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DOI: 10.1055/s-0044-1791281
Lymphatic Malformations: Review of Diagnosis and Management for the Interventional Radiologist
Abstract
Lymphatic malformations (LMs) arise from errors in lymphatic vascular development during embryogenesis and encompass an array of conditions that span from common cystic LMs to complex lymphatic anomalies (CLAs). Manifestations of LMs are wide-ranging, from clinically inconsequential to life-threatening. Proper diagnosis and management can be challenging and often benefit from an experienced multidisciplinary team. Cystic LMs are localized entities for which percutaneous sclerotherapy is the mainstay treatment. CLAs, on the other hand, are more diffuse in involvement and typically require multimodal therapy. With advances in the genetic understanding of LMs, targeted systemic therapies have been increasingly utilized with promising results. Thoracic duct interventions, both surgical and percutaneous, have a limited role in CLAs and should be approached cautiously to avoid significant complications. In this review, we discuss the genetic basis, imaging findings, and management options for LMs, with a particular focus on relevant interventional radiology techniques.
Publication History
Article published online:
07 November 2024
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References
- 1 International Society for the Study of Vascular Anomalies. ISSVA Classification for Vascular Anomalies. 2018 ). Accessed September 5, 2024 at: issva.org/classification
- 2 Hsu MC, Itkin M. Lymphatic anatomy. Tech Vasc Interv Radiol 2016; 19 (04) 247-254
- 3 Loukas M, Wartmann CT, Louis Jr RG. et al. Cisterna chyli: a detailed anatomic investigation. Clin Anat 2007; 20 (06) 683-688
- 4 Hematti H, Mehran RJ. Anatomy of the thoracic duct. Thorac Surg Clin 2011; 21 (02) 229-238 , ix
- 5 Langford RJ, Daudia AT, Malins TJ. A morphological study of the thoracic duct at the jugulo-subclavian junction. J Craniomaxillofac Surg 1999; 27 (02) 100-104
- 6 Fishman S. Slow-flow vascular malformations. In: Mulliken J, Burrows P, Fishman S. . eds. Mulliken & Young's Vascular Anomalies: Hemangiomas and Malformations. Vol. 2. Oxford: Oxford University Press; 2013
- 7 Trenor III CC, Chaudry G. Complex lymphatic anomalies. Semin Pediatr Surg 2014; 23 (04) 186-190
- 8 Mäkinen T, Boon LM, Vikkula M, Alitalo K. Lymphatic malformations: genetics, mechanisms and therapeutic strategies. Circ Res 2021; 129 (01) 136-154
- 9 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
- 10 Madsen RR, Vanhaesebroeck B, Semple RK. Cancer-associated PIK3CA mutations in overgrowth disorders. Trends Mol Med 2018; 24 (10) 856-870
- 11 Brouillard P, Schlögel MJ, Homayun Sepehr N. et al. Non-hotspot PIK3CA mutations are more frequent in CLOVES than in common or combined lymphatic malformations. Orphanet J Rare Dis 2021; 16 (01) 267
- 12 Rauen KA. The RASopathies. Annu Rev Genomics Hum Genet 2013; 14: 355-369
- 13 Rodriguez-Laguna L. et al. Somatic activating mutations in PIK3CA cause generalized lymphatic anomaly. J Exp Med 2019; 216 (02) 407-418
- 14 Acevedo JL, Shah RK, Brietzke SE. Nonsurgical therapies for lymphangiomas: a systematic review. Otolaryngol Head Neck Surg 2008; 138 (04) 418-424
- 15 Bruder E, Perez-Atayde AR, Jundt G. et al. Vascular lesions of bone in children, adolescents, and young adults. A clinicopathologic reappraisal and application of the ISSVA classification. Virchows Arch 2009; 454 (02) 161-179
- 16 Phang MJ, Courtemanche DJ, Bucevska M, Malic C, Arneja JS. Spontaneously resolved macrocystic lymphatic malformations: predictive variables and outcomes. Plast Surg (Oakv) 2017; 25 (01) 27-31
- 17 Perkins JA, Maniglia C, Magit A, Sidhu M, Manning SC, Chen EY. Clinical and radiographic findings in children with spontaneous lymphatic malformation regression. Otolaryngol Head Neck Surg 2008; 138 (06) 772-777
