Metachronous Multifocal Placental Transmogrification of the Lung: A Nodular Subtype with Microscopic Emphysematous Changes

Metachronous Multifocal Placental Transmogrification of the Lung: A Nodular Subtype with Microscopic Emphysematous Changes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Metachronous Multifocal Placental Transmogrification of the Lung: A Nodular Subtype with Microscopic Emphysematous Changes Sang Yun Song, Woo Roe Choe, Kyo Seon Lee, Yoo-Duk Choi, Ju Sik Yun This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8952689/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 17 You are reading this latest preprint version Abstract Placental transmogrification of the lung (PTL) is a rare benign pulmonary lesion with limited longitudinal data. We report the case of a 49-year-old man who underwent video-assisted thoracoscopic surgery wedge resection of a 12-mm right-upper-lobe pulmonary nodule subsequently diagnosed as PTL on histopathology. Seven months after surgery, surveillance chest computed tomography (CT) revealed a newly developed 10-mm solid nodule in the right lower lobe, which was resected 12 months after the initial operation and was confirmed as PTL. This case demonstrates metachronous multifocal disease arising in different ipsilateral lobes after complete resection. Histologic examination of the second lesion was consistent with PTL and showed microscopic emphysematous remodeling, despite the absence of bullous changes on preoperative CT. This finding indicates radiologic–pathologic discordance, suggesting that microscopic emphysematous remodeling precedes radiologically apparent bullous changes. The observed temporal course supports the need for structured postoperative surveillance, particularly during the early postoperative period. Pulmonary placental transmogrification of the lung metachronous multifocal disease solitary pulmonary nodule Placenta Figures Figure 1 Figure 2 Background Placental transmogrification of the lung (PTL), first described by McChesney in 1979, is characterized histologically by papillary structures resembling placental villi. Most reported cases have been associated with unilateral giant bullae; however, PTL may also present as a solitary pulmonary nodule, with or without concomitant emphysematous changes [ 1 – 3 ]. Its clinical presentation ranges from incidental detection in asymptomatic individuals to symptoms related to bullous lung disease, including dyspnea, chronic cough, and chest discomfort [ 4 , 5 ]. Owing to its rarity, standard management guidelines for PTL have not yet been established. Nevertheless, complete surgical excision is considered definitive in most reported cases [ 6 , 7 ]. Although lobectomy or pneumonectomy was more frequently performed in earlier case reports, recent studies favor parenchyma-sparing approaches, such as wedge resection or volume-reduction surgery, depending on the lesion size and location [ 7 , 8 ]. Reports of multifocal PTL are rare, and no reports have clearly delineated the timing and sequence of lesion appearance. To our knowledge, this is the first report of a metachronous multifocal PTL occurring after complete resection of the lung nodule, providing insights into the clinical characteristics of this rare entity and underscoring the need for structured postoperative surveillance. Case presentation A 49-year-old man with no significant comorbidities and a 45-pack-year smoking history was referred to our institution after a 12-mm subpleural cavitary nodule was detected in the right upper lobe on chest computed tomography (CT) performed as part of routine health screening (Fig. 1 A). Although follow-up CT at 3 months showed no changes in nodule size or morphology, surgical resection was performed to exclude granulomatous diseases, including pulmonary tuberculosis and malignancy. The patient underwent video-assisted thoracic surgery (VATS) wedge resection of the right upper lobe. Intraoperatively, a well-demarcated reddish-lobulated subpleural lesion without gross pleural invasion was identified. Precise localization by finger palpation was limited by the soft consistency of the lesion. The patient’s postoperative course was uneventful, and he was discharged without complications. The resected specimen appeared hyperemic, and sectioning revealed grape-like vesicular spaces suggestive of a villiform structural pattern. Histopathological examination revealed villiform papillary projections lined with pneumocytes overlying edematous fibrovascular stroma. Clusters of interstitial clear cells with a clear glycogen-rich cytoplasm were present within the papillary cores (Fig. 1 B, C). Immunohistochemical staining was positive for TTF-1, CK7, and napsin A. No evidence of malignancy or bullous changes was found. Based on these findings, the definitive diagnosis was nodular-type PTL without emphysematous changes. Seven months after the initial surgery, follow-up CT revealed a newly developed 10-mm solid nodule in the right lower lobe with no abnormality at the previous resection site (Fig. 2 A). Repeat CT performed 5 months later confirmed the persistence of the