Lymphangiomatosis with pulmonary, mediastinal, and spinal Involvement in a pediatric patient: a case report

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This report describes the case of an 8-year-old male patient with lymphangiomatosis involving the lungs, mediastinum, and spine, with the objective of promoting awareness and understanding of this condition. Case presentation An 8-year-old male patient presented with chest tightness. The patient had a history of chylothorax and chylopericardium two years earlier. Chest CT revealed thickening of the interlobular septa and peribronchovascular interstitial tissue in both lungs. Spinal MRI showed scoliosis in the cervicothoracic region, flattening of several vertebral bodies, and multiple osteolytic lesions. Pathological examination of mucosal tissue obtained from the basal segment of the left lower lobe of the lung via bronchoscopy confirmed a diagnosis of lymphangiomatosis. The patient’s condition improved significantly after three weeks of treatment with sirolimus and bevacizumab, with marked alleviation of the chest tightness symptoms during the 23-month follow-up period. Conclusion Lymphangiomatosis is associated with indolent progression and non-specific clinical/radiological features, frequently manifesting as multiorgan involvement. Diagnostic suspicion should arise when chylous effusions coexist with osteolytic lesions, although histopathological verification remains the gold standard. Although there is no current consensus on therapeutic strategies, emerging pharmacological interventions including the use of sirolimus, bevacizumab, propranolol, interferon-α, and tyrosine kinase inhibitors, which demonstrate variable efficacy. This case underscores the importance of multidisciplinary collaboration in the management of complex lymphatic malformations and indicates the potential of targeted therapies in pediatric patients. pediatric population lymphangiomatosis clinical characteristics Figures Figure 1 Figure 2 Background Lymphangiomatosis is a rare disorder characterized by the abnormal proliferation and dilation of lymphatic vessels, typically presenting with diffuse or multifocal distributions within tissues. The condition predominantly involves the lungs, mediastinum, liver, spleen, and bones. Lymphangiomatosis lacks specific clinical symptoms, leading to a high risk of underdiagnosis or misdiagnosis. This report describes a patient with lymphangiomatosis involving the lungs, mediastinum, and spine who was treated at our institution. The relevant literature is also reviewed and the diagnostic challenges and therapeutic approaches for this disease are discussed. Case presentation Patient presentation An 8-year-old male patient was admitted to our hospital in February 2023 for evaluation and treatment of chest tightness that had lasted for one week. The patient presented with chest discomfort, dyspnea on exertion, and labored breathing. A chest X-ray performed at another institution had indicated pneumonia with lung consolidation; however, antimicrobial therapy did not lead to significant improvement. The past medical history was significant, with the occurrence of right-sided pyothorax with fibrous pleural thickening two years before, which had required decortication surgery. Two months after the surgery, the patient developed pericardial effusion and underwent pericardiocentesis, during which milky serosanguineous fluid was drained. The patient’s personal history revealed no consumption of unpasteurized water or raw meat/crabs. There was no known exposure to tuberculosis and the family history was unremarkable. Physical examination The results of the physical examination indicated a heart rate of 108 beats per minute, a respiratory rate of 38 breaths per minute, and a body weight of 19 kg. The patient showed significant emaciation and exhibited a trilateral depression sign. There was notable asymmetry of the thorax, with elevation of the left side relative to the right, accompanied by thoracic vertebral scoliosis. Coarse breath sounds were present bilaterally without rales. No hepatosplenomegaly was observed. Clubbing of the fingers was noted, and there was evidence of scar resulting from Bacillus Calmette-Guerin (BCG) vaccination. Laboratory findings The results of routine blood and urine tests, tests for liver and kidney function, myocardial injury markers, erythrocyte sedimentation rate, anti-neutrophil cytoplasmic antibody (ANCA), interleukin-6 (IL-6), lymphocyte subset analysis, and (1,3)-β-D-glucan detection for fungi were all within the reference ranges. Immunological testing revealed a positive antinuclear antibody (ANA) reaction with a nuclear granular pattern and a titer of 1:1000. Quantitative determination of total serum IgE showed an elevated level of 1486 IU/mL (reference value, < 60). Coagulation function tests indicated a reduced fibrinogen concentration of 1.17 g/L (reference range, 2‒4 g/L) and a prolonged prothrombin time of 15.8 seconds (reference range, 11‒14.5 seconds). The results of both the tuberculin test and the interferon-γ release assay were negative. Cytological examination of the bone marrow aspirate showed no abnormalities. Imaging data Chest computed tomography (CT) findings revealed thickening of the interlobular septa as well as peribronchovascular interstitial thickening in both lungs, along with heterogeneous and reduced bone density in the thoracic vertebrae and ribs. Bilateral pleural effusions were also noted (Fig. 1 A). Spinal magnetic resonance imaging (MRI) indicated flattening of the T1-T8 vertebral bodies, with destruction of the vertebral body and appendage bone, as well as multiple abnormal signals in the prevertebral, paravertebral spaces, soft tissues, muscle spaces, and mediastinal vascular regions (Fig. 1 B). Lymphoscintigraphy showed slightly delayed lymphatic drainage in both lower extremities and increased radiotracer uptake in the cervical root, right axilla, mediastinum, hilar regions, and hepatogastric space, predominantly on the right side. Additionally, multiple irregular cystic lesions were identified on CT. Pathological examination A bronchoscopy was performed to further clarify the diagnosis. The bronchoscopic examination showed significant congestion and edema in the mucosa of the first- to fourth-order bronchi in both lungs, with a tendency to bleed easily. A small amount of viscous secretion was observed within the bronchial lumen (Fig. 1 C). Biopsy specimens were collected from the mucosal tissue of the basal segment of the left lower lobe, and subsequent histopathological examination revealed fibrous and