{"paper_id":"594c855b-999d-4ed6-9702-3dbdc7c6c372","body_text":"Medical Studies/Studia Medyczne 2021; 37/3\nReview paper\nEndometrial cyst and its changes during pregnancy – a narrative \nreview of the literature \nTorbiel endometrialna i jej zmiany w trakcie ciąży – przegląd piśmiennictwa\nJakub Młodawski1,2, Marta Mlodawska1, Mariusz Malmur2, Justyna Płusajska1,2, Grzegorz Świercz1,2  \nMarek Sikorski1\n1Collegium Medicum, Jan Kochanowski University, Kielce, Poland \n Head of the Collegium: Prof. Marianna Janion MD, PhD \n2Clinic of Obstetrics and Gynaecology, Provincial Combined Hospital, Kielce, Poland \n Head of the Clinic: Grzegorz Swiercz MD, PhD\nMedical Studies/Studia Medyczne 2021; 37 (3): 226–231\nDOI: https://doi.org/10.5114/ms.2021.109511\nKey words: endometrial cyst, chocolate cyst, endometrioma, pregnancy.\nSłowa kluczowe: torbiel endometrialna, torbiel czekoladowa, endometrioma, ciąża.\nAbstract\nEndometrioma of the ovary (chocolate cyst) is one of the most common tumours of the appendages diagnosed in pregnant \npatients. In approximately 12% of pregnancies with diagnosed ovarian endometriomas, the process of decidualization, i.e. \ntumour secretory transformation, occurs under the influence of high progesterone concentrations. Decidualized endome -\ntrioma is a benign lesion, but its ultrasound appearance imitates a malignancy; therefore, knowledge of the process and \ndiagnostic possibilities is extremely important for the clinician, and it may limit the number of surgical interventions in \npregnant patients. This review discusses the decidualization of endometriosis as well as the ultrasound and biochemical \ndiagnostics of this entity.\nStreszczenie\nTorbiel endometrialna jajnika (torbiel czekoladowa) jest jednym z najczęstszych guzów przydatków diagnozowanych u pa -\ncjentek ciężarnych.  W ok. 12% przypadków w ciąży dochodzi do procesu decydualizacji zmiany, tj. przemiany sekrecyjnej \ntkanki guza pod wpływem dużego stężenia progesteronu. Zmiana, która uległa decydualizacji, histologicznie ma łagodny \ncharakter,  jednak obraz ultrasonograficzny może imitować raka jajnika. Znajomość procesu decydualizacji ma duże zna -\nczenie dla klinicystów, ponieważ może ograniczyć liczbę interwencji chirurgicznych u pacjentek ciężarnych. W niniejszym \nprzeglądzie zostało omówione zjawisko decydualizacji torbieli endometrialnej w ciąży, jak również możliwości diagnostyki \nultrasonograficznej i biochemicznej. \nEndometriosis in the population of pregnant \npatients\nEndometriosis is associated with the presence of \nglands and endometrial stroma outside the uterine \ncavity. The disease affects about 10% of women of \nreproductive age, 50% of patients diagnosed for in -\nfertility, and 70% diagnosed for chronic abdominal \npain [1, 2]. The highest prevalence of endometriosis \noccurs in patients between 25 and 35 years of age [3]; \nthis is also the age of peak procreation in Europe. En -\ndometriosis affects the quality of life of patients and \ntheir procreative plans. The most frequent location of \nlesions is the ovary (67% of patients with laparoscopi-\ncally confirmed endometriosis) [4]. Ovarian endome -\ntriosis most often takes the form of a cyst – endome -\ntrioma (so-called “chocolate cyst”). Given the average \nage of procreation in Europe, the age range of patients \nwith the highest prevalence of endometriosis, and the \ntendency to relapse after treatment, the coexistence \nof pregnancy and endometriosis is often observed in \nclinical practice [5].\nPregnancy in patients with endometriosis\nPain, infertility or subfertility are typical symp -\ntoms of endometriosis. Pain in patients suffering from \nendometriosis during pregnancy usually disappears \nor alleviates, and endometrial lesions decrease in size \n[6]. Factors influencing changes in endometrial lesions \nare the period of gestation (the chance of regression \nof the lesion increases with the progression of preg -\n\n227Endometrial cyst and its changes during pregnancy – a narrative review of the literature \nMedical Studies/Studia Medyczne 2021; 37/3\nnancy) and the size of the lesion (greater tendency to \ncomplete regression in the case of diameter < 20 mm). \nThe literature also describes histological features of \nendometriosis foci increasing susceptibility to regres -\nsion under the influence of gestagens [6]. However, \npatients who become pregnant have an increased risk \nof certain