{"paper_id":"42a6c666-b5c1-4b4e-a266-618ae2778934","body_text":"25\nORIGINAL RESEARCH    GYNECOLOGY\nBULLETIN OF RSMU   6, 2021   VESTNIKRGMU.RU| |\nGerasimova AA1,2, Asyrafyan LA3, Manuchin IB4, Shamarakova MV2, Miryasova MS5, Klimenko PA6\nFEATURES OF THE DECIDUALIZED ENDOMETRIOSIS DIAGNOSIS AND COURSE DURING PREGNANCY \nCurrently, surgical treatment aimed to exclude the malignant ovarian tumors is performed in almost 90% of patients with decidualized endometrial cysts (DEC). However, \nunnecessary surgical interventions increase the risk to maternal and fetal health. The study was aimed to perform a differential diagnosis of DEC in pregnant women \nin order to define the rational treatment. A total of 82 female patients were included in the study: 63 had endometrial cysts (EC), 16 had DEC, 3 had rare forms of \nendometriosis, and 10 had ovarian serous papillary borderline tumors. When performing the diagnostic ultrasound, our proposed model was used. The ultrasound \nimaging data obtained were juxtaposed with the concentration of the protein tumor markers (СА-125), the risk of malignancy index (RMI) was calculated, and the \nmorphological assessment of the masses was performed. The ultrasound imaging parameters, being the most valuable for differential diagnosis of EC, DEC, and serous \nborderline tumors, were as follows: the altered mass wall thickness, the existence and shape of papillary masses, avascular echogenic inclusions with blurry contour, \nblood circulation and arrangement of blood vessels, ascites. The frequency analysis revealed the differences between groups based on the ultrasound imaging data (in \n60–100% of observations). Histological examination revealed the differences between groups in 100% of observations. Our findings have made it impossible to prolong \npregnancy in patients with DEC without performing surgery. The results of treatment provided to patients with DEC during pregnancy were worse compared to those in \npatients with no prominent decidualization in ovarian EC. Today, the diagnosis of DEC and the treatment of patients during pregnancy remain unsophisticated. Further \nclinical observation and the search for more reliable methods of the diagnosis and rational treatment of pregnant women with DEC are required.\nKeywords: ultrasound examination, morphological analysis, ovarian tumors, pregnant women\nCorrespondence should be addressed: Pyotr A. Klimenko\nSevastolopsky prospect, 24а, Moscow, 117209, Russia; pa.klimenko@mail.ru\n1 Peoples' Friendship University of Russia, Moscow, Russia\n2 Family Planning and Reproduction Center, Moscow, Russia\n3 Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia\n4 Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia\n5 Sechenov First Moscow State Medical University, Moscow, Russia\n6 Pirogov Russian National Research Medical University, Moscow, Russia\nReceived: 23.11.2021 Accepted: 06.12.2021 Published online: 12.12.2021\nDOI: 10.24075/brsmu.2021.059\nAuthor contributions: the authors contributed to the study and preparation of the article equally, they read and approved the final version of the article prior to publication.\nCompliance with ethical standards: the study was approved by the Ethics Committee of Pirogov Russian National Research Medical University (protocol № 176 \ndated June 25, 2018). The informed consent was submitted by all patients.\nА. А. Г ерасимова1,2, Л. А. Ашрафян 3, И. Б. Манухин4, М. В. Шамаракова 2, М. С. Мирясова 5, П. А. Клименко6\nОСОБЕННОСТИ ДИАГНОСТИКИ И ТЕЧЕНИЯ ЭНДОМЕТРИОЗА С ДЕЦИДУАЛЬНЫМ \nМЕТАМОРФОЗОМ ВО ВРЕМЯ БЕРЕМЕННОСТИ\nВ настоящее время при наличии децидуализированных эндометриоидных кист яичников (ДЭК) хирургическое лечение для исключения злокачественных \nопухолей яичников выполняют практически в 90% случаев. Неоправданные хирургические вмешательства при этом увеличивают риск для здоровья \nматери и плода. Целью исследования было провести дифференциальную диагностику ДЭК у беременных для определения рационального лечения. В \nисследование включены 82 пациентки: 63 из них были с эндометриоидными кистами (ЭК), 16 — с ДЭК, 3 — с редкими формами эндометриоза и 10 — с \nсерозными папиллярными пограничными опухолями яичников. Для ультразвуковой (УЗ) диагностики использовали предложенную авторами модель. \nПолученные УЗ-данные сопоставляли с концентрацией белка-онкомаркера (СА-125), рассчитывали индекс RMI (risk of malignancy index), выполняли \nморфологическое исследование образований. Особо ценными УЗ-параметрами при дифференциальной диагностике ЭК, ДЭК и пограничных \nсерозных опухолей были: измененная толщина стенки образования, наличие и форма папиллярных образований, аваскулярные эхогенные включения \nбез четких контуров, кровоток и расположение сосудов, асцит. Результаты частотного анализа показали различия между группами по данным УЗИ (в \n60–100% наблюдений). Гистологическое исследование выявило различие между группами в 100% наблюдений. Полученные результаты не позволили \nнам пролонгировать беременность при ДЭК без выполнения хирургического лечения. Результаты лечения пациенток с ДЭК во время беременности \nбыли хуже таковых без выраженной децидуальной трансформации ЭК яичников. В настоящее время диагностика ДЭК и лечение больных во время \nбеременности остаются несовершенными. Необходимы дальнейшие клинические наблюдения и поиск более надежных способов диагностики \nи рационального лечения беременных с ДЭК.