A rare case of combined endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrical deep endometriosis

A rare case of combined endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrical deep endometriosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A rare case of combined endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrical deep endometriosis Cailu Zhou, Xiaojing Luo, Mengjie Tang, Fangyuan Luo, Zhi Liao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3832190/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Aug, 2024 Read the published version in BMC Women's Health → Version 1 posted 9 You are reading this latest preprint version Abstract Background Carcinomatous changes from the ectopic endometrial glands in endometriosis have been reported in many studies, but malignant transformation from uterine adenomyosis/adenomyoma is rare. And clear cell-like adenocarcinoma represents a seldom-encountered malignant pathological variant of ectopic endometrium. Case presentation This case report presents a case of a 44-year-old nulliparous woman begun with abdominal pain and intestinal obstruction. Past medical history showed laparoscopic ovarian endometriotic cyst excision. Ultrasound indicated adenomyoma and a parametrical hypoechoic nodule with abundant blood flow signals and unclear boundaries. Deep invasive endometriosis was considered preoperatively. The patient underwent laparoscopic subextensive hysterectomy and bilateral adnexa resection. Chocolate cyst-like lesion was observed in the parametral lesion. Postoperative pathological examinations suggested endometrioid adenocarcinoma arising from eutropic endometrium and adenomyoma. Left parametrical lesions suggested poorly differentiated endometrioid adenocarcinoma combined with clear cell carcinoma. CD10 + endometrial stromal cells were observed surrounding tumor cell masses. The patient underwent subsequent transabdominal tumor cell reduction surgery and chemotherapy. Combined with surgical founding and pathological characters of the left parametrical adenocarcinoma, the parametrial lesions were more likely to be carcinomatous changes of the original deep endometriosis. Conclusion We herein present a rare case of combined endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrical deep endometriosis that may help inspire additional studies in the future. Adenocarcinoma Adenomyoma Endometriosis Case report Figures Figure 1 Figure 2 Figure 3 1. Background Endometriosis is a chronic benign disease and its malignant transformation rate is approximately 1%.[ 1 ] The most common site of endometriosis malignancy is ovary. Other locations also include the intestine, abdominal wall, vagina, cervix, bladder, ureter, pelvic floor muscles, and recto-vaginal septum.[ 2 ][ 3 ][ 4 ][ 5 ][ 6 ][ 7 ] Malignant transformation from adenomyosis is extremely rare.[ 8 ][ 9 ][ 10 ][ 11 ] The most common malignant pathological type in ectopic endometrium is endometrioid adenocarcinoma. Other pathological types also include clear cell-like adenocarcinoma, squamous cell carcinoma, endometrial stromal sarcoma, and Mullerian carcinosarcoma.[ 12 ][ 13 ][ 14 ] This case presented one rare case of carcinomatous changes of both uterine adenomyoma and deep endometriotic lesions that induced hydronephrosis and intestinal obstruction. We had received the signed informed consent from the patient for this case report and publication and patient anonymity was preserved. 2. Case presentation The patient was a 44-year-old Chinese woman with G1P0 + 1 and body mass index of 19. She sought treatment in our emergency surgery department due to sudden onset of intermittent abdominal colic with vomiting for 1 + days after eating indigestible food. The patient also had the symptoms of intestinal obstruction such as nausea, anal pendant expansion, and no gas nor defecation but did not have discomforts such as fever, bloody stool and vaginal bleeding. The patient underwent laparoscopic cyst excision due to ovarian endometriotic cysts 7 years ago and laparoscopic separating surgery due to infertility 4 years ago. The patient had regular menstrual periods and secondary infertility for 20 years. She received one in vitro fertilization and the embryo transfer 4 years ago; however, embryo implantation failed. Physical examination discovered a 2cm ovarian cyst 1 year ago but the patient did not receive treatment and follow up. The patient did not have a history of long-term exposure to estrogen, oral short-acting contraceptives, or other drugs. She had no known family history of cancer. Abdominal examination suggested lower abdomen tenderness without rebound pain and no palpable abdominal mass. Gynecological examination revealed smooth cervical appearance, uniformly enlarged uterus with a size close to the size of a 2-month pregnancy, left adnexa had patchy thickness, and left parametrical tissues had a palpable hard and irregular nodule of approximately 3cm that involved left vaginal fornix. Gynecological color ultrasound indicated that the endometrium was 0.6cm. The thickness of the anterior and posterior walls of myometrium was not even, myometrial echo was coarse and uneven especially the posterior wall, and there was an echo from a mass with unclear boundaries at the size of 3.9*3.3cm. The posterior cervical wall had a detected hypoechoic nodule at the size of 1.7*1.5cm, there were abundant blood flow signals, and the boundaries were clear. The renogram showed the curve of left renal incomplete obstruction. The transrectal contrast-enhanced ultrasound examination detected a solid hypoechoic mass of approximately 1.8*3.5cm in posterior cervical wall; the mass had irregular morphology and unclear boundary, the mass invaded the anterior wall of rectum through the rectouterine pouch. The color Doppler flow imaging suggested that there were more abundant blood flow signals in the hypoechoic mass. Gastroscopy and colonoscopy did not show obvious abnormality. The patient had normal liver and kidney functions, CA-125 