Cystic lymphangioma (CL) is a benign rare malformation of the lymphatic system 1, consisting of masses of abnormal lymphatic channels 2, occurring in one out of 2000–4000 live births 3.
The lesion can arise anywhere, but is usually found in the region of the neck and axillary. It may also arise from the abdominal wall, inguinal region, buttocks, anogenital region, and retroperitoneal areas 4. Other rare sites include the tongue 5, parotid 6, mediastinum 7, spleen 8, and prostate 9. The tissue of origin is usually the subcutaneous tissue, but it may also arise from muscles, bone, or rarely from internal organs 10.
CL usually presents in neonatal and infancy periods; however, it may present in adulthood, as mesenteric and/or retroperitoneal CL 11.
The condition presents with a soft partially compressible swelling in the affected area, and may have a bluish hue. Sudden enlargement may result from infections or intracystic hemorrhage. Patients could present with dysphagia or signs of upper airway obstruction (e.g. dyspnea, stridor, and cyanotic attacks), and tracheostomies may be required. Involvement of the skin (lymphangioma cutis) may produce puckering of the skin or vesicles that exude a clear yellowish fluid 12.
Microscopically, CL consists of multiple loculi filled with lymph. In the depth the loculi are quite large, but they decrease in size toward the surface 13.
Landing and Farber 14 classified lymphangioma into three groups: (i) lymphangioma simplex, composed of small capillary-sized, thin-walled lymphatic channels; (ii) cavernous lymphangioma, comprising of dilated lymphatic channels, often with an adventitious covering; and (iii) CL (cystic hygroma), consisting of multiple cystic cavities filled with a straw-colored fluid.
The terms ‘cystic hygroma’ and ‘lymphangioma’ are often used interchangeably, and it is the most commonly occurring lymphangioma in children 15.
Well-localized lesions are easily characterized by ultrasonography and computed tomography. MRI, however, provides the most reliable diagnosis of more complex lesions, and their macrocytic and microcytic components or a combination thereof provide diagnostic confirmation, delineate anatomical extension and relationship with surrounding vital structures, and document potential complicating factors such as an associated venous malformation component or prominent draining blood vessels 16–19.
Conventional surgical excision remains the most popular method of treatment in many developing countries despite the dangers associated with this treatment modality. Surgery may be multiple, complex, and may have to be staged before complete excision can be achieved 20.
Although complete CL excision is desired, subtotal or partial removal may be dictated by specific organ involvement or proximity to neurovascular structures 21 or in cases with diffuse infiltration with an obscured anatomy 22. Although residual CL is left in such circumstances, incomplete excision does not absolutely imply recurrence requiring an additional therapeutic intervention 23.
The surgical procedure is sometimes complex and requires a multidisciplinary team for evaluation and management, particularly those cases with the involvement of the tongue, oral floor, and mandible 24.
The timing of surgery depends on the site of the lesion and its potential complications. In certain instances when lesions may potentially cause severe compression on the airway, surgery may even be indicated during pregnancy (ex-utero intrapartum treatment), which involves the partial delivery of fetuses at risk for postnatal upper airway obstruction by cesarean section and establishing airway control while maintaining placental circulation and oxygenation 25.
Recent advances in sclerotherapy have expanded contemporary management options, particularly when complete surgical resection is difficult because of the presence of multiple loculi and extensive lesions. Sclerotherapy provides a treatment option in such patients, offering a viable alternative to surgery 26–29.
The popularity of sclerotherapy in the treatment of CL is growing, and several substances are used as sclerosants. OK-432 (a lyophilized mixture of group A Streptococcus pyogenes and benzylpenicillin) is believed to exert its effect by inducing endothelial damage occurring secondary to the activation of the host immune system 30,31. Bleomycin exerts a mild inflammatory effect on endothelial cells 32. Other sclerosants in use are doxycycline (a broad-spectrum antibiotic) 33, acetic acid at a 40–50% concentration, absolute ethanol 34, and hypertonic saline 35.
This study aims to review our experience in the management of CL over a 3-year period in two referral institutes.