- 18 Laje P, Peranteau WH, Hedrick HL. et al. Ex utero intrapartum treatment (EXIT) in the management of cervical lymphatic malformation. J Pediatr Surg 2015; 50 (02) 311-314
- 19 Snyder EJ, Sarma A, Borst AJ, Tekes A. Lymphatic anomalies in children: update on imaging diagnosis, genetics, and treatment. AJR Am J Roentgenol 2022; 218 (06) 1089-1101
- 20 White CL, Olivieri B, Restrepo R, McKeon B, Karakas SP, Lee EY. Low-flow vascular malformation pitfalls: from clinical examination to practical imaging evaluation - Part 1, lymphatic malformation mimickers. AJR Am J Roentgenol 2016; 206 (05) 940-951
- 21 Zobel MJ, Nowicki D, Gomez G. et al. Management of cervicofacial lymphatic malformations requires a multidisciplinary approach. J Pediatr Surg 2021; 56 (05) 1062-1067
- 22 Kulungowski AM, Patel M. Lymphatic malformations. Semin Pediatr Surg 2020; 29 (05) 150971
- 23 Hurewitz AN, Lidonicci K, Wu CL, Reim D, Zucker S. Histologic changes of doxycycline pleurodesis in rabbits. Effect of concentration and pH. Chest 1994; 106 (04) 1241-1245
- 24 Franco C, Ho B, Mulholland D. et al. Doxycycline alters vascular smooth muscle cell adhesion, migration, and reorganization of fibrillar collagen matrices. Am J Pathol 2006; 168 (05) 1697-1709
- 25 Burrows PE, Mitri RK, Alomari A. et al. Percutaneous sclerotherapy of lymphatic malformations with doxycycline. Lymphat Res Biol 2008; 6 (3-4): 209-216
- 26 Cahill AM, Nijs E, Ballah D. et al. Percutaneous sclerotherapy in neonatal and infant head and neck lymphatic malformations: a single center experience. J Pediatr Surg 2011; 46 (11) 2083-2095
- 27 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
- 28 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
- 29 Chaudry G, Burrows PE, Padua HM, Dillon BJ, Fishman SJ, Alomari AI. Sclerotherapy of abdominal lymphatic malformations with doxycycline. J Vasc Interv Radiol 2011; 22 (10) 1431-1435
- 30 Burrows PE. Endovascular treatment of slow-flow vascular malformations. Tech Vasc Interv Radiol 2013; 16 (01) 12-21
- 31 Thomas DM, Wieck MM, Grant CN. et al. Doxycycline sclerotherapy is superior in the treatment of pediatric lymphatic malformations. J Vasc Interv Radiol 2016; 27 (12) 1846-1856
- 32 Acord M, Srinivasan AS, Cahill AM. Percutaneous treatment of lymphatic malformations. Tech Vasc Interv Radiol 2016; 19 (04) 305-311
- 33 Alqahtani A, Nguyen LT, Flageole H, Shaw K, Laberge J-M. 25 years' experience with lymphangiomas in children. J Pediatr Surg 1999; 34 (07) 1164-1168
- 34 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
- 35 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
- 36 Wiegand S, Dietz A, Wichmann G. Efficacy of sirolimus in children with lymphatic malformations of the head and neck. Eur Arch Otorhinolaryngol 2022; 279 (08) 3801-3810
- 37 Adams DM, Ricci KW. Vascular anomalies: diagnosis of complicated anomalies and new medical treatment options. Hematol Oncol Clin North Am 2019; 33 (03) 455-470
- 38 Venot Q, Blanc T, Rabia SH. et al. Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature 2018; 558 (7711) 540-546
- 39 Canaud G, Lopez Gutierrez JC, Irvine AD. et al. Alpelisib for treatment of patients with PIK3CA-related overgrowth spectrum (PROS). Genet Med 2023; 25 (12) 100969
- 40 Glade RS, Buckmiller LM. CO2 laser resurfacing of intraoral lymphatic malformations: a 10-year experience. Int J Pediatr Otorhinolaryngol 2009; 73 (10) 1358-1361
- 41 Zhou Q, Zheng JW, Mai HM. et al. Treatment guidelines of lymphatic malformations of the head and neck. Oral Oncol 2011; 47 (12) 1105-1109
- 42 García-Montero P, Del Boz J, Baselga-Torres E. et al. Use of topical rapamycin in the treatment of superficial lymphatic malformations. J Am Acad Dermatol 2019; 80 (02) 508-515
