Familial Pulmonary Endometriosis in Three Sisters: A Case Series and Review of the Literature

Familial Pulmonary Endometriosis in Three Sisters: A Case Series and Review of the Literature | 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 Familial Pulmonary Endometriosis in Three Sisters: A Case Series and Review of the Literature Katayoon Berjis, Zahra Kuroshli, Fatemeh Babamohammadi, Nahid Maleki This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-10342209/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background: Catamenial pneumothorax (CP) is the most common manifestation of thoracic endometriosis syndrome and is characterized by recurrent spontaneous pneumothorax occurring in temporal association with menstruation. Although familial aggregation is well recognized in pelvic endometriosis, familial occurrence of catamenial pneumothorax remains exceptionally rare in the literature. Thoracic endometriosis often lacks histopathological confirmation, making diagnosis dependent on clinical, radiological, and surgical findings. Case Presentation We report three sisters who developed recurrent right-sided spontaneous pneumothorax associated with menstruation. The eldest sister experienced recurrent menstrual-related pneumothorax and was managed surgically. The second sister underwent video-assisted thoracoscopic surgery (VATS), wedge resection, pleural biopsy, and pleurodesis. Histopathological examination revealed severe pulmonary hemorrhage, hemosiderin-laden macrophages, bleb formation, and reactive eosinophilic pleuritis without definitive evidence of thoracic endometriosis. She had documented pelvic endometriosis and subsequently underwent right oophorectomy followed by total abdominal hysterectomy because of recurrent disease. The youngest sister also presented with recurrent right-sided catamenial pneumothorax and underwent VATS with wedge resection and pleurodesis. Histopathology demonstrated emphysematous lung tissue, chronic pleural inflammation with eosinophilic infiltration, and bullous changes without definite endometrial tissue. Pelvic ultrasonography revealed findings suggestive of adenomyosis and pelvic adhesions. No parental history of pneumothorax or endometriosis was identified. Conclusions This case series describes an unusual familial clustering of catamenial pneumothorax affecting three sisters. Despite the absence of histologically confirmed thoracic endometriosis in two surgically treated patients, the cyclical relationship with menstruation, right-sided predominance, operative findings, and concomitant pelvic endometriosis strongly supported the diagnosis. These cases highlight the diagnostic challenges of thoracic endometriosis syndrome and suggest a possible familial or genetic predisposition. Recognition of familial clustering may facilitate earlier diagnosis and multidisciplinary management of affected women. Catamenial pneumothorax Thoracic endometriosis Familial clustering Endometriosis Case series Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Endometriosis is a benign gynecological condition in which ectopic, endometrium-like cells are located outside of the uterine cavity [1] and is associated with infertility, subfertility, dysmenorrhea, Pain during intercourse (dyspareunia), menorrhagia, and chronic pelvic pain( 1 ). Other presentations associated with endometriosis include irritable bowel syndrome, painful bladder syndrome, abdominal pain, adnexal masses, migraine, fatigue and loss of quality of life ( 2 – 4 ). The most commonly accepted theory for the pathogenesis of endometriosis is retrograde menstruation where endometrial cells reach the abdomino-pelvic cavity via the fallopian tubes during menses, and depending on local and host immunologic factors, the ectopic endometrial cells go through neo angiogenesis, survive and implant ( 3 ). This theory is supported by the finding that the most frequently encountered sites of endometrial implants are located within the dependent aspects of the pelvis, such as the pouch of Douglas, retrocervix, uterosacral ligaments, rectosigmoid, and bladder ( 5 , 6 ). Deep endometriosis is differentiated from peritoneal (or superficial) and ovarian endometriosis types by the presence of endometriotic nodules larger than 5 mm ( 7 ). It has been found in extra-pelvic sites, such as the upper abdominal visceral organs, abdominal wall, diaphragm and pleura, perhaps as a result of peritoneal dissemination of endometrial implants and metaplasia ( 5 ). It also has been reported in even more distant sites, such as the central nervous system (brain, vertebral nerves) and the peripheral nervous system, perhaps by lymphatic or hematologic spread ( 8 , 9 ). Thoracic endometriosis is a form of extra-pelvic endometriosis that can be classified as either pleural or pulmonary. Pulmonary endometriosis is an extremely rare disease with complex causes and pathogeneses that remain unclear( 10 ). There is no reliable serum maker for this disease, and imaging still leaves much of it undiagnosed ( 11 , 12 ). There is no definite cure for endometriosis, and so the main focus of management is to control the associated pain, which is achieved by hormonal suppression of the disease or surgical excision( 13 ). When extensive deep endometriosis involving distant sites and/or critical organs are encountered, the diagnosis and management of non-pelvic endometriosis can be extremely challenging and may result in delay in treatment. The main objective of this paper is to describe three cases of pulmonary endometriosis manifestation associated with the menstrual cycle. These cases are being reported to alert clinicians to the fact that pulmonary endometriosis can be readily misdiagnosed as a systemic disease because of its clinical manifestations and imaging signs. These cases provide a reference for diagnosis and treatment of pulmonary endometriosis. Case Presentation A remarkable familial clustering was observed in this family. Three biological sisters, born in 1970, 1976, and 1983, developed recurrent right-sided spontaneous/catamenial