Patients and methods
This study is a retrospective file review. The records of all cases of lymphangioma seen at the Pediatric Surgical Unit from in Mansoura and Tanta University hospitals in the period from January 2007 to November 2010 were reviewed. Special charts were designed to retrieve the following data from the records: age at presentation, sex, site of the pathology, clinical presentation, investigations, management modality, and outcome of treatment.
A full informed consent was obtained from the patients’ custodians, and those who agreed to injection sclerotherapy were injected; otherwise, surgery was performed. The study was approved by the ethical committee in both institutes.
There were 93 children with CL within the 3-year period; 40 (43%) were males and 53 (57%) were females (M : F=7 : 9) ranging in age from one month to 5 years. Their ages at presentation are shown in Table 1. Majority (92.5%) of the patients were younger than 1 year of age.
The cervical region (Fig. 1) was the most frequent site of involvement, followed by the axillary region (Fig. 2). In the patients with cervical CL, the lesion was on the left side of the neck in 20 cases. Other sites of involvement were the face (Fig.3), breast (Fig.4), abdominal wall (Fig.5), thigh (Fig. 6), mesenteric (Fig. 7), and retroperitoneal area (Fig. 8) (Table 2).
The diagnosis was made on the basis of the clinical characteristics and ultrasonography. In cases with cervicofacial or abdominal locations, MRI was used to accurately characterize the swelling with respect to extensions and in relation to nerves and major vessels. In the seven cases with abdominal locations, six cases presented with a palpable abdominal mass and were further investigated by ultrasonography, computed tomography, or MRI. In one case, CL was an incidental finding.
Antenatal detection was carried out in seven cases with a large cervical lesion during an antenatal ultrasonographic examination.
In 56 cases, the lesion was a well-localized lymphangiomatous malformation, and we decided on surgery to remove the entire lesion in a single setting (Figs 9 and 10). The remaining 33 cases, however, were complex, involving more than one anatomical region. For these cases, a staged approach was utilized, removing as much as possible from the lesion without injury to the neighboring vital structures.
For lesions that involved the parotid and cervicoaxillary regions, we used a nerve stimulator (Stimuplex DIG RC; B. Braun Co., Melsungen, Germany) to identify the related nerves and avoid injury to them.
All of the abdominal cases were operated by a laparotomy incision; we did not use laparoscopy for any patient.
In four cases, we used sclerosing therapy for treatment using bleomycin injection as the primary intervention. In another five cases, injection was used for recurrence.
Under general or local anesthesia, depending on the patient’s age, as much cystic fluid as possible was aspirated. After aspiration, bleomycin solution (at a concentration of 1 mg (1 U) in 1 ml normal saline solution) was injected into the cystic lesions at a dosage of 0.3–0.6 mg/kg depending on the size of the lesion, at a maximum dose of not more than 10 mg/injection.
The patient was hospitalized for 24 h after injection to monitor any adverse reaction, and was then discharged to attend an outpatient counseling after 4 weeks. A radiograph was ordered 6 months after injection to detect any pulmonary complication. The results were classified as an ‘excellent’ response if the masses had disappeared completely, as a ‘good’ response if the masses had reduced considerably (over 50% reduction) with some residual lesions, and as a ‘poor’ response if the masses reduced only slightly (<50% reduction) or did not change in size.
In cases where injection was the primary line of intervention, three patients showed an excellent response; all of them required a single injection. Reduction in size started within the first week and complete disappearance occurred by the first month. Another patient showed a good response. In one patient, injection was followed by swelling and inflammation of the lesion, followed by cellulitis. Immediate antibiotic therapy was initiated, but the case was lost to follow-up.
In five recurrent patients who were injected, a good response was achieved in two patients, whereas the other three patients were re-operated for complete excision.
The injected patients developed some minor side effects including local swelling, redness, pain, and low-grade fever during the first 24, which required only symptomatic treatment. No patient developed pulmonary interstitial fibrosis.
Sixteen patients developed recurrences (Fig. 11), including seven patients who previously had cervical CL, four patients who previously had axillary CL, three patients who previously had parotid CL, one patient who previously had abdominal CL, and one patient who previously had thigh CL (Table 3).