\nКлючевые слова:  ультразвуковое исследование, морфологическое исследование, опухоли яичников, беременность\nДля корреспонденции: Петр Афанасьевич Клименко\nСевастопольский проспект, д. 24а, г. Москва, 117209, Россия; pa.klimenko@mail.ru \n1 Российский университет дружбы народов, Москва, Россия\n2 Центр планирования семьи и репродукции, Москва, Россия\n3 Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени В. И. Кулакова, Москва, Россия\n4 Московский государственный медико-стоматологический университет имени А. И. Евдокимова, Москва, Россия\n5 Первый Московский государственный медицинский университет имени И. М. Сеченова, Москва\n6 Российский национальный исследовательский медицинский университет имени Н. И. Пирогова, Москва, Россия\nСтатья получена: 23.11.2021 Статья принята к печати: 06.12.2021 О публикована онлайн: 12.12.2021\nDOI: 10.24075/vrgmu.2021.059\nВклад авторов:  авторы внесли равнозначный вклад в проведение исследования и подготовку статьи, прочли и одобрили ее финальную версию перед \nпубликацией.\nСоблюдение этических стандартов:  исследование одобрено этическим комитетом РНИМУ им. Н. И. Пирогова (протокол № 176 от 25 июня 2018 г.). \nВсе пациенты подписали информированное согласие на участие в исследовании.\n\n26\nОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕ    ГИНЕКОЛОГИЯ\nВЕСТНИК РГМУ   6, 2021   VESTNIKRGMU.RU| |\nFig. 1. ROC curve of the model for identification of endometrial cysts\nROC curve\nSensitivity\nSpecificity\n1.0\n0.5\n0.0\n0.8\n0.2\n0.4\n0.0 0.4 0.80.2 0.6 1.0\nOvarian endometriosis is a chronic tumor-like lesion observed \nin 1–2% of pregnant women [1]. In 12% of women, the foci \nof endometriosis may undergo decidualization, and emerge as \nearly as at 9 weeks of gestation [2].\nDecidualization is a benign transient lesion, observed during \ngestation. It is usually found during the caesarian section or \nsurgical treatment of masses with high risk of malignization. \nThe decidual regression occurs in 4–6 weeks after delivery [3]. \nAccording to some reports, lower levels of decidualization in the \npostpartum period [4] are associated with high progesterone \nlevels, absence of menstrual periods, and increased apoptosis \nbeing the key factor of endometriosis regression. \nDecidualized endometrial cysts (DEC) are almost always \nasymptomatic during pregnancy. When performing the \nultrasound examination of DEC, the majority of authors \ndistinguish the combination of the cystic cavity with a large \namount of suspended debris, typical for EC, and papillary \nprojections with increased vascularity. These echographic \ncharacteristics are similar to those of malignant ovarian tumors. \nSurgical interventions aimed to exclude the malignant ovarian \ntumors in patients with DEC are performed in almost 90% of \nobservations [5, 6]. Unnecessary surgical interventions increase \nthe risk to maternal and fetal health [7–11]. \nThus, despite the fact that in pregnant women \ndecidualization is characterized by benign course, it becomes \nthe cause of numerous complications, and the presence of \nmacroscopic features similar to those of malignant tumors may \nresult in unnecessary therapeutic interventions.\nThe study was aimed to perform a differential diagnosis of \nDEC in pregnant women in order to define the rational treatment.\nMETHODS\nA total of 82 female patients with endometriosis verified by \nhistology were enrolled in the study, which was carried out in \n2000–2021. The age of the patients examined varied between \n19–41 years (the median age was 31 years). Inclusion criteria: \nconsent to participate in the study; pregnancy; ultrasonography \nconfirmed ovarian endometriosis in the pregravid period or during \npregnancy; subsequent surgical treatment and morphological \nverification. Exclusion criteria: pregnant woman's refusal \nto participate in the study; threatened abortion; intrauterine \ninfection; prenatal injury identified before the study. \nIn group 1 (control group), ultrasound examination performed \nduring pregnancy revealed no signs of decidualization in 63 \npatients out of 82. These patients had a caesarean delivery \ndue to combined indications: endometriosis and breech \npresentation in 9 patients, acute fetal hypoxia in 10 patients, \nunprepared birth canal and hypotonic labor in 11 patients, \npostterm pregnancy and threats to the fetus in 10 patients, \nsevere preeclampsia in 4 patients, symphysitis in 5 patients, \nuterine scar in 6 patients, placenta praevia in 4 patients, primary \ninfertility and  in vitro  fertilization (IVF) in 4 patients. After the \ndelivery and histological examination of ovarian masses (OM), \ndecidualization in the ovaries was the finding revealed in 43 of \nthese patients.