{"paper_id":"086df9c3-7c5e-46c9-b1bd-267540d7007b","body_text":"This is an open access article under the CC BY 4.0 license ( https://creativecommons.org/licenses/by/4.0/).\nEur. J. Gynaecol. Oncol. 2023 vol.44(1), 115-118 ©2023 The Author(s). Published by MRE Press. https://www.ejgo.net/\nSubmitted: 20 September, 2022 Accepted: 25 November, 2022 Published: 15 February, 2023 DOI:10.22514/ejgo.2023.014\nC A S E R E P O R T\nEndometrioid carcinoma associated with ovarian\nendometriosis: need for cautions during treatment\nWoo Yeon Hwang1,*\n1Department of Obstetrics and\nGynecology, Kyung Hee University\nSchool of Medicine, Kyung Hee\nUniversity Medical Center, 02447 Seoul,\nRepublic of Korea\n*Correspondence\nwooyeonhwang@naver.com\n(Woo Yeon Hwang)\nAbstract\nAlthough endometriosis could be associated with certain epithelial ovarian cancers and\nelevated serum cancer antigen (CA) 19-9 levels, it is difficult to diagnose endometriosis\nusing this marker. We report an unusual case of endometriosis that evolved into\nendometrioid carcinoma in an asymptomatic 38-year-old woman with elevated CA 19-9\nlevels who presented to our clinic. Transvaginal ultrasound and computed tomography\nof the abdomen and pelvis revealed endometriosis of the right ovary. A laparoscopy\nwas performed to evaluate for chocolate cysts. However, based on the postoperative\npathological assessment, she was diagnosed with endometrioid carcinoma associated\nwith endometriosis and was reoperated for surgical staging. This case indicates that\nsudden elevation of CA 19-9 level might be a sign of malignancy, small asymptomatic\nendometriosis should not be ignored, and incidental diagnosis of ovarian cancer should\nbe carefully assessed by surgical staging.\nKeywords\nEndometrioid carcinoma; Endometriosis; CA 19-9; Surgical staging\n1. Introduction\nEndometriosis is a benign, gynecologic, estrogen-dependent\ndisease characterized by the presence of endometrial glands\nand stroma outside the uterine cavity [ 1]. Endometriosis\naffects approximately 10% of women of reproductive age\n[2]. Although endometriosis is considered a benign condition,\nhistological and molecular data from previous studies indicated\npossible risks for malignancy [1]. Endometriosis is more com-\nmonly associated with endometrioid and clear cell carcinoma\nsubtypes of ovarian cancer than with serous or mucinous sub-\ntypes [1]. The absolute risk of developing ovarian cancer from\novarian endometriosis remains minimal despite the possibility\nof an increase in the relative risk of the disease. In a previous\nstudy, the investigators found that there were about two cases\nper 1000 patients with ovarian endometriosis upon comparing\npatients with and without ovarian endometriosis during a 10-\nyear period [3].\nTumor markers are valuable for the differential assessment\nof ovarian masses. Cancer antigen 19-9 (CA 19-9) is a mucin\nprotein commonly used to diagnose benign and malignant gas-\ntrointestinal, biliary tract and pancreatic diseases [4]. High CA\n19-9 positivity rates have been reported in ovarian malignan-\ncies such as mucinous adenocarcinoma, endometrioid adeno-\ncarcinoma and mucinous borderline ovarian tumors. Patients\nwith benign tumors, i.e., ovarian endometriosis and mature\ncystic teratoma, have also been observed to have increased\nCA19-9 values [5].\nHowever, the incidence of endometrioid cancer in patients\nwith endometriosis and increased CA 19-9 levels associated\nis not well documented. Herein, report an unusual case of\nendometriosis that evolved into endometrioid carcinoma in a\npatient with elevated CA 19-9 level.\n2. Case presentation\nA 38-year-old female patient (gravida 2, para 1) was referred\nto the Gastroenterology department of our hospital after she\nwas found to have elevated serum CA 19-9 level (61.8 IU/mL)\nbut without specific findings on abdominal ultrasonography at\na primary hospital. Therefore, a follow-up visit was scheduled\nfor the next three months after the initial visit to examine the tu-\nmor maker levels. At the three-month follow-up, her serum CA\n19-9 level had increased to 352.15 IU/mL, whereas other tumor\nmarker levels, including CA 125, carcinoembryonic antigen,\nalpha-fetoprotein and beta-human chorionic gonadotrophin,\nwere within normal limits.