Download PDF
Semin intervent Radiol 2022; 39(05): 498-507
DOI: 10.1055/s-0042-1757940
Review Article

Venous Malformations

Nihal D. Patel
1   Division of Vascular and Interventional Radiology, Department of Radiology, NYU Grossman School of Medicine, New York, New York
,
Anthony T. Chong
1   Division of Vascular and Interventional Radiology, Department of Radiology, NYU Grossman School of Medicine, New York, New York
,
Avani M. Kolla
2   Ronald O. Perelman Department of Dermatology, NYU Grossman School of Medicine, New York, New York
,
Tarub S. Mabud
1   Division of Vascular and Interventional Radiology, Department of Radiology, NYU Grossman School of Medicine, New York, New York
,
Kopal Kulkarni
1   Division of Vascular and Interventional Radiology, Department of Radiology, NYU Grossman School of Medicine, New York, New York
,
Karim Masrouha
4   Department of Orthopedic Surgery, NYU Grossman School of Medicine, New York, New York
,
Bedros Taslakian
1   Division of Vascular and Interventional Radiology, Department of Radiology, NYU Grossman School of Medicine, New York, New York
,
Frederic J. Bertino
1   Division of Vascular and Interventional Radiology, Department of Radiology, NYU Grossman School of Medicine, New York, New York
3   Division of Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia
› Author Affiliations Funding None.
› Further Information
Also available at
    Permissions and Reprints

Abstract

Venous malformations, the most common type of vascular malformation, are slow-flow lesions resulting from disorganized angiogenesis. The International Society for the Study of Vascular Anomalies (ISSVA) classification offers a categorization scheme for venous malformations based on their genetic landscapes and association with congenital overgrowth syndromes. Venous malformations present as congenital lesions and can have broad physiologic and psychosocial sequelae depending on their size, location, growth trajectory, and tissue involvement. Diagnostic evaluation is centered around clinical examination, imaging evaluation with ultrasound and time-resolved magnetic resonance imaging, and genetic testing for more complex malformations. Interventional radiology has emerged as first-line management of venous malformations through endovascular treatment with embolization, while surgery and targeted molecular therapies offer additional therapeutic options. In this review, an updated overview of the genetics and clinical presentation of venous malformations in conjunction with key aspects of diagnostic imaging and treatment are discussed.

Keywords

anomalies - malformations - vascular - venous


Publication History

Article published online:
20 December 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Hawkins CM, Chewning RH. Diagnosis and management of extracranial vascular malformations in children: arteriovenous malformations, venous malformations, and lymphatic malformations. Semin Roentgenol 2019; 54 (04) 337-348
    CrossrefPubMedGoogle Scholar
  • 2 Eifert S, Villavicencio JL, Kao TC, Taute BM, Rich NM. Prevalence of deep venous anomalies in congenital vascular malformations of venous predominance. J Vasc Surg 2000; 31 (03) 462-471
    CrossrefPubMedGoogle Scholar
  • 3 Sadick M, Müller-Wille R, Wildgruber M, Wohlgemuth WA. Vascular anomalies (Part I): Classification and diagnostics of vascular anomalies. Röfo Fortschr Geb Röntgenstr Neuen Bildgeb Verfahr 2018; 190 (09) 825-835
