Catamenial pneumothorax with diaphragmatic perforation and herniation of endometrial tissue: a case report

Catamenial pneumothorax with diaphragmatic perforation and herniation of endometrial tissue: a case report | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Catamenial pneumothorax with diaphragmatic perforation and herniation of endometrial tissue: a case report Xinghua Zhang, Ping Dong, Xiao Luo, Fei Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-10525507/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: Catamenial pneumothorax is a rare form of spontaneous pneumothorax that occurs in reproductive-age women in temporal association with menstruation. It is the most common thoracic manifestation of endometriosis syndrome. Its pathogenesis remains controversial, and direct visualization of herniated endometrial tissue through a diaphragmatic perforation is exceptionally uncommon. Case presentation: A 30-year-old married nulliparous woman of Chinese ethnicity with a history of recurrent dysmenorrhea presented with a one-year history of recurrent right-sided chest tightness and mild dyspnea. She experienced four episodes of right-sided spontaneous pneumothorax over one year. Two episodes required closed pleural drainage, and two resolved spontaneously with oxygen therapy. Serial chest CT scans revealed no bullae or parenchymal abnormalities. Following the fourth episode, we performed a two-port VATS exploration on day 27 of her menstrual cycle. Intraoperatively, we observed pronounced erythema of the right hemidiaphragm but no endometriotic implants on the visceral or parietal pleura. A 6-mm perforation was identified at the central tendon of the right hemidiaphragm, through which endometrial tissue was herniated into the thoracic cavity. The lesion was resected with an endoscopic stapler, and the resection margin was reinforced with a barbed suture (SXPP1A405, Ethicon, USA). Mechanical pleural abrasion was performed, and no apical lung resection was undertaken. Histopathological examination confirmed endometriosis, with immunohistochemistry positive for estrogen receptor (ER), progesterone receptor (PR), and CD10. The patient recovered uneventfully and remained recurrence-free through four menstrual cycles of follow-up. Conclusions: This case provides direct intraoperative evidence of diaphragmatic perforation with herniation of endometrial tissue in catamenial pneumothorax, supported by immunohistochemical confirmation of endometriosis, lending support to the retrograde menstruation theory. Surgical repair of the diaphragmatic defect combined with mechanical pleurodesis appears effective without the need for pulmonary resection, and perimenstrual surgical timing facilitates visualization of characteristic findings. Catamenial pneumothorax Diaphragmatic defect Endometriosis Thoracic endometriosis syndrome Herniation of endometrial tissue Figures Figure 1 Figure 2 Introduction Catamenial pneumothorax is a rare form of spontaneous pneumothorax that occurs in reproductive-age women in temporal association with menstruation. It is the most common thoracic manifestation of endometriosis syndrome. Its pathogenesis remains controversial, and direct visualization of herniated endometrial tissue through a diaphragmatic perforation is exceptionally uncommon. Three main pathogenic hypotheses have been proposed: the retrograde menstruation theory (endometrial tissue refluxes through the fallopian tubes, implants on the diaphragm, and causes diaphragmatic perforation under cyclical hormonal stimulation), the metastatic theory (hematogenous or lymphatic spread), and the physiological theory (elevated prostaglandin F2 levels causing bronchiolar constriction and alveolar rupture) [1]. The diagnostic challenge lies in the low sensitivity of conventional imaging. High-resolution CT often fails to detect subtle diaphragmatic perforations or endometriotic implants, leading to diagnostic delay [3]. Surgical exploration remains the gold standard, with diaphragmatic perforation being the most common intraoperative finding. However, direct visualization of pathognomonic signs—air bubbling or herniation of endometrial tissue—remains rare. Perimenstrual surgery improves diagnostic yield [4]. We report a case in which VATS on day 27 of the menstrual cycle revealed a solitary diaphragmatic perforation with herniation of endometrial tissue, with histopathological and immunohistochemical confirmation of endometriosis, providing compelling evidence for the retrograde menstruation mechanism. Case presentation A 30-year-old married nulliparous woman of Chinese ethnicity with a history of recurrent dysmenorrhea presented with a one-year history of recurrent right-sided chest tightness and mild dyspnea. She experienced four episodes of right-sided spontaneous pneumothorax, all occurring within 48 hours before menstruation. The first and third episodes resolved with oxygen therapy; the second and fourth required closed pleural drainage. The patient had no history of thoracic trauma, prior surgery, or pulmonary disease, and denied smoking, alcohol use, or oral contraceptives. There was no family history of pneumothorax or endometriosis. She strongly desired future childbearing, which became a critical factor in treatment decision-making. Serial high-resolution chest CT scans consistently demonstrated right-sided pneumothorax but revealed no bullae or parenchymal abnormalities. Laboratory findings were unremarkable. Following the fourth episode, a multidisciplinary discussion involving thoracic surgeons and gynecologists resulted in a working diagnosis of catamenial pneumothorax. Elective two-port VATS exploration was scheduled