concepts, the menstrual cycle is divided into:

• 1) proliferation phase:
  • Early stage - 5-7 days
  • Middle stage - 8-10 days
  • Late stage - 10-14 days
• 2) secretion phase:
  • Early stage (first signs of secretory transformations) - 15-18 days
  • The middle stage (the most pronounced secretion) - 19-23 days
  • Late stage (beginning regression) - 24-25 days
  • Regression with ischemia - 26-27 days
• 3) phase of bleeding - menstruation:
  • Desquamation - 28-2 days
  • Regeneration - 3-4 days

When assessing the changes occurring in the endometrium according to the days of the menstrual cycle, it is necessary to take into account:

• 1) the duration of the cycle in this woman (28- or 21-day cycle);
• 2) the period of ovulation that has occurred, which under normal conditions is observed on average from the 13th to the 16th day of the cycle; (therefore, depending on the time of ovulation, the structure of the endometrium of one or another stage of the secretion phase varies within 2-3 days).

The proliferation phase lasts 14 days, however, and under physiological conditions it can be extended or shortened within 3 days. The changes observed in the endometrium of the proliferation phase result from the action of an increasing amount of estrogens secreted by the growing and maturing follicle.

The most pronounced morphological changes in the proliferation phase are noted in the glands. In the early stage, the glands look like straight or cast convoluted tubules with a narrow lumen, the contours of the glands are rounded or oval. The epithelium of the glands is single-row low cylindrical, the nuclei are oval, located at the base of the cells, intensely stained with hematoxylin. In the late stage, the glands acquire a sinuous, sometimes corkscrew-shaped outline with a slightly expanded lumen. The epithelium becomes high prismatic, there is a large number of mitoses. As a result of intensive division and an increase in the number of epithelial cells, their nuclei are at different levels. The epithelial cells of the glands of the early phase of proliferation are characterized by the absence of glycogen and moderate activity of alkaline phosphatase. By the end of the proliferation phase in the glands, the appearance of small dust-like glycogen granules and high activity of alkaline phosphatase are noted.

In the stroma of the endometrium, during the proliferation phase, there is an increase in dividing cells, as well as thin-walled vessels.

Endometrial structures corresponding to the proliferation phase, observed under physiological conditions in the first half of the biphasic nick, may reflect hormonal disorders if they are detected:

• 1) during the second half of the menstrual cycle; this may indicate an anovulatory monophasic cycle or an abnormal, prolonged proliferative phase with delayed ovulation. in a biphasic cycle:
• 2) with glandular hyperplasia of the endometrium in various parts of the hyperplastic mucosa;
• 3) three dysfunctional uterine bleeding in women at any age.

The secretion phase, directly related to the hormonal activity of the menstrual corpus luteum and the corresponding secretion of progesterone, lasts 14 ± 1 days. Shortening or lengthening of the secretion phase by more than two days in women in the reproductive period should be considered a pathological condition, since such cycles are sterile.

During the first week of the secretion phase, the day of ovulation that occurred is determined by changes in the epithelium of the glands, while in the second week this day can be most accurately determined by the state of the endometrial stroma cells.

So, on the 2nd day after ovulation (16th day of the cycle) in the epithelium of the glands appear subnuclear vacuoles. On the 3rd day after ovulation (17th day of the cycle), subnuclear vacuoles push the nuclei into the apical sections of the cells, as a result of which the latter are at the same level. On the 4th day after ovulation (18th day of the cycle), the vacuoles partially move from the basal to the apical regions, and by the 5th day (19th day of the cycle), almost all vacuoles move to the apical regions of the cells, and the nuclei shift to the basal departments. In the subsequent 6th, 7th and 8th days after ovulation, i.e. on the 20th, 21st and 22nd days of the cycle, pronounced processes of apocrine secretion are noted in the cells of the epithelium of the glands, as a result of which apical “ Paradise cells have, as it were, notches, uneven. The lumen of the glands during this period is usually expanded, filled with eosinophilic secretion, the walls of the glands become folded. On the 9th day after ovulation (23rd day of the menstrual cycle), the secretion of the glands is completed.

The use of histochemical methods made it possible to establish that subnuclear vacuoles contain large glycogen granules, which are released into the lumen of the glands by apocrine secretion during the early and early middle stages of the secretion phase. Along with glycogen, the lumen of the glands also contains acid mucopolysaccharides. With the accumulation of glycogen and its secretion into the lumen of the glands, there is a clear decrease in the activity of alkaline phosphatase in the epithelial cells, which almost completely disappears by the 20-23rd day of the cycle.

in the stroma characteristic changes for the secretion phase begin to appear on the 6th, 7th day after ovulation (20th, 21st day of the cycle) in the form of a perivascular decidua-like reaction. This reaction is most pronounced in the cells of the stroma of the compact layer and is accompanied by an increase in the cytoplasm of the cells, they acquire polygonal or rounded outlines, and glycogen accumulation is noted. Characteristic of this stage of the secretion phase is also the appearance of tangles of spiral vessels not only in the deep sections of the functional layer, but also in the superficial compact layer.

It should be emphasized that the presence of spiral arteries in the functional layer of the endometrium is one of the most reliable signs that determine the full progestogen effect.

On the contrary, subnuclear vacuolization in the epithelium of the glands is not always a sign indicating that ovulation has occurred and the secretion of progesterone by the corpus luteum has begun.

Subnuclear vacuoles can sometimes be found in the glands of the mixed hypoplastic endometrium with dysfunctional uterine bleeding in women of any age, including menopause (O. I. Topchieva, 1962). However, in the endometrium, where the occurrence of vacuoles is not associated with ovulation, they are contained in individual glands or in a group of glands, as a rule, only in a part of the cells. The vacuoles themselves have a different size, most often they are small.

In the late stage of the secretion phase, from the 10th day after ovulation, i.e. on the 24th day of the cycle, in conjunction with the onset of regression of the corpus luteum and a decrease in the level of progesterone in the blood, morphological signs of regression are observed in the endometrium, and on 26 th and 27th day signs of ischemia join. As a result of wrinkling of the stroma of the functional layer of the gland, they acquire star-shaped outlines on transverse sections and sawtooth on longitudinal ones.