pneumothorax and were subsequently diagnosed with pelvic endometriosis. The parents had no known history of pneumothorax, thoracic endometriosis, or pelvic endometriosis. Histopathological evaluation was available for the two younger sisters, whereas original medical records for the eldest sister were unavailable. The pedigree of the family is shown in Fig. 1 . Filled symbols indicate individuals affected by recurrent catamenial/spontaneous pneumothorax. II-2 and II-3 had histopathologic evaluation. All affected individuals also had pelvic endometriosis. Parents had no known history of pneumothorax or endometriosis. Three biological sisters were diagnosed with thoracic endometriosis presenting with recurrent right-sided thoracic manifestations. The clinical features, management, and outcomes of each patient are described below. Case 1 A 42-year-old married housewife presented with recurrent right-sided pneumothorax accompanied by chest pain. Initial laboratory investigations revealed a hemoglobin level of 13.6 g/dL and serum creatinine of 1.0 mg/dL. Due to recurrent right pneumothorax, she underwent bronchoscopy and right video-assisted thoracoscopic surgery (VATS) on July 17, 2022. Surgical management included wedge resection of the right apical lung, parietal pleurectomy, and complete pleural scarification. The postoperative course was uneventful, and the patient was discharged after eight days in good general condition. Despite surgical treatment, recurrence occurred several months later. She was readmitted with recurrent right-sided catamenial pneumothorax in November 2022, requiring chest tube insertion. Subsequently, on December 15, 2022, she underwent repeat surgery consisting of bronchoscopy, right posterolateral thoracotomy, pneumolysis, complete parietal pleurectomy, resection of two diaphragmatic lesions with two-layer diaphragmatic repair, and wedge resection of the right lower lobe including a suspicious pulmonary nodule. Recovery was satisfactory, and the patient was discharged in stable condition with acceptable postoperative chest radiography findings. Detailed medical records and histopathologic specimens were unavailable for retrospective review. Case 2 was a 26-year-old woman with recurrent right-sided catamenial pneumothorax. Pelvic evaluation revealed mild pelvic endometriosis, diffuse adenomyosis, uterosacral ligament thickening, and a 12-mm endometrial polyp. She underwent VATS and wedge resection. Histopathology demonstrated severe fresh hemorrhage, hemosiderin-laden macrophages, bleb formation, and reactive eosinophilic pleuritis, without definitive evidence of thoracic endometriosis. Despite postoperative hormonal therapy with a GnRH agonist, recurrence occurred within several months, necessitating right lobectomy. Owing to persistent cyclic symptoms and concern for recurrence, total abdominal hysterectomy was subsequently performed. ( Fig. 2 , 3 ). Case 3 The youngest sister, born in 1983, presented with recurrent right-sided thoracic manifestations, including two episodes of pulmonary hemorrhage involving the right lower lobe. Recurrent right-sided pneumothorax required tube thoracostomy on two separate occasions. Imaging studies demonstrated right pneumothorax associated with focal pleural thickening and subcutaneous emphysema. Because of persistent symptoms, she underwent right-sided pulmonary surgery at Masih Daneshvari Hospital, including wedge resection of the affected lung tissue and resection of bullous lesions. Histopathological examination revealed emphysematous lung tissue with mild patchy interstitial thickening, chronic pleural inflammation containing scattered eosinophils, and edematous multicystic bullous tissue with eosinophilic inflammatory infiltrates. No definitive endometrial glands or stroma were identified in the examined specimens. Postoperatively, treatment with leuprolide acetate was initiated approximately two weeks after surgery and continued for two months. However, cyclical thoracic pain persisted despite hormonal therapy. Owing to persistent symptoms and concern regarding disease recurrence, she subsequently underwent total abdominal hysterectomy with preservation of a portion of one ovary. At follow-up, the patient remained clinically stable without major postoperative complications. Chest radiography at presentation demonstrated right-sided pneumothorax (Fig. 4 ). Discussion An important finding in the present report is the familial clustering of disease. As illustrated in the pedigree (Fig. 1 ), three sisters were affected by recurrent catamenial pneumothorax, whereas no known history of pneumothorax or thoracic endometriosis was reported in either parent. This pattern raises the possibility of a familial predisposition and provides a unique opportunity to explore the relationship between hereditary factors and thoracic endometriosis syndrome. Catamenial pneumothorax (CP) is the most common clinical manifestation of thoracic endometriosis syndrome (TES), a rare disorder characterized by the presence of ectopic endometrial tissue within thoracic structures. CP is classically defined as recurrent spontaneous pneumothorax occurring within 72 hours before or after the onset of menstruation and demonstrates a marked right-sided predominance( 14 ). The present report describes an unusual familial clustering of catamenial pneumothorax in three sisters. Although familial aggregation is well recognized in pelvic endometriosis, reports of thoracic endometriosis syndrome or catamenial pneumothorax affecting multiple members of the same family are exceedingly rare. The occurrence of recurrent right-sided pneumothorax in all three sisters, together with evidence of pelvic endometriosis or adenomyosis in two of them, suggests the possibility of a shared genetic or familial susceptibility( 15 , 16 ). Several mechanisms have been proposed to explain the pathogenesis of CP, including transdiaphragmatic migration of endometrial tissue through diaphragmatic fenestrations, coelomic metaplasia, lymphatic or hematogenous dissemination, and