{"paper_id":"6b0b79db-8661-4deb-8041-7e454bb62c27","body_text":"158\nReceived: November 14, 2019  Revised: November 17, 2019  Accepted: November 18, 2019\nAddress for Correspondence: Sa Ra Lee , Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of \nMedicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea\nTel: 82-2-3010-3648, E-mail: leesr@amc.seoul.kr, ORCID: https://orcid.org/0000-0002-7890-8348\nORIGINAL ARTICLE\nCopyright © by The Korean Society of Meno pause\nThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License  (http://creativecommons.org/licenses/by-nc/4.0/).\nINTRODUCTION\nPelvic sonography via transvaginal or transrectal ap-\nproach is used as a first-line investigation in patients \nwith abnormal uterine bleeding and it can provide \nnot only anatomical assessment but also physiological \nchanges accompanied with menstrual cycle [1]. Various \ngynecologic conditions can make endometrium thick \nabove the normal sonographic reference range con -\nsidering the patient’ s menstrual cycle and menopausal \nstatus. There is no widely accepted threshold for abnor-\nmal endometrial thickness in premenopausal women, \nalthough typically diffuse homogeneous thickening \ngreater than 16 mm in the secretory phase is used [2]. \nFor postmenopausal women, the endometrial thickness \nthresholds are known to be 4 mm or 5 mm [3,4]. Even \nasymptomatic postmenopausal women, an endometrial \nthickness more than 10 mm carries a 5.8% risk of en -\ndometrial cancer [5]. In addition to the finding of thick \nendometrium, multiple foci of cystic change in endo -\nmetrium accompanied with it and it is called as a hon-\neycomb or “Swiss cheese” appearance. The most com-\nmonly known endometrial conditions which can cause \nthick endometrium with “Swiss cheese” appearance in \nhttps://doi.org/10.6118/jmm.19015\nJ Menopausal Med 2019;25:158-163\npISSN: 2288-6478, eISSN: 2288-6761\nThick “Swiss Cheese” Appearance of Uterine Endometrium \nin Postmenopausal Women with Different Gynecologic \nConditions\nYuri Ko, Jinha Chung, Sa Ra Lee, Sung Hoon Kim, Heedong Chae, Byung-Moon Kang \nDepartment of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea\nObjectives:  To uncover gynecologic conditions with similar transvaginal sonographic findings of thick uterine endometrium with \nhoneycomb appearance in pre-and postmenopausal women.\nMethods: We retrospectively reviewed cases of patients with endometrial tissue biopsy from January 2010 to December 2016. We \nalso collected office flexible hysteroscopic findings and surgical pathologic results. We analyzed data from 393 patients with confirmed \nendometrial pathology. Among these patients, 69 had transvaginal ultrasonographic images with thick uterine endometrium and \nhoneycomb or “Swiss cheese” appearance.\nResults:  We found gynecologic conditions such as submucosal leiomyoma with degeneration, endometrial polyp, pseudocystic \nendometrial change associated with tamoxifen use, progesterone associated endometrial change, pyometra, retained placenta, and \nuterine synechiae manifested with similar thick endometrium with “Swiss cheese” appearance in transvaginal sonographic images. The \nmost common diagnosis in postmenopausal women was atrophic endometritis, followed by endometrial cancer and endometrial polyps. \nThe most common diagnosis in premenopausal women was abnormal uterine bleeding without pathologic conditions.\nConclusions: Sonographic findings of thick uterine endometrium with “Swiss cheese” appearance need to be considered together with \na thorough review of the patient’s history and chief complaint before making a tentative diagnosis due to the various conditions sharing \nthe feature.\nKey Words: Endometrium, Hyperplasia, Leiomyoma, Menopause, Polyps\n\n159\nThick Uterine Endometrium with Swiss Cheese Appearance in Postmenopausal Women\nsonography are endometrial polyp, hyperplasia, and \nendometrial cancer [6]. Hydatidiform mole and arte -\nrio-venous malformation (AVM) also were reported to \nbe related with thick endometrial sonographic finding \n[7]. However, various gynecologic conditions such as \nsubmucosal leiomyoma with degeneration, adenomyo-\nmatous endometrial polyp, and pseudocystic endome-\ntrial change associated with tamoxifen use, progester -\none associated endometrial change, pyometra, retained \nplacenta, and uterine synechiae also can be manifested \nas similar finding of thick endometrium with “Swiss \ncheese” appearance in transvaginal sonography [8,9]. \nTherefore, we want to present several cases of diverse \nendometrial pathology with similar sonographic find-\ning of thick endometrium with “Swiss cheese” appear-\nance in pre- and postmenopausal women to analysis of \nvarious gynecologic situations with the similar trans -\nvaginal sonographic findings of thick uterine endome-\ntrium with “Swiss cheese” appearance.