{"paper_id":"2db71ca0-8937-4135-86ef-577387953d47","body_text":"Renal endometriosis mimicking a malignancy– a rare case of Reno-Mullerian fusion? | 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 Research Article Renal endometriosis mimicking a malignancy– a rare case of Reno-Mullerian fusion? Diarmuid O' Connor, Kevin Gerard Byrnes, Kilian Walsh, Gerard O'Sullivan, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-425619/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Endometriosis is a common gynaecological condition characterised by ectopic endometrial tissue growth beyond the uterine cavity. Urinary tract endometriosis represents only 1.2% of all cases, with renal endometriosis accounting for less than 1% of urinary tract involvement. An asymptomatic, 49-year-old, perimenopausal Irish female was found to have an incidental mass at the upper pole of the right kidney on imaging studies. Histological analysis was recommended to outrule a renal malignancy and an open radical nephrectomy was performed following multidisciplinary input. Histological analysis surprisingly revealed the presence of endometriosis and endosalpingiosis, accompanied by a significant smooth muscle component, which mimicked a renal neoplasm. The aetiology of renal endometriosis remains unclear. However, given the lack of a history of endometriosis and the absence of other foci of disease in this patient, together with the smooth muscle predominant phenotype, this may represent a case of reno-mullerian fusion or endometrial displacement during gestational development. Keywords Endometriosis, smooth muscle, reno-mullerian fusion, malignancy Clinical Pharmacology Endometriosis smooth muscle reno-mullerian fusion malignancy Introduction Endometriosis is a common gynaecological condition characterised by ectopic endometrial tissue growth beyond the uterine cavity (1). There are several hypotheses as to how endometriosis originates, including the implantation theory (retrograde menstruation), coelomic metaplasia (metaplastic processes of the peritoneal mesothelium) and even Mullerian duct abnormalities during embryogenesis (2). Endometriosis is the second most common pathology in the female pelvis, affecting 15% of women of reproductive age (3). While most cases occur in the pelvis, extra-pelvic endometriosis can rarely involve sites such as the urinary tract and skin (4). Urinary tract endometriosis represents only 1.2% of all cases and typically occurs in the bladder and ureters, with renal endometriosis accounting for less than 1% of urinary tract involvement (3). Here, we report a rare case of renal endometriosis that mimicked a malignancy and explore its possible aetiology. Case Report An asymptomatic, 49-year-old, perimenopausal Irish female underwent abdominal ultrasound imaging for workup of abnormal liver function tests. Sonographically, a 4.2 cm mass in the upper pole of the right kidney was incidentally identified. Following Computed Tomography imaging (Image 3), which characterised this lesion as a nodular, thick-walled, enhancing mass with possible central necrosis and perinephric fat stranding, the differential diagnoses included a renal malignancy or a haemorrhagic cyst. On Magnetic Resonance Imaging (Image 3), the lesion demonstrated different signal characteristics compared to the renal cortex and significant enhancement following contrast administration, therefore histological analysis was recommended to exclude a neoplasm. Following review of imaging studies at a multidisciplinary team meeting and subsequent patient counselling, the decision was made to proceed directly to an open radical nephrectomy. An open approach was preferred given the adherence of the lesion to the inferior vena cava and diaphragm. The procedure was completed without any intraoperative complications and the patient had a successful postoperative recovery. On gross dissection in the Histopathology laboratory, the resected nephrectomy specimen weighed 516 g and measured 154 x 105 x 55 mm. At the upper pole and adjacent perinephric fat, sectioning revealed an ill-defined, fibrosing mass lesion with variegated golden yellow deposits, primarily involving the perinephric fat with a minimal focus of attachment to the renal parenchyma. Histological analysis surprisingly revealed the presence of endometriosis and endosalpingiosis with an accompanying histiocytic inflammatory reaction and prominent lymphoid aggregates (Image 1), supported by immunohistochemical staining with PAX8, AE1/3, CD10, CK7 and p16. Endometrial glandular tissue was accompanied by endometrial stroma and a significant smooth muscle component (Image 2), as demonstrated by actin