\nAmong 63 deliveries, 5 (7.9%) were preterm. Of those in \n1 case severe preeclampsia developed at 29 weeks, and the \ntreatment was ineffective; in 2 cases at 32 weeks there were \nplacenta previa with hemorrhage (1 patient) and premature \nrupture of membranes (PROM) (1 patient); in 2 cases at 35–36 \nweeks there were placenta previa with hemorrhage (1 patient) \nand acute fetal hypoxia (1 patient). \nIn 16 patients of group 2, decidualization in the ovary \nwas found at 16–28 weeks (the median value was 17) of \npregnancy, having the signs resembling malignization, that is \nwhy laparoscopic adnexectomy (one case) with oophorectomy \n(four cases) was performed, as well as laparotomy with \nadnexectomy (four cases) and oophorectomy (seven cases). \nWhen performing laparotomy, the abdominal cavity revision \nwas performed, together with tissue specimen collection and \nrapid morphological examination. \nThree patients had the severe decidual reaction and rare \ncomplications of endometriosis. In one patient, who had the \ncaesarian delivery, endometrial implants were found during the \nsurgical procedure. The foci of deciduosis were located on the \nuterine surface, omentum, peritoneum, and were represented \nby numerous yellowish elastic nodules of various sizes, the \nlargest of which were almost 4 cm in diameter. In two women, \ndecidualization was diagnosed in the colon wall, resected on days \n2 and 5 after delivery due to the symptoms of acute abdomen.\nWhen performing a differential diagnosis of DEC, we used \nthe earlier results (control group 2) [12] obtained for 10 patients \nwith ovarian serous papillary borderline tumors.\nUltrasound examination was performed with the Voluson \nЕ8 ultrasound machine (General Electric; USA) with the use of \n\n27\nORIGINAL RESEARCH    GYNECOLOGY\nBULLETIN OF RSMU   6, 2021   VESTNIKRGMU.RU| |\nFig. 2. Doppler ultrasonography of the endometrial cyst. Longitudinal transabdominal \nscan. Multiple coloured loci of blood flow and low resistive index values\nFig. 3. ROC curve of the model for diagnosis of malignant and borderline tumors in \npregnant women\nROC curve\nSensitivity\nSpecificity\n1.0\n0.5\n0.0\n0.8\n0.2\n0.4\n0.0 0.4 0.80.2 0.6 1.0\ntransabdominal and transvaginal color Doppler imaging and \npulsed wave Doppler velocimetry. Ultrasound characteristics of \nthe tumors were assessed using the earlier proposed models \n[13]. The 2D and 3D comprehensive ultrasound examination \nwas combined with color Doppler (CD) and power Doppler \n(PD), as well as with 3D angiography. Diagnostic ultrasound \nwas performed with the use of our proposed model, allowing \none to distinguish between benign, borderline and malignant \ntumors [13]. When assessing the model accuracy, sensitivity \n(Se) and specificity (Sp) were used along with the count of \ncorrect assignments. \nThe concentration of СА-125 was assessed by enzyme \nimmunoassay using the test system (Siemens; Germany). \nRMI was defined in accordance with the guidelines [14, 15] \nusing the following formula: \nRMI = М × U × CA-125,\nwhere М — menopausal status in points, U — ultrasound \nresults in points, C — serum CA-125 level (IU/mL). \nRMI ≥ 200 was regarded as a sign of the high likelihood of \nepithelial ovarian cancer.\nTissue specimens stained with hematoxylin and eosin \nwere assessed by different pathologists. Morphological \ndiagnosis was established in accordance with the WHO \nclassification of tumours of the female reproductive organs \n(2014). Paraffin-embedded tissue blocks were selected for \nimmunohistochemistry: 15 blocks from patients with EC, and \n10 blocks from patients with DEC. Morphological assessment \nwas performed by standard methods. The diagnosis of \ndeciduosis was confirmed by immunohistochemistry with the \nuse of Vimentin (3B4, Ventana) and CD10 (56C6, Ventana) \nantibodies, being the markers of mesenchymal tissue and \nendometrial stroma, respectively. Intestinal tissue specimens \nwere used as a positive control when assessing the expression \nof Vimentin, and the tonsillar tissue specimens were used \nwhen studying the CD10 immunoreactivity; when performing \nimmunohistochemistry, the samples of the studied tissue \nnot treated with primary antibodies were used as a negative \ncontrol for both markers. Positive staining for both markers was \nsubjectively classified as weak, moderate, or strong.\nIn addition, medical records together with the pregnancy \nand childbirth outcomes were studied in these 82 patients after \ntreatment.\nStatistical data processing was carried out using the SPSS \n15.0 software package (IBM; USA). The data were subjected \nto frequency analysis by constructing the crosstabs. The \ndifferences were considered significant when p < 0.05. \nRESULTS\nUltrasonography showed that in the majority of observations \nin group 1, EC ( n = 63) were small, located inside the ovaries, \nwith smooth outer and inner contours, the cyst content was of \nmoderate or high echogenicity, blood vessels were visible in the \nwalls. A total of 60 EC (95%) were unilateral: right-sided in 18 \npatients (30%), left-sided in 42 patients (70%). Bilateral cysts \nwere found in three observations (5%). \nThe cyst size varied between 25 × 20 and 127 × 83 mm, \nthe average size was 47.5 ± 4.8 × 31.8 ± 3.1 mm, (the median \nvalue was 41.5 × 28.5 mm). In 48 pregnant women (76%) \nof group 1, EC had the characteristic echographic features \n(lied in a fixed position close to the posterior uterine wall, had \na thickened wall, creating the effect of double contour, non-\nmovable finely dispersed suspended material (ground-glass \nopacity)), not differing substantially from the typical echographic \nfeatures observed in the non-pregnant state. CD and PD \nrevealed the sporadic coloured loci with high or medium \nresistance blood flow within a cyst wall. Bilateral cysts were \nfound in three observations. In about 5% of 63 observations, \nEC had intracystic masses of moderate or high echogenicity \nin the form of blood clots and multiple sponge-like zones with \nundulating contour in the inner surface of the mass. In 12 \nobservations (19%), EC visible on the image looked like serous \ncystadenomas, round shaped hypoechoic masses with small \namount of suspended material, avascular on CD images.