\nMATERIALS AND METHODS \nWe retrospectively collected ultrasonographic im -\nages of thick uterine endometrium with “Swiss cheese” \nappearance from January 2010 to December 2016 in \na single training university-based Ewha Womans Uni-\nversity Medical Center. We used generally accepted \nthresholds for abnormal endometrial thickening, \ngreater than 5 mm for postmenopausal women not on \nhormone therapy and more than 16 mm for premeno-\npausal women. A total of 393 cases of pathologically \nproven endometrial tissue biopsy performed with dila-\ntation and curettage, pipelle biopsy, or hysteroscopic \nbiopsy were included. Among these patients, 69 cases \nof transvaginal ultrasonographic images of thick uter-\nine endometrium with “Swiss cheese” appearance were \nincluded in the final analysis. Twelve cases of premeno-\npausal women and 57 cases of postmenopausal women \nwere included. The incidence of final diagnosis with \npathologically proven was classified according to the \nmenopausal status. All included sonographic images \nwere obtained from transvaginal ultrasonography per-\nformed by a gynecologist with over 15 years of experi-\nences in gynecologic sonography. \nRESULTS \nDiverse gynecologic conditions, such as submuco -\nsal leiomyoma with degeneration, adenomyomatous \nendometrial polyp, pseudocystic endometrial change \nTable 1. Summary of clinical and sonographic findings of cases and final diagnosis pathologically confirmed\nCase Age\n(yr) MP state Chief complaint Medication\na EM thickness\n(mm)\nb TVS findings Final diagnosis\nA 60 Post-MP Referred from health screening \ncenter for thick EM\nNone 16.6 (> 4) Thick EM with Swiss cheese  appearance \nwith blood flow in power Doppler exam\nSM leiomyoma\nB 47 Pre-MP Thick EM during follow-up Tamoxifen \nfor 3 years\n12.0 (> 8) Thick EM with Swiss cheese  appearance \nwith blood flow in power Doppler exam\nSM leiomyoma with \ndegeneration\nC 58 Post-MP Referred from health screening \ncenter for thick EM\nNone 12.7 (> 4) Thick EM with swiss cheese  appearance SM leiomyoma with \ndegeneration\nD 55 Post-MP Referred from health screening \ncenter for thick EM\nNone 15.7 (> 4) Thick EM with Swiss cheese  appearance SM leiomyoma with \ndegeneration\nE 43 Pre-MP Thick EM during follow-up SPRM for  \n3 months\n23.1 (> 20) Thick EM with Swiss cheese  appearance PAEC\nF 58 Post-MP Referred from health screening \ncenter for thick EM\nNone 5.6 (> 4) Thick EM with Swiss cheese  appearance Uterine synechiae\nG 73 Post-MP Referred from health screening \ncenter for thick EM\nNone 6.0 (> 4) Thick EM with Swiss cheese  appearance Adenomyomatous \nendometrial polyp\nH 36 Pre-MP Abnormal vaginal bleeding in \nearly proliferative phase\nNone 16.8 (> 3–5) EM with Swiss cheese  appearance Retained placenta with \nendometrial polyp\nMP: menopause, EM: endometrium, TVS: transvaginal sonography, SPRM: selective progesterone receptor modulator, SM: submucosal, PAEC: progesterone \nassociated endometrial change.\na\nMedication refer to current medication which can affect endometrium including postmenopausal hormone therapy. \nb\nNormal range of EM thickness considering patient’s menstrual cycle, menopausal status and medications.\nhttps://doi.org/10.6118/jmm.19015\n\nYuri Ko, et al.\n160\nwww.e-jmm.org\nassociated with tamoxifen use, progesterone associ -\nated endometrial change (PAEC), pyometra, retained \nplacenta, and uterine synechiae showed as similar find-\nings of thick uterine endometrium with “Swiss cheese” \nappearance in transvaginal sonography. The clinical \nand transvaginal sonographic findings with or without \nhysteroscopic findings of these cases were summarized \nin Table 1 and the sonographic and hysteroscopic im-\nages of the patients are in Figure 1. In postmenopausal \nwomen group, 7 cases of malignant cases, 6 cases of \nendometrial cancer, and 1 case of cervical cancer were \nthe leading causes and 3 cases of endometrial polyp \nand 1 case of degenerated submucosal myoma were fol-\nlowed. Two cases of endometritis and the others were \natrophy without evidence of endometrial pathology. \nIn premenopausal women group, there was no case of \nmalignant lesion and 1 case of simple hyperplasia and \n1 case of complex hyperplasia were noted. One case of \nacute pyometritis, 1 case of chronic