In the phase of bleeding (menstruation), processes of desquamation and regeneration occur in the endometrium. A morphological feature characteristic of the endometrium of the menstrual phase is the presence, in the hemorrhagic, decaying tissue, of collapsed glands or their fragments, as well as tangles of spiral arteries. Complete rejection of the functional layer usually ends on the 3rd day of the cycle.

Regeneration of the endometrium occurs due to the proliferation of cells of the basal glands and ends within 24-48 hours.

CHANGES IN THE ENDOMETRIUM IN DISTURBANCE OF THE ENDOCRINE FUNCTION OF THE OVARIAN

From the point of view of etiology, pathogenesis, as well as taking into account clinical symptoms, morphological changes in the endometrium that occur when the endocrine function of the ovaries is impaired can be divided into three groups:

1. Changes in the endometrium in violation of secretion estrogenic hormones.
2. Changes in the endometrium in violation of secretion progestative hormones.
3. Changes in the endometrium of the “mixed type”, in which structures are simultaneously found that reflect the effects of estrogen and progestative hormones.

Regardless of the nature of the disorders of ovarian endocrine function listed above, the most common symptoms encountered by clinicians and morphologists are uterine bleeding and amenorrhea.

A special place in its extremely important clinical significance is occupied by uterine bleeding in women in menopause, since among the various causes that cause such bleeding, about 30% are malignant neoplasms of the endometrium (V.A. Mandelstam 1971).

1. Changes in the endometrium in violation of the secretion of estrogen hormones

Violation of the secretion of estrogenic hormones manifests itself in two main forms:

a) in an insufficient amount of estrogens and the formation of a non-functioning (resting) endometrium.

Under physiological conditions, the resting endometrium briefly exists during menstrual cycles - after regeneration of the mucosa before the onset of proliferation. Non-functioning endometrium is also observed in elderly women with the extinction of the hormonal function of the ovaries and is a stage of transition to atrophic endometrium. Morphological signs of a non-functioning endometrium - the glands look like straight or slightly twisted tubules. The epithelium is low, cylindrical, the cytoplasm is basophilic, the nuclei are elongated, occupying most of the cell. Mitoses are absent or extremely rare. The stroma is rich in cells. When these changes are stressed, the endometrium turns from non-functioning to atrophic with small glands lined with cuboidal epithelium.

b) in prolonged secretion of estrogens from persistent follicles, accompanied by anovulatory monophasic cycles. Elongated single-phase cycles resulting from prolonged follicle persistence lead to the development of dyshormonal proliferation of the endometrium of the type glandular or glandular cystic hyperplasia.

As a rule, the endometrium with dyshormonal proliferation is thickened, its height reaches 1-1.5 cm or more. Microscopically, there is no division of the endometrium into layers - compact and spongy, there is also no correct distribution of glands in the stroma; Characteristics of racemose enlarged glands. The number of glands (more precisely glandular tubules) does not increase (as opposed to atypical glandular hyperplasia - adenomatosis). But in connection with the increased proliferation, the glands acquire a convoluted shape, and on a section passing through individual turns of the same glandular tube, the impression of a large number of glands is created.

The structure of glandular hyperplasia of the endometrium, which does not contain racemose enlarged glands, is called ".simple hyperplasia."

Depending on the severity of proliferative processes, endometrial glandular hyperplasia is divided into “active” and “resting” (which correspond to the states of “acute” and “chronic” estrogens). The active form is characterized by a large number of mitoses both in the epithelial cells of the glands and in the cells of the stroma, high activity of alkaline phosphatase, and the appearance of accumulations of “light” cells in the glands. All of these signs point to intense estrogen stimulation ("acute estrogenism").

The “resting” form of glandular hyperplasia, corresponding to the state of “chronic estrothenia”, occurs under conditions of prolonged exposure to low levels of estrogen hormones on the endometrium. Under these conditions, the endometrial tissue acquires similarities with a resting, non-functioning endometrium: the nuclei of the epithelium are intensely stained, the cytoplasm is basophilic, mitoses are very rare or do not occur at all. The “resting” form of glandular hyperplasia is most often observed in the menopause, with the extinction of ovarian function.

It should be remembered that the occurrence of glandular hyperplasia - especially its active form - in women many years after the onset of menopause, with a tendency to relapse, should be regarded as an unfavorable factor in relation to the possible occurrence of endometrial cancer.

It must also be borne in mind that dyshormonal proliferation of the endometrium can also occur in the presence of cilioepithelial and pseudomucinous ovarian cystomas, both malignant and benign, as well as in some other ovarian neoplasms, for example, with a Brenner tumor (M. F. Glazunov 1961).

2. Changes in the endometrium in violation of the secretion of gestagens

Violation of the secretion of hormones of the menstrual corpus luteum appears both in the form of insufficient secretion of progesterone, and with its increased and prolonged secretion (persistence of the corpus luteum).

Hypolyutein cycles with corpus luteum insufficiency are shortened in 25% of cases; ovulation usually occurs on time, but the secretory phase can be shortened to 8 days. Coming ahead of time, menstruation is associated with the premature death of an inferior corpus luteum and the cessation of secretion of testerone.

Histological changes in the endometrium during hypoluteal cycles consist in uneven and insufficient secretory transformation of the mucosa. So, for example, shortly before the onset of menstruation, during the 4th week of the cycle, along with the glands characteristic of the late stage of the secretion phase, there are glands that sharply lag behind in their secretory function and correspond only to the beginning phases secretions.

Predecidual transformations of the connective tissue cells are very weak or absent at all, the spiral vessels are underdeveloped.

Persistence of the corpus luteum may be accompanied by full secretion of progesterone and prolongation of the secretion phase. In addition, there are cases with reduced secretion of progesterone by the wooly corpus luteum.

In the first case, the changes that occur in the endometrium were called ultramenstrual hypertrophy and are similar to structures seen in early pregnancy. The mucosa is thickened up to 1 cm, the secretion is intense, there is a pronounced decidua-like transformation of the stroma and the development of spiral arteries. Differential diagnosis with impaired pregnancy (in women of reproductive age) is extremely difficult. The possibility of such changes in the endometrium of menopausal women (in which pregnancy can be excluded) is noted.

