Lymphatic malformations are benign congenital malformations of lymphatic vessels and channels that are caused by the failure of lymph spaces to connect to the rest of the lymphatic system. They are lined by endothelial cells and separated by a scant intervening connective tissue stroma that often contains lymphoid aggregates.1 Classical treatment is surgical excision. However, complications such as damage to the nervous and vascular structures, incomplete excision, fistula formation, wound infection, or wound dehiscence may occur. Thus, sclerotherapy using ethanol, bleomycin, doxycycline, or OK-432 was the preferred treatment of macrocystic lymphatic malformation. Currently, the two most extensively investigated sclerosing agents are bleomycin and OK-432.234

We present herein a case of a patient with cervical lymphatic malformation who was cured with sclerotherapy using povidone-iodine. To our best knowledge, this is the first report of the use of povidone-iodine sclerotherapy for cervical lymphatic malformation.

A 24-year-old woman with a 1-week history of neck swelling visited our outpatient clinic. The patient had no significant medical or family history. On physical examination, the patient was found to have a soft, smooth, non-tender mass at the right posterior neck area. Computed tomography revealed a fluid-filled cyst in the right posterior fossa, extending to the right omohyoid muscle, compatible with lymphatic malformation. The cyst was 5.5×3.8×5.4 cm in size and had a heterogeneous density, suggesting blood in the cyst (Fig. 1). Ultrasonography-guided percutaneous drainage and sclerotherapy were performed because the size of the cyst did not change after 2 months of observation. Daily povidone-iodine sclerotherapy was performed for 3 days. Before the procedure, authors checked the patient's history of allergic reaction to povidone-iodine. Because povidone-iodine is one of the easily obtainable antiseptics, the patient had the experience of povidone-iodine usage and denied allergic reaction. In the supine position, the patient underwent percutaneous puncture of the cystic lymphatic malformation and drainage of fluid content with an 8.5 F pigtail catheter (Cook, Bloomington, IN, USA). After aspiration of clear and yellow fluid (70 mL), a mixture of 0.5% lidocaine (10 mL), contrast medium (15 mL), and normal saline (15 mL) was injected in the cyst in order to do intracystic anesthesia and ensure that there is no fluid leak from the cyst (Fig. 2). After making sure that there is no pericatheter contrast leakage, 40 mL of a 10% povidone-iodine was injected through the catheter, and then the percutaneous catheter drainage (PCD) was locked. The PCD was unlocked after 6 hours, and fluid was drained naturally. The same procedures were repeated on the second and third day. The content of the cyst was drained naturally for 2 days after completion of the 3-day sclerotherapy, until a 24-hour total drainage volume of less than 10 mL was collected. During admission and after hospital discharge, the patient had no fever, only mild pain and tenderness (visual analogue scale score for pain, <2) in the lesion area for several days. No bacterium was isolated in the bacterial culture of fluid from the cyst. After 8 months, the lesion was no longer palpable, and the patient felt no pain and tenderness in the right neck. Ultrasonography of the right neck revealed complete shrinkage of the cervical lymphatic malformation without finding of any complication (Fig. 3).

Classical treatment for lymphatic malformation consists of surgical excision with preservation of the nervous and vascular structures. However, this is not always possible because damage to these structures may occur during surgery, and postoperative events such as fistula formation, infection, and wound dehiscence may develop. The limitation of surgical treatment led to the development of other forms of therapy, such as application of sclerosing agents, that aim to achieve total or partial regression of lymphatic malformations.567

Bleomycin was first described as an anticancer drug. It was also shown to have a sclerosing effect on endothelial cells via a non-specific inflammatory reaction and was used for the first time as a sclerosing agent for lymphatic malformation in 1977.2 The adverse effects of this agent are described as minimal, including local swelling and inflammation. However, bleomycin is a less attractive sclerosing agent because it confers a risk of pulmonary fibrosis and the reported deaths related to bleomycin sclerotherapy.48

OK-432 is a lyophilized incubation mixture of group 1 Streptococcus pyogenes of human origin, which has been used as an immunopotentiating anticancer drug since 1975.9 The clinical effect occurs via damage to the endothelium of the lymphatic malformation, secondary to activation of the immune system (macrophages, NK cells, and LAK cytotoxic T lymphocytes).2 Thus, its injection initially results in an inflammatory response associated with swelling, erythema, pain, and fever for several days. Consequently, these systemic reactions restricted the use of OK-432 in the United States.

Doxycycline has some advantages over other sclerosing agents. It has been well tolerated with minimal side effects and is widely available. However, complications reported after dox-ycycline sclerotherapy in the head and neck lymphatic malformation include cellulitis, scarring, skin excoriation, and Horner's syndrome. Tooth discoloration and medication allergies are also potential risks.10

Compared with other sclerosing agents, povidone-iodine is less toxic, less irritant, economical, and easily available. It has local sclerosing action and antiseptic, antibacterial, and antifungal actions, and it is easy to prepare in the desired concentration.11 A 10% povidone-iodine solution contains 1% available iodine but free-iodine is at 0.1% concentration. It is well demonstrated that skin exposure causes irritant rather than allergic dermatitis. Rare cases of allergic dermatitis to povidone-iodine have been reported in the literature.12 In a well-documented study, only 2 of 500 patients were allergic to povidone-iodine (prevalence: 0.4%).13 In a systemic review, no harmful effect of iodine on thyroid function and no major adverse effects were seen with iodine regarding allergic responses or cytotoxicity.14 In previous studies, povidone-iodine was injected and left for 30 minutes twice daily, and then spontaneous drainage was allowed for the treatment of postoperative lymphoceles.1516 The total time that the catheter was left in the lesions ranged from 15 to 37 days in these studies. In our patient, however, the catheter was placed only for 5 days. Although it is difficult to compare postoperative lymphoceles directly with lymphatic malformation, we employed the protocol of clamping for 6 hours after povidone-iodine injection daily to be more effective than that of clamping for 30 minutes twice daily as in the previous studies.

The optimal sclerosing agent has not been elucidated yet. It should induce total shrinkage of the lymphatic malformation, have no systemic toxicity, and minimize the damage to surrounding tissue. Here, we propose povidone-iodine as an alternative means of treating cervical lymphatic malformations. However, further research in this direction is necessary and a long-term, large-scale prospective study to compare the efficiency and complications of povidone-iodine as a sclerosing agent is greatly needed.