immunostain positivity. There was no evidence of atypia or malignancy. On histological analysis, the lesion demonstrated glandular structures accompanied by endometrial stroma with a prominent smooth muscle component, associated with a histiocytic inflammatory reaction and prominent lymphoid aggregates. Although endometrial glands and stroma were identified and a renal cell carcinoma excluded, the key differential diagnoses that remained were an angiomyolipoma (a differential diagnosis encountered in previous similar case reports (5)) or a mixed epithelial/stromal tumour. Renal angiomyolipomas are mesenchymal tumours that often present in the kidneys on a background of underlying Tuberous Sclerosis, a rare autosomal dominant disease (6), of which our patient had no history. Angiomyolipomas contain variable amounts of smooth muscle but also adipose tissue and dystrophic blood vessels; the latter were not present in this case. In addition, they typically stain positively for HMB45 (a melanocytic marker), which was negative. In the consideration of mixed epithelial/stromal tumours, they are known to have similar combinations of smooth muscle and glandular structures as endometriosis, but are typically well circumscribed with prominent cysts and centred on the renal medulla, which was not the case here. Discussion Several case studies have identified the diagnostic difficulty posed by renal endometriosis, particularly in its differentiation from a neoplasm. Conventional imaging modalities are limited in discriminating between endometriosis and a cystic malignancy (7). The majority of previously reported cases were indeed cystic or demonstrated a cystic component. Although a cystic component was suspected radiologically in our case, this was not found at gross inspection, with the inflammation and associated edema possibly accounting for this radiological impression. Clinically, endometriotic lesions with a prominent smooth muscle component may give rise to a significant mass effect, which can mimic a malignancy on imaging studies. Several reports have identified that endometriosis has the potential to mimic a neoplasm, as the disease presents with multiple components in varying quantities, such as smooth muscle (8). Large amounts of fibromuscular tissue are more associated with deeply infiltrating endometriosis (9). The fact that renal endometriosis is exceedingly rare, accounting for 0.1-1% of all cases (3), coupled with the knowledge that lesions with a smooth muscle predominance are atypical and difficult to separate from a neoplastic process, contributed to the diagnostic dilemma in our case. Pre-operative distinction from an angiomyolipoma on core biopsy can be difficult in lesions that have a prominent smooth muscle component, with endometrial glands in endometriosis and entrapped renal tubules in an angiomyolipoma both demonstrating positivity for PAX8. In this situation, CD10 and ER/PR immunohistochemistry, confirming endometrial stroma, is necessary. In addition, smooth muscle predominant angiomyolipomas may be negative for HMB45, especially in a core biopsy. The right kidney was involved in our case, and in previous case reports where laterally is indicated, the majority of the lesions were also right-sided (3, 5, 7, 10). Additionally, the concurrence or history of other foci of endometriosis outside of the kidney is mentioned in only two of the thirteen previous cases. The curious right-sided predilection and the frequent absence of endometriosis elsewhere suggests that renal endometriosis may develop from a residual Mullerian remnant in or adjacent to the kidney, rather than through retrograde menstruation or a metaplastic process. The proximity of the paramesonephric duct to the mesonephros during embryogenesis may account for this phenomenon. During embryonic development, the urogenital ridges eventually differentiate into the kidneys, ureters, reproductive ducts and gonads (11). The same primitive coelomic epithelium also invaginates near the anterior aspect of the mesonephros (foetal kidney) and expands caudally to form the Mullerian ducts, which are the origin of the female reproductive tract (11). The intermediate mesoderm eventually develops into the kidneys and parts of the reproductive system. Another possible hypothesis for the occurrence of endometriosis in this case is ectopic implantation of endometrial tissue, known as Mullerianosis. The embryonic rest theory proposes that cells of Mullerian origin within the peritoneal cavity may be induced to form endometrial tissue, which can result in endometriosis at various locations along the migration pathway of the Mullerian system (12). In one study