Skip to main content

Advertisement

Log in

Contemporary management of extracranial vascular malformations

  • Musculoskeletal imaging
  • Published:
Pediatric Radiology Aims and scope Submit manuscript

Abstract

Vascular malformations are congenital vascular anomalies that originate because of disorganized angiogenesis, most commonly from spontaneous somatic genetic mutations. The modern management of vascular malformations requires a multidisciplinary team that offers patients the gamut of medical, surgical, and percutaneous treatment options with supportive care. This manuscript discusses the standard and contemporary management strategies surrounding extracranial vascular malformations and overgrowth syndromes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Dasgupta R, Fishman SJ (2014) ISSVA classification. Semin Pediatr Surg 23:158–161. https://doi.org/10.1053/j.sempedsurg.2014.06.016

    Article  PubMed  Google Scholar 

  2. Hawkins CM, Chewning RH (2019) Diagnosis and Management of extracranial vascular malformations in children: arteriovenous malformations, venous malformations, and lymphatic malformations. Semin Roentgenol. https://doi.org/10.1053/j.ro.2019.06.004

    Article  PubMed  Google Scholar 

  3. Bertino F, Braithwaite KA, Hawkins CM et al (2019) Congenital limb overgrowth syndromes associated with vascular anomalies. RadioGraphics 39:491–515. https://doi.org/10.1148/rg.2019180136

    Article  PubMed  Google Scholar 

  4. Classification | International Society for the Study of Vascular Anomalies. http://www.issva.org/classification. Accessed 25 Jul 2019

  5. Bertino F, Chaudry G (2019) Overgrowth syndromes associated with vascular anomalies. Semin Roentgenol. https://doi.org/10.1053/j.ro.2019.06.005

    Article  PubMed  Google Scholar 

  6. Nosher JL, Murillo PG, Liszewski M et al (2014) Vascular anomalies: a pictorial review of nomenclature, diagnosis and treatment. World Radiol. 6(9):677. https://doi.org/10.4329/wjr.v6.i9.677

    Article  Google Scholar 

  7. Jarrett DY, Ali M, Chaudry G (2013) Imaging of vascular anomalies. Dermatol Clin 31:251–266. https://doi.org/10.1016/j.det.2012.12.004

    Article  CAS  PubMed  Google Scholar 

  8. Alomari A, Dubois J (2011) Interventional management of vascular malformations. Tech Vasc Interv Radiol 14:22–31. https://doi.org/10.1053/j.tvir.2010.07.006

    Article  PubMed  Google Scholar 

  9. Burrows PE (2013) Endovascular treatment of slow-flow vascular malformations. Tech Vasc Interv Radiol 16:12–21. https://doi.org/10.1053/j.tvir.2013.01.003

    Article  PubMed  Google Scholar 

  10. Cahill AM, Nijs ELF (2011) Pediatric vascular malformations: pathophysiology, diagnosis, and the role of interventional radiology. Cardiovasc Intervent Radiol 34:691–704. https://doi.org/10.1007/s00270-011-0123-0

    Article  PubMed  Google Scholar 

  11. Bertino F, Trofimova AV, Gilyard SN, Hawkins CM (2021) Vascular anomalies of the head and neck: diagnosis and treatment. Pediatr Radiol 51:1162–1184. https://doi.org/10.1007/s00247-021-04968-2

    Article  PubMed  Google Scholar 

  12. Chaudry G, Burrows PE, Padua HM et al (2011) Sclerotherapy of abdominal lymphatic malformations with doxycycline. J Vasc Interv Radiol 22:1431–1435. https://doi.org/10.1016/j.jvir.2011.06.021

    Article  PubMed  Google Scholar 

  13. Cheng J (2015) Doxycycline sclerotherapy in children with head and neck lymphatic malformations. J Pediatr Surg 50:2143–2146. https://doi.org/10.1016/j.jpedsurg.2015.08.051

    Article  PubMed  Google Scholar 

  14. Farnoosh S, Don D, Koempel J et al (2015) Efficacy of doxycycline and sodium tetradecyl sulfate sclerotherapy in pediatric head and neck lymphatic malformations. Int J Pediatr Otorhinolaryngol 79:883–887. https://doi.org/10.1016/j.ijporl.2015.03.024