Complications included recurrence in 16 patients, a disfiguring scar in nine patients, seroma in seven patients, skin disruption, hematoma, and hypoglossal nerve palsy in two patients, facial nerve palsy in one patient, and cellulitis following a sclerosant injection in one patient.
The development of the lymphatic system can be explained by two theories: the centripetal and centrifugal theories. Lewis 36 supported the centrifugal theory, and, according to this hypothesis, the lymphatic system develops as mesenchymal spaces that later coalesce into a system of vessels that eventually join the venous system. Huntington and McClure supported the centripetal theory, which proposes that the jugular and posterior lymphatics form as outgrowths of endothelium from veins into the surrounding mesenchyme 36.
This study showed that CL occurs more commonly in the cervicoaxillary region compared with other regions of the body. This distribution pattern is similar to that reported by other studies 8,15,20.
Most patients (92.5%) presented before the age 1 year. Late presentation (after the neonatal period) in this study was because of reluctancy to medical consultation by some parents living in rural areas who have low socioeconomic status. The seven patients who presented after 1 year had abdominal CLs with late presentation. All reviews have reported that presentation of CL in adulthood is rare 11,13.
An antenatal diagnosis was made in seven (7.5%) patients. This low rate of diagnosis is because of in the lack of antenatal care in remote, rural areas.
The primary indications for a surgical intervention in the patients of the series were esthetic reasons, and compression on airway and digestive systems. We did not encounter other indications for an urgent intervention such as sudden enlargement with respiratory compromise 37.
A surgical approach was favored in this series over injection sclerotherapy; although it is gaining popularity in the west 32, surgery is still the first line of management in the developing countries 20.
Surgery for CLs is difficult and may have to be multistage to remove the lesion. We decided on a multistage operative approach for 37 cases (all of them were in the cervical and axillary regions). This is in agreement with other authors 2 who have used this approach to avoid injury to vital structures in the neck and axilla.
Although spontaneous regression has been observed by some authors and thus required conservative management, particularly for macrocytic lymphangiomas located in the posterior triangle of the neck 3,38, we operated on all patients without awaiting spontaneous regression.
We used the sclerotherapy approach as the primary line for treatment in four patients and as management for recurrence in five patients. Evacuation of most of the fluid out of the lesion is a crucial step for success, as it facilitates more contact between the sclerosant and the endothelial lining of the lymphangioma. The amount injected must not distend the lesion markedly as this may precipitate inflammation. The total dose of injection must not exceed 10 mg per injection setting; otherwise, there may be a risk of development of pulmonary interstitial fibrosis, a well-documented complication for this sclerosant 32. To report the results of sclerotherapy, we used the criteria for response on the basis of previous reports to classify results into excellent, good, and poor responses 39,40.
Recurrence was the most common complication (17.2%) in our study. Recurrence after CL excision is high because of the infiltrative nature of the lesion and the involvement of vital structures, making its complete elimination very difficult in ∼60% of cases 41. The remaining small lymphatics expand and form the lesion again. In this respect, our results are in agreement with those of other reports in the literature 39.
Although we used a nerve stimulator to identify the related nerves during dissection of the anomaly, we had two cases of a hypoglossal nerve and one facial nerve palsy, which indicates that nerve injury may occur despite efforts to prevent this.
The rate of development of other complications (seroma, hematoma, unsightly scar, wound disruption) was similar to that of other reports in the literature 28.
CL has a variable presentation in children. A staged operative procedure may be necessary in order to reduce mortality and morbidity including the risk of injury to the neighboring structures. Sclerotherapy has almost the same efficacy as the first line of management as surgery, although it is not widely practiced in developing countries.
There is a high postoperative complication associated with surgical excision, especially with head and neck CLs. Anesthesia in these patients requires careful monitoring. Long-term follow-up is desirable after excision because of the possibility of recurrence.
Conflicts of interest
There are no conflicts of interest.