investigating this theory, 4 out of 36 foetuses examined at post-mortem demonstrated the presence of misplaced endometrium in five different ectopic sites (13). This suggests that one cause of endometriosis may be the dislocation of primitive endometrial tissue outside of the uterine cavity during gestational development, as opposed to retrograde menstruation. Such ectopic misplacement or fusion of tissue at embryogenesis is recognised in other areas of human biology. For example, adrenal cortical rests in the testes and testicular adnexa occur frequently, not just in exclusive cases of congenital adrenal hyperplasia (14). In addition, splenogonadal fusion is a recognised anomaly, which is characterised by congenital fusion between the spleen and testicular tissue, often presenting as a testicular mass. This specific congenital malformation is believed to occur due to the close proximity of the developing gonad and spleen during gestational development, resulting in an abnormal connection between these structures during early embryological development, which facilitates their fusion. Following this fusion, once gonadal descent begins, the attached splenic tissue subsequently follows the gonadal path (15). Misplacement of endometrial tissue or indeed fusion of the developing kidney and Mullerian ducts may account for the rare presence of renal endometriosis in our case. In conclusion, this is a rare case of renal endometriosis, which clinically and radiologically mimicked a neoplastic process due to the prominent smooth muscle component and associated inflammation and edema. Histopathological correlation with multidisciplinary team input and collaboration was required to accurately diagnose this entity and ensure that an appropriate management plan was implemented. The aetiology of renal endometriosis remains unclear with several theories hypothesised (2); however, given the lack of a history of endometriosis and the absence of other foci of disease in this patient, together with the smooth muscle predominant phenotype, this may represent a case of reno-mullerian fusion or endometrial displacement during gestational development. Declarations Funding: The authors did not receive support from any organization for the submitted work. Conflicts of interest/Competing interests (include appropriate disclosures): The authors have no conflicts of interest to declare that are relevant to the content of this article. Ethics approval (include appropriate approvals or waivers): Not applicable. Consent to participate (include appropriate statements): Informed written patient consent was obtained. Consent for publication (include appropriate statements): Informed written consent was obtained from the patient. Availability of data and material (data transparency): Data sharing not applicable to this article as no datasets were generated or analysed during the current study. Code availability (software application or custom code): Not applicable. Compliance with Ethical Standards: Funding: The authors did not receive support from any organization for the submitted work. Conflict of Interest: The authors have no conflicts of interest to declare that are relevant to the content of this article. Contributions: (where each author will need to specify what aspects of the manuscript and/or research they contributed to; ensure that all authors are named individually within the Contribution statement.) Diarmuid O’Connor: Primary author of the manuscript; editor of the manuscript; sourced and formatted all histology images utilised. Kevin Gerard Byrnes: Editor of the manuscript; gained written consent from the patient. Professor Kilian Walsh: Editor of the manuscript. Professor Gerard O’Sullivan: Sourced and vetted all radiology images utilised. Teresa McHale: Supervising consultant of the case report; selected the case as a case of interest; editor of the manuscript; vetted all images utilised. References Giambelluca D, Albano D, Giambelluca E, Bruno A, Panzuto F, Agrusa A, et al. Renal endometriosis mimicking complicated cysts of kidney: report of two cases. Il Giornale di chirurgia. 2017;38(5):250-5. Makiyan Z. Endometriosis origin from primordial germ cells. Organogenesis. 2017;13(3):95-102. Cheng C-H, Kuo H-C, Su B. Endometriosis in a kidney with focal xanthogranulomatous pyelonephritis and a perinephric abscess. BMC Research Notes. 2015;8(1):591. Jubanyik KJ, Comite F. EXTRAPELVIC ENDOMETRIOSIS. Obstetrics and Gynecology Clinics of North America. 1997;24(2):411-40. Jiang Y-H, Kuo H-C, Hsu Y-H. Renal endometriosis mimicking an angiomyolipoma. Urological Science. 