What is the secretion phase and the proliferation phase. Cyclic changes in the endometrium under the influence of steroid hormones. Changes in the endometrium in the proliferation phase

To find out what a proliferative type of endometrium is, it is necessary to understand how the female body functions. Inner part uterus, lined with endometrium, undergoes cyclical changes during 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 (stromas), equipped with glands and a large number branched blood vessels. AT normal condition 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 necessary conditions for the onset and successful course of pregnancy, when it increases the number of glands and blood vessels that make up the structure of the placenta. One of the appointments children's place- supplying the embryo with nutrients and oxygen. Another function is to prevent the opposite walls of the uterus from sticking together.

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AT female body monthly changes occur, during which favorable conditions 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 appear indirect division. The stroma becomes loose and edematous.

For 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 up more round 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 uneven thickening of the endometrium on inner walls folds appear in the uterus. In the proliferation phase, the back wall and bottom normally have the thickest mucous layer, and the anterior wall and Bottom part children's place - the most subtle. 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 individual standards.

The hysteroscopic picture of the unchanged endometrium depends on the phase of the menstrual cycle (in reproductive period) and the duration of menopause (in the postmenopausal period). As you know, the management of the normal menstrual cycle occurs at the level of specialized brain neurons that receive information about the state of the external environment, convert it into neurohormonal signals (norepinephrine), which subsequently enter the neurosecretory cells of the hypothalamus.

In the hypothalamus (at the base of the third ventricle), under the influence of norepinephrine, gonadotropin-releasing factor (GTRF) is synthesized, which ensures the release of hormones of the anterior pituitary gland into the bloodstream - follicle-stimulating (FSH), luteinizing (LH) and lactotropic (prolactin, PRL) hormones. The role of FSH and LH in the regulation of the menstrual cycle is quite clearly defined: FSH stimulates the growth and maturation of follicles, LH stimulates steroidogenesis. Under the influence of FSH and LH, the ovaries produce estrogens and progesterone, which, in turn, cause cyclic transformations in target organs - the uterus, fallopian tubes ah, the vagina, as well as in the mammary glands, skin, hair follicles, bones, adipose tissue.

The secretion of estrogens and progesterone by the ovaries is accompanied by cyclic transformations both in the muscular and mucous membranes of the uterus. In the follicular phase of the cycle, hypertrophy of myometrial cells occurs, in the luteal phase - their hyperplasia. In the endometrium, the follicular and luteal phases correspond to periods of proliferation and secretion (in the absence of conception, the secretion phase is replaced by the desquamation phase - menstruation). The proliferative phase begins with slow growth of the endometrium. The early proliferative phase (up to 7-8 days of the menstrual cycle) is characterized by the presence of short elongated glands with narrow lumens lined with a cylindrical epithelium, in the cells of which numerous mitoses are observed.

There is a rapid growth of the spiral arteries. The middle proliferative phase (up to 10-12 days of the menstrual cycle) is characterized by the appearance of elongated tortuous glands and moderate edema of the stroma. The spiral arteries become tortuous due to their greater rapid growth compared to endometrial cells. AT late phase proliferation of the gland continues to increase, become sharply convoluted, acquire an oval shape.

In the early phase of secretion (the first 3-4 days after ovulation, up to the 17th day of the menstrual cycle), there is further development glands and expansion of their lumen. Mitoses disappear in epithelial cells, and the concentration of lipids and glycogen in the cytoplasm increases. The middle stage of secretion (19-23 days of the menstrual cycle) reflects the transformations characteristic of the heyday corpus luteum, i.e. period of maximum gestagenic saturation. The functional layer becomes higher, distinctly divided into deep (spongiform) and superficial (compact) layers.

The glands expand, their walls become folded; a secret containing glycogen and acidic glycosaminoglucuronglycans (mucopolysaccharides) appears in the lumen of the glands. Stroma with the phenomena of perivascular decidual reaction, in the interstitial substance it increases the amount of acid glycosaminoglucuronglycans. Spiral arteries are sharply tortuous, form "balls" (the most reliable sign that determines the luteinizing effect).

Late stage of secretion (24-27 days of the menstrual cycle): during this period, processes associated with the regression of the corpus luteum and, consequently, a decrease in the concentration of hormones produced by it, are observed - the trophism of the endometrium is disturbed, its degenerative changes are formed, morphologically the endometrium regresses, signs of its ischemia appear . This reduces the juiciness of the tissue, which leads to wrinkling of the stroma of the functional layer. Folding of the walls of the glands increases.