In the case of a decrease in the hormonal function of the corpus luteum, when it undergoes an incomplete gradual regression, the process of rejection of the endometrium slows down and is accompanied by lengthening phases bleeding in the form of menorrhagia.

The microscopic picture of scrapings of the endometrium obtained with such bleeding after the 5th day seems to be very variegated: the scrapings show areas of necrotic tissue, areas in a state of regression, secretory and proliferative endometrium. Such changes in the endometrium can be found in women with acyclic dysfunctional uterine bleeding who are in the menopause.

Sometimes exposure to low concentrations of progesterone leads to a slowdown in its rejection, involution, i.e., the reverse development of the deep sections of the functional layer. This process creates conditions for the return of the endometrium to the original structure that was before the onset of cyclic changes and there are three amenorrheas due to the so-called “hidden cycles” or hidden menstruation (E.I. Kvater 1961).

3. Endometrium “mixed type”

The endometrium is called mixed if its tissue contains structures that simultaneously reflect the effects of estrogen and progestogen hormones.

There are two forms of mixed endometrium: a) mixed hypoplastic, b) mixed hyperplastic.

The structure of the mixed hypoplastic endometrium presents a motley picture: the functional layer is poorly developed and is represented by glands of an indifferent type, and also areas with secretory changes, mitoses are extremely rare.

Such an endometrium occurs in women of reproductive age with ovarian hypofunction, in menopausal women with dysfunctional uterine bleeding, and in menopausal bleeding.

Glandular hyperplasia of the endometrium with pronounced signs of exposure to progestogen hormones can be attributed to hyperplastic mixed endometrium. If among the tissues of glandular hyperplasia of the endometrium, along with typical glands that reflect the estrogenic effect, there are areas with groups of glands in which secretory signs, then such a structure of the endometrium is called a mixed form of glandular hyperplasia. Along with secretory changes in the glands, there are also changes in the stroma, namely: focal decidua-like transformation of connective tissue cells and the formation of tangles of spiral vessels.

PRECANCER CONDITIONS AND ENDOMETRIAL CANCER

Despite the great inconsistency of data on the possibility of endometrial cancer on the background of glandular hyperplasia, most authors believe that the possibility of a direct transition of glandular hyperplasia to endometrial cancer is unlikely (A. I. Serebrov 1968; Ya. V. Bokhmai 1972), However, unlike the usual (typical) glandular hyperplasia of the endometrium, the atypical form (adenomatosis) is considered by many researchers as a precancer (A. I. Serebrov 1968, L. A. Novikova 1971, etc.).

Adenomatosis is a pathological proliferation of the endometrium, in which the features characteristic of hormonal hyperplasia are lost and atypical structures appear that resemble malignant growths. Adenomatosis is divided according to prevalence into diffuse and focal, and according to the severity of proliferative processes - into mild and pronounced forms (B.I. Zheleznoy, 1972).

Despite a significant variety of morphological features of adenomatosis, most of the forms encountered in the practice of a pathologist have a number of characteristic morphological features.

The glands are strongly convoluted, often have numerous branches with numerous papillary protrusions into the lumen. In some places, the glands are closely located next to each other, almost not separated by connective tissue. Epithelial cells have large or oval, elongated, pale staining nuclei with signs of polymorphism. Structures corresponding to endometrial adenomatosis can be found over a large extent or in limited areas against the background of endometrial glandular hyperplasia. Sometimes in the glands, nested groups of light cells are found that have a morphological similarity to the squamous epithelium - adenoid acanthosis. Foci of pseudosquamous structures are sharply demarcated from the cylindrical epithelium of the glands and connective tissue cells of the stroma. Such foci can occur not only with adenomatosis, but also with endometrial adenocarcinoma (adenoacanthoma). In some rare forms of adenomatosis, there is an accumulation of a large number of “light” cells (ciliated epithelium) in the epithelium of the glands.

Significant difficulties arise for a morphologist when trying to make a differential diagnosis between pronounced proliferative forms of adenomatosis and highly differentiated variants of endometrial cancer. Expressed forms of adenomatosis are characterized by intense proliferation and atypism of the glandular epithelium in the form of an increase in the size of cells and nuclei, which allowed Hertig et al. (1949) to call such forms of adenomatosis "zero stage" of endometrial cancer.

However, due to the lack of clear morphological criteria for this form of endometrial cancer (unlike a similar form of cervical cancer), the use of this term in the diagnosis of endometrial scrapings does not seem justified (E. Novak 1974, B. I. Zheleznov 1973).

endometrial cancer

Most of the existing classifications of epithelial malignant tumors of the endometrium are based on the principle of the degree of tumor differentiation (M.F. Glazunov, 1947; P.V. Simpovsky and O.K. Khmelnitsky, 1963; E.N. Petrova, 1964; N.A. Kraevsky , 1969).

The same principle underlies the latest International Classification of Endometrial Cancer, developed by a group of experts from the World Health Organization (Poulsen and Taylor, 1975).

According to this classification, the following morphological forms of endometrial cancer are distinguished:

• a) Adenocarcinoma (highly, moderately and poorly differentiated forms).
• b) Clear cell (mesonephroid) adenocarcinoma.
• c) Squamous cell carcinoma.
• d) Glandular-squamous (mucoepidermoid) cancer.
• e) Undifferentiated cancer.

It should be emphasized that more than 80% of malignant epithelial tumors of the endometrium are adenocarcinomas of varying degrees of differentiation.

A distinctive feature of tumors with histological structures of highly differentiated endometrial cancers is that the glandular structures of the tumor, although they have signs of atypia, nevertheless still resemble normal endometrial epithelium. Glandular growths of the endometrium of the epithelium with papillary outgrowths are surrounded by scanty layers of connective tissue with a small number of vessels. The glands are lined with high- and low-prismatic epithelium with mild polymorphism and relatively rare mitoses.

As differentiation decreases, glandular cancers lose the features characteristic of the endometrial epithelium, glandular structures of the alveolar, tubular or papillary structure begin to predominate in them, which do not differ in their structure from glandular cancers of other localization.