2013;24(1):24-6. Lin C, Jin L, Yang Y, Ding Y, Wu X, Ni L, et al. Tuberous sclerosis-associated renal angiomyolipoma: A report of two cases and review of the literature. Mol Clin Oncol. 2017;7(4):706-8. Badri AV, Jennings R, Patel P, Eun DD. Renal Endometriosis: The Case of an Endometrial Implant Mimicking a Renal Mass. Journal of Endourology Case Reports. 2018;4(1):176-8. Anaf V, Simon P, Fayt I, Noel JC. Smooth muscles are frequent components of endometriotic lesions. Human Reproduction. 2000;15(4):767-71. van Kaam KJAF, Schouten JP, Nap AW, Dunselman GAJ, Groothuis PG. Fibromuscular differentiation in deeply infiltrating endometriosis is a reaction of resident fibroblasts to the presence of ectopic endometrium. Human Reproduction. 2008;23(12):2692-700. Yang J, Song RJ, Xu C, Zhang SQ, Zhang W. Renal endometriosis tends to be misdiagnosed as renal tumor: a rare case report. Int Surg. 2015;100(2):376-80. Dubeau L, Teixeira J, Birrer MJ, Ceppi L. Chapter 1 - Origins of Epithelial Ovarian Cancer. Translational Advances in Gynecologic Cancers. Boston: Academic Press; 2017. p. 3-17. Sasson IE, Taylor HS. Stem cells and the pathogenesis of endometriosis. Ann N Y Acad Sci. 2008;1127:106-15. Signorile PG, Baldi F, Bussani R, D'Armiento M, De Falco M, Baldi A. Ectopic endometrium in human foetuses is a common event and sustains the theory of müllerianosis in the pathogenesis of endometriosis, a disease that predisposes to cancer. J Exp Clin Cancer Res. 2009;28(1):49. Marianovsky V, Bogdanova O, Tsvetkov M, Serteva D, Mladenov B. Testicular Adrenal Rest Tumors (TARTS) With Unusual Histological Features in Congenital Adrenal Hyperplasia (CAH). Urol Case Rep. 32015. p. 126-8. Bhutani N, Kajal P, Sangwan V. Splenogonadal fusion. Journal of Pediatric Surgery Case Reports. 2020;59:101514. Supplementary Files Imagesforcasereport.docx Consentformendometriosiscasereport.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Minor revisions 02 Jun, 2021 Reviews received at journal 24 May, 2021 Reviewers invited by journal 13 Apr, 2021 First submitted to journal 07 Jan, 2021 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-425619\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":29849252,\"identity\":\"2f815d64-4df6-40c0-8993-8c3d5fd550d4\",\"order_by\":0,\"name\":\"Diarmuid O' Connor\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYDCCw8icD0DMxk6KFsYZIC3MhLQcQGIz84BJAjr4jjM/+3Sjwk7OXLr52GebX9vk+ZgZGD98zMGtRfIwm/HsnDPJxpZzjiXPzu27bdjGzMAsOXMbbi0GhxmMmXPbDiRuuJEDZPTcZgRqYWPmxauF/TNCi2XPbXsitPAg2cLw43YiQS2Sh3mKmUF+MbiRlszY23A7uY2ZsRmvX/jOH9/MnAMMMYMbyYcZfvy5bTu/vfngh494tKACxjYw2UCsehD4Q4riUTAKRsEoGCkAAODzTeTWo4p1AAAAAElFTkSuQmCC\",\"orcid\":\"https://orcid.org/0000-0002-7826-5434\",\"institution\":\"University Hospital Galway: Galway University Hospitals\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Diarmuid\",\"middleName\":\"O'\",\"lastName\":\"Connor\",\"suffix\":\"\"},{\"id\":29849253,\"identity\":\"333bb851-39d5-4d20-9004-bec0c4c1b5de\",\"order_by\":1,\"name\":\"Kevin Gerard Byrnes\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University Hospital Galway: Galway University Hospitals\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Kevin\",\"middleName\":\"Gerard\",\"lastName\":\"Byrnes\",\"suffix\":\"\"},{\"id\":29849254,\"identity\":\"8de0283a-59e1-4f8b-aa71-85c0d7d881a9\",\"order_by\":2,\"name\":\"Kilian Walsh\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University Hospital Galway: Galway University Hospitals\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Kilian\",\"middleName\":\"\",\"lastName\":\"Walsh\",\"suffix\":\"\"},{\"id\":29849255,\"identity\":\"eedd376a-3055-44dc-9578-5c3c721a08d5\",\"order_by\":3,\"name\":\"Gerard O'Sullivan\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University Hospital Galway: Galway University Hospitals\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Gerard\",\"middleName\":\"\",\"lastName\":\"O'Sullivan\",\"suffix\":\"\"},{\"id\":29849256,\"identity\":\"06bbd3f5-4f44-4c4c-a939-1c229777ffa8\",\"order_by\":4,\"name\":\"Teresa McHale\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University Hospital Galway: Galway University Hospitals\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Teresa\",\"middleName\":\"\",\"lastName\":\"McHale\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2021-04-15 11:28:16\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-425619/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-425619/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":13695962,\"identity\":\"7b9c538d-4c68-41e5-bd8f-ed89139acb73\",\"added_by\":\"auto\",\"created_at\":\"2021-09-17 13:00:44\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":157101,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-425619/v1/1da0e123-f9d0-4f0b-891e-23f31da9e0f3.pdf\"},{\"id\":9847757,\"identity\":\"dc5d77f3-ed3a-45e4-8ace-96c4b351417f\",\"added_by\":\"auto\",\"created_at\":\"2021-06-01 18:40:10\",\"extension\":\"docx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":11388406,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Imagesforcasereport.