Extra-gonadal Endometrioid Borderline Ovarian Tumor Associated with Endometriotic Cyst

Extra-gonadal Endometrioid Borderline Ovarian Tumor Associated with Endometriotic Cyst | 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 Extra-gonadal Endometrioid Borderline Ovarian Tumor Associated with Endometriotic Cyst Katrina Dimaano, Marianna Sarkissyan, Beverley A. Petrie, Meifang Wu, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4791357/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Borderline ovarian tumors (BOT) are rare ovarian tumors that present at a younger age than other ovarian carcinomas. These tumors present a challenge given the complex diagnostic and surgical considerations that need to be navigated for patient care. Notably, fertility sparing among younger woman is preferable surgically but may place patient at a higher rate of recurrence. The purpose of this report is to review the work-up and surgical management of an extra-gonadal endometroid BOT. Case Presentation: Patient is a 32-year-old female with history of polycystic ovary syndrome, type II diabetes mellitus, and morbid obesity who presented with abdominal pain and vomiting. She underwent extensive work-up including computer tomography (CT), magnetic resonance imaging (MRI), transvaginal ultrasound (TVUS), colonoscopy, and diagnostic laparoscopy. After multidisciplinary discussion, this was managed with oncologic en bloc resection of the lesion and adherent colon. In order to maintain fertility, her ovaries and uterus were spared. She continued with surveillance and at three month follow up had no evidence of disease. The purpose of this report is to review the work-up and surgical management of an extra-gonadal endometroid BOT. Conclusions This report reviews the work-up and surgical management of an extra-gonadal endometroid BOT to inform clinicians on management of these rare tumors. endometrioid borderline ovarian tumor endometriosis fertility sparing surgery ovarian cancer Figures Figure 1 Figure 2 Figure 3 BACKGROUND Borderline ovarian tumors (BOTs) are uncommon tumors described as intermediate between benign and malignant. The most common subtypes of BOTs are serous and mucinous, while endometrioid, clear cell and Brenner subtypes are rare and account for 3–4% of all BOTs [ 1 , 2 ]. The average age of presentation is 45 years; however, up to one third of patients present at an age less than 40 years rendering fertility an important consideration in treatment. [ 2 – 4 ]. BOTs are often asymptomatic or associated with nonspecific symptoms such as abdominal pain or distention. Diagnostic work up includes transvaginal ultrasound (TVUS), which can aid in distinguishing between benign and malignant masses of the ovary. Further imaging is typically not warranted. When ovarian malignancy is suspected, surgery is indicated [ 2 ]. The gold standard of treatment for BOTs historically is radical surgery, which includes hysterectomy, bilateral salpingo-oophorectomy, staging omentectomy, peritoneal biopsies and cytology. Conservative fertility-sparing treatments where the uterus and at least one ovary is spared have also been described [ 3 , 4 ]. Given BOTs present at a younger age than malignant ovarian tumors, there has been effort to balance risk of disease progression and preserving fertility in this population [ 5 , 6 ]. There has only been one case report of extra-gonadal BOT within endometriotic cyst to date, and there is no standardized treatment for this rare pathology [ 7 ].We present a case of a solid-cystic right lower quadrant (RLQ) mass adherent to the colon and retroperitoneum managed with en bloc resection and oncologic resection of colon. Final pathology showed a rare histologic subtype of BOT, endometroid borderline ovarian tumor with osseous metaplasia associated with endometriosis. CASE PRESENTATION The patient is a 32-year-old female with history of polycystic ovary syndrome, type II diabetes mellitus, and morbid obesity (Body Mass Index = 43) who presented with abdominal pain and vomiting. Initial workup included an abdominal computed tomography of the abdomen and pelvis (CT) which revealed a 10 x 10 x 5.3cm heterogeneous mass in the RLQ adjacent to the cecum and extending into right paracolic gutter with moderate ascites. Laboratory work up was notable for elevated cancer antigen-125 (CA-125) ~ 18000 U/mL and normal carcinoembryonic antigen 1.9 µg/mL, and alpha-fetoprotein 2.2 µg/mL. She subsequently underwent diagnostic abdominal paracentesis to evaluate for malignant ascites with return of brown viscous fluid with final pathology showing benign mesothelial cells. Colonoscopy was obtained given the possible colonic involvement and was unremarkable. TVUS showed normal adnexa. Magnetic Resonance Imaging (MRI) of pelvis showed a 13.8 x 11 x 5.8cm RLQ mass with mural nodules (Fig. 1). Patient was then taken to the operating room and underwent