    Article  PubMed  Google Scholar 

  15. Thomas DM, Wieck MM, Grant CN et al (2016) Doxycycline sclerotherapy is superior in the treatment of pediatric lymphatic malformations. J Vasc Interv Radiol 27:1846–1856. https://doi.org/10.1016/j.jvir.2016.08.012

    Article  PubMed  Google Scholar 

  16. Nehra D, Jacobson L, Barnes P et al (2008) Doxycycline sclerotherapy as primary treatment of head and neck lymphatic malformations in children. J Pediatr Surg 43:451–460. https://doi.org/10.1016/j.jpedsurg.2007.10.009

    Article  PubMed  Google Scholar 

  17. Sood A, Kotamarti VS, Therattil PJ, Lee ES (2017) Sclerotherapy for the management of seromas: a systematic review. Eplasty 17:e25

    PubMed  PubMed Central  Google Scholar 

  18. Mack JM, Crary SE (2022) How we approach coagulopathy with vascular anomalies. Pediatr Blood Cancer 69:e29353. https://doi.org/10.1002/pbc.29353

  19. Zhang J, LI HB, ZHOU SY et al (2013) Comparison between absolute ethanol and bleomycin for the treatment of venous malformation in children. Exp Ther Med 6:305–309. https://doi.org/10.3892/etm.2013.1144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Braun A, Hohenwalter EJ, Rilling WS (2013) Percutaneous sclerotherapy of venous malformations: efficacy and safety of ethanol and sotradecol. J Vasc Interv Radiol 24:S26–S27. https://doi.org/10.1016/j.jvir.2013.01.058

    Article  Google Scholar 

  21. Lee C-H, Chen S-G (2005) Direct percutaneous ethanol instillation for treatment of venous malformation in the face and neck. Br J Plast Surg 58:1073–1078. https://doi.org/10.1016/j.bjps.2005.04.014

    Article  PubMed  Google Scholar 

  22. Siniluoto TMJ, Svendsen PA, Wikholm GM et al (1997) Percutaneous Sclerotherapy of Venous Malformations of the Head and Neck Using Sodium Tetradecyl Sulphate (Sotradecol). Scand J Plast Reconstr Surg Hand Surg 31:145–150. https://doi.org/10.3109/02844319709085481

    Article  CAS  PubMed  Google Scholar 

  23. Jenkinson HA, Wilmas KM, Silapunt S (2017) Sodium tetradecyl sulfate: a review of clinical uses. Dermatol Surg 43:1313–1320. https://doi.org/10.1097/DSS.0000000000001143

    Article  CAS  PubMed  Google Scholar 

  24. McAree B, Ikponmwosa A, Brockbank K et al (2012) Comparative stability of sodium tetradecyl sulphate (STD) and polidocanol foam: impact on vein damage in an in-vitro model. Eur J Vasc Endovasc Surg 43:721–725. https://doi.org/10.1016/j.ejvs.2012.02.026

    Article  CAS  PubMed  Google Scholar 

  25. Whiteley MS, Patel SB (2015) Modified Tessari Tourbillon technique for making foam sclerotherapy with silicone-free syringes. Phlebology 30:614–617. https://doi.org/10.1177/0268355514554476

    Article  PubMed  Google Scholar 

  26. Ono Y, Osuga K, Takura T et al (2016) Cost-effectiveness analysis of percutaneous sclerotherapy for venous malformations. J Vasc Interv Radiol 27:831–837. https://doi.org/10.1016/j.jvir.2015.12.019

    Article  PubMed  Google Scholar 

  27. van der Vleuten CJM, Kater A, Wijnen MHWA et al (2014) Effectiveness of sclerotherapy, surgery, and laser therapy in patients with venous malformations: a systematic review. Cardiovasc Intervent Radiol 37:977–989. https://doi.org/10.1007/s00270-013-0764-2

    Article  PubMed  Google Scholar 

  28. Chewning RH, Monroe EJ, Lindberg A, et al (2018) Combined glue embolization and excision for the treatment of venous malformations. CVIR Endovasc 1:.https://doi.org/10.1186/s42155-018-0028-y

  29. Tieu DD, Ghodke BV, Vo NJ, Perkins JA (2013) Single-stage excision of localized head and neck venous malformations using preoperative glue embolization. Otolaryngol Neck Surg 148:678–684. https://doi.org/10.1177/0194599813475586