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-425619/v1/3f0a8e560d49e851380a1e3c.docx\"},{\"id\":9847142,\"identity\":\"7c567029-5bd2-4100-a0aa-14809c2f29ba\",\"added_by\":\"auto\",\"created_at\":\"2021-06-01 18:37:10\",\"extension\":\"pdf\",\"order_by\":2,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":70376,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Consentformendometriosiscasereport.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-425619/v1/5bb7a61364d95f0abf7011b8.pdf\"}],\"financialInterests\":\"\",\"formattedTitle\":\"Renal endometriosis mimicking a malignancy– a rare case of Reno-Mullerian fusion?\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eEndometriosis is a common gynaecological condition characterised by ectopic endometrial tissue growth beyond the uterine cavity (1). There are several hypotheses as to how endometriosis originates, including the implantation theory (retrograde menstruation), coelomic metaplasia (metaplastic processes of the peritoneal mesothelium) and even Mullerian duct abnormalities during embryogenesis (2).\\u003c/p\\u003e\\n\\u003cp\\u003eEndometriosis is the second most common pathology in the female pelvis, affecting 15% of women of reproductive age (3). While most cases occur in the pelvis, extra-pelvic endometriosis can rarely involve sites such as the urinary tract and skin (4). \\u0026nbsp;Urinary tract endometriosis represents only 1.2% of all cases and typically occurs in the bladder and ureters, with renal endometriosis accounting for less than 1% of urinary tract involvement (3). Here, we report a rare case of renal endometriosis that mimicked a malignancy and explore its possible aetiology.\\u003c/p\\u003e\"},{\"header\":\"Case Report\",\"content\":\"\\u003cp\\u003eAn asymptomatic, 49-year-old, perimenopausal Irish female underwent abdominal ultrasound imaging for workup of abnormal liver function tests. Sonographically, a 4.2 cm mass in the upper pole of the right kidney was incidentally identified.\\u003c/p\\u003e\\n\\u003cp\\u003eFollowing Computed Tomography imaging (Image 3), which characterised this lesion as a nodular, thick-walled, enhancing mass with possible central necrosis and perinephric fat stranding, the differential diagnoses included a renal malignancy or a haemorrhagic cyst. On Magnetic Resonance Imaging (Image 3), the lesion demonstrated different signal characteristics compared to the renal cortex and significant enhancement following contrast administration, therefore histological analysis was recommended to exclude a neoplasm.\\u003c/p\\u003e\\n\\u003cp\\u003eFollowing review of imaging studies at a multidisciplinary team meeting and subsequent patient counselling, the decision was made to proceed directly to an open radical nephrectomy. An open approach was preferred given the adherence of the lesion to the inferior vena cava and diaphragm. The procedure was completed without any intraoperative complications and the patient had a successful postoperative recovery.\\u003c/p\\u003e\\n\\u003cp\\u003eOn gross dissection in the Histopathology laboratory, the resected nephrectomy specimen weighed 516 g and measured 154 x 105 x 55 mm. At the upper pole and adjacent perinephric fat, sectioning revealed an ill-defined, fibrosing mass lesion with variegated golden yellow deposits, primarily involving \\u0026nbsp;the perinephric fat with a minimal focus of attachment to the renal parenchyma.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eHistological analysis surprisingly revealed the presence of endometriosis and endosalpingiosis with an accompanying histiocytic inflammatory reaction and prominent lymphoid aggregates (Image 1), supported by immunohistochemical staining with PAX8, AE1/3, CD10, CK7 and p16. Endometrial glandular tissue was accompanied by endometrial stroma and a significant smooth muscle component (Image 2), as demonstrated by actin immunostain positivity. There was no evidence of atypia or malignancy.