diagnostic laparoscopy which showed a large multilocular cystic mass located in RLQ attached to the cecum (Fig. 2). A biopsy was not taken due to risk of cyst rupture. Endometrial curettage showed endometrial hyperplasia without atypia. A multidisciplinary discussion with members of gynecologic oncology, colorectal surgery, and radiology determined that the work up was concerning for endometriosis with possible malignant transformation. The decision was made to forego tissue biopsy given concern for tumor seeding. The patient underwent an exploratory laparotomy for excision of the mass. Intraoperatively, 520mL of chocolate colored cystic fluid was encountered. The cystic RLQ mass was noted to be densely adherent to the cecum and right retroperitoneum. En bloc resection of the mass and right colon was performed following usual oncologic principles. Omentectomy was separately performed. The patient subsequently recovered well post-operatively. The final pathology was notable for Stage IIIB endometrioid BOT with osseous metaplasia associated with the endometriotic cyst. The mass was adherent to the cecum and right retroperitoneum but without invasion into these structures (Fig. 3 ). The BOT measured 2cm and was completely removed within the 17cm cyst. No tumor was identified in 25 mesocolic lymph nodes. At three month follow up the patient had resolution of symptoms and interval CT scan did not show any further intraperitoneal disease. The patient was undecided about future childbearing and decided to forego hysterectomy and bilateral salpingo-oophorectomy, and decided to continue with surveillance. DISCUSSION AND CONCLUSIONS BOTs are uncommon neoplasms that present at a mean age of 45 years, 10 years younger than ovarian carcinomas [ 2 , 3 ]. Histologically BOTs generally have mild to moderate nuclear atypia, but with no more than 5mm of stromal invasion [ 1 , 8 ]. They are described as intermediate tumors characterized as having low malignant potential. Endometroid BOTs originate from either ovarian epithelial cells or endometriosis, and are synchronous with endometriosis in 46–63% of cases. Potential for progression to endometrioid carcinoma is low [ 1 , 2 , 9 ]. Approximately 75% of BOTs present as Federation of Gynecology and Obstetrics (FIGO) Stage I, confined to the ovaries [ 1 , 10 ]. They have an excellent prognosis with an overall 10-year survival of 97% [ 1 ]. Diagnostic work up of BOTs must include TVUS, as it can reliably distinguish between benign and malignant ovarian lesions. The characteristics of BOTs on sonography include uni- or multi-locular cyst, solid-cystic mass, and papillary projections [ 2 , 11 ]. MRI can be used as an adjunct to detect solid components of ovarian lesions; however, it has not been shown to distinguish between BOTs and other malignant tumors [ 9 , 12 ]. MRI was valuable in this case by elucidating nodular components within the cyst, not seen on CT, thereby raising concern for malignancy and guiding approach during surgery. CA-125 is negative in 53% of cases and is not a useful maker for diagnosing BOTs [ 2 ]. In this patient, it is unclear if the CA-125 elevation was due to the BOT and/or endometriosis. Radical surgery is the gold standard management of BOTs, though several studies describe the safety and efficacy of fertility sparing surgery [ 2 , 3 , 5 , 6 ]. The overall recurrence rate is 13.9% after resection. However, it is significantly higher for fertility sparing conservative surgery versus radical resection (21.3% and 1.8%, respectively) [ 1 , 5 , 6 , 10 ]. Despite this, conservative surgery maintains a good prognosis and does not impact overall survival [ 5 , 6 , 8 ]. Additional risk factors for recurrence include increased CA-125 levels, advanced FIGO stage, younger age, residual tumor, and incomplete staging [ 2 , 4 , 6 , 8 ]. The rate of malignant transformation after recurrence with advanced disease is estimated as 0.5-4% [ 2 , 13 ]. As in this case, it is imperative to include endometrial curettage when pursuing conservative surgery for endometroid BOT, as 50% of cases are found concomitant with another disorder of the endometrium such as polyps, hyperplasia, and carcinoma [ 1 , 13 ]. The 2024 NCCN guidelines recommend surveillance after surgery without evidence of residual disease to include clinic visits every 3–12 months for at least 5 years with pelvic exam and CA-125. In addition, the guidelines recommend TVUS for those who undergo fertility sparing surgery. Relapse from BOT can have late recurrences after 10–20 years supporting potentially longer duration of surveillance [ 2 , 14 ]. There are no standardized treatments or surveillance strategy for primary extra-gonadal manifestations of BOTs. Our patient was staged FIGO IIIB, defined by macroscopic, extra-pelvic, peritoneal metastasis > 2cm. She is at a higher risk of recurrence given her young age and higher FIGO stage at diagnosis. However, given