lesion. Approximately 12 months after the first surgery, the patient underwent VATS wedge resection of the right lower lobe. Intraoperatively, a focal area of pleural discoloration overlying the nodule helped localize the lesion and no pleural invasion was observed. The postoperative course was uneventful, and the patient remained under radiological surveillance. Histological evaluation of the second lesion revealed villiform and placenta-like papillary structures consistent with PTL. In contrast to the first lesion, focal microscopic emphysematous remodeling was identified despite the absence of bullous changes on preoperative CT (Fig. 2 B). This radiologic–pathologic discordance suggests that lesions with a gross nodular appearance may lie along a morphological continuum with bullous lesions. The final diagnosis was metachronous multifocal nodular-type PTL, with the second lesion identified 7 months after the initial resection. Discussion PTL remains poorly characterized because of its rarity. PTL is more commonly associated with unilateral giant bullae, and Fidler et al. (1995) interpreted it as secondary to pre-existing bullous emphysema rather than a primary independent lesion [ 1 , 2 , 5 ]. However, nodular PTL without overt bullous changes supports the hypothesis of developmental or malformative lesions, rather than lesions secondary to pre-existing bullous lung disease. Based on a histological review of 38 cases of pulmonary hamartomas, Xu et al. [ 1 ] suggested that PTL may represent a histological pattern within a pulmonary fibrochondromatous hamartoma. This lesion is not a form of emphysema, but results from primary benign proliferation of distinctive interstitial clear cells, leading to secondary cystic changes [ 2 , 3 ]. Ma et al. reported a circumscribed emphysematous mass containing soft tissues and fatty components, suggesting a possible association with pulmonary lipomatosis [ 8 ]. Collectively, these observations support the notion that the PTL may encompass a spectrum of related morphological entities rather than a single uniform disease. Kim et al. classified PTL into three radiologic patterns: bullous emphysema, a mixed pattern of thin-walled cystic lesions and nodules, and solitary nodules [ 9 ]. Whether these categories correspond to distinct biological behaviors or natural histories remains uncertain. In the present case, although the lesion appeared nodular on gross and radiologic examinations, microscopic emphysematous remodeling was identified in the second lesion. This finding suggests that microscopic emphysematous remodeling may occur before radiologically apparent bullous or emphysematous changes. In turn, this radiologic–pathologic discordance supports the hypothesis that nodular and bullous PTL represents a continuous morphological spectrum rather than discrete entities. These observations highlight the need for an integrated classification that incorporates radiological, gross, and microscopic features. From a clinical perspective, this case provides two important observations. First, it documents metachronous multifocal PTL, with a second lesion arising in a different ipsilateral lobe despite complete surgical resection of the index lesion. Although Abdulelah et al. reported a case of multifocal PTL diagnosed using CT-guided core biopsy and followed up for 8 years without surgical resection, the timing and sequence of lesion appearance (synchronous vs. metachronous) were not determined [ 10 ]. Second, this case suggests that additional PTL lesions may be detected within a short interval after the resection of an index lesion. This short-interval metachronous pattern may fall within the clinical spectrum of PTL. However, conclusions regarding the natural history of PTL cannot be drawn from a single case study. Complete surgical excision remains the treatment of choice for PTL, with a preference for parenchyma-sparing approaches when feasible [ 7 , 8 ]. However, the occurrence of metachronous multifocal disease in this case underscores the importance of postoperative surveillance, particularly during the early postoperative period. At present, a postoperative surveillance strategy for PTL has not been clearly defined, and additional cases are warranted to establish appropriate follow-up intervals and durations after surgical resection. This report has limitations, including its single-case nature and the absence of molecular characterization. Nevertheless, this case provides novel observations on metachronous multifocal disease arising in different ipsilateral lobes and on radiologic–pathologic discordance, thereby offering new insights into the pathophysiology and clinical characteristics of PTL. Conclusions We report a case of metachronous multifocal PTL in which a second lesion developed in a different ipsilateral lobe 7 months after complete surgical resection. Despite the absence of bullous changes on preoperative CT, microscopic emphysematous remodeling was identified in the second lesion, demonstrating radiologic–pathologic discordance and supporting the hypothesis that PTL exists along a continuous morphologic spectrum rather