{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:07:14Z","timestamp":1789589234950,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010475","name":"American Society of Pediatric Otolaryngology","doi-asserted-by":"publisher","award":["1060516"],"award-info":[{"award-number":["1060516"]}],"id":[{"id":"10.13039\/100010475","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Orbital lymphatic malformations (OLMs) are a rare type of lymphatic malformation involving the soft tissues within the bony orbit. OLMs present specific treatment challenges and cause significant morbidity. The contribution of pathologic genetic variants and potential association of intracranial vascular anomalies with OLMs has yet to be described. We hypothesized that (1) OLMs are indicators of underlying cerebrofacial venous metameric syndrome (CVMS) and are associated with intracranial vascular anomalies, and (2) OLMs are caused by\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      variants and are candidates for targeted medical therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Retrospective case review was performed for patients with OLMs treated at a single institution from 2000 to 2025. Diagnosis of CVMS was made via magnetic resonance imaging (MRI) based on established criteria of segmental distribution of ocular, facial, and cerebral vascular malformations. Symptoms, MRI and genetic findings, and management are described.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seven of 412 patients with head and neck lymphatic malformations had OLM. Common symptoms included eye swelling (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097), ptosis (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093), and headache (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095). All patients were diagnosed with CVMS on MRI. All patients underwent surgical resection and were candidates for targeted medical therapy after tissue\u2010based DNA sequencing revealed \u201chotspot\u201d\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      variants p.E542K (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094) and p.H1047R (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093). Five patients were started on alpelisib, resulting in symptom improvement at 6\u2009months of treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      OLMs were associated with intracranial vascular anomalies, meeting radiographic criteria for CVMS. All patients had \u201chotspot\u201d\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      variants on tissue\u2010based genetic testing. Screening for intracranial vascular anomalies and targeted medical therapy with PI3K\/AKT\/mTOR pathway inhibitors should be considered in OLM management.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence<\/jats:title>\n                    <jats:p>3.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lary.70826","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T09:18:30Z","timestamp":1787131110000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Orbital Lymphatic Malformations Are Associated With Intracranial Vascular Anomalies"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3792-5130","authenticated-orcid":false,"given":"Kelsey A.","family":"Loy","sequence":"first","affiliation":[{"name":"Division of Pediatric Otolaryngology \u2010 Head &amp; Neck Surgery, Department of Surgery Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Siu","sequence":"additional","affiliation":[{"name":"Division of Pediatric Otolaryngology \u2010 Head &amp; Neck Surgery, Department of Surgery Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Richardson","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology Phoenix Children's Hospital  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Nathaniel","family":"Perkins","sequence":"additional","affiliation":[{"name":"Division of Pediatric Otolaryngology \u2010 Head &amp; Neck Surgery, Department of Surgery Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5856-4357","authenticated-orcid":false,"given":"Kaitlyn","family":"Zenner","sequence":"additional","affiliation":[{"name":"Division of Pediatric Otolaryngology \u2010 Head &amp; Neck Surgery, Department of Surgery Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Koo","sequence":"additional","affiliation":[{"name":"Department of Radiology Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Radiology Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Bennett","sequence":"additional","affiliation":[{"name":"Division of Pediatric Otolaryngology \u2010 Head &amp; Neck Surgery, Department of Surgery Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5308-527X","authenticated-orcid":false,"given":"Randall","family":"Bly","sequence":"additional","affiliation":[{"name":"Division of Pediatric Otolaryngology \u2010 Head &amp; Neck Surgery, Department of Surgery Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danial","family":"K. Hallam","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Geddis","sequence":"additional","affiliation":[{"name":"Department of Hematology\u2010Oncology Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0181-3997","authenticated-orcid":false,"given":"Jonathan A.","family":"Perkins","sequence":"additional","affiliation":[{"name":"Division of Pediatric Otolaryngology \u2010 Head &amp; Neck Surgery, Department of Surgery Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"issue":"1","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/01.PRS.0000145633.99581.98","article-title":"Periorbital Lymphatic Malformation: Clinical Course and Management in 42 Patients","volume":"115","author":"Greene A. 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