According to histochemical features, highly differentiated glandular cancers resemble the endometrial epithelium, since they contain glycogen in a significant percentage and react to alkaline phosphatase. In addition, these forms of endometrial cancer are highly sensitive to hormone therapy with synthetic gestagens (17-hydroxyprogesterone capronoate), under the influence of which secretory changes develop in tumor cells, glycogen accumulates, and alkaline phosphatase activity decreases (V. A. Pryanishnikov, Ya. V. Bohman, O. F. Che-pick 1976). Much less often, such a differentiating effect of gestagens develops in cells of moderately differentiated endometrial cancers.

CHANGES IN THE ENDOMETRIUM DURING THE PRESENTATION OF HORMONAL DRUGS

Currently, estrogen and gestagen preparations are widely used in gynecological practice for the treatment of dysfunctional uterine bleeding, some forms of amenorrhea, and also as contraceptives.

Using various combinations of estrogens and gestagens, it is possible to artificially obtain morphological changes in the human endometrium that are characteristic of one or another phase of the menstrual cycle with normally functioning ovaries. The principles underlying the hormone therapy of dysfunctional uterine bleeding and amenorrhea are based on the general patterns inherent in the action of estrogens and progestogens on normal human endometrium.

The introduction of estrogen leads, depending on the duration and dose, to the development of proliferative processes in the endometrium up to glandular hyperplasia. With prolonged use of estrogens against the background of proliferation, abundant acyclic uterine bleeding may occur.

The introduction of progesterone in the proliferative phase of the cycle leads to inhibition of the proliferation of the epithelium of the glands and suppresses ovulation. The effect of progesterone on the proliferating endometrium depends on the duration of hormone administration and manifests itself in the form of the following morphological changes:

• - the stage of "stopped proliferation" in the glands;
• - atrophic changes in the glands with decidua-like transformation of stromal cells;
• - atrophic changes in the epithelium of the glands and stroma.

With the joint administration of estrogens and progestogens, changes in the endometrium depend on the quantitative ratio of hormones, as well as on the duration of their administration. So, for the proliferating endometrium under the influence of estrogens, the daily dose of progesterone, which causes secretory changes in the glands in the form of accumulation of glycogen granules, is 30 mg. In the presence of severe glandular hyperplasia of the endometrium, to achieve a similar effect, it is necessary to administer 400 mg of progesterone daily (Dallenbach-Helwig, 1969).

For a morphologist and clinician-gynecologist, it is important to know that the selection of the dosage of estrogens and progestins in the treatment of menstrual disorders and pathological conditions of the endometrium should be carried out under histological control, by sampling repeated endometrial trains.

When using combined hormonal contraceptives in the normal endometrium of a woman, regular morphological changes occur, depending primarily on the duration of the drug.

First of all, there is a shortening of the proliferative phase with the development of defective glands, in which abortive secretion subsequently develops. These changes are due to the fact that when taking these drugs, the gestagens contained in them inhibit the processes of proliferation in the glands, as a result of which the latter do not reach their full development, as is the case with a normal cycle. Secretory changes that develop in such glands have an unexpressed abortive character,

Another typical feature of changes in the endometrium when taking hormonal contraceptives is a pronounced focality, diversity of the morphological picture of the endometrium, namely: the existence of different degrees of maturity of glands and stroma that do not correspond to the day of the cycle. These patterns are characteristic of both proliferative and secretory phases of the cycle.

Thus, when taking combined hormonal contraceptives in the endometrium of women, there are pronounced deviations from the morphological picture of the endometrium of the corresponding phases of the normal cycle. However, as a rule, after discontinuation of the drugs, there is a gradual and complete restoration of the morphological structure of the uterine mucosa (the only exception is cases when the drugs were taken for a very long time - 10-15 years).

CHANGES IN THE ENDOMETRIUM ARISING DURING PREGNANCY AND ITS TERMINATION

When pregnancy occurs, implantation of a fertilized egg - a blastocyst occurs on the 7th day after ovulation, that is, on the 20th - 22nd day of the menstrual cycle. At this time, the recurrent reaction of the endometrial stroma is still very weakly expressed. The most rapid formation of decidual tissue occurs in the zone of blastocyst implantation. As for changes in the endometrium outside of implantation, the decidual tissue becomes clearly expressed only from the 16th day after ovulation and fertilization, i.e., when menstruation is already delayed by 3-4 days. This is observed in the endometrium equally in both uterine and ectopic pregnancy.

In the decidua lining the walls of the uterus along its entire length, with the exception of the zone of implantation of the blastocyst, a compact layer and a spongy layer are distinguished.

In a compact layer of decidual tissue in early pregnancy, two types of cells are found: large, vesicle-shaped cells with a pale staining nucleus and smaller oval or polygonal cells with a darker nucleus. Large decidual cells are the final form of development of small cells.

The spongy layer differs from the compact layer in the exceptionally strong development of the glands, which are closely adjacent to each other and form a tissue, the general appearance of which may have some resemblance to an adenoma.

In histological diagnosis based on scrapings and tissues released spontaneously from the uterine cavity, it is necessary to distinguish between trophoblast cells and decidual cells, especially when it comes to differential diagnosis between uterine and ectopic pregnancy.

Cells trophoblast, that make up the reservoir are polymorphic with a predominance of small polygonal ones. There are no vessels, fibrous structures, leukocytes in the formation. If among the cells that make up the layer, there are single large syncytial formations, then this immediately solves the question of whether it belongs to the trophoblast.

Cells decidual fabrics also have different sizes, but they are larger, oval. The cytoplasm is homogeneous, pale; nuclei are vesicular. The layer of decidual tissue contains vessels and leukocytes.

In case of violation of pregnancy, the formed tissue of the decidual shell becomes necrotic and is usually completely rejected. If the pregnancy is violated in the early stages, when the decidual tissue is still completely undeveloped, then it undergoes reverse development. An undoubted sign that the endometrial tissue was subjected to reverse development after pregnancy, disturbed in the early stages, is the presence of tangles of spiral arteries in the functional layer. A characteristic, but not absolute, sign is also the presence of the Arias-Stella phenomenon (the appearance in the glands of cells with a very large hyperchromic nucleus).

