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Introduction. Most pelvic tumors originate from reproductive organs. Even using the up-to-date imaging techniques, radiologists experience difficulties in determining the source of the lesion since a wide range of tumors look similar to each other on the distorted backdrop of pelvic anatomy, large invasive formations, and an active inflammatory reaction of the pelvic peritoneum.Aim: to evaluate “pitfalls” in the preoperative noninvasive diagnosis of female pelvic tumors by applying the clinical diagnostic tools.Materials and methods. Four rare clinical cases were analyzed; all of them posed difficulties in interpreting the diagnostic examination due to their atypical characteristics. There were 2 cases of ovarian cancer, initially identified by an experienced team of radiologists as benign pelvic pathology. Also, there were fibroids with degeneration, marked proliferative activity, and a massive inflammatory reaction of the peritoneum – that was diagnosed as a malignant ovarian tumor. Tumor biopsies were examined using morphological and immunohistochemical methods (with the р16, Ki-67, p53, CD 117, S 100, CD 34 markers). Immunohistochemical (IHC) studies were performed with formalin-fixed paraffin materials using the avidin-biotin-peroxidase method. Antibodies to estrogen receptor (ER), progesterone receptor (PR), cytokeratin 7 (CK7), cytokeratin 20 (CK20) and Wilms tumor protein 1 (WT1) were also used.Results. A thorough analysis of the clinical picture and a joint multidisciplinary discussion (gynecologist, oncologist, radiologist, etc.) made it possible to avoid diagnostic errors.Conclusion. These observations demonstrate the difficulties of differential diagnosis between ovarian metastases of uterine cancer and primary multiple ovarian and uterine cancer, as well between leiomyosarcoma and uterine myoma with high mitotic activity. Obviously, the change in diagnosis calls for a change in the treatment strategy.

Extensive studies of the rudimental tissues taken from patients with aplasia of the uterus and vagina are aimed at elucidation of the mechanisms of the genesis of these malformations and at the search of the ways of their correction. We performed a histological examination of human uterine rudiments and immunohistochemical analysis of the expression of estrogen and progesterone receptors, VEGF, and stem/progenitor cell markers in these tissues. We found that the rudimental tissues show signs of disorganized histogenesis, but retain activity and contain cells expressing estrogen and progesterone receptors and VEGF as well as poorly differentiated precursor cells or stem cells. The presented data contribute to the in-depth studies of the mechanisms of formation of uterine rudiments and development of methods of their correction.

Aim. To conduct a retrospective analysis and evaluate the morphological methods for HPV-related intraepithelial lesions detection in women of reproductive age. Materials and methods. The data of cytological diagnosis, as well as the results of histological reports were analyzed for the period from 2018 to 2019. A comparative analysis was performed in 415 patients with HPV-related intraepithelial lesions, who applied to the scientific and polyclinic department of the Kulakov National Research Medical Center at the age of 19 to 45 years. Morphological examination was carried out by specialists of the 1st pathology department of the Center. Results. According to the results of a comparative analysis of cytological and histological conclusions, 3 groups were formed: 1 the group of coincidence (agree) of cytological and histological conclusions; 2 group of minor discrepancies (minor under/ over) between cytological and histological finding; 3 group of major discrepancies (major under/ over) between cytological and histological findings. Cytological and histological compliance was achieved in 194 (46.74%) patients. The total number of minor nonconformities was 192 (46%) cases. The total number of significant discrepancies between cytological and histological findings was 29 (6.9%) patients: 20 (4.8%) cases were found in the group NILM, hr. cervicitis HSIL and 9 (2.1%) cases in the group HSIL hr. cervicitis according to the results of histological examination. Conclusion. Cervical screening reduces the risk of breast cancer due to cytological examination of the cervix, but histological examination is crucial in making a correct diagnosis, since its result determines the choice of treatment method. The comparative analysis showed that in all groups there were cases of hypo- and hyperdiagnostics during cytological examination although the major discrepancies which can change treatment algorithm, were found only in 6.8% cases.

Ovarian cystadenofibroma (CAF) is a rare ovarian tumor originating both from epithelial and stromal components being, however, classified as epithelial tumors. CAF prevalence among all ovarian tumors does not exceed more than 1.7 %. CAFs are commonly asymptomatic, in extremely rare cases of large tumor or ovarian torsion pain sensation may be noted. External genital endometriosis (EGE) is a chronic gynecological disorder that occurs in women of reproductive age and cause infertility and pelvic pain. EGE prevalence comprises around 10 % in women of reproductive age, 20–50 % in women with infertility, and almost 90 % in women with chronic pelvic pain. Magnetic resonance imaging (MRI) is method of choice in diagnostics of such pathology due to the high natural soft tissue contrast and functional techniques such as diffusion-weighted images (DWI) and dynamic contrast enhancement (DCE). Surgery planning, necessity for systemic therapy or follow-up directly depend on imaging and diagnostic laparoscopy results. Here we present a clinical case of rarely combined serous papillary CAF with extended EGE accompanied with consequences of intra-tumoral hemorrhage. Case study demonstrates main visualization characteristics that provide correct differential diagnosis and exclude malignancy transformation.