\nWhen performing the differential diagnosis of EC with the \nuse of our proposed method [13], the patient's age, blood \nvessel arrangement, and the resistive index (RI) were of the \ngreatest informational value. The maximum EC score obtained \nusing the decision procedure did not exceed 2 points.\nPerformance of the model for EC identification (Fig. 1) was \n84%, however, the area under the ROC curve was very large, \nindicating the high quality of the model.\nPreoperative evaluation of the patients in group 1 revealed \nno peculiarities in the ultrasound imaging parameters, СА-125, \nRMI in puerperant women with no deciduosis and those \nwho had deciduosis, which was identified as a finding when \nperforming the histological examination.\nBlood levels of СА-125 in patients varied between 7.3 \nand 131.2 U/mL, the average level was 61.1 ± 8.5 U/mL \n\n28\nОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕ    ГИНЕКОЛОГИЯ\nВЕСТНИК РГМУ   6, 2021   VESTNIKRGMU.RU| |\nFig. 4. Endometrial cyst with prominent decidualization and the formation of pseudopapillary structures. А. DEC (hematoxylin and eosin, ×50). B. CD10 — \nprominent diffuse membranous and cytoplasmic expression. C. Vimentin — prominent diffuse cytoplasmic expression\nА B C\nTable. Comparative characteristics of EC, DEC and borderline tumors\nStudied parameters EC DEC Borderline tumors\nLocation of the mass Posterior to the uterus, \nfixed low\nPosterior to the uterus, fixed \nlow\nBeside the uterus, often at the level of \nthe fundus\nStructure: cystic, cystic and solid Cystic Cystic and solid Cystic and solid\nType of suspended debris: coarse echogenic \n(ground-glass opacity), finely dispersed echogenic \nGround-glass opacity — \ncoarse echogenic\nGround-glass opacity — \ncoarse echogenic Finely dispersed echogenic \nStructure: unilocular, bilocular, trilocular Unilocular Unilocular, bilocular, trilocular Unilocular, bilocular, trilocular\nWall of the mass: thickness, size of altered locus Fragmented up to 2 mm Total up to 3–6 mm Fragmented up to 2 mm\nPapillary growths: presence and shape No Regular round shape in 100% Irregular shape in 100% (of cauliflower \ntype)\nAvascular echogenic inclusions with blurry \ncontour Extremely rare Up to 97% No\nRI (resistive index) 0.54 (0.41–0.69) 0.44 (0.24–0.62) 0.42 (0.19–0.58)\nPSV (peak systolic velocity) 9.6 (9.2–14.3) 13.2 (6.0–17.0) 14 (3.9–21.9)\nPI (pulsatility index ) 0.82 (0.51–1.22) 0.55 (0.25–0.87) 0.54 (0.27–0.88)\nBlood circulation (arrangement of blood vessels) No, single loci Moderate to high circulation \nintensity \nHigh circulation intensity in the wall, \nsepta, and papillary growths\nAscites no no present in 60% \nСА-125 (U/mL) 61.1 ± 8.5 (median 53) 120 ± 31.6 (median 70.5) 135.4 ± 55.1 (median 80.5)\nRMI 65.4 ± 9 (median 59) 348 ± 97 (median 212) 334.1 ± 147 (median 241.5)\nHistological examination Histological features of \novarian EC\nHistological features of ovarian \nDEC\nHistological features of ovarian serous \npapillary borderline tumors\n(the median value was 53 U/mL). Furthermore, in 19 patients \n(30%), this value was below the threshold (7.3–33.4 U/mL). \nIn 31 patients (49%), this indicator showed the upward trend \n(44–94 U/mL), and in 13 patients (21%) the value exceeded \n100 U/mL (100.2–131.2 U/mL). Our records show that СА-125 \nvaries in the range of 8.5–280 U/mL during normal pregnancy \n(the median value is 95.6 U/mL).\nRMI varied between 7.3 and 131.2, the average value was \n65.4 ± 9 (the median value was 59). In the group of patients \nwith EC, about 98% had RMI of less than 200. Moreover, in \n19 patients (31%), RMI was below 25, in 28 patients (44%), it \nwas 25–100, and only in 16 patients (25%), the observed RMI \nvalues exceeded 100, but never reached 200.\nThe planned caesarean section results in this group were \nas follows: all children were born in satisfactory condition. The \nApgar score was 6–8 (the median value was 7.8) in premature \nbabies and 8–9 (the median value was 8.9) in full-term babies. \nThe birth weight was 1880–2840 g (the median value was 2640 \ng) in premature babies and 2660–4480 g (the median value was \n3530 g) in full-term babies. Three premature babies needed \nthe 2nd stage developmental care. In other babies, the early \nneonatal period went smoothly, the patients and their babies \nwere discharged from the maternity hospital on day 5–7 after \nsurgery. The morbidity rate was 3.2%.