In violation of pregnancy, one of the most important questions that a morphologist has to answer is the question of uterine or ectopic pregnancy. The absolute signs of uterine pregnancy are the presence in the scraping of chorionic villi, decidual tissue with invasion of the chorionic epithelium, the deposition of fibrinoid in the form of foci and strands in the decidual tissue and in the walls of venous vessels.

In those cases when decidual tissue without chorion elements is found in the scraping, this is possible both with uterine and ectopic pregnancy. In this regard, both the morphologist and the clinician should remember that if curettage was performed no earlier than 50 days after the last menstruation, when the area of ​​​​the ovum is large enough, then chorionic villi are almost always found in the uterine form of pregnancy. Their absence suggests an ectopic pregnancy.

At an earlier pregnancy, the absence of chorion elements in the scraping does not always indicate an ectopic pregnancy, since an unnoticed spontaneous miscarriage cannot be ruled out: during bleeding, a small fetal egg could stand out completely even before curettage.

All-Union Scientific and Methodological Center for the Pathological and Anatomical Service of the Institute of Human Morphology of the USSR Academy of Medical Sciences
Leningrad State Order of Lenin Institute for the Improvement of Physicians. CM. Kirov
I Leningrad Order of the Red Banner of Labor Medical Institute. I. P. Pavlova

Editor - Professor O. K. Khmelnitsky

Early stage of the proliferation phase. In this phase of the menstrual cycle, the mucosa is traced in the form of a narrow echo-positive strip ("traces of the endometrium") of a homogeneous structure, 2-3 mm thick, located centrally.

Colpocytology. The cells are large, light, with medium-sized nuclei. Moderate folding of cell edges. The number of eosinophilic and basophilic cells is approximately the same. Cells are placed in groups. There are few leukocytes.

Histology of the endometrium. The surface of the mucous membrane is covered with flattened cylindrical epithelium, which has a cubic shape. The endometrium is thin, there is no division of the functional layer into zones. The glands look like straight or several winding tubes with a narrow lumen. On transverse sections, they have a round or oval shape. The epithelium of the glandular crypts is prismatic, the nuclei are oval, located at the base, stain well. The cytoplasm is basophilic, homogeneous. The apical edge of the epithelial cells is even, clearly defined. On its surface, using electron microscopy, long microvilli are determined, which contribute to an increase in the surface of the cell. The stroma consists of spindle-shaped or stellate reticular cells with delicate processes. Little cytoplasm. It is barely noticeable around the nuclei. In stromal cells, as well as in epithelial cells, single mitoses appear.

Hysteroscopy. In this phase of the menstrual cycle (up to the 7th day of the cycle), the endometrium is thin, even, of a pale pink color, small hemorrhages are visible in some areas, single areas of the endometrium of a pale pink color are visible, which are not torn away. The eyes of the fallopian tubes are well traced.

Middle phase of proliferation. The middle stage of the proliferation phase lasts from 4-5 to 8-9 days after menstruation. The thickness of the endometrium continues to grow up to 6-7 mm, its structure is homogeneous or with a zone of increased density in the center - a zone of contact between the functional layers of the upper and lower walls.

Colpocytology. A large number of eosinophilic cells (up to 60%). Cells are scattered. There are few leukocytes.

Histology of the endometrium. The endometrium is thin, there is no separation of the functional layer. The surface of the mucous membrane is covered with high prismatic epithelium. The glands are somewhat tortuous. The nuclei of epithelial cells are locally located at different levels, numerous mitoses are observed in them. Compared with the early phase of proliferation, the nuclei are enlarged, less intensely stained, some of them contain small nucleoli. From the 8th day of the menstrual cycle, a layer containing acidic mucoid forms on the apical surface of the epithelial cells. Alkaline phosphatase activity increases. The stroma is swollen, loosened, a narrow strip of cytoplasm is visible in the connective tissues. The number of mitoses increases. The vessels of the stroma are solitary, with thin walls.

Hysteroscopy. In the middle stage of the proliferation phase, the endometrium gradually thickens, becomes pale pink in color, and the vessels are not visible.

Late stage of proliferation. In the late stage of the proliferation phase (lasting about 3 days), the thickness of the functional layer reaches 8-9 mm, the shape of the endometrium is usually teardrop-shaped, the central echo-positive line remains unchanged throughout the first phase of the menstrual cycle. Against the general echo-negative background, it is possible to distinguish short, very narrow echo-positive layers of low and medium density, which reflect the delicate fibrous structure of the endometrium.

Colpocytology. The smear mainly contains eosinophilic superficial cells (70%), there are few basophilic cells. In the cytoplasm of eosinophilic cells, granularity is found, the nuclei are small, pyknotic. There are few leukocytes. Characterized by a large amount of mucus.

Histology of the endometrium. Some thickening of the functional layer, but no division into zones. The surface of the endometrium is lined with high columnar epithelium. The glands are more tortuous, sometimes corkscrew-like. Their lumen is somewhat expanded, the epithelium of the glands is high, prismatic. The apical margins of the cells are smooth and distinct. As a result of intensive division and an increase in the number of epithelial cells, the nuclei are at different levels. They are enlarged, still oval, contain small nucleoli. Closer to the 14th day of the menstrual cycle, you can see a large number of cells containing glycogen. The activity of alkaline phosphatase in the epithelium of the glands reaches the highest degree. The nuclei of connective tissue cells are larger, rounded, stained less intensely, an even more noticeable halo of cytoplasm appears around them. The spiral arteries that grow from the basal layer at this time already reach the surface of the endometrium. They are still slightly curvy. Under the microscope, only one or two adjacent peripheral vessels are determined.

Psteroscopy. In the late phase of proliferation, the time on the endometrium in certain areas is determined in the form of thickened folds. It is important to note that if menstrual cycle proceeds normally, then in the proliferation phase the endometrium can have a different thickness, depending on the localization - thickened in the days and the back wall of the uterus, thinner on the anterior wall and in the lower third of the body of the uterus.

Early stage of the secretion phase. In this phase of the menstrual cycle (2-4 days after ovulation), the thickness of the endometrium reaches 10-13 mm. After ovulation, due to secretory changes (the result of the production of progesterone by the menstrual corpus luteum of the ovary), the structure of the endometrium becomes homogeneous again until the onset of menstruation. During this period, the thickness of the endometrium increases faster than in the first phase (by 3-5 mm).