than as discrete entities. Further studies incorporating radiologic–pathologic correlations and longitudinal follow-ups are required to clarify the pathogenesis, refine the classification, and inform optimal follow-up strategies for this rare disease. Abbreviations PTL Placental transmogrification of the lung CT computed tomography VATS video-assisted thoracic surgery RUL right upper lobe RLL right lower lobe Declarations Ethics approval and consent to participate Not applicable. Consent for publication Written nformed consent was obtained from the patient for publication of this report. Availability of data and materials Data that support the findings of this study are available from the corresponding author upon reasonable request. Competing interests The authors declare no conflict of interest Funding This study was financially supported by Chonnam National University (Grant number: 2025-0357-01). Authors' contributions Conception and design: Ju Sik Yun, Woo Roe Choe, Sang Yun Song (II) Administrative support: Kyo Seon Lee, Sang Yun Song (III) Provision of study materials or patients: Ju Sik Yun, Sang Yun Song (IV) Collection and assembly of data: Ju Sik Yun, Kyo Seon Lee, Yoo-Duk Choi (V) Data analysis and interpretation: Ju Sik Yun, Yoo-Duk Choi, Sang Yun Song (VI) Manuscript writing: All authors (VII) Final approval of manuscript: All authors References Xu R, Murray M, Jagirdar J, Delgado Y, Melamed J. Placental transmogrification of the lung is a histologic pattern frequently associated with pulmonary fibrochondromatous hamartoma. Arch Pathol Lab Med. 2002;126(5):562–6. Cavazza A, Lantuejoul S, Sartori G, Bigiani N, Maiorana A, Pasquinelli G, et al. Placental transmogrification of the lung: clinicopathologic, immunohistochemical and molecular study of two cases, with particular emphasis on the interstitial clear cells. Hum Pathol. 2004;35(4):517–21. Saito Y, Ikeya T, Hoshi E, Takahashi N, Murai K, Kawabata Y, et al. Placental transmogrification of the lung presenting as a small solitary nodule. Ann Thorac Surg. 2009;87(3):950–2. Ferretti GR, Kocier M, Moro-Sibilot D, Brichon PY, Lantuejoul S. Placental transmogrification of the lung: CT-pathologic correlation of a rare pulmonary nodule. AJR Am J Roentgenol. 2004;183(1):99–101. Marchevsky AM, Guintu R, Koss M, Fuller C, Houck W, McKenna RJ. Swyer-James (MacLeod) syndrome with placental transmogrification of the lung: a case report and review of the literature. Arch Pathol Lab Med. 2005;129(5):686–9. Shapiro M, Vidal C, Lipskar AM, Gil J, Litle VR. Placental transmogrification of the lung presenting as emphysema and a lung mass. Ann Thorac Surg. 2009;87(2):615–6. Ortiz S, Tortosa F. Pulmonary placental transmogrification: The last 16 years in a reference centre. Rev Port Pneumol (2006). 2017;23(3):164-6. Ma DJ, Liu HS, Li SQ, Zhou XY, Cui YS, Wu HW, et al. Placental transmogrification of the lung: Case report and systematic review of the literature. Med (Baltim). 2017;96(35):e7733. Kim JW, Park IH, Kwon W, Eom MS, Kim YJ, Oh JH. Placental transmogrification of the lung. Korean J Radiol. 2013;14(6):977–80. Abdulelah M, Kasher N, Primera G, Matta J, Patel R, Anis K, et al. Is There a Baby in the Lung? A Case of Placental Transmogrification of the Lung. J Investig Med High Impact Case Rep. 2024;12:23247096241261322. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8952689","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":610150233,"identity":"ccc3d028-4249-4816-9fc5-827fe00b5f35","order_by":0,"name":"Sang Yun Song","email":"","orcid":"","institution":"Chonnam National University Hwasun Hospital, Chonnam National University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Sang","middleName":"Yun","lastName":"Song","suffix":""},{"id":610150237,"identity":"59ef1a18-1939-44cd-aedf-52d36490644c","order_by":1,"name":"Woo Roe Choe","email":"","orcid":"","institution":"Chonnam National University Hospital, Chonnam National University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Woo","middleName":"Roe","lastName":"Choe","suffix":""},{"id":610150239,"identity":"74dc63a4-acfb-422e-88ce-ac75cf79140d","order_by":2,"name":"Kyo Seon Lee","email":"","orcid":"","institution":"Chonnam National University Hospital, Chonnam National University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Kyo","middleName":"Seon","lastName":"Lee","suffix":""},{"id":610150240,"identity":"e537db97-d0ef-409a-a1c7-5b47cef239bc","order_by":3,"name":"Yoo-Duk Choi","email":"","orcid":"","institution":"Chonnam National University Hospital, Chonnam National University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Yoo-Duk","middleName":"","lastName":"Choi","suffix":""},{"id":610150242,"identity":"6c1866fa-52dc-4ba0-8c4c-4469257a8a3d","order_by":4,"name":"Ju Sik Yun","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYBACxgYGhoNAzMAP4iUUkKJFEkQkGJBgE4PBARCTGC3MM9IfHpzZdjjP+PzqxA8PDBjk+cUOELBhRo7BwY1th4vNbrzdLAF0mOHM2QkEtTAcfNh2OHHbjbMbQFoSDG4T1JL+AKxl84yzm38QqSUB7LDEDfy924i0peeNwcEZ59ITZ9zg3WaRYCBB2C+G7emPP/aUWSf295/dfPNHhY08vzQhLQ0gq9iAhARYpQR+5SAgDyb/ADH/AcKqR8EoGAWjYGQCADN5T4SMyzMzAAAAAElFTkSuQmCC","orcid":"","institution":"Chonnam National University Hwasun Hospital, Chonnam National University Medical School","correspondingAuthor":true,"prefix":"","firstName":"Ju","middleName":"Sik","lastName":"Yun","suffix":""}],"badges":[],"createdAt":"2026-02-24 04:53:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8952689/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8952689/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105296982,"identity":"5fc5633a-4bd7-4432-8c5a-a345d3c3583b","added_by":"auto","created_at":"2026-03-24 13:15:21","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":623322,"visible":true,"origin":"","legend":"\u003cp\u003eChest CT and histopathological images of the first lesion.