was 183.4U/ml, and CA-199 was 66.7U/ml. Therefore, adenomyosis combined with adenomyoma and deep endometriosis combined with ureteral obstruction and intestinal obstruction were considered. The patient underwent robot-assisted laparoscopic subextensive hysterectomy + bilateral adnexa resection + deep endometriosis lesion resection + bilateral ureteral stent placement in the Department of Genecology of our hospital. The surgery showed that uterus enlarged to the size of approximately 2 month pregnancy, the appearance of bilateral oviducts did not have obvious abnormality, the surface of left ovary had brown endometriotic lesions, the right ovary was swelling with a diameter of 3cm and had adhesion with the posterior wall of the uterus and rectum, and the proper ligament of the left ovary had dense adhesion with left ureter, left posterior wall of uterus, rectum (Fig. 1 a/b). There was a 3cm hard lesion with unclear boundaries in the adhesion area that involved left vaginal fornix, lower segment of left ureter, and rectum. There was a chocolate cyst-like lesion of 1cm that contained chocolate-like old bleeding fluid (Fig. 1 c). The lower segment of left ureter at length of 10cm had thickened and was hard and the segment of rectum at approximately 4cm behind cervix had thickened and hard muscular wall. There was no lesion involvement in the upper abdomen. Dissection of endometrium after hysterectomy did not show obvious lesions, the myometrium was diffuse and thickened, and the posterior wall of uterus had an adenomyoma-like lesion of approximately 4cm. Postoperative pathological examinations suggested eutropic endometrium had multifocal atypical hyperplasia of endometrial glands and formations of highly/moderately differentiated endometrioid adenocarcinoma. The maximum diameter of intramyometrial adenomyosis was 5cm and most gland components exhibited atypical hyperplasia and highly/moderately differentiated endometrioid adenocarcinoma. Other myometrium wall tissues were scattered in the ectopic endometrium tissues combined with atypical hyperplasia and formation of endometrioid adenocarcinoma (Fig. 2 ). Left parametrical lesions suggested poorly differentiated endometrioid adenocarcinoma combined with partial clear cell carcinoma involvement (Fig. 3 ). Uterine specimens showed tumor thrombus in vessels and perineurium invasion. There was no tumor involvement in cervix. Left ovary had endometriotic cysts with no tumor involvement, and right ovary had tumor involvement. Immunohistochemistry results of left parametrical lesions suggested ER(+)PR(+); CK7(+); CD10(-); CEA(+); Ki67 (50%)(Fig. 3 ). Immunohistochemistry results of adenomyosis suggested ER(+); PR(+); CK7(+); CD10(-); CEA(focal+); Ki67(20%). The patient was considered to havecarcinomatous changes of both uterine adenomyoma and deep endometriotic lesions. On 8th day after the first surgery, the patient underwent transabdominal tumor cell reduction surgery including greater omentum resection + appendectomy + pelvic lymph node dissection + para-abdominal aortic lymph node dissection + partial rectectomy + intestinal anastomosis + resection of the lower segment of left ureter + left ureteral cystoplasty + left ureteral stent implantation. Postoperative pathological examination suggested that ureter had tumor infiltration, bilateral pelvic lymph nodes and para-abdominal aorta lymph nodes all had tumor metastases, tumor infiltration was observed on the serosal surface of the intestinal wall of of partial rectum, the muscular layer of intestinal wall had tumor infiltration, and the appendix and greater omentum did not have tumor infiltration. After a satisfactory postoperative recovery, the patient was treated with Taxol + Carboplatin chemotherapy regimen. 3. Discussion In 1959, Colman and Rosenthal modified Sampson’s criteria to apply to carcinomas developing from adenomyosis: (i) carcinoma should be absent from the normally situated endometrium and anywhere else in the pelvis; (ii) the carcinoma should be actually observed to be arising from the epithelium of the areas of adenomyosis and not invading from another source; and (iii) endometrial stromal cells should surround the aberrant glands to support a diagnosis of adenomyosis.[ 13 ] In this case, Co-existence of normal endometrial glands, atypical hyperplastic glands, and cancerous glands were observed both in eutropic endometrium and ectopic endometrium in uterine adenomyoma lesions. In addition, obvious endometrial stromal cells surrounding cancerous glands were observed. These observations were sufficient to prove that eutropic endometrium and ectopic endometrium in myometrium both had malignant transformation and they were both primary. In reported cases of carcinomatous change of uterine adenomyoma or adenomyosis, the probability of simultaneous malignant transformation of eutropic endometrium was approximately 20%.[ 9 ][ 11 ] Bingjian Lu and colleagues reported 3 cases of serous carcinoma in uterine cervical adenomyosis. Among them, one case did not have carcinomatous changes, one case had serous carcinoma, and one case had endometrioid adenocarcinoma in eutropic endometrium.[ 9 ] The most important feature of this case was that whether the poorly differentiated endometrioid adenocarcinoma in the left parametrical area combined with partial clear cell carcinoma was the carcinomatous changes of the original deep endometriosis or carcinomatous changes and metastasis of uterine adenomyoma or eutopic endometrium. HE staining showed that the structure and morphology of parametrical tumor cells was different from those of adenomyosis and tumor cells in eutropic endometrium. Because normal endometriotic glands surrounding parametrical lesions or in lesions were not found, diagnostic criteria of carcinomatous changes of endometriosis proposed by Sampson in 1925 could not be completely met.