\nShe visited our Gynecology department for routine exam-\ninations as she had undergone a left ovarian cystectomy for\nmucinous cystadenoma in 2015 and a myomectomy in 2017\nat our hospital. She came to our Gynecology department\non the scheduled date, two months after undergoing the ab-\ndominal ultrasound examination at the primary hospital, and\nwe performed transvaginal ultrasonography, which revealed\na bilocular cystic mass measuring 3.8 cm × 3.3 cm, with\ndiffuse, low-level echoes and a regular smooth cystic wall in\nthe right ovary (Fig. 1A). Computed tomography (CT) of the\nabdomen and pelvis showed a 4.0 cm, low attenuation, thin-\nwalled and unilocular cyst in the right ovary without any solid\n\n116\nF I G U R E 1. Imaging of the right ovarian cystic mass. A. Transvaginal ultrasound image of the 3.8 × 3.3 cm right ovarian\ncystic mass. The tumor was homogeneous, composed of low-level echoes, and the cyst wall was regular and smooth. B.\nAbdominal and pelvic computed tomography of the 3.5 cm right ovarian cystic mass showed that the tumor was a low-attenuation,\nthin-walled, unilocular cyst without solid components.\ncomponent (Fig. 1B). Her laboratory test results were within\nnormal ranges.\nThe patient underwent laparoscopic right ovarian cystec-\ntomy, following which we observed a smooth-walled cyst that\ncontained chocolate-like fluid with severe pelvic adhesions\n(Fig. 1B). Contrary to expectations, postoperative pathology\nrevealed an International Federation of Gynecology and Ob-\nstetrics (FIGO) grade 1 endometrioid carcinoma associated\nwith endometriosis (Fig. 2). Imaging tests, including pelvic\nmagnetic resonance imaging, chest CT and positron emission\ntomography, were also performed and the results showed a\nmild hypermetabolic lesion in the right pelvic cavity. How-\never, no other abnormal findings, such as lymph nodes or\ndistant metastases, were noted. In addition, the patient’s serum\nCA 19-9 level returned to the normal range after surgery.\nThereafter, she was reoperated for surgical staging. Pathologi-\ncal examination confirmed the presence of residual endometri-\noid carcinoma in the right ovary (Fig. 3), which was confirmed\nto be a FIGO stage IC1 tumor, and she underwent paclitaxel\nplus carboplatin as adjuvant chemotherapy.\n3. Discussion\nOvarian endometriosis, which occurs when tissues similar to\nthe endometrium grow within the ovaries, is the most common\nform of endometriosis, accounting for 67% of all cases [ 6, 7].\nAlthough endometriosis is usually considered a benign disease,\nit can be associated with malignancy. In 1925, Sampson\nfirst proposed the following criteria for the diagnosis of ovar-\nian malignancy associated with endometriosis: (i) evidence\nof endometriosis in proximity to the tumor, (ii) presence of\ncancer within an ovary with endometriosis but not elsewhere,\nand (iii) histological appearance consistent with the origin\nof endometriosis [ 8]. In 1953, Scott further expanded the\ncriteria by adding histological evidence of the transition from\nendometriosis to neoplasm [9], raising the question of whether\n\n117\nF I G U R E 2. Surgical depiction of the right ovarian cyst.\nA. The laparoscopic image of the right ovarian cyst. B. The\nright ovarian cyst contained a chocolate-brown fluid.\nF I G U R E 3. The histological section of the endometrioid\ncarcinoma shows loss of glandular architecture and stroma\n(hematoxylin and eosin; ×400).\nendometriosis is a pre-malignant condition.\nEndometriosis treatment options include pain relievers, hor-\nmone therapy such as a combination of oral contraceptive\npills and progestins, and surgical resection. The severity\nof symptoms and infertility are crucial considerations when\nassessing the indications for surgical resection. The European\nSociety of Human Reproduction and Embryology (ESHRE)\n2022 guideline recommends surgeons to perform cystectomy\nrather than drainage and coagulation during the surgical treat-\nment of women with ovarian endometrioma because cystec-\ntomy can decrease endometriosis-related pain and increase the\nlikelihood of continued pregnancy. In addition, cystectomy\nhas also been found to potentially reduce the recurrence of\nendometrioma [10].\nTransvaginal ultrasonography is a crucial investigational\ntechnique for endometriosis. Typical benign endometriomas\ncan be identified as unilocular or multilocular cystic lesions\nwith consistent low-level echoes (ground glass appearance)\n[11]. The International Ovarian Tumor Analysis (IOTA) clas-\nsification system is critical for distinguishing suspicious fea-\ntures as it can help differentiate benign from malignant en-\ndometriomas [12]. Malignant tumors are more likely to have\nsolid mural nodules with Doppler flow showing vascularity.