\nMorphological examination of non-decidualized EC \nshowed that the walls of ovarian cysts consisted of ovarian \ntissue with fibrotic changes, inner layer of cytogenic stroma \nwith hemorrhages and hemosiderin deposition, and the lining \nepithelium was of endometrioid type. In DEC identified as \nfindings, the fragments of the cystic ovarian endometrioma \nwall were defined with no lining epithelium, large areas of \ndecidualization involving hypertrophy of endometrial stromal \ncells into polygonal cells with clear margins, abundant \neosinophilic cytoplasm, round to oval nuclei with fine granular \nchromatin; no mitosis was detected. \nWhen performing ultrasound examination in group 2 (n = 16), \nDEC were identified as the masses secured to the walls of the \npelvis, located low relative to the gravid uterus. In 10 pregnant \nwomen (62.5%), DEC were unilateral, right-sided DEC were \nfound in 7 patients (70%), and left-sided DEC were identified in \nthree patients (30%). Bilateral ovarian lesions were reported in \nsix observations (37.5%).\nThe cyst size varied between 20 × 30 and 108 × 161 mm, \nthe average size was 73.7 ± 6.2 × 96.5 ± 7.5 mm (the median \nvalue was 76.5 × 108.5 mm) (significant differences with group 1, \nр < 0.001–0.05).\nDEC were characterized by cystic and solid ovarian mass \nstructure in all observations, multiloculated structure in four \npatients (25%), or incomplete septa in four observations \n(25%), irregular wall thickening with highly vascularized mural \nstructures having multiple coloured loci of blood flow and low \nresistive index values in all masses. \n\n29\nORIGINAL RESEARCH    GYNECOLOGY\nBULLETIN OF RSMU   6, 2021   VESTNIKRGMU.RU| |\nFig. 5. Multiple regions of decidualization\nWhen performing the differential diagnosis of DEC with \nthe use of our proposed method [13], such factors as ovarian \ntissue, RI, PSV, and blood vessel arrangement were of great \nprognostic value. The maximum DEC score obtained using the \ndecision procedure exceeded 4 points. Based on the ultrasound \nfeatures, DEC (Fig. 2) could be identified as a malignant tumor.\nThe model obtained showed sensitivity of 100% and \nspecificity of 92.3% in the test sample, with the overall accuracy \nof 92.8% (Fig. 3).\nBlood levels of СА-125 in patients of group 2 varied \nbetween 17.6 and 361 U/mL, the average level was 120.1 ± \n31.6 U/mL (the median value was 70.5 U/mL). Furthermore, \nin two pregnant women (12.5%), this value was below the \nthreshold, in nine observations (56.25%), this indicator showed \nthe upward trend (from 47.8 to 82.67 U/mL), and in five patients \n(31.25%), the value exceeded the threshold and reached \n361 U/mL.\n RMI varied between 69 and 1083, the average value was \n348 ± 97 (the median value was 212, р < 0.001–0.05). In the \ngroup of patients with DEC, seven pregnant women (43.75%) \nhad RMI values significantly higher than 200 (207–1083), five \npatients (31.25%) had RMI not exceeding 200, and only four \npatients (25%) had RMI values below 100.\nIn patients of group 2 with decidualization in the ovary, \npregnancy evolved in different ways. In four patients out of 16 \n(25.0%), pregnancy was complicated by miscarriage after the \nsurgical treatment due to suspected malignancy, performed \nat week 12–27 of pregnancy. Perinatal death at 23 weeks of \ngestation occurred in one patient, three patients gave birth \nprematurely, and 12 patients had a full term delivery. The \nApgar scores of premature babies varied between 6–8 and \n7–8 (the median value was 6–7). The birth weight of premature \nbabies was 1880–2640 g, (the median value was 2010 g). \nIn patients, who had a full term delivery, the Apgar scores of \nthe newborns varied between 8–9 and 9–9 (the median value \nwas 8–9), the Silverman Anderson score was 2–3, and the \nbirth weight was 2810–3720 g (the median value was 3185 \ng). In one observation, the early neonatal period was spent in \nthe intensive care unit, and in three observations, respiratory \nsupport and the treatment of respiratory distress syndrome \nwere required. Subsequently, three newborns were transferred \nto the multidisciplinary children's hospital for the 2nd stage \ndevelopmental care. Thus, perinatal mortality in group 2 was \n62.5‰, and morbidity was 25.0%.\nFig. 4А demonstrates the wall of the cystic ovarian \nendometrioma with no lining epithelium, fibrotic changes of \novarian tissue, and prominent hypertrophy of endometrial \nstromal cells with the formation of the well vascularized papillary \nstructures. \nImmunohistochemistry performed in the group 2 on \n10 selected paraffin-embedded tissue blocks confirmed \ndecidualization in the cystic ovarian endometrioma walls in \nall observations. Morphological evaluation showed that the \nlatter had a typical structure, were lined with epithelium of \nendometrioid type, with hemorrhagic foci and hemosiderin \ndeposition within the wall. Immunohistochemistry revealed \nmoderate positive cytoplasmic expression of CD10 in the \nstromal cells of the foci with decidualization (Fig. 4B) together \nwith strong positive cytoplasmic immunoreactivity for Vimentin \n(Fig. 4C).\nDISCUSSION\nWhen reviewing the data obtained, it should be noted that \nEC with no prominent decidualization during pregnancy have \na latent favorable course and do not result in pathological \npregnancy and labor course, increased perinatal morbidity and \nmortality.