on day 27 of her menstrual cycle. Written informed consent was obtained. Intraoperative findings Under general anesthesia with double-lumen endotracheal intubation for selective left-lung ventilation, the patient was placed in the left lateral decubitus position. A two-port approach was used, with the camera port at the eighth intercostal space in the midaxillary line and the working port at the fifth intercostal space in the anterior axillary line. A 10-mm 30-degree thoracoscope was introduced. The pleural cavity contained no effusion or hemothorax. The visceral pleura of the right upper, middle, and lower lobes appeared normal, with no bullae or endometriotic implants. The parietal pleura also showed no abnormalities. The right hemidiaphragm showed pronounced erythema. At the central tendon, a solitary 6-mm perforation was identified, through which endometrial tissue was herniated into the thoracic cavity and moved with respiratory excursions (Fig. 1 A). After reduction of the herniated tissue, the perforation was clearly visualized (Fig. 1 B). Surgical intervention Surgical intervention After reduction of the herniated endometrial tissue, the diaphragmatic perforation was resected en bloc with a margin of healthy tissue using an endoscopic linear stapler (Fig. 1 C). The resection margin was reinforced with a running barbed suture (SXPP1A405, Ethicon, USA) (Fig. 1 D). Mechanical pleural abrasion was performed to promote pleurodesis. No apical lung resection was undertaken, as no pulmonary pathology was identified. The specimen was sent for histopathological examination. Postoperative recovery was uneventful. Chest drainage was maintained for 48 hours and removed after full lung expansion with no air leak. The patient was discharged on postoperative day 3. Pathological findings Histopathological examination of the resected diaphragmatic specimen revealed endometrial glands and stroma within fibromuscular tissue, consistent with endometriosis. Immunohistochemical staining demonstrated positive expression of estrogen receptor (ER), progesterone receptor (PR), and CD10, further confirming the diagnosis of endometriosis (Fig. 2 ). The presence of hormone receptor positivity supports the hormonal responsiveness of the ectopic endometrial tissue and its role in cyclical diaphragmatic perforation. Postoperative follow-up GnRH-a therapy was recommended but declined by the patient due to her strong desire for future childbearing, as the treatment would temporarily suppress ovulation and preclude pregnancy. Given the radical resection of the diaphragmatic lesion and immunohistochemical confirmation of complete excision, we respected her decision and planned regular follow-up. The patient remained recurrence-free through four menstrual cycles of follow-up, with no further episodes of chest tightness or pneumothorax. Patient perspective The patient expressed that the recurrent episodes of pneumothorax had caused significant anxiety and disruption to her daily life and work over the past year. She was relieved that a definitive diagnosis was finally established through surgery. Regarding the decision to decline GnRH-a therapy, she stated that preserving her fertility was her highest priority, and she was willing to accept the potential risk of recurrence in exchange for the opportunity to conceive. She appreciated that the surgical team respected her fertility goals and felt empowered by the shared decision-making process. She reported satisfactory recovery with minimal postoperative pain and was grateful for the thorough explanation of her condition and treatment options. Discussion This case demonstrates a 6-mm diaphragmatic perforation with herniation of endometrial tissue at the central tendon of the right hemidiaphragm, identified on day 27 of the menstrual cycle, with histopathological and immunohistochemical confirmation of endometriosis (ER+, PR+, CD10+). Similar to the 2021 report by Dong et al. [5], who visualized air bubbling through a diaphragmatic defect, our case provides similarly compelling intraoperative evidence that acquired diaphragmatic perforation is a key pathogenic mechanism. The immunohistochemical confirmation of hormone receptor positivity in our case further strengthens the evidence for the retrograde menstruation theory. The right-sided predominance of catamenial pneumothorax (> 85%) supports the retrograde menstruation theory [1]. Peritoneal fluid preferentially flows along the right paracolic gutter toward the right subphrenic space, creating a microenvironment favorable for implantation of refluxed endometrial cells. Deissner et al. [6] reported that diaphragmatic defects were the most common intraoperative finding, while histopathological confirmation of endometriosis in patients with catamenial pneumothorax remains challenging, emphasizing that diagnosis should be based on clinical presentation, menstrual association, and intraoperative findings rather than pathology alone. Our case, however, achieved definitive pathological and immunohistochemical confirmation, which adds diagnostic certainty. Ahmed et al. [7] described a similar case with negative pathology, highlighting the variability in histopathological yield. Our case exemplifies an integrated diagnostic strategy combining clinical history, imaging, timely VATS exploration, and immunohistochemical confirmation. The spectrum of diaphragmatic involvement in catamenial pneumothorax ranges from isolated microscopic perforations to massive defects with solid organ herniation, as recently demonstrated by Srihattapadungkit et al. [8]. Our case, with a 6-mm isolated perforation and herniation of endometrial tissue, represents the