[ 15 ] Therefore, the possibility that this lesion was from metastasis could not be ruled out. Normal endometrial glands could not be found in left parametrical adenocarcinoma that had involvement of rectum, ureter, and right ovary. Thus, the possibility of metastasis of carcinomatous change of adenomyosis to left parametrical was more likely. However, combined with surgery and pathological evidence, we considered that the left parametrical adenocarcinoma was more likely to be carcinomatous changes of the original deep endometriosis. First, the left parametrical lesion was generally not adjacent to the adenomyoma lesion and the left parametrial adenocarcinoma lesion contained chocolate-like fluid, indicating that this site was likely to have the original deep endometriosis. Next, tumor cells in parametrical adenocarcinoma lesions and endometrial tumor cells in endometrium and adenomyosis had significant differences at differentiation level, structure and morphology. In addition, there were CD10 + endometrial stromal cells surrounding tumor cell masses in parametrical lesions, indicating that tumor cells were from endometrial glands. Finally, normal endometriotic glands were not found in left parametrical adenocarcinoma lesions; which might be associated with insufficient or biased material collection in pathological examination or carcinomatous change of all endometriotic glands in that place. Immunohistochemical staining of microsatellite instability in left parametrical adenocarcinoma lesions that had clear cell components and eutropic endometrioid adenocarcinoma was performed. MLH1, MSH2, MSH6, and PMS2 were all positive in parametrical lesions, whereas PMS2 was negative in eutropic endometrioid adenocarcinoma lesions. The microsatellite instability levels between these two were not consistent, indicating that the pathogenic mechanisms of these two carcinomatous changes might be different and the parametrical lesion was likely to be the carcinomatous change of the original deep endometriosis. It is considered that obesity and unopposed estrogen use are high-risk factors leading to carcinomatous change of endometriosis.However, the patient did not have the above high risk factors and did not have a family history. The eutopic and ectopic endometrium both had carcinomatous changes, suggesting that the genetic factor of the patient might play a critical role in disease pathogenesis. There is still controversy about the adjuvant treatment of carcinomatous change of endometriosis after surgery. Some scholars consider that radiotherapy can benefit patients more than chemotherapy. However, considering the ovarian and colorectal involvement in this patient, chemotherapy was chosen. This patient had a history of endometriotic cysts and dysmenorrhea but did not have menstrual disorders. Therefore, it was diagnosed as deeply infiltrating endometriosis before surgery. Tumors were discovered in pathological examination after hysterectomy. However, retrospective analysis of preoperative examination showed that the patient had CA125 of 183.4U/ml and color ultrasound suggested abundant blood flow in the posterior cervical wall lesion. These results all suggested the possibility of carcinomatous changes. 4. Conclusions The treatment experiences on this patient were summarized. For patients suspected to have adenomyosis combined with deep invasive endometriosis, physicians should be alert for physical signs and features of ectopic endometrial malignant transformation such as obesity, diabetes mellitus, history of unopposed estrogen use, abnormal uterine bleeding symptom, CA125 over 200 U/ml, and abundant blood flow signals in lesions suggested by color ultrasound should be cautious. Early surgical diagnosis and satisfactory tumor reduction surgery are the keys to treatment. Declarations Acknowledgments: We would like to express our gratitude to all those who helped us during the writing of this manuscript and to all the peer reviewers for their opinions and suggestions. Author contributions CLZ, XJL and MJT collected data and wrote the manuscript. FYL and ZLcontributed to the revision and fnal approval of the manuscript. All authors read and approved the final manuscript. Fundings This study has received funding by key projects of Sichuan Science and Technology Department (Grant No.2021YFS0209). Availability of data and materials The data supporting the conclusions of this article is available from corresponding author Ethics approval and consent to participate We had received the signed informed consent from the patient for this case report and publication and patient anonymity was preserved. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images Conflict of interest The authors declare that they have no conflicts of interest. References Sapalidis K, Machairiotis N, Zarogoulidis P, et al. Genes' Interactions: A Major Contributor to the Malignant Transformation of Endometriosis. Int J Mol Sci . 2019;20(8):1842. Published 2019 Apr 14. McCluggage WG. Endometriosis-related pathology: a discussion of selected uncommon benign, premalignant and malignant lesions. Histopathology . 2020;76(1):76-92. Barra F, Scala C, Biscaldi E, et al. Ureteral endometriosis: a systematic review of epidemiology, pathogenesis, diagnosis, treatment, risk of malignant transformation and fertility. Hum Reprod Update . 2018;24(6):710-730. Ait Benkaddour Y, El Farji A, Soummani A. Endometriosis of the vesica-vaginal septum: a rare and unusual localization (case report). BMC women's health 2020;20(1):179. Chen S, Gu Z, Sun J, et al. Clinicopathologic characteristics of primary vaginal clear cell carcinoma in China and an endometriosis malignant transformation case: a case series. Chin Med J (Engl). 2022;135(6):738-740. Published 2022 Mar 20. Kvaskoff, Marina et al. “Endometriosis and cancer: a systematic review and meta-analysis.” Human reproduction update vol. 27,2 (2021): 393-420. Crispi CP, Jr., Crispi CP, de Paula Crispi F, Cardeman L, Salomao A, de Freitas Fonseca M. Endometriosis infiltrating the pelvic floor muscles with histopathological correlation-A case report. The journal of obstetrics and gynaecology research 2019;45(10):2116-20. Guo SW. Cancer-associated mutations in endometriosis: shedding light on the pathogenesis and pathophysiology. Hum Reprod Update. 