On the 26-27th day of the menstrual cycle, lacunar expansion of capillaries and focal hemorrhages in the stroma are observed in the surface layers of the compact layer; due to the melting of fibrous structures, areas of separation of the cells of the stroma and epithelium of the glands appear. This condition of the endometrium is referred to as "anatomical menstruation" and immediately precedes clinical menstruation.

In the mechanism of menstrual bleeding importance it is assigned to circulatory disorders caused by prolonged spasm of the arteries (stasis, thrombus formation, fragility and permeability of the vascular wall, hemorrhage into the stroma, leukocyte infiltration). The result of these transformations are tissue necrobiosis and its melting. Due to the expansion of blood vessels that occurs after a long spasm, a large amount of blood enters the endometrial tissue, which leads to rupture of blood vessels and rejection (desquamation) of the necrotic sections of the functional layer of the endometrium, i.e. to menstrual bleeding.

The regeneration phase is rather short and is characterized by the regeneration of the endometrium from the cells of the basal layer. Epithelialization of the wound surface occurs from the marginal sections of the basement membrane glands, as well as from the non-torn off deep sections of the functional layer.

Normally, the uterine cavity has the shape of a triangular slit, in upper divisions which the mouths of the fallopian tubes open, and its lower section communicates with the cervical canal through the internal opening. It is advisable to evaluate the endoscopic picture of the uterine mucosa during an undisturbed menstrual cycle, taking into account the following criteria:
1) the nature of the mucosal surface;
2) the height of the functional layer of the endometrium;
3) the state of the tubular glands of the endometrium;
4) the structure of the mucosal vessels;
5) the state of the mouths of the fallopian tubes.

In the early phase of proliferation endometrium pale pink or yellow-pink, thin (up to 1-2 mm). The excretory ducts of the tubular glands are clearly visualized, evenly spaced. A dense vascular network is identified through the thin mucosa. In some areas, small hemorrhages are translucent. The mouths of the fallopian tubes are free, easily defined in the form of oval or slit-like passages, localized in the recesses of the lateral sections of the uterine cavity.

1 - the mouth of the fallopian tube is free, defined as a slit-like passage

1 - endocervix; 2 - the bottom of the uterus; 3 - the mouth of the fallopian tube; in this phase, the lumen of the glands is less noticeable, but the vessels can be identified

in the specified period, dark-purple layers are identified, freely hanging into the uterine cavity - fragments of the torn endometrium (1)

In the postmenopausal period in the reproductive system of women, involutive processes progress due to a decrease in the regenerative potential of cells. In all organs reproductive system atrophic processes are observed: the ovaries shrink and sclerosis; the mass of the uterus decreases, its muscular elements are replaced by connective tissue; the epithelium of the vagina becomes thinner. In the early years of menopause, the endometrium has a transitional structure characteristic of the premenopausal period.

In the future (as the progressive fading of ovarian function) resting non-functioning endometrium is transformed into atrophic. In low atrophic endometrium, the functional layer is indistinguishable from the basal layer. The wrinkled compact stroma, rich in fibers, including collagen, contains small single glands lined with low single-row cylindrical epithelium. The glands look like straight tubes with a narrow lumen. Distinguish between simple and cystic atrophy. Cystically enlarged glands are lined with low single-row cylindrical epithelium.

Hysteroscopic picture in postmenopause is determined by its duration. In the period corresponding to the transitional mucosa, the latter is characterized by a pale pink color, a weak vascular pattern, single point and scattered hemorrhages. The mouths of the fallopian tubes are free, and near them the surface of the uterine cavity is pale yellow with a dull tint. Atrophic endometrium has a uniform pale or pale yellow color, the functional layer is not identified. The vascular network is often not visualized, although mucosal varicose veins may be observed. The uterine cavity is sharply reduced, the mouths of the fallopian tubes are narrowed.

With induced atrophy of the endometrium due to exposure to exogenous hormones (the so-called glandular hypoplasia with glandular-stromal dissociation), the mucosal surface is uneven ("cobblestone"), yellow-brown in color. The height of the functional layer does not exceed 1-2 mm. Between the "cobblestones" deep stromal vessels are visible. The mouths of the fallopian tubes are well visualized, their lumen is narrowed.

