Journal of vascular anomalies最新文献

{"title":"Somatic Genetic Testing Provides Diagnosis of Verrucous Venous Malformation in an Individual with Discrepant Radiology, Pathology, and Clinical Findings.","authors":"Allison Britt, Amber Bolli, James Treat, Anne Marie Cahill, Denise Adams, Arupa Ganguly, Maria Queenan, Lea Surrey, David Low, Sarah Sheppard","doi":"10.1097/jova.0000000000000120","DOIUrl":"10.1097/jova.0000000000000120","url":null,"abstract":"<p><p>Verrucous venous malformation (VVM) is frequently misdiagnosed. This individual demonstrates the value of genetic testing to inform correct diagnosis. Consent was provided for retrospective chart review and publication. At birth, the affected individual had a red flat patch with overgrowth of his right hand, arm, and shoulder. The overgrowth and red color persisted and began to cause pain, which prompted his initial evaluation at age 10 years, leading to a diagnosis of a capillary vascular malformation and overgrowth. Routine magnetic resonance imaging of the right arm showed no definitive vascular anomaly. At 12 years old, hyperkeratosis prompted a biopsy for diagnosis. Pathology from 2 skin biopsies was most consistent with a capillary malformation and showed mildly acanthotic epidermis with hyperkeratosis overlying dilated, thin-walled vascular channels. We performed a 34-gene somatic genetic testing panel on the biopsy tissue. Results showed a likely pathogenic variant in the <i>MAP3K3</i> gene c.674C>T, p.Ser225Phe at variant allele fraction of 4.2%-4.6% from sample 1 and 7.3%-8.0% from sample 2, confirming the diagnosis of VVM. Somatic genetic testing provided this affected individual with the diagnosis of VVM when radiology, pathology, and clinical findings were discrepant. This new genetic diagnosis influences treatment and prognosis.</p>","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trametinib normalizes angiopoietin-2 levels and successfully treats kaposiform lymphangiomatosis.","authors":"C Griffin McDaniel, Svatava Merkle, Sophia Lacuna, Stephanie Cooper, Rebecca Courtemanche, Tram Nguyen, Timothy D Le Cras","doi":"10.1097/jova.0000000000000124","DOIUrl":"10.1097/jova.0000000000000124","url":null,"abstract":"<p><p>Kaposiform lymphangiomatosis (KLA) is a complex lymphatic anomaly with high morbidity and mortality. Angiopoietin-2 (Ang-2) levels are elevated in the blood of patients with KLA and can be used to aid in diagnosis and monitor treatment response. We report a male child with hydrocele, a left-sided pleural effusion, splenomegaly, and consumptive coagulopathy who was eventually diagnosed with KLA. Sirolimus did not provide a lasting therapeutic response, so treatment was switched to trametinib. The patient had an excellent response to trametinib with resolution of the pleural effusion, splenomegaly, and coagulopathy; normalization of Ang-2 levels; and significant improvement in clinical symptoms.</p>","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updated Classification of Vascular Anomalies. A living document from the International Society for the Study of Vascular Anomalies Classification Group.","authors":"Dov Charles Goldenberg, Miikka Vikkula, Anthony Penington, Francine Blei, Leo Schultze Kool, Michel Wassef, Ilona J Frieden","doi":"10.1097/JOVA.0000000000000113","DOIUrl":"10.1097/JOVA.0000000000000113","url":null,"abstract":"<p><strong>Introduction: </strong>The International Society for the Study of Vascular Anomalies developed in 1996 a Classification of Vascular Anomalies that became internationally accepted. The main feature was the division of vascular anomalies in 2 categories, vascular tumors and malformations. Major revisions occurred in 2014 and 2018, for updates and inclusion of newly described lesions. Major advances occurred in recent years, with improved understanding of genetic basis of vascular anomalies and its relevance in therapeutics. It created a demand for a new revision of ISSVA Classification, and the process is presented in this study.</p><p><strong>Methods: </strong>A group was created in 2019, joining experts from different specialties and coordinated by ISSVA Scientific Committee, to reevaluate the 2018 Classification on each subtype of vascular anomaly, considering the clinical presentation, histological subtypes, flow velocity and genetic aspects. After several multidisciplinary online discussions and in person meetings at ISSVA Congresses (2022, 2023 and 2024) the proposal for the new classification was presented for ISSVA Members ratification, after an opening window for comments and suggestions. A new tool was created, named <i>\"Glossary of Vascular Anomalies\"</i>, along the contours of a medical dictionary.