    Article  Google Scholar 

  30. Mulligan PR, Prajapati HJS, Martin LG, Patel TH (2014) Vascular anomalies: classification, imaging characteristics and implications for interventional radiology treatment approaches. Br J Radiol 87:.https://doi.org/10.1259/bjr.20130392

  31. Finn MC, Glowacki J, Mulliken JB (1983) Congenital vascular lesions: clinical application of a new classification. J Pediatr Surg 18:894–900. https://doi.org/10.1016/s0022-3468(83)80043-8

    Article  CAS  PubMed  Google Scholar 

  32. Cho SK, Do YS, Shin SW et al (2006) Arteriovenous malformations of the body and extremities: analysis of therapeutic outcomes and approaches according to a modified angiographic classification. J Endovasc Ther 13:527–538. https://doi.org/10.1583/05-1769.1

    Article  PubMed  Google Scholar 

  33. Yakes W, Baumgartner I (2014) Interventional treatment of arterio-venous malformations. Gefässchirurgie 19:325–330. https://doi.org/10.1007/s00772-013-1303-9

    Article  Google Scholar 

  34. Yakes WF (2004) Endovascular management of high-flow arteriovenous malformations. Semin Interv Radiol 21:49–58. https://doi.org/10.1055/s-2004-831405

    Article  Google Scholar 

  35. Vogelzang RL, Atassi R, Vouche M et al (2014) Ethanol embolotherapy of vascular malformations: clinical outcomes at a single center. J Vasc Interv Radiol 25:206–213. https://doi.org/10.1016/j.jvir.2013.10.055

    Article  PubMed  Google Scholar 

  36. Jin Y, Yang X, Hua C et al (2018) Ethanol embolotherapy for the management of refractory chronic skin ulcers caused by arteriovenous malformations. J Vasc Interv Radiol 29:107–113. https://doi.org/10.1016/j.jvir.2017.09.013

    Article  PubMed  Google Scholar 

  37. Shin BS, Do YS, Cho HS et al (2010) Effects of repeat bolus ethanol injections on cardiopulmonary hemodynamic changes during embolotherapy of arteriovenous malformations of the extremities. J Vasc Interv Radiol 21:81–89. https://doi.org/10.1016/j.jvir.2009.09.026

    Article  PubMed  Google Scholar 

  38. Soltanolkotabi M, Schoeneman SE, Alden TD et al (2013) Onyx embolization of intracranial arteriovenous malformations in pediatric patients: Clinical article. J Neurosurg Pediatr 11:431–437. https://doi.org/10.3171/2013.1.PEDS12286

    Article  PubMed  Google Scholar 

  39. Giurazza F, Corvino F, Cangiano G et al (2019) Transarterial embolization of peripheral high-flow arteriovenous malformation with ethylene vinyl alcohol copolymer (Onyx®): single-center 10-year experience. Radiol Med (Torino) 124:154–162. https://doi.org/10.1007/s11547-018-0948-6

    Article  PubMed  Google Scholar 

  40. Jin Y, Zou Y, Hua C et al (2017) Treatment of early-stage extracranial arteriovenous malformations with intralesional interstitial bleomycin injection: a pilot study. Radiology 287:194–204. https://doi.org/10.1148/radiol.2017162076

    Article  PubMed  Google Scholar 

  41. Thiex R, Wu I, Mulliken JB et al (2011) Safety and clinical efficacy of onyx for embolization of extracranial head and neck vascular anomalies. AJNR Am J Neuroradiol 32:1082–1086. https://doi.org/10.3174/ajnr.A2439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Blei F (2015) Overgrowth syndromes with vascular anomalies. Curr Probl Pediatr Adolesc Health Care 45:118–131. https://doi.org/10.1016/j.cppeds.2015.03.002

    Article  PubMed  Google Scholar 

  43. Revencu N, Boon LM, Mulliken JB et al (2008) Parkes Weber syndrome, vein of Galen aneurysmal malformation, and other fast-flow vascular anomalies are caused by RASA1 mutations. Hum Mutat 29:959–965. https://doi.org/10.1002/humu.20746

    Article  CAS  PubMed  Google Scholar 

  44. Wang MX, Kamel S, Elsayes KM et al (2022) Vascular anomaly syndromes in the ISSVA classification system: imaging findings and role of interventional radiology in management. RadioGraphics 42:1598–1620. https://doi.org/10.1148/rg.210234