\nAccording to literary sources, decidualized EC occurs in \n12–20% of observations; the cyst size is reduced in 52% of \nobservations, increased in 20% of observations, and unaffected \nin 28% of observations. Furthermore, the rate of DEC rupture \nis 3–4%, and the abscess formation is revealed in 4% of \nobservations [16, 17].\nDifferential diagnosis of ovarian EC and DEC in pregnant \nwomen remains an obstetric challenge. Most authors \ndistinguish the combination of the cystic cavity with a large \namount of suspended debris, typical for EC, and papillary \nprojections with increased vascularity among the echographic \nsigns of DEC [7–11]. When there is a DEC, the sonographic \nfeatures are similar to those observed in patients with malignant \novarian tumors based on the echographic characteristics. Our \nrecords (Table) show that today the use of generally accepted \nnon-invasive preoperative diagnostic tests makes it possible \nto distinguish between EC, DEC, and borderline tumors with a \nhigh probability. The comparison of DEC with borderline tumors \n(with the control group 2) revealed significant fluctuations in the \nstudied indicators, however, based on the ultrasound imaging \ndata, these were distinguishable in the majority of observations. \nIn modern medicine, the good test (marker) is the one that is \nnot found in 70% of the comparison group when comparing \ntwo groups.\nWhen performing the differential diagnosis of the studied \ngroups (Table), the following ultrasound imaging parameters \nwere the most valuable: the altered mass wall thickness, the \nexistence and shape of papillary masses, avascular echogenic \ninclusions with blurry contour, blood circulation and arrangement \nof blood vessels, ascites. The frequency analysis showed that \nthe DEC group differed from the groups with EC and borderline \ntumors in 60–100% of observations based on the sonographic \nmarkers. The results of histological examination made it possible \nto perform a differential diagnosis of EC, DEC, and borderline \ntumors in 100% of observations.\nGiven that the assessment of the studied sonographic \nmarkers is still subjective, and the findings have made it \nimpossible to eliminate the high risk of the mass malignization \nin patients with DEC, these patients have undergone surgery \nin early pregnancy. Echographic image of DEC suspicious for \nmalignization has made it impossible to prolong pregnancy \nfor ethical reasons, even with the possibility of the increased \nrate of perinatal complications. The need for surgical treatment \n\n30\nОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕ    ГИНЕКОЛОГИЯ\nВЕСТНИК РГМУ   6, 2021   VESTNIKRGMU.RU| |\naimed to exclude the malignant ovarian tumors in patients with \ndecidualized EC (DEC) is in line with literature data [5, 6], this \ntreatment method is applied in almost 90% of observations. \nAdverse pregnancy outcomes in patients with endometriosis \nrelate primarily to miscarriage, high risk of preterm labor and \nlow birth weight babies [18–20]. \nPregnancy and labor in patients with endometriosis are \nassociated with high risk of complications, such as hemoperitoneum, \nbowel perforation, appendicitis, and EC rupture [19, 20].\nOther complications of pregnancy are observed in patients \nwith decidualization. Thus, in one of the trials, histological \nexamination revealed decidual changes in all layers of appendix \non day 5 after caesarian section and gangrenous appendicitis \n[21]. During our study, multiple yellowish elastic nodules of \nvarious size (up to 4 cm), located on the uterine surface, \nomentum, and peritoneum, were found during the surgical \nprocedure in one patient, who had caesarian section for \nobstetric reasons (Fig. 5). \nThe fragments of omentum were resected for further \nhistological examination, which revealed prominent decidual \nchanges. In the other two patients, we had to perform re-surgery \nduring the postoperative period (on days 2–5 after the caesarian \nsection performed for obstetric reasons) due to acute abdomen. \nThe macroscopically altered fragments of the colon with \ndecidualization in the wall and multiple endometrioid heterotopias \nwith decidual changes in all layers of the colon wall were resected.\nThere is evidence of similar immunohistochemistry features \nin the extrauterine mesenchymal cells that have undergone the \ndecidual reaction, and decidualized endometrial stromal \ncells with positive expression of mesenchymal markers \n(Vimentin, Desmin), and progesterone receptors [22]. Reduced \nconcentration of progesterone, resulting from pregnancy \ntermination triggers the involution of foci with decidualization, \nwhich in some cases is followed by severe circulatory disorder \nand decidual tissue destruction, probably entailing the \npain symptoms and hemorrhage [23, 24]. Intra-abdominal \nhemorrhage was revealed on day 7 after the caesarian section \nin the patient, having the focus with decidualization, located in \nthe area of the uterine posterior wall on the left [25, 26].\nThus, decidualization in pregnant women is characterized by \na benign course, however, it becomes the cause of numerous \ncomplications. The presence of macroscopic features similar \nto those of malignant tumors may result in unnecessary \ntherapeutic interventions.