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Cervicofacial Lymphangiomas
Cervicofacial Lymphangiomas
Author
Ted L Tewfik, MD Professor of Otolaryngology-Head and Neck Surgery, Professor of
Pediatric Surgery, McGill University Faculty of Medicine; Senior Staff, Montreal Children's
Hospital, Montreal General Hospital, and Royal Victoria Hospital
BACKGROUND
The natural history of cervicofacial lymphangioma is the presence of a mass in the
head and neck area. Cervicofacial lymphangioma is noted before birth, at birth, or in the first
few months of life in less than 50% of patients with this condition. The initial appearance of
cystic hygroma or lymphangioma in adulthood is less common. The growth rate of this
neoplasm is variable. Slow progression followed by pseudoregression eventually gives rise to
reappearance. Rapid growth or engorgement with lymph or blood is often associated with
direct infection, trauma, or a secondary respiratory or skin infection. Spontaneous regression
has been reported in as many as 15% of patients with cervicofacial lymphangioma. Malignant
change has not been reported.
An image depicting a lymphatic malformation can be seen below.
EPIDEMIOLOGY
Frequency
ETIOLOGY
The origin of lymphangiomas is controversial. Theories include lymphangiomas as
true neoplasms, hamartomas, or congenital dysplasias of the lymphatics. To determine the
role of angiogenesis in the pathogenesis of lymphangioma, Sidle et al (2005) examined
patients' specimens for expression of angiogenic inducer vascular endothelial growth factor
(VEGF) and angiogenic inhibitor pigment epithelium-derived factor (PEDF) using
immunohistochemical analysis.[1] Staining patterns of VEGF and PEDF were evaluated.
Histological evidence of increased angiogenesis, including microvascular density, stromal
fibrosis, and inflammation, were graded in each group and correlated with recurrence.
Lymphangioma specimens demonstrated histological evidence of increased
angiogenic activity including multiple areas of increased VEGF staining combined with little
PEDF staining. Recurrent specimens had increased histological evidence of angiogenesis as
well as increased VEGF and decreased PEDF activity compared with nonrecurrent lesions.
They concluded that lymphangiomas exhibit tumorlike pathogenesis owing to the
high expression of angiogenic inducers compared with the low expression of inhibitors.
Recurrence may be influenced by this imbalance of angiogenic mediators. Further research
with antiangiogenic therapy using agents such as PEDF analogues or anti-VEGF receptor
antibodies is indicated.
However, most physicians favor the theory that dysplastic lymphatic tissue is
sequestered in a target tissue space or organ during fetal development. Sabin (1909) proposed
that lymphatics are derived from primitive veins by budding endothelial cells.[2] Because
jugular sacs are the largest formations, the high incidence in the neck correlates well with
clinical studies and experience. Incomplete canalization of the lymphatics causes obstruction
of lymph flow and cyst or cavern development. These formations are analogous to blood-
containing cavernous hemangiomas. Target organs and tissues include the retroperitoneum,
chest wall, lung, mesentery, pancreas, scrotum, tongue, floor of the mouth, larynx, neck, lip,
mediastinum, parotid gland, adrenal gland, axilla, diaphragm, gallbladder, spleen, skull base,
colon, breast, subdural space, and pelvis.
A recent case series (2013) of 141 patients concluded that airway involvement of
lymphatic malformations predominantly affects the oral cavity and oropharynx and no cases
of glottis, subglottic, or tracheal involvement have been seen.[3]
Pathophysiology
Macroscopically, lymphangiomas are large cavernous, cystic, or complex multilocular
masses that extend into tissue fascial planes. Patients usually present with a painless
enlarging mass. Cystic types infiltrate into the surrounding tissue by fingerlike multiloculated
extensions. Within these multiloculated honeycombed cysts is a clear-to-cloudy, sometimes
blood-tinged, fluid with the consistency of uncooked egg whites. Cyst walls are indistinct;
penetration and decompression of the cyst is a common occurrence during surgical excision.
In many cases, cervical fetal lymphangi oma may be diagnosed before birth by means of
ultrasonography. Before 30 weeks' gestation, cervical lesion is almost always associated with
chromosomal abnormalities and congenital cardiac malformations usually in the septated
type. A high rate of spontaneous abortion is encountered in this type.
The different types of cervicofacial lymphangioma are classified as follows:
Lymphangioma circumscriptum is a simplex superficial red macular or vesicular lesion of
mucous membranes or skin.
Lymphangioma capillary type is a simplex lesion of dilated capillarylike channels.