\\u003c/p\\u003e\\n\\u003cp\\u003eOn histological analysis, the lesion demonstrated glandular structures accompanied by endometrial stroma with a prominent smooth muscle component, associated with a histiocytic inflammatory reaction and prominent lymphoid aggregates. Although endometrial glands and stroma were identified and a renal cell carcinoma excluded, the key differential diagnoses that remained were an angiomyolipoma (a differential diagnosis encountered in previous similar case reports (5)) or a mixed epithelial/stromal tumour. Renal angiomyolipomas are mesenchymal tumours that often present in the kidneys on a background of underlying Tuberous Sclerosis, a rare autosomal dominant disease (6), of which our patient had no history. Angiomyolipomas contain variable amounts of smooth muscle but also adipose tissue and dystrophic blood vessels; the latter were not present in this case. In addition, they typically stain positively for HMB45 (a melanocytic marker), which was negative. In the consideration of mixed epithelial/stromal tumours, they are known to have similar combinations of smooth muscle and glandular structures as endometriosis, but are typically well circumscribed with prominent cysts and centred on the renal medulla, which was not the case here.\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eSeveral case studies have identified the diagnostic difficulty posed by renal endometriosis, particularly in its differentiation from a neoplasm. Conventional imaging modalities are limited in discriminating between endometriosis and a cystic malignancy (7). The majority of previously reported cases were indeed cystic or demonstrated a cystic component. Although a cystic component was suspected radiologically in our case, this was not found at gross inspection, with the inflammation and associated edema possibly accounting for this radiological impression.\\u003c/p\\u003e\\n\\u003cp\\u003eClinically, endometriotic lesions with a prominent smooth muscle component may give rise to a significant mass effect, which can mimic a malignancy on imaging studies. Several reports have identified that endometriosis has the potential to mimic a neoplasm, as the disease presents with multiple components in varying quantities, such as smooth muscle (8). Large amounts of fibromuscular tissue are more associated with deeply infiltrating endometriosis (9). The fact that renal endometriosis is exceedingly rare, accounting for 0.1-1% of all cases (3), coupled with the knowledge that lesions with a smooth muscle predominance are atypical and difficult to separate from a neoplastic process, contributed to the diagnostic dilemma in our case.\\u003c/p\\u003e\\n\\u003cp\\u003ePre-operative distinction from an angiomyolipoma on core biopsy can be difficult in lesions that have a prominent smooth muscle component, with endometrial glands in endometriosis and entrapped renal tubules in an angiomyolipoma both demonstrating positivity for PAX8.\\u0026nbsp; In this situation, CD10 and ER/PR immunohistochemistry, confirming endometrial stroma, is necessary. In addition, smooth muscle predominant angiomyolipomas may be negative for HMB45, especially in a core biopsy.\\u003c/p\\u003e\\n\\u003cp\\u003eThe right kidney was involved in our case, and in previous case reports where laterally is indicated, the majority of the lesions were also right-sided (3, 5, 7, 10). Additionally, the concurrence or history of other foci of endometriosis outside of the kidney is mentioned in only two of the thirteen previous cases. The curious right-sided predilection and the frequent absence of endometriosis elsewhere suggests that renal endometriosis may develop from a residual Mullerian remnant in or adjacent to the kidney, rather than through retrograde menstruation or a metaplastic process. The proximity of the paramesonephric duct to the mesonephros during embryogenesis may account for this phenomenon. During embryonic development, the urogenital ridges eventually differentiate into the kidneys, ureters, reproductive ducts and gonads (11). The same primitive coelomic epithelium also invaginates near the anterior aspect of the mesonephros (foetal kidney) and expands caudally to form the Mullerian ducts, which are the origin of the female reproductive tract (11). The intermediate mesoderm eventually develops into the kidneys and parts of the reproductive system.\\u003c/p\\u003e\\n\\u003cp\\u003eAnother possible hypothesis for the occurrence of endometriosis in this case is ectopic implantation of endometrial tissue, known as Mullerianosis. The embryonic rest theory proposes that cells of Mullerian origin within the peritoneal cavity may be induced to form endometrial tissue, which can result in endometriosis at various locations along the migration pathway of the Mullerian system (12). In one study investigating this theory, 4 out of 36 foetuses examined at post-mortem demonstrated the presence of misplaced endometrium in five different ectopic sites (13). This suggests that one cause of endometriosis may be the dislocation of primitive endometrial tissue outside of the uterine cavity during gestational development, as opposed to retrograde menstruation.