glandular tissues with proliferated and dilated lymphatic vessels. In some areas, the surfaces were lined with ciliated columnar epithelial cells, while other regions showed degenerative changes accompanied by infiltration of lymphocytes, neutrophils, eosinophils, and histiocytes (Figs. 2 A and 2 B). Immunohistochemical staining indicated CD1α (-), S-100 (focal +), Langerin (-), Ki-67 (+, 10%), CD31 (+) (Fig. 2 C), and D2-40 (+) (Fig. 2 D). Diagnosis, treatment, and follow-up Based on the medical history, chest and spinal imaging results, and pathological findings, the child was diagnosed with lymphangiomatosis. The parents requested a referral to an external hospital for further treatment. Follow-up by telephone 23 months later, in January 2025, revealed that the treatment plan involved gradual increases in the oral dose of sirolimus from 1.0 mg to 1.5 mg once daily, as well as intravenous administration of bevacizumab infusions. The patient’s condition improved markedly after three weeks of treatment, with sustained alleviation of chest tightness during the 23-month follow-up period. Discussion and Conclusions Lymphangiomatosis is a rare, insidious disease characterized by the abnormal proliferation and dilation of lymphatic vessels. It can affect multiple tissues and organs throughout the body, with an unclear pathogenesis and slow progression. The clinical manifestations are nonspecific and vary depending on the tissues and organs involved, as well as the extent of involvement, leading to marked variations in symptom severity. Common symptoms include cough, wheezing, hemoptysis, chest pain, dyspnea, pathologic fracture, and recurrent pleural effusion. In some cases, patients may develop disseminated intravascular coagulation (DIC) [ 1 ]. Pleural effusions are often chylous but can also be hemorrhagic [ 2 ]. Rarely, hemorrhagic pericardial effusion may occur [ 3 ]. Patients with pleural and/or pulmonary involvement are at high risk of respiratory failure, representing a common cause of mortality in these cases [ 2 , 3 ]. Typical high-resolution computed tomography (HRCT) findings in cases with pulmonary involvement show the presence of thickened bronchovascular bundles, interlobular septal thickening, pleural thickening, pleural effusion, and mediastinal soft tissue infiltration [ 4 ]. Bone lesions can be found in the skull, ribs, spine, pelvis, and humerus, with imaging features typically showing multiple osteolytic lesions, rounded or oval in shape, with clear margins, and often accompanied by sclerosis [ 5 ]. MRI provides clear visualization of lesions in the skeletal system, spleen, neck, and soft tissues [ 6 ]. Lymphatic scintigraphy indicates the direction of flow in lymphatic vessels and can identify signs such as lymphatic dilation and chylous leakage; however, it is unable to display details of anatomical structures [ 7 ]. Direct lymphangiography (DLG) can not only clearly visualize lymphatic vessel morphology but can also observe lymphatic return, enabling the precise localization of lymphatic leakages, fistulae, and obstruction. Nevertheless, this technique is both invasive and technically challenging, with a risk of serious complications from lipiodol extravasation, including pulmonary, cerebral, and renal embolism, which has limited its widespread clinical application [ 8 ]. Intranodal lymphangiography offers a simpler and safer alternative to the conventional approach [ 9 ]. Following DLG, computed tomography lymphangiography (CTL) can show extensive distributions of contrast medium, enabling the identification of abnormalities, such as dilation, distortion, and fistulae, as well as lymphatic reflux dysfunction, providing a critical foundation for the diagnosis and treatment of lymphangiomatosis [ 10 ]. In this case, chest CT demonstrated characteristic signs of soft tissue infiltration in the lung and mediastinum, while spinal MRI provided a clear visualization of skeletal lesions, and lymphatic radionuclide imaging conducted at other institutions revealed the presence of bilateral pulmonary lymphatic reflux disorder and abnormal lymphatic dilation in the neck root, mediastinum, bilateral hilum, and other regions, all of which were crucial for the final diagnosis. The diagnosis of lymphangiomatosis relies essentially on pathological examinations. Histopathological findings typically include irregular, diffuse proliferation and complex dilation of lymphatic vessels, along with non-specific changes, such as fibrosis, edema, focal hemorrhage, and varying degrees of inflammatory cell infiltration [ 11 , 12 ]. Immunohistochemical staining typically reveals D2-40 (+) and CD31 (+) in the abnormal lymphatic vessels [ 13 , 14 ]. Biopsy sites can be selected from the mediastinum, pleura, or lung tissue. Notably, bronchoscopic bronchopulmonary biopsy carries a significant risk of pulmonary hemorrhage and even mortality, and its use requires careful evaluation [ 15 ]. In comparison, bronchial mucosal biopsy poses fewer risks although it may still result in complications such as bleeding, limited sampling, and potential misdiagnosis. As lymphangiomatosis often involves multiple systems, biopsy can also be performed at relatively low-risk sites, including extrapulmonary lymph nodes, surrounding soft tissues, limb bones, and mediastinal soft tissues [ 12 , 13 , 16 ]. It is important to note, however, that rib biopsy may lead to refractory pleural effusion and should thus be approached with caution [ 11 ]. Lymphangiomatosis requires differentiation from congenital lymphangioma, primary lymphangiectasia, and Gorham-Stout disease (GSD). Congenital lymphangioma presents predominantly as localized masses in the head, neck, and axillary regions, with lung involvement being rare, accounting for only approximately 1% of cases [ 17 ]. In contrast, primary lymphangiectasia typically manifests after birth. Unlike the irregular hyperplasia typical of lymphangiomatosis, the dilated lymphatic vessels in primary lymphangiectasia exhibit a regular morphology [ 18 ]. Histopathologically, distinguishing between GSD and lymphangiomatosis can be challenging; however, GSD is characterized by cortical bone destruction, whereas lymphangiomatosis primarily affects the bone marrow cavity [ 19 ]. There is currently no unified treatment plan for lymphangiomatosis. The primary goals of treatment include the alleviation of clinical symptoms, while reducing chyle accumulation and inhibiting lymphoid tissue hyperplasia. Surgical methods essentially involve tumor resection, thoracic duct ligation, and lung transplantation, among others. Despite a relatively high risk