</p><p><strong>Results: </strong>A new layout of the classification was designed. The visualization begins with a general \"Landing Page\" where the basic division into vascular tumors and malformations are specified. For vascular tumors, the subdivision was kept between Benign, Borderline and Malignant tumors. For vascular malformations, the divisions were presented as Fast-flow lesions, Slow-flow lesions, and Developmental Anomalies of Named Vessels. A Full Classification Table page with all updated modifications followed the Landing Page. All changes and new terms are described in detail and summarized in a table. The glossary lists and explains, in alphabetic order, all technical terms, abbreviations, acronyms, eponyms, genes and syndromes related to vascular anomalies.</p><p><strong>Conclusions: </strong>The presented updated ISSVA classification of vascular anomalies reflects our evolving understanding of vascular anomalies which will be continuously updated by a dedicated Committee of ISSVA.</p>","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12237419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Size-dependent Nanoparticle Accumulation In Venous Malformations.","authors":"Kathleen Cullion, Claire A Ostertag-Hill, Weimin Tang, Michelle Pan, Daniel S Kohane","doi":"10.1097/JOVA.0000000000000103","DOIUrl":"10.1097/JOVA.0000000000000103","url":null,"abstract":"<p><strong>Objective: </strong>The current treatment of venous malformations (VMs) consists of medications with systemic toxicity and procedural interventions with high technical difficulty and risk of hemorrhage. Using nanoparticles (NPs) to enhance drug delivery to VMs could enhance efficacy and decrease systemic toxicity. NPs can accumulate in tissues with abnormal vasculature, a concept known as the enhanced permeation and retention (EPR) effect. EPR has been documented in tumors, bioengineered vessels, and VMs. However, in VMs, it is unknown if NP size affects EPR and if so, which particle size improves NP accumulation.</p><p><strong>Methods: </strong>In this study, we used a murine model of subcutaneous VMs using human umbilical vein endothelial cells that express the most frequent VM-causing tyrosine kinase with immunoglobulin and EGF homology domains mutation, tyrosine kinase with immunoglobulin and EGF homology domains-L914F. Hollow silica NPs coated in polyethylene glycol (PEG) and conjugated to a fluorophore were administered systemically via tail vein injection. We studied the accumulation of a range of NP sizes within the VM and organs using confocal microscopy and an in vivo imaging system.</p><p><strong>Results: </strong>The 20, 50, 80, and 180 nm PEGylated, fluorophore-tagged hollow silica NPs were spherical and had hydrodynamic diameters of 31.6 ± 0.9, 58.5 ± 0.1, 87.1 ± 2.4, and 232 ± 1.26 nm, respectively. Following systemic NP administration, 20 nm NPs had 2 times more fluorescence accumulation within VMs compared with 50 nm, and 6 times more fluorescence accumulation compared with larger (greater than 80 nm) NPs (<i>P</i> < .01).</p><p><strong>Conclusion: </strong>This study helps to determine the optimal NP size for passive accumulation within VMs and lays the foundation for engineering NPs for the treatment of VMs.</p>","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"5 4","pages":"e00103"},"PeriodicalIF":0.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rheumatological Diseases and Lower Extremity Edema: A Lymphoscintigram Study.","authors":"Michal Ad, Arin K Greene","doi":"10.1097/jova.0000000000000098","DOIUrl":"10.1097/jova.0000000000000098","url":null,"abstract":"<p><p>\"Lymphedema\" is commonly used as a generic term to describe any form of leg swelling; 25% of patients referred to our center with \"lymphedema\" do not have the condition. The purpose of this study was to evaluate the lymphatic function of subjects with rheumatologic disease. Five individuals with a rheumatologic disease and leg edema underwent a lymphoscintigram. All individuals had normal lymphatic function. Patients presenting with lower extremity swelling and a rheumatologic condition do not have lymphedema. The etiology of their leg swelling is by mechanisms other than lymphatic dysfunction.</p>","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"5 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13001728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147500933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"R183Q GNAQ Sturge-Weber syndrome Leptomeningeal and Cerebrovascular Developmental Mouse Model.","authors":"C R Solomon, M McCann, P Singh, C L Nemeth, A Comi","doi":"10.1097/jova.0000000000000099","DOIUrl":"10.1097/jova.0000000000000099","url":null,"abstract":"<p><strong>Objectives: </strong>Sturge-Weber syndrome (SWS), a rare neurovascular malformation disorder, is usually caused by the R183Q GNAQ somatic mosaic mutation enriched in brain endothelial cells. A developmental mouse model of SWS brain involvement is needed to investigate mutation impact upon brain vascular development and to facilitate preclinical drug studies.