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Mulligan PR, Prajapati HJ, Martin LG, Patel TH. Vascular anomalies: classification, imaging characteristics and implications for interventional radiology treatment approaches. Br J Radiol 2014; 87 (1035): 20130392
    CrossrefPubMedGoogle Scholar
  • 5 Burrows PE. Endovascular treatment of slow-flow vascular malformations. Tech Vasc Interv Radiol 2013; 16 (01) 12-21
    CrossrefPubMedGoogle Scholar
  • 6 Bertino F, Trofimova AV, Gilyard SN, Hawkins CM. Vascular anomalies of the head and neck: diagnosis and treatment. Pediatr Radiol 2021; 51 (07) 1162-1184
    CrossrefPubMedGoogle Scholar
  • 7 Du Z, Liu JL, You YH. et al. Genetic landscape of common venous malformations in the head and neck. J Vasc Surg Venous Lymphat Disord 2021; 9 (04) 1007-1016.e7
    CrossrefPubMedGoogle Scholar
  • 8 ISSVA Classification of Vascular Anomalies. International Society for the Study of Vascular Anomalies. Accessed October 3, 2022 at: issva.org/classification
    PubMedGoogle Scholar
  • 9 Soblet J, Limaye N, Uebelhoer M, Boon LM, Vikkula M. Variable somatic TIE2 mutations in half of sporadic venous malformations. Mol Syndromol 2013; 4 (04) 179-183
    CrossrefPubMedGoogle Scholar
  • 10 Boscolo E, Limaye N, Huang L. et al. Rapamycin improves TIE2-mutated venous malformation in murine model and human subjects. J Clin Invest 2015; 125 (09) 3491-3504
    CrossrefPubMedGoogle Scholar
  • 11 Bertino F, Braithwaite KA, Hawkins CM. et al. Congenital limb overgrowth syndromes associated with vascular anomalies. Radiographics 2019; 39 (02) 491-515
    CrossrefPubMedGoogle Scholar
  • 12 Alomari AI, Spencer SA, Arnold RW. et al. Fibro-adipose vascular anomaly: clinical-radiologic-pathologic features of a newly delineated disorder of the extremity. J Pediatr Orthop 2014; 34 (01) 109-117
    CrossrefPubMedGoogle Scholar
  • 13 Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004; 18 (16) 1926-1945
    CrossrefPubMedGoogle Scholar
  • 14 Brouillard P, Boon LM, Mulliken JB. et al. Mutations in a novel factor, glomulin, are responsible for glomuvenous malformations (“glomangiomas”). Am J Hum Genet 2002; 70 (04) 866-874
    CrossrefPubMedGoogle Scholar
  • 15 Boon LM, Mulliken JB, Enjolras O, Vikkula M. Glomuvenous malformation (glomangioma) and venous malformation: distinct clinicopathologic and genetic entities. Arch Dermatol 2004; 140 (08) 971-976
    PubMedGoogle Scholar
  • 16 Bertino F, Chaudry G. Overgrowth syndromes associated with vascular anomalies. Semin Roentgenol 2019; 54 (04) 349-358
    CrossrefPubMedGoogle Scholar
  • 17 Nosher JL, Murillo PG, Liszewski M, Gendel V, Gribbin CE. Vascular anomalies: a pictorial review of nomenclature, diagnosis and treatment. World J Radiol 2014; 6 (09) 677-692
    CrossrefPubMedGoogle Scholar
  • 18 Legiehn GM, Heran MKS. Venous malformations: classification, development, diagnosis, and interventional radiologic management. Radiol Clin North Am 2008; 46 (03) 545-597 , vi
    CrossrefPubMedGoogle Scholar
  • 19 Jarrett DY, Ali M, Chaudry G. Imaging of vascular anomalies. Dermatol Clin 2013; 31 (02) 251-266
    CrossrefPubMedGoogle Scholar
  • 20 Han YY, Sun LM, Yuan SM. Localized intravascular coagulation in venous malformations: a system review. Phlebology 2021; 36 (01) 38-42
    CrossrefPubMedGoogle Scholar
  • 21 Mazoyer E, Enjolras O, Laurian C, Houdart E, Drouet L. Coagulation abnormalities associated with extensive venous malformations of the limbs: differentiation from Kasabach-Merritt syndrome. Clin Lab Haematol 2002; 24 (04) 243-251