1. Makni A, Chebbi F, Fetirich F, Ksantini R, Bedioui H, Jouini M, et al. Surgical management of intra-abdominal cystic lymphangioma. Report of 20 cases. World J Surg. 2012;36:1037–1043
2. Perkins JA, Manning SC, Tempero RM, Cunningham MJ, Edmonds JL Jr, Hoffer FA, Egbert MA. Lymphatic malformations: review of current treatment. Otolaryngol Head Neck Surg. 2010;142:795–803 803.e1
3. Kennedy TL, Whitaker M, Pellitteri P, Wood WE. Cystic hygroma/lymphangioma: a rational approach to management. Laryngoscope. 2001;111(11 I):1929–1937
4. Temizkan O, Abike F, Ayvaci H, Demirag E, Görücü Y, Isik E. Fetal axillary cystic hygroma: a case report and review. Rare Tumors. 2011;3:122–125
5. Nitnaware AZ, Sakhare PT, Kapre GM. Cystic hygroma with extensive tongue involvement. Indian J Otolaryngol Head Neck Surg. 2011;63:89–92
6. Lee GS, Perkins JA, Oliaei S, Manning SC. Facial nerve anatomy, dissection and preservation in lymphatic malformation management. Int J Pediatr Otorhinolaryngol. 2008;72:759–766
7. Impellizzeri P, Romeo C, Borruto FA, Granata F, Scalfari G, Saverio De Ponte F, Longo M. Sclerotherapy for cervical cystic lymphatic malformations in children. Our experience with computed tomography-guided 98% sterile ethanol insertion and a review of the literature. J Pediatr Surg. 2010;45:2473–2478
8. Mirza B, Ijaz L, Saleem M, Sharif M, Sheikh A. Cystic hygroma: an overview. J Cutan Aesthet Surg. 2010;3:139–144
9. Chowdhury MM, Abdulkarim JA. Multilocular cystadenoma of the prostate presenting as a giant pelvic mass. Br J Radiol. 2009;82:e200–e201
10. Smithers CJ, Fishman SJHolcomb GW III, Murphy P. Vascular anomalies. Ashcraft's Pediatric Surgery. 5th ed. Philadelphia, USA Saunders-Elsevier:982–996
11. Gow L, Gulati R, Khan A, Mihaimeed F. Adult-onset cystic hygroma: a case report and review of management. Grand Rounds. 2011;11:5–11
12. Brooks JE. Cystic hygroma of the neck. Laryngoscope. 1973;83:117–128
13. Shetty DC, Urs AB, Rai HC, Ahuja N, Manchanda A. Case series on vascular malformation and their review with regard to terminology and categorization. Contemp Clin Dent. 2010;1:259–262
14. Landing BH, Farber S Tumors of the cardiovascular system. Atlas of tumor pathology. 1956;Vol. 7 Washington, DC United States Armed Force Institute of Pathology:124–135
15. Stal S, Hamilton S, Spira M. Hemangiomas, lymphangiomas, and vascular malformations of the head and neck. Otolaryngol Clin North Am. 1986;19:769–796
16. Eisbrenner K, Steffensen TS, Whiteman VE, Gilbert-Barness E. De novo translocation t(5;9)(q11.2;p22) associated with hydrops fetalis and cystic hygroma. Fetal Pediatr Pathol. 2012;31:39–42
17. Alpman A, Cogulu O, Akgul M, Ataman Arikan E, Durmaz B, Karaca E, et al. Prenatally diagnosed Turner syndrome and cystic hygroma: incidence and reasons for referrals. Fetal Diagn Ther. 2009;25:58–61
18. Borecky N, Gudinchet F, Laurini R, Duvoisin B, Hohlfeld J, Schnyder P. Imaging of cervico-thoracic lymphangiomas in children. Pediatr Radiol. 1995;25:127–130
19. Legiehn GM, Heran MKS. Classification, diagnosis, and interventional radiologic management of vascular malformations. Orthop Clin North Am. 2006;37:435–474
20. Sowande OA, Adejuyigbe O, Abubakar AM. Management of cystic lymphangiomas in Ile-Ife, Nigeria. Nig J Surg Res. 2003;5:32–37