Lymphangioma cavernosa is a simplex lesion of dilated lymphatic channels with deep
extension and without cyst formation.
Lymphangioma cystica (ie, cystic hygroma) is composed of large lymphatic cysts that
expand into adjacent soft tissue planes and are well defined, circumscribed, or lobulated.
Lymphangioma complex is composed of multiloculated poorly defined cysts extending to
more than one anatomic area, tissue plane, or organ system.
PRESENTATION
Children or, less commonly, adults usually present with a mass in the head and neck area.
Approximately 90% of cases of cervicofacial lymphangioma become clinically apparent by
the patient's third year of life. Common head and neck sites in childhood are the cervical area,
floor of the mouth, and the tongue. Orofacial manifestations include mandibular or maxillary
deformation, rotation, and malocclusion (ie, crossbite). In a study by Orvidas et al, the most
common location involved was the submandibular region, followed by the parotid and
cheek.[4]
Obtain a careful history.
Perform a complete head and neck examination as well as a general examination.
Lymphangioma in the head and neck generally involves a swelling or mass that is soft to
palpation and well circumscribed or diffuse. It may have defined or ill-defined borders and
is often associated with a bluish discoloration.
Regional venous congestion and the absence of pain are common.
Common additional symptoms and findings include diplopia, proptosis, respiratory
distress, dysphagia, and dysphonia.
Children with massive head and neck and chest lymphangiomas have higher mortality and
morbidity. The involvement of the airway is an important prognostic factor. [5]
Differential diagnosis consideration
Cystic lymphatic malformation is more common in the neck, while the cavernous type
usually appears in the lips, tongue, cheek, and floor of the mouth. The anterior two thirds of
the tongue is the most common intraoral site, producing macroglossia. Enlargement of this
congenital rest in the upper aerodigestive tract can result in airway distress, dysphagia,
aspiration, and difficulty breastfeeding in a child. Cystic hygroma may be a solitary or
complex opaque neck mass that spreads along multiple tissue planes.
Cavernous lymphangioma may be well circumscribed or diffuse. Extension into the
skin produces a bluish discoloration. The diffuse form tends to infiltrate into the surrounding
tissue planes, around blood vessels and nerves with poorly defined borders. An attempt at
staging has been reported. This system stages lymphangioma from early T1 to late T4 disease
and is based on cosmetic changes, functional deficits, age of patient at diagnosis, and the
number of sites involved.
INDICATIONS
Indications for therapy in the neonate with cervical lymphangioma are complex.
Severe cosmetic changes do not necessitate immediate intervention unless functional
impairment is occurring. Failure to thrive because of ineffective breastfeeding in a child and
aspiration and airway compromise during the first 3 months of life are clear indications for
immediate intervention. Rapid growth at any age is another indication for immediate
intervention. Assess persistence or recurrence of disease in older age groups according to
location, functional loss, and cosmetic impairment. Lymphangioma is best treated by means
of surgical resection. However, surgical resection may be associated with a significant
neurologic deficit and high rate of recurrence of the lymphangioma, which is reported to
approach 81% in the cystic type arising above the hyoid bone.
CONTRAINDICATIONS
The principle contraindication to surgery is the circumstance in which further
intervention will result in serious functional or cosmetic consequences rendering the quality
of life below the standards of a reasonable functional life. This problem often arises in
clinical situations in which previous therapy has resulted in significant complications that are
often neurologic. Multiple recurrences usually indicate that the probability of cure from
additional surgery is low. These recurrences are usually associated with lymphangiomas
diagnosed in patients younger than 1 year or with lymphangiomas involving the lip,
hypopharynx, larynx, tongue, and floor of the mouth.
References
1. Sidle DM, Maddalozzo J, Meier JD, et al. Altered pigment epithelium-derived factor
and vascular endothelial growth factor levels in lymphangioma pathogenesis and
clinical recurrence. Arch Otolaryngol Head Neck Surg. 2005 Nov. 131(11):990-5.
2. Sabin FR. The lymphatic system in human embryos, with a consideration of the
morphology of the system as a whole. Am J Anat. 1909. 9:43-91.
3. O TM, Rickert SM, Diallo AM, Scheuermann-Poley C, Otokiti A, Hong M, et al.
Lymphatic malformations of the airway. Otolaryngol Head Neck Surg. 2013 Jul.
149(1):156-60.
4. Orvidas LJ, Kasperbauer JL. Pediatric lymphangiomas of the head and neck. Ann Otol
Rhinol Laryngol. 2000 Apr. 109(4):411-21.