    Article  PubMed  Google Scholar 

  45. Keppler-Noreuil KM, Rios JJ, Parker VER et al (2015) PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation. Am J Med Genet A 167A:287–295. https://doi.org/10.1002/ajmg.a.36836

    Article  CAS  PubMed  Google Scholar 

  46. Fernandez-Pineda I, Marcilla D, Downey-Carmona FJ et al (2014) Lower extremity fibro-adipose vascular anomaly (FAVA): a new case of a newly delineated disorder. Ann Vasc Dis 7:316–319. https://doi.org/10.3400/avd.cr.14-00049

    Article  PubMed  PubMed Central  Google Scholar 

  47. Eskew JE, Gill AE, Swerdlin R, et al (2021) Percutaneous cryoablation for treatment of biopsy-proven fibroadipose vascular anomaly: a single-center experience. J Vasc Anom 2:e005. https://doi.org/10.1097/JOVA.0000000000000005

  48. Shaikh R, Alomari AI, Kerr CL et al (2016) Cryoablation in fibro-adipose vascular anomaly (FAVA): a minimally invasive treatment option. Pediatr Radiol 46:1179–1186. https://doi.org/10.1007/s00247-016-3576-0

    Article  PubMed  Google Scholar 

  49. Kaufman C, Frodsham A, Arnold R (2021) Cryoablation as second-line therapy for fibroadipose vascular anomaly. J Vasc Anom 2:e008. https://doi.org/10.1097/JOVA.0000000000000008

  50. Ramaswamy RS, Tiwari T, Darcy MD et al (2019) Cryoablation of low-flow vascular malformations. Diagn Interv Radiol Ank Turk 25:225–230. https://doi.org/10.5152/dir.2019.18278

    Article  Google Scholar 

  51. Peterman CM, Fevurly RD, Alomari AI, et al (2017) Sonographic screening for Wilms tumor in children with CLOVES syndrome. Pediatr Blood Cancer 64:n/a-n/a. https://doi.org/10.1002/pbc.26684

  52. Gripp KW, Baker L, Kandula V et al (2016) Nephroblastomatosis or Wilms tumor in a fourth patient with a somatic PIK3CA mutation. Am J Med Genet A 170:2559–2569. https://doi.org/10.1002/ajmg.a.37758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Watson KD, Kim KR, Blatt J (2022) How we approach complex vascular anomalies and overgrowth syndromes. Pediatr Blood Cancer 69:e29273. https://doi.org/10.1002/pbc.29273

  54. Girón-Vallejo O, López-Gutiérrez JC, Fernández-Pineda I (2013) Diagnosis and treatment of Parkes Weber syndrome: a review of 10 consecutive patients. Ann Vasc Surg 27:820–825. https://doi.org/10.1016/j.avsg.2013.01.001

    Article  PubMed  Google Scholar 

  55. Manresa-Manresa F, Iribarren-Marín MA, Gómez-Ruiz FT (2015) Parkes-Weber syndrome. Rev Espanola Cardiol Engl Ed 68:67. https://doi.org/10.1016/j.rec.2014.02.022

    Article  Google Scholar 

  56. Plasencia AR, Santillan A (2014) Giant arteriovenous fistula in Parkes Weber syndrome. J Vasc Surg 60:233. https://doi.org/10.1016/j.jvs.2013.08.041

    Article  PubMed  Google Scholar 

  57. Oduber CEU, Young-Afat DA, van der Wal AC et al (2013) The persistent embryonic vein in Klippel-Trenaunay syndrome. Vasc Med Lond Engl 18:185–191. https://doi.org/10.1177/1358863X13498463

    Article  Google Scholar 

  58. Baskerville PA, Ackroyd JS, Thomas ML, Browse NL (1985) The Klippel-Trenaunay syndrome: clinical, radiological and haemodynamic features and management. BJS Br J Surg 72:232–236. https://doi.org/10.1002/bjs.1800720331

    Article  CAS  Google Scholar 

  59. Ndzengue A, Rafal RB, Balmir S, et al (2012) Klippel–Trenaunay syndrome: an often overlooked risk factor for venous thromboembolic disease. Int J Angiol Off Publ Int Coll Angiol Inc 21:233–236. https://doi.org/10.1055/s-0032-1328969