\u003c/p\u003e\n\u003cp\u003eA) A 12-mm cavitary lesion located in the RUL (arrow).\u003c/p\u003e\n\u003cp\u003eB) Well-demarcated lesion showing villiform placenta-like papillae. (hematoxylin–eosin staining, x40)\u003c/p\u003e\n\u003cp\u003eC) Villiform, placenta-like papillae lined by pneumocytes overlying edematous, fibrovascular stroma. Numerous clear interstitial cells are present within the papillary cores. (hematoxylin–eosin staining, x200)\u003c/p\u003e\n\u003cp\u003eCT: computed tomography; RUL: right upper lobe\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8952689/v1/47fa21c53cf1037d7874ecd7.jpg"},{"id":105296983,"identity":"55f522cf-bcaa-4b07-92e8-f1cac1a1d8ca","added_by":"auto","created_at":"2026-03-24 13:15:21","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":295136,"visible":true,"origin":"","legend":"\u003cp\u003eChest CT and histopathological images of the metachronous multifocal placental transmogrification of the lung.\u003c/p\u003e\n\u003cp\u003eA) Follow-up chest CT 7 months after the first surgery shows a newly developed 10-mm solid nodule in the RLL (arrow), without evidence of bullous changes on preoperative CT.\u003c/p\u003e\n\u003cp\u003eB) Histopathology of the RLL lesion showing placenta-like papillae (lower right) with cystic spaces (upper left) and emphysematous changes (center). (hematoxylin–eosin staining, x40)\u003c/p\u003e\n\u003cp\u003eCT: computed tomography; RLL: right lower lobe\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8952689/v1/3cb374d8a03e719c8357c67b.jpg"},{"id":105296988,"identity":"edb33fb2-74d3-49c8-a138-235db6365f4e","added_by":"auto","created_at":"2026-03-24 13:15:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1260655,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8952689/v1/9e27212e-c8ac-434d-8979-bd7788bca245.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Metachronous Multifocal Placental Transmogrification of the Lung: A Nodular Subtype with Microscopic Emphysematous Changes","fulltext":[{"header":"Background","content":"\u003cp\u003ePlacental transmogrification of the lung (PTL), first described by McChesney in 1979, is characterized histologically by papillary structures resembling placental villi. Most reported cases have been associated with unilateral giant bullae; however, PTL may also present as a solitary pulmonary nodule, with or without concomitant emphysematous changes [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Its clinical presentation ranges from incidental detection in asymptomatic individuals to symptoms related to bullous lung disease, including dyspnea, chronic cough, and chest discomfort [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOwing to its rarity, standard management guidelines for PTL have not yet been established. Nevertheless, complete surgical excision is considered definitive in most reported cases [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Although lobectomy or pneumonectomy was more frequently performed in earlier case reports, recent studies favor parenchyma-sparing approaches, such as wedge resection or volume-reduction surgery, depending on the lesion size and location [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eReports of multifocal PTL are rare, and no reports have clearly delineated the timing and sequence of lesion appearance. To our knowledge, this is the first report of a metachronous multifocal PTL occurring after complete resection of the lung nodule, providing insights into the clinical characteristics of this rare entity and underscoring the need for structured postoperative surveillance.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 49-year-old man with no significant comorbidities and a 45-pack-year smoking history was referred to our institution after a 12-mm subpleural cavitary nodule was detected in the right upper lobe on chest computed tomography (CT) performed as part of routine health screening (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Although follow-up CT at 3 months showed no changes in nodule size or morphology, surgical resection was performed to exclude granulomatous diseases, including pulmonary tuberculosis and malignancy.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe patient underwent video-assisted thoracic surgery (VATS) wedge resection of the right upper lobe. Intraoperatively, a well-demarcated reddish-lobulated subpleural lesion without gross pleural invasion was identified. Precise localization by finger palpation was limited by the soft consistency of the lesion. The patient\u0026rsquo;s postoperative course was uneventful, and he was discharged without complications.