Background. The frequency of adenomyosis varies from 10 to 61%. Currently used methods of surgical treatment of adenomyosis are discussable. A hysterectomy it is not appropriate for women who wish to realize reproductive function or spare the uterus. Now it is very important to perform uterus-sparing surgery for treatment diffuse adenomyosis with severe manifestation of symptoms. Adenomyomecomy with hysteroplasty is modern method of surgical treatment for repair uterus anatomy and functions. Aim. To demonstrate methods of uterus-sparing surgical treatment in diffuse adenomyosis (stages III and IV). Materials and methods. In Surgical Department of Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology since January 2019 till June 2021 we performed 30 uterus-sparing adenomyomectomies with hysteroplasty in women with diffuse adenomyosis (stages III and IV). Results. There are some advantages of adenomyomectomies with hysteroplasty: it is possible to perform this method laparoscopically assisted; also special performing double-flaps recovery of myometrium (like a “frock coat”) allow to avoid uterine scar defects and uterine rapture during pregnancy. Conclusion. One of options of uterus-sparing surgical treatment for women with diffuse adenomyosis who wish to save their uterus and realize reproductive function is adenomyomectomy with hysteroplasty. Women who underwent this method notes pain relief and normalization of menstrual function and improvement life quality.

Simple Summary Vulvar squamous cell carcinoma (VSCC) is the most frequent malignant vulvar tumor, with a peak incidence in the 7–8th decades of life. However, VSCCs can also occur in young women. This unfortunate event is even rarer and more worrisome in pregnant women, being hard to manage for gynecologists, oncologists, and radiotherapists. Very few cases have been reported and we felt the need for an updated review on this topic. Thus, we performed a systematic literature review of VSCCs diagnosed during pregnancy, discussing the clinic-pathologic features, the implications in pregnancy outcomes, and the effects of such a diagnosis in the management of mothers and their babies. Abstract According to our systematic literature review (PRISMA guidelines), only 37 vulvar squamous cell carcinomas (VSCCs) were diagnosed during pregnancy (age range: 17–41 years). The tumor size range was 0.3–15 cm. The treatment was performed after (14/37, 38%), before (10/37, 27%), or before-and-after delivery (11/37, 30%). We found that 21/37 (57%) cases were stage I, 2 II (5%), 11 III (30%), and 3 IVB (8%). HPV-related features (condylomas/warts; HPV infection; high-grade squamous intraepithelial lesion) were reported in 11/37 (30%) cases. We also found that 9/37 (24%) patients had inflammatory conditions (lichen sclerosus/planus, psoriasis, chronic dermatitis). The time-to-recurrence/progression (12/37, 32%) ranged from 0 to 36 (mean 9) months. Eight women died of disease (22%) 2.5–48 months after diagnosis, 2 (5%) were alive with disease, and 23 (62%) were disease-free at the end of follow-up. Pregnant patients must be followed-up. Even if they are small, newly arising vulvar lesions should be biopsied, especially in women with risk factors (HPV, dermatosis, etc.). The treatment of VSCCs diagnosed in late third trimester might be delayed until postpartum. Elective cesarean section may prevent vulvar wound dehiscence. In the few reported cases, pregnancy/fetal outcomes seemed to not be affected by invasive treatments during pregnancy. However, clinicians must be careful; larger cohorts should define the best treatment. Definite guidelines are lacking, so a multidisciplinary approach and discussion with patients are mandatory.

BackgroundStruma ovarii is a variant of monodermal teratoma, consisting of morphologically benign, atypical, or frankly malignant thyroid tissue. Morphologic features may or may not correlate with biologic behavior. Albeit this case report is not unique, ovarian tumor developed with peritoneal dissemination and bone metastasis, which is highly unlikely clinical complication. Additionally, we summarized previously cases of struma ovarii with an emphasis on correlation between morphological appearances, clinical course and providing treatment. Case presentationWe present the 38-year-old patient who was hospitalized for ovarian tumor. The diagnostic laparoscopy revealed lesions of peritoneum, sigmoid serosa and omentum and left ovarian mass. We diagnosed left ovarian mature teratoma without struma tissue and metastatic lesions with struma morphology which can be related to her history of left ovarian struma in 2016. Taking into account the metastatic lesions revealed in 2020, the tumor removed in 2016 was assessed as highly differentiated follicular carcinoma arising in struma ovarii. ConclusionsPrediction of biologic behavior of struma ovarii is still to be to diagnostic challenge, therefore multidisciplinary approach including clinical a n d laboratory findings, radiologic details and histopathological features is required. Providing additional data, the present case report contributes to expending the knowledge of these peculiar neoplasms.