her uncertain desire for future childbearing, the shared decision was made to forego completion radical surgery, and she proceeded with surveillance protocol extrapolated from the guidelines for primary ovarian BOTs. Yazawa and colleagues described an extra-gonadal giant endometrial cyst with endometroid BOT. The tumor was connected to the uterus and portions of the left and right uterosacral ligaments. The attachments to these structures were divided and the tumor was removed [ 7 ]. In that case, the patient did not desire future childbearing and bilateral adenectomy, hysterectomy, and partial omentectomy were performed. To the best of our knowledge, this is the first reported case of extra-gonadal endometrioid BOT within an endometriotic cyst that was adherent to the colon. In these rare presentations, it is prudent to hold a multidisciplinary discussion and participate in shared decision making with the patient to determine appropriate diagnosis and management. CONCLUSION Diagnosis and management of extra-gonadal presentations of BOT can be challenging. TVUS and MRI are necessary to evaluate potential high-risk features. In addition, if fertility preserving surgery is planned, then endometrial curettage is warranted. Preoperative colonoscopy, if there is concern for colon/rectal involvement, is prudent. We advise against transabdominal biopsy to decrease risk of peritoneal tumor seeding. In circumstances where extra-gonadal BOT is adherent to the colon, as in the case presented, we recommend en bloc resection employing standard oncologic principles. The decision to pursue radical surgery, including hysterectomy and bilateral oophorectomy, should be individualized carefully weighing the risk of recurrence with the desire for future childbearing. Abbreviations BOT: borderline ovarian tumors CA-125: cancer Antigen-125 CT: computer tomography FIGO: Federation of Gynecology and Obstetrics MRI: magnetic resonance imaging PCOS : polycystic ovary syndrome RLQ: right lower quadrant T2DM : type II diabetes mellitus TVUS : transvaginal ultrasound Declarations Ethics approval and consent to participate: Ethical review and approval were waived for this study; single patient case report does not meet the definition of research by The Lundquist Institute. Consent for publication: Written informed consent has been obtained from the patient to publish this paper. Availability of data and materials: All data generated or analyzed during this study are included in this published article Competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper Funding: No funding to declare. Authors' contributions: Writing – original draft, K.D; original draft and editing M.S; Pathology slide preparation and review, M.W. and L.M.; Writing - review and editing, H.L. and B.P. Acknowledgements: We thank the patient for agreeing to participate in this informative case report. References Hauptmann S, Friedrich K. Ovarian borderline tumors in the 2014 WHO classification: evolving concepts and diagnostic criteria. Virchows Arch . 2016;470:125-142. doi:10.1007/s00428-016-2040-8 Fischerova D, Zikan M, Dundr P, Cibula D. Diagnosis, Treatment, and Follow-Up of Borderline Ovarian Tumors. The Oncologist . 2012;17:1515-1553. doi:10.1634/theoncologist.2012-0139 Vera S, Kipp B. Ultraconservative, Fertility Sparing Treatment of Bilateral Borderline Ovarian Tumors: A Case Report of a 26-Year-Old, 0-Gravida with an Endometrioid Borderline Ovarian Tumor of the Right Ovary and a Sero-Mucinous Borderline Ovarian Tumor of the Left Ovary and a Review of the Literature. International Journal of Women’s Health . 2022;12:601-611. doi:10.2147/IJWH.S258478 Canlorbe G, Chabbert-Buffet N, Uzan C. Fertility-Sparing Surgery for Ovarian Cancer. Journal of Clinical Medicine . 2021;10(4235). doi:10.3390/jcm10184235 Kasaven L, Chawla M, Jones BP, et al. Fertility Sparing Surgey and Borderline Ovarian Tumours. Cancers . 2022;14(1485). doi:10.3390/ cancers14061485 Seong SJ, Kim DH, Kim MK, Song T. Controversies in borderline ovarian tumors. Journal of Gynecologic Oncology . 2015;26(4):343-349. doi:10.3802/jgo.2015.26.4.343 Yazawa H, Imaizumi K, Kato A, Takiguchi K. Extragonadal Giant Endometrial Cyst with Endometrioid Borderline Tumor. Gynecology and Minimally Invasive Therapy . 2019;8:179-184. doi:10.4103/GMIT.GMIT_85_18 Niu L, Tian H, Cao J. Recurrence characteristics and clinicopathological resuts of borderline ovarian tumors. BMC Women’s Health . 2021;21(134). doi:10.1186/s12905-021-01263-y Nakagawa E, Abiko K, Kido, Kitamura S, Yamaguchi, Baba T. Four cases of endometrioid borderline ovarian tumor: case reports and literature review. BJR Case Rep . 2017;4(201870062). doi:10.1259/bjrcr.20170062 MD B. PDQ® Adult Treatment Editorial Board. PDQ Ovarian Low Malignant Potential Tumors Treatment. Published online December 22, 2021. https://www.cancer.gov/types/ovarian/hp/ovarian-low-malignant-treatment-pdq Exacoustos C, Romanini ME, Rinaldo D, et al. Preoperative sonographic features of borderline ovarian tumors. Ultrasound Obstetrics Gynecology . 