\u003c/p\u003e \u003cp\u003eThe resected specimen appeared hyperemic, and sectioning revealed grape-like vesicular spaces suggestive of a villiform structural pattern. Histopathological examination revealed villiform papillary projections lined with pneumocytes overlying edematous fibrovascular stroma. Clusters of interstitial clear cells with a clear glycogen-rich cytoplasm were present within the papillary cores (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB, C). Immunohistochemical staining was positive for TTF-1, CK7, and napsin A. No evidence of malignancy or bullous changes was found. Based on these findings, the definitive diagnosis was nodular-type PTL without emphysematous changes.\u003c/p\u003e \u003cp\u003eSeven months after the initial surgery, follow-up CT revealed a newly developed 10-mm solid nodule in the right lower lobe with no abnormality at the previous resection site (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). Repeat CT performed 5 months later confirmed the persistence of the lesion. Approximately 12 months after the first surgery, the patient underwent VATS wedge resection of the right lower lobe. Intraoperatively, a focal area of pleural discoloration overlying the nodule helped localize the lesion and no pleural invasion was observed. The postoperative course was uneventful, and the patient remained under radiological surveillance.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eHistological evaluation of the second lesion revealed villiform and placenta-like papillary structures consistent with PTL. In contrast to the first lesion, focal microscopic emphysematous remodeling was identified despite the absence of bullous changes on preoperative CT (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). This radiologic\u0026ndash;pathologic discordance suggests that lesions with a gross nodular appearance may lie along a morphological continuum with bullous lesions. The final diagnosis was metachronous multifocal nodular-type PTL, with the second lesion identified 7 months after the initial resection.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePTL remains poorly characterized because of its rarity. PTL is more commonly associated with unilateral giant bullae, and Fidler et al. (1995) interpreted it as secondary to pre-existing bullous emphysema rather than a primary independent lesion [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, nodular PTL without overt bullous changes supports the hypothesis of developmental or malformative lesions, rather than lesions secondary to pre-existing bullous lung disease.\u003c/p\u003e \u003cp\u003eBased on a histological review of 38 cases of pulmonary hamartomas, Xu et al. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] suggested that PTL may represent a histological pattern within a pulmonary fibrochondromatous hamartoma. This lesion is not a form of emphysema, but results from primary benign proliferation of distinctive interstitial clear cells, leading to secondary cystic changes [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Ma et al. reported a circumscribed emphysematous mass containing soft tissues and fatty components, suggesting a possible association with pulmonary lipomatosis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Collectively, these observations support the notion that the PTL may encompass a spectrum of related morphological entities rather than a single uniform disease.\u003c/p\u003e \u003cp\u003eKim et al. classified PTL into three radiologic patterns: bullous emphysema, a mixed pattern of thin-walled cystic lesions and nodules, and solitary nodules [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Whether these categories correspond to distinct biological behaviors or natural histories remains uncertain. In the present case, although the lesion appeared nodular on gross and radiologic examinations, microscopic emphysematous remodeling was identified in the second lesion. This finding suggests that microscopic emphysematous remodeling may occur before radiologically apparent bullous or emphysematous changes. In turn, this radiologic\u0026ndash;pathologic discordance supports the hypothesis that nodular and bullous PTL represents a continuous morphological spectrum rather than discrete entities. These observations highlight the need for an integrated classification that incorporates radiological, gross, and microscopic features.\u003c/p\u003e \u003cp\u003eFrom a clinical perspective, this case provides two important observations. First, it documents metachronous multifocal PTL, with a second lesion arising in a different ipsilateral lobe despite complete surgical resection of the index lesion. Although Abdulelah et al. reported a case of multifocal PTL diagnosed using CT-guided core biopsy and followed up for 8 years without surgical resection, the timing and sequence of lesion appearance (synchronous vs. metachronous) were not determined [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Second, this case suggests that additional PTL lesions may be detected within a short interval after the resection of an index lesion. This short-interval metachronous pattern may fall within the clinical spectrum of PTL. However, conclusions regarding the natural history of PTL cannot be drawn from a single case study.