CASO CLÍNICO

 

Cervical lymphangioma: therapeutic management with OK-432 (Picibanil)

Linfangioma cervical: manejo terapéutico con OK-432 (Picibanil)

 

 

E. Valle Rodríguez¹, V. Villanueva San Vicente², M.A. Rodríguez González², D. Segarra Fenoll², M.J. García Mateos², S. Méndez-Trujillo³

¹ Médico Residente.
² Médico Adjunto.
³ Jefe de Servicio. Servicio de Cirugía Oral y Maxilofacial.
Hospital Virgen de la Arrixaca, Murcia.

Correspondence

 

 

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ABSTRACT

Introduction: Lymphangioma is a malformation of the lymphatic system. The classic approach is surgery. OK-432 (Picibanil) has sclerosing action and is being used as the first therapeutic step. The objective was to report a new case of lymphangioma treated with OK-432 and to review the literature.
Material and method: We report the case of a 16-year-old man with a 10x6-cm macrocystic cervical lymphangioma treated with a dose of OK-432.
Results: At 16 weeks of treatment, the size of the lymphangioma was 6x2 cm and it was clinically unappreciable.
Discussion: OK-432 treatment has a high cure rate, low recurrence rate, and fibrosis circumscribed to the lesion. Compared to surgery, scars and possible harm to vital structures are avoided.

Key words: Lymphangioma; Sclerosis; OK-432; Picibanil.

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RESUMEN

Introducción: El linfangioma es una malformación del sistema linfático. El abordaje clásico ha sido la cirugía. El OK-432 (Picibanil) tiene acción esclerosante y se está utilizando cómo primer escalón terapéutico. El objetivo es aportar un nuevo caso de linfangioma tratado con OK-432 y hacer una revisión de la literatura.
Material y método: Aportamos un varón de 16 años con un linfangioma cervical macroquístico de 10 x 6 cm tratado con una dosis de OK-432.
Resultados: A las 16 semanas del tratamiento, el tamaño del linfangioma era de 6 x 2 cm, siendo clínicamente inapreciable.
Discusión: El tratamiento con OK-432 tiene una alta tasa de curación, con una baja tasa de recidiva y una fibrosis circunscrita a la lesión. En relación con la cirugía, se evitan cicatrices y posibles lesiones de estructuras vitales.

Palabras clave: Linfangioma; Esclerosis; OK-432; Picibanil.

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Introduction

Lymphangioma is a congenital malformation of the lymphatic system that occasionally is acquired after traumatic, infectious, iatrogenic or neoplastic action.^1,2 It occurs as a slow-growing benign mass of soft consistency that usually is asymptomatic. It can cause cosmetic and functional problems like dysphagia and dyspnea, particularly when it increases in size quickly due to infection or bleeding when vascular lesions are present. There are no differences between sexes.^1,2,4-6 Morbidity and mortality are related to the size and young age of the patient.² Up to 90% of lymphangiomas are diagnosed before the age of 2 years and up to 50% at birth.⁴ The most frequent location of lymphangioma is the cervical region (75%) and within this area, the posterior triangle. ⁷ Other locations follow, e.g., the submentonian region, tongue, oropharynx and parotid cell.

Lymphangioma is classified as capillary, cavernous, and cystic; different forms can coexist in same lymphangioma. The location, structure, and consistency of the surrounding tissues can condition different histologic types. Cystic lymphangioma consists of cysts delimited by a layer of endothelium. It occurs in areas of lax tissue and numerous fascias, such as the cervical region.^1,2 It can be subclassified, in turn, by size. We define lesions with cysts larger than 2 cm as macrocystic and lesions con cysts smaller than 2 cm as microcystic. Mixed lymphangiomas that are predominantly macrocystic or microcystic exist.

Anatomically, the tumors are cavities filled with lymphatic fluid, delimited by vascular endothelium, and connected with the peripheral lymphatic system as a result of erroneous embryogenesis.⁸