of recurrence, surgical resection remains the preferred treatment option for patients with localized lymphangiomatosis [ 20 ]. While treatment with various drugs, such as glucocorticoids, cyclophosphamide, interferon-α, sildenafil, sirolimus, bevacizumab, and tyrosine kinase inhibitors, as well as sclerotherapy and radiotherapy, has been reported for treating lymphangiomatosis, the treatment efficacy varies [ 17 , 20 – 22 ]. Studies have shown that vascular endothelial growth factor (VEGF) is not only an angiogenic factor but also a lymphangiogenic factor. Propranolol and bevacizumab both inhibit VEGF production, thus exerting therapeutic effects [ 20 , 23 ]. In addition, abnormal activation of the PI3K-AKT-mTOR signaling pathway plays an important role in the pathogenesis of lymphangiomatosis [ 24 ]. Therefore, sirolimus, an mTOR inhibitor, has been found effective in alleviating clinical symptoms, improving lung function and retarding disease progression [ 20 ]. While this drug has good tolerance, it increases the risk of infection, especially pulmonary infection and cellulitis [ 25 ]. In summary, lymphangiomatosis lacks specific clinical and imaging features, and itd diagnosis is thus dependent on pathological examination. For patients presenting with unexplained dyspnea, wheezing, shortness of breath, chest pain, hemoptysis, and associated chylous pleural effusion and/or pericardial effusion, accompanied by thickening of the bronchovascular bundles and interlobular septa on chest CT, together with mediastinal soft tissue infiltration and osteolytic lesions, the possibility of lymphangiomatosis should be considered. While the primary treatment approach is pharmacotherapy, surgical resection may be considered for localized lesions, although the overall therapeutic outcomes remain suboptimal. Abbreviations CT: computed tomography BCG: Bacillus Calmette-Guerin ANA: anti-neutrophil cytoplasmic antibody IL-6: interleukin-6 ANA: antinuclear antibody MRI: magnetic resonance imaging DIC: disseminated intravascular coagulation HRCT: high-resolution computed tomography DLG: direct lymphangiography CTL: computed tomography lymphangiography GSD: Gorham-Stout disease VEGF: vascular endothelial growth factor Declarations Author contributions LT designed the study; YXS and JZ reviewed the literature and contributed to manuscript drafting；XQH and ML provided clinical data; all authors took part in writing the manuscript and approved the final, submitted version. Funding This work was supported by the 2022 Annual Project for Key Clinical Specialty Construction in Kunming City - Department of Pediatric Infectious Diseases ; The 14th Five-Year Plan Project for Key Clinical Specialty Construction in Yunnan Province - Department of Infectious Diseases. Data availability The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethical approval This study was approved by the Ethics Committee of Children's Hospital Affiliated to Kunming Medical University (Approval Number:2025-05-017-K01). All the research procedures were carried out in accordance with the principles of the Helsinki Declaration. The patients and their parents provided written informed consent for participating in this study. Consent for publication Written informed consent to publish this case was obtained from the patient and her parents, including case descriptions and medical data. Competing interests The authors declare no competing interests. Clinical trial number: not applicable. References Tamay Z, Saribeyoglu E, Ones U, Anak S, Güler N, Bilgic B, Yilmazbayhan D, Gun F. Diffuse thoracic lymphangiomatosis with disseminated intravascular coagulation in a child. J Pediatr Hematol Oncol. 2005 Dec;27(12):685-7. Kadakia KC, Patel SM, Yi ES, Limper AH. Diffuse pulmonary lymphangiomatosis. Can Respir J. 2013 Jan-Feb;20(1):52-4. Kothari SS, Sharma S, Bhatt K, Ray R, Bakhshi S, Chowdhury U. Recurrent hemorrhagic pericardial effusion in a child due to diffuse lymphangiohemangiomatosis: a case report. J Med Case Rep. 2010 Feb 22;4:62. Yekeler E, Dursun M, Yildirim A, Tunaci M. Diffuse pulmonary lymphangiomatosis: imaging findings. Diagn Interv Radiol. 2005 Mar;11(1):31-4. Ozturk A, Yousem DM. Magnetic resonance imaging findings in diffuse lymphangiomatosis: neuroradiological manifestations. Acta Radiol. 2007 Jun;48(5):560-4. Ozel A, Uysal E, Dokucu AI, Erturk SM, Basak M, Cantisani V. US, CT and MRI findings in a case of diffuse lymphangiomatosis and cystic hygroma. J Ultrasound. 2008 Mar;11(1):22-5. Turpin S, Lambert R. Lymphoscintigraphy of Chylous Anomalies: Chylothorax, Chyloperitoneum, Chyluria, and Lymphangiomatosis-15-Year Experience in a Pediatric Setting and Review of the Literature. J Nucl Med Technol. 2018 Jun;46(2):123-128. Deso S, Ludwig B, Kabutey NK, Kim D, Guermazi A. Lymphangiography in the diagnosis and localization of various chyle leaks. Cardiovasc Intervent Radiol. 2012 Feb;35(1):117-26. Rajebi MR, Chaudry G, Padua HM, Dillon B, Yilmaz S, Arnold RW, Landrigan-Ossar MF, Alomari AI. Intranodal lymphangiography: feasibility and preliminary experience in children. J Vasc Interv Radiol. 2011 Sep;22(9):1300-5. Jin D, Sun X, Shen W, Zhao Q, Wang R. Diagnosis of Lymphangiomatosis: A Study Based on CT Lymphangiography. Acad Radiol. 2020 Feb;27(2):219-226. Trenor CC 3rd, Chaudry G. Complex lymphatic anomalies. Semin Pediatr Surg. 2014 Aug;23(4):186-90. Sun X, Lu C, Huang Z, Xu J, Zhu H, Yang S, Chen D. Diagnosis and treatment of diffuse pulmonary lymphangioma in children: A case report. Exp Ther Med. 2023 Mar 7;25(4):175. Fang X, Huang Z, Zeng Y, Zhu X, Wang S, Yu X, Li X, Wu C, Yi X. Lymphangiomatosis involving the pulmonary and extrapulmonary lymph nodes and surrounding soft tissue: A rare case report. Medicine (Baltimore). 2017 Dec;96(49):e9032. Ramani P, Shah A. Lymphangiomatosis. Histologic and immunohistochemical analysis of four cases. Am J Surg Pathol. 1993 Apr;17(4):329-35. Shen QY, Nong GM, Gu YY. [Diffuse pulmonary lymphangiomatosis: two cases report]. Zhonghua Er Ke Za Zhi. 2016 Oct 2;54(10):781-782. Tran D, Fallat ME, Buchino JJ. Lymphangiomatosis: a case report. South Med J. 2005 Jun;98(6):669-71. Faul JL, Berry GJ, Colby TV, Ruoss SJ, Walter MB, Rosen GD, Raffin TA. Thoracic lymphangiomas, lymphangiectasis, lymphangiomatosis, and lymphatic dysplasia syndrome. Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):1037-46. Yuan SM. Congenital pulmonary lymphangiectasia. J Perinat Med. 2017 Dec 20;45(9):1023-1030. Ozeki M, Fujino A, Matsuoka K, Nosaka S, Kuroda T, Fukao T. Clinical Features and Prognosis of Generalized Lymphatic Anomaly, Kaposiform Lymphangiomatosis, and Gorham-Stout Disease. Pediatr Blood Cancer. 