milder end of this spectrum. Several features of our case warrant discussion: First, the absence of endometriotic implants on the visceral and parietal pleura supports the view that catamenial pneumothorax results primarily from diaphragmatic perforation rather than from pleural lesions. This observation is consistent with what some authors have termed "diaphragmatic perforation syndrome." The immunohistochemical confirmation of ER, PR, and CD10 positivity in the resected specimen provides biological plausibility for the cyclical nature of diaphragmatic perforation under hormonal influence. Second, surgery on day 27 (premenstrual phase) enabled observation of diaphragmatic erythema and herniation of endometrial tissue. Bagan et al. [4] demonstrated that perimenstrual VATS optimizes diagnostic yield. Our findings corroborate this recommendation. Third, we performed radical resection of the perforation with a margin of healthy tissue using an endoscopic stapler, followed by margin reinforcement—a strategy consistent with current recommendations to minimize recurrence risk. Simple closure without excision may leave microscopic endometriotic foci, as supported by the presence of hormone receptor-positive endometrial tissue in our specimen. Fourth, we performed mechanical pleurodesis but avoided apical lung resection, as no pulmonary pathology was identified. Previous studies have shown excellent outcomes with isolated diaphragmatic repair in such patients. Fertility consideration The patient's nulliparous status and strong desire for future childbearing fundamentally shaped our treatment strategy. Although GnRH-a therapy is widely used to suppress ovarian function and prevent recurrence, it temporarily inhibits ovulation, precluding pregnancy during the 4–6 month treatment period. Kim et al. [9] demonstrated that diaphragmatic resection was the only significant protective factor against recurrence (HR = 0.16, p = 0.022), while postoperative hormonal therapy did not significantly affect recurrence rates. Thus, our decision to forego GnRH-a therapy was not merely a concession to the patient's fertility preference but was supported by evidence that surgical radicality—rather than endocrine manipulation—is the primary driver of recurrence-free survival. The patient remained recurrence-free through four menstrual cycles, supporting this individualized approach. Diagnostic delay remains a critical issue in TES patients. Pietrzak et al. [10] documented the protracted journey from initial presentation to definitive diagnosis, a pattern that mirrors our patient's four recurrences before surgical confirmation. Both cases underscore the need for heightened clinical awareness and a low threshold for VATS exploration in reproductive-age women with unexplained recurrent right-sided pneumothorax. This case illustrates several key principles for clinical practice: (1) catamenial pneumothorax should be suspected in reproductive-age women with recurrent right-sided pneumothorax and negative CT findings; (2) perimenstrual surgical timing should be prioritized; (3) systematic exploration of the diaphragm, particularly the central tendon, is essential; (4) radical resection with margin reinforcement is the preferred surgical approach; (5) pulmonary resection may be avoided in the absence of identifiable lung pathology; (6) fertility considerations should be incorporated into treatment decisions; and (7) immunohistochemical confirmation (ER, PR, CD10) should be pursued to establish a definitive diagnosis. Limitations: This is a single case report with relatively short follow-up (four menstrual cycles). Long-term recurrence outcomes require further observation. Conclusions This case provides direct intraoperative evidence supporting the retrograde menstruation theory in catamenial pneumothorax. Definitive histopathological and immunohistochemical confirmation (ER+, PR+, CD10+) of endometriosis was obtained. Radical resection of the diaphragmatic lesion with margin reinforcement and mechanical pleurodesis, without pulmonary resection, achieved excellent short-term outcomes and avoided postoperative hormonal therapy in a nulliparous patient with strong fertility desires. We recommend this individualized approach and emphasize the importance of perimenstrual surgical timing and immunohistochemical confirmation. Abbreviations VATS Video-assisted thoracoscopic surgery TES Thoracic endometriosis syndrome GnRH-a Gonadotropin-releasing hormone agonist HRCT High-resolution computed tomography ER Estrogen receptor PR Progesterone receptor. Declarations Ethics approval and consent to participate: This study was approved by the Institutional Review Board of Renmin Hospital of Wuhan University and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from the patient. Consent for publication: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Funding: This case report received no specific grant from any funding agency. Author Contribution XZ and PD conceived and designed the report, performed the surgery, and drafted the manuscript. XL and FW collected data, performed literature review, and revised the manuscript. XZ is the corresponding author and provided overall supervision. All authors read and approved the final manuscript. Acknowledgement The authors thank the patient for granting permission to publish this case report. Availability of data and materials: Not applicable. Competing interests: The authors declare that they have no competing interests. References Joseph J, Sahn SA. Thoracic endometriosis syndrome: new observations from an analysis of 110 cases. Am J Med. 1996;100(2):164 − 70. Alifano M, Trisolini R, Cancellieri A, Regnard JF. Thoracic endometriosis: current knowledge. Ann Thorac Surg. 2006;81(2):761-9. Lojanica MV, Ivanovic S, Milic N, Jovic N, Rakic N, Pilic I, et al. Thoracic endometriosis and catamenial pneumothorax: imaging pitfalls and an integrated diagnostic approach. J Clin Med. 2026;15(12):4517. Bagan P, Le Pimpec Barthes F, Assouad J, Souilamas R, Riquet M. Catamenial pneumothorax: retrospective study of surgical treatment. Ann Thorac Surg. 2003;75(2):378 − 81. Dong B, Wu CL, Sheng YL, Wu B, Ye GC, Liu YF, et al. Catamenial pneumothorax with bubbling up on the diaphragmatic defects: a case report. BMC Womens Health. 