2020;26(3):423-449. Lu B, Chen Q, Zhang X, Cheng L. Serous carcinoma arising from uterine adenomyosis/adenomyotic cyst of the cervical stump: a report of 3 cases. Diagn Pathol. 2016;11(1):46. Published 2016 Jun 4. Kiuchi K, Hasegawa K, Kanamori A, Machida H, Kojima M, Fukasawa I. Carcinosarcoma arising from uterine adenomyosis: A case report. The journal of obstetrics and gynaecology research 2016;42(3):358-62. Lu B, Chen Q, Zhang X, Cheng L. Serous carcinoma arising from uterine adenomyosis/adenomyotic cyst of the cervical stump: a report of 3 cases. Diagnostic pathology 2016;11(1):46. Tsuruga T, Hirata T, Akiyama I, Matsumoto Y, Oda K, Fujii T, et al. Mixed endometrioid and clear cell carcinoma arising from laparoscopic trocar site endometriosis. Journal of Obstetrics and Gynaecology Research 2019;45(8):1613-8. Colman HI RA. Carcinoma developing in areas of adenomyosis. Obstet Gynecol 1959;14:342-8. Miller EM, Sun Y, Richardson I, Frimer M. Vesical clear cell adenocarcinoma arising from endometriosis: A mullerian tumor, indistinguishable from ovarian clear cell adenocarcinoma. Gynecologic oncology reports 2016;18:8-10. JA S. Endometrial carcinoma of the ovary, arising in endometrial tissue in that organ. Arch Surg 1925;10:1 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 02 Aug, 2024 Read the published version in BMC Women's Health → Version 1 posted Editorial decision: Revision requested 25 Apr, 2024 Reviewers agreed at journal 22 Apr, 2024 Reviews received at journal 21 Apr, 2024 Reviewers agreed at journal 16 Apr, 2024 Reviewers invited by journal 03 Apr, 2024 Editor invited by journal 03 Apr, 2024 Editor assigned by journal 03 Apr, 2024 Submission checks completed at journal 18 Jan, 2024 First submitted to journal 03 Jan, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3832190","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":267793007,"identity":"6fcaf4f4-89e4-46f4-9c5d-3906d0764b0b","order_by":0,"name":"Cailu Zhou","email":"","orcid":"","institution":"Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Cailu","middleName":"","lastName":"Zhou","suffix":""},{"id":267793008,"identity":"a21790fc-321b-45bd-a32a-5eaed6d3a589","order_by":1,"name":"Xiaojing Luo","email":"","orcid":"","institution":"University of Electronic Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Xiaojing","middleName":"","lastName":"Luo","suffix":""},{"id":267793009,"identity":"8cd0a698-b166-4415-ab51-cec594d7b5f6","order_by":2,"name":"Mengjie Tang","email":"","orcid":"","institution":"University of Electronic Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Mengjie","middleName":"","lastName":"Tang","suffix":""},{"id":267793010,"identity":"e89725cc-e77e-4123-a795-faf8ce45b0cc","order_by":3,"name":"Fangyuan Luo","email":"","orcid":"","institution":"Sichuan Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Fangyuan","middleName":"","lastName":"Luo","suffix":""},{"id":267793011,"identity":"f0b5e9d2-7eb4-44d7-8613-3a80b3dfc0b9","order_by":4,"name":"Zhi Liao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzElEQVRIiWNgGAWjYBACPmYgwdggwSPPzHzgwIcfRGhhg2qRMWxvSzw4s4cYLQxgLQw2DGfOGB/mYCNGCzvzw4c/d1jwMM7I+XCYgYdBnl/sACGHsRkbSJ6R4GGXyN1wuMCCwXDm7ASCfjGTMGyTANoC1DKDhyHB4DZBLezfJBKBWhhu5Dw4zMNGlBYeM4mDIC1nzjAQraXYsBGoBRjIBsBAliDsF37+4xsf/myrswdG5eMPH37YyPNLE9CCDiRIUz4KRsEoGAWjADsAAGPhPQ4RBnPsAAAAAElFTkSuQmCC","orcid":"","institution":"Southwest Medical University","correspondingAuthor":true,"prefix":"","firstName":"Zhi","middleName":"","lastName":"Liao","suffix":""}],"badges":[],"createdAt":"2024-01-03 15:33:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3832190/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3832190/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12905-024-03170-4","type":"published","date":"2024-08-02T15:57:36+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":49976187,"identity":"e7708117-17ec-45eb-a3d1-9b54c6aa50fa","added_by":"auto","created_at":"2024-01-22 14:50:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":6377252,"visible":true,"origin":"","legend":"\u003cp\u003ea/b. The outer appearance of endometriosis lesions and the left parametricallesions in left adnexa; c. chocolate-like fluid in the lesion( red line indicated he proper ligament of the left ovary, purple line indicated left ureter, and the yellow area indicated rectum); d. Bladder valvuloplasty after partial ureterectomy\u003c/p\u003e","description":"","filename":"FIG1.png","url":"https://assets-eu.researchsquare.com/files/rs-3832190/v1/dc601fcd27e3a57ec1b8ff30.png"},{"id":49976190,"identity":"10b14b87-5002-4975-aa75-478ed69c5cab","added_by":"auto","created_at":"2024-01-22 14:50:11","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":11906058,"visible":true,"origin":"","legend":"\u003cp\u003eMalignant transformation of endometrial glands in eutropicendometrium and ectopic endometrium of adenomyoma (green arrow indicated normal gland, yellow indicated atypical hyperplasia, and red showed carcinomatous gland).\u003c/p\u003e","description":"","filename":"FIG2.png","url":"https://assets-eu.researchsquare.com/files/rs-3832190/v1/95e000ec15e9f7d1179b52d7.png"},{"id":49976188,"identity":"2afce261-36bc-45c8-8b13-c3052a2473e6","added_by":"auto","created_at":"2024-01-22 14:50:11","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":14485050,"visible":true,"origin":"","legend":"\u003cp\u003eLeft parametrical endometrioid adenocarcinoma combined with clear cell differentiation and the immunohistochemical staining. a/b. Endometrioid adenocarcinoma with clear cell components (red arrow) at the vagina wall near the parametrical location (black arrow); c. clear cell carcinoma: hobnail-like cancer cells in glands were observed; d. ER+; e. CK7+, f. adenocarcinoma cells surrounded by CD10+ endometrial stromal cells.