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Husanghodjaeva Malika Tursunkhodzhaevna, Head of the Department of Emergency Gynecology Republican Scientific Center of Emergency E-mail: medical center, Uzbekistan E-mail: [email protected]
MORPHOLOGICAL, MORPHOMETRIC CHANGES IN MOMOMATOUS NODES IN WOMEN WITH UTERINE MOMORY
Abstract: The development of proliferative processes is due not only to the increased proliferation of cells, but also to the weakening of the induction of apoptosis. With low proliferative activity (simple MM), the level of apoptotic activity is high enough. With a high activity of proliferative processes, the level of apoptosis is sharply reduced, i.e. tumor growth can be considered as a consequence of the imbalance between cell proliferation and apoptosis.
Keywords: Myoma of the uterus, myomatous node, proliferation, apoptosis.
Myoma of the uterus (MM) is the most common pathological anatomy of RSCEMP (head of department,
reproductive tract tumor in women of childbearing age and occupies one of the leading places in the pathology of the reproductive system [1,2]. In the dynamics of recurrent MM after ME, morphological and morphomet-ric features of simple and proliferative MM were studied during and outside of pregnancy, complementing the understanding of the pathogenesis of the disease and tumor recurrence after ME. The participation of apoptosis processes in the development of simple and proliferating MM is characterized [3, 4, 5].
The main causative factors and prognostic criteria for relapse of MM after ME have been established (clinico-morphological studies). In the prognosis of relapse, the leading factors were proliferating histotype of MM, hyperplastic processes in the endometrium, endometriosis disease. The proliferating tumor histotype is present in the recurrence of MM after ME with more pronounced mitotic activity compared to the initial parameters. It has been established, in case of relapse of MM after ME, the histological picture of the removed uterus was characterized by multiple true growth zones, rapid and synchronous growth of MU.
Purpose. The study of morphological, morphomet-ric changes in myomatous nodes (MN) in women with uterine myoma (MM).
Materials and methods of research
Morphological, morphometric and immuno-histo-chemical studies were performed in the department of
MD, professor BA Magrupov). This work is based on a prospective sample survey, conservative and operative treatment of 285 women with MM of reproductive age who entered the emergency gynecology department. In the morphological study, macro-preparations, MN, removed during the operation, were studied. For this purpose, in each case, MN was taken from the central and peripheral zones, and in the presence of macroscopically visible focal changes - also several pieces of tissue from such foci.
Results of the study and their discussion
Morphological changes in the MN itself had a progressive character and depended on the size and location of MN and the gestational age. The first signs of a disturbance in the blood supply of MN and evidence of compensatory processes developing in the tissue in response to hypoxia were a new formation of capillary vessels, the number of which in the field of view reached 50-60. There were no proliferative changes around the vessels. In the area of ischemia, areas with poorly expressed in-termnscular edema with preservation of myocyte nuclei were found. Dystrophic changes increased, manifested by more and more increasing edema of the tissue with the expansion of intermnscular spaces. The vessels of the microcirculatory bed in the zone of pathology were unevenly expanded, full-blooded, single leukocytes appeared in the lumen of individual capillaries. Ischemic changes were followed by the development of necrosis of MN. In the cells of MN, still retaining their structure,
signs of dystrophic polymorphism, the amount of chromatin, indicating the apparent non-viability of the dystrophic cells were determined. Later, with the progression of the circulatory disturbance in MN, pronounced intermnscular edema with a sharp expansion of tissue gaps was observed. Foci of necrosis are formed. Massive leukocyte infiltration completely occupied the whole zone of necrosis, in the same zone there were extensive foci of hemorrhages. Capillary vessels and small arterioles were in the state of paretic expansion, in their lumen were determined fibrin clots, and around perivascular hemorrhages. Edema became massive, forming extensive cavities, delaminating intermnscular gaps, and the phenomenon of myxomatosis appeared.
Regardless of the contingent of patients, proliferative MM during ME was met in 11.3% of women. This indicator is almost the same for non-pregnant and pregnant women, traditionally operated, and significantly higher than in women after LME (20 (12.1%) and 1 (3.3%, P <0.05), respectively. women with SS MN who underwent LME, and such localization of MN is not typical for proliferating MM.