\nCONCLUSIONS\nCurrently, the diagnosis of DEC and the treatment of patients \nduring pregnancy give rise to many questions. Further clinical \nobservation and the search for more reliable methods of the \nDEC diagnosis and rational treatment in pregnant women are \nrequired.\nReferences\n1. Marino T, Craigo SD. Managing adnexal masses in pregnancy. \nContemp Obstet Gynecol. 2000; 45: 130–43.\n2. Kommos F, Pfisterer J, Peters F, et al. Ektope Dezidualreaktion — \nmöglicher Anlass zur kolposkopischen, histologischen und \nintraoperativen Fehldiagnose. Geburtsh Frauenheilk. 1998; 58: \n446–50. \n3. Adhikari LJ, Rulong SR. Florid diffuse peritoneal deciduosis \nmimicking carcinomatosis in a primigravida patient: a case report \nand review of the literature. Int J Clin Exp Pathol. 2013; 6 (11): \n2615–9.\n4. Meresman GF, Auge L, Baranao RI, et al. Oral contraceptives \nsuppress cell proliferation and enhance apoptosis of eutopic \nendometrial tissue from patients with endometriosis. Fertil Steril. \n2002; 77: 1141–7.\n5. Pateman K, Moro F, Mavrelos D, et al. Natural history of ovarian \nendometrioma in pregnancy. BMC Womens Health. 2014; 14: 128.\n6. Leone Roberti Maggiore U, Ferrero S, Mangili G, et al. A \nsystematic review on endometriosis during pregnancy: diagnosis, \nmisdiagnosis, complications and outcomes. Hum Reprod \nUpdate. 2016; 22 (1): 70–103.\n7. Groszmann Y, Howitt BE, Bromley B, Feltmate CM, Benacerraf BR. \nDecidualized endometrioma masquerading as ovarian cancer in \npregnancy. J Ultrasound Med. 2014; 33 (11): 1909–15. DOI: \n10.7863/ultra.33.11.1909.\n8. Bailleux M, Bernard JP , Benachi A, Deffieux X. Ovarian \nendometriosis during pregnancy: a series of 53 endometriomas. \nEur J Obstet Gynecol Reprod Biol. 2017; 209: 100–4. DOI: \n10.1016/j.ejogrb.2015.09.037.\n9. Mascilini F, Moruzzi C, Giansiracusa С, et al. Imaging in \ngynecological disease. 10: Clinical and ultrasound characteristics \nof decidualized endometriomas surgically removed during \npregnancy. Ultrasound Obstet Gynecol. 2014; 3 (44): 354–60.\n10. Barbieri M, Somigliana E, Oneda S, et al. Decidualized ovarian \nendometriosis in pregnancy: a challenging diagnostic entity. Hum  \nReprod. 2009; 8 (24): 1818–24.\n11. Graupera B, Pascual M, Hereter L, et al. Dezidualization of \nendometrioma during pregnancy mimicking a malignant ovarian \ntumor. Ultrasound Obstet Gynecol. 2013; 42 (S1): 71.\n12. Ashrafjan LA, Kurcer MA, Gerasimova AA, Klimenko PA. \nPogranichnye i zlokachestvennye opuholi jaichnikov vo vremja \nberemennosti. Onkoginekologija. 2019; 3 (31): 68–77. Russian.\n13. Gerasimova AA, Shvyrev SL, Solomatina AA, Gus AI, Klimenko PA. \nSposob vyjavlenija haraktera jaichnikovyh obrazovanij. Onkologija. \n2013; 1; 34–40. Russian.\n14. Tingulstad S, Hagen B, Skjeldestad FE, et al. Evaluation of a risk \nof malignancy index based on serum CA125, ultrasound findings \nand menopausal status in the preoperative diagnosis of pelvic \nmasses. Brit. J. Obstet. Gynaecol. 1996; 103 (8): 826–31.\n15. Jacobs I, Oram D, Fairbanks J, et al. A risk of malignancy index \nincorporating CA125, ultrasound and menopausal status for the \naccurate pre-operative diagnosis of ovarian cancer. Brit J Obstet \nGynaecol. 1990; 97; 922–9.\n16. Bulanov MN, Gorta RN. Ul'trazvukovoe issledovanie jendometrioidnyh \nkist jaichnikov vo vremja beremennosti. Ul'trazvukovaja i \nfunkcional'naja diagnostika. 2015; 1: 55–71. Russian.\n17. Bromley B, Benacerraf B. Adnexal masses during pregnancy: \naccuracy of sonographic diagnosis and outcome. J Ultrasound \nMed. 1997; 7 (16); 447–52. \n18. Ueda Y, Enomoto T, Miyatake T, et al. A retrospective analysis of \novarian endometriosis during pregnancy. Fertil Steril. 2010; 94 (1): \n78–84.\n19. Fruscella E, Testa AC, Ferrandina G, et al. Sonographic features \nof decidualized ovarian endometriosis suspicious for malignancy. \nUltrasound Obstet Gynecol. 2004; 5 (24): 578–80.\n20. Carvalho LFP , Rossener R, Azeem A, et al. From conception to \nbirth — how endometriosis affects the development of each stage \nof reproductive life Minerva Ginecol. 2013; 65 (2): 181–98.\n21. Vercellini P , Parazzini F, Pietropaolo G, et al. Pregnancy outcome in \nwomen with peritoneal, ovarian and rectovaginal endometriosis: a \nretrospective cohort study. BJOG. 2012; 119 (12): 1538–43. DOI: \n10.1111/j.1471-0528.2012.03466.x.\n22. Papp Z, Petri I, Vill ányi E, Tiszlavicz L, Ugocsai G. Deciduosis \ncausing perforating appendicitis in the early postpartum period \nfollowing caesarean section. Orv Hetil. 2008; 149 (7): 329–31. \nDOI: 10.1556/OH.2008.28227.\n23. Heatley MK, Maxwell P , Toner PG. The immunophenotype \n\n31\nORIGINAL RESEARCH    GYNECOLOGY\nBULLETIN OF RSMU   6, 2021   VESTNIKRGMU.RU| |\nЛитература\n1. Marino T, Craigo SD. Managing adnexal masses in pregnancy. \nContemp Obstet Gynecol. 2000; 45: 130–43.\n2. Kommos F, Pfisterer J, Peters F, et al. Ektope Dezidualreaktion — \nmöglicher Anlass zur kolposkopischen, histologischen und \nintraoperativen Fehldiagnose. Geburtsh Frauenheilk. 1998; 58: \n446–50. \n3. Adhikari LJ, Rulong SR. Florid diffuse peritoneal deciduosis \nmimicking carcinomatosis in a primigravida patient: a case report \nand review of the literature. Int J Clin Exp Pathol. 2013; 6 (11): \n2615–9.\n4. Meresman GF, Auge L, Baranao RI, et al. Oral contraceptives \nsuppress cell proliferation and enhance apoptosis of eutopic \nendometrial tissue from patients with endometriosis. Fertil Steril. \n2002; 77: 1141–7.