\u003c/p\u003e","description":"","filename":"FIG3.png","url":"https://assets-eu.researchsquare.com/files/rs-3832190/v1/3a7dcc483ea3e11555246ebf.png"},{"id":61793560,"identity":"cb50b957-451f-425b-9b3a-d16b8da27ed0","added_by":"auto","created_at":"2024-08-05 16:13:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":46972142,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3832190/v1/7435f000-159e-4604-a41e-ea37bcb5689a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A rare case of combined endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrical deep endometriosis","fulltext":[{"header":"1. Background","content":"\u003cp\u003eEndometriosis is a chronic benign disease and its malignant transformation rate is approximately 1%.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] The most common site of endometriosis malignancy is ovary. Other locations also include the intestine, abdominal wall, vagina, cervix, bladder, ureter, pelvic floor muscles, and recto-vaginal septum.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e][\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e][\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e][\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e][\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e][\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] Malignant transformation from adenomyosis is extremely rare.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e][\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e][\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e][\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] The most common malignant pathological type in ectopic endometrium is endometrioid adenocarcinoma. Other pathological types also include clear cell-like adenocarcinoma, squamous cell carcinoma, endometrial stromal sarcoma, and Mullerian carcinosarcoma.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e][\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e][\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] This case presented one rare case of carcinomatous changes of both uterine adenomyoma and deep endometriotic lesions that induced hydronephrosis and intestinal obstruction. We had received the signed informed consent from the patient for this case report and publication and patient anonymity was preserved.\u003c/p\u003e"},{"header":"2. Case presentation","content":"\u003cp\u003eThe patient was a 44-year-old Chinese woman with G1P0\u0026thinsp;+\u0026thinsp;1 and body mass index of 19. She sought treatment in our emergency surgery department due to sudden onset of intermittent abdominal colic with vomiting for 1\u0026thinsp;+\u0026thinsp;days after eating indigestible food. The patient also had the symptoms of intestinal obstruction such as nausea, anal pendant expansion, and no gas nor defecation but did not have discomforts such as fever, bloody stool and vaginal bleeding. The patient underwent laparoscopic cyst excision due to ovarian endometriotic cysts 7 years ago and laparoscopic separating surgery due to infertility 4 years ago. The patient had regular menstrual periods and secondary infertility for 20 years. She received one in vitro fertilization and the embryo transfer 4 years ago; however, embryo implantation failed. Physical examination discovered a 2cm ovarian cyst 1 year ago but the patient did not receive treatment and follow up. The patient did not have a history of long-term exposure to estrogen, oral short-acting contraceptives, or other drugs. She had no known family history of cancer. Abdominal examination suggested lower abdomen tenderness without rebound pain and no palpable abdominal mass. Gynecological examination revealed smooth cervical appearance, uniformly enlarged uterus with a size close to the size of a 2-month pregnancy, left adnexa had patchy thickness, and left parametrical tissues had a palpable hard and irregular nodule of approximately 3cm that involved left vaginal fornix. Gynecological color ultrasound indicated that the endometrium was 0.6cm. The thickness of the anterior and posterior walls of myometrium was not even, myometrial echo was coarse and uneven especially the posterior wall, and there was an echo from a mass with unclear boundaries at the size of 3.9*3.3cm. The posterior cervical wall had a detected hypoechoic nodule at the size of 1.7*1.5cm, there were abundant blood flow signals, and the boundaries were clear. The renogram showed the curve of left renal incomplete obstruction. The transrectal contrast-enhanced ultrasound examination detected a solid hypoechoic mass of approximately 1.8*3.5cm in posterior cervical wall; the mass had irregular morphology and unclear boundary, the mass invaded the anterior wall of rectum through the rectouterine pouch. The color Doppler flow imaging suggested that there were more abundant blood flow signals in the hypoechoic mass. Gastroscopy and colonoscopy did not show obvious abnormality. The patient had normal liver and kidney functions, CA-125 was 183.4U/ml, and CA-199 was 66.7U/ml. Therefore, adenomyosis combined with adenomyoma and deep endometriosis combined with ureteral obstruction and intestinal obstruction were considered. The patient underwent robot-assisted laparoscopic subextensive hysterectomy\u0026thinsp;+\u0026thinsp;bilateral adnexa resection\u0026thinsp;+\u0026thinsp;deep endometriosis lesion resection\u0026thinsp;+\u0026thinsp;bilateral ureteral stent placement in the Department of Genecology of our hospital. The surgery showed that uterus enlarged to the size of approximately 2 month pregnancy, the appearance of bilateral oviducts did not have obvious abnormality, the surface of left ovary had brown endometriotic lesions, the right ovary was swelling with a diameter of 3cm and had adhesion with the posterior wall of the uterus and rectum, and the proper ligament of the left ovary had dense adhesion with left ureter, left posterior wall of uterus, rectum (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea/b). There was a 3cm hard lesion with unclear boundaries in the adhesion