Colpocytology. Characteristic deformed cells are wavy, with curved edges, as if folded in half, the cells are located in dense clusters, layers. Cell nuclei are small, pycnotic. The number of basophilic cells is growing.

Histology of the endometrium. The thickness of the endometrium moderately increases compared to the proliferation phase. The glands become more tortuous, their lumen is expanded. The most characteristic sign of the secretion phase, in particular its early stage, is the appearance of subnuclear vacuoles in the epithelium of the glands. Glycogen granules become large, cell nuclei move from the basal to the central regions (indicating that ovulation has occurred). The nuclei, pushed aside by vacuoles to the central parts of the cell, are initially located at different levels, but on the 3rd day after ovulation (day 17 of the cycle), the nuclei that lie above the large vacuoles are located at the same level. On the 18th day of the cycle, in some cells, glycogen granules move to the apical regions of the cells, as if bypassing the nucleus. As a result of this, the nuclei again descend to the base of the cell, and glycogen granules are placed above them, which are located in the apical parts of the cells. The nuclei are more rounded. Mitoses are absent. The cytoplasm of the cells is basophilic. Acid mucoids continue to appear in their apical regions, while the activity of alkaline phosphatase decreases. The stroma of the endometrium is slightly swollen. The spiral arteries are tortuous.

Hysteroscopy. In this phase of the menstrual cycle, the endometrium is swollen, thickened, and forms folds, especially in the upper third of the uterine body. The color of the endometrium becomes yellowish.

Middle stage of the secretion phase. The duration of the middle stage of the second phase is from 4 to 6-7 days, which corresponds to the 18-24th day of the menstrual cycle. During this period, the greatest severity of secretory changes in the endometrium is noted. Sonographically, this is manifested by a thickening of the endometrium by another 1-2 mm, the diameter of which reaches 12-15 mm, and in its even greater density. At the border of the endometrium and myometrium, a rejection zone begins to form in the form of an echo-negative, clearly defined rim, the severity of which reaches a maximum before menstruation.

Colpocytology. Characteristic folding of cells, curved edges, accumulation of cells in groups, the number of cells with pyknotic nuclei decreases. The number of leukocytes moderately increases.

Histology of the endometrium. The functional layer becomes higher. It is clearly divided into deep and superficial parts. The deep layer is spongy. It contains highly developed glands and a small amount of stroma. The surface layer is compact, it contains less tortuous glands and many connective tissue cells. On the 19th day of the menstrual cycle, most of the nuclei are located in the basal part of the epithelial cells. All nuclei are rounded, light. The apical section of the epithelial cells becomes dome-shaped, glycogen accumulates here and begins to be released into the lumen of the glands by apocrine secretion. The lumen of the glands expands, their walls gradually become more folded. The epithelium of the glands is single-row, with nuclei located basally. As a result of intense secretion, the cells become low, their apical edges are indistinctly expressed, as if with teeth. Alkaline phosphatase completely disappears. In the lumen of the glands is a secret that contains glycogen and acid mucopolysaccharides. On the 23rd day, the secretion of the glands ends. A perivascular decidual reaction of the endometrial stroma appears, then the decidual reaction acquires a diffuse character, especially in the superficial parts of the compact layer. The connective tissue cells of the compact layer around the vessels become large, round and polygonal in shape. Glycogen appears in their cytoplasm. Islets of predecidual cells are formed. A reliable indicator of the middle stage of the secretion phase, which indicates a high concentration of progesterone, are changes in the spiral arteries. The spiral arteries are sharply tortuous, form "coils", they can be found not only in the spongy, but also in the superficial parts of the compact layer. Until the 23rd day of the menstrual cycle, the tangles of the spiral arteries are most clearly expressed. Insufficient development of "coils" of spiral arteries in the endometrium of the secretory phase is characterized as a manifestation of a weak function of the corpus luteum and insufficient preparation of the endometrium for implantation. The structure of the endometrium of the secretory phase, the middle stage (22-23 days of the cycle), can be observed with prolonged and increased hormonal function of the menstrual corpus luteum - persistence of the corpus luteum, and in early pregnancy - during the first days after implantation, with uterine pregnancy outside the implantation zone ; with progressive ectopic pregnancy evenly in all parts of the mucous membrane of the uterine body.

Hysteroscopy. In the middle phase of the secretion stage, the hysteroscopic picture of the endometrium does not differ significantly from that in the early phase of this stage. Often, the folds of the endometrium acquire a polypoid shape. If the distal end of the hysteroscope is placed close to the endometrium, the ducts of the glands can be examined.

Late stage of the secretion phase. Late stage of the second phase of the menstrual cycle (lasts 3-4 days). In the endometrium, there are pronounced trophic disorders due to a decrease in the concentration of progesterone. Echographic changes in the endometrium associated with polymorphic vascular reactions in the form of hyperemia, spasms and thrombosis with the development of hemorrhages, necrosis and other dystrophic changes, a slight heterogeneity (spotting) of the mucosa appears due to the appearance of small areas (dark "spots" - zones of vascular disorders), becomes clearly visible the rim of the rejection zone (2-4 mm), and the three-layer structure of the mucosa characteristic of the proliferative phase is transformed into a homogeneous tissue. There are cases when the echo-negative zones of the endometrial thickness in the preovulatory period are mistakenly regarded by ultrasound as its pathological changes.

Colpocytology. The cells are large, pale-colored, foamy basophilic, without inclusions in the cytoplasm, the contours of the cells are indistinct, vague.

Histology of the endometrium. The folding of the gland walls is enhanced, it has a dust-like shape on longitudinal sections, and a star-like shape on transverse sections. The nuclei of some epithelial gland cells are pyknotic. The stroma of the functional layer is wrinkled. Predecidual cells are brought together and diffusely distributed around the spiral vessels throughout the compact layer. Among the predecidual cells are small cells with dark nuclei - endometrial granular cells, which are transformed from connective tissue cells. On the 26-27th day of the menstrual cycle, lacunar expansion of capillaries into the stroma is observed in the surface areas of the compact layer. In the premenstrual period, spiralization becomes so pronounced that blood circulation slows down and stasis and thrombosis occur. The day before the onset of menstrual bleeding, the state of the endometrium occurs, which Schroeder called "anatomical menstruation." At this time, you can find not only dilated and blood-filled vessels, but also their spasm and thrombosis, as well as small bonfire hemorrhages, edema, and leukocyte infiltration of the stroma.