    CrossrefPubMedGoogle Scholar
  • 22 Hage AN, Chick JFB, Srinivasa RN. et al. Treatment of venous malformations: the data, where we are, and how it is done. Tech Vasc Interv Radiol 2018; 21 (02) 45-54
    CrossrefPubMedGoogle Scholar
  • 23 Dompmartin A, Acher A, Thibon P. et al. Association of localized intravascular coagulopathy with venous malformations. Arch Dermatol 2008; 144 (07) 873-877
    CrossrefPubMedGoogle Scholar
  • 24 Kasabach HH, Merritt KK. Capillary hemangioma with extensive purpura: report of a case. Am J Dis Child 1940; 59 (05) 1063-1070
    CrossrefPubMedGoogle Scholar
  • 25 Trop I, Dubois J, Guibaud L. et al. Soft-tissue venous malformations in pediatric and young adult patients: diagnosis with Doppler US. Radiology 1999; 212 (03) 841-845
    CrossrefPubMedGoogle Scholar
  • 26 Dubois J, Soulez G, Oliva VL, Berthiaume MJ, Lapierre C, Therasse E. Soft-tissue venous malformations in adult patients: imaging and therapeutic issues. Radiographics 2001; 21 (06) 1519-1531
    CrossrefPubMedGoogle Scholar
  • 27 Oe Y, Orr L, Laifer-Narin S. et al. Contrast-enhanced sonography as a novel tool for assessment of vascular malformations. J Angiogenes Res 2010; 2: 25
    CrossrefPubMedGoogle Scholar
  • 28 Dubois JM, Sebag GH, De Prost Y, Teillac D, Chretien B, Brunelle FO. Soft-tissue venous malformations in children: percutaneous sclerotherapy with Ethibloc. Radiology 1991; 180 (01) 195-198
    CrossrefPubMedGoogle Scholar
  • 29 Zhang W, Chen G, Ren JG, Zhao YF. Bleomycin induces endothelial mesenchymal transition through activation of mTOR pathway: a possible mechanism contributing to the sclerotherapy of venous malformations. Br J Pharmacol 2013; 170 (06) 1210-1220
    CrossrefPubMedGoogle Scholar
  • 30 Chaudry G, Guevara CJ, Rialon KL. et al. Safety and efficacy of bleomycin sclerotherapy for microcystic lymphatic malformation. Cardiovasc Intervent Radiol 2014; 37 (06) 1476-1481
    CrossrefPubMedGoogle Scholar
  • 31 Zhang J, Li HB, Zhou SY. et al. Comparison between absolute ethanol and bleomycin for the treatment of venous malformation in children. Exp Ther Med 2013; 6 (02) 305-309
    CrossrefPubMedGoogle Scholar
  • 32 Nevesny F, Chevallier O, Falvo N. et al. Bleomycin for percutaneous sclerotherapy of venous and lymphatic malformations: a retrospective study of safety, efficacy and mid-term outcomes in 26 patients. J Clin Med 2021; 10 (06) 1302
    CrossrefPubMedGoogle Scholar
  • 33 Lee HJ, Kim TW, Kim JM. et al. Percutaneous sclerotherapy using bleomycin for the treatment of vascular malformations. Int J Dermatol 2017; 56 (11) 1186-1191
    CrossrefPubMedGoogle Scholar
  • 34 Mohan AT, Adams S, Adams K, Hudson DA. Intralesional bleomycin injection in management of low flow vascular malformations in children. J Plast Surg Hand Surg 2015; 49 (02) 116-120
    CrossrefPubMedGoogle Scholar
  • 35 Wohlgemuth WA, Müller-Wille R, Meyer L. et al. Bleomycin electrosclerotherapy in therapy-resistant venous malformations of the body. J Vasc Surg Venous Lymphat Disord 2021; 9 (03) 731-739
    CrossrefPubMedGoogle Scholar
  • 36 Horbach SER, Rigter IM, Smitt JHS, Reekers JA, Spuls PI, van der Horst CMAM. Intralesional bleomycin injections for vascular malformations: a systematic review and meta-analysis. Plast Reconstr Surg 2016; 137 (01) 244-256
    CrossrefPubMedGoogle Scholar