\u003c/p\u003e \u003cp\u003eComplete surgical excision remains the treatment of choice for PTL, with a preference for parenchyma-sparing approaches when feasible [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, the occurrence of metachronous multifocal disease in this case underscores the importance of postoperative surveillance, particularly during the early postoperative period. At present, a postoperative surveillance strategy for PTL has not been clearly defined, and additional cases are warranted to establish appropriate follow-up intervals and durations after surgical resection.\u003c/p\u003e \u003cp\u003eThis report has limitations, including its single-case nature and the absence of molecular characterization. Nevertheless, this case provides novel observations on metachronous multifocal disease arising in different ipsilateral lobes and on radiologic\u0026ndash;pathologic discordance, thereby offering new insights into the pathophysiology and clinical characteristics of PTL.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eWe report a case of metachronous multifocal PTL in which a second lesion developed in a different ipsilateral lobe 7 months after complete surgical resection. Despite the absence of bullous changes on preoperative CT, microscopic emphysematous remodeling was identified in the second lesion, demonstrating radiologic\u0026ndash;pathologic discordance and supporting the hypothesis that PTL exists along a continuous morphologic spectrum rather than as discrete entities.\u003c/p\u003e \u003cp\u003eFurther studies incorporating radiologic\u0026ndash;pathologic correlations and longitudinal follow-ups are required to clarify the pathogenesis, refine the classification, and inform optimal follow-up strategies for this rare disease.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePTL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePlacental transmogrification of the lung\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecomputed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVATS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003evideo-assisted thoracic surgery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRUL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eright upper lobe\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRLL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eright lower lobe\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\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten nformed consent was obtained from the patient for publication of this report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was financially supported by Chonnam National University (Grant number: 2025-0357-01).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception and design: Ju Sik Yun, Woo Roe Choe, Sang Yun Song\u003c/p\u003e\n\u003cp\u003e(II) Administrative support: Kyo Seon Lee, Sang Yun Song\u003c/p\u003e\n\u003cp\u003e(III) Provision of study materials or patients: Ju Sik Yun, Sang Yun Song\u003c/p\u003e\n\u003cp\u003e(IV) Collection and assembly of data: Ju Sik Yun, Kyo Seon Lee,\u0026nbsp;Yoo-Duk Choi\u003c/p\u003e\n\u003cp\u003e(V) Data analysis and interpretation: Ju Sik Yun, Yoo-Duk Choi,\u0026nbsp;Sang Yun Song\u003c/p\u003e\n\u003cp\u003e(VI) Manuscript writing: All authors\u003c/p\u003e\n\u003cp\u003e(VII) Final approval of manuscript: All authors\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eXu R, Murray M, Jagirdar J, Delgado Y, Melamed J. Placental transmogrification of the lung is a histologic pattern frequently associated with pulmonary fibrochondromatous hamartoma. Arch Pathol Lab Med. 2002;126(5):562\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCavazza A, Lantuejoul S, Sartori G, Bigiani N, Maiorana A, Pasquinelli G, et al. Placental transmogrification of the lung: clinicopathologic, immunohistochemical and molecular study of two cases, with particular emphasis on the interstitial clear cells. Hum Pathol. 2004;35(4):517\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaito Y, Ikeya T, Hoshi E, Takahashi N, Murai K, Kawabata Y, et al. Placental transmogrification of the lung presenting as a small solitary nodule. Ann Thorac Surg. 2009;87(3):950\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerretti GR, Kocier M, Moro-Sibilot D, Brichon PY, Lantuejoul S. Placental transmogrification of the lung: CT-pathologic correlation of a rare pulmonary nodule. AJR Am J Roentgenol. 2004;183(1):99\u0026ndash;101.