  60. Gianlupi A, Harper RW, Dwyre DM, Marelich GP (1999) Recurrent pulmonary embolism associated with Klippel-Trenaunay-Weber syndrome. Chest 115:1199–1201. https://doi.org/10.1378/chest.115.4.1199

    Article  CAS  PubMed  Google Scholar 

  61. Labropoulos N, Bekelis K, Leon LR (2008) Thrombosis in unusual sites of the lower extremity veins. J Vasc Surg 47:1022–1027. https://doi.org/10.1016/j.jvs.2007.12.044

    Article  PubMed  Google Scholar 

  62. Chaudry G, Guevara CJ, Rialon KL et al (2014) Safety and efficacy of bleomycin sclerotherapy for microcystic lymphatic malformation. Cardiovasc Intervent Radiol 37:1476–1481. https://doi.org/10.1007/s00270-014-0932-z

    Article  PubMed  Google Scholar 

  63. Rebuffini E, Zuccarino L, Grecchi E et al (2012) Picibanil (OK-432) in the treatment of head and neck lymphangiomas in children. Dent Res J 9:S192–S196. https://doi.org/10.4103/1735-3327.109752

    Article  CAS  Google Scholar 

  64. Tanigawa N, Shimomatsuya T, Takahashi K et al (1987) Treatment of cystic hygroma and lymphangioma with the use of bleomycin fat emulsion. Cancer 60:741–749. https://doi.org/10.1002/1097-0142(19870815)60:4%3c741::AID-CNCR2820600406%3e3.0.CO;2-2

    Article  CAS  PubMed  Google Scholar 

  65. Umezawa H (1976) Structure and action of bleomycin. Prog Biochem Pharmacol 11:18–27

    CAS  PubMed  Google Scholar 

  66. Zhang H, Zhang H-S, Chen A-W et al (2020) Modified method to increase the volume and stability of bleomycin foam: an experimental study. Dermatol Surg Off Publ Am Soc Dermatol Surg Al 46:1030–1034. https://doi.org/10.1097/DSS.0000000000002221

    Article  CAS  Google Scholar 

  67. Mohan AT, Adams S, Adams K, Hudson DA (2015) Intralesional bleomycin injection in management of low flow vascular malformations in children. J Plast Surg Hand Surg 49:116–120. https://doi.org/10.3109/2000656X.2014.951051

    Article  PubMed  Google Scholar 

  68. Sainsbury DCG, Kessell G, Fall AJ et al (2011) Intralesional bleomycin injection treatment for vascular birthmarks: a 5-year experience at a single United Kingdom unit. Plast Reconstr Surg 127:2031–2044. https://doi.org/10.1097/PRS.0b013e31820e923c

    Article  CAS  PubMed  Google Scholar 

  69. Nevesny F, Chevallier O, Falvo N et al (2021) 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 10:1302. https://doi.org/10.3390/jcm10061302

    Article  PubMed  PubMed Central  Google Scholar 

  70. Oron A, Netzer N, Rosinsky P et al (2018) Diagnosing acute compartment syndrome: are current textbooks misleading? Curr Orthop Pract 29:527–529. https://doi.org/10.1097/BCO.0000000000000693

    Article  Google Scholar 

  71. Horbach SER, Rigter IM, Smitt JHS et al (2016) Intralesional bleomycin injections for vascular malformations: a systematic review and meta-analysis. Plast Reconstr Surg 137:244–256. https://doi.org/10.1097/PRS.0000000000001924

    Article  CAS  PubMed  Google Scholar 

  72. Lee H-J, Kim T-W, Kim J-M et al (2017) Percutaneous sclerotherapy using bleomycin for the treatment of vascular malformations. Int J Dermatol 56:1186–1191. https://doi.org/10.1111/ijd.13733

    Article  CAS  PubMed  Google Scholar 

  73. Hashimoto N, Phan SH, Imaizumi K et al (2010) Endothelial–mesenchymal transition in bleomycin-induced pulmonary fibrosis. Am J Respir Cell Mol Biol 43:161–172. https://doi.org/10.1165/rcmb.2009-0031OC

    Article  CAS  PubMed  Google Scholar 

  74. Rashid RS (2009) Bleomycin lung: a case report. BMJ Case Rep 2009:bcr11.2008.1175. https://doi.org/10.1136/bcr.11.2008.1175