Female urethral diverticulum is a fairly rare pathology, the frequency of which ranges from 0.02 to 6.00% of women worldwide. The stones inside urethra diverticulum even more rare. The most common reasons of urethral diverticula are frequent bladder catheterizations, labour trauma, infections. Clinically is may present with the dysuria, dyspareunia, dribble, urinary incontinence, vaginal discomfort. Voiding cystourethrography and cystourethroscopy are the most accurate methods of diagnosis for urethral diverticula. The presented article describes the clinical case in women with urethral diverticulum who complained on the vaginal discomfort, dyspareunia and presentation of the brown stones in vagina and underwent surgical excision of diverticulum with urethral reconstruction.

Aim. To analyze the literature data on modern approaches to morcellation of myomatous nodes in laparoscopic surgery and to highlight this area in a historical aspect. To form an idea of the main difficulties associated with morcellation, which contributed to and contribute to the improvement of the technique of this manipulation. Materials and methods. The review includes data from foreign articles published in the elibrary.ru and PubMed databases on this topic. Results. It describes both modern trends in the surgical treatment of patients with uterine myoma, and historical aspects of improving methods aimed at reducing risks, reducing the time of surgical intervention and improving its safety. Analyzed data on the use of electromorcellation, carried out both with the use of plastic containers, and without them. Conclusion. High requirements for surgical interventions contributed to the emergence of such a method of intracorporeal fragmentation of drugs, such as morcellation, which led to a significant reduction in the proportion of laparotomic operations in the treatment of patients with my uterus. The introduction of laparoscopy in the surgical treatment of uterine myoma allowed to achieve a fundamentally new high level of rehabilitation of patients. Removing removed drugs from the abdominal cavity is associated with a certain risk. Despite the significant number of proposed methods and devices for morcellation, they all require further improvement, since it is necessary to completely exclude contact of the myoma node tissue with abdominal organs in the extraction process. Currently, active research continues on ways to realize all the benefits of minimally invasive technologies in compliance with the rules of oncological safety.

Study Objective To analyze the histological and immunohistochemical features of ovarian tissue and endometrium in women with diminished ovarian reserve and to investigate the correlation between these parameters and the effectiveness of infertility treatment Design Prospective study, Level II. Setting National Medical Research Center. Patients or Participants 70 patients with diminished ovarian reserve who underwent drug-free in vitro activation using a modified surgical technique. Two bilateral ovarian cortical tissue samples and one endometrial sample were obtained from each patient during the surgery. 40 patients out of 70 underwent ovarian stimulation after at least a one-month postoperative period. Interventions Bilateral ovarian cortex biopsy via laparoscopy, ovarian tissue fragmentation in aliquots of 1 mm2, and hysteroscopy with endometrial biopsy were performed in all patients, followed by histological and immunohistochemical analysis (expression of proteins of the Hippo signaling pathway (YAP, MST-1, LATS-1) and PTEN (inhibitor of PI3K signaling pathway). The Human Protein Atlas datasets were used as a comparison group. Measurements and Main Results We revealed an impaired functioning of intracellular signaling pathways (primarily YAP- and PTEN-dependent) both in ovarian tissue and endometrial samples. Moreover, the expression of the proteins targeted in the study was significantly reduced in patients who responded to stimulation (n=31). Histological analysis of tissue samples of patients with diminished ovarian reserve indicated profound changes in various structures of the ovaries: surface epithelium, vascular component, stroma of ovarian cortex. In 25% of patients, chronic endometritis was also determined. Conclusion Specific histological and immunohistochemical features of ovarian tissue and endometrium associated with diminished ovarian reserve and the outcome of ovarian stimulation were shown.

The goal is to assess the sensitivity and specificity of transvaginal ultrasound (USI) in the diagnosis of localization of foci of deep infiltrative endometriosis. Materials and methods. The study included 142 patients with deep infiltrative endometriosis, who underwent surgery in the surgical department of the V.I.Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of Russian Federation in the period 2014-2016. Criteria for inclusion in the study: informed agreement of the patient, the reproductive age (from 18 to 44 years), deep infiltrative endometriosis with a confirmed histological conclusion. Exclusion criteria were malignant tumors of the pelvis and abdomen, refusal to undergo surgical treatment of deep infiltrative endometriosis, and malformations of the urogenital system. Results. Transvaginal echography in identifying the localization of foci of deep infiltrative endometriosis is highly sensitive in the diagnosis of colorectal endometriosis (88.9%) and endometriosis of the bladder (96%) with a relatively low specificity of the study (35%). The sizes of endometrial infiltrates of the intestine, retrocervical endometriosis, and bladder intraoperatively were large in comparison with the data obtained with transvaginal ultrasound. When assessing the accuracy of the diagnostic method, it was found that transvaginal ultrasound evaluates retrocervical endometriosis with an accuracy of 41.5%, endometriosis of the intestine - 37.7%, bladder - 54.8%. Conclusion. Transvaginal echography, based on a quantitative assessment of the characteristic curve by calculating the area under it, the size of the infiltrate and their localization, showed that our study have middle diagnostic quality and visualization of DIE lesions with enough specify.

The article deals with the clinical case of a patient with giant uterine myoma. It presents the features of surgical intervention and postoperative management of the patient. In the publication, the authors discuss the issues concerning the scope of the surgery in patients with large and giant uterine myomas and prognosis of reproductive outcomes in this cohort of women.