2016 May;63(5):832-8. Gurskytė V, Zeleckienė I, Maskoliūnaitė V, Mickys U, Šileikienė V. Successful treatment of diffuse pulmonary lymphangiomatosis with sirolimus. Respir Med Case Rep. 2020 Feb 1;29:101014. Hangul M, Kose M, Ozcan A, Unal E. Propranolol treatment for chylothorax due to diffuse lymphangiomatosis. Pediatr Blood Cancer. 2019 May;66(5):e27592. Ozeki M, Funato M, Kanda K, Ito M, Teramoto T, Kaneko H, Fukao T, Kondo N. Clinical improvement of diffuse lymphangiomatosis with pegylated interferon alfa-2b therapy: case report and review of the literature. Pediatr Hematol Oncol. 2007 Oct-Nov;24(7):513-24. Rotter A, de Oliveira ZNP. Infantile hemangioma: pathogenesis and mechanisms of action of propranolol. J Dtsch Dermatol Ges. 2017 Dec;15(12):1185-1190. Rodriguez-Laguna L, Agra N, Ibañez K, Oliva-Molina G, Gordo G, Khurana N, Hominick D, Beato M, Colmenero I, Herranz G, Torres Canizalez JM, Rodríguez Pena R, Vallespín E, Martín-Arenas R, Del Pozo Á, Villaverde C, Bustamante A, Ayuso C, Lapunzina P, Lopez-Gutierrez JC, Dellinger MT, Martinez-Glez V. Somatic activating mutations in PIK3CA cause generalized lymphatic anomaly. J Exp Med. 2019 Feb 4;216(2):407-418. Ozeki M, Nozawa A, Yasue S, Endo S, Asada R, Hashimoto H, Fukao T. The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with lymphatic anomalies. Orphanet J Rare Dis. 2019 Jun 13;14(1):141. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 04 Jul, 2025 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 28 May, 2025 Reviews received at journal 18 May, 2025 Reviewers agreed at journal 11 May, 2025 Reviewers agreed at journal 10 May, 2025 Reviews received at journal 03 May, 2025 Reviewers agreed at journal 26 Apr, 2025 Reviewers agreed at journal 25 Apr, 2025 Reviewers agreed at journal 23 Apr, 2025 Reviewers invited by journal 17 Mar, 2025 Editor invited by journal 17 Mar, 2025 Editor assigned by journal 14 Mar, 2025 Submission checks completed at journal 14 Mar, 2025 First submitted to journal 12 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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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-6210632","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":430652328,"identity":"51627009-3c00-4179-945d-1b74cd7dce9a","order_by":0,"name":"Yuxing Sun","email":"","orcid":"","institution":"Kunming Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuxing","middleName":"","lastName":"Sun","suffix":""},{"id":430652329,"identity":"17b9eef8-ad9b-487d-b8c7-4aa910a97e41","order_by":1,"name":"Jun Zhou","email":"","orcid":"","institution":"Kunming Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Zhou","suffix":""},{"id":430652330,"identity":"f729550b-098e-4769-9886-ef7173be25db","order_by":2,"name":"Xiaoqin Hu","email":"","orcid":"","institution":"Kunming Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiaoqin","middleName":"","lastName":"Hu","suffix":""},{"id":430652331,"identity":"b1768999-ad9b-4fc3-995c-8f7d1ee5a4db","order_by":3,"name":"Ming Li","email":"","orcid":"","institution":"Kunming Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ming","middleName":"","lastName":"Li","suffix":""},{"id":430652332,"identity":"8f7eba38-3bde-4af5-8f46-4fb6e5de0d07","order_by":4,"name":"Li Tan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsUlEQVRIiWNgGAWjYBACfmb+jw8+GNTIEa9Fsp3B2HBGxTFj4rUY9DOYSfOcYU5sIF4LM0OyMW8bW3rf8QTGDx9ziNBizsxw8OHcNpncmWceMEvO3EaEFstmxmaDt21suRtuJLAx8xKjxeAwM5sEbxtzugEJWtjYJIHeTyBei2QzDzMokA1nnnnYTJxf+PnPMIKiUp7vePLBDx+J0YIAB0iIGpiWBFJ1jIJRMApGwUgBAKNZN0uWfYWrAAAAAElFTkSuQmCC","orcid":"","institution":"Kunming Children’s Hospital","correspondingAuthor":true,"prefix":"","firstName":"Li","middleName":"","lastName":"Tan","suffix":""}],"badges":[],"createdAt":"2025-03-12 09:23:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6210632/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6210632/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-025-05884-2","type":"published","date":"2025-07-04T15:57:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79172811,"identity":"9374ee41-4058-4a32-a3c3-41543f588f6c","added_by":"auto","created_at":"2025-03-25 09:44:21","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2446600,"visible":true,"origin":"","legend":"\u003cp\u003eThe imaging findings of the patient. \u003cstrong\u003eA\u003c/strong\u003e CT findings showed thickened interlobular septa and peribronchovascular tissues in both lungs, heterogeneous and reduced bone density in thoracic vertebrae and ribs, and bilateral pleural effusions. \u003cstrong\u003eB\u003c/strong\u003e MRI showed flattening of T1-T8 vertebral bodies with destruction of the vertebrae and appendages, and multiple abnormal signals in the prevertebral, paravertebral, soft tissue, muscle, and mediastinal vascular areas. \u003cstrong\u003eC \u003c/strong\u003eThe bronchoscopic examination showed significant congestion and edema in both lungs, with a tendency to bleed easily.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6210632/v1/12fadbb6a752bc8998f7a82c.png"},{"id":79172815,"identity":"ed80380f-f4ea-4cf5-9524-2cf1c628477a","added_by":"auto","created_at":"2025-03-25 09:44:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":8561309,"visible":true,"origin":"","legend":"\u003cp\u003ePathological results of the patient.\u003cstrong\u003e A\u003c/strong\u003e HE staining (×200); \u003cstrong\u003eB\u003c/strong\u003e HE staining (×200); \u003cstrong\u003eC\u003c/strong\u003e Immunostaining for CD31 is positive (×200); \u003cstrong\u003eD\u003c/strong\u003e Immunostaining for D2-40 is positive (×200)\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6210632/v1/c1e42c93e7f2a8801717fb3e.png"},{"id":86179736,"identity":"d46fd492-f163-4a28-b8c5-ad063482a533","added_by":"auto","created_at":"2025-07-07 16:19:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":13548377,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6210632/v1/83753b62-5ac2-4411-9e60-cf2a9cd86554.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eLymphangiomatosis with pulmonary, mediastinal, and spinal Involvement in a pediatric patient: a case report\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eLymphangiomatosis is a rare disorder characterized by the abnormal proliferation and dilation of lymphatic vessels, typically presenting with diffuse or multifocal distributions within tissues. The condition predominantly involves the lungs, mediastinum, liver, spleen, and bones. Lymphangiomatosis lacks specific clinical symptoms, leading to a high risk of underdiagnosis or misdiagnosis. This report describes a patient with lymphangiomatosis involving the lungs, mediastinum, and spine who was treated at our institution. The relevant literature is also reviewed and the diagnostic challenges and therapeutic approaches for this disease are discussed.