  75. Jules-Elysee K, White DA (1990) Bleomycin-induced pulmonary toxicity. Clin Chest Med 11:1–20

    Article  CAS  PubMed  Google Scholar 

  76. Atwa K, Abuhasna S, Shihab Z et al (2010) Acute pulmonary toxicity following intralesional administration of bleomycin for a lymphovenous malformation. Pediatr Pulmonol 45:192–196. https://doi.org/10.1002/ppul.21139

    Article  PubMed  Google Scholar 

  77. Cho AL, Kiang SC, Lodenkamp J et al (2020) Fatal lung toxicity after intralesional bleomycin sclerotherapy of a vascular malformation. Cardiovasc Intervent Radiol 43:648–651. https://doi.org/10.1007/s00270-020-02420-w

    Article  PubMed  Google Scholar 

  78. Méndez-Echevarría A, Fernandez-Prieto A, de la Serna O, et al (2018) Acute lung toxicity after intralesional bleomycin sclerotherapy. Pediatrics 141:e20161787. https://doi.org/10.1542/peds.2016-1787

  79. Davis KP, Gaffey MM, Kompelli AR, Richter GT (2022) Cutaneous hyperpigmentation following bleomycin sclerotherapy for vascular malformations. Pediatr Dermatol 39:103–106. https://doi.org/10.1111/pde.14869

    Article  PubMed  Google Scholar 

  80. Milbar HC, Jeon H, Ward MA et al (2019) Hyperpigmentation after foamed bleomycin sclerotherapy for vascular malformations. J Vasc Interv Radiol 30:1438–1442. https://doi.org/10.1016/j.jvir.2018.10.007

    Article  PubMed  Google Scholar 

  81. Hage AN, Chick JFB, Srinivasa RN et al (2018) Treatment of venous malformations: the data, where we are, and how it is done. Tech Vasc Interv Radiol 21:45–54. https://doi.org/10.1053/j.tvir.2018.03.001

    Article  PubMed  Google Scholar 

  82. Wohlgemuth WA, Müller-Wille R, Meyer L et al (2021) Bleomycin electrosclerotherapy in therapy-resistant venous malformations of the body. J Vasc Surg Venous Lymphat Disord 9:731–739. https://doi.org/10.1016/j.jvsv.2020.09.009

    Article  PubMed  Google Scholar 

  83. Cornelis F, Neuville A, Labrèze C et al (2013) Percutaneous cryotherapy of vascular malformation: initial experience. Cardiovasc Intervent Radiol 36:853–856. https://doi.org/10.1007/s00270-012-0434-9

    Article  CAS  PubMed  Google Scholar 

  84. Fish A, Moushey A, Chan SM et al (2022) Cryoablation of venous malformations: a systematic review. J Vasc Interv Radiol 33:993–1000. https://doi.org/10.1016/j.jvir.2022.04.010

    Article  PubMed  Google Scholar 

  85. Prologo JD, Johnson C, Hawkins CM et al (2020) Natural history of mixed and motor nerve cryoablation in humans—a cohort analysis. J Vasc Interv Radiol 31:912-916.e1. https://doi.org/10.1016/j.jvir.2019.11.026

    Article  PubMed  Google Scholar 

  86. Sag AA, Bittman R, Prologo F et al (2022) Percutaneous image-guided cryoneurolysis: applications and techniques. RadioGraphics 42:1776–1794. https://doi.org/10.1148/rg.220082

    Article  PubMed  Google Scholar 

  87. Friedman MV, Hillen TJ, Wessell DE et al (2014) Hip chondrolysis and femoral head osteonecrosis: a complication of periacetabular cryoablation. J Vasc Interv Radiol 25:1580–1588. https://doi.org/10.1016/j.jvir.2014.06.016

    Article  PubMed  Google Scholar 

  88. Cho SJ, Lee JH, Chung SR et al (2020) Radiofrequency ablation of facial venolymphatic malformations: assessment of efficacy and safety and the role of injectable electrodes. J Vasc Interv Radiol 31:544–550. https://doi.org/10.1016/j.jvir.2019.04.006

    Article  PubMed  Google Scholar 

  89. Vikingstad EM, de Ridder GG, Glisson RR et al (2015) Comparison of acute histologic and biomechanical effects of radiofrequency ablation and cryoablation on periarticular structures in a swine model. J Vasc Interv Radiol 26:1221-1228.e1. https://doi.org/10.1016/j.jvir.2015.04.013