\\u003c/p\\u003e\\n\\u003cp\\u003eSuch ectopic misplacement or fusion of tissue at embryogenesis is recognised in other areas of human biology. For example, adrenal cortical rests in the testes and testicular adnexa occur frequently, not just in exclusive cases of congenital adrenal hyperplasia (14). In addition, splenogonadal fusion is a recognised anomaly, which is characterised by congenital fusion between the spleen and testicular tissue, often presenting as a testicular mass. This specific congenital malformation is believed to occur due to the close proximity of the developing gonad and spleen during gestational development, resulting in an abnormal connection between these structures during early embryological development, which facilitates their fusion. Following this fusion, once gonadal descent begins, the attached splenic tissue subsequently follows the gonadal path (15). Misplacement of endometrial tissue or indeed fusion of the developing kidney and Mullerian ducts may account for the rare presence of renal endometriosis in our case.\\u003c/p\\u003e\\n\\u003cp\\u003eIn conclusion, this is a rare case of renal endometriosis, which clinically and radiologically mimicked a neoplastic process due to the prominent smooth muscle component and associated inflammation and edema. Histopathological correlation with multidisciplinary team input and collaboration was required to accurately diagnose this entity and ensure that an appropriate management plan was implemented. The aetiology of renal endometriosis remains unclear with several theories hypothesised (2); however, given the lack of a history of endometriosis and the absence of other foci of disease in this patient, together with the smooth muscle predominant phenotype, this may represent a case of reno-mullerian fusion or endometrial displacement during gestational development.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003eFunding: The authors did not receive support from any organization for the submitted work.\\u003c/p\\u003e\\n\\u003cp\\u003eConflicts of interest/Competing interests\\u0026nbsp;(include appropriate disclosures): The authors have no conflicts of interest to declare that are relevant to the content of this article.\\u003c/p\\u003e\\n\\u003cp\\u003eEthics approval\\u0026nbsp;(include appropriate approvals or waivers): Not applicable.\\u003c/p\\u003e\\n\\u003cp\\u003eConsent to participate\\u0026nbsp;(include appropriate statements): Informed written patient consent was obtained.\\u003c/p\\u003e\\n\\u003cp\\u003eConsent for publication\\u0026nbsp;(include appropriate statements): Informed written consent was obtained from the patient.\\u003c/p\\u003e\\n\\u003cp\\u003eAvailability of data and material\\u0026nbsp;(data transparency): Data sharing not applicable to this article as no datasets were generated or analysed during the current study.\\u003c/p\\u003e\\n\\u003cp\\u003eCode availability\\u0026nbsp;(software application or custom code): Not applicable.\\u003c/p\\u003e\\n\\u003cp\\u003eCompliance with Ethical Standards:\\u003c/p\\u003e\\n\\u003cp\\u003eFunding: The authors did not receive support from any organization for the submitted work.\\u003c/p\\u003e\\n\\u003cp\\u003eConflict of Interest: The authors have no conflicts of interest to declare that are relevant to the content of this article.\\u003c/p\\u003e\\n\\u003cp\\u003eContributions: (where each author will need to specify what aspects of the manuscript and/or research they contributed to; ensure that all authors are named individually within the Contribution statement.)\\u003c/p\\u003e\\n\\u003col\\u003e\\n\\u003cli\\u003eDiarmuid O\\u0026rsquo;Connor: Primary author of the manuscript; editor of the manuscript; sourced and formatted all histology images utilised.\\u003c/li\\u003e\\n\\u003cli\\u003eKevin Gerard Byrnes: Editor of the manuscript; gained written consent from the patient.\\u003c/li\\u003e\\n\\u003cli\\u003eProfessor Kilian Walsh: Editor of the manuscript.\\u003c/li\\u003e\\n\\u003cli\\u003eProfessor Gerard O\\u0026rsquo;Sullivan: Sourced and vetted all radiology images utilised.\\u003c/li\\u003e\\n\\u003cli\\u003eTeresa McHale: Supervising consultant of the case report; selected the case as a case of interest; editor of the manuscript; vetted all images utilised.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eGiambelluca D, Albano D, Giambelluca E, Bruno A, Panzuto F, Agrusa A, et al. Renal endometriosis mimicking complicated cysts of kidney: report of two cases. Il Giornale di chirurgia. 2017;38(5):250-5.