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient presentation\u003c/h2\u003e \u003cp\u003eAn 8-year-old male patient was admitted to our hospital in February 2023 for evaluation and treatment of chest tightness that had lasted for one week. The patient presented with chest discomfort, dyspnea on exertion, and labored breathing. A chest X-ray performed at another institution had indicated pneumonia with lung consolidation; however, antimicrobial therapy did not lead to significant improvement. The past medical history was significant, with the occurrence of right-sided pyothorax with fibrous pleural thickening two years before, which had required decortication surgery. Two months after the surgery, the patient developed pericardial effusion and underwent pericardiocentesis, during which milky serosanguineous fluid was drained. The patient\u0026rsquo;s personal history revealed no consumption of unpasteurized water or raw meat/crabs. There was no known exposure to tuberculosis and the family history was unremarkable.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePhysical examination\u003c/h3\u003e\n\u003cp\u003eThe results of the physical examination indicated a heart rate of 108 beats per minute, a respiratory rate of 38 breaths per minute, and a body weight of 19 kg. The patient showed significant emaciation and exhibited a trilateral depression sign. There was notable asymmetry of the thorax, with elevation of the left side relative to the right, accompanied by thoracic vertebral scoliosis. Coarse breath sounds were present bilaterally without rales. No hepatosplenomegaly was observed. Clubbing of the fingers was noted, and there was evidence of scar resulting from Bacillus Calmette-Guerin (BCG) vaccination.\u003c/p\u003e\n\u003ch3\u003eLaboratory findings\u003c/h3\u003e\n\u003cp\u003eThe results of routine blood and urine tests, tests for liver and kidney function, myocardial injury markers, erythrocyte sedimentation rate, anti-neutrophil cytoplasmic antibody (ANCA), interleukin-6 (IL-6), lymphocyte subset analysis, and (1,3)-β-D-glucan detection for fungi were all within the reference ranges. Immunological testing revealed a positive antinuclear antibody (ANA) reaction with a nuclear granular pattern and a titer of 1:1000. Quantitative determination of total serum IgE showed an elevated level of 1486 IU/mL (reference value, \u0026lt; 60). Coagulation function tests indicated a reduced fibrinogen concentration of 1.17 g/L (reference range, 2‒4 g/L) and a prolonged prothrombin time of 15.8 seconds (reference range, 11‒14.5 seconds). The results of both the tuberculin test and the interferon-γ release assay were negative. Cytological examination of the bone marrow aspirate showed no abnormalities.\u003c/p\u003e\n\u003ch3\u003eImaging data\u003c/h3\u003e\n\u003cp\u003eChest computed tomography (CT) findings revealed thickening of the interlobular septa as well as peribronchovascular interstitial thickening in both lungs, along with heterogeneous and reduced bone density in the thoracic vertebrae and ribs. Bilateral pleural effusions were also noted (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Spinal magnetic resonance imaging (MRI) indicated flattening of the T1-T8 vertebral bodies, with destruction of the vertebral body and appendage bone, as well as multiple abnormal signals in the prevertebral, paravertebral spaces, soft tissues, muscle spaces, and mediastinal vascular regions (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). Lymphoscintigraphy showed slightly delayed lymphatic drainage in both lower extremities and increased radiotracer uptake in the cervical root, right axilla, mediastinum, hilar regions, and hepatogastric space, predominantly on the right side. Additionally, multiple irregular cystic lesions were identified on CT.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003ePathological examination\u003c/h3\u003e\n\u003cp\u003eA bronchoscopy was performed to further clarify the diagnosis. The bronchoscopic examination showed significant congestion and edema in the mucosa of the first- to fourth-order bronchi in both lungs, with a tendency to bleed easily. A small amount of viscous secretion was observed within the bronchial lumen (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). Biopsy specimens were collected from the mucosal tissue of the basal segment of the left lower lobe, and subsequent histopathological examination revealed fibrous and glandular tissues with proliferated and dilated lymphatic vessels. In some areas, the surfaces were lined with ciliated columnar epithelial cells, while other regions showed degenerative changes accompanied by infiltration of lymphocytes, neutrophils, eosinophils, and histiocytes (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Immunohistochemical staining indicated CD1α (-), S-100 (focal +), Langerin (-), Ki-67 (+, 10%), CD31 (+) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC), and D2-40 (+) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDiagnosis, treatment, and follow-up\u003c/h2\u003e \u003cp\u003eBased on the medical history, chest and spinal imaging results, and pathological findings, the child was diagnosed with lymphangiomatosis. The parents requested a referral to an external hospital for further treatment. Follow-up by telephone 23 months later, in January 2025, revealed that the treatment plan involved gradual increases in the oral dose of sirolimus from 1.0 mg to 1.5 mg once daily, as well as intravenous administration of bevacizumab infusions. The patient\u0026rsquo;s condition improved markedly after three weeks of treatment, with sustained alleviation of chest tightness during the 23-month follow-up period.