Abnormal uterine bleeding (AUB) is one of the most common indications for hysteroscopy. Most of the AUB cases occur due to endometrial or myometrium pathology. Among it, endometrial polyps (EP) and chronic endometritis (CE) prevalent in reproductive age, while endometrial hyperplasia (EH) and EP dominate in perimenopause. It was determined that EP and CE are characterized with menorrhagia and metrorrhagia approximately equally, whereas EH reveals AUB with oligomenorrhoea. Verification of exact endometrial pathology by ultrasound examination is hindered, that results in deviations of ultrasound and histological diagnosis. The usage of ultrasound data and AUB’s characteristics may improve the diagnostic accuracy on preadmission period.

Study Objective Patients with critically diminished ovarian reserve have few remaining follicles and using donated eggs becomes the only chance of getting pregnant. Kawamura et al. have invented a method for the activation of dormant follicles using PI3K stimulator and PTEN inhibitors, but later showed that ovarian tissue fragmentation alone with returning to the contralateral ovary could also lead to follicular growth. Our purpose was to optimize infertility treatment in patients with diminished ovarian reserve using a new modified surgical technique with ipsilateral ovarian tissue reimplantation. Design Prospective study, Level II. Setting National Medical Research Center. Patients or Participants 70 patients with diminished ovarian reserve and no successful results from previous treatment, including ART methods. Interventions Bilateral ovarian cortex biopsy via laparoscopy, ovarian tissue fragmentation in aliquots of 1 mm2, and hysteroscopy with endometrial biopsy were performed in all patients, followed by histological examination. Collected tissue fragments were grafted into a formed space between the ovarian cortex and medulla ipsilaterally. To date 40 patients underwent ovarian stimulation after at least a one-month postoperative period. Measurements and Main Results Our study demonstrated at least a triple increase in estradiol level in 5 days after surgery, progressive decrease in gonadotropins levels, increase in the number of growing follicles in all patients after our modified surgical approach. 31 out of 40 patients have responded to ovarian stimulation. Moreover, in 25 out of 31 patients we revealed an increase in the number of oocytes, fertilization rates, and high-quality embryo rates. 10 patients became pregnant after the surgery (3 spontaneous pregnancies, 7 - after ovarian stimulation). Conclusion Our data shows that drug-free IVA with our modified surgical technique is associated with favorable clinical outcomes for infertility treatment in patients with diminished ovarian reserve.