Psteroscopy. In the late phase of the secretion stage, the endometrium acquires a reddish tint. Due to the pronounced thickening and folding of the mucosa, the eyes of the fallopian tubes can not always be seen. Before the menstruation itself, the appearance of the endometrium can be mistakenly interpreted as a pathology of the endometrium (polypoid hyperplasia). Therefore, the time of hysteroscopy must be fixed for the pathologist.

Bleeding phase (desquamation). During menstrual bleeding due to a violation of the integrity of the endometrium due to its rejection, the presence of hemorrhages and blood clots in the uterine cavity, the echographic picture changes over the days of menstruation as parts of the endometrium with menstrual blood depart. At the beginning of menstruation, the rejection zone is still visible, although not entirely. The structure of the endometrium is heterogeneous. Gradually, the distance between the walls of the uterus decreases and before the end of menstruation, they "close" to each other.

Colpocytology. In the smear foamy basophilic cells with large nuclei. A large number of erythrocytes, leukocytes, endometrial cells, histocytes are found.

Histology of the endometrium(28-29 days). Tissue necrosis, autolysis develops. This process begins with the surface layers of the endometrium and is of a bonfire character. As a result of vasodilation, which occurs after a long spasm, a significant amount of blood enters the endometrial tissue. This leads to rupture of blood vessels and detachment of necrotic sections of the functional layer of the endometrium.

Morphological features characteristic of the endometrium of the menstrual phase are: the presence in the tissue permeated with hemorrhages, areas of necrosis, leukocyte infiltration, a partially preserved area of ​​the endometrium, as well as tangles of spiral arteries.

Hysteroscopy. In the first 2-3 days of menstruation, the uterine cavity is filled with a large number of fragments of the endometrium from pale pink to dark purple, especially in the upper third. In the lower and middle third of the uterine cavity, the endometrium is thin, pale pink in color, with small punctate hemorrhages and areas of old hemorrhages. If the menstrual cycle was full, then by the second day of menstruation, almost complete rejection of the uterine mucosa takes place, only small fragments of the mucosa are determined in some of its sections.

Regeneration(3-4 days of the cycle). After rejection of the necrotic functional layer, regeneration of the endometrium from the tissues of the basal layer is observed. The epithelialization of the wound surface occurs due to the marginal sections of the glands of the basal layer, from which epithelial cells move to the wound surface in all directions and close the defect. With normal menstrual bleeding under conditions of a normal two-phase cycle, the entire wound surface is epithelialized on the 4th day of the cycle.

Hysteroscopy. During the regeneration stage, against a pink background with areas of mucosal hyperemia, small hemorrhages shine through in some areas, single areas of the endometrium of a pale pink color can be found. As the endometrium regenerates, areas of hyperemia disappear, changing color to pale pink. The corners of the uterus are well visible.

Content

The endometrium covers the entire uterus from the inside and is distinguished by a mucous structure. It is updated monthly and performs several important functions. The secretory endometrium has numerous blood vessels that supply blood to the body of the uterus.

The structure and purpose of the endometrium

The endometrium in its structure is basal and functional. The first layer remains practically unchanged, and the second regenerates the functional layer during menstruation. If there are no pathological processes in the woman's body, then its thickness is 1-1.5 centimeters. The functional layer of the endometrium changes regularly. Such processes are associated with the fact that during menstruation in the uterine cavity separate sections of the walls exfoliate.

Damage appears during labor, during mechanical abortion or diagnostic sampling for histology.

The endometrium performs an extremely important function in the body of a woman and helps the successful course of pregnancy. The fruit is attached to its walls. Nutrients and oxygen necessary for life come to the embryo. Thanks to the mucous layer of the endometrium, the opposite walls of the uterus do not stick together.

menstruation cycle in women

In the female body, changes occur every month that help create optimal conditions for conceiving and bearing a child. The period between them is called the menstrual cycle. On average, its duration is 20-30 days. The beginning of the cycle is the first day of menstruation. At the same time, the endometrium is updated and cleansed.

If during the menstrual cycle in women deviations are noted, then this indicates serious disorders in the body. The cycle is divided into several phases:

• proliferation;
• secretion;
• menstruation.

Proliferation refers to the processes of reproduction and division of cells that contribute to the growth of the internal tissues of the body. During the proliferation of the endometrium in the mucous membrane of the uterine cavity, normal cells begin to divide. Such changes can take place during menstruation or have a pathological origin.

Duration of proliferation averages up to two weeks. In the body of a woman, estrogen begins to increase intensively, which produces an already mature follicle. This phase can be divided into early, middle and late stages. At an early stage (5-7 days) in the uterine cavity, the surface of the endometrium is covered with epithelial cells that have a cylindrical shape. In this case, the blood arteries remain unchanged.

The middle stage (8-10 days) is characterized by the lining of the mucosal plane with epithelial cells that have a prismatic appearance. The glands are distinguished by a light tortuous shape, and the core has a less intense shade, increases in size. A huge number of cells appear in the uterine cavity, which arose as a result of division. The stroma becomes edematous and rather loose.

The late stage (11-15 days) is characterized by a single-layer epithelium, which has many rows. The gland becomes tortuous, and the nuclei are located at different levels. Some cells contain small vacuoles that contain glycogen. The vessels are distinguished by a tortuous shape, the cell nuclei gradually acquire a rounded shape and greatly increase in size. The stroma becomes engorged.

The endometrium of the uterus of the secretory type can be divided into several stages:

• early (15-18 days of the menstrual cycle);
• medium (20-23 days, pronounced secretion is observed in the body);
• late (24-27 days, secretion gradually fades in the uterine cavity).