area that involved left vaginal fornix, lower segment of left ureter, and rectum. There was a chocolate cyst-like lesion of 1cm that contained chocolate-like old bleeding fluid (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec). The lower segment of left ureter at length of 10cm had thickened and was hard and the segment of rectum at approximately 4cm behind cervix had thickened and hard muscular wall. There was no lesion involvement in the upper abdomen. Dissection of endometrium after hysterectomy did not show obvious lesions, the myometrium was diffuse and thickened, and the posterior wall of uterus had an adenomyoma-like lesion of approximately 4cm. Postoperative pathological examinations suggested eutropic endometrium had multifocal atypical hyperplasia of endometrial glands and formations of highly/moderately differentiated endometrioid adenocarcinoma. The maximum diameter of intramyometrial adenomyosis was 5cm and most gland components exhibited atypical hyperplasia and highly/moderately differentiated endometrioid adenocarcinoma. Other myometrium wall tissues were scattered in the ectopic endometrium tissues combined with atypical hyperplasia and formation of endometrioid adenocarcinoma (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Left parametrical lesions suggested poorly differentiated endometrioid adenocarcinoma combined with partial clear cell carcinoma involvement (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Uterine specimens showed tumor thrombus in vessels and perineurium invasion. There was no tumor involvement in cervix. Left ovary had endometriotic cysts with no tumor involvement, and right ovary had tumor involvement. Immunohistochemistry results of left parametrical lesions suggested ER(+)PR(+); CK7(+); CD10(-); CEA(+); Ki67 (50%)(Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Immunohistochemistry results of adenomyosis suggested ER(+); PR(+); CK7(+); CD10(-); CEA(focal+); Ki67(20%). The patient was considered to havecarcinomatous changes of both uterine adenomyoma and deep endometriotic lesions. On 8th day after the first surgery, the patient underwent transabdominal tumor cell reduction surgery including greater omentum resection\u0026thinsp;+\u0026thinsp;appendectomy\u0026thinsp;+\u0026thinsp;pelvic lymph node dissection\u0026thinsp;+\u0026thinsp;para-abdominal aortic lymph node dissection\u0026thinsp;+\u0026thinsp;partial rectectomy\u0026thinsp;+\u0026thinsp;intestinal anastomosis\u0026thinsp;+\u0026thinsp;resection of the lower segment of left ureter\u0026thinsp;+\u0026thinsp;left ureteral cystoplasty\u0026thinsp;+\u0026thinsp;left ureteral stent implantation. Postoperative pathological examination suggested that ureter had tumor infiltration, bilateral pelvic lymph nodes and para-abdominal aorta lymph nodes all had tumor metastases, tumor infiltration was observed on the serosal surface of the intestinal wall of of partial rectum, the muscular layer of intestinal wall had tumor infiltration, and the appendix and greater omentum did not have tumor infiltration. After a satisfactory postoperative recovery, the patient was treated with Taxol\u0026thinsp;+\u0026thinsp;Carboplatin chemotherapy regimen.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"3. Discussion","content":"\u003cp\u003eIn 1959, Colman and Rosenthal modified Sampson\u0026rsquo;s criteria to apply to carcinomas developing from adenomyosis: (i) carcinoma should be absent from the normally situated endometrium and anywhere else in the pelvis; (ii) the carcinoma should be actually observed to be arising from the epithelium of the areas of adenomyosis and not invading from another source; and (iii) endometrial stromal cells should surround the aberrant glands to support a diagnosis of adenomyosis.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] In this case, Co-existence of normal endometrial glands, atypical hyperplastic glands, and cancerous glands were observed both in eutropic endometrium and ectopic endometrium in uterine adenomyoma lesions. In addition, obvious endometrial stromal cells surrounding cancerous glands were observed. These observations were sufficient to prove that eutropic endometrium and ectopic endometrium in myometrium both had malignant transformation and they were both primary. In reported cases of carcinomatous change of uterine adenomyoma or adenomyosis, the probability of simultaneous malignant transformation of eutropic endometrium was approximately 20%.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e][\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] Bingjian Lu and colleagues reported 3 cases of serous carcinoma in uterine cervical adenomyosis. Among them, one case did not have carcinomatous changes, one case had serous carcinoma, and one case had endometrioid adenocarcinoma in eutropic endometrium.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe most important feature of this case was that whether the poorly differentiated endometrioid adenocarcinoma in the left parametrical area combined with partial clear cell carcinoma was the carcinomatous changes of the original deep endometriosis or carcinomatous changes and metastasis of uterine adenomyoma or eutopic endometrium. HE staining showed that the structure and morphology of parametrical tumor cells was different from those of adenomyosis and tumor cells in eutropic endometrium. Because normal endometriotic glands surrounding parametrical lesions or in lesions were not found, diagnostic criteria of carcinomatous changes of endometriosis proposed by Sampson in 1925 could not be completely met.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] Therefore, the possibility that this lesion was from metastasis could not be ruled out. Normal endometrial glands could not be found in left parametrical adenocarcinoma that had involvement of rectum, ureter, and right ovary. Thus, the possibility of metastasis of carcinomatous change of adenomyosis to left parametrical was more likely.