To investigate the expression of proliferation and apoptotic factors (Ki-67, Bcl-2), inflammatory factors (NF-kβ p65, COX-2), adhesion factors (β-catenin), estrogen (ER-α) and progesterone receptors (PR-α) in ovarian endometrioma (OE) in patients with recurrent OE by an immunohistochemical assay.This investigation enrolled 48 reproductive-aged patients with OE. According to the course of the disease during a follow-up period of 1.5 years after surgical treatment, the biomaterial obtained from the examined patients was divided into two groups: 1) an OE capsule from 19 patients with recurrent OE (a study group); 2) an OE capsule from 28 patients without recurrent OE (a comparison group). This investigation used histological and immunohistochemical examinations. The histological analysis of the OE capsule was performed following a standard procedure. Their immunohistochemical analysis was carried out using the Tissue-Tek Quick-Ray kit that allows the preparation of paraffin blocks with a large number of tissue samples (tissue microarrays). Antibodies to Ki-67 (clone 30-9, VENTANA), Bcl-2 (clone 124, VENTANA), NF-kβ p65 (clone p65, 'Spring Bioscience Corp.'), COX-2 (clone CX-294, Agilent), β-catenin (clone 14, VENTANA), ER-α (clone SP1, VENTANA), and PR-α (clone 1E2, VENTANA) were also employed in the investigation. The specimens were prepared according to a standard protocol using a Ventana Ultra immunohistostainer. Positive and negative controls were used to correctly carry out immunohistochemical tests. Statistical analysis was performed using the applied statistical analysis programs Statistica 10.0 and Microsoft Excel.The patients with recurrent OE had a significantly decreased expression of Ki-67 (2.86% vs. 9.69%; р=0.044) in the epithelial component of the OE capsule; a significantly lower expression of NF-kβ p65 (2.54 vs. 3.5; р=0.0082) and СОХ-2 (0.231 vs. 1.381; р=0.0025) in the stromal component of the OE capsule, a significantly increased expression of β-catenin (2.5 vs. 1.59; р=0.017) in the stromal component of the OE capsule; a significantly increased expression of PR-α (188.46 vs. 71.15; р=0.028) in the epithelial component of an OE capsule. The expression of ER-α (stromal component, 266 vs. 256.84; p=0.48; epithelial component, 251.54 vs. 233.85, p=0.82) and Bcl-2 (stromal component, 0.33 vs. 0.25; p=0.85; epithelial component, 0.944 vs. 0.625; p=0.31) in the OE capsule is not statistically significantly different between the study patient groups.The immunohistochemical difference in the expression of a number of the markers under study can serve as the basis for a further investigation of these markers as predictors of recurrent OE after surgical treatment. Further investigations of these factors will also be able to examine the molecular mechanisms underlying the pathogenesis of recurrent OE, which will make it possible to affect these mechanisms in order to eliminate the fundamental causes of a recurrence of this disease.Цель исследования - изучить экспрессию факторов пролиферации и апоптоза (Ki-67, Bcl-2), воспалительных факторов (NF-kβ p65, COX-2), факторов адгезии (β-катенин), эстрогеновых (ER-α) и прогестероновых (PR-α) рецепторов в эндометриоидной кисте яичника (ЭКЯ) у пациенток с рецидивирующим течением ЭКЯ иммуногистохимическим методом. Материал и методы. В исследование включены 48 пациенток репродуктивного возраста с ЭКЯ. В зависимости от течения заболевания за период наблюдения 1,5 года после оперативного лечения биоматериал обследуемых пациенток разделен на две группы: 1-я группа - капсула ЭКЯ от 19 пациенток с рецидивирующим течением ЭКЯ (основная группа); 2-я - капсула ЭКЯ от 29 пациенток без рецидива ЭКЯ (группа сравнения). В работе использовали гистологический и иммуногистохимический методы исследования. Гистологическое исследование капсулы ЭКЯ проводили по стандартной методике. Иммуногистохимическое исследование капсулы ЭКЯ осуществляли при помощи набора Tissue-Tek Quick-Ray, который позволяет изготавливать парафиновые блоки с большим количеством образцов тканей (тканевые матрицы). В исследовании использовали антитела к Ki-67 (clone 30-9, VENTANA), Bcl-2 (clone 124, VENTANA), NF-kβ p65 (clone p65, 'Spring Bioscience Corp.'), COX-2 (clone СХ-294, 'Agilent'), β-катенину (clone 14, VENTANA), ER-α (clone SP1, VENTANA) и PR-α (clone 1E2, VENTANA). Препараты готовили по стандартному протоколу с использованием иммуногистостейнера Ventana Ultra. Для правильной постановки иммуногистохимических реакций ставили положительные и отрицательные контроли. Статистический анализ проводили с использованием программ прикладного статистического анализа (Statistica 10.0, Microsoft Excel). Результаты. У пациенток с рецидивирующим течением ЭКЯ достоверно понижена экспрессия Ki-67 (2,86% против 9,69%; р=0,044) в эпителиальном компоненте капсулы ЭКЯ, достоверно понижена экспрессия NF-kb p65 (2,54 против 3,5; р=0,0082) и СОХ-2 (0,231 против 1,381; р=0,0025) в стромальном компоненте капсулы ЭКЯ, достоверно повышена экспрессия β-катенина (2,5 против 1,59; р=0,017) в стромальном компоненте капсулы ЭКЯ и достоверно повышена экспрессия PR-α (188,46 против 71,15; р=0,028) в эпителиальном компоненте капсулы ЭКЯ. Экспрессия ER-α (стромальный компонент 266 против 256,84; р=0,48, эпителиальный компонент 251,54 против 233,85; р=0,82) и Вcl-2 (стромальный компонент 0,33 против 0,25; р=0,85, эпителиальный компонент 0,944 против 0,625; р=0,31) в капсуле ЭКЯ статистически значимо не различается между обследуемыми группами пациенток. Заключение. Иммуногистохимическая разница экспрессии ряда маркеров выступает в качестве основы для дальнейшего исследования этих маркеров как предикторов рецидивирования ЭКЯ после оперативного лечения. Дальнейшие исследования этих факторов также позволят изучить молекулярные механизмы, лежащие в основе патогенеза рецидивирования ЭКЯ, что даст возможность воздействовать на эти механизмы для устранения фундаментальных причин рецидива данного заболевания.

Introduction/Background Physiological changes in the mother’s body during pregnancy with the primary aim to support the fetus’s growth may also suspected to worsen the natural course of various malignancies with even poorer prognosis then in non-pregnant women. Though borderline ovarian tumors generally have an excellent prognosis, the risk of their progression during gestation remain has yet to be investigated. The purpose of this study was to assess the expression of epithelial-mesenchymal markers, angiogenesis and the extent of natural killers in samples of ovarian borderline tumors in pregnant and non-pregnant women. Methodology Twenty three samples [13 from pregnant (30,5±4,7 years) and 10 from non-pregnant women (33,6±5,8 years)] were investigated morphologically and immunohistochemically with VEGF, CD31, CD105, CD56, E-cadherin, Vimentin, Mann-Whitney test was used for statistics. Results Serous borderline tumors were diagnosed more frequently in pregnant and in non-pregnant women. In addition we diagnosed endometrioid and mucinous borderline tumors with welldiffentiated components in both groups. CD31 expression in pregnant women was significantly higher than that in non-pregnant patients (p 0.05). Conclusion Borderline ovarian tumors in pregnant women were characterized by an enhanced CD31 expression compared with non-pregnant patients. The increase level of CD31 expression in pregnant women is supposed to be enhanced be pregestrone activity through progestindependent angiogenesis activation. We speculate that the similarity in VEGF, CD-105, Ecadgerin, Vimentin, CD56 expression in pregnant and non-pregnant women’s indicates lack of stimulation in these agents-dependent signal pathways on borderline ovarian tumors progression complicating pregnancy Disclosure Nothing to disclose.