2005;25:50-59. doi:10.1002/uog.1823 Kim SH. Assessment of solid components of borderline ovarian tumor and stage I carcinoma: added value of combined diffusion- and perfusion-weighted magnetic resonance imaging. Yeungnam UNiv J Med . 2019;36(3):231-240. doi:10.12701/yujm.2019.00234 Reichenbach J, Schmoeckel E, Mahner S, Trillsch F. Diagnostic workup for endometrioid borderline ovarian tumors (eBOT) requires histopathological evaluation of the uterus. Journal of Ovarian Research . 2021;14(89). doi:10.1186/s13048-021-00839-4 National Comprehensive Cancer Network. Ovarian Cancer (Version 1.2022). Accessed July 17, 2024. https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf Additional Declarations No competing interests reported. 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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-4791357","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":342147903,"identity":"1e1cfc28-4a43-441e-814f-33c90876f992","order_by":0,"name":"Katrina Dimaano","email":"","orcid":"","institution":"Harbor-UCLA Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Katrina","middleName":"","lastName":"Dimaano","suffix":""},{"id":342147904,"identity":"4164d062-2c2e-46f5-9c0b-a659122ef956","order_by":1,"name":"Marianna Sarkissyan","email":"","orcid":"","institution":"Harbor-UCLA Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Marianna","middleName":"","lastName":"Sarkissyan","suffix":""},{"id":342147905,"identity":"4d4c9d7e-bea0-49b6-b898-1daa4e6b3580","order_by":2,"name":"Beverley A. Petrie","email":"","orcid":"","institution":"Harbor-UCLA Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Beverley","middleName":"A.","lastName":"Petrie","suffix":""},{"id":342147906,"identity":"86944c60-89c1-44b0-aba6-afecece01964","order_by":3,"name":"Meifang Wu","email":"","orcid":"","institution":"Harbor-UCLA Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Meifang","middleName":"","lastName":"Wu","suffix":""},{"id":342147907,"identity":"11c38810-c9a6-46ec-aadc-c9fb8b91cb9b","order_by":4,"name":"Laron W. McPhaul","email":"","orcid":"","institution":"Harbor-UCLA Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Laron","middleName":"W.","lastName":"McPhaul","suffix":""},{"id":342147908,"identity":"77b26919-dd4e-4ab0-a252-651b7c4fa509","order_by":5,"name":"Hanjoo Lee","email":"data:image/png;base64,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","orcid":"","institution":"Harbor-UCLA Medical Center","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Hanjoo","middleName":"","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2024-07-23 22:55:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4791357/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4791357/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63297907,"identity":"219faadc-da68-4cab-ab6f-79e0f961dde8","added_by":"auto","created_at":"2024-08-26 15:42:41","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":237660,"visible":true,"origin":"","legend":"\u003cp\u003eMRI of Right Lower Quadrant Mass\u003c/p\u003e\n\u003cp\u003eMRI of RLQ mass demonstrated two mural nodules. Larger 2cm mural nodule (red arrow) with mild peripheral contrast enhancement and T1 hyperintensity. Smaller 1.1cm mural nodule (white arrow) with T2 hyperintensity. (a)\u003cstrong\u003e \u003c/strong\u003eMRI\u003cstrong\u003e \u003c/strong\u003eT2 weighted with contrast; (b) MRI T1 fat saturated weighted.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4791357/v1/82527ff60ede2e8f1cd08f78.png"},{"id":63297909,"identity":"88778b9c-353d-4808-a194-4a3351fb870b","added_by":"auto","created_at":"2024-08-26 15:42:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":563708,"visible":true,"origin":"","legend":"\u003cp\u003eImages From Diagnostic Laparoscopy\u003c/p\u003e\n\u003cp\u003eDiagnostic laparoscopy demonstrated (a) right hemi-pelvic multilocular cyst (white arrow) attached to cecum and right abdominal wall separate from adnexal structures; (b) normal right adnexa and uterus (red arrow)\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4791357/v1/31776d09e81a04fbec9f98ab.png"},{"id":63297908,"identity":"d6837ad1-bf7d-489d-b0d2-46cb4ec7b8dd","added_by":"auto","created_at":"2024-08-26 15:42:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":450150,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative Images from Pathology\u003c/p\u003e\n\u003cp\u003eEndometrioid borderline tumor with osseous metaplasia, associated with endometriotic cyst, adherent to colon; (a) tumor adherent to colon; (b) osseous metaplasia of tumor; (c) endometrioid glands with architectural complexity and mild nuclear atypia, consistent with endometrioid borderline tumor; (d) tumor cells were positive for PAX-8 by immunohistochemical