\n5. Pateman K, Moro F, Mavrelos D, et al. Natural history of ovarian \nendometrioma in pregnancy. BMC Womens Health. 2014; 14: \n128.\n6. Leone Roberti Maggiore U, Ferrero S, Mangili G, et al. A \nsystematic review on endometriosis during pregnancy: diagnosis, \nmisdiagnosis, complications and outcomes. Hum Reprod \nUpdate. 2016; 22 (1): 70–103.\n7. Groszmann Y, Howitt BE, Bromley B, Feltmate CM, Benacerraf BR. \nDecidualized endometrioma masquerading as ovarian cancer in \npregnancy. J Ultrasound Med. 2014; 33 (11): 1909–15. DOI: \n10.7863/ultra.33.11.1909.\n8. Bailleux M, Bernard JP , Benachi A, Deffieux X. Ovarian \nendometriosis during pregnancy: a series of 53 endometriomas. \nEur J Obstet Gynecol Reprod Biol. 2017; 209: 100–4. DOI: \n10.1016/j.ejogrb.2015.09.037.\n9. Mascilini F, Moruzzi C, Giansiracusa С, et al. Imaging in \ngynecological disease. 10: Clinical and ultrasound characteristics \nof decidualized endometriomas surgically removed during \npregnancy. Ultrasound Obstet Gynecol. 2014; 3 (44): 354–60.\n10. Barbieri M, Somigliana E, Oneda S, et al. Decidualized ovarian \nendometriosis in pregnancy: a challenging diagnostic entity. Hum  \nReprod. 2009; 8 (24): 1818–24.\n11. Graupera B, Pascual M, Hereter L, et al. Dezidualization of \nendometrioma during pregnancy mimicking a malignant ovarian \ntumor. Ultrasound Obstet Gynecol. 2013; 42 (S1): 71.\n12. Ашрафян Л. А., Курцер М. А., Г ерасимова А. А., Клименко П. А. \nПограничные и злокачественные опухоли яичников во время \nбеременности. Онкогинекология. 2019; 3 (31): 68–77.\n13. Г ерасимова А. А., Швырев С. Л., Соломатина А. А., Гус А. И., \nКлименко П. А. Способ выявления характера яичниковых \nобразований. Онкология. 2013; 1; 34–40.\n14. Tingulstad S, Hagen B, Skjeldestad FE, et al. Evaluation of a risk \nof malignancy index based on serum CA125, ultrasound findings \nand menopausal status in the preoperative diagnosis of pelvic \nmasses. Brit. J. Obstet. Gynaecol. 1996; 103 (8): 826–31.\n15. Jacobs I, Oram D, Fairbanks J, et al. A risk of malignancy index \nincorporating CA125, ultrasound and menopausal status for the \naccurate pre-operative diagnosis of ovarian cancer. Brit J Obstet \nGynaecol. 1990; 97; 922–9.\n16. Буланов М. Н., Г орта Р . Н. Ультразвуковое исследование \nэндометриоидных кист яичников во время беременности. \nУльтразвуковая и функциональная диагностика. 2015; 1: \n55–71.\n17. Bromley B, Benacerraf B. Adnexal masses during pregnancy: \naccuracy of sonographic diagnosis and outcome. J Ultrasound \nMed. 1997; 7 (16); 447–52. \n18. Ueda Y, Enomoto T, Miyatake T, et al. A retrospective analysis of \novarian endometriosis during pregnancy. Fertil Steril. 2010; 94 (1): \n78–84.\n19. Fruscella E, Testa AC, Ferrandina G, et al. Sonographic features \nof decidualized ovarian endometriosis suspicious for malignancy. \nUltrasound Obstet Gynecol. 2004; 5 (24): 578–80.\n20. Carvalho LFP , Rossener R, Azeem A, et al. From conception to \nbirth — how endometriosis affects the development of each stage \nof reproductive life Minerva Ginecol. 2013; 65 (2): 181–98.\n21. Vercellini P , Parazzini F, Pietropaolo G, et al. Pregnancy outcome in \nwomen with peritoneal, ovarian and rectovaginal endometriosis: a \nretrospective cohort study. BJOG. 2012; 119 (12): 1538–43. DOI: \n10.1111/j.1471-0528.2012.03466.x.\n22. Papp Z, Petri I, Vill ányi E, Tiszlavicz L, Ugocsai G. Deciduosis \ncausing perforating appendicitis in the early postpartum period \nfollowing caesarean section. Orv Hetil. 2008; 149 (7): 329–31. \nDOI: 10.1556/OH.2008.28227.\n23. Heatley MK, Maxwell P , Toner PG. The immunophenotype \nof human decidua and extrauterine decidual reactions. \nHistopathology. 1996; 29: 437–42.\n24. Lockwood CJ, Kayisli UA, Stocco C, et al. Abruption-induced \npreterm delivery is associated with thrombin-mediated functional \nprogesterone withdrawal in decidual cells. Am J Pathol. 2012; \n181: 2138–48. DOI: 10.1016/j.ajpath.2012.08.036.\n25. Lier MCI, Brosens IA, Mijatovic V, Habiba M, Benagiano G. \nDecidual bleeding as a cause of spontaneous hemoperitoneum in \npregnancy and risk of preterm birth. Gynecol Obstet Invest. 2017; \n82 (4): 313–21. DOI: 10.1159/000468933.\n26. L üdders DW, Henke RP , Saba M, et al. Severe maternal pre- \nand postpartum intra-abdominal bleeding due to deciduosis. \nGeburtshilfe Frauenheilkd. 2015; 75 (3): 259–62. DOI: 10.1055/s-\n0035-1545876.\nof human decidua and extrauterine decidual reactions. \nHistopathology. 1996; 29: 437–42.\n24. Lockwood CJ, Kayisli UA, Stocco C, et al. Abruption-induced \npreterm delivery is associated with thrombin-mediated functional \nprogesterone withdrawal in decidual cells. Am J Pathol. 2012; \n181: 2138–48. DOI: 10.1016/j.ajpath.2012.08.036.\n25. Lier MCI, Brosens IA, Mijatovic V, Habiba M, Benagiano G. \nDecidual bleeding as a cause of spontaneous hemoperitoneum in \npregnancy and risk of preterm birth. Gynecol Obstet Invest. 2017; \n82 (4): 313–21. DOI: 10.1159/000468933.\n26. L üdders DW, Henke RP , Saba M, et al. Severe maternal pre- \nand postpartum intra-abdominal bleeding due to deciduosis. \nGeburtshilfe Frauenheilkd. 2015; 75 (3): 259–62. DOI: 10.1055/s-\n0035-1545876.","source_license":"CC0","license_restricted":false}