Introduction/Background Serous tubal intraepithelial carcinoma (STIC) is known to be a putative precursor for the most common and aggressive ovarian carcinomas, namely ovarian high-grade serous carcinoma. Precise and early diagnose this disease is therefore one of the priorities for tissue diagnosis in gynecologic oncology. At the same time routinely applied algorithm for STIC diagnosis could not cover some grey zones in its diagnostics. Methodology The study included 70 patients (125 fallopian tubes), all of the specimens were investigated morphologically and immunohistochemically (p53, Ki-67, p16, stathmin1 and laminingamma1). Statistics involved exact Fisher’s test, χ2-test, Cohen’s kappa Results Expression of p16, stathmin1 and laminin-gamma1 was revealed in 85%, 77,5% and 90% of STIC consequently. In 4 tubes with STIC, only one of these tree markers was positive but we has no cases with all three negative expression. In STIC cases, expression of p16, stathmin1 and laminin-gamma1 was high both in the presence and in the absence of p53 expression in atypical cells. In most cases, positive expression of at least two of the three studied markers was shown. p16, stathmin1 and laminin-gamma1expressin does not differ between p53positive and p53-negative STICs. Cohen’s kappa for STICs with ambiguous p53 expression was moderate (0.55) when we used only p53 and ki-67 expression. P16/laminingamma1/stathmin1 diagnostic panel let us increased Cohen’s kappa to good reproducibility (0.72), (p Conclusion Lack of grey zones in STIC diagnostics and good reproducibility of diagnoses allows us to recommend p16, stathmin1 and laminin-gamma1 diagnostic panel for STIC diagnostics, especially in case of ambiguous p53 expression and/or borderline KI-67 expression. Disclosure Nothing to disclose.