hormonally induced pleural or alveolar fragility. No single theory adequately explains all clinical presentations, and CP is likely a heterogeneous disorder with multifactorial pathogenesis( 17 ). An important observation in our series is the discrepancy between clinical suspicion and histopathological confirmation. In the second sister, pathological examination demonstrated severe pulmonary hemorrhage, hemosiderin-laden macrophages, bleb formation, and reactive eosinophilic pleuritis, while no definite evidence of thoracic endometriosis was identified. Similarly, the third sister showed emphysematous lung changes, chronic pleural inflammation with eosinophilic infiltration, and bullous lesions without histologically proven endometriosis. This finding is consistent with previous reports demonstrating that histologic confirmation of thoracic endometriosis is frequently absent despite a highly suggestive clinical presentation. Endometrial implants may be microscopic, intermittently present, destroyed by cyclical hemorrhage, or missed during sampling. Consequently, the diagnosis often relies on the temporal relationship with menstruation, surgical findings, and exclusion of alternative causes( 14 ). The predominance of right-sided disease in all three sisters is also noteworthy. Right hemithoracic involvement has been reported in approximately 80–90% of patients with thoracic endometriosis syndrome and is generally attributed to preferential transdiaphragmatic migration of endometrial tissue through the right hemidiaphragm and clockwise peritoneal fluid circulation( 14 , 18 ). Another remarkable aspect of this family is the coexistence of thoracic manifestations with pelvic disease. The second sister had documented pelvic endometriosis requiring subsequent right oophorectomy and eventually total abdominal hysterectomy, while the third sister demonstrated adenomyosis, pelvic adhesions, and an endometrial polyp on gynecologic evaluation. Previous studies have shown that pelvic endometriosis is present in approximately 20–70% of women with catamenial pneumothorax, supporting the concept that thoracic and pelvic disease may represent different manifestations of a common pathological process( 15 , 19 ). Familial endometriosis has been extensively documented, with first-degree relatives of affected women demonstrating a substantially increased risk of disease development. Nevertheless, familial thoracic endometriosis remains poorly characterized. The occurrence of catamenial pneumothorax in three sisters born to unaffected parents may reflect multifactorial inheritance, incomplete penetrance, shared environmental influences, or as-yet unidentified genetic variants associated with thoracic manifestations of endometriosis. Further genetic investigation of such families may provide valuable insight into the mechanisms underlying thoracic endometriosis syndrome( 17 , 19 ). This case series highlights the importance of considering catamenial pneumothorax in reproductive-age women presenting with recurrent spontaneous pneumothorax, particularly when episodes demonstrate a cyclical relationship with menstruation. Recognition of familial clustering may facilitate earlier diagnosis, appropriate surgical management, and multidisciplinary follow-up involving thoracic surgeons, pulmonologists, and gynecologists ( 20 ). Limitations Histopathological confirmation of thoracic endometriosis was not obtained in all affected sisters. In addition, genetic testing was not available; therefore, a hereditary predisposition could not be formally evaluated. Nevertheless, the occurrence of recurrent catamenial pneumothorax in three sisters strongly suggests a familial association deserving further investigation. Declarations Ethics approval and consent to participate Written informed consent for publication of clinical details and accompanying images was obtained from all three patients. Copies of the signed consent forms are available for review by the Editor-in-Chief upon reasonable request) code of ethics: IR.SHMU.REC.1404.023) Consent for publication Consent to participate are taken from each three sisters Competing interests The authors declare no competing interests. Funding This research was supported by Shahroud University of Medical Sciences (grant number 14040028) Author Contribution KB, ZK, FB and NM were involved in Conceptualization, and KB and ZK collected the data. KB, ZK, FB and NM analyzed the data. KB, ZK, FB and NM were involved in the methodology. KB, and NM was project administrator and supervised the project. KB and NM validated all stages of the project. KB, ZK, FB and NM wrote the original draft of the manuscript and editing was done by KB, ZK, FB and NM. Acknowledgement Special thanks go to the vice-chancellor of the Research, School of Nursing and Midwifery, Shahroud University of Medical Sciences. Availability of data and materials On reasonable request, the corresponding author is willing to provide the documents used and analyzed during the present study References Tennfjord MK, Gabrielsen R, Tellum T. Effect of physical activity and exercise on endometriosis-associated symptoms: a systematic review. BMC Womens Health. 2021;21(1):355. Affaitati G, Costantini R, Tana C, Cipollone F, Giamberardino MA. Co-occurrence of pain syndromes. J Neural Transm. 2020;127(4):625–46. van Aken MA, Oosterman JM, Van Rijn C, Ferdek MA, Ruigt GS, Peeters B, et al. Pain cognition versus pain intensity in patients with endometriosis: toward personalized treatment. Fertil Steril. 2017;108(4):679–86. Viganò D, Zara F, Usai P. Irritable bowel syndrome and endometriosis: New insights for old diseases. Dig liver disease. 2018;50(3):213–9. Johnson NP, Hummelshoj L, Adamson GD, Keckstein J, Taylor HS, Abrao MS, et al. World Endometriosis Society consensus on the classification of endometriosis. Hum Reprod. 2017;32(2):315–24. Koninckx PR, Ussia A, Adamyan L, Wattiez A, Gomel V, Martin DC. Pathogenesis of endometriosis: the genetic/epigenetic theory. Fertil Steril. 2019;111(2):327–40. Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril. 1997;68(4):585–96. Jerman LF, Hey-Cunningham AJ. The role of the lymphatic system in endometriosis: a comprehensive review of the literature. Biol Reprod. 2015;92(3):64. Matalliotakis M, Goulielmos GN, Kalogiannidis I, Koumantakis G, Matalliotakis I, Arici A. Extra pelvic endometriosis: retrospective analysis on 200 cases in two different countries. Eur J Obstet Gynecol Reproductive Biology. 2017;217:34–7. Tong S-S, Yin X-Y, Hu S-S, Cui Y, Li H-T. Case report of pulmonary endometriosis and review of the literature. J Int Med Res. 2019;47(4):1766–70. Guerriero S, Ajossa S, Minguez JA, Jurado M, Mais V, Melis GB, et al. Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in uterosacral ligaments, rectovaginal septum, vagina and bladder: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2015;46(5):534–45. Guerriero S, Mais V, Ajossa S, Paoletti AM, Angiolucci M, Labate F, et al. The role of endovaginal ultrasound in differentiating endometriomas from other ovarian cysts. Clin Exp Obstet Gynecol. 1995;22(1):20–2. Zondervan K, Becker C, Koga K, Missmer S, Taylor R, Viganò P. Endometriosis Nat Rev Dis Primers. 2018; 4: 9. Article. Visouli AN, Zarogoulidis K, Kougioumtzi I, Huang H, Li Q, Dryllis G, et al. Catamenial pneumothorax. J Thorac disease. 2014;6(Suppl 4):S448. Nezhat C, Lindheim SR, Backhus L, Vu M, Vang N, Nezhat A, et al. Thoracic endometriosis syndrome: a review of diagnosis and management. JSLS: J Soc Laparoendoscopic Surg. 2019;23(3):e2019. Scarnecchia E, Inzirillo F, Declich P, Della Pona C. Thoracic endometriosis-related non-catamenial pneumothorax with peculiar histological findings. Gen Thorac Cardiovasc Surg. 2020;68(9):1040–2. Johnson MM. Catamenial pneumothorax and other thoracic manifestations of endometriosis. Clin Chest Med. 2004;25(2):311–9. Marjański T, Sowa K, Czapla A, Rzyman W. Catamenial pneumothorax–a review of the literature. Kardiochirurgia i Torakochirurgia Polska/Polish J Thorac Cardiovasc Surg. 2016;13(2):117–21. Chien C-H, Hsieh M-J, Wang C-W, Hsu C-C. Catamenial Pneumothorax With Diaphragmatic Endometriosis: View From the Thoracoscope. J Minim Invasive Gynecol. 2025;32(4):304–7. Fukuda S, Hirata T, Neriishi K, Nakazawa A, Takamura M, Izumi G, et al. Thoracic endometriosis syndrome: Comparison between catamenial pneumothorax or endometriosis-related pneumothorax and catamenial hemoptysis. Eur J Obstet Gynecol Reproductive Biology. 2018;225:118–23. Additional Declarations No competing interests reported. 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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-10342209","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":693843183,"identity":"3915a28b-3cbc-4d18-993f-114d6632ffa4","order_by":0,"name":"Katayoon Berjis","email":"","orcid":"","institution":"Mirza–Koochak–Khan Infertility Center, Tehran University of Medical Sciences, Tehran, Iran","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Katayoon","middleName":"","lastName":"Berjis","suffix":""},{"id":693843186,"identity":"40bda514-63e0-4944-bcbb-8c6c06234f88","order_by":1,"name":"Zahra 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05:49:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":211282,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePelvic ultrasound showing findings suggestive of pelvic endometriosis.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-10342209/v1/6f6e52b1c80b24aa72c025d8.png"},{"id":117156985,"identity":"4e7d8191-4806-4361-b6e6-dc51f8ff919b","added_by":"auto","created_at":"2026-08-12 10:37:40","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1131349,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHistopathologic findings demonstrating hemorrhage, hemosiderin-laden macrophages, and reactive eosinophilic pleuritis.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-10342209/v1/d09bf059390990452a3b26a4.jpeg"},{"id":117156587,"identity":"271f302d-be35-4579-8a7a-115390998b1b","added_by":"auto","created_at":"2026-08-12 10:36:08","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":648710,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePreoperative chest radiograph of Case 3 showing right-sided pneumothorax\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-10342209/v1/705783e6d94ba0b6f61c01d3.jpeg"},{"id":117161188,"identity":"1aa697b8-b8d8-420d-b092-3501cdd3ea64","added_by":"auto","created_at":"2026-08-12 13:01:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3283416,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-10342209/v1/c4f69d10-c473-48ba-aad8-29f1a39ccb37.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Familial Pulmonary Endometriosis in Three Sisters: A Case Series and Review of the Literature","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEndometriosis is a benign gynecological condition in which ectopic, endometrium-like cells are located outside of the uterine cavity [1] and is associated with infertility, subfertility, dysmenorrhea, Pain during intercourse (dyspareunia), menorrhagia, and chronic pelvic pain(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOther presentations associated with endometriosis include irritable bowel syndrome, painful bladder syndrome, abdominal pain, adnexal masses, migraine, fatigue and loss of quality of life (\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The most commonly accepted theory for the pathogenesis of endometriosis is retrograde menstruation where endometrial cells reach the abdomino-pelvic cavity via the fallopian tubes during menses, and depending on local and host immunologic factors, the ectopic endometrial cells go through neo angiogenesis, survive and implant (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). This theory is supported by the finding that the most frequently encountered sites of endometrial implants are located within the dependent aspects of the pelvis, such as the pouch of Douglas, retrocervix, uterosacral ligaments, rectosigmoid, and bladder (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Deep endometriosis is differentiated from