FP688 : Sclerotherapy for Lymphangioma

Dr.Bejjanki Kavya Madhuri, B18698, Dr.Tarjani Dave

Orbital Lymphangiomas are benign unencapsulated vascular hamartomatous tumors. Although benign in nature, they tend to invade and intertwine with surrounding tissues, which makes treatment difficult. Clinically, lymphangiomas are associated with decreased vision, ocular pain, decreased extraocular motility, proptosis, displaced globe, and ptosis. Symptoms typically are present in childhood, which poses a particular problem because amblyopia may develop secondarily. Ocular emergencies such as spontaneous intraorbital hemorrhages may occur, which leads to optic neuropathies and permanent visual disturbances.

Orbital lymphangiomas present a treatment challenge, and conservative approaches are preferred. Radiotherapy is unsuccessful because of the slow turnover rate of the tumor. Surgical excision has been reported; however, the procedure often is difficult because of the intricate architecture of the lesion and the associated risk of hemorrhage. Complications such as cicatrisation, residual tumor, and symptomatic recurrence have been reported. Further, multiple surgical resections may be needed to obtain a satisfactory result. Alternatives to surgical excision include observation, needle decompression, carbon dioxide laser debulking, and systemic corticosteroids, all of which displayed varied success in the past.  The use of sclerosing agents for the treatment of lymphangiomas have been used in previous experiments. The purpose of the current study was to to study the safety and efficacy of bleomycin and sodium tetradecyl sulphate (STS) for treatment of orbital and peri-orbital lymphatic malformations.

Methods:

Retrospective study of 13 patients with orbital and per-orbital Lymphangioma treated with bleomycin and sodium tetradecyl sulphate (STS) at Ophthalmic plastic services, L V Prasad Eye Institute from March 2013 to December 2018.

The diagnosis of lymphangioma in these patients was made on the basis of clinical examination and imaging findings, mainly computed tomography (CT), and in some cases magnetic resonance imaging (MRI). The tumours were classified based on the imaging appearance into three different subtypes: macrocystic, mixed and microcystic lymphangiomas. Patients with predominantly microcystic type of lymphangioma where the cysts were less than 1 cm in diameter, predominantly macrocystic disease included cysts greater than 1 cm in diameter, and mixed is combination of both. Under aseptic precaution, the macrocystic components were aspirated with a hypodermic syringe and 18G needle, while keeping the tip of aspiration needle within the cystic lumen, STS injected 1/10^th of volume of aspirate; for microcystic components, 0.5 mg per kg body weight of bleomycin aqueous solution (1 IU/ml) was injected. Patients were discharged the same day. This procedure was repeated after 6 weeks if the cystic component persisted. The maximum cumulative dose of bleomycin allowed was 5 mg/kg body weight.

Follow-up and additional injections were given until the lesion completely resolved. The response was graded as complete resolution (total disappearance), good response (showing > 50% reduction in size) and poor response (showing < 50% reduction or no change in size). Recurrence was defined as reappearance of the tumour after complete resolution or increase in size after initial significant reduction in size. Photographs were taken at follow-up for ease of comparison. When bleomycin sclerotherapy was no longer required or no longer feasible, the follow-up period was increased to 3 monthly, then 6 monthly until the size of the lesion was stable, and then yearly.

Results:

The 13 patients were aged between 3 years and 54 years. Majority of patients had proptosis (n = 11, 85%). Other symptoms included ptosis (n=9, 70%), strabismus (3, 23%), exposure keratopathy (2, 15%). No signs of compressive optic neuropathy noted in any patient. Imaging shows 9 microcystic disease, 1 macrocystic disease, 3 mixed disease. Out of 13 patients, 9 had both orbit and palpaebral component, 2 had purely orbit, 2 had purely palpebral components. The number of procedures per patient varied from 1 to 3 sittings with average of 2 sittings. Complete resolution was seen in 70% of lesions, 20% had good response and the remaining 10% had poor respons. The observations were recorded at the end of follow-up or at the time the patient was last seen in the clinic. Complications reported include inflammatory signs in 3 patients in immediate phase, which were controlled by systemic steroids and periocular pigmentation in 4 patients in late phase. However, no life- threatening complications such as respiratory obstruction and severe hypersensitivity reaction to bleomycin were observed. No patient developed excessive scarring as a result of the procedure.

Discussion:

The idea of using sclerotherapy in the treatment of lymphangioma occurred when it was noted that lymphatic malformations spontaneously involute when they became infected and the infection resolved. The first case of lymphangioma treated by sclerotherapy was reported in 1933, using sodium morrhuate. Complete tumour regression was noted in 6 weeks following intralesional injection. Since then various sclerosing agents have been used, namely iodine, ethanolamine oleate, alcohol, ethibloc, tetracycline and cyclophosphamide. Bleomycin and Sodium tetra decyl sulphate are currently the most popular sclerosants. However, no studies have been conducted to compare the efficacy between these two agents.

Bleomycin is an anti-neoplastic antibiotic, produced by the fermentation of streptomyces verticillus. Discovered in 1965, this drug was found to cause single- and double-strand DNA breaks and inhibition of DNA and RNA synthesis. Since then it has been used for its anti-neoplastic property to treat malignancy. In the treatment of malignant pleural effusion, it was observed that bleomycin caused marked fibrosis and scarring. This sclerosing property was first put into use in the treatment of lymphatic malformation in 1977. In this series, 12 patients who either had incomplete surgical resection, recurrent or non-resectable lymphangioma were treated with bleomycin. Good results were reported in these patients.

Studies using bleomycin have produced promising results. Our study indicated that intralesional bleomycin therapy was very effective and the results were comparable to these published series. Different authors have quoted success rates of between 36 to 63% for complete tumour regression, of up to 88% significant lesion regression, and poor response of between 12 to 23% using either bleomycin or OK432.

In this study, bleomycin aqueous solution was injected directly into a cyst after nil aspirate from the cyst content. Unlike STS, most authors advise against injecting bleomycin into the microcystic part component of the tumour. This is where STS has an advantage over bleomycin. Macrocystic injection of STS was performed without significant clinical side effects. Thus, this drug can be used to treat macrocystic lymphangioma.

No recurrences of tumour were observed in this study. No serious complications were seen as a result of intralesional bleomycin therapy. Most patients complained of mild skin erythema, local swelling and mild tenderness. These symptoms lasted for a day or two but did not prolong their stay in hospital.

In patients with complete resolution, there was no undesired excessive scarring but periocular pigmentation noted at the injection site.

Conclusion:

Intralesional bleomycin and STS therapy is a safe and effective method of treatment for lymphangioma. The results from our series are comparable with other published series. No serious side effects from intralesional bleomycin therapy were observed. Our results, support the continued use of sclerotherapy with bleomycin in the treatment of lymphangioma. Sclerotherapy is recommended in place of surgery as the first-line treatment modality. The latter must be reserved for those lesions where sclerotherapy had failed.