obstetric complications compared to preg -\nnant patients without diagnosed endometriosis. Such \ncomplications include miscarriage – OR (odds ratio) \n= 1.76 (95% CI: 1.44–2.15), ectopic pregnancy – OR \n= 2.70 (95% CI: 1.09–6.72), pre-eclampsia (OR = 1.18, \n95% CI: 1.01–1.39), gestational diabetes (RR (relative \nrisk) = 1.26, 95% CI: 1.03–1.55), gestational cholestasis \n(OR = 4.87, 95% CI: 1.85–12.83), placenta previa (OR \n= 3.31, 95% CI: 2.37–4.63), antepartum haemorrhage \n(OR = 1.69, 95% CI: 1.38–2.07), and antepartum hos -\npital admissions (OR = 3.18, 95% CI: 2.60–3.87). There \nis also a higher risk of neonatal complications such as \npreterm premature rupture of membranes (OR = 2.33, \n95% CI: 1.39–3.90), stillbirth (OR = 1.29, 95% CI: 1.10–\n1.52), preterm birth (OR = 1.70, 95% CI: 1.40–2.06), \nsmall for gestational age (< 10 percentile) (OR = 1.28, \n95% CI: 1.11–1.49), and admission to a neonatal inten-\nsive care unit (OR = 1.39, 95% CI: 1.08–1.78) [7–11]. \nThe literature also presents cases of surgical complica -\ntions of visceral endometriosis such as intestinal per -\nforation, appendicitis, rapture of endometriomas and \nfallopian tubes, or spontaneous pneumothorax [6].\nEndometrioma during pregnancy  \nand decidualization process\nThe occurrence of endometrioma in the popula -\ntion of pregnant patients is estimated at approx. 0.5% \n[12]. Population studies indicate that ultrasound ex -\namination of the ovaries with a vaginal probe in the \n1\nst trimester of pregnancy during 1st trimester prena -\ntal examinations (11–13 +6 weeks of gestation) allows \nvisualization in approx. 11% of patients with adnexal \ntumours (taking into account only complex and sim -\nple cysts with a diameter greater than 5 cm) [13]. In the \ncohort presented in a study among patients who un -\nderwent enucleation of an ovarian cyst during preg -\nnancy due to pain, suspected cancer, or the patient’s \nrequest, histopathological diagnosis of endometrioma \nwas made in 24.2% of cases and was the second most \ncommon diagnosis after dermoid cysts (36.4%) [13].\nUltrasound diagnosis of an endometrial cyst is \nrather straightforward: unilocular cyst with low-lev -\nel homogenic internal echoes (“ground glass”), clear \ndemarcation from ovarian parenchyma, increased \nthrough-transmission of acoustic beam, usually with \nno solid areas and papillary projections (Figure 1). \nSuch an image of endometrioma is not universal, but \nit affects up to 80% of tumours [14].\nThe goal of endometrioma treatment outside preg-\nnancy is to reduce pain and prevent complications re-\nlated to rupture and torsion of the ovary, as well as to \ntreat infertility while maintaining ovarian reserve. An \nimportant element is also the exclusion of cancer. En -\ndometriosis is associated with a small increased risk of \novarian cancer (standardized incidence ratio (SIR) 1.76, \n95% CI: 1.47–2.08). This relationship is mainly related \nto endometrioid (SIR = 3.12, 95% CI: 2.15–4.38) and \nclear cell (SIR = 5.17, 95% CI: 3.20–7.89) cancer [15, 16]. \nPatients should be informed about the increased risk of \novarian cancer. The increase in life-time absolute risk \nof ovarian cancer for patients with endometriosis is \nsmall and amounts to 1.8% (in the general population \nthe risk is 1.31%) [17]. A definite histological diagnosis \ncan only be made after surgical removal of cysts. Surgi-\ncal treatment, despite the advantages of direct evalua-\ntion of the tissue collected, is limited due to potential \npostoperative complications [18, 19]. \nMedical treatment is an alternative to surgical \ntreatment. Commonly used therapies are progesto -\ngens alone, estrogen-progestin contraceptive pills or \nGnRH agonists. This treatment is aimed at decidual -\nizing endometriotic foci (secretory transformation), \nfollowed by ectopic endometrial atrophy. This process \nreduces bleeding from ectopic endometrial lesions \nand reduces the local inflammatory reaction, and thus \nthe patient’s pain. Despite the lack of access to the ab-\ndominal cavity and the histological examination of \nthe lesion, such a procedure avoids the risk associated \nwith the surgery and its potential complications.