peritoneal (or superficial) and ovarian endometriosis types by the presence of endometriotic nodules larger than 5 mm (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). It has been found in extra-pelvic sites, such as the upper abdominal visceral organs, abdominal wall, diaphragm and pleura, perhaps as a result of peritoneal dissemination of endometrial implants and metaplasia (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). It also has been reported in even more distant sites, such as the central nervous system (brain, vertebral nerves) and the peripheral nervous system, perhaps by lymphatic or hematologic spread (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Thoracic endometriosis is a form of extra-pelvic endometriosis that can be classified as either pleural or pulmonary. Pulmonary endometriosis is an extremely rare disease with complex causes and pathogeneses that remain unclear(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere is no reliable serum maker for this disease, and imaging still leaves much of it undiagnosed (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). There is no definite cure for endometriosis, and so the main focus of management is to control the associated pain, which is achieved by hormonal suppression of the disease or surgical excision(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhen extensive deep endometriosis involving distant sites and/or critical organs are encountered, the diagnosis and management of non-pelvic endometriosis can be extremely challenging and may result in delay in treatment. The main objective of this paper is to describe three cases of pulmonary endometriosis manifestation associated with the menstrual cycle.\u003c/p\u003e \u003cp\u003eThese cases are being reported to alert clinicians to the fact that pulmonary endometriosis can be readily misdiagnosed as a systemic disease because of its clinical manifestations and imaging signs. These cases provide a reference for diagnosis and treatment of pulmonary endometriosis.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA remarkable familial clustering was observed in this family. Three biological sisters, born in 1970, 1976, and 1983, developed recurrent right-sided spontaneous/catamenial pneumothorax and were subsequently diagnosed with pelvic endometriosis. The parents had no known history of pneumothorax, thoracic endometriosis, or pelvic endometriosis. Histopathological evaluation was available for the two younger sisters, whereas original medical records for the eldest sister were unavailable. The pedigree of the family is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eFilled symbols indicate individuals affected by recurrent catamenial/spontaneous pneumothorax.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eII-2 and II-3 had histopathologic evaluation.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAll affected individuals also had pelvic endometriosis.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eParents had no known history of pneumothorax or endometriosis.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eThree biological sisters were diagnosed with thoracic endometriosis presenting with recurrent right-sided thoracic manifestations. The clinical features, management, and outcomes of each patient are described below.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCase 1\u003c/h2\u003e \u003cp\u003eA 42-year-old married housewife presented with recurrent right-sided pneumothorax accompanied by chest pain. Initial laboratory investigations revealed a hemoglobin level of 13.6 g/dL and serum creatinine of 1.0 mg/dL.\u003c/p\u003e \u003cp\u003eDue to recurrent right pneumothorax, she underwent bronchoscopy and right video-assisted thoracoscopic surgery (VATS) on July 17, 2022. Surgical management included wedge resection of the right apical lung, parietal pleurectomy, and complete pleural scarification. The postoperative course was uneventful, and the patient was discharged after eight days in good general condition.\u003c/p\u003e \u003cp\u003eDespite surgical treatment, recurrence occurred several months later. She was readmitted with recurrent right-sided catamenial pneumothorax in November 2022, requiring chest tube insertion. Subsequently, on December 15, 2022, she underwent repeat surgery consisting of bronchoscopy, right posterolateral thoracotomy, pneumolysis, complete parietal pleurectomy, resection of two diaphragmatic lesions with two-layer diaphragmatic repair, and wedge resection of the right lower lobe including a suspicious pulmonary nodule. Recovery was satisfactory, and the patient was discharged in stable condition with acceptable postoperative chest radiography findings.\u003c/p\u003e \u003cp\u003eDetailed medical records and histopathologic specimens were unavailable for retrospective review.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCase 2\u003c/h3\u003e\n \u003cp\u003ewas a 26-year-old woman with recurrent right-sided catamenial pneumothorax. Pelvic evaluation revealed mild pelvic endometriosis, diffuse adenomyosis, uterosacral ligament thickening, and a 12-mm endometrial polyp. She underwent VATS and wedge resection. Histopathology demonstrated severe fresh hemorrhage, hemosiderin-laden macrophages, bleb formation, and reactive eosinophilic pleuritis, without definitive evidence of thoracic endometriosis. Despite postoperative hormonal therapy with a GnRH agonist, recurrence occurred within several months, necessitating right lobectomy. Owing to persistent cyclic symptoms and concern for recurrence, total abdominal hysterectomy was subsequently performed. \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, 3\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \n\u003ch3\u003eCase 3\u003c/h3\u003e\n\u003cp\u003eThe youngest sister, born in 1983, presented with recurrent right-sided thoracic manifestations, including two episodes of pulmonary hemorrhage involving the right lower lobe. Recurrent right-sided pneumothorax required tube thoracostomy on two separate occasions. Imaging studies demonstrated right pneumothorax associated with focal pleural thickening and subcutaneous emphysema.