2021;21(1):167. Deissner H, Niedermaier B, Griffo R, Wimmer C, Polke M, Trudzinski FC, et al. Catamenial pneumothorax as an underrecognized manifestation of thoracic endometriosis: a 25-year single-center experience. J Clin Med. 2026;15(13):4941. Ahmed A, Shaikh N, Ummunnisa F, Amara UE, Nashrah UE. Catamenial pneumothorax without thoracic endometriosis: a case report from the Gulf Cooperation Council (GCC) region. Cureus. 2025;17(10):e94888. Srihattapadungkit S, Dantis K, Yu J, Laohathai S. Catamenial pneumothorax complicated by massive right diaphragmatic hernia with solid organ herniation. Pneumologie. 2026 Jul 6. doi: 10.1055/a-2882-7406. Online ahead of print. Kim JH, Woo WG, Jung YH, Moon DH, Lee S. Recurrence-free survival after postoperative hormone therapy for catamenial pneumothorax. J Chest Surg. 2024;57(5):484-9. Pietrzak K, Szablewska AW, Pryba B, Gaworska-Krzeminska A. From first breathless episode to final diagnosis and treatment: a case report on thoracic endometriosis syndrome. J Clin Med. 2025;14(17):6240. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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 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-10525507","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":707969727,"identity":"6e4bd750-732f-4be5-af37-65aa4ec1a393","order_by":0,"name":"Xinghua Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIiWNgGAWjYDCCAwxsYNqAvQHMYGwgXgvPAZK1SCQQqYXv9vFnD37uqE3cLvnG7DEPg43shgPMzx7g0yJ5LiHdsPfMcWPL2TnmxjwMacYbDrCZG+DTYnCG4ZgEb9sxOYPbudukeRgOJ244wMMmgV8LY5vk37ZjPAY3z4K0/CdGCzObNG9bjZzBDV6QlgOEtUieYWOTlm07YGxwJv+b5ByDZOOZh9nM8GrhO8P+TPJtW13ihuPH0iTeVNjJ9h1vfoZXCxQchrkTiJmJUA8EdcQpGwWjYBSMgpEJALK7STkq+IgIAAAAAElFTkSuQmCC","orcid":"","institution":"Renmin Hospital of Wuhan University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Xinghua","middleName":"","lastName":"Zhang","suffix":""},{"id":707969728,"identity":"8eff5520-4a0a-4719-8d08-76209dd85845","order_by":1,"name":"Ping Dong","email":"","orcid":"","institution":"Renmin Hospital of Wuhan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"Dong","suffix":""},{"id":707969729,"identity":"9d910021-4ce2-4233-ac3b-cb17f53ccb18","order_by":2,"name":"Xiao Luo","email":"","orcid":"","institution":"Yicheng People's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiao","middleName":"","lastName":"Luo","suffix":""},{"id":707969730,"identity":"0a26aacd-f4f7-4ef0-9cf4-0c767f5475ec","order_by":3,"name":"Fei Wang","email":"","orcid":"","institution":"Yicheng People's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fei","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2026-07-29 13:24:48","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-10525507/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-10525507/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":119201706,"identity":"7583c5c0-9c38-4960-a502-e9673b62469b","added_by":"auto","created_at":"2026-09-04 06:44:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1729638,"visible":true,"origin":"","legend":"\u003cp\u003eIntraoperative findings under VATS. (A) A diaphragmatic perforation at the central tendon of the right hemidiaphragm with herniation of endometrial tissue into the thoracic cavity (black arrow). (B) After reduction of the herniated tissue, the 6-mm diaphragmatic perforation was clearly visualized (black arrowhead). (C) The diaphragmatic lesion was resected using an endoscopic linear stapler. (D) The resected diaphragmatic tissue specimen, revealing the perforation and the ectopic endometrial tissue attached to the peritoneal side of the diaphragm (white arrow).\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-10525507/v1/3a68881b3121ffd2f906a5f8.png"},{"id":119055747,"identity":"c4537fe9-f934-4f61-b331-b4b9fb4bc3e5","added_by":"auto","created_at":"2026-09-02 16:27:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2921512,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathological and immunohistochemical findings of the resected specimen. Hematoxylin and eosin staining （A）showed endometrial glands and stroma within fibromuscular tissue (original magnification ×100). Immunohistochemistry demonstrated positive expression of estrogen receptor (ER)（B）, progesterone receptor (PR)(C), and CD10 （D）(original magnification ×100), confirming the diagnosis of endometriosis.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-10525507/v1/e77f927e13f8f24d38e45b3a.png"},{"id":119204137,"identity":"fbacd3d2-1ac4-426b-a399-a6c90fa76eed","added_by":"auto","created_at":"2026-09-04 06:48:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5628727,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-10525507/v1/0707fb5e-3c4f-4271-9133-14644c6dc397.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Catamenial pneumothorax with diaphragmatic perforation and herniation of endometrial tissue: a case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCatamenial pneumothorax is a rare form of spontaneous pneumothorax that occurs in reproductive-age women in temporal association with menstruation. It is the most common thoracic manifestation of endometriosis syndrome. Its pathogenesis remains controversial, and direct visualization of herniated endometrial tissue through a diaphragmatic perforation is exceptionally uncommon.