</p><p><strong>Methods: </strong>A new Tet-ON R183Q GNAQ transgenic mouse line was paired with rtTA tet transactivator mice under the <i>Tie2</i> promoter to generate mice expressing endothelial R183Q GNAQ in the presence of doxycycline. Litters were perfused at P14-17; half received a sub-seizure dose (1.5 mg/kg; i.p.) of kainate an hour before perfusion. A subset were perfused with Evans blue. Fixed mouse brains were stained with X-gal, DAPI, and antibodies for Gαq, Tie2, phosphorylated-S6, and claudin-5. Images were scored for vessel staining intensity.</p><p><strong>Results: </strong>X-gal staining was seen only in mutant mice; leptomeningeal endothelial X-gal staining was more frequent in kainate-treated mice (<i>p</i> < 0.001). When perfused with Evans blue, only mutant brains showed severe staining (<i>p</i> = 0.028). Median phosphorylated-S6 vessel scores were significantly higher in the leptomeninges of mutant mice (<i>p</i> = 0.035). Mutant cortical microvessels demonstrated discontinuous claudin-5 and phosphorylated-S6 staining as well as increased vessel length in kainate-treated mice (<i>p</i> = 0.024).</p><p><strong>Conclusions: </strong>The new R183Q GNAQ Tet-ON developmental mouse brain model of SWS demonstrates endothelial expression of mutant Gαq associated with blood brain barrier breakdown, altered vascular mTOR activity, and abnormal cortical microvessel structure. This new translational model can be used to develop new drug targets and treatments for SWS.</p>","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"5 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12711316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Once a day administration of R(+) propranolol is sufficient to block vasculogenesis in a xenograft model of infantile hemangioma.","authors":"Annegret Holm, Jerry Wei Heng Tan, Luke Borgelt, John B Mulliken, Joyce Bischoff","doi":"10.1097/jova.0000000000000096","DOIUrl":"10.1097/jova.0000000000000096","url":null,"abstract":"<p><strong>Objectives: </strong>Infantile hemangioma (IH) is a benign vascular tumor that occurs in 5% of infants, predominantly in female and preterm neonates. Propranolol is the mainstay of treatment for IH. Given the short half-life of propranolol regarding β-adrenergic receptor inhibition as well as its side effects, propranolol is administered to infants 2-3 times daily with 1 mg/kg/dose. We previously demonstrated propranolol inhibits IH vessel formation via an effect of its R(+) enantiomer on the endothelial-specific transcription factor SRY box 18 (SOX18). In light of this, we hypothesized that R(+) propranolol inhibition of SOX18 is long-lived compared to the beta-blocker effects, and therefore administration of R(+) propranolol once a day would be sufficient to block IH vessel formation.</p><p><strong>Methods: </strong>We tested the effect of one dose versus two doses of R(+) propranolol in a xenograft model of IH wherein patient-derived hemangioma stem cells (HemSC) were implanted subcutaneously into nude mice. Mice were treated for 7 days with 2 × 12.5 mg/kg/day (n=12) versus 1 × 25 mg/kg/day (n=14) as well as PBS (vehicle control) (n=16) via intraperitoneal injections. The doses were estimated to correlate with those given to infants with IH.</p><p><strong>Results: </strong>Treatment with R(+) propranolol significantly inhibited vasculogenesis in our IH xenograft model at both 2 × 12.5 mg/kg/day and 1 × 25 mg/kg/day, compared to vehicle controls. No significant difference was observed between the two treatment regimens.</p><p><strong>Conclusions: </strong>Our results suggest implications for the clinical management of infants with IH: Administration of R(+) propranolol can possibly minimize or omit concerning β-adrenergic side effects while only requiring one dose per day.</p>","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"5 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Genetic Mutations in Vascular Anomalies Using a Sequencing Panel for Childhood Cancers: A Pilot Study","authors":"Elis Yuexian Lee, Y. Ang, C. Kuick, Y. Mok, Kenneth Tou En Chang, Luke Han Wei Toh, Mei Yoke Chan, Mark Jean Aan Koh","doi":"10.1097/jova.0000000000000094","DOIUrl":"https://doi.org/10.1097/jova.0000000000000094","url":null,"abstract":"\u0000 \u0000 Genetic mutations have been identified in the pathogenesis of vascular anomalies. Due to overlaps in genetic variants causing vascular anomalies and cancer, we used a next-generation sequencing panel for genomic profiling of childhood cancers to detect somatic mutations in children with vascular anomalies. We aim to review the utility of an oncology panel for the molecular diagnosis of vascular anomalies.