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eLymphangiomatosis is a rare, insidious disease characterized by the abnormal proliferation and dilation of lymphatic vessels. It can affect multiple tissues and organs throughout the body, with an unclear pathogenesis and slow progression. The clinical manifestations are nonspecific and vary depending on the tissues and organs involved, as well as the extent of involvement, leading to marked variations in symptom severity. Common symptoms include cough, wheezing, hemoptysis, chest pain, dyspnea, pathologic fracture, and recurrent pleural effusion. In some cases, patients may develop disseminated intravascular coagulation (DIC) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Pleural effusions are often chylous but can also be hemorrhagic [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Rarely, hemorrhagic pericardial effusion may occur [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Patients with pleural and/or pulmonary involvement are at high risk of respiratory failure, representing a common cause of mortality in these cases [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Typical high-resolution computed tomography (HRCT) findings in cases with pulmonary involvement show the presence of thickened bronchovascular bundles, interlobular septal thickening, pleural thickening, pleural effusion, and mediastinal soft tissue infiltration [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Bone lesions can be found in the skull, ribs, spine, pelvis, and humerus, with imaging features typically showing multiple osteolytic lesions, rounded or oval in shape, with clear margins, and often accompanied by sclerosis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMRI provides clear visualization of lesions in the skeletal system, spleen, neck, and soft tissues [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Lymphatic scintigraphy indicates the direction of flow in lymphatic vessels and can identify signs such as lymphatic dilation and chylous leakage; however, it is unable to display details of anatomical structures [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Direct lymphangiography (DLG) can not only clearly visualize lymphatic vessel morphology but can also observe lymphatic return, enabling the precise localization of lymphatic leakages, fistulae, and obstruction. Nevertheless, this technique is both invasive and technically challenging, with a risk of serious complications from lipiodol extravasation, including pulmonary, cerebral, and renal embolism, which has limited its widespread clinical application [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Intranodal lymphangiography offers a simpler and safer alternative to the conventional approach [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Following DLG, computed tomography lymphangiography (CTL) can show extensive distributions of contrast medium, enabling the identification of abnormalities, such as dilation, distortion, and fistulae, as well as lymphatic reflux dysfunction, providing a critical foundation for the diagnosis and treatment of lymphangiomatosis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In this case, chest CT demonstrated characteristic signs of soft tissue infiltration in the lung and mediastinum, while spinal MRI provided a clear visualization of skeletal lesions, and lymphatic radionuclide imaging conducted at other institutions revealed the presence of bilateral pulmonary lymphatic reflux disorder and abnormal lymphatic dilation in the neck root, mediastinum, bilateral hilum, and other regions, all of which were crucial for the final diagnosis.\u003c/p\u003e \u003cp\u003eThe diagnosis of lymphangiomatosis relies essentially on pathological examinations. Histopathological findings typically include irregular, diffuse proliferation and complex dilation of lymphatic vessels, along with non-specific changes, such as fibrosis, edema, focal hemorrhage, and varying degrees of inflammatory cell infiltration [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Immunohistochemical staining typically reveals D2-40 (+) and CD31 (+) in the abnormal lymphatic vessels [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Biopsy sites can be selected from the mediastinum, pleura, or lung tissue. Notably, bronchoscopic bronchopulmonary biopsy carries a significant risk of pulmonary hemorrhage and even mortality, and its use requires careful evaluation [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In comparison, bronchial mucosal biopsy poses fewer risks although it may still result in complications such as bleeding, limited sampling, and potential misdiagnosis. As lymphangiomatosis often involves multiple systems, biopsy can also be performed at relatively low-risk sites, including extrapulmonary lymph nodes, surrounding soft tissues, limb bones, and mediastinal soft tissues [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. It is important to note, however, that rib biopsy may lead to refractory pleural effusion and should thus be approached with caution [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLymphangiomatosis requires differentiation from congenital lymphangioma, primary lymphangiectasia, and Gorham-Stout disease (GSD). Congenital lymphangioma presents predominantly as localized masses in the head, neck, and axillary regions, with lung involvement being rare, accounting for only approximately 1% of cases [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In contrast, primary lymphangiectasia typically manifests after birth. Unlike the irregular hyperplasia typical of lymphangiomatosis, the dilated lymphatic vessels in primary lymphangiectasia exhibit a regular morphology [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Histopathologically, distinguishing between GSD and lymphangiomatosis can be challenging; however, GSD is characterized by cortical bone destruction, whereas lymphangiomatosis primarily affects the bone marrow cavity [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere is currently no unified treatment plan for lymphangiomatosis. The primary goals of treatment include the alleviation of clinical symptoms, while reducing chyle accumulation and inhibiting lymphoid tissue hyperplasia. Surgical methods essentially involve tumor resection, thoracic duct ligation, and lung transplantation, among others. Despite a relatively high risk of recurrence, surgical resection remains the preferred treatment option for patients with localized lymphangiomatosis [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. While treatment with various drugs, such as glucocorticoids, cyclophosphamide, interferon-α, sildenafil, sirolimus, bevacizumab, and tyrosine kinase inhibitors, as well as sclerotherapy and radiotherapy, has been reported for treating lymphangiomatosis, the treatment efficacy varies [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Studies have shown that vascular endothelial growth factor (VEGF) is not only an angiogenic factor but also a lymphangiogenic factor. Propranolol and bevacizumab both inhibit VEGF production, thus exerting therapeutic effects [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In addition, abnormal activation of the PI3K-AKT-mTOR signaling pathway plays