staining\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4791357/v1/be04b19eecfdb5e702cfd39b.png"},{"id":67626654,"identity":"5cc7fb31-551f-49b1-99d4-73ba19d097c5","added_by":"auto","created_at":"2024-10-28 08:02:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1845340,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4791357/v1/ab784282-d732-4b07-ba40-30b4cc19b38a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Extra-gonadal Endometrioid Borderline Ovarian Tumor Associated with Endometriotic Cyst","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eBorderline ovarian tumors (BOTs) are uncommon tumors described as intermediate between benign and malignant. The most common subtypes of BOTs are serous and mucinous, while endometrioid, clear cell and Brenner subtypes are rare and account for 3\u0026ndash;4% of all BOTs [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The average age of presentation is 45 years; however, up to one third of patients present at an age less than 40 years rendering fertility an important consideration in treatment. [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. BOTs are often asymptomatic or associated with nonspecific symptoms such as abdominal pain or distention. Diagnostic work up includes transvaginal ultrasound (TVUS), which can aid in distinguishing between benign and malignant masses of the ovary. Further imaging is typically not warranted. When ovarian malignancy is suspected, surgery is indicated [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe gold standard of treatment for BOTs historically is radical surgery, which includes hysterectomy, bilateral salpingo-oophorectomy, staging omentectomy, peritoneal biopsies and cytology. Conservative fertility-sparing treatments where the uterus and at least one ovary is spared have also been described [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Given BOTs present at a younger age than malignant ovarian tumors, there has been effort to balance risk of disease progression and preserving fertility in this population [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. There has only been one case report of extra-gonadal BOT within endometriotic cyst to date, and there is no standardized treatment for this rare pathology [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].We present a case of a solid-cystic right lower quadrant (RLQ) mass adherent to the colon and retroperitoneum managed with en bloc resection and oncologic resection of colon. Final pathology showed a rare histologic subtype of BOT, endometroid borderline ovarian tumor with osseous metaplasia associated with endometriosis.\u003c/p\u003e"},{"header":"CASE PRESENTATION","content":"\u003cp\u003eThe patient is a 32-year-old female with history of polycystic ovary syndrome, type II diabetes mellitus, and morbid obesity (Body Mass Index\u0026thinsp;=\u0026thinsp;43) who presented with abdominal pain and vomiting.\u003c/p\u003e \u003cp\u003eInitial workup included an abdominal computed tomography of the abdomen and pelvis (CT) which revealed a 10 x 10 x 5.3cm heterogeneous mass in the RLQ adjacent to the cecum and extending into right paracolic gutter with moderate ascites. Laboratory work up was notable for elevated cancer antigen-125 (CA-125)\u0026thinsp;~\u0026thinsp;18000 U/mL and normal carcinoembryonic antigen 1.9 \u0026micro;g/mL, and alpha-fetoprotein 2.2 \u0026micro;g/mL. She subsequently underwent diagnostic abdominal paracentesis to evaluate for malignant ascites with return of brown viscous fluid with final pathology showing benign mesothelial cells. Colonoscopy was obtained given the possible colonic involvement and was unremarkable. TVUS showed normal adnexa. Magnetic Resonance Imaging (MRI) of pelvis showed a 13.8 x 11 x 5.8cm RLQ mass with mural nodules (Fig.\u0026nbsp;1).\u003c/p\u003e \u003cp\u003ePatient was then taken to the operating room and underwent diagnostic laparoscopy which showed a large multilocular cystic mass located in RLQ attached to the cecum \u003cb\u003e(Fig.\u0026nbsp;2).\u003c/b\u003e A biopsy was not taken due to risk of cyst rupture. Endometrial curettage showed endometrial hyperplasia without atypia.\u003c/p\u003e \u003cp\u003eA multidisciplinary discussion with members of gynecologic oncology, colorectal surgery, and radiology determined that the work up was concerning for endometriosis with possible malignant transformation. The decision was made to forego tissue biopsy given concern for tumor seeding.\u003c/p\u003e \u003cp\u003eThe patient underwent an exploratory laparotomy for excision of the mass. Intraoperatively, 520mL of chocolate colored cystic fluid was encountered. The cystic RLQ mass was noted to be densely adherent to the cecum and right retroperitoneum. En bloc resection of the mass and right colon was performed following usual oncologic principles. Omentectomy was separately performed. The patient subsequently recovered well post-operatively.