\u003c/p\u003e \u003cp\u003eBecause of persistent symptoms, she underwent right-sided pulmonary surgery at Masih Daneshvari Hospital, including wedge resection of the affected lung tissue and resection of bullous lesions. Histopathological examination revealed emphysematous lung tissue with mild patchy interstitial thickening, chronic pleural inflammation containing scattered eosinophils, and edematous multicystic bullous tissue with eosinophilic inflammatory infiltrates. No definitive endometrial glands or stroma were identified in the examined specimens.\u003c/p\u003e \u003cp\u003ePostoperatively, treatment with leuprolide acetate was initiated approximately two weeks after surgery and continued for two months. However, cyclical thoracic pain persisted despite hormonal therapy. Owing to persistent symptoms and concern regarding disease recurrence, she subsequently underwent total abdominal hysterectomy with preservation of a portion of one ovary. At follow-up, the patient remained clinically stable without major postoperative complications. Chest radiography at presentation demonstrated right-sided pneumothorax (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAn important finding in the present report is the familial clustering of disease. As illustrated in the pedigree (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), three sisters were affected by recurrent catamenial pneumothorax, whereas no known history of pneumothorax or thoracic endometriosis was reported in either parent. This pattern raises the possibility of a familial predisposition and provides a unique opportunity to explore the relationship between hereditary factors and thoracic endometriosis syndrome.\u003c/p\u003e \u003cp\u003eCatamenial pneumothorax (CP) is the most common clinical manifestation of thoracic endometriosis syndrome (TES), a rare disorder characterized by the presence of ectopic endometrial tissue within thoracic structures. CP is classically defined as recurrent spontaneous pneumothorax occurring within 72 hours before or after the onset of menstruation and demonstrates a marked right-sided predominance(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe present report describes an unusual familial clustering of catamenial pneumothorax in three sisters. Although familial aggregation is well recognized in pelvic endometriosis, reports of thoracic endometriosis syndrome or catamenial pneumothorax affecting multiple members of the same family are exceedingly rare. The occurrence of recurrent right-sided pneumothorax in all three sisters, together with evidence of pelvic endometriosis or adenomyosis in two of them, suggests the possibility of a shared genetic or familial susceptibility(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSeveral mechanisms have been proposed to explain the pathogenesis of CP, including transdiaphragmatic migration of endometrial tissue through diaphragmatic fenestrations, coelomic metaplasia, lymphatic or hematogenous dissemination, and hormonally induced pleural or alveolar fragility. No single theory adequately explains all clinical presentations, and CP is likely a heterogeneous disorder with multifactorial pathogenesis(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAn important observation in our series is the discrepancy between clinical suspicion and histopathological confirmation. In the second sister, pathological examination demonstrated severe pulmonary hemorrhage, hemosiderin-laden macrophages, bleb formation, and reactive eosinophilic pleuritis, while no definite evidence of thoracic endometriosis was identified. Similarly, the third sister showed emphysematous lung changes, chronic pleural inflammation with eosinophilic infiltration, and bullous lesions without histologically proven endometriosis. This finding is consistent with previous reports demonstrating that histologic confirmation of thoracic endometriosis is frequently absent despite a highly suggestive clinical presentation. Endometrial implants may be microscopic, intermittently present, destroyed by cyclical hemorrhage, or missed during sampling. Consequently, the diagnosis often relies on the temporal relationship with menstruation, surgical findings, and exclusion of alternative causes(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe predominance of right-sided disease in all three sisters is also noteworthy. Right hemithoracic involvement has been reported in approximately 80\u0026ndash;90% of patients with thoracic endometriosis syndrome and is generally attributed to preferential transdiaphragmatic migration of endometrial tissue through the right hemidiaphragm and clockwise peritoneal fluid circulation(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAnother remarkable aspect of this family is the coexistence of thoracic manifestations with pelvic disease. The second sister had documented pelvic endometriosis requiring subsequent right oophorectomy and eventually total abdominal hysterectomy, while the third sister demonstrated adenomyosis, pelvic adhesions, and an endometrial polyp on gynecologic evaluation. Previous studies have shown that pelvic endometriosis is present in approximately 20\u0026ndash;70% of women with catamenial pneumothorax, supporting the concept that thoracic and pelvic disease may represent different manifestations of a common pathological process(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFamilial endometriosis has been extensively documented, with first-degree relatives of affected women demonstrating a substantially increased risk of disease development. Nevertheless, familial thoracic endometriosis remains poorly characterized. The occurrence of catamenial pneumothorax in three sisters born to unaffected parents may reflect multifactorial inheritance, incomplete penetrance, shared environmental influences, or as-yet unidentified genetic variants associated with thoracic manifestations of endometriosis. Further