Of the 23 patients with a relapse of MM, repeated ME was performed in 16. Macroscopically, the MN of the relapsed MM had borders with the adjacent myo-metrium, but their consistency was milder than that of the simple MM. On a cut they had the appearance of a homogeneous tissue, often with mnltiple hemorrhages, in the form of mnltiple MNs. In a number of cases, there was a picture of MN necrosis and secondary dystrophic changes in the form of hemorrhage into the tissue of MN, edema, the appearance of leukocytes in the tissue lesion zone. "Endometrioid explants in the myometrium formed" growth zone ", and in the endometrium were
clearly expressed signs of glandular hyperplasia. In all 16 women, the recurring MM was proliferating. Foci of proliferation of tumor cells were most often localized in the perivascular spaces around the vessels.
In some cases, the entire MM was MN from proliferating myocytes with sinusoidal vessels. The size of myocyte nuclei was fairly homogeneous. Tumor cells maintained monomorphy, mitoses were single, or their number was 5-10 in 10 fields of vision. An increased amount of mitosis was observed predominantly around sinusoidal vessels in growth zones. Myometrium outside MN is hypertrophic. In the stroma, there was an increased
number of capillaries per unit area and their fullness. In addition to the main MN, small MNs were found in the stroma. When the proliferative variant of MM recurred, the histological pattern remained the same. In the tissue, there was an increased formation of new vessels, around them a number of zones of growth of tumor myocytes were determined, and signs of proliferative activity persisted. In all 16 cases of repeated MEA due to the relapse of MM, the proliferating type of MM was detected. Taking into account that the same woman can have different histotypes of MM (mnltinodular growth), and SS MN are more often simple MM, it can be assumed that a relatively larger relapse rate of MM is associated with more frequent loss of MIs not noticed during LME. The number of myocytes in a simple MM exceeded the norm by 1.5 times, in proliferative - by 4.1 times. The ratio of the area of myocytes and interMNscular space in the uterus without any pathology was 55.9% to 44%, respectively, in a simple MM - 25.3% to 74.6%. Reduction of the area occupied by myocytes with a simnltaneous increase in the area of intermnscular space is probably associated with pronounced dystrophic changes in MN and tissue edema, disorders of hemo- and lymphodynamics, destructive changes and necrosis of myocytes. In the proliferating MM, the ratio of the area of myocytes and intermnscular space was 70.7% to 29.1%, which is associated with the pronounced proliferation activity of smooth mnscle cells and an increase in their number per unit area. The increase in the volume of MN in the proliferating version of MM is due to cell hyperplasia, and the high proliferative activity of myometrium cells indicates a high potential of tumor growth.
The process offormation of growth zones ofMN is inextricably linked with the processes of angiogenesis. The growth and development ofMM was accompanied by the formation of new microvessels from existing ones. At the same time, the vessels of the MM differed from normal ones, since they had a sinusoidal structure, which can not be attributed either to the arterial or venous system, and had pronounced morphological features, due to the lack of mnscular and adventitious membranes in their structure. The vascular network of simple MMs was expressed in varying degrees. In the morphometric study of a simple MM, the number of vessels of sinusoidal type averaged 85.38 ± 2.6 per unit area under study. The increase in the size of MN with a simple MM was due to a violation of
microcirculation and the development of dystrophic and necrobiotic processes. In such MN, the number of sinusoids increased on average to 100.1 ± 3.9, which probably served as a manifestation of compensatory processes developing in tissues in response to hypoxia. Proliferating MM were characterized by active angiogenesis processes representing sites with a number of vessels of sinusoidal type and the formation of "growth zones" both in the MN itself and in the surrounding myometrium. The presence of many small, chaotically scattered vessels along the periphery and in the center ofthe MN was noted, their number on the average reached 227.1 ± 10.0. Foci of tumor cell proliferation most often localized in the perivascu-lar spaces around the vessels, as well as in the peripheral parts of the MN. In a morphometric study of recurrence ofproliferating MM, the number of sinusoidal vessels on average was 190.6 ± 7.4 per unit area. The increase in the number of vessels in the proliferative variant compared with the simple version of MM was 2.7, in comparison with the relapse of 2.2. In the proliferating MM, unlike simple MM, mnltiple "growth zones" around the vessels were formed and the processes of neoangiogenesis in these MNs were actively proceeding. The high density of microvessels due to the increase in their number in MN was the most significant component in the initiation of tumor growth and it was the presence of sinusoidal vessels that indicated active angiogenesis and the formation of active growth zones in myometrium.