The menstrual phase can be divided into several periods:

1. Desquamation. This phase runs from the 28th to the 2nd day of the menstrual cycle and occurs when fertilization has not occurred in the uterine cavity.
2. Regeneration. This phase lasts from the third to the fourth day. It begins before the complete separation of the functional layer of the endometrium, along with the beginning of the growth of epithelial cells.

normal structure

Hysteroscopy helps the doctor examine the uterine cavity to assess the structure of the glands, new blood vessels and determine the thickness of the endometrial cell layer.

If you conduct a study in different phases of the menstrual cycle, the result of the examination will be different. For example, by the end of the proliferation period, the basal layer begins to increase, so it does not respond to any hormonal influences. At the very beginning of the cycle period, the internal uterine mucosa has a pinkish tint, a smooth surface and small areas of an incompletely separated functional layer.

At the next stage, the endometrium of the proliferative type begins to grow in the woman's body, which is associated with cell division. Blood vessels are located in folds and result from uneven thickening of the endometrial layer. If there are no pathological changes in the woman's body, then the functional layer should be completely rejected.

Deviation forms

Any deviations in the thickness of the endometrium arise as a result of functional causes or pathological changes. Functional disorders appear in the early stages of pregnancy or a week after the fertilization of the egg. In the uterine cavity, the child's place gradually thickens.

Pathological processes arise as a result of the chaotic division of healthy cells, which form excess soft tissues. In this case, neoplasms and tumors of a malignant nature are formed in the body of the uterus. These changes most often occur as a result of hormonal failure in endometrial hyperplasia. Hyperplasia comes in several forms.

1. glandular. In this case, there is no clear separation between the basal and functional layers. The number of glands increases.
2. Glandular cystic form. A certain part of the glands forms a cyst.
3. Focal. In the uterine cavity, epithelial tissues begin to grow and numerous polyps form.
4. Atypical. In the body of a woman, the structure of the structure of the endometrium changes and the number of connective cells decreases.

Endometrium of the uterus secretory type appears in the second phase of the menstrual cycle, in case of conception, it helps the ovum to attach to the wall of the uterus.

secretory type

During the menstrual cycle, most of the endometrium dies, but when menstruation occurs, it is restored by cell division. After five days, the structure of the endometrium becomes renewed and is quite thin. The endometrium of the uterus of the secretory type has an early and late phase. It has the ability to grow and increases several times with the onset of menstruation. In the first stage, the inner lining of the uterus is covered with a cylindrical low epithelium, which has tubular glands. In the second cycle, the endometrium of the uterus of the secretory type is covered with a thick layer of epithelium. The glands in it begin to lengthen and acquire a wavy shape.

In the stage of the secretory form, the endometrium changes its original shape and significantly increases in size. The structure of the mucous membrane becomes saccular, glandular cells appear, through which mucus is secreted. The secretory endometrium is characterized by a dense and smooth surface with a basal layer. However, he is not active. The secretory type of the endometrium coincides with the period of formation and further development of follicles.

In the cells of the stroma, glycogen gradually accumulates, and a certain part of them is transformed into decidual cells. At the end of the period, the corpus luteum begins to involute, and the work of progesterone stops. In the secretory phase of the endometrium, glandular and glandular cystic hyperplasia may develop.

Causes of glandular cystic hyperplasia

Glandular cystic hyperplasia occurs in women of all ages. In most cases, formations occur in the secretory type of the endometrium during the period of hormonal changes.

Congenital causes of glandular cystic hyperplasia include:

• hereditary genetic abnormalities;
• hormonal failure during puberty in adolescents.

Acquired pathologies include:

• problems of hormonal dependence are endometriosis and mastopathy;
• inflammatory processes in the genitals;
• infectious pathologies in the pelvic organs;
• gynecological manipulations;
• curettage or abortion;
• violations in the proper functioning of the endocrine system;
• excess body weight;
• polycystic ovaries;
• arterial hypertension;
• depressed function of the liver, mammary gland and adrenal glands.

If in the family one of the women was diagnosed with glandular cystic hyperplasia of the endometrium, then other girls need to be especially attentive to their health. It is important to regularly come for a preventive examination to a gynecologist who will be able to identify possible deviations or pathological disorders in the uterine cavity in time.

Clinical manifestations

Glandular cystic hyperplasia, which is formed in the secretory endometrium, is manifested by the following symptoms.

• Menstrual disorders. Spotting spotting between menses.
• The discharge is not profuse, but with bloody dense clots. With prolonged blood loss, patients may experience anemia.
• Pain and discomfort in the lower abdomen.
• Lack of ovulation.

Pathological changes can be determined at the next preventive examination by a gynecologist. Glandular cystic hyperplasia of the secretory endometrium does not resolve on its own, so it is important to seek help from a qualified doctor in time. Only after a comprehensive diagnosis, the specialist will be able to prescribe therapeutic treatment.

Diagnostic methods

It is possible to diagnose glandular cystic hyperplasia of the secretory endometrium using the following diagnostic methods.

• Diagnostic examination by a gynecologist.
• Analysis of the patient's history, as well as the determination of hereditary factors.
• Ultrasound examination of the uterine cavity and pelvic organs. A special sensor is inserted into the uterus, thanks to which the doctor examines and measures the endometrium of the uterus of a secretory type. It also checks for polyps, cystic masses, or nodules. But, ultrasound does not give the most accurate result, so other methods of examination are prescribed for patients.
• Hysteroscopy. Such an examination is carried out with a special medical optical apparatus. During the diagnosis, differential curettage of the secretory endometrium of the uterus is done. The resulting sample is sent for histological examination, which will determine the presence of pathological processes and the type of hyperplasia. This technique should be carried out before the onset of menstruation. The results obtained are the most informative, so gynecologists will be able to make a correct and accurate diagnosis. With the help of hysteroscopy, it is possible not only to determine the pathology, but also to perform surgical treatment of the patient.
• aspiration biopsy. During a gynecological examination, the doctor makes a scraping of the secretory endometrium. The resulting material is sent for histology.
• Histological examination. This diagnostic method determines the morphology of the diagnosis, as well as the type of hyperplasia.
• Laboratory studies on the level of hormones in the body. If necessary, hormonal disorders are checked in the thyroid gland and adrenal glands.

Only after a thorough and comprehensive examination, the doctor will be able to make the correct diagnosis, as well as prescribe an effective treatment. The gynecologist will individually select medicines and their exact dosages.