  • 37 Jenkinson HA, Wilmas KM, Silapunt S. Sodium tetradecyl sulfate: a review of clinical uses. Dermatol Surg 2017; 43 (11) 1313-1320
    CrossrefPubMedGoogle Scholar
  • 38 Tisi PV, Beverley C, Rees A. Injection sclerotherapy for varicose veins. Cochrane Database Syst Rev 2006; (04) CD001732
    PubMedGoogle Scholar
  • 39 Goldman MP, Weiss RA, Brody HJ, Coleman III WP, Fitzpatrick RE. Treatment of facial telangiectasia with sclerotherapy, laser surgery, and/or electrodesiccation: a review. J Dermatol Surg Oncol 1993; 19 (10) 899-906 , quiz 909–910
    CrossrefPubMedGoogle Scholar
  • 40 Alakailly X, Kummoona R, Quereshy FA, Baur DA, González AE. The use of sodium tetradecyl sulphate for the treatment of venous malformations of the head and neck. J Maxillofac Oral Surg 2015; 14 (02) 332-338
    CrossrefPubMedGoogle Scholar
  • 41 Critello CD, Fiorillo AS, Matula TJ. Size of sclerosing foams prepared by ultrasound, mechanical agitation, and the Handmade Tessari method for treatment of varicose veins. J Ultrasound Med 2017; 36 (03) 649-658
    CrossrefPubMedGoogle Scholar
  • 42 Park HS, Do YS, Park KB. et al. Clinical outcome and predictors of treatment response in foam sodium tetradecyl sulfate sclerotherapy of venous malformations. Eur Radiol 2016; 26 (05) 1301-1310
    CrossrefPubMedGoogle Scholar
  • 43 Tan KT, Kirby J, Rajan DK, Hayeems E, Beecroft JR, Simons ME. Percutaneous sodium tetradecyl sulfate sclerotherapy for peripheral venous vascular malformations: a single-center experience. J Vasc Interv Radiol 2007; 18 (03) 343-351
    CrossrefPubMedGoogle Scholar
  • 44 Sotradecol Sodium Teradecyl Sulfate. NIH US National Library of Medicine. Accessed October 3, 2022 at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c59db022-bda8-1732-e053-2a95a90a24f8
    PubMedGoogle Scholar
  • 45 Lee BB, Kim DI, Huh S. et al. New experiences with absolute ethanol sclerotherapy in the management of a complex form of congenital venous malformation. J Vasc Surg 2001; 33 (04) 764-772
    CrossrefPubMedGoogle Scholar
  • 46 van der Vleuten CJ, Kater A, Wijnen MH, Schultze Kool LJ, Rovers MM. Effectiveness of sclerotherapy, surgery, and laser therapy in patients with venous malformations: a systematic review. Cardiovasc Intervent Radiol 2014; 37 (04) 977-989
    PubMedGoogle Scholar
  • 47 Johnson AB, Richter GT. Surgical considerations in vascular malformations. Tech Vasc Interv Radiol 2019; 22 (04) 100635
    CrossrefPubMedGoogle Scholar
  • 48 Adams DM, Trenor III CC, Hammill AM. et al. Efficacy and safety of sirolimus in the treatment of complicated vascular anomalies. Pediatrics 2016; 137 (02) e20153257
    CrossrefPubMedGoogle Scholar
  • 49 Hammill AM, Wentzel M, Gupta A. et al. Sirolimus for the treatment of complicated vascular anomalies in children. Pediatr Blood Cancer 2011; 57 (06) 1018-1024
    CrossrefPubMedGoogle Scholar
  • 50 Freixo C, Ferreira V, Martins J. et al. Efficacy and safety of sirolimus in the treatment of vascular anomalies: a systematic review. J Vasc Surg 2020; 71 (01) 318-327
    CrossrefPubMedGoogle Scholar
  • 51 Kangas J, Nätynki M, Eklund L. Development of molecular therapies for venous malformations. Basic Clin Pharmacol Toxicol 2018; 123 (Suppl. 05) 6-19
    CrossrefPubMedGoogle Scholar
  • 52 Rodon J, Tabernero J. Improving the armamentarium of PI3K inhibitors with isoform-selective agents: a new light in the darkness. Cancer Discov 2017; 7 (07) 666-669