\nPregnancy is a physiological condition associated \nwith elevated progesterone levels. It is initially pro -\nduced by the corpus luteum. Later, between the 7\nth and \n10th week of pregnancy, the placenta becomes its pri -\nmary production site. At the beginning of pregnancy, \nits serum concentration ranges from 8 to 48 ng/ml, \nwhile its concentration in the serum is between 100 and \n200 ng/ml during full-term pregnancy [20]. On the one \nhand, high progesterone concentrations in pregnancy \nresult in the reduction of the patient’s pain, but may \nlead to the initiation of the process of endometrioma \ndecidualization, i.e. secretory transformation. The pro-\nFigure 1. Endometrioma with typical ultrasound image\n\nJakub Młodawski, Marta Mlodawska, Mariusz Malmur, Justyna Płusajska, Grzegorz Świercz, Marek Sikorski\n228\nMedical Studies/Studia Medyczne 2021; 37/3\ncess itself has no implications for the patient’s health \nbut is a diagnostic challenge for the doctor. Knowledge \nabout this process is essential because it can imitate \novarian cancer in ultrasound. The process of endome -\ntrioma growth in pregnancy concerns about 20% of \ncases. Tumour growth is not always associated with \ndecidualization, and ultrasound enlargement may also \noccur as a result of abscess formation or rupture [12]. \nIn half of the cases the size of the endometrioma is \nreduced, and in 28% it remains unchanged [12]. \nUltrasound features of the decidualization  \nof endometriomas\nDecidualized endometrioma has no pathogno -\nmonic ultrasound features. In the initial stage of de -\ncidualization, an increase in the echogenicity of the \ncontents of the inside of the cyst can be observed (Fig-\nure 2); with time, the most disturbing symptom for \nan ultrasound examiner is papillary projection into \nthe lumen of the cyst (Figure 3). In the literature, we \ncan find mainly case series. On this basis, research -\ners are trying to establish common diagnostic features \nthat help differentiate endometrioma decidualization \nfrom ovarian cancer. However, differentiation is not \neasy, especially in the case of de novo diagnosis in \npatients whose ovarian lesions were not diagnosed in \nthe first trimester of pregnancy. Most of the tumours \nsubject to decidualization present in the ultrasound \nthe morphology of unilocular cysts with solid com -\nponents (52%), and in 39% they present the multi -\nlocular form with solid components. The number of \npapillary outgrowths in the lumen of the cyst varies \nsignificantly between tumours; however, most often \nthese are 3 papillary projections (33% of decidualized \nendometriomas), and they have a maximum diameter \nbetween 6 mm and 79 mm and a height of 3–33 mm. \nAlmost all the projections show colour or power Dop -\npler signals (94%); this signal is usually well expressed \n(colour score 3 – 72%) (Figures 4 A, B). A feature that \nseems to be characteristic is the smooth surface of pap-\nillary projections (82% of decidualized endometrio -\nmas) (21) (Figure 3). Papillary projections are clearly \nvisible in macroscopic preparations of excised lesions \n(Figure 5). Commonly used in the medical commu -\nnity, ultrasound diagnostic models of ovarian lesions \nsuch as Simple Rules (International Ovarian Tumour \nAnalysis – IOTA) or mixed models also using other \nclinical data (including Ca125 concentration) such as \nADNEX (IOTA) or RMI (risk malignancy index) are \nnot standardized to the population of pregnant pa -\ntients, which may lead to a high false positive ratio.\nThe diagnostics of endometrioma decidualization \nis a  challenge for the ultrasound examiner. In one \nstudy, 18 cysts diagnosed postoperatively as endo -\nmetrioma decidualization were subjected to an ultra -\nsound evaluation of the lesion. In 56% of the cysts, the \nultrasound examiner was not able to assess the malig -\nFigure 2. The decidualization process begins. Ultrasound “density” of the cyst contents\n\n229Endometrial cyst and its changes during pregnancy – a narrative review of the literature \nMedical Studies/Studia Medyczne 2021; 37/3\nnancy potential, and only in 17% was the examiner \nsure that the lesion was benign. Borderline tumour \nwas suspected in 44% of cases [21]. \nIn such a  situation, the most valuable diagnostic \nclue seems to be a typical image of endometrioma in \nan ultrasound examination before pregnancy or in \nthe first trimester, before the decidualization process \nbegins. \n \nSerum markers in the process  \nof differentiating malignant changes  \nfrom decidualized endometriomas\nIn the process of differentiation of decidualized \nendometrioma and ovarian cancer, tumour