\u003c/p\u003e \u003cp\u003eThree main pathogenic hypotheses have been proposed: the retrograde menstruation theory (endometrial tissue refluxes through the fallopian tubes, implants on the diaphragm, and causes diaphragmatic perforation under cyclical hormonal stimulation), the metastatic theory (hematogenous or lymphatic spread), and the physiological theory (elevated prostaglandin F2 levels causing bronchiolar constriction and alveolar rupture) [1].\u003c/p\u003e \u003cp\u003eThe diagnostic challenge lies in the low sensitivity of conventional imaging. High-resolution CT often fails to detect subtle diaphragmatic perforations or endometriotic implants, leading to diagnostic delay [3]. Surgical exploration remains the gold standard, with diaphragmatic perforation being the most common intraoperative finding. However, direct visualization of pathognomonic signs\u0026mdash;air bubbling or herniation of endometrial tissue\u0026mdash;remains rare. Perimenstrual surgery improves diagnostic yield [4].\u003c/p\u003e \u003cp\u003eWe report a case in which VATS on day 27 of the menstrual cycle revealed a solitary diaphragmatic perforation with herniation of endometrial tissue, with histopathological and immunohistochemical confirmation of endometriosis, providing compelling evidence for the retrograde menstruation mechanism.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 30-year-old married nulliparous woman of Chinese ethnicity with a history of recurrent dysmenorrhea presented with a one-year history of recurrent right-sided chest tightness and mild dyspnea. She experienced four episodes of right-sided spontaneous pneumothorax, all occurring within 48 hours before menstruation. The first and third episodes resolved with oxygen therapy; the second and fourth required closed pleural drainage. The patient had no history of thoracic trauma, prior surgery, or pulmonary disease, and denied smoking, alcohol use, or oral contraceptives. There was no family history of pneumothorax or endometriosis. She strongly desired future childbearing, which became a critical factor in treatment decision-making.\u003c/p\u003e \u003cp\u003eSerial high-resolution chest CT scans consistently demonstrated right-sided pneumothorax but revealed no bullae or parenchymal abnormalities. Laboratory findings were unremarkable.\u003c/p\u003e \u003cp\u003eFollowing the fourth episode, a multidisciplinary discussion involving thoracic surgeons and gynecologists resulted in a working diagnosis of catamenial pneumothorax. Elective two-port VATS exploration was scheduled on day 27 of her menstrual cycle. Written informed consent was obtained.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eIntraoperative findings\u003c/h2\u003e \u003cp\u003eUnder general anesthesia with double-lumen endotracheal intubation for selective left-lung ventilation, the patient was placed in the left lateral decubitus position. A two-port approach was used, with the camera port at the eighth intercostal space in the midaxillary line and the working port at the fifth intercostal space in the anterior axillary line. A 10-mm 30-degree thoracoscope was introduced.\u003c/p\u003e \u003cp\u003eThe pleural cavity contained no effusion or hemothorax. The visceral pleura of the right upper, middle, and lower lobes appeared normal, with no bullae or endometriotic implants. The parietal pleura also showed no abnormalities. The right hemidiaphragm showed pronounced erythema. At the central tendon, a solitary 6-mm perforation was identified, through which endometrial tissue was herniated into the thoracic cavity and moved with respiratory excursions (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). After reduction of the herniated tissue, the perforation was clearly visualized (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSurgical intervention\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eSurgical intervention\u003c/div\u003e \u003cp\u003eAfter reduction of the herniated endometrial tissue, the diaphragmatic perforation was resected en bloc with a margin of healthy tissue using an endoscopic linear stapler (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). The resection margin was reinforced with a running barbed suture (SXPP1A405, Ethicon, USA) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD). Mechanical pleural abrasion was performed to promote pleurodesis. No apical lung resection was undertaken, as no pulmonary pathology was identified. The specimen was sent for histopathological examination.\u003c/p\u003e \u003cp\u003ePostoperative recovery was uneventful. Chest drainage was maintained for 48 hours and removed after full lung expansion with no air leak. The patient was discharged on postoperative day 3.\u003c/p\u003e\n\u003ch3\u003ePathological findings\u003c/h3\u003e\n\u003cp\u003eHistopathological examination of the resected diaphragmatic specimen revealed endometrial glands and stroma within fibromuscular tissue, consistent with endometriosis. Immunohistochemical staining demonstrated positive expression of estrogen receptor (ER), progesterone receptor (PR), and CD10, further confirming the diagnosis of endometriosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The presence of hormone receptor positivity supports the hormonal responsiveness of the ectopic endometrial tissue and its role in cyclical diaphragmatic perforation.