5. Greinwald J Jr, Cohen AP, Hemanackah S, Azizkhan RG. Massive lymphatic
malformations of the head, neck, and chest. J Otolaryngol Head Neck Surg. 2008 Apr.
37(2):169-73.
6. Kura MM, Rane VK. Cervicofacial actinomycosis mimicking lymphangioma
circumscriptum. Indian J Dermatol. 2011 May. 56(3):321-3.
7. Angiero F, Benedicenti S, Benedicenti A, Arcieri K, Berne E. Head and neck
hemangiomas in pediatric patients treated with endolesional 980-nm diode
laser. Photomed Laser Surg. 2009 Aug. 27(4):553-9.
8. Peral Cagigal B, Serrat Soto A, Calero H, Verrier Hernandez A. [OK-432 therapy for
cervicofacial lymphangioma in adults]. Acta Otorrinolaringol Esp. 2007 May.
58(5):222-4. [Medline].
9. Ozeki M, Kanda K, Kawamoto N, Ohnishi H, Fujino A, Hirayama M, et al.
Propranolol as an alternative treatment option for pediatric lymphatic
malformation. Tohoku J Exp Med. 2013. 229(1):61-6.
10. Ozen IO, Moralioglu S, Karabulut R, et al. Surgical treatment of cervicofacial cystic
hygromas in children.ORL J Otorhinolaryngol Relat Spec. 2005. 67(6):331-4.
11. Liu DY, Guan J, He HX. [Diagnosis and surgical treatment of cervical
lymphangioma]. Zhonghua Yi Xue Za Zhi. 2009 Dec 29. 89(48):3413-6.
12. Anadol AZ, Oguz M, Bayramoglu H, et al. Cystic lymphangioma of the spleen
mimicking hydatid disease.J Clin Gastroenterol. 1998 Jun. 26(4):309-11.
13. Anderson NG, Kennedy JC. Prognosis in fetal cystic hygroma. Aust N Z J Obstet
Gynaecol. 1992 Feb. 32(1):36-9.
14. Antoniades K, Kiziridou A, Psimopoulou M. Traumatic cervical cystic hygroma. Int J
Oral Maxillofac Surg. 2000 Feb. 29(1):47-8.
15. Baer S, Davis J. Cystic hygroma presenting in adulthood. J Laryngol Otol. 1989 Oct.
103(10):976-7.
16. Bagwell CE. CO2 laser excision of pediatric airway lesions. J Pediatr Surg. 1990
Nov. 25(11):1152-6.
17. Borecky N, Gudinchet F, Laurini R, et al. Imaging of cervico-thoracic
lymphangiomas in children. Pediatr Radiol. 1995. 25(2):127-30.
18. Boxen I, Zhang ZM, Filler RM. Lymphoscintigraphy for cystic hygroma. J Nucl Med.
1990 Apr. 31(4):516-8.
19. Bronshtein M, Bar-Hava I, Blumenfeld I, et al. The difference between septated and
nonseptated nuchal cystic hygroma in the early second trimester. Obstet Gynecol.
1993 May. 81(5 (Pt 1)):683-7.
20. Caro PA, Mahboubi S, Faerber EN. Computed tomography in the diagnosis of
lymphangiomas in infants and children. Clin Imaging. 1991 Jan-Mar. 15(1):41-6.
21. Chappuis JP. [Current aspects of cystic lymphangioma in the neck]. Arch Pediatr.
1994 Feb. 1(2):186-92.
22. Charabi B, Bretlau P, Bille M, et al. Cystic hygroma of the head and neck--a long-
term follow-up of 44 cases. Acta Otolaryngol Suppl. 2000. 543:248-50.
23. Chong KT, Ong CL. Cystic hygroma in adulthood. Singapore Med J. 1997 Jun.
38(6):261-2.
24. Claesson G, Gordon L, Kuylenstierna R. [A revolutionary Japanese method for
treatment of lymphangioma]. Lakartidningen. 1998 Apr 29. 95(18):2074-7.
25. Duman L, Karnak I, Akinci D, et al. Extensive cervical-mediastinal cystic lymphatic
malformation treated with sclerotherapy in a child with Klippel-Trenaunay
syndrome. J Pediatr Surg. 2006 Jan. 41(1):e21-4.
26. Edwards PD, Rahbar R, Ferraro NF, et al. Lymphatic malformation of the lingual
base and oral floor. Plast Reconstr Surg. 2005 Jun. 115(7):1906-15.