    Article  PubMed  Google Scholar 

  90. Imray C, Grieve A, Dhillon S (2009) Cold damage to the extremities: frostbite and non-freezing cold injuries. Postgrad Med J 85:481. https://doi.org/10.1136/pgmj.2008.068635

    Article  CAS  PubMed  Google Scholar 

  91. Adams DM, Trenor CC, Hammill AM, et al (2016) Efficacy and Safety of sirolimus in the treatment of complicated vascular anomalies. Pediatrics 137:.https://doi.org/10.1542/peds.2015-3257

  92. Freixo C, Ferreira V, Martins J et al (2020) Efficacy and safety of sirolimus in the treatment of vascular anomalies: a systematic review. J Vasc Surg 71:318–327. https://doi.org/10.1016/j.jvs.2019.06.217

    Article  PubMed  Google Scholar 

  93. Hammill AM, MarySue W, Anita G et al (2011) Sirolimus for the treatment of complicated vascular anomalies in children. Pediatr Blood Cancer 57:1018–1024. https://doi.org/10.1002/pbc.23124

    Article  PubMed  Google Scholar 

  94. Lackner H, Karastaneva A, Schwinger W et al (2015) Sirolimus for the treatment of children with various complicated vascular anomalies. Eur J Pediatr 174:1579–1584. https://doi.org/10.1007/s00431-015-2572-y

    Article  CAS  PubMed  Google Scholar 

  95. Ricci KW, Hammill AM, Mobberley-Schuman P, et al (2019) Efficacy of systemic sirolimus in the treatment of generalized lymphatic anomaly and Gorham-Stout disease. Pediatr Blood Cancer 66:e27614. https://doi.org/10.1002/pbc.27614

  96. Wiegand S, Wichmann G, Dietz A (2018) Treatment of lymphatic malformations with the mTOR inhibitor sirolimus: a systematic review. Lymphat Res Biol 16:330–339. https://doi.org/10.1089/lrb.2017.0062

    Article  CAS  PubMed  Google Scholar 

  97. Shimano KA, Eng W, Adams DM (2022) How we approach the use of sirolimus and new agents: medical therapy to treat vascular anomalies. Pediatr Blood Cancer 69:e29603. https://doi.org/10.1002/pbc.29603

  98. Nozawa A, Ozeki M, Yasue S et al (2020) Immunologic effects of sirolimus in patients with vascular anomalies. J Pediatr Hematol Oncol 42:e355–e360. https://doi.org/10.1097/MPH.0000000000001650

    Article  CAS  PubMed  Google Scholar 

  99. Durand R, Reid JR, Belasco JB et al (2021) MRI for response assessment of extensive lymphatic malformations in children treated with sirolimus. Am J Roentgenol 217:741–752. https://doi.org/10.2214/AJR.20.24378

    Article  Google Scholar 

  100. Boscolo E, Limaye N, Huang L et al (2015) Rapamycin improves TIE2-mutated venous malformation in murine model and human subjects. J Clin Invest 125:3491–3504. https://doi.org/10.1172/JCI76004

    Article  PubMed  PubMed Central  Google Scholar 

  101. Soblet J, Limaye N, Uebelhoer M et al (2013) Variable somatic TIE2 mutations in half of sporadic venous malformations. Mol Syndromol 4:179–183. https://doi.org/10.1159/000348327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Limaye N, Kangas J, Mendola A et al (2015) Somatic activating PIK3CA mutations cause venous malformation. Am J Hum Genet 97:914–921. https://doi.org/10.1016/j.ajhg.2015.11.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Limaye N, Wouters V, Uebelhoer M et al (2009) Somatic mutations in the angiopoietin-receptor TIE2 can cause both solitary and multiple sporadic venous malformations. Nat Genet 41:118–124. https://doi.org/10.1038/ng.272

    Article  CAS  PubMed  Google Scholar 

  104. Maruani A, Tavernier E, Boccara O et al (2021) Sirolimus (rapamycin) for slow-flow malformations in children: the observational-phase randomized clinical PERFORMUS trial. JAMA Dermatol 157:1289–1298. https://doi.org/10.1001/jamadermatol.2021.3459