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003ePostoperative follow-up\u003c/h3\u003e\n\u003cp\u003eGnRH-a therapy was recommended but declined by the patient due to her strong desire for future childbearing, as the treatment would temporarily suppress ovulation and preclude pregnancy. Given the radical resection of the diaphragmatic lesion and immunohistochemical confirmation of complete excision, we respected her decision and planned regular follow-up. The patient remained recurrence-free through four menstrual cycles of follow-up, with no further episodes of chest tightness or pneumothorax.\u003c/p\u003e\n\u003ch3\u003ePatient perspective\u003c/h3\u003e\n\u003cp\u003eThe patient expressed that the recurrent episodes of pneumothorax had caused significant anxiety and disruption to her daily life and work over the past year. She was relieved that a definitive diagnosis was finally established through surgery. Regarding the decision to decline GnRH-a therapy, she stated that preserving her fertility was her highest priority, and she was willing to accept the potential risk of recurrence in exchange for the opportunity to conceive. She appreciated that the surgical team respected her fertility goals and felt empowered by the shared decision-making process. She reported satisfactory recovery with minimal postoperative pain and was grateful for the thorough explanation of her condition and treatment options.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case demonstrates a 6-mm diaphragmatic perforation with herniation of endometrial tissue at the central tendon of the right hemidiaphragm, identified on day 27 of the menstrual cycle, with histopathological and immunohistochemical confirmation of endometriosis (ER+, PR+, CD10+). Similar to the 2021 report by Dong et al. [5], who visualized air bubbling through a diaphragmatic defect, our case provides similarly compelling intraoperative evidence that acquired diaphragmatic perforation is a key pathogenic mechanism. The immunohistochemical confirmation of hormone receptor positivity in our case further strengthens the evidence for the retrograde menstruation theory.\u003c/p\u003e \u003cp\u003eThe right-sided predominance of catamenial pneumothorax (\u0026gt;\u0026thinsp;85%) supports the retrograde menstruation theory [1]. Peritoneal fluid preferentially flows along the right paracolic gutter toward the right subphrenic space, creating a microenvironment favorable for implantation of refluxed endometrial cells. Deissner et al. [6] reported that diaphragmatic defects were the most common intraoperative finding, while histopathological confirmation of endometriosis in patients with catamenial pneumothorax remains challenging, emphasizing that diagnosis should be based on clinical presentation, menstrual association, and intraoperative findings rather than pathology alone. Our case, however, achieved definitive pathological and immunohistochemical confirmation, which adds diagnostic certainty. Ahmed et al. [7] described a similar case with negative pathology, highlighting the variability in histopathological yield. Our case exemplifies an integrated diagnostic strategy combining clinical history, imaging, timely VATS exploration, and immunohistochemical confirmation.\u003c/p\u003e \u003cp\u003eThe spectrum of diaphragmatic involvement in catamenial pneumothorax ranges from isolated microscopic perforations to massive defects with solid organ herniation, as recently demonstrated by Srihattapadungkit et al. [8]. Our case, with a 6-mm isolated perforation and herniation of endometrial tissue, represents the milder end of this spectrum.\u003c/p\u003e \u003cp\u003eSeveral features of our case warrant discussion:\u003c/p\u003e \u003cp\u003eFirst, the absence of endometriotic implants on the visceral and parietal pleura supports the view that catamenial pneumothorax results primarily from diaphragmatic perforation rather than from pleural lesions. This observation is consistent with what some authors have termed \"diaphragmatic perforation syndrome.\" The immunohistochemical confirmation of ER, PR, and CD10 positivity in the resected specimen provides biological plausibility for the cyclical nature of diaphragmatic perforation under hormonal influence.\u003c/p\u003e \u003cp\u003eSecond, surgery on day 27 (premenstrual phase) enabled observation of diaphragmatic erythema and herniation of endometrial tissue. Bagan et al. [4] demonstrated that perimenstrual VATS optimizes diagnostic yield. Our findings corroborate this recommendation.\u003c/p\u003e \u003cp\u003eThird, we performed radical resection of the perforation with a margin of healthy tissue using an endoscopic stapler, followed by margin reinforcement\u0026mdash;a strategy consistent with current recommendations to minimize recurrence risk. Simple closure without excision may leave microscopic endometriotic foci, as supported by the presence of hormone receptor-positive endometrial tissue in our specimen.\u003c/p\u003e \u003cp\u003eFourth, we performed mechanical pleurodesis but avoided apical lung resection, as no pulmonary pathology was identified. Previous studies have shown excellent outcomes with isolated diaphragmatic repair in such patients.\u003c/p\u003e \u003cp\u003eFertility consideration\u003c/p\u003e \u003cp\u003eThe patient's nulliparous status and strong desire for future childbearing fundamentally shaped our treatment strategy. Although GnRH-a therapy is widely used to suppress ovarian function and prevent recurrence, it temporarily inhibits ovulation, precluding pregnancy during the 4\u0026ndash;6 month treatment period. Kim et al. [9] demonstrated that diaphragmatic resection was the only significant protective factor against recurrence (HR\u0026thinsp;=\u0026thinsp;0.16, p\u0026thinsp;=\u0026thinsp;0.022), while postoperative hormonal therapy did not significantly affect recurrence rates. Thus, our decision to forego GnRH-a therapy was not merely a concession to the patient's fertility preference but was supported by evidence that surgical radicality\u0026mdash;rather than endocrine manipulation\u0026mdash;is the primary driver of recurrence-free survival. The patient remained recurrence-free through four menstrual cycles, supporting this individualized approach.