markers \nare limited of use. Before pregnancy, in patients suf -\nfering from endometriosis, the concentration of the \nCa125 marker is usually already slightly elevated or \nwithin the upper limits of the normal range, and is \ncharacterized by a greater population spread (median \n– 44 U/ml, 75\nth percentile – 85 U/ml) and significantly \nhigher than in the case of other benign cysts of the \novary (median – 15 U/ml, 75\nth percentile – 24 U/ml) \n[14]. Serum Ca125 levels are elevated in most ovarian \ncancer cases. Meta-analysis shows an overall sensi -\ntivity and specificity (Ca125 > 35 U/ml) of 78% [22]. \nHowever, the sensitivity of the test depends on the \nstage of the ovarian cancer and the type of cancer (it \nis lower in mucous and clear cell carcinomas) [23, 24]. \nThe use of a pregnancy test at the cut-off point for the \npremenopausal population may result in a significant \nreduction in specificity and an increase in the false \npositive ratio. Ca125 may be useful in differentiating \novarian cancer from a benign lesion after 15 weeks of \ngestation until the moment of delivery; at this time, \nsignificantly elevated levels (> 1000 U/ml) usually \nsuggest a proliferative disease, but concentrations of \nlower order of magnitude (100–150 U/ml) are not rare \nat this stage of pregnancy and do not provide addi -\ntional diagnostic information [25]. \nConcentrations of other cancer markers that \nmay be helpful in the diagnosis of ovarian cancer \nin pregnancy, i.e. carcinoembryonic antigen (CEA), \nFigure 5. Macroscopic preparation of decidualized endo-\nmetrioma\nFigure 3. Decidualized endometrioma. Smooth surface of \npapillary projections\nB\nA\nB\nFigure 4. A, B – Papillary outgrowths with intensive Dop-\npler colour score 3 signal\n\nJakub Młodawski, Marta Mlodawska, Mariusz Malmur, Justyna Płusajska, Grzegorz Świercz, Marek Sikorski\n230\nMedical Studies/Studia Medyczne 2021; 37/3\nα-fetoprotein (AFP), and human chorionic gonadotro-\npins (hCG), are usually increased during pregnancy \nand are characterized by high variability during preg -\nnancy; additionally, their concentrations may be af -\nfected by maternal or foetal complications [25]. In \ncontrast, the median HE4 concentration during preg -\nnancy is lower compared to non-pregnant patients in \nreproductive age [26, 27]. \nAll cancer markers have limited usefulness in dif -\nferentiating between endometrioma decidualization \nand ovarian cancer. \nConclusions\nEndometrioma decidualization is not a  common \nprocess among patients with diagnosed endome -\ntrioma, but it is a process that every clinician should \nknow about, given the benign nature and the ultra -\nsound image imitating ovarian cancer. In our opinion, \novaries should be examined ultrasonographically for \npathological changes in the first trimester in pregnan-\ncy. The presentation of a typical endometrial cyst im -\nage supports the diagnostic process of decidualization \nin the second trimester of pregnancy. Due to the small \nnumber of cases described in the literature, there are \ncurrently no standards (expectant management/sur -\ngical procedure) in the case of patients with endome -\ntrial decidualization image; each patient requires an \nindividualised approach. Further research is needed \nto search for ultrasound and biochemical markers of \nthe decidualization process. \nAcknowledgments\nProject financed under the program of the Minis -\nter of Science and Higher Education called “Region -\nal Initiative of Excellence” in the years 2019-2022, \nproject no. 024/RID/2018/19, amount of financing  \n11 999 000.00 zł.\nConflict of interest\nThe authors declare no conflict of interest.\nReferences\n1. Lin KY, Chang CY, Lin WC, Wan L. Increased risk of en-\ndometriosis in patients with endometritis – a nationwide \ncohort study involving 84,150 individuals. Ginekol Pol \n2020; 91: 193-200. \n2. Gica N, Panaitescu AM, Iancu G, Botezatu R, Peltecu G, \nGica C. 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Re-\nkomendacje Sekcji Ultrasonografii Polskiego Towarzy-\nstwa Ginekologów i Położników w zakresie przesiewowej \ndiagnostyki ultrasonograficznej w ciąży o przebiegu pra-\nwidłowym – 2020 r. Ginekol Pol 2020; 91: 490-501.\nAddress for correspondence:\nJakub Młodawski MD\nCollegium Medicum\nJan Kochanowski University\nKielce, Poland\nE-mail: jakub.mlodawski@ujk.edu.pl","source_license":"CC0","license_restricted":false}