genetic investigation of such families may provide valuable insight into the mechanisms underlying thoracic endometriosis syndrome(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis case series highlights the importance of considering catamenial pneumothorax in reproductive-age women presenting with recurrent spontaneous pneumothorax, particularly when episodes demonstrate a cyclical relationship with menstruation. Recognition of familial clustering may facilitate earlier diagnosis, appropriate surgical management, and multidisciplinary follow-up involving thoracic surgeons, pulmonologists, and gynecologists (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eLimitations\u003c/h3\u003e\n\u003cp\u003eHistopathological confirmation of thoracic endometriosis was not obtained in all affected sisters. In addition, genetic testing was not available; therefore, a hereditary predisposition could not be formally evaluated. Nevertheless, the occurrence of recurrent catamenial pneumothorax in three sisters strongly suggests a familial association deserving further investigation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eWritten informed consent for publication of clinical details and accompanying images was obtained from all three patients. Copies of the signed consent forms are available for review by the Editor-in-Chief upon reasonable request) code of ethics: IR.SHMU.REC.1404.023)\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eConsent to participate are taken from each three sisters\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research was supported by Shahroud University of Medical Sciences (grant number 14040028)\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eKB, ZK, FB and NM were involved in Conceptualization, and KB and ZK collected the data. KB, ZK, FB and NM analyzed the data. KB, ZK, FB and NM were involved in the methodology. KB, and NM was project administrator and supervised the project. KB and NM validated all stages of the project. KB, ZK, FB and NM wrote the original draft of the manuscript and editing was done by KB, ZK, FB and NM.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eSpecial thanks go to the vice-chancellor of the Research, School of Nursing and Midwifery, Shahroud University of Medical Sciences.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e \u003cp\u003eOn reasonable request, the corresponding author is willing to provide the documents used and analyzed during the present study\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTennfjord MK, Gabrielsen R, Tellum T. Effect of physical activity and exercise on endometriosis-associated symptoms: a systematic review. BMC Womens Health. 2021;21(1):355.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAffaitati G, Costantini R, Tana C, Cipollone F, Giamberardino MA. Co-occurrence of pain syndromes. J Neural Transm. 2020;127(4):625\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Aken MA, Oosterman JM, Van Rijn C, Ferdek MA, Ruigt GS, Peeters B, et al. Pain cognition versus pain intensity in patients with endometriosis: toward personalized treatment. Fertil Steril. 2017;108(4):679\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVigan\u0026ograve; D, Zara F, Usai P. Irritable bowel syndrome and endometriosis: New insights for old diseases. Dig liver disease. 2018;50(3):213\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohnson NP, Hummelshoj L, Adamson GD, Keckstein J, Taylor HS, Abrao MS, et al. World Endometriosis Society consensus on the classification of endometriosis. Hum Reprod. 2017;32(2):315\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoninckx PR, Ussia A, Adamyan L, Wattiez A, Gomel V, Martin DC. Pathogenesis of endometriosis: the genetic/epigenetic theory. Fertil Steril. 2019;111(2):327\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril. 1997;68(4):585\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJerman LF, Hey-Cunningham AJ. The role of the lymphatic system in endometriosis: a comprehensive review of the literature. Biol Reprod. 2015;92(3):64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatalliotakis M, Goulielmos GN, Kalogiannidis I, Koumantakis G, Matalliotakis I, Arici A. Extra pelvic endometriosis: retrospective analysis on 200 cases in two different countries. Eur J Obstet Gynecol Reproductive Biology. 2017;217:34\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTong S-S, Yin X-Y, Hu S-S, Cui Y, Li H-T. Case report of pulmonary endometriosis and review of the literature. J Int Med Res. 2019;47(4):1766\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuerriero S, Ajossa S, Minguez JA, Jurado M, Mais V, Melis GB, et al. Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in uterosacral ligaments, rectovaginal septum, vagina and bladder: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2015;46(5):534\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuerriero S, Mais V, Ajossa S, Paoletti AM, Angiolucci M, Labate F, et al. The role of endovaginal ultrasound in differentiating endometriomas from other ovarian cysts. Clin Exp Obstet Gynecol. 1995;22(1):20\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZondervan K, Becker C, Koga K, Missmer S, Taylor R, Vigan\u0026ograve; P. Endometriosis Nat Rev Dis Primers. 2018; 4: 9. Article.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVisouli AN, Zarogoulidis K, Kougioumtzi I, Huang H, Li Q, Dryllis G, et al. Catamenial pneumothorax. J Thorac disease. 2014;6(Suppl 4):S448.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNezhat C, Lindheim SR, Backhus L, Vu M, Vang N, Nezhat A, et al. Thoracic endometriosis syndrome: a review of diagnosis and management. JSLS: J Soc Laparoendoscopic Surg. 2019;23(3):e2019.