The study of the endoscopic anatomy of the endometrium and the walls of the uterine cavity allows not only to assess the cyclic changes in the mucosa of patients examined for infertility, but also to carry out differential diagnosis between the norm and pathological transformation of the endometrium. Briefly, the main provisions of this chapter can be presented as follows:

• proliferation phase:

• secretion phase:

• endometrial atrophy:

• induced endometrial atrophy:

A.N. Strizhakov, A.I. Davydov

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The endometrium is the outer mucous layer that lines the uterine cavity. It is completely hormone-dependent, and it is he who undergoes the greatest changes during the menstrual cycle, it is his cells that are rejected and come out with the secretions during menstruation. All these processes proceed in accordance with certain phases, and deviations in the passage or duration of these phases can be considered pathological. Proliferative endometrium - a conclusion that can often be seen in the description of ultrasound - is the endometrium in the proliferative phase. About what this phase is, what stages it has and what it is characterized by, is described in this material.

Definition

What it is? The proliferative phase is the stage of active cell division of any tissue (while its activity does not exceed normal, that is, it is not pathological). As a result of this process, tissues are restored, regenerated, and grow. When dividing, normal, non-atypical cells appear, from which healthy tissue is formed, in this case, endometrium.

But in the case of the endometrium, this is a process of active increase in the mucosa, its thickening. Such a process can be called as natural causes(phase of the menstrual cycle), and pathological.

It is worth noting that proliferation is a term applicable not only to the endometrium, but also to some other tissues in the body.

The reasons

The endometrium of the proliferative type often appears because during the course of menstruation many cells of the functional (renewal) part of the endometrium were rejected. As a result, he became significantly thinner. The features of the cycle are such that for the onset of the next menstruation, this mucous layer must restore its thickness of the functional layer, otherwise there will be nothing to update. This is exactly what happens in the proliferative stage.

In some cases, such a process can be caused by pathological changes. In particular, endometrial hyperplasia (a disease that can, without proper treatment, lead to infertility), is also characterized by increased cell division, leading to a thickening of the functional layer of the endometrium.

Phases of proliferation

Proliferation of the endometrium is a normal process that occurs with the passage of several stages. These stages are always present in the norm, the absence or violation of the course of any of these stages indicates the beginning of the development of the pathological process. The phases of proliferation (early, middle and late) differ depending on the rate of cell division, the nature of tissue growth, etc.

The whole process takes about 14 days. During this time, the follicles begin to mature, they produce estrogen, and it is under the action of this hormone that growth occurs.

Early

This stage occurs approximately from the fifth to the seventh day of the menstrual cycle. On it, the mucous membrane has the following features:

1. Epithelial cells are present on the surface of the layer;
2. The glands are elongated, straight, oval or round in cross section;
3. The glandular epithelium is low, and the nuclei are of intense color, and are located at the base of the cells;
4. Stroma cells are spindle-shaped;
5. The blood arteries are not tortuous at all or are minimally tortuous.

The early stage ends 5-7 days after the end of menstruation.

Medium

This is a short stage that lasts approximately two days from the eighth to the tenth day of the cycle. At this stage, the endometrium undergoes further changes. It acquires the following features and characteristics:

• epithelial cells that line outer layer endometrium, have a prismatic appearance, they are high;
• The glands become slightly more tortuous compared to the previous stage, their nuclei are less brightly colored, they become larger, there is no steady tendency to any of their location - they are all at different levels;
• The stroma becomes edematous and loose.

endometrium middle stage the secretion phase is characterized by the appearance of a certain number of cells formed by the method of indirect division.

Late

The endometrium of the late stage of proliferation is characterized by convoluted glands, the nuclei of all cells of which are located at different levels. The epithelium has one layer and many rows. Vacuoles with glycogen appear in a number of epithelial cells. The vessels are also tortuous, the state of the stroma is the same as in the previous stage. Cell nuclei are round and large. This stage lasts from the eleventh to the fourteenth day of the cycle.

Phases of secretion

The secretion phase occurs almost immediately after proliferation (or after 1 day) and is inextricably linked with it. It also distinguishes a number of stages - early, middle and late. They are characterized by a number of typical changes that prepare the endometrium and the body as a whole for the menstrual phase. The endometrium of the secretory type is dense, smooth, and this applies to both the basal and functional layers.

Early

This stage lasts approximately from the fifteenth to the eighteenth day of the cycle. It is characterized by a weak expression of secretion. At this stage, it is just beginning to develop.