\u003c/p\u003e \u003cp\u003eThe final pathology was notable for Stage IIIB endometrioid BOT with osseous metaplasia associated with the endometriotic cyst. The mass was adherent to the cecum and right retroperitoneum but without invasion into these structures (Fig.\u0026nbsp;3\u003cb\u003e).\u003c/b\u003e The BOT measured 2cm and was completely removed within the 17cm cyst. No tumor was identified in 25 mesocolic lymph nodes.\u003c/p\u003e \u003cp\u003eAt three month follow up the patient had resolution of symptoms and interval CT scan did not show any further intraperitoneal disease. The patient was undecided about future childbearing and decided to forego hysterectomy and bilateral salpingo-oophorectomy, and decided to continue with surveillance.\u003c/p\u003e"},{"header":"DISCUSSION AND CONCLUSIONS","content":"\u003cp\u003eBOTs are uncommon neoplasms that present at a mean age of 45 years, 10 years younger than ovarian carcinomas [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Histologically BOTs generally have mild to moderate nuclear atypia, but with no more than 5mm of stromal invasion [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. They are described as intermediate tumors characterized as having low malignant potential. Endometroid BOTs originate from either ovarian epithelial cells or endometriosis, and are synchronous with endometriosis in 46\u0026ndash;63% of cases. Potential for progression to endometrioid carcinoma is low [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Approximately 75% of BOTs present as Federation of Gynecology and Obstetrics (FIGO) Stage I, confined to the ovaries [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. They have an excellent prognosis with an overall 10-year survival of 97% [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDiagnostic work up of BOTs must include TVUS, as it can reliably distinguish between benign and malignant ovarian lesions. The characteristics of BOTs on sonography include uni- or multi-locular cyst, solid-cystic mass, and papillary projections [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. MRI can be used as an adjunct to detect solid components of ovarian lesions; however, it has not been shown to distinguish between BOTs and other malignant tumors [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. MRI was valuable in this case by elucidating nodular components within the cyst, not seen on CT, thereby raising concern for malignancy and guiding approach during surgery. CA-125 is negative in 53% of cases and is not a useful maker for diagnosing BOTs [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In this patient, it is unclear if the CA-125 elevation was due to the BOT and/or endometriosis.\u003c/p\u003e \u003cp\u003eRadical surgery is the gold standard management of BOTs, though several studies describe the safety and efficacy of fertility sparing surgery [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The overall recurrence rate is 13.9% after resection. However, it is significantly higher for fertility sparing conservative surgery versus radical resection (21.3% and 1.8%, respectively) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Despite this, conservative surgery maintains a good prognosis and does not impact overall survival [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Additional risk factors for recurrence include increased CA-125 levels, advanced FIGO stage, younger age, residual tumor, and incomplete staging [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The rate of malignant transformation after recurrence with advanced disease is estimated as 0.5-4% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. As in this case, it is imperative to include endometrial curettage when pursuing conservative surgery for endometroid BOT, as 50% of cases are found concomitant with another disorder of the endometrium such as polyps, hyperplasia, and carcinoma [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe 2024 NCCN guidelines recommend surveillance after surgery without evidence of residual disease to include clinic visits every 3\u0026ndash;12 months for at least 5 years with pelvic exam and CA-125. In addition, the guidelines recommend TVUS for those who undergo fertility sparing surgery. Relapse from BOT can have late recurrences after 10\u0026ndash;20 years supporting potentially longer duration of surveillance [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. There are no standardized treatments or surveillance strategy for primary extra-gonadal manifestations of BOTs. Our patient was staged FIGO IIIB, defined by macroscopic, extra-pelvic, peritoneal metastasis\u0026thinsp;\u0026gt;\u0026thinsp;2cm. She is at a higher risk of recurrence given her young age and higher FIGO stage at diagnosis. However, given her uncertain desire for future childbearing, the shared decision was made to forego completion radical surgery, and she proceeded with surveillance protocol extrapolated from the guidelines for primary ovarian BOTs.