\u003c/p\u003e \u003cp\u003eDiagnostic delay remains a critical issue in TES patients. Pietrzak et al. [10] documented the protracted journey from initial presentation to definitive diagnosis, a pattern that mirrors our patient's four recurrences before surgical confirmation. Both cases underscore the need for heightened clinical awareness and a low threshold for VATS exploration in reproductive-age women with unexplained recurrent right-sided pneumothorax.\u003c/p\u003e \u003cp\u003eThis case illustrates several key principles for clinical practice: (1) catamenial pneumothorax should be suspected in reproductive-age women with recurrent right-sided pneumothorax and negative CT findings; (2) perimenstrual surgical timing should be prioritized; (3) systematic exploration of the diaphragm, particularly the central tendon, is essential; (4) radical resection with margin reinforcement is the preferred surgical approach; (5) pulmonary resection may be avoided in the absence of identifiable lung pathology; (6) fertility considerations should be incorporated into treatment decisions; and (7) immunohistochemical confirmation (ER, PR, CD10) should be pursued to establish a definitive diagnosis.\u003c/p\u003e \u003cp\u003eLimitations: This is a single case report with relatively short follow-up (four menstrual cycles). Long-term recurrence outcomes require further observation.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis case provides direct intraoperative evidence supporting the retrograde menstruation theory in catamenial pneumothorax. Definitive histopathological and immunohistochemical confirmation (ER+, PR+, CD10+) of endometriosis was obtained. Radical resection of the diaphragmatic lesion with margin reinforcement and mechanical pleurodesis, without pulmonary resection, achieved excellent short-term outcomes and avoided postoperative hormonal therapy in a nulliparous patient with strong fertility desires. We recommend this individualized approach and emphasize the importance of perimenstrual surgical timing and immunohistochemical confirmation.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVATS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVideo-assisted thoracoscopic surgery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTES\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThoracic endometriosis syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGnRH-a\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGonadotropin-releasing hormone agonist\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHRCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHigh-resolution computed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eER\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEstrogen receptor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProgesterone receptor.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e \u003cp\u003eThis study was approved by the Institutional Review Board of Renmin Hospital of Wuhan University and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from the patient.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication:\u003c/strong\u003e \u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis case report received no specific grant from any funding agency.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eXZ and PD conceived and designed the report, performed the surgery, and drafted the manuscript. XL and FW collected data, performed literature review, and revised the manuscript. XZ is the corresponding author and provided overall supervision. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors thank the patient for granting permission to publish this case report.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials:\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003cp\u003eCompeting interests: The authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJoseph J, Sahn SA. Thoracic endometriosis syndrome: new observations from an analysis of 110 cases. Am J Med. 1996;100(2):164\u0026thinsp;\u0026minus;\u0026thinsp;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlifano M, Trisolini R, Cancellieri A, Regnard JF. Thoracic endometriosis: current knowledge. Ann Thorac Surg. 2006;81(2):761-9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLojanica MV, Ivanovic S, Milic N, Jovic N, Rakic N, Pilic I, et al. Thoracic endometriosis and catamenial pneumothorax: imaging pitfalls and an integrated diagnostic approach. J Clin Med. 2026;15(12):4517.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBagan P, Le Pimpec Barthes F, Assouad J, Souilamas R, Riquet M. Catamenial pneumothorax: retrospective study of surgical treatment. Ann Thorac Surg. 2003;75(2):378\u0026thinsp;\u0026minus;\u0026thinsp;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDong B, Wu CL, Sheng YL, Wu B, Ye GC, Liu YF, et al. Catamenial pneumothorax with bubbling up on the diaphragmatic defects: a case report. BMC Womens Health. 2021;21(1):167.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeissner H, Niedermaier B, Griffo R, Wimmer C, Polke M, Trudzinski FC, et al. Catamenial pneumothorax as an underrecognized manifestation of thoracic endometriosis: a 25-year single-center experience. J Clin Med. 2026;15(13):4941.