The level of expression of the proapoptotic factor CD-95 (FAS / Apo receptor) was highest in the simple MM (54 ± 3.9%), the mean in the proliferating factor (32.5 ± 1.7%), and its lowest value was determined in MN with the relapse of proliferating MM (9.7 ± 1.1%), which indicated a low readiness for apoptosis of tumor cells, contributing to an increase in its size.
Thus, the development ofproliferative processes is due not only to increased proliferation of cells, but also to the weakening of the induction of apoptosis. With low proliferative activity (simple MM), the level of apoptotic activity is high enough. With a high activity of proliferative processes, the level of apoptosis is sharply reduced, i.e. tumor growth can be considered as a consequence of the imbalance between cell proliferation and apoptosis. The source of the proliferation foci in the perivascular zone is vascular wall cells, which is confirmed by studies of expression of the CD-34 marker ofthe endothelium. In MN, CD-34 was
detected not only in the endothelium of microvessels, but also in individual cells of the vascular wall and perivascular tissue, in the endothelium of the myometrium vessels. A large number of vessels in proliferating MM indicated an increase in the process of neoangiogenesis.
Examination of Ki67 marker expression allowed to evaluate proliferative activity of stromal cells, as the main growth mechanism in MN is the increase of cell proliferation activity. The reaction product of Ki67 was found in the nuclei of the fibroblastic elements of the stroma in the proliferative version of MM and in cases of relapse.
Thus, the results of the studies showed that there is a close relationship between the processes of neoan-giogenesis, apoptosis, proliferation, and growth activity in simple and proliferating MM. In simple MM, tumor growth during pregnancy is primarily due to myotocyte hypertrophy and secondary changes, myocyte proliferation is low, with low angiogenesis, expression of apopto-sis markers is high, growth zones are few. At the base of MN growth during pregnancy (proliferating MM) there is a pronounced proliferation of myocytes, to a lesser extent stromobrazovanie, active angiogenesis, apoptosis sharply reduced.
The mechanism of growth of simple MM in pregnant women is due to stromal-parenchymal relationships and in 39 out of 45 it was characterized by slow proliferative growth and, as a rule, single MN, located predominantly IMI and intermnscularly in the bottom and the uterus. The growth of the tumor during pregnancy was primarily due to myotocyte hypertrophy and secondary changes with microcirculation disorders and the development of necrobiotic processes. There were no growth zones in the surrounding myometrium and remote areas of the uterus, proliferative and mitotic activity was low. Secondary changes in MN tumors developed quite often and were manifested by red and hyaline degeneration, edema, necrosis. At there was an accelerated death of myocytes in the central zone of MN. The change in the volume of MN in these terms was associated with tissue swelling, disorders of hemo- and lymphodynamics, destructive changes and necrosis. Morphological changes in NPMNs were clearly related to time boundaries. First, microcirculation disorders and the growth of tissue hypoxia caused compensatory changes in smooth mnscle cells, then decompensation ensued - edema developed, and cell destruction began. Dystrophic changes in the tumor should be considered
not as complications in the development of the latter, but as links in a single process. Pregnancy was the cause of destabilization of blood circulation in MN.
Proliferating MM outside and during pregnancy during relapse is caused by rapid growth, large size, large amount of MN, mainly intermnscular arrangement, more often taking a centripetal growth direction, causing deformation of the uterine cavity. The growth of MN during pregnancy was due to hypertrophy of myocytes and their hyperplasia, active angiogenesis and to a lesser extent stromobrazovanie. In women with repeated ME, conducted in connection with relapse of MM in terms of 1-4 years, proliferating MM was observed in all cases, without exception, characterized by rapid growth, mn-ltiple MNs having CM and IMSM location.
Conclusion. The tumor growth was caused, first, by hyperplasia of myocytes with high proliferative activity of myometrium cells, indicating a high potential of tumor growth. Areas of growth are MNltiple. Proliferating MM was combined with endometriosis (adenomyosis), which potentiated their growth. Secondary changes in MN tumors among non-pregnant women were no different from similar changes in the group of pregnant women. The active form of endometrial hyperplasia was associated with proliferating MM (in patients outside of pregnancy). The expression level of the proapoptotic factor CD-95 (FAS / Apo receptor) was minimal in MN with a pattern of recurrence of proliferative MM in pregnant and non-pregnant women. The processes of proliferation prevailed over the processes of apoptosis.
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