    Article  PubMed  Google Scholar 

  105. Castillo SD, Tzouanacou E, Zaw-Thin M, et al (2016) Somatic activating mutations in Pik3ca cause sporadic venous malformations in mice and humans. Sci Transl Med 8:332ra43. https://doi.org/10.1126/scitranslmed.aad9982

  106. Kangas J, Nätynki M, Eklund L (2018) Development of molecular therapies for venous malformations. Basic Clin Pharmacol Toxicol 123:6–19. https://doi.org/10.1111/bcpt.13027

    Article  CAS  PubMed  Google Scholar 

  107. André F, Ciruelos EM, Juric D et al (2021) Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2–negative advanced breast cancer: final overall survival results from SOLAR-1. Ann Oncol 32:208–217. https://doi.org/10.1016/j.annonc.2020.11.011

    Article  CAS  PubMed  Google Scholar 

  108. André F, Ciruelos E, Rubovszky G et al (2019) Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med 380:1929–1940. https://doi.org/10.1056/NEJMoa1813904

    Article  PubMed  Google Scholar 

  109. Copur MS (2020) Alpelisib to treat breast cancer. Drugs Today 56:357. https://doi.org/10.1358/dot.2020.56.6.3137526

    Article  CAS  Google Scholar 

  110. Vernieri C, Corti F, Nichetti F et al (2020) Everolimus versus alpelisib in advanced hormone receptor-positive HER2-negative breast cancer: targeting different nodes of the PI3K/AKT/mTORC1 pathway with different clinical implications. Breast Cancer Res 22:33. https://doi.org/10.1186/s13058-020-01271-0

    Article  PubMed  PubMed Central  Google Scholar 

  111. Novartis Pharmaceuticals (2022) EPIK-P2: a phase II double-blind study with an upfront, 16-week randomized, placebo-controlled period, to assess the efficacy, safety and pharmacokinetics of alpelisib (BYL719) in pediatric and adult patients with PIK3CA-related overgrowth spectrum (PROS). clinicaltrials.gov

  112. Couto JA, Huang AY, Konczyk DJ et al (2017) Somatic MAP2K1 mutations are associated with extracranial arteriovenous malformation. Am J Hum Genet 100:546–554. https://doi.org/10.1016/j.ajhg.2017.01.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Nguyen H-L, Boon LM, Vikkula M (2022) Trametinib as a promising therapeutic option in alleviating vascular defects in an endothelial KRAS-induced mouse model. Hum Mol Genet ddac169. https://doi.org/10.1093/hmg/ddac169

  114. Li D, March ME, Gutierrez-Uzquiza A et al (2019) ARAF recurrent mutation causes central conducting lymphatic anomaly treatable with a MEK inhibitor. Nat Med 25:1116–1122. https://doi.org/10.1038/s41591-019-0479-2

    Article  CAS  PubMed  Google Scholar 

  115. Lekwuttikarn R, Lim YH, Admani S et al (2019) Genotype-guided medical treatment of an arteriovenous malformation in a child. JAMA Dermatol 155:256–257. https://doi.org/10.1001/jamadermatol.2018.4653

    Article  PubMed  PubMed Central  Google Scholar 

  116. Edwards EA, Phelps AS, Cooke D, et al (2020) Monitoring arteriovenous malformation response to genotype-targeted therapy. Pediatrics 146:e20193206. https://doi.org/10.1542/peds.2019-3206

  117. Nicholson CL, Flanagan S, Murati M et al (2022) Successful management of an arteriovenous malformation with trametinib in a patient with capillary-malformation arteriovenous malformation syndrome and cardiac compromise. Pediatr Dermatol 39:316–319. https://doi.org/10.1111/pde.14912

    Article  PubMed  Google Scholar 

  118. Teng J (2022) Phase II clinical trial of MEK inhibitor trametinib in the treatment of complicated extracranial arterial venous malformation (VM). clinicaltrials.gov

  119. Borst AJ, Swerdlin RF, Phillips JD, et al (2022) How we established a multidisciplinary program for vascular anomalies. Pediatr Blood Cancer 69:e28863. https://doi.org/10.1002/pbc.28863

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Frederic J. Bertino.

Ethics declarations

Conflicts of interest

None

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bertino, F.J., Hawkins, C.M. Contemporary management of extracranial vascular malformations. Pediatr Radiol 53, 1600–1617 (2023). https://doi.org/10.1007/s00247-023-05670-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00247-023-05670-1

Keywords

Navigation