{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:40:56Z","timestamp":1790109656021,"version":"4.0.1"},"reference-count":46,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Lymphatic Research and Biology"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Generalized lymphatic anomaly (GLA), Gorham-Stout disease (GSD), kaposiform lymphangiomatosis (KLA), and central conducting lymphatic anomaly (CCLA) are rare, multisystem lymphatic disorders, referred to as complex lymphatic anomalies (CLAs). Their etiology remains poorly understood; however, somatic activating mutations have recently been discovered, and the results of targeted treatments are promising. This study aimed to elaborate on the phenotypic description of CLA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Thirty-six consecutive patients were recruited for the \u201cGLA\/GSD Registry\u201d of the University Hospital of Freiburg, Germany (2015\u20132021). Clinical data were prospectively collected provided that a signed informed consent form was obtained. The latest proposed diagnostic guidelines were retrospectively applied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Thirty-two patients (38% males) were included in the study; 15 GLA, 10 GSD, 3 KLA, and 4 CCLA patients were identified. Eighty-four percent already had symptoms by the age of 15 years. Osteolysis and periosseous soft-tissue infiltration were associated with GSD (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.001 and\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.011, respectively), ascites and protein-losing enteropathy with CCLA (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.007 and\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.004, respectively), and consumption coagulopathy with KLA (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.006). No statistically significant differences were found in organ involvement, distribution of osteolytic lesions, number of affected bones and fractures. Twenty-five patients had complications; one patient with GLA died despite multimodal treatment. Spontaneous regression was seen in one patient with untreated KLA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>CLA are rare, and their overlapping clinical presentations make differential diagnosis difficult. The characterization of our case series contributes to the phenotypic description and differentiation of these four clinical entities. A further understanding of their pathogenesis is crucial for evaluating targeted therapies and optimizing medical care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/lrb.2022.0041","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T17:00:58Z","timestamp":1674838858000},"page":"230-243","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Complex Lymphatic Anomalies: Report on a Patient Registry Using the Latest Diagnostic Guidelines"],"prefix":"10.1177","volume":"21","author":[{"given":"Themis-Areti A.","family":"Andreoti","sequence":"first","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics, Inselspital\u2014University Hospital of Bern, University of Bern, Bern, Switzerland."},{"name":"Graduate School for Health Sciences, University of Bern, Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Berg","sequence":"additional","affiliation":[{"name":"Division of Pediatric Radiology, Department of Radiology, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annegret","family":"Holm","sequence":"additional","affiliation":[{"name":"VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, Germany."},{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."},{"name":"Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Angerer","sequence":"additional","affiliation":[{"name":"VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, Germany."},{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Oberlin","sequence":"additional","affiliation":[{"name":"VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, Germany."},{"name":"Foeldiclinic, Hinterzarten, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etelka","family":"Foeldi","sequence":"additional","affiliation":[{"name":"VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, Germany."},{"name":"Foeldiclinic, Hinterzarten, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Baumgartner","sequence":"additional","affiliation":[{"name":"Division of Angiology, Swiss Cardiovascular Center, Inselspital\u2014University Hospital of Bern, University of Bern, Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte M.","family":"Niemeyer","sequence":"additional","affiliation":[{"name":"VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, Germany."},{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4022-4917","authenticated-orcid":false,"given":"Jochen","family":"R\u00f6ssler","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics, Inselspital\u2014University Hospital of Bern, University of Bern, Bern, Switzerland."},{"name":"VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, Germany."},{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich G.","family":"Kapp","sequence":"additional","affiliation":[{"name":"VASCERN (European Network of rare vascular diseases) HCP (Health Care Provider) Freiburg-Hinterzarten, 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