an important role in the pathogenesis of lymphangiomatosis [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Therefore, sirolimus, an mTOR inhibitor, has been found effective in alleviating clinical symptoms, improving lung function and retarding disease progression [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. While this drug has good tolerance, it increases the risk of infection, especially pulmonary infection and cellulitis [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn summary, lymphangiomatosis lacks specific clinical and imaging features, and itd diagnosis is thus dependent on pathological examination. For patients presenting with unexplained dyspnea, wheezing, shortness of breath, chest pain, hemoptysis, and associated chylous pleural effusion and/or pericardial effusion, accompanied by thickening of the bronchovascular bundles and interlobular septa on chest CT, together with mediastinal soft tissue infiltration and osteolytic lesions, the possibility of lymphangiomatosis should be considered. While the primary treatment approach is pharmacotherapy, surgical resection may be considered for localized lesions, although the overall therapeutic outcomes remain suboptimal.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCT:\u0026nbsp;computed tomography\u003c/p\u003e\n\u003cp\u003eBCG: Bacillus Calmette-Guerin\u003c/p\u003e\n\u003cp\u003eANA:\u0026nbsp;anti-neutrophil cytoplasmic antibody\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIL-6: interleukin-6\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eANA: antinuclear antibody\u003c/p\u003e\n\u003cp\u003eMRI: magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003eDIC:\u0026nbsp;disseminated intravascular coagulation\u003c/p\u003e\n\u003cp\u003eHRCT:\u0026nbsp;high-resolution computed tomography\u003c/p\u003e\n\u003cp\u003eDLG: direct lymphangiography\u003c/p\u003e\n\u003cp\u003eCTL: computed tomography\u003cins cite=\"mailto:jun%20zhou\" datetime=\"2025-03-05T14:27\"\u003e\u0026nbsp;\u003c/ins\u003elymphangiography\u003c/p\u003e\n\u003cp\u003eGSD: Gorham-Stout disease\u003c/p\u003e\n\u003cp\u003eVEGF: vascular endothelial growth factor\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLT designed the study; YXS and JZ reviewed the literature and contributed to manuscript drafting；XQH and ML provided clinical data; all authors took part in writing the manuscript and approved the final, submitted version. \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the 2022 Annual Project for Key Clinical Specialty Construction in Kunming City - Department of Pediatric Infectious Diseases\u0026nbsp;; The 14th Five-Year Plan Project for Key Clinical Specialty Construction in Yunnan Province - Department of Infectious Diseases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Children\u0026apos;s Hospital Affiliated to Kunming Medical University (Approval Number:2025-05-017-K01). All the research procedures were carried out in accordance with the principles of the Helsinki Declaration. The patients and their parents provided written informed consent for participating in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent to publish this case was obtained from the patient and her parents, including case descriptions and medical data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number:\u0026nbsp;\u003c/strong\u003enot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eTamay Z, Saribeyoglu E, Ones U, Anak S, G\u0026uuml;ler N, Bilgic B, Yilmazbayhan D, Gun F. Diffuse thoracic lymphangiomatosis with disseminated intravascular coagulation in a child. J Pediatr Hematol Oncol. 2005 Dec;27(12):685-7.\u003c/li\u003e\n \u003cli\u003eKadakia KC, Patel SM, Yi ES, Limper AH. Diffuse pulmonary lymphangiomatosis. Can Respir J. 2013 Jan-Feb;20(1):52-4.\u003c/li\u003e\n \u003cli\u003eKothari SS, Sharma S, Bhatt K, Ray R, Bakhshi S, Chowdhury U. Recurrent hemorrhagic pericardial effusion in a child due to diffuse lymphangiohemangiomatosis: a case report. J Med Case Rep. 2010 Feb 22;4:62.\u003c/li\u003e\n \u003cli\u003eYekeler E, Dursun M, Yildirim A, Tunaci M. Diffuse pulmonary lymphangiomatosis: imaging findings. Diagn Interv Radiol. 2005 Mar;11(1):31-4.\u003c/li\u003e\n \u003cli\u003eOzturk A, Yousem DM. Magnetic resonance imaging findings in diffuse lymphangiomatosis: neuroradiological manifestations. Acta Radiol. 2007 Jun;48(5):560-4.\u003c/li\u003e\n \u003cli\u003eOzel A, Uysal E, Dokucu AI, Erturk SM, Basak M, Cantisani V. US, CT and MRI findings in a case of diffuse lymphangiomatosis and cystic hygroma. J Ultrasound. 2008 Mar;11(1):22-5.\u003c/li\u003e\n \u003cli\u003eTurpin S, Lambert R. Lymphoscintigraphy of Chylous Anomalies: Chylothorax, Chyloperitoneum, Chyluria, and Lymphangiomatosis-15-Year Experience in a Pediatric Setting and Review of the Literature. J Nucl Med Technol. 2018 Jun;46(2):123-128.\u003c/li\u003e\n \u003cli\u003eDeso S, Ludwig B, Kabutey NK, Kim D, Guermazi A. Lymphangiography in the diagnosis and localization of various chyle leaks. Cardiovasc Intervent Radiol. 2012 Feb;35(1):117-26.\u003c/li\u003e\n \u003cli\u003eRajebi MR, Chaudry G, Padua HM, Dillon B, Yilmaz S, Arnold RW, Landrigan-Ossar MF, Alomari AI. Intranodal lymphangiography: feasibility and preliminary experience in children. J Vasc Interv Radiol. 2011 Sep;22(9):1300-5.\u003c/li\u003e\n \u003cli\u003eJin D, Sun X, Shen W, Zhao Q, Wang R. Diagnosis of Lymphangiomatosis: A Study Based on CT Lymphangiography. Acad Radiol. 2020 Feb;27(2):219-226.\u003c/li\u003e\n \u003cli\u003eTrenor CC 3rd, Chaudry G. Complex lymphatic anomalies. Semin Pediatr Surg. 2014 Aug;23(4):186-90.\u003c/li\u003e\n \u003cli\u003eSun X, Lu C, Huang Z, Xu J, Zhu H, Yang S, Chen D. Diagnosis and treatment of diffuse pulmonary lymphangioma in children: A case report. Exp Ther Med. 2023 Mar 7;25(4):175.\u003c/li\u003e\n \u003cli\u003eFang X, Huang Z, Zeng Y, Zhu X, Wang S, Yu X, Li X, Wu C, Yi X. Lymphangiomatosis involving the pulmonary and extrapulmonary lymph nodes and surrounding soft tissue: A rare case report. Medicine (Baltimore). 2017 Dec;96(49):e9032.\u003c/li\u003e\n \u003cli\u003eRamani P, Shah A. Lymphangiomatosis. Histologic and immunohistochemical analysis of four cases. Am J Surg Pathol. 1993 Apr;17(4):329-35.\u003c/li\u003e\n \u003cli\u003eShen QY, Nong GM, Gu YY. [Diffuse pulmonary lymphangiomatosis: two cases report]. Zhonghua Er Ke Za Zhi. 2016 Oct 2;54(10):781-782.\u003c/li\u003e\n \u003cli\u003eTran D, Fallat ME, Buchino JJ. Lymphangiomatosis: a case report. South Med J. 2005 Jun;98(6):669-71.