to investigate the frequency of the types of fallopian tubal secretory cell expansion (SCE) in diseases of the reproductive organs and to determine the immunophenotype and biological role of the cells in the early stages of the pathogenesis of high-grade ovarian serous carcinomas (HGOSC).The investigation enrolled 287 patients with extraovarian diseases and ovarian serous tumors varying in grade, whose fallopian tubes were morphologically and immunohistochemically examined using p53, Ki-67, PAX2, Bcl-2, beta-catenin, and ALDH1 markers. The material was statistically processed applying the Mann-Whitney test and χ2 test.The rate of secretory cell proliferation (SCP) (more than 10 consecutive secretory cells) and that of secretory cell overgrowth (SCO) (more than 30 consecutive secretory cells) increase with age in all investigated reproductive system diseases. The rate of SCP in the corpus fimbriatum of the patients with HGOSC was 5.9 times higher than that in those with extraovarian disease (p0.01); when comparing the same patient groups, that of SCO was 3.4 times higher (p0.05). The immunohistochemical characteristics of the investigated lesions (in scores) were as follows: PAX2 was expressed in the intact epithelium (2.8), in SCP (1.3), in SCO (1.2), in serous tubal intraepithelial carcinoma (STIC) (1.0), and in HGOSC (0.9); Bcl-2 was in the intact epithelium (2.2), in SCP (2.1), STIC (0.9), and in HGOSC (0.6), β-catenin was in the intact epithelium (0.5), in SCP (2.85), in SCO (2.95), in STIC (0.6), and in HGOSC (0.5); ALDH1 was in the intact epithelium (0.5), in SCP (2.91), in SCO (2.92), in STIC (1.2), and in HGOSC (0.6). There were statistically significant differences with a 95% confidence interval (p0.05) for: 1) PAX2 between the intact epithelium and pathology (fallopian tube lesions and HGOSC); 2) Bcl-2 between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 3) beta-catenin between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 4) ALDH1 between the intact epithelium and SCE, between and SCE and STIC, and between STIC and HGOSC.SCE was shown to be an independent intraepithelial lesion. The incidence of this abnormality increased with age and significantly differed in the patients with fallopian tubal lesions in extraovarian diseases from that in those with malignant ovarian serous tumors (by 5.3 times), while these groups showed a three-fold difference in SCO. Thus, SCP may serve as a more sensitive marker for the early stages of the pathogenesis of ovarian serous carcinoma. The studied types of SCE demonstrated multiple molecular events (loss of PAX2 expression and increased Bcl-2, beta-catenin, and ALDH1 expressions), some of which underwent considerable changes, by increasing the severity of a pathological process (loss of ALDH1, and beta-catenin, and bcl-2 expressions). Thus, therapeutic exposure in the early stages of pathogenesis may have a few points of application and just several molecules can serve as independent markers for early pathological changes in the fallopian tubal epithelium.Цель исследования - изучить частоту возникновения вариантов экспансии секреторных клеток эпителия маточной трубы при патологии органов репродуктивной системы, определить их иммунофенотип и биологическую роль на ранних этапах патогенеза серозных карцином яичника высокой степени злокачественности (СКЯВСЗ). Материал и методы. В исследование включены 287 пациенток с экстраяичниковой патологией и серозными опухолями яичника разной степени злокачественности, маточные трубы которых исследованы морфологически и иммуногистохимически (с маркерами р53, Ki-67, PAX2, Вcl-2, β-catenin, ALDH1). Статистическая обработка материала выполнена с использованием критериев Манна-Уитни и χ2. Результаты. Частота возникновения пролиферации секреторных клеток - ПСК (более 10 секреторных клеток подряд) и разрастания секреторных клеток - РСК (более 30 секреторных клеток подряд) возрастает с возрастом при всех изученных патологиях репродуктивной системы. В фимбриальном отделе частота ПСК в маточных трубах пациенток СКЯВСЗ в 5,9 раза выше, чем у пациенток с экстраяичниковой патологией (p0,01), частота РСК при сопоставлении тех же групп была в 3,4 раза выше (p0,05). Иммуногистохимическая характеристика изученных поражений была следующей (в баллах): экспрессия PAX2 составила в нормальном эпителии 2,8, в ПСК 1,3, в РСК 1,2, в серозной трубной интраэпителиальной карциноме (СТИК) 1,0, в СКЯВСЗ 0,9, экспрессия Вcl-2 составила в нормальном эпителии 2,2, в ПСК 2,1, в СТИК 0,9, в СКЯВСЗ 0,6, экспрессия β-catenin составила в нормальном эпителии 0,5, в ПСК 2,85, в РСК 2,95, в СТИК 0,6, в СКЯВСЗ 0,5, экспрессия ALDH1 составила в нормальном эпителии 0,5, в ПСК 2,91, в РСК 2,92, в СТИК 1,2, в СКЯВСЗ 0,6. Статистически значимые различия с доверительным интервалом 95% (p0,05) выявлены: 1) в отношении PAX2 между нормальным эпителием и патологией (поражениями маточной трубы и СКЯВСЗ); 2) в отношении Вcl-2 между нормальным эпителием и экспансией секреторных клеток (ПСК и РСК), а также между экспансией секреторных клеток и СКЯВСЗ; 3) в отношении β-catenin между нормальным эпителием и экспансией секреторных клеток (ПСК и РСК), а также между экспансией секреторных клеток и СКЯВСЗ; 4) в отношении ALDH1 между нормальным эпителием и экспансией секреторных клеток, между экспансией секреторных клеток и СТИК, а также между СТИК и СКЯВСЗ. Заключение. Показано, что пролиферация секреторных клеток является самостоятельным интраэпителиальным поражением. Частота данной патологии увеличивалась с возрастом, а также достоверно различалась у больных с поражением маточных труб при экстраяичниковой патологии от таковой у пациенток со злокачественными серозными опухолями яичника (в 5,3 раза), при этом уровень разрастания секреторных клеток в данных группах больных различался в 2 раза. Таким образом, пролиферация секреторных клеток может служить более чувствительным маркером ранних этапов патогенеза серозной карциномы яичника. Для изученных типов экспансии секреторных клеток продемонстрированы множественные молекулярные события (утрата экспрессии PAX2, усиление экспрессии Вcl-2, β-catenin и ALDH1), некоторые из которых претерпевали значительные изменения с усилением тяжести патологического процесса (утрата экспрессии ALDH1, β-catenin, Вcl-2). Таким образом, терапевтическое воздействие на ранних этапах патогенеза может иметь несколько точек приложения и сразу несколько молекул могут служить независимыми маркерами ранних патологических изменений эпителия маточной трубы.

The article presents a clinical case of cryopreservation of ovarian tissue in a patient 15 years with the bulk formation of a single ovary, is made on the basis of V.I.Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation.

Study Objective To evaluate the occurrence of the autophagic process in ovarian endometriomas (OE), rectocervical endometriosis (RE), adenomyosis (A), and peritoneal endometriosis (PE) compared with eutopic endometrium. Design Prospective cohort study, Level II-1. Setting National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Healthcare of the Russian Federation. Patients or Participants We recruited 120 patients with endometriosis and adenomyosis: 47 patients with (OE), 20 patients with (RE), 20 patients with (A), 33 patients with (PE). Interventions All patients had laparoscopic surgery performed in the proliferative non-menstrual phase of their menstrual cycle. Histological analysis was carried out according to a standard procedure. Immuno-histochemical analysis of ectopic and eutopic endometrium samples was carried out using the Tissue-Tek Quick-Ray kit, which allows for the preparation of paraffin blocks with a large number of tissue samples (tissue microarray). Antibodies to LAMP 1 (1:100), LC3 (1:50), bcl-2 (1:50), (Ventana, Roche) were used. Measurements and Main Results In patients with EO, RE, A and PE, we noticed a significant down-regulation of autophagy (LAMP1 and LC3 expression) and up-regulation of beta-catenin expression in ectopic endometrium compared with the eutopic endometrium of affected women (p0.05). This data is consistent with our previous observation made on smaller number of patents, possibly confirming the data. Conclusion We hypothesized that there is a relationship between autophagy and wnt/signaling pathway regulation, demonstrating the inverse ratio between beta-catenin and autophagy-marker expression. Based on the results in this study, we can say with increased certainty that increased beta-catenin could suppress autophagy, supporting ectopic endometrium through anoikis and other types of apoptosis. So we can suppose that target-based therapy suppressing the wnt/beta-catenin pathway can activate autophagy in endometriosis and, pending clinical studies, become a part of target-based pre-surgical, intra-operative, an post-operative endometriosis therapy.