\u003c/p\u003e \u003cp\u003eHowever, combined with surgery and pathological evidence, we considered that the left parametrical adenocarcinoma was more likely to be carcinomatous changes of the original deep endometriosis. First, the left parametrical lesion was generally not adjacent to the adenomyoma lesion and the left parametrial adenocarcinoma lesion contained chocolate-like fluid, indicating that this site was likely to have the original deep endometriosis. Next, tumor cells in parametrical adenocarcinoma lesions and endometrial tumor cells in endometrium and adenomyosis had significant differences at differentiation level, structure and morphology. In addition, there were CD10\u0026thinsp;+\u0026thinsp;endometrial stromal cells surrounding tumor cell masses in parametrical lesions, indicating that tumor cells were from endometrial glands. Finally, normal endometriotic glands were not found in left parametrical adenocarcinoma lesions; which might be associated with insufficient or biased material collection in pathological examination or carcinomatous change of all endometriotic glands in that place.\u003c/p\u003e \u003cp\u003eImmunohistochemical staining of microsatellite instability in left parametrical adenocarcinoma lesions that had clear cell components and eutropic endometrioid adenocarcinoma was performed. MLH1, MSH2, MSH6, and PMS2 were all positive in parametrical lesions, whereas PMS2 was negative in eutropic endometrioid adenocarcinoma lesions. The microsatellite instability levels between these two were not consistent, indicating that the pathogenic mechanisms of these two carcinomatous changes might be different and the parametrical lesion was likely to be the carcinomatous change of the original deep endometriosis. It is considered that obesity and unopposed estrogen use are high-risk factors leading to carcinomatous change of endometriosis.However, the patient did not have the above high risk factors and did not have a family history. The eutopic and ectopic endometrium both had carcinomatous changes, suggesting that the genetic factor of the patient might play a critical role in disease pathogenesis.\u003c/p\u003e \u003cp\u003eThere is still controversy about the adjuvant treatment of carcinomatous change of endometriosis after surgery. Some scholars consider that radiotherapy can benefit patients more than chemotherapy. However, considering the ovarian and colorectal involvement in this patient, chemotherapy was chosen. This patient had a history of endometriotic cysts and dysmenorrhea but did not have menstrual disorders. Therefore, it was diagnosed as deeply infiltrating endometriosis before surgery. Tumors were discovered in pathological examination after hysterectomy. However, retrospective analysis of preoperative examination showed that the patient had CA125 of 183.4U/ml and color ultrasound suggested abundant blood flow in the posterior cervical wall lesion. These results all suggested the possibility of carcinomatous changes.\u003c/p\u003e"},{"header":"4. Conclusions","content":"\u003cp\u003eThe treatment experiences on this patient were summarized. For patients suspected to have adenomyosis combined with deep invasive endometriosis, physicians should be alert for physical signs and features of ectopic endometrial malignant transformation such as obesity, diabetes mellitus, history of unopposed estrogen use, abnormal uterine bleeding symptom, CA125 over 200 U/ml, and abundant blood flow signals in lesions suggested by color ultrasound should be cautious. Early surgical diagnosis and satisfactory tumor reduction surgery are the keys to treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe\u0026nbsp;would like to express our gratitude to all those who\u0026nbsp;helped us during the writing of this manuscript and to all the\u0026nbsp;peer reviewers for their opinions and suggestions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eCLZ, XJL and MJT\u0026nbsp;collected data and wrote the manuscript.\u0026nbsp;FYL and ZLcontributed to the revision and fnal approval of the manuscript.\u0026nbsp;All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFundings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has received funding by\u0026nbsp;key projects of Sichuan Science and Technology Department (Grant No.2021YFS0209).\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe data supporting the conclusions of this article is available from corresponding author\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe had received the signed informed consent from the patient for\u0026nbsp;this\u0026nbsp;case report and publication and patient anonymity was preserved.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSapalidis K, Machairiotis N, Zarogoulidis P, et al. Genes\u0026apos; Interactions: A Major Contributor to the Malignant Transformation of Endometriosis. \u003cem\u003eInt J Mol Sci\u003c/em\u003e. 2019;20(8):1842. Published 2019 Apr 14.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMcCluggage WG. Endometriosis-related pathology: a discussion of selected uncommon benign, premalignant and malignant lesions. \u003cem\u003eHistopathology\u003c/em\u003e. 2020;76(1):76-92.\u003c/li\u003e\n \u003cli\u003eBarra F, Scala C, Biscaldi E, et al. Ureteral endometriosis: a systematic review of epidemiology, pathogenesis, diagnosis, treatment, risk of malignant transformation and fertility. \u003cem\u003eHum Reprod Update\u003c/em\u003e. 2018;24(6):710-730.\u003c/li\u003e\n \u003cli\u003eAit Benkaddour Y, El Farji A, Soummani A. Endometriosis of the vesica-vaginal septum: a rare and unusual localization (case report). BMC women\u0026apos;s health 2020;20(1):179.\u003c/li\u003e\n \u003cli\u003eChen S, Gu Z, Sun J, et al. Clinicopathologic characteristics of primary vaginal clear cell carcinoma in China and an endometriosis malignant transformation case: a case series. Chin Med J (Engl). 2022;135(6):738-740. Published 2022 Mar 20.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKvaskoff, Marina et al. \u0026ldquo;Endometriosis and cancer: a systematic review and meta-analysis.