- 43 Ricci KW, Iacobas I. How we approach the diagnosis and management of complex lymphatic anomalies. Pediatr Blood Cancer 2022; 69 (Suppl. 03) e28985
- 44 Ozeki M, Fujino A, Matsuoka K, Nosaka S, Kuroda T, Fukao T. Clinical features and prognosis of generalized lymphatic anomaly, Kaposiform lymphangiomatosis, and Gorham-Stout disease. Pediatr Blood Cancer 2016; 63 (05) 832-838
- 45 Ricci KW, Hammill AM, Mobberley-Schuman P. et al. Efficacy of systemic sirolimus in the treatment of generalized lymphatic anomaly and Gorham-Stout disease. Pediatr Blood Cancer 2019; 66 (05) e27614
- 46 Croteau SE, Kozakewich HP, Perez-Atayde AR. et al. Kaposiform lymphangiomatosis: a distinct aggressive lymphatic anomaly. J Pediatr 2014; 164 (02) 383-388
- 47 Chavhan GB, Amaral JG, Temple M, Itkin M. MR lymphangiography in children: technique and potential applications. Radiographics 2017; 37 (06) 1775-1790
- 48 Chen E, Itkin M. Thoracic duct embolization for chylous leaks. Semin Intervent Radiol 2011; 28 (01) 63-74
- 49 Benjamin J, O'Leary C, Hur S, Gurevich A, Klein WM, Itkin M. Imaging and interventions for lymphatic and lymphatic-related disorders. Radiology 2023; 307 (03) e220231
- 50 Bhardwaj R, Vaziri H, Gautam A, Ballesteros E, Karimeddini D, Wu GY. Chylous ascites: a review of pathogenesis, diagnosis and treatment. J Clin Transl Hepatol 2018; 6 (01) 105-113
- 51 Gray M, Kovatis KZ, Stuart T. et al. Treatment of congenital pulmonary lymphangiectasia using ethiodized oil lymphangiography. J Perinatol 2014; 34 (09) 720-722
- 52 Hubrechts J, Wåhlander H, Kjellberg-Olofsson C, Maleux G, Gewillig M. Case report: disseminated systemic embolism of lipiodol after lymphography for plastic bronchitis after Fontan repair. Front Pediatr 2020; 8: 584185
- 53 Taki Y, Sato S, Suzuki K. et al. A case of acute respiratory distress syndrome due to lymphography with lipiodol for chylothorax after esophagectomy. Surg Case Rep 2019; 5 (01) 1
- 54 Chaudry G. Complex lymphatic anomalies and therapeutic options. Tech Vasc Interv Radiol 2019; 22 (04) 100632
- 55 Itkin M, Krishnamurthy G, Naim MY, Bird GL, Keller MS. Percutaneous thoracic duct embolization as a treatment for intrathoracic chyle leaks in infants. Pediatrics 2011; 128 (01) e237-e241
- 56 Majdalany BS, Saad WA, Chick JFB, Khaja MS, Cooper KJ, Srinivasa RN. Pediatric lymphangiography, thoracic duct embolization and thoracic duct disruption: a single-institution experience in 11 children with chylothorax. Pediatr Radiol 2018; 48 (02) 235-240
- 57 Lee EW, Shin JH, Ko HK, Park J, Kim SH, Sung KB. Lymphangiography to treat postoperative lymphatic leakage: a technical review. Korean J Radiol 2014; 15 (06) 724-732
- 58 Stecker MS, Fan C-M. Lymphangiography for thoracic duct interventions. Tech Vasc Interv Radiol 2016; 19 (04) 277-285
- 59 Johnson OW, Chick JF, Chauhan NR. et al. The thoracic duct: clinical importance, anatomic variation, imaging, and embolization. Eur Radiol 2016; 26 (08) 2482-2493
- 60 Chung A, Gill AE, Rahman FN, Hawkins CM. Retrograde thoracic duct embolization in a pediatric patient with total cavopulmonary connection and plastic bronchitis. J Vasc Interv Radiol 2015; 26 (11) 1743-1746
- 61 Homayun-Sepehr N, McCarter AL, Helaers R. et al. KRAS-driven model of Gorham-Stout disease effectively treated with trametinib. JCI Insight 2021; 6 (15) e149831 DOI: 10.1172/jci.insight.149831.
- 62 Foster JB, Li D, March ME. et al. Kaposiform lymphangiomatosis effectively treated with MEK inhibition. EMBO Mol Med 2020; 12 (10) e12324
- 63 Li D, March ME, Gutierrez-Uzquiza A. et al. ARAF recurrent mutation causes central conducting lymphatic anomaly treatable with a MEK inhibitor. Nat Med 2019; 25 (07) 1116-1122
- 64 Welsh SJ, Corrie PG. Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma. Ther Adv Med Oncol 2015; 7 (02) 122-136