to study the incidence of fallopian tube lesions (secretory cell proliferations (SCP), p53 signature, serous tubal intraepithelial lesions (STIL), and serous tubal intraepithelial carcinomas (STIC) in ovarian epithelial tumors and to propose their pathogenetic association with a certain histotype of the ovarian tumor.The investigation enrolled 136 patients with ovarian epithelial tumors, whose fallopian tubes were morphologically and immunohistochemically (IHC) examined using p53, Ki-67, and PAX2. Statistical analysis was carried out applying the Mann-Whitney test and χ(2) test.Lesions meeting the STIC criteria were found in 14.7% of cases (only in ovarian serous carcinoma (OSC)), those suspecting STICs were in 25.7%, and those without signs of STICs were in 59.6%. IFC examination diagnosed STIC in 10% of cases (only in OSC), STIL in 13.3%, p53 signature in 11.7% (only in serous tumors), and the normal/reactively changed tubal epithelium in 65%. The incidence of STILs correlated with the malignant potential of serous tumors significantly (p0.05). There were significant differences in the incidence of STILs in patients with different histotypes of ovarian carcinomas (p0.05). PAX2-negative SCP was detected in 75% of OSC, 60% of serous borderline tumors, and 40% of serous cystadenomas. The differences in the incidence of SCP between serous tumors of varying grade, between serous tumors and non-serous carcinomas, between OSC and non-serous carcinomas were significant (p0.05).The investigation has shown that IHC examination should be used for the accurate diagnosis of STILs. It has also provided evidence for the pathogenetic association between STIC and high-grade OSC and revealed significant differences in the incidence of other fallopian tubal intraepithelial lesions in serous cystadenomas, borderline tumors, and OSC, in different ovarian carcinomas. The findings may suggest that the earliest stage in the pathogenesis of OSC is the development of SCP, followed by the formation of p53 signatures that may further give rise to STIL, and finally STC (due to the acquisition of additional mutations).Цель исследования - изучить частоту возникновения поражений маточной трубы (разрастаний секреторных клеток (РСК), p53-signature, серозных трубных интраэпителиальных поражений (СТИП), серозных трубных интраэпителиальных карцином (СТИК) при эпителиальных опухолях яичника) и высказать предположение об их патогенетической связи с определенным гистотипом опухоли яичника. Материал и методы. В исследование включены 136 пациенток с эпителиальными опухолями яичника, маточные трубы которых исследованы морфологически и иммуногистохимически (ИГХ) (р53, Ki-67, PAX2). Статистическая обработка материала выполнена с использованием критериев Манна-Уитни и χ2. Результаты. Поражения, соответствующие критериям СТИК, выявлены в 14,7% случаев (только при серозной карциноме яичника - СКЯ), подозрительные в отношении СТИК - в 25,7% случаев, не имеющие признаков СТИК - в 59,6%. После ИГХ-исследования СТИК диагностирована в 10% случаев (только при СКЯ), СТИП - в 13,3%, р53-signature - в 11,7% (только при серозных опухолях), нормальный/с реактивными изменениями трубный эпителий - в 65% случаев. Частота возникновения интраэпителиальных поражений маточной трубы достоверно коррелировала со злокачественным потенциалом серозных опухолей (p0,05). Достоверные различия в частоте возникновения интраэпителиальных поражений маточной трубы выявлены среди пациенток с карциномами яичника разных гистотипов (p0,05). PAX2-негативные РСК диагностированы при 75% СКЯ, 60% серозных пограничных опухолей, 40% серозных цистаденом. Достоверно значимыми были различия во встречаемости РСК между серозными опухолями различной степени злокачественности, серозными опухолями и несерозными карциномами, СКЯ и несерозными карциномами (p0,05). Заключение. Показано, что для точной диагностики интраэпителиальных поражений маточной трубы необходимо применение ИГХ-исследования. Подтверждена патогенетическая связь между СТИК и СКЯ высокой степени злокачественности и выявлены значимые различия во встречаемости других интраэпителиальных поражений маточной трубы при серозных цистаденомах, пограничных опухолях и СКЯ, при различных карциномах яичника. На основании полученных результатов можно предположить, что наиболее ранним этапом в патогенезе СКЯ является развитие РСК, далее образуются р53-signature, которые в дальнейшем могут дать начало развитию СТИП и, наконец, СТИК (при приобретении дополнительных мутаций).