\u003c/p\u003e \u003cp\u003eYazawa and colleagues described an extra-gonadal giant endometrial cyst with endometroid BOT. The tumor was connected to the uterus and portions of the left and right uterosacral ligaments. The attachments to these structures were divided and the tumor was removed [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In that case, the patient did not desire future childbearing and bilateral adenectomy, hysterectomy, and partial omentectomy were performed. To the best of our knowledge, this is the first reported case of extra-gonadal endometrioid BOT within an endometriotic cyst that was adherent to the colon. In these rare presentations, it is prudent to hold a multidisciplinary discussion and participate in shared decision making with the patient to determine appropriate diagnosis and management.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eDiagnosis and management of extra-gonadal presentations of BOT can be challenging. TVUS and MRI are necessary to evaluate potential high-risk features. In addition, if fertility preserving surgery is planned, then endometrial curettage is warranted. Preoperative colonoscopy, if there is concern for colon/rectal involvement, is prudent. We advise against transabdominal biopsy to decrease risk of peritoneal tumor seeding. In circumstances where extra-gonadal BOT is adherent to the colon, as in the case presented, we recommend en bloc resection employing standard oncologic principles. The decision to pursue radical surgery, including hysterectomy and bilateral oophorectomy, should be individualized carefully weighing the risk of recurrence with the desire for future childbearing.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eBOT:\u0026nbsp;\u003c/strong\u003eborderline ovarian tumors\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCA-125:\u003c/strong\u003e cancer Antigen-125\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCT:\u003c/strong\u003e computer tomography\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFIGO:\u003c/strong\u003e Federation of Gynecology and Obstetrics\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMRI:\u003c/strong\u003e magnetic resonance imaging\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePCOS\u003c/strong\u003e: polycystic ovary syndrome\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRLQ:\u003c/strong\u003e right lower quadrant\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eT2DM\u003c/strong\u003e: type II diabetes mellitus\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTVUS\u003c/strong\u003e: transvaginal ultrasound\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e Ethical review and approval were waived for this study; single patient case report does not meet the definition of research by The Lundquist Institute.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Written informed consent has been obtained from the patient to publish this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eAll data generated or analyzed during this study are included in this published article\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e No funding to declare.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e Writing \u0026ndash; original draft, K.D; original draft and editing M.S; Pathology slide preparation and review, M.W. and L.M.;\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eWriting - review and editing, H.L. and B.P.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e We thank the patient for agreeing to participate in this informative case report.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHauptmann S, Friedrich K. Ovarian borderline tumors in the 2014 WHO classification: evolving concepts and diagnostic criteria. \u003cem\u003eVirchows Arch\u003c/em\u003e. 2016;470:125-142. doi:10.1007/s00428-016-2040-8 \u003c/li\u003e\n\u003cli\u003eFischerova D, Zikan M, Dundr P, Cibula D. Diagnosis, Treatment, and Follow-Up of Borderline Ovarian Tumors. \u003cem\u003eThe Oncologist\u003c/em\u003e. 2012;17:1515-1553. doi:10.1634/theoncologist.2012-0139\u003c/li\u003e\n\u003cli\u003eVera S, Kipp B. Ultraconservative, Fertility Sparing Treatment of Bilateral Borderline Ovarian Tumors: A Case Report of a 26-Year-Old, 0-Gravida with an Endometrioid Borderline Ovarian Tumor of the Right Ovary and a Sero-Mucinous Borderline Ovarian Tumor of the Left Ovary and a Review of the Literature. \u003cem\u003eInternational Journal of Women\u0026rsquo;s Health\u003c/em\u003e. 2022;12:601-611. doi:10.2147/IJWH.S258478\u003c/li\u003e\n\u003cli\u003eCanlorbe G, Chabbert-Buffet N, Uzan C. Fertility-Sparing Surgery for Ovarian Cancer. \u003cem\u003eJournal of Clinical Medicine\u003c/em\u003e. 2021;10(4235). doi:10.3390/jcm10184235\u003c/li\u003e\n\u003cli\u003eKasaven