\u0026rdquo;\u0026nbsp;Human reproduction update\u0026nbsp;vol. 27,2 (2021): 393-420.\u003c/li\u003e\n \u003cli\u003eCrispi CP, Jr., Crispi CP, de Paula Crispi F, Cardeman L, Salomao A, de Freitas Fonseca M. Endometriosis infiltrating the pelvic floor muscles with histopathological correlation-A case report. The journal of obstetrics and gynaecology research 2019;45(10):2116-20.\u003c/li\u003e\n \u003cli\u003eGuo SW. Cancer-associated mutations in endometriosis: shedding light on the pathogenesis and pathophysiology.\u0026nbsp;Hum Reprod Update. 2020;26(3):423-449.\u003c/li\u003e\n \u003cli\u003eLu B, Chen Q, Zhang X, Cheng L. Serous carcinoma arising from uterine adenomyosis/adenomyotic cyst of the cervical stump: a report of 3 cases. Diagn Pathol. 2016;11(1):46. Published 2016 Jun 4.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKiuchi K, Hasegawa K, Kanamori A, Machida H, Kojima M, Fukasawa I. Carcinosarcoma arising from uterine adenomyosis: A case report. The journal of obstetrics and gynaecology research 2016;42(3):358-62.\u003c/li\u003e\n \u003cli\u003eLu B, Chen Q, Zhang X, Cheng L. Serous carcinoma arising from uterine adenomyosis/adenomyotic cyst of the cervical stump: a report of 3 cases. Diagnostic pathology 2016;11(1):46.\u003c/li\u003e\n \u003cli\u003eTsuruga T, Hirata T, Akiyama I, Matsumoto Y, Oda K, Fujii T, et al. Mixed endometrioid and clear cell carcinoma arising from laparoscopic trocar site endometriosis. Journal of Obstetrics and Gynaecology Research 2019;45(8):1613-8.\u003c/li\u003e\n \u003cli\u003eColman HI RA. Carcinoma developing in areas of adenomyosis. Obstet Gynecol 1959;14:342-8.\u003c/li\u003e\n \u003cli\u003eMiller EM, Sun Y, Richardson I, Frimer M. Vesical clear cell adenocarcinoma arising from endometriosis: A mullerian tumor, indistinguishable from ovarian clear cell adenocarcinoma. Gynecologic oncology reports 2016;18:8-10.\u003c/li\u003e\n \u003cli\u003eJA S. Endometrial carcinoma of the ovary, arising in endometrial tissue in that organ. Arch Surg 1925;10:1\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Adenocarcinoma, Adenomyoma, Endometriosis, Case report","lastPublishedDoi":"10.21203/rs.3.rs-3832190/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3832190/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cb\u003eBackground\u003c/b\u003e Carcinomatous changes from the ectopic endometrial glands in endometriosis have been reported in many studies, but malignant transformation from uterine adenomyosis/adenomyoma is rare. And clear cell-like adenocarcinoma represents a seldom-encountered malignant pathological variant of ectopic endometrium.\u003c/p\u003e \u003cp\u003e \u003cb\u003eCase presentation\u003c/b\u003e This case report presents a case of a 44-year-old nulliparous woman begun with abdominal pain and intestinal obstruction. Past medical history showed laparoscopic ovarian endometriotic cyst excision. Ultrasound indicated adenomyoma and a parametrical hypoechoic nodule with abundant blood flow signals and unclear boundaries. Deep invasive endometriosis was considered preoperatively. The patient underwent laparoscopic subextensive hysterectomy and bilateral adnexa resection. Chocolate cyst-like lesion was observed in the parametral lesion. Postoperative pathological examinations suggested endometrioid adenocarcinoma arising from eutropic endometrium and adenomyoma. Left parametrical lesions suggested poorly differentiated endometrioid adenocarcinoma combined with clear cell carcinoma. CD10\u0026thinsp;+\u0026thinsp;endometrial stromal cells were observed surrounding tumor cell masses. The patient underwent subsequent transabdominal tumor cell reduction surgery and chemotherapy. Combined with surgical founding and pathological characters of the left parametrical adenocarcinoma, the parametrial lesions were more likely to be carcinomatous changes of the original deep endometriosis.\u003c/p\u003e \u003cp\u003e \u003cb\u003eConclusion\u003c/b\u003e We herein present a rare case of combined endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrical deep endometriosis that may help inspire additional studies in the future.\u003c/p\u003e","manuscriptTitle":"A rare case of combined endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrical deep endometriosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-22 14:50:07","doi":"10.21203/rs.3.rs-3832190/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-04-25T21:36:11+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"c9007a50-7381-4bd6-a25d-001f6e54beb8","date":"2024-04-22T11:27:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-21T21:04:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"f09bb540-612d-49d5-a958-a07795d43d66","date":"2024-04-16T09:38:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-03T10:32:40+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-04-03T10:19:57+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-03T09:33:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-01-18T08:59:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Women's Health","date":"2024-01-03T15:23:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2049795b-5161-4c97-a891-b3b90c924632","owner":[],"postedDate":"January 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-05T16:03:42+00:00","versionOfRecord":{"articleIdentity":"rs-3832190","link":"https://doi.org/10.1186/s12905-024-03170-4","journal":{"identity":"bmc-womens-health","isVorOnly":false,"title":"BMC Women's Health"},"publishedOn":"2024-08-02 15:57:36","publishedOnDateReadable":"August 2nd, 2024"},"versionCreatedAt":"2024-01-22 14:50:07","video":"","vorDoi":"10.1186/s12905-024-03170-4","vorDoiUrl":"https://doi.org/10.1186/s12905-024-03170-4","workflowStages":[]},"version":"v1","identity":"rs-3832190","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3832190","identity":"rs-3832190","version":["v1"]},"buildId":"0U-iFTyB6qxOgVj8rjrZV","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}