27. Emery PJ, Bailey CM, Evans JN. Cystic hygroma of the head and neck. A review of
37 cases. J Laryngol Otol. 1984 Jun. 98(6):613-9.
28. Emran MA, Dubois J, Laberge L, et al. Alcoholic solution of zein (Ethibloc)
sclerotherapy for treatment of lymphangiomas in children. J Pediatr Surg. 2006 May.
41(5):975-9.
29. Fageeh N, Manoukian J, Tewfik T, et al. Management of head and neck lymphatic
malformations in children. J Otolaryngol. 1997 Aug. 26(4):253-8.
30. Farmand M, Kuttenberger JJ. A new therapeutic concept for the treatment of cystic
hygroma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996 Apr. 81(4):389-
95.
31. Figi FA. Radium in treatment of multilocular lymph cysts of neck in children. AJR
Am J Roentgenol. 1929. 21:473-80.
32. Filston HC. Hemangiomas, cystic hygromas, and teratomas of the head and
neck. Semin Pediatr Surg. 1994 Aug. 3(3):147-59.
33. Giguere CM, Bauman NM, Sato Y, et al. Treatment of lymphangiomas with OK-432
(Picibanil) sclerotherapy: a prospective multi-institutional trial. Arch Otolaryngol
Head Neck Surg. 2002 Oct. 128(10):1137-44.
34. Giguere CM, Bauman NM, Smith RJ. New treatment options for lymphangioma in
infants and children. Ann Otol Rhinol Laryngol. 2002 Dec. 111(12 Pt 1):1066-75.
35. Goshen S, Ophir D. Cystic hygroma of the parotid gland. J Laryngol Otol. 1993 Sep.
107(9):855-7.
36. Grosfeld JL, Skinner MA, Rescorla FJ, et al. Mediastinal tumors in children:
experience with 196 cases.Ann Surg Oncol. 1994 Mar. 1(2):121-7.
37. Hancock BJ, St-Vil D, Luks FI, et al. Complications of lymphangiomas in children. J
Pediatr Surg. 1992 Feb. 27(2):220-4; discussion 224-6.
38. Hase T, Kodama M, Sano H, et al. Successful treatment of a recurrent large cystic
hygroma in a child with intracystic injection of OK-432. Eur J Pediatr. 1996 May.
155(5):424.
39. Holland AJ. OK-432 and lymphatic malformations in children: The Starship
Children's Hospital experience.J Pediatr Surg. 2005 Jul. 40(7):1214.
40. Hutchinson I. Mandibular enlargement: an unusual complication of a cervical cystic
hygroma. Int J Paediatr Dent. 1996 Jun. 6(2):123-7.
41. Ikarashi T, Inamura K, Kimura Y. Cystic lymphangioma and plunging ranula treated
by OK-432 therapy: a report of two cases. Acta Otolaryngol Suppl. 1994. 511:196-9.
42. Kennedy TL, Whitaker M, Pellitteri P, et al. Cystic hygroma/lymphangioma: a
rational approach to management. Laryngoscope. 2001 Nov. 111(11 Pt 1):1929-37.
43. Lacosta JL, Zabaleta M, Sanchez Galan L. [Congenital cervical deformities]. An
Otorrinolaringol Ibero Am. 1998. 25(2):173-83.
44. Landing BH, Farber S. Tumors of the cardiovascular system. Atlas of Tumor
Pathology. Washington, DC: Armed Forces Institute of Pathology; 1956. 124-38.
45. Mahboubi S, Potsic WP. Computed tomography of cervical cystic hygroma in the
neck. Int J Pediatr Otorhinolaryngol. 1989 Sep. 18(1):47-51.
46. Mikhail M, Kennedy R, Cramer B, et al. Sclerosing of recurrent lymphangioma using
OK-432. J Pediatr Surg. 1995 Aug. 30(8):1159-60.
47. Ogita S, Tsuto T, Nakamura K, et al. OK-432 therapy for lymphangioma in children:
why and how does it work?. J Pediatr Surg. 1996 Apr. 31(4):477-80.
48. Ogita S, Tsuto T, Tokiwa K, et al. Treatment of cystic hygroma in children with
special reference to OK-432 therapy. Z Kinderchir. 1987 Oct. 42(5):279-81.
49. Orford J, Barker A, Thonell S, et al. Bleomycin therapy for cystic hygroma. J Pediatr
Surg. 1995 Sep. 30(9):1282-7.