    CrossrefPubMedGoogle Scholar
  • 53 Furet P, Guagnano V, Fairhurst RA. et al. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg Med Chem Lett 2013; 23 (13) 3741-3748
    CrossrefPubMedGoogle Scholar
  • 54 Limaye N, Kangas J, Mendola A. et al. Somatic activating PIK3CA mutations cause venous malformation. Am J Hum Genet 2015; 97 (06) 914-921
    CrossrefPubMedGoogle Scholar
  • 55 Castel P, Carmona FJ, Grego-Bessa J. et al. Somatic PIK3CA mutations as a driver of sporadic venous malformations. Sci Transl Med 2016; 8 (332) 332ra42
    CrossrefPubMedGoogle Scholar
  • 56 Garreta Fontelles G, Pardo Pastor J, Grande Moreillo C. Alpelisib to treat CLOVES syndrome, a member of the PIK3CA-related overgrowth syndrome spectrum. Br J Clin Pharmacol 2022; 88 (08) 3891-3895
    CrossrefPubMedGoogle Scholar
  • 57 van Geel RMJM, Tabernero J, Elez E. et al. A Phase Ib dose-escalation study of encorafenib and cetuximab with or without alpelisib in metastatic BRAF-mutant colorectal cancer. Cancer Discov 2017; 7 (06) 610-619
    CrossrefPubMedGoogle Scholar
  • 58 Mayer IA, Abramson VG, Formisano L. et al. A Phase Ib study of alpelisib (BYL719), a PI3Kα-specific inhibitor, with letrozole in ER+/HER2- metastatic breast cancer. Clin Cancer Res 2017; 23 (01) 26-34
    CrossrefPubMedGoogle Scholar
  • 59 di Blasio L, Puliafito A, Gagliardi PA. et al. PI3K/mTOR inhibition promotes the regression of experimental vascular malformations driven by PIK3CA-activating mutations. Cell Death Dis 2018; 9 (02) 45
    CrossrefPubMedGoogle Scholar
  • 60 Janku F, Yap TA, Meric-Bernstam F. Targeting the PI3K pathway in cancer: are we making headway?. Nat Rev Clin Oncol 2018; 15 (05) 273-291
    CrossrefPubMedGoogle Scholar
  • 61 Lim Y, Fereydooni A, Brahmandam A, Dardik A, Choate K, Nassiri N. Mechanochemical and surgical ablation of an anomalous upper extremity marginal vein in CLOVES syndrome identifies PIK3CA as the culprit gene mutation. J Vasc Surg Cases Innov Tech 2020; 6 (03) 438-442
    CrossrefPubMedGoogle Scholar
  • 62 Lambert G, Teplisky D, Cabezas M. et al. Mechanochemical endovenous ablation of varicose veins in pediatric patients with Klippel-Trénaunay syndrome: feasibility, safety, and initial results. J Vasc Interv Radiol 2021; 32 (01) 80-86
    CrossrefPubMedGoogle Scholar
  • 63 Durr ML, Meyer AK, Kezirian EJ, Mamlouk MD, Frieden IJ, Rosbe KW. Sleep-disordered breathing in pediatric head and neck vascular malformations. Laryngoscope 2017; 127 (09) 2159-2164
    CrossrefPubMedGoogle Scholar
  • 64 Stimpson P, Hewitt R, Barnacle A, Roebuck DJ, Hartley B. Sodium tetradecyl sulphate sclerotherapy for treating venous malformations of the oral and pharyngeal regions in children. Int J Pediatr Otorhinolaryngol 2012; 76 (04) 569-573
    CrossrefPubMedGoogle Scholar
  • 65 Khandpur S, Sharma VK. Utility of intralesional sclerotherapy with 3% sodium tetradecyl sulphate in cutaneous vascular malformations. Dermatol Surg 2010; 36 (03) 340-346
    CrossrefPubMedGoogle Scholar
  • 66 Siniluoto TM, Svendsen PA, Wikholm GM, Fogdestam I, Edström S. Percutaneous sclerotherapy of venous malformations of the head and neck using sodium tetradecyl sulphate (Sotradecol). Scand J Plast Reconstr Surg Hand Surg 1997; 31 (02) 145-150
    CrossrefPubMedGoogle Scholar
  • 67 Chen RJ, Vrazas JI, Penington AJ. Surgical management of intramuscular venous malformations. J Pediatr Orthop 2021; 41 (01) e67-e73
    CrossrefPubMedGoogle Scholar