Medium

At this stage, secretion proceeds as actively as possible, especially in the middle of the phase. A slight extinction of the secretory function is observed only at the very end of this stage. It lasts from the twentieth to the twenty-third day

Late

The late stage of the secretion phase is characterized by a gradual extinction of the secretory function, with a complete convergence to nothing at the very end of this stage, after which the woman begins menstruation. This process lasts 2-3 days in the period from the twenty-fourth to the twenty-eighth day. It is worth noting a feature that is characteristic of all stages - they last for 2-3 days, while the exact duration depends on how many days are in the menstrual cycle of a particular patient.

Proliferative diseases

The endometrium in the proliferation phase grows very actively, its cells divide under the influence of various hormones. Potentially, this condition is dangerous development various kinds diseases associated with pathological cell division - neoplasms, tissue growths, etc. Some failures in the process of passing through the stages can lead to the development of pathologies of this type. At the same time, the secretory endometrium is almost completely not subject to such danger.

The most typical disease that develops as a result of a violation of the phase of mucosal proliferation is hyperplasia. This is a condition of pathological growth of the endometrium. The disease is quite serious and requires timely treatment, as it causes severe symptoms (bleeding, pain) and can lead to complete or partial infertility. The percentage of cases of its degeneration into oncology, however, is very low.

Hyperplasia occurs with violations in the hormonal regulation of the division process. As a result, cells divide longer and more actively. The mucous layer thickens considerably.

Why does the proliferation process slow down?

Inhibition of endometrial proliferation processes is a process, also known as insufficiency of the second phase of the menstrual cycle, characterized by the fact that the proliferation process is not active enough or does not go at all. This is a symptom of menopause, ovarian failure and lack of ovulation.

The process is natural and helps predict the onset of menopause. But it can also be pathological if it develops in a woman of reproductive age, this indicates a hormonal imbalance that needs to be corrected, since it can lead to dysmenorrhea and infertility.

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 is 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 by scrapings of the endometrium has 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 uterus is produced. 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.

If there is bleeding, especially in women who are in menopause or in menopause, you should 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 women in order to identify precancerous conditions and endometrial cancer in “groups increased risk". 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 function 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. Can also be used accelerated method pouring into paraffin according to G.A. Merkulov with fixation in formalin, heated to 37°C in a thermostat in within 1-2 hours.

AT daily 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°С, 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 secretion phase-in 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 vasodilating action 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 date of the occurred ovulation, which in normal conditions 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 located on various levels. The epithelial cells of the glands of the early phase of proliferation are characterized by the absence of glycogen and moderate activity. 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 gestagenic 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. Morphological feature characteristic of the endometrium 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, because among various reasons causing such bleeding, about 30% are malignant neoplasms 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, occupy most cells. 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 after many years. After the onset of menopause, with a tendency to relapse, should be regarded as unfavorable factor in a relationship possible occurrence 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 decreased secretion progesterone in a 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 endometrial scrapings obtained with such bleeding after the 5th day seems to be very variegated: scrapings show areas of necrotic tissue, areas in a state of reverse development, 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 impact low concentrations 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 nested groups of light cells are found in the glands, which have morphological similarities with squamous epithelium- adenocantosis. 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 is the basis. International classification 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 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 in gynecological practice estrogen and progestin preparations are widely used to treat 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. At long-term use estrogen against the background of proliferation may occur abundant acyclic uterine bleeding.

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 drugs, there is a gradual and full recovery 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 only strong development glands that are closely adjacent to each other and form 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 reservoir. 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 case of violation of pregnancy, one of the most important issues that the morphologist has to answer is the question of uterine or ectopic pregnancy. Absolute signs 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 former last menstrual period, when the area of ​​​​location of the fetal egg is large enough, then with the uterine form of pregnancy, chorionic villi are almost always found. Their absence suggests ectopic pregnancy.

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

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

One of the most common tests functional diagnostics is a histological examination of scrapings of the endometrium. For the purposes of functional diagnostics, the so-called “dash scraping” is usually used, in which a small strip of the endometrium is taken with a small curette. Clinical-morphological and differential diagnosis phases of the 28-day menstrual cycle according to the structures of the endometrium is clearly shown in the work of O. I. Topchieva (1967) and can be recommended for practical use. The whole is divided into 3 phases: proliferation, secretion, bleeding, and the phases of proliferation and secretion are divided into early, middle and late stages, and the bleeding phase into desquamation and regeneration.