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhmed A, Shaikh N, Ummunnisa F, Amara UE, Nashrah UE. Catamenial pneumothorax without thoracic endometriosis: a case report from the Gulf Cooperation Council (GCC) region. Cureus. 2025;17(10):e94888.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSrihattapadungkit S, Dantis K, Yu J, Laohathai S. Catamenial pneumothorax complicated by massive right diaphragmatic hernia with solid organ herniation. Pneumologie. 2026 Jul 6. doi: 10.1055/a-2882-7406. Online ahead of print.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim JH, Woo WG, Jung YH, Moon DH, Lee S. Recurrence-free survival after postoperative hormone therapy for catamenial pneumothorax. J Chest Surg. 2024;57(5):484-9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePietrzak K, Szablewska AW, Pryba B, Gaworska-Krzeminska A. From first breathless episode to final diagnosis and treatment: a case report on thoracic endometriosis syndrome. J Clin Med. 2025;14(17):6240.\u003c/span\u003e\u003c/li\u003e\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":"Catamenial pneumothorax, Diaphragmatic defect, Endometriosis, Thoracic endometriosis syndrome, Herniation of endometrial tissue","lastPublishedDoi":"10.21203/rs.3.rs-10525507/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-10525507/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Catamenial pneumothorax is a rare form of spontaneous pneumothorax that occurs in reproductive-age women in temporal association with menstruation. It is the most common thoracic manifestation of endometriosis syndrome. Its pathogenesis remains controversial, and direct visualization of herniated endometrial tissue through a diaphragmatic perforation is exceptionally uncommon.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e A 30-year-old married nulliparous woman of Chinese ethnicity with a history of recurrent dysmenorrhea presented with a one-year history of recurrent right-sided chest tightness and mild dyspnea. She experienced four episodes of right-sided spontaneous pneumothorax over one year. Two episodes required closed pleural drainage, and two resolved spontaneously with oxygen therapy. Serial chest CT scans revealed no bullae or parenchymal abnormalities. Following the fourth episode, we performed a two-port VATS exploration on day 27 of her menstrual cycle. Intraoperatively, we observed pronounced erythema of the right hemidiaphragm but no endometriotic implants on the visceral or parietal pleura. A 6-mm perforation was identified at the central tendon of the right hemidiaphragm, through which endometrial tissue was herniated into the thoracic cavity. The lesion was resected with an endoscopic stapler, and the resection margin was reinforced with a barbed suture (SXPP1A405, Ethicon, USA). Mechanical pleural abrasion was performed, and no apical lung resection was undertaken. Histopathological examination confirmed endometriosis, with immunohistochemistry positive for estrogen receptor (ER), progesterone receptor (PR), and CD10. The patient recovered uneventfully and remained recurrence-free through four menstrual cycles of follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eThis case provides direct intraoperative evidence of diaphragmatic perforation with herniation of endometrial tissue in catamenial pneumothorax, supported by immunohistochemical confirmation of endometriosis, lending support to the retrograde menstruation theory. Surgical repair of the diaphragmatic defect combined with mechanical pleurodesis appears effective without the need for pulmonary resection, and perimenstrual surgical timing facilitates visualization of characteristic findings.\u003c/p\u003e","manuscriptTitle":"Catamenial pneumothorax with diaphragmatic perforation and herniation of endometrial tissue: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-09-02 16:27:12","doi":"10.21203/rs.3.rs-10525507/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":"51409714-61c4-46f3-bb2a-3bae50b836a3","owner":[],"postedDate":"September 2nd, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-09-02T15:48:46+00:00","index":36,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-09-02T10:28:20+00:00","index":35,"fulltext":""},{"type":"reviewerAgreed","content":"73728775511725674150711044242297065453","date":"2026-08-31T13:25:21+00:00","index":34,"fulltext":""},{"type":"reviewerAgreed","content":"105834629682239277721157049491810485250","date":"2026-08-27T08:55:34+00:00","index":31,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-08-27T07:28:32+00:00","index":30,"fulltext":""},{"type":"reviewerAgreed","content":"61678827635321875596656206772853199140","date":"2026-08-27T07:05:56+00:00","index":29,"fulltext":""},{"type":"reviewerAgreed","content":"126235867603666848398942671527002125963","date":"2026-08-26T20:20:24+00:00","index":28,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-08-26T11:30:05+00:00","index":27,"fulltext":""},{"type":"reviewerAgreed","content":"157502940003397110909490786038641624607","date":"2026-08-26T11:21:14+00:00","index":26,"fulltext":""},{"type":"reviewersInvited","content":"17","date":"2026-08-26T09:14:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-08-26T08:49:10+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-09-02T16:27:12+00:00","versionOfRecord":[],"versionCreatedAt":"2026-09-02 16:27:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-10525507","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-10525507","identity":"rs-10525507","version":["v1"]},"buildId":"CiT4i_kKBbxQbnFL0ufpk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}