\nAdditionally, malignant lesions are more likely to contain\npapillary projections than benign endometrioid cysts. Thus,\nclinicians should not neglect the risk of malignancy when\ncommunicating and treating endometriosis patients. On aver-\nage, the risk of endometriomas developing into cancer is less\nthan 0.8%. One study found that the risk of cancer increased\nwith lesion size ( >9 cm) and age ( >45 years) [ 13]. Another\nstudy reported that the median maximum diameter of malig-\nnant endometriotic tumors was 10.7 cm, while the median\nmaximum diameter of benign endometriomas was 5.8 cm (p <\n0.0001), and that malignant endometriomas were more likely\nto be multilocular (47% vs. 9.7%) [ 14]. Comparatively, in\nour presented case, the ovarian cyst had a diameter less than\n4 cm and the patient was younger than 45 years old, yet,\nshe was diagnosed with cancer based on the final surgical\nbiopsy. If conservative care rather than ovarian cystectomy\nhad been performed, the latent early-stage cancer would have\nbeen missed.\nCurrently, there are no biomarkers that can reliably diag-\nnose or differentiate endometriosis. Endometriosis is often\nassociated with high levels of CA 125. Since serum CA 125\nlevel is also elevated in ovarian malignancies, it is generally\nnot useful for differentiating benign ovarian endometriomas\nfrom ovarian malignancies [15]. CA 19-9 is another biomarker\nassociated with endometriosis. A limited number of studies\nshowed a significant association between CA 19-9 level and\nendometrioma. The exact mechanism behind the increased\nserum level of CA 19-9 in patients with endometrioma re-\nmains unclear. However, a hypothesis proposed by some\nresearchers suggests that fluid from a ruptured endometrioid\ncould be absorbed into the body’s blood circulation in serum\nexchange, resulting in a marked increase in CA 19-9 level\n[16]. Previous research indicates that CA 19-9 is a useful\nmarker for distinguishing endometrioma from other cancers\n[15]. As in our study, a sudden increase in serum CA 19-9\nlevel may indicate malignancy; hence, it should be carefully\nassessed and addressed. However, unusual increases in CA\n19-9 levels can also be identified in benign conditions [ 17].\nConsequently, it should be emphasized that the assessment of\nbiomarker levels for ovarian mass could induce unnecessary\nstress in patients and increase overtreatment risks. However,\nit is challenging for clinicians to timely determine the risk of\nmalignancy in ovarian endometriosis based on aberrant levels\n\n118\nof tumor markers.\nOvarian malignancies might be inadvertently diagnosed af-\nter surgical treatments. This present case emphasized the sig-\nnificance of surgical staging, despite the absence of abnormal-\nities on additional imaging or blood tests even when a tumor of\nstage 1 is anticipated. In this study, after ovarian cystectomy,\nno residual lesions were discovered on imaging examinations;\nhowever, lesions were observed in the pathology reports, high-\nlighting the need to treat patients in compliance with accepted\nclinical practice guidelines. The preoperative diagnosis of\novarian endometriosis is challenging. This present case high-\nlighted some critical points that could help better manage\nendometriosis cases. First, asymptomatic endometriosis less\nthan 4 cm in size should not be neglected. Second, although\nit is not suggested to use tumor marker levels such as CA 19-\n9 to diagnose endometriosis-associated malignancy, a sudden\nincrease in CA 19-9 levels should be carefully evaluated.\nLastly, surgical staging according to approved guidelines is\ncrucial when ovarian cancer is inadvertently discovered after\nsurgery.\nAVA I L A B I L I T Y O F DATA A N D M AT E R I A L S\nThe data are contained within this article.\nA U T H O R CO N T R I B U T I O N S\nWYH—performed the investigation, writing, review & editing\nand approved the final manuscript.\nE T H I C S A P P R OVA L A N D CO N S E N T TO\nPA R T I C I PAT E\nInstitutional Review Board of Kyung Hee University Medical\nCenter approved a waiver of informed consent (approval num-\nber: KHUH 2022-11-071).\nAC K N OW L E D G M E N T\nNot applicable.\nF U N D I N G\nThis research received no external funding.\nCO N F L I C T O F I N T E R E S T\nThe author declares no conflict of interest.\nR E F E R E N C E S\n[1] Paik ES, Kim TJ, Choi CH, Kim BG, Bae DS, Lee JW. 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Endometrioid\ncarcinoma associated with ovarian endometriosis: need for\ncautions during treatment. European Journal of Gynaecological\nOncology. 2023; 44(1): 115-118. doi: 10.22514/ejgo.2023.014.","source_license":"CC0","license_restricted":false}