endometritis, and \n8 cases of normal endometrial tissue were noted. Nine \nout of 12 cases in premenopausal women and 19 out of \n57 cases in postmenopausal women did not show vagi-\nnal bleeding. The other cases had vaginal bleeding. All \n2 cases of endometrial hyperplasia in premenopausal \nwomen showed vaginal bleeding and 6 out of 7 malig-\nnant cases in postmenopausal women accompanied \nvaginal bleeding. \nDISCUSSION \nThe most important endometrial conditions which \nshould be differentiated are endometrial hyperplasia \nand endometrial cancer. These two conditions can be \nmanifested as thick endometrium with “Swiss cheese” \nappearance in pelvic sonography [6]. The clinical char-\nacteristics including abnormal uterine bleeding, post -\nmenopausal state, unopposed estrogen, estrogen secret-\ning ovarian tumor, and obesity are the well-known risk \nfactor of these conditions. More than 90% of endome-\ntrial cancer occurs after age 50, with the most common \nsymptom by far being abnormal vaginal bleeding [10]. \nFor differential diagnosis of these pre-malignant and \nmalignant endometrial lesions with other benign con-\nditions before making decision on endometrial tissue \nbiopsy, we sometimes perform additional diagnostic \nimaging. In case of suspected endometrial pathologic \ncondition, the saline infusion sonography (SIS) is con-\nsidered as an option for more clear visualization of \nA\nB\nC\nD\nE\nF\nG\nH\nFig. 1. Gray-scale image, color Doppler sonographic image, and hysteroscopic image (from left to right) of patients with thick endometrium with \n“Swiss cheese” appearance on transvaginal sonography.\n\n161\nThick Uterine Endometrium with Swiss Cheese Appearance in Postmenopausal Women\nendometrial condition. Hysteroscopy, especially office \nflexible hysteroscopy, has become the new good option \nfor this purpose because of its ability to visualize direct-\nly the endometrium and perform directed biopsies as \nindicated. As office-based hysteroscopy becomes more \npractical and widespread, the technique may become \nmore cost-effective [11]. In addition to that, office \nhysteroscopy usually causes no or minimal discomfort \nto patients and shorter time compared with SIS. An \nevaluation plan using transvaginal sonography as the \ninitial screening evaluation followed by endometrial \nbiopsy or, more likely, hysteroscopy is likely to become \nthe standard of care [11]. Therefore in our gynecologic \nclinic, in case of suspected endometrial disease other \nthan endometrial hyperplasia or endometrial cancer, \ntransvaginal sonography as the initial screening evalu-\nation followed by office flexible hysteroscopy in the \nsame day is become increasing. \nIn terms of thick uterine endometrium with “Swiss \ncheese” appearance in transvaginal sonography, there \nwere few reports describing the underlying endometrial \npathologies other than commonly well-known condi -\ntions such as endometrial hyperplasia, endometrial \ncancer, hydatidiform mole, and AVM [12]. Cohen et al. \n[11] reported a series of cases with submucosal fibroids \nundergoing cystic degeneration showed a distinct so -\nnographic \"Swiss cheese\" pattern and erroneously diag-\nnosed as endometrial hyperplasia.\nIn our case series, even in postmenopausal women \nwho are not taking postmenopausal hormone therapy \nwith very thick endometrium measured to be over 12 \nmm, the possibility of endometrial hyperplasia or can-\ncer may be low unless presented with abnormal vaginal \ndischarge, vaginal spotting, or bleeding. Therefore, of-\nfice hysteroscopy with or without pipelle biopsy may \nbe the better options for the next step evaluation after \ntransvaginal sonography instead of dilatation and cu -\nrettage (D&C) requiring anesthesia and abstinence of \nfood and drink for several hours because the pipelle \nbiopsy is known to be comparable to the D&C method \nin evaluating endometrial pathology [13-15]. Endome-\ntrial biopsy with D&C method may be reserved in case \nof thick endometrium with clinically suspected in an \nelderly postmenopausal woman with vaginal discharge \nor bleeding.\nWe have to differentiate the thickening endometrium \nitself and the presence of endometrial mass when we \nencounter thick endometrial finding on ultrasonogra-\nphy. The thorough examination of vaginal sonography \ncan reveal hypoechoic space between normal appearing \nhyperechoic endometrium and “Swiss cheese” like en-\ndometrial mass (Fig. 2). That finding suggests the thick \nendometrium is caused by the presence of endometrial \nmass and not a real thickening of endometrium such as \nendometrial hyperplasia, pyometra, tamoxifen user, or \nPAEC. SIS is also helpful to differentiate the thick en -\ndometrium and endometrial mass.