L, Chawla M, Jones BP, et al. Fertility Sparing Surgey and Borderline Ovarian Tumours. \u003cem\u003eCancers\u003c/em\u003e. 2022;14(1485). doi:10.3390/ cancers14061485\u003c/li\u003e\n\u003cli\u003eSeong SJ, Kim DH, Kim MK, Song T. Controversies in borderline ovarian tumors. \u003cem\u003eJournal of Gynecologic Oncology\u003c/em\u003e. 2015;26(4):343-349. doi:10.3802/jgo.2015.26.4.343 \u003c/li\u003e\n\u003cli\u003eYazawa H, Imaizumi K, Kato A, Takiguchi K. Extragonadal Giant Endometrial Cyst with Endometrioid Borderline Tumor. \u003cem\u003eGynecology and Minimally Invasive Therapy\u003c/em\u003e. 2019;8:179-184. doi:10.4103/GMIT.GMIT_85_18\u003c/li\u003e\n\u003cli\u003eNiu L, Tian H, Cao J. Recurrence characteristics and clinicopathological resuts of borderline ovarian tumors. \u003cem\u003eBMC Women\u0026rsquo;s Health\u003c/em\u003e. 2021;21(134). doi:10.1186/s12905-021-01263-y\u003c/li\u003e\n\u003cli\u003eNakagawa E, Abiko K, Kido, Kitamura S, Yamaguchi, Baba T. Four cases of endometrioid borderline ovarian tumor: case reports and literature review. \u003cem\u003eBJR Case Rep\u003c/em\u003e. 2017;4(201870062). doi:10.1259/bjrcr.20170062\u003c/li\u003e\n\u003cli\u003eMD B. PDQ\u0026reg; Adult Treatment Editorial Board. PDQ Ovarian Low Malignant Potential Tumors Treatment. Published online December 22, 2021. https://www.cancer.gov/types/ovarian/hp/ovarian-low-malignant-treatment-pdq\u003c/li\u003e\n\u003cli\u003eExacoustos C, Romanini ME, Rinaldo D, et al. Preoperative sonographic features of borderline ovarian tumors. \u003cem\u003eUltrasound Obstetrics Gynecology\u003c/em\u003e. 2005;25:50-59. doi:10.1002/uog.1823\u003c/li\u003e\n\u003cli\u003eKim SH. Assessment of solid components of borderline ovarian tumor and stage I carcinoma: added value of combined diffusion- and perfusion-weighted magnetic resonance imaging. \u003cem\u003eYeungnam UNiv J Med\u003c/em\u003e. 2019;36(3):231-240. doi:10.12701/yujm.2019.00234\u003c/li\u003e\n\u003cli\u003eReichenbach J, Schmoeckel E, Mahner S, Trillsch F. Diagnostic workup for endometrioid borderline ovarian tumors (eBOT) requires histopathological evaluation of the uterus. \u003cem\u003eJournal of Ovarian Research\u003c/em\u003e. 2021;14(89). doi:10.1186/s13048-021-00839-4\u003c/li\u003e\n\u003cli\u003eNational Comprehensive Cancer Network. Ovarian Cancer (Version 1.2022). Accessed July 17, 2024. https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"endometrioid borderline ovarian tumor, endometriosis, fertility sparing surgery, ovarian cancer","lastPublishedDoi":"10.21203/rs.3.rs-4791357/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4791357/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eBorderline ovarian tumors (BOT) are rare ovarian tumors that present at a younger age than other ovarian carcinomas. These tumors present a challenge given the complex diagnostic and surgical considerations that need to be navigated for patient care. Notably, fertility sparing among younger woman is preferable surgically but may place patient at a higher rate of recurrence. The purpose of this report is to review the work-up and surgical management of an extra-gonadal endometroid BOT.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e \u003cp\u003ePatient is a 32-year-old female with history of polycystic ovary syndrome, type II diabetes mellitus, and morbid obesity who presented with abdominal pain and vomiting. She underwent extensive work-up including computer tomography (CT), magnetic resonance imaging (MRI), transvaginal ultrasound (TVUS), colonoscopy, and diagnostic laparoscopy. After multidisciplinary discussion, this was managed with oncologic en bloc resection of the lesion and adherent colon. In order to maintain fertility, her ovaries and uterus were spared. She continued with surveillance and at three month follow up had no evidence of disease. The purpose of this report is to review the work-up and surgical management of an extra-gonadal endometroid BOT.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis report reviews the work-up and surgical management of an extra-gonadal endometroid BOT to inform clinicians on management of these rare tumors.\u003c/p\u003e","manuscriptTitle":"Extra-gonadal Endometrioid Borderline Ovarian Tumor Associated with Endometriotic Cyst","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-26 15:42:36","doi":"10.21203/rs.3.rs-4791357/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"38e98580-9a70-49b1-81bd-94c1ed405b86","owner":[],"postedDate":"August 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-28T07:54:07+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-26 15:42:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4791357","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4791357","identity":"rs-4791357","version":["v1"]},"buildId":"ehx78VzkSd0WSzXnipQa-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}