\u003c/li\u003e\n \u003cli\u003eFaul JL, Berry GJ, Colby TV, Ruoss SJ, Walter MB, Rosen GD, Raffin TA. Thoracic lymphangiomas, lymphangiectasis, lymphangiomatosis, and lymphatic dysplasia syndrome. Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):1037-46.\u003c/li\u003e\n \u003cli\u003eYuan SM. Congenital pulmonary lymphangiectasia. J Perinat Med. 2017 Dec 20;45(9):1023-1030.\u003c/li\u003e\n \u003cli\u003eOzeki M, Fujino A, Matsuoka K, Nosaka S, Kuroda T, Fukao T. Clinical Features and Prognosis of Generalized Lymphatic Anomaly, Kaposiform Lymphangiomatosis, and Gorham-Stout Disease. Pediatr Blood Cancer. 2016 May;63(5):832-8.\u003c/li\u003e\n \u003cli\u003eGurskytė V, Zeleckienė I, Maskoliūnaitė V, Mickys U, \u0026Scaron;ileikienė V. Successful treatment of diffuse pulmonary lymphangiomatosis with sirolimus. Respir Med Case Rep. 2020 Feb 1;29:101014.\u003c/li\u003e\n \u003cli\u003eHangul M, Kose M, Ozcan A, Unal E. Propranolol treatment for chylothorax due to diffuse lymphangiomatosis. Pediatr Blood Cancer. 2019 May;66(5):e27592.\u003c/li\u003e\n \u003cli\u003eOzeki M, Funato M, Kanda K, Ito M, Teramoto T, Kaneko H, Fukao T, Kondo N. Clinical improvement of diffuse lymphangiomatosis with pegylated interferon alfa-2b therapy: case report and review of the literature. Pediatr Hematol Oncol. 2007 Oct-Nov;24(7):513-24.\u003c/li\u003e\n \u003cli\u003eRotter A, de Oliveira ZNP. Infantile hemangioma: pathogenesis and mechanisms of action of propranolol. J Dtsch Dermatol Ges. 2017 Dec;15(12):1185-1190.\u003c/li\u003e\n \u003cli\u003eRodriguez-Laguna L, Agra N, Iba\u0026ntilde;ez K, Oliva-Molina G, Gordo G, Khurana N, Hominick D, Beato M, Colmenero I, Herranz G, Torres Canizalez JM, Rodr\u0026iacute;guez Pena R, Vallesp\u0026iacute;n E, Mart\u0026iacute;n-Arenas R, Del Pozo \u0026Aacute;, Villaverde C, Bustamante A, Ayuso C, Lapunzina P, Lopez-Gutierrez JC, Dellinger MT, Martinez-Glez V. Somatic activating mutations in \u003cem\u003ePIK3CA\u003c/em\u003e cause generalized lymphatic anomaly. J Exp Med. 2019 Feb 4;216(2):407-418.\u003c/li\u003e\n \u003cli\u003eOzeki M, Nozawa A, Yasue S, Endo S, Asada R, Hashimoto H, Fukao T. The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with lymphatic anomalies. Orphanet J Rare Dis. 2019 Jun 13;14(1):141.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"pediatric population, lymphangiomatosis, clinical characteristics","lastPublishedDoi":"10.21203/rs.3.rs-6210632/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6210632/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003cbr\u003e\nLymphangiomatosis is a rare disorder characterized by abnormal proliferation and dilation of lymphatic vessels, resulting in non-specific clinical manifestations. This report describes the case of an 8-year-old male patient with lymphangiomatosis involving the lungs, mediastinum, and spine, with the objective of promoting awareness and understanding of this condition.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003cbr\u003e\nAn 8-year-old male patient presented with chest tightness. The patient had a history of chylothorax and chylopericardium two years earlier. Chest CT revealed thickening of the interlobular septa and peribronchovascular interstitial tissue in both lungs. Spinal MRI showed scoliosis in the cervicothoracic region, flattening of several vertebral bodies, and multiple osteolytic lesions. Pathological examination of mucosal tissue obtained from the basal segment of the left lower lobe of the lung \u003cem\u003evia\u003c/em\u003ebronchoscopy confirmed a diagnosis of lymphangiomatosis. The patient’s condition improved significantly after three weeks of treatment with sirolimus and bevacizumab, with marked alleviation of the chest tightness symptoms during the 23-month follow-up period.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003cbr\u003e\nLymphangiomatosis is associated with indolent progression and non-specific clinical/radiological features, frequently manifesting as multiorgan involvement. Diagnostic suspicion should arise when chylous effusions coexist with osteolytic lesions, although histopathological verification remains the gold standard. Although there is no current consensus on therapeutic strategies, emerging pharmacological interventions including the use of sirolimus, bevacizumab, propranolol, interferon-α, and tyrosine kinase inhibitors, which demonstrate variable efficacy. This case underscores the importance of multidisciplinary collaboration in the management of complex lymphatic malformations and indicates the potential of targeted therapies in pediatric patients.\u003c/p\u003e","manuscriptTitle":"Lymphangiomatosis with pulmonary, mediastinal, and spinal Involvement in a pediatric patient: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-25 09:44:16","doi":"10.21203/rs.3.rs-6210632/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-28T10:23:13+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-18T08:24:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"322750761398811002591300171556024202367","date":"2025-05-11T20:25:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"111491989435820653472458536146410638920","date":"2025-05-10T06:38:59+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-03T15:19:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"83822456757048293286536634520334425616","date":"2025-04-26T21:37:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"330375118990313613086736546680364128567","date":"2025-04-25T07:44:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"72867938933990521508219576101225639986","date":"2025-04-23T16:58:02+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-17T16:53:50+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-03-17T07:22:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-15T02:04:13+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-15T02:04:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2025-03-12T09:16:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0aa640fa-ddc0-4174-810c-a0d23da659c7","owner":[],"postedDate":"March 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-07T16:10:41+00:00","versionOfRecord":{"articleIdentity":"rs-6210632","link":"https://doi.org/10.1186/s12887-025-05884-2","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2025-07-04 15:57:45","publishedOnDateReadable":"July 4th, 2025"},"versionCreatedAt":"2025-03-25 09:44:16","video":"","vorDoi":"10.1186/s12887-025-05884-2","vorDoiUrl":"https://doi.org/10.1186/s12887-025-05884-2","workflowStages":[]},"version":"v1","identity":"rs-6210632","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6210632","identity":"rs-6210632","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}