\nThorough reviewing the medications which the pa -\ntients are taking is important, the reason for this is \nmedications especially tamoxifen and selective pro -\ngesterone receptor modulator (SPRM) can make a \nchange in endometrium to be multicystic endometrial \nthicening. In terms of PAEC, some patients who are \ntaking SPRM such as ulipristal acetate (UPA; Inisia ®) \nfor medical treatment for uterine myoma with men -\norrhagia can experience endometrial change which \nis not a pathologic finding and returned to normal \nendometrium. The endometrial changes proven micro-\nscopically contained abortive subnuclear vacuolization, \noccasional mitoses, and apoptosis [16]. Small and large \ncysts and focal septum like thickening are observed in \nhysteroscopy in our experience and it was in accordance \nwith previously reporting finding [17]. This PAEC can \nalso be observed in magnetic resonance imaging (MRI) \nhttps://doi.org/10.6118/jmm.19015\nA B C\nSpace between endometrium and mass\nFig. 2. The thorough examination of vaginal sonographic image can reveal space between normal appearing endometrium and “Swiss cheese” like \nendometrial mass. (A) Endometrial hyperplasia. (B) Endometrial cancer. (C) Submucosal leiomyoma with cystic degeneration.\n\nYuri Ko, et al.\n162\nwww.e-jmm.org\nand fat suppression mode was more clearly showed this \nchange than in T1-weighted or T2-weighted image and \ndisappeared after spontaneous menstruation finishing 1 \ncycle of UPA treatment (Fig. 3). \nIn case of tamoxifen user, the normal range of endo-\nmetrium was reported as below 8 mm and most cases \nof endometrial changes related with tamoxifen were re-\nported to a cystic endometrial changes or endometrial \npolyp [16]. Rarely the risk of endometrial proliferation, \nhyperplasia, or cancer, and uterine sarcoma are associ-\n10 cm 10 cm 10 cmA B C\nD E\nFig. 3.  The magnetic resonance imaging (MRI) of progesterone associated endometrial change (PAEC). (A) T1-weighted image of MRI. (B) T2-\nweighted image of MRI. (C) Fat suppression image of MRI. The transvaginal sonographic image of PAEC before (D) and after (E) menstruation \nshowed the “Swiss cheese” appearance of (D) is disappeared in (E) showing triple laminar feature of normal endometrium.\nThick EM with\n\"Swiss\ncheese\"\nPre-MP women\n>1 6 mm,\nPost-MP women\n> 4~5 mm\nTreatment\nOffice\nBlind EM\nbiopsy\nwithout\nanesthesia\nD&C\nUnder the\nsetting of\noperative\nhysteroscopy\nWithout\npathologic\ndiagnosis and\nremained thick\nEM\nOffice\nHystero-\nscopy\nWith pathologic\ndiagnosis Treatment\nFig. 4.  Proposed diagnostic algorithm for managing thick uterine endometrium with “Swiss cheese” appearance. EM: endometrium, MP:  \nmenopause, D&C: dilatation and curettage.\n\n163\nThick Uterine Endometrium with Swiss Cheese Appearance in Postmenopausal Women\nated with tamoxifen. Although the risk of endometrial \ncancer is comparable to the control patients who are \ntaking placebo, women with abnormal vaginal bleed -\ning, bloody vaginal discharge, staining, or spotting who \nare taking tamoxifen should be investigated [17]. If a \nblind endometrial biopsy was negative in case of mul-\nticystic endometrial thickening, office hysteroscopic \nexamination will be the good next step for avoiding \nrepeat D&C under anesthesia. This is especially helpful \nin patients without symptoms such as vaginal bleeding \nor discharge. It would be better to perform D&C under \nthe setting of operative hysteroscopy for resection of \nendometrial polyp or degenerated submuscosal myo -\nma, which usually cannot be clearly resected with D&C \n(Fig. 4).\nIn conclusion, we have to take into consideration \nthese diverse conditions when we encounter the so -\nnographic finding of thick endometrium with “Swiss \ncheese” appearance. We can make a tentative diagnosis \nonly after thorough reviewing the medical and surgical \nhistory and chief complaint of the patient for cases with \nsimilar sonographic finding of uterine endometrium. \nCONFLICT OF INTEREST \nNo potential conflict of interest relevant to this article \nwas reported.\nREFERENCES\n 1. American Institute of Ultrasound in Medicine (AIUM); American \nCollege of Radiology (ACR); American College of Obstetricians \nand Gynecologists (ACOG); Society for Pediatric Radiology (SPR); \nSociety of Radiologists in Ultrasound (SRU). 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