\u0000 \u0000 \u0000 \u0000 Nine patients with histologically confirmed vascular anomalies were included. DNA was extracted from formalin-fixed paraffin-embedded tissue specimens obtained from affected tissue following diagnostic punch biopsies of the skin and core biopsies of the vascular malformation or tumor during sclerotherapy or surgical excision. Molecular analysis of the tissue samples was performed using AmpliSeq for Childhood Cancer DNA Assay Panel.\u0000 \u0000 \u0000 \u0000 Two patients had antenatally detected vascular anomalies. The median age at diagnosis for the remaining patients was 7.0 years (IQR, 0.6–10.0 years). Seven were diagnosed with vascular malformations, while 2 had vascular tumors. Pathological somatic mutations were identified in 4 patients, leading to a diagnostic yield of 44.4%. Two different PIK3CA mutations were identified in 3 cases: 1 in a case of macrocystic lymphatic malformation, the other in a case of Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevus, Spinal/Skeletal anomalies syndrome and Klippel–Trenaunay syndrome. BRAF mutation was identified in a patient with a veno-lymphatic malformation.\u0000 \u0000 \u0000 \u0000 An oncology next-generation sequencing panel can be used for genetic profiling of vascular anomalies. However, a more customized and sensitive panel may be of better diagnostic yield, as detection of somatic mutations in vascular anomalies is challenging due to tissue mosaicism, low-abundant genetic variants, and specimen limitations.\u0000","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"13 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141690996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Pitfalls: Soft Tissue Lymphoma: Superficial Soft Tissue Lymphoma Mimicking a Venous Malformation","authors":"Victoire Roblot, Valérie Bousson, Annouk Bisdorff","doi":"10.1097/jova.0000000000000095","DOIUrl":"https://doi.org/10.1097/jova.0000000000000095","url":null,"abstract":"In this case report, 3 patients addressed to our vascular anomalies reference center to manage a slow-flow vascular anomaly were reported. Our objective is to highlight that a discrepancy between clinical and radiological data should suggest a differential diagnosis and a percutaneous biopsy be considered. In our 3 patients, the biopsy provided a diagnosis of soft tissue lymphoma. Some red flags should not be overlooked to avoid missing this diagnosis, patient's past medical history of lymphoma and clinical palpation of a nondepressible hard lesion. On magnetic resonance imaging, the lesion shape and contours particularly the presence of spicules appear to be interesting features to consider lymphoma (this sign is absent in common venous malformation). Therefore, the triad past medical history and clinical and imaging data (ultrasound and MRI) are mandatory for an accurate diagnosis of vascular malformations.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"49 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141343791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidisciplinary Fusion: A recurrent expansive prevertebral vascular anomaly with EWSR1::NFATC2 fusion","authors":"Samantha J. DeMarsh, Bradford Siegele, V. Zavaletta, A. Annam, Ann M. Kulungowski, Lauren R. Hill, Nathan Donaldson, Taizo A Nakano","doi":"10.1097/jova.0000000000000093","DOIUrl":"https://doi.org/10.1097/jova.0000000000000093","url":null,"abstract":"The field of vascular anomalies has seen a rapid paradigm shift from descriptive to molecular diagnoses, with DNA-based next-generation sequencing becoming standard practice in the workup and characterization of lesions. RNA-based panels for fusion transcripts have been less utilized in the field of vascular anomalies. We report a recurrent, infiltrative prevertebral vascular tumor negative for known somatic variants but positive for an Ewing sarcoma breakpoint region 1::nuclear factor of activated T-cells cytoplasmic 2 fusion transcript. This lesion demonstrated intermediate malignant potential with morphologic atypia, novel intraluminal endothelial growth, and atypical mitoses, which have not previously been reported. RNA-based panels for fusion transcripts may represent the next impactful evolution of molecular characterization of vascular malformations and tumors.","PeriodicalId":74008,"journal":{"name":"Journal of vascular anomalies","volume":"10 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141348677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}