50. Pia F, Aluffi P, Olina M. [Cystic lymphangioma in the head and neck region]. Acta
Otorhinolaryngol Ital. 1999 Apr. 19(2):87-90.
51. Pui MH, Li ZP, Chen W, et al. Lymphangioma: imaging diagnosis. Australas Radiol.
1997 Nov. 41(4):324-8.
52. Ricciardelli EJ, Richardson MA. Cervicofacial cystic hygroma. Patterns of recurrence
and management of the difficult case. Arch Otolaryngol Head Neck Surg. 1991 May.
117(5):546-53.
53. Ruiz E Jr, Valera ET, Verissimo F, et al. [OK-432 therapy for lymphangioma in
children]. J Pediatr (Rio J). 2004 Mar-Apr. 80(2):154-8.
54. Samuel M, McCarthy L, Boddy SA. Efficacy and safety of OK-432 sclerotherapy for
giant cystic hygroma in a newborn. Fetal Diagn Ther. 2000 Mar-Apr. 15(2):93-6.
55. Sato K, Maekawa T, Yabuki K, et al. Cystic lymphangiomas of the colon. J
Gastroenterol. 1999 Aug. 34(4):520-4.
56. Sermon A, Gruwez JA, Lateur L, et al. The importance of magnetic resonance
imaging in the diagnosis and treatment of diffuse lymphangioma. Acta Chir Belg.
1999 Oct. 99(5):230-5.
57. Shimizu K, Nishino M, Arita K. Cystic lymphangioma: its orofacial
manifestations. ASDC J Dent Child. 1999 Nov-Dec. 66(6):377-82, 366.
58. Smith RJ, Burke DK, Sato Y, et al. OK-432 therapy for lymphangiomas. Arch
Otolaryngol Head Neck Surg. 1996 Nov. 122(11):1195-9.
59. Stein M, Hsu RK, Schneider PD, et al. Alcohol ablation of a mesenteric
lymphangioma. J Vasc Interv Radiol. 2000 Feb. 11(2 Pt 1):247-50.
60. Suzuki Y, Obana A, Gohto Y, et al. Management of orbital lymphangioma using
intralesional injection of OK- 432. Br J Ophthalmol. 2000 Jun. 84(6):614-7.
61. Takinami S, Kaga M, Yahata H, et al. Radiation-induced hypoplasia of the teeth and
mandible. A case report. Oral Surg Oral Med Oral Pathol. 1994 Sep. 78(3):382-4.
62. Tanigawa N, Shimomatsuya T, Takahashi K, et al. Treatment of cystic hygroma and
lymphangioma with the use of bleomycin fat emulsion. Cancer. 1987 Aug 15.
60(4):741-9.
63. Thomas RL. Prenatal diagnosis of giant cystic hygroma: prognosis, counselling, and
management; case presentation and review of the recent literature. Prenat Diagn.
1992 Nov. 12(11):919-23.
64. Tibesar RJ, Rimell FL, Michel E. Cystic hygroma of the skull base. Arch Otolaryngol
Head Neck Surg. 1999 Dec. 125(12):1390-3.
65. Turner C, Gross S. Treatment of recurrent suprahyoid cervicofacial lymphangioma
with intravenous cyclophosphamide. Am J Pediatr Hematol Oncol. 1994 Nov.
16(4):325-8.
66. Vigil DV, DiFiori JP, Puffer JC, et al. Arachnoid cyst and subdural hygroma in a high
school football player.Clin J Sport Med. 1998 Jul. 8(3):234-7.
67. Watson WL, McCarthy WD. Blood and lymph vessel tumors. A report of 1,056
cases. Urg Gynecol Obstet. 1940. 71:569-71.
68. White CW, Wolf SJ, Korones DN, et al. Treatment of childhood angiomatous
diseases with recombinant interferon alfa-2a. J Pediatr. 1991 Jan. 118(1):59-66.
69. Yang AD, Chang YL, Chaou WT. A huge cystic hygroma of the neck associated with
intraventricular haemorrhage in a term neonate. Acta Paediatr. 1999 Mar. 88(3):344-
6.
70. Yuh WT, Buehner LS, Kao SC, et al. Magnetic resonance imaging of pediatric head
and neck cystic hygromas. Ann Otol Rhinol Laryngol. 1991 Sep. 100(9 Pt 1):737-42.
71. Zheng JW, Qin ZP, Zhang ZY. [Management of lymphatic malformations in oral and
maxillofacial regions: the rationale according to the new classification]. Shanghai
Kou Qiang Yi Xue. 2005 Dec. 14(6):553-6.