When assessing the changes occurring in the endometrium, it is necessary to take into account the duration of the cycle, its clinical manifestations(presence or absence of premenstrual and postmenstrual bleeding, duration of menstrual bleeding, amount of blood loss, etc.).

Early stage phases of proliferation(5-7th day) is characterized by the fact that the surface of the mucosa is lined with cuboidal epithelium, the endometrial glands look like straight tubes with a narrow lumen, on the cross section the contours of the glands are round or oval; the epithelium of the glands is prismatic, low, the nuclei are oval, located at the base of the cells, intensely stained. The stroma consists of spindle-shaped cells with large nuclei. The spiral arteries are slightly tortuous.

In the middle stage (8-10th day), the surface of the mucosa is lined with high prismatic epithelium. The glands are slightly tortuous. Numerous mitoses are determined in the nuclei. On the apical edge of some cells, a border of mucus may be found. The stroma is edematous, loosened.

In the late stage (11-14th day), the glands acquire a sinuous outline. Their lumen is expanded, the nuclei are located at different levels. AT basal departments some cells begin to show small vacuoles containing glycogen. The stroma is juicy, the nuclei increase, round and stain less intensely. Vessels take on a convoluted shape.

The described changes, characteristic of a normal cycle, can occur in pathology: a) during the second half of the menstrual cycle in anovulatory cycles; b) with dysfunctional uterine bleeding due to anovulatory processes; c) with glandular hyperplasia - in various parts of the endometrium.

If tangles of spiral vessels are found in the functional layer of the endometrium of the proliferation phase, this indicates that the previous cycle was two-phase, and when next menstruation there was no rejection of the entire functional layer and it only underwent reverse development.

Early stage secretion phases(15-18th day) subnuclear vacuolization is found in the epithelium of the glands; vacuoles push nuclei into central departments cells; nuclei are located on the same level; vacuoles contain glycogen particles. The lumen of the glands is enlarged, traces of the secret can already be determined in them. The stroma of the endometrium is juicy, loose. The vessels become even more tortuous. A similar structure of the endometrium can occur with the following hormonal disorders: a) with an inferior corpus luteum at the end of the menstrual cycle; b) with a delayed onset of ovulation; c) with cyclic bleeding that occurs as a result of the death of the corpus luteum, which has not reached the flowering stage; d) with acyclic bleeding due to the early death of an inferior corpus luteum.

In the middle stage of the secretion phase (19-23rd day), the lumen of the glands is expanded, their walls become folded. Epithelial cells are low, filled with a secret that separates into the lumen of the gland. In the stroma, by the 21st-22nd day, a decidua-like reaction begins to occur. Spiral arteries are sharply tortuous, form tangles, which is one of the most reliable signs of a full-fledged luteal phase. A similar structure of the endometrium can be observed with prolonged and increased function corpus luteum or when taking large doses progesterone, with an early uterine period (outside the implantation zone), with a progressive ectopic pregnancy.

In the late stage of the secretion phase (24-27th day), due to the regression of the corpus luteum, the juiciness of the tissue decreases; the functional layer decreases in height. The folding of the glands increases, acquiring a sawtooth shape in longitudinal and star-shaped in transverse sections. In the lumen of the glands is a secret. Perivascular decidua-like reaction of the stroma is intense. Spiral vessels form coils closely adjacent to each other. By the 26-27th day venous vessels engorged with blood clots. In the stroma of the compact layer, leukocyte infiltration occurs; focal hemorrhages and areas of edema appear and grow. A similar condition must be differentiated from endometritis, in which the cellular infiltrate is localized mainly around the vessels and glands.

In the bleeding (menstruation) phase, the desquamation stage (28-2nd day) is characterized by an increase in the changes noted for the late secretory stage. Rejection of the endometrium begins with the surface layers and is focal in nature. Complete desquamation is completed by the third day of menstruation. A morphological sign of the menstrual phase is the discovery in the necrotic tissue of collapsed glands with stellate outlines. Regeneration (3-4th day) occurs from the tissues of the basal layer. To fourth day The mucosa is normally epithelized. Violation of rejection and regeneration of the endometrium may be due to a slowdown in the process or incomplete rejection with the reverse development of the endometrium.

The pathological state of the endometrium is characterized by the so-called hyperplastic proliferative changes (glandular hyperplasia, glandular-cystic hyperplasia, mixed form of hyperplasia, adenomatosis) and hypoplastic conditions (resting, non-functioning endometrium, transitional endometrium, dysplastic, hypoplastic, mixed endometrium).