\\u003c/li\\u003e\\n\\u003cli\\u003eMakiyan Z. Endometriosis origin from primordial germ cells. Organogenesis. 2017;13(3):95-102.\\u003c/li\\u003e\\n\\u003cli\\u003eCheng C-H, Kuo H-C, Su B. Endometriosis in a kidney with focal xanthogranulomatous pyelonephritis and a perinephric abscess. BMC Research Notes. 2015;8(1):591.\\u003c/li\\u003e\\n\\u003cli\\u003eJubanyik KJ, Comite F. EXTRAPELVIC ENDOMETRIOSIS. Obstetrics and Gynecology Clinics of North America. 1997;24(2):411-40.\\u003c/li\\u003e\\n\\u003cli\\u003eJiang Y-H, Kuo H-C, Hsu Y-H. Renal endometriosis mimicking an angiomyolipoma. Urological Science. 2013;24(1):24-6.\\u003c/li\\u003e\\n\\u003cli\\u003eLin C, Jin L, Yang Y, Ding Y, Wu X, Ni L, et al. Tuberous sclerosis-associated renal angiomyolipoma: A report of two cases and review of the literature. Mol Clin Oncol. 2017;7(4):706-8.\\u003c/li\\u003e\\n\\u003cli\\u003eBadri AV, Jennings R, Patel P, Eun DD. Renal Endometriosis: The Case of an Endometrial Implant Mimicking a Renal Mass. Journal of Endourology Case Reports. 2018;4(1):176-8.\\u003c/li\\u003e\\n\\u003cli\\u003eAnaf V, Simon P, Fayt I, Noel JC. Smooth muscles are frequent components of endometriotic lesions. Human Reproduction. 2000;15(4):767-71.\\u003c/li\\u003e\\n\\u003cli\\u003evan Kaam KJAF, Schouten JP, Nap AW, Dunselman GAJ, Groothuis PG. Fibromuscular differentiation in deeply infiltrating endometriosis is a reaction of resident fibroblasts to the presence of ectopic endometrium. Human Reproduction. 2008;23(12):2692-700.\\u003c/li\\u003e\\n\\u003cli\\u003eYang J, Song RJ, Xu C, Zhang SQ, Zhang W. Renal endometriosis tends to be misdiagnosed as renal tumor: a rare case report. Int Surg. 2015;100(2):376-80.\\u003c/li\\u003e\\n\\u003cli\\u003eDubeau L, Teixeira J, Birrer MJ, Ceppi L. Chapter 1 - Origins of Epithelial Ovarian Cancer. Translational Advances in Gynecologic Cancers. Boston: Academic Press; 2017. p. 3-17.\\u003c/li\\u003e\\n\\u003cli\\u003eSasson IE, Taylor HS. Stem cells and the pathogenesis of endometriosis. Ann N Y Acad Sci. 2008;1127:106-15.\\u003c/li\\u003e\\n\\u003cli\\u003eSignorile PG, Baldi F, Bussani R, D'Armiento M, De Falco M, Baldi A. Ectopic endometrium in human foetuses is a common event and sustains the theory of m\\u0026uuml;llerianosis in the pathogenesis of endometriosis, a disease that predisposes to cancer. J Exp Clin Cancer Res. 2009;28(1):49.\\u003c/li\\u003e\\n\\u003cli\\u003eMarianovsky V, Bogdanova O, Tsvetkov M, Serteva D, Mladenov B. Testicular Adrenal Rest Tumors (TARTS) With Unusual Histological Features in Congenital Adrenal Hyperplasia (CAH). Urol Case Rep. 32015. p. 126-8.\\u003c/li\\u003e\\n\\u003cli\\u003eBhutani N, Kajal P, Sangwan V. Splenogonadal fusion. Journal of Pediatric Surgery Case Reports. 2020;59:101514.\\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\":\"info@researchsquare.com\",\"identity\":\"sn-comprehensive-clinical-medicine\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"sncm\",\"sideBox\":\"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)\",\"snPcode\":\"42399\",\"submissionUrl\":\"https://submission.nature.com/new-submission/42399/3\",\"title\":\"SN Comprehensive Clinical Medicine\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"stoa\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false},\"keywords\":\"Endometriosis, smooth muscle, reno-mullerian fusion, malignancy\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-425619/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-425619/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003eEndometriosis is a common gynaecological condition characterised by ectopic endometrial tissue growth beyond the uterine cavity. Urinary tract endometriosis represents only 1.2% of all cases, with renal endometriosis accounting for less than 1% of urinary tract involvement. An asymptomatic, 49-year-old, perimenopausal Irish female was found to have an incidental mass at the upper pole of the right kidney on imaging studies. Histological analysis was recommended to outrule a renal malignancy and an open radical nephrectomy was performed following multidisciplinary input. Histological analysis surprisingly revealed the presence of endometriosis and endosalpingiosis, accompanied by a significant smooth muscle component, which mimicked a renal neoplasm. The aetiology of renal endometriosis remains unclear. However, given the lack of a history of endometriosis and the absence of other foci of disease in this patient, together with the smooth muscle predominant phenotype, this may represent a case of reno-mullerian fusion or endometrial displacement during gestational development. 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