21. Riechelmann H, Muehlfay G, Keck T, Maufeldt T, Rettinger G. Total, subtotal, and partial surgical removal of cervicofacial lymphangiomas. Arch Otolaryngol Head Neck Surg. 1999;125:643–648
22. Fliegelman LJ, Friedland D, Brandwein M, Rothschild M. Lymphatic malformation: predictive factors for recurrence. Otolaryngol Head Neck Surg. 2000;123:706–710
23. Raveh E, Dejong AL, Taylor GP, Forte V. Prognostic factors in the treatment of lymphatic malformations. Arch Otolaryngol Head Neck Surg. 1997;123:1061–1065
24. Bloom DC, Perkins JA, Manning SC. Management of lymphatic malformations. Curr Opin Otolaryngol Head Neck Surg. 2004;12:500–504
25. Stefini S, Bazzana T, Smussi C, Piccioni M, Frusca T, Taddei F, et al. EXIT (Ex utero Intrapartum Treatment) in lymphatic malformations of the head and neck: discussion of three cases and proposal of an EXIT-TTP (Team Time Procedure) list. Int J Pediatr Otorhinolaryngol. 2012;76:20–27
26. Smith RJH, Burke DK, Sato Y, Poust RI, Kimura K, Bauman NM. OK-432 therapy for lymphangiomas. Arch Otolaryngol Head Neck Surg. 1996;122:1195–1199
27. Orford J, Barker A, Thonell S, King P, Murphy J. Bleomycin therapy for cystic hygroma. J Pediatr Surg. 1995;30:1282–1287
28. Okazaki T, Iwatani S, Yanai T, Kobayashi H, Kato Y, Marusasa T, et al. Treatment of lymphangioma in children: our experience of 128 cases. J Pediatr Surg. 2007;42:386–389
29. Ogita S, Tsuto T, Tokiwa K, Takahashi T. Intracystic injection of OK-432: a new sclerosing therapy for cystic hygroma in children. Br J Surg. 1987;74:690–691
30. Smith MC, Zimmerman MB, Burke DK, Bauman NM, Sato Y, Smith RJH. Efficacy and safety of OK-432 immunotherapy of lymphatic malformations. Laryngoscope. 2009;119:107–115
31. Saito M, Ebina T, Koi M. Induction of interferon-γ in mouse spleen cells by OK-342, a preparation of Streptococcus pyogenes.
Cell Immunol. 1982;68:187–192
32. Muir T, Kirsten M, Fourie P, Dippenaar N, Ionescu GO. Intralesional bleomycin injection (IBI) treatment for haemangiomas and congenital vascular malformations. Pediatr Surg Int. 2004;19:766–773
33. Alomari AI, Karian VE, Lord DJ, Padua HM, Burrows PE. Percutaneous sclerotherapy for lymphatic malformations: a retrospective analysis of patient-evaluated improvement. J Vasc Interv Radiol. 2006;17:1639–1648
34. Lee BB, Kim YW, Seo JM, Hwang JH, Do YS, Kim DI, et al. Current concepts in lymphatic malformation. Vasc Endovasc Surg. 2005;39:67–81
35. Dubois J, Garel L, Abela A, Laberge L, Yazbeck S. Lymphangiomas in children: percutaneous sclerotherapy with an alcoholic solution of zein. Radiology. 1997;204:651–654
36. Lewis FT. The development of the lymphatic system in rabbits. Am J Anat. 1905;5:95–111
37. Emery PJ, Bailey CM, Evans JNG. Cystic hygroma of the head and neck. A review of 37 cases. J Laryngol Otol. 1984;98:613–619
38. 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;138:772–777
39. Niramis R, Watanatittan S, Rattanasuwan T. Treatment of cystic hygroma by intralesional bleomycin injection: experience in 70 patients. Eur J Pediatr Surg. 2010;20:178–182
40. Tanaka K, Inomata Y, Utsunomiya H, Uemoto S, Asonuma K, Katayama T, et al. Sclerosing therapy with bleomycin emulsion for lymphangioma in children. Pediatr Surg Int. 1990;5:270–273
41. Ameh EA, Nmadu PT. Cervical cystic hygroma: pre-, intra-, and post-operative morbidity and mortality in Zaria, Nigeria. Pediatr Surg Int. 2001;17:342–343