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarchevsky AM, Guintu R, Koss M, Fuller C, Houck W, McKenna RJ. Swyer-James (MacLeod) syndrome with placental transmogrification of the lung: a case report and review of the literature. Arch Pathol Lab Med. 2005;129(5):686\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShapiro M, Vidal C, Lipskar AM, Gil J, Litle VR. Placental transmogrification of the lung presenting as emphysema and a lung mass. Ann Thorac Surg. 2009;87(2):615\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrtiz S, Tortosa F. Pulmonary placental transmogrification: The last 16 years in a reference centre. Rev Port Pneumol (2006). 2017;23(3):164-6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa DJ, Liu HS, Li SQ, Zhou XY, Cui YS, Wu HW, et al. Placental transmogrification of the lung: Case report and systematic review of the literature. Med (Baltim). 2017;96(35):e7733.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim JW, Park IH, Kwon W, Eom MS, Kim YJ, Oh JH. Placental transmogrification of the lung. Korean J Radiol. 2013;14(6):977\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbdulelah M, Kasher N, Primera G, Matta J, Patel R, Anis K, et al. Is There a Baby in the Lung? A Case of Placental Transmogrification of the Lung. J Investig Med High Impact Case Rep. 2024;12:23247096241261322.\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":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pulmonary placental transmogrification of the lung, metachronous multifocal disease, solitary pulmonary nodule, Placenta","lastPublishedDoi":"10.21203/rs.3.rs-8952689/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8952689/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePlacental transmogrification of the lung (PTL) is a rare benign pulmonary lesion with limited longitudinal data. We report the case of a 49-year-old man who underwent video-assisted thoracoscopic surgery wedge resection of a 12-mm right-upper-lobe pulmonary nodule subsequently diagnosed as PTL on histopathology. Seven months after surgery, surveillance chest computed tomography (CT) revealed a newly developed 10-mm solid nodule in the right lower lobe, which was resected 12 months after the initial operation and was confirmed as PTL. This case demonstrates metachronous multifocal disease arising in different ipsilateral lobes after complete resection.\u003c/p\u003e \u003cp\u003eHistologic examination of the second lesion was consistent with PTL and showed microscopic emphysematous remodeling, despite the absence of bullous changes on preoperative CT. This finding indicates radiologic\u0026ndash;pathologic discordance, suggesting that microscopic emphysematous remodeling precedes radiologically apparent bullous changes. The observed temporal course supports the need for structured postoperative surveillance, particularly during the early postoperative period.\u003c/p\u003e","manuscriptTitle":"Metachronous Multifocal Placental Transmogrification of the Lung: A Nodular Subtype with Microscopic Emphysematous Changes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-24 13:15:15","doi":"10.21203/rs.3.rs-8952689/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-02T09:44:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-01T06:31:09+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-30T11:55:34+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-26T14:40:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-23T05:53:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"303078971278429338191835947827273631734","date":"2026-04-21T14:17:17+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-20T13:15:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"15881575900871776851338752549916613041","date":"2026-04-20T08:20:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"27024492086794004225692460358861497324","date":"2026-04-20T06:04:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"175329727057219523637785996290619404820","date":"2026-04-19T11:46:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"224200262726343935111885269838063814732","date":"2026-04-19T11:28:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"28906596271299486179006587979953479415","date":"2026-04-19T11:28:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"139249742663348815211669436202576836084","date":"2026-03-22T13:57:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-19T05:15:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-26T13:18:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-26T13:18:19+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Cardiothoracic Surgery","date":"2026-02-24T04:43:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9eb66257-c537-4b4f-a896-c390ea851f18","owner":[],"postedDate":"March 24th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-02T09:44:21+00:00","index":122,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-01T06:31:09+00:00","index":121,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-30T11:55:34+00:00","index":120,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-24T13:15:16+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-24 13:15:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8952689","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8952689","identity":"rs-8952689","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}