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScarnecchia E, Inzirillo F, Declich P, Della Pona C. Thoracic endometriosis-related non-catamenial pneumothorax with peculiar histological findings. Gen Thorac Cardiovasc Surg. 2020;68(9):1040\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohnson MM. Catamenial pneumothorax and other thoracic manifestations of endometriosis. Clin Chest Med. 2004;25(2):311\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarjański T, Sowa K, Czapla A, Rzyman W. Catamenial pneumothorax\u0026ndash;a review of the literature. Kardiochirurgia i Torakochirurgia Polska/Polish J Thorac Cardiovasc Surg. 2016;13(2):117\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChien C-H, Hsieh M-J, Wang C-W, Hsu C-C. Catamenial Pneumothorax With Diaphragmatic Endometriosis: View From the Thoracoscope. J Minim Invasive Gynecol. 2025;32(4):304\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFukuda S, Hirata T, Neriishi K, Nakazawa A, Takamura M, Izumi G, et al. Thoracic endometriosis syndrome: Comparison between catamenial pneumothorax or endometriosis-related pneumothorax and catamenial hemoptysis. Eur J Obstet Gynecol Reproductive Biology. 2018;225:118\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Catamenial pneumothorax, Thoracic endometriosis, Familial clustering, Endometriosis, Case series","lastPublishedDoi":"10.21203/rs.3.rs-10342209/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-10342209/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Catamenial pneumothorax (CP) is the most common manifestation of thoracic endometriosis syndrome and is characterized by recurrent spontaneous pneumothorax occurring in temporal association with menstruation. Although familial aggregation is well recognized in pelvic endometriosis, familial occurrence of catamenial pneumothorax remains exceptionally rare in the literature. Thoracic endometriosis often lacks histopathological confirmation, making diagnosis dependent on clinical, radiological, and surgical findings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe report three sisters who developed recurrent right-sided spontaneous pneumothorax associated with menstruation. The eldest sister experienced recurrent menstrual-related pneumothorax and was managed surgically. The second sister underwent video-assisted thoracoscopic surgery (VATS), wedge resection, pleural biopsy, and pleurodesis. Histopathological examination revealed severe pulmonary hemorrhage, hemosiderin-laden macrophages, bleb formation, and reactive eosinophilic pleuritis without definitive evidence of thoracic endometriosis. She had documented pelvic endometriosis and subsequently underwent right oophorectomy followed by total abdominal hysterectomy because of recurrent disease. The youngest sister also presented with recurrent right-sided catamenial pneumothorax and underwent VATS with wedge resection and pleurodesis. Histopathology demonstrated emphysematous lung tissue, chronic pleural inflammation with eosinophilic infiltration, and bullous changes without definite endometrial tissue. Pelvic ultrasonography revealed findings suggestive of adenomyosis and pelvic adhesions. No parental history of pneumothorax or endometriosis was identified.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case series describes an unusual familial clustering of catamenial pneumothorax affecting three sisters. Despite the absence of histologically confirmed thoracic endometriosis in two surgically treated patients, the cyclical relationship with menstruation, right-sided predominance, operative findings, and concomitant pelvic endometriosis strongly supported the diagnosis. These cases highlight the diagnostic challenges of thoracic endometriosis syndrome and suggest a possible familial or genetic predisposition. Recognition of familial clustering may facilitate earlier diagnosis and multidisciplinary management of affected women.\u003c/p\u003e","manuscriptTitle":"Familial Pulmonary Endometriosis in Three Sisters: A Case Series and Review of the Literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-08-12 05:49:50","doi":"10.21203/rs.3.rs-10342209/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-08-16T16:33:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"66733505544598344957829338231573355916","date":"2026-08-07T20:40:24+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-08-07T11:42:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-08-07T05:23:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"319997629065048065094626395529411141771","date":"2026-08-07T05:04:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"142357448074707178209423719330203794608","date":"2026-08-07T04:44:00+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-08-07T00:27:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-08-07T00:26:28+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-07-27T09:49:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-07-25T11:06:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Women's Health","date":"2026-07-25T11:00:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6303a7a7-638d-4223-a202-efb3644d3e36","owner":[],"postedDate":"August 12th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-08-16T16:33:09+00:00","index":43,"fulltext":""},{"type":"reviewerAgreed","content":"66733505544598344957829338231573355916","date":"2026-08-07T20:40:24+00:00","index":42,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-08-07T11:42:57+00:00","index":41,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-08-07T05:23:16+00:00","index":38,"fulltext":""},{"type":"reviewerAgreed","content":"319997629065048065094626395529411141771","date":"2026-08-07T05:04:03+00:00","index":37,"fulltext":""},{"type":"reviewerAgreed","content":"142357448074707178209423719330203794608","date":"2026-08-07T04:44:00+00:00","index":36,"fulltext":""},{"type":"reviewersInvited","content":"10","date":"2026-08-07T00:27:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-08-07T00:26:28+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-08-12T05:49:50+00:00","versionOfRecord":[],"versionCreatedAt":"2026-08-12 05:49:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-10342209","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-10342209","identity":"rs-10342209","version":["v1"]},"buildId":"zQwnuV7TCBrMSSSToR1PI","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}