The diagnosis is based on clinical manifestations and imaging techniques. MRI is the technique that yields the best definition, extension of the lesion, and view of neighboring structures. Doppler sonography is useful for differentiating lymphangioma from vascular malformations or mixed lymphangiomas by the presence of vascular flow. MRI may not distinguish lymphangioma from venous malformations, which is why the use of contrast can help in the diagnosis of these cases.⁴ FNAB can also be used as a diagnostic method.¹ The differential diagnosis includes branchial cyst, thyroglossal cyst, laryngocele, thyroid mass, lipoma, and vascular malformations. Treatment can be surgical excision or sclerosis of the lesion using sclerosing agents. OK-432, also known as Picibanil, is noteworthy among them. It is a low-virulence, lyophilyzed compound obtained from Streptococcus pyogenes group A bacteria of human origin. It has been incubated in penicillin G, which incapacitates it to produce streptolysin S.⁵ Its use in patients allergic to b-lactams is contraindicated due to the risk of anaphylaxis.⁶ The use of concomitant antibiotic therapy at the time of OK-432 administration can diminish its effectiveness.⁴ Ogita et al.⁹ described its mechanism of action: increased number of inflammatory cells (especially neutrophils and macrophages), natural killer cells (CD56+) and lymphocytes T (CD3+), and an increase in TNF and IL-6 that enhances the endothelial permeability of the lymphangioma, producing lymphatic drainage, emptying and collapse of cystic spaces, and sclerosis confined to the walls of the lesion.^10,11

 

Material and Method

We report the clinical case of a 16-year-old male who came to the clinic with a right laterocervical mass that was totally asymptomatic, of soft consistency, 10x6 cm in size, and had an evident esthetic impact (Fig. 1). As referred by the patient, the mass appeared fairly rapidly when he was 7 years old as a result of intense trauma to the region. MRI revealed macrocystic cervical lymphangioma (Figs. 2 and 3). The decision to use OK-432 treatment was based on this diagnosis. In the operating room, under propofol sedation and without guided ultrasonography due to the size of the lymphangioma, a single dose of 0.2 mg of OK-432 dissolved in 20 ml saline solution was administered. We inserted a needle in the lymphangioma after disinfecting the skin with iodinated povidone. We extracted 20 ml of the content and, without removing the needle or catheter, injected 20 ml saline solution with 0.2 mg OK-432 dissolved. There were no intraoperative complications. The patient was administered prophylactic paracetamol, which prevented fever, but not pain and local inflammation. The tumor swelled to 14x10 cm and impeded neck movement. The airway remained patent at all times, so tracheotomy did not have to be performed. During admission, continuous analgesic perfusion was administered (3 vials of metamizole in 500 cc glucose solution infused at 21 ml/h; tramadole was added to the perfusion as demanded by the patient). The patient was released once the pain was controlled, 7 days after admission.

 

Results

Twenty-three days after injecting OK-432, the patient experienced frank reduction in the lymphangioma, which disappeared clinically in the next 3 days. Sixteen weeks post-injection, a follow-up MRI disclosed a right cervical lymphangioma of 6x2 cm (Figs. 4 and 5), which had passed unnoticed clinically (Photograph 6). We ruled out a new injection of OK-432 with the patient. After a post-treatment follow- up of 42 weeks, the patient showed no clinical signs of lymphangioma and had a totally normal life.

Discussion

The classic treatment of lymphangioma is surgery.³ Alternatively, different sclerosing agents have been used, including steroids, dextrose, tetracycline, ethanol, and bleomycin. These agents have the disadvantage of producing sclerosis outside the walls of the lymphangioma, as in the case of bleomycin, which causes pulmonary fibrosis. The advantage is that the lesions to blood vessels, nerves, and adjacent vital structures that can occur with surgery are avoided.

In 1987, Ogita et al.¹² published the first study in patients with lymphangioma in which an agent used previously as an immunomodulator in tumoral processes, called OK-432, was injected. It was shown to have a sclerosing action without perilesional fibrosis.^10,11 As reported by Ogita et al.,¹² the maximum dose of OK- 432 for lymphangioma is 0.2 mg dissolved in 20 ml saline solution. Mean response time to the first injection is 2-6 weeks. No minimum or maximum age for using this treatment has been described. OK-432 is injected under general anesthesia in children and with sedation in adults. Insertion of the needle under ultrasonographic guidance is not required systematically. The adverse effects most commonly reported are fever, erythema, pain, and local inflammation, which in very few cases require tracheotomy. The overall response differs in accordance with the classification of the lymphangioma. Macrocystic and mixed lymphangiomas respond far better than microcystic lymphangiomas or mixed vascular lesions. There is no effect on cavernous or capillary lymphangiomas.^4-6,13 This may be explained by the larger number of communications existing between the intralesional spaces of macrocystic lymphangiomas, which improves the diffusion of the sclerosing agent in the lesion.⁵

Recurrence of lymphangioma after OK-432 treatment, according to Luzzatto et al.,⁶ is 11%. Spontaneous lymphangioma regression has been reported in up to 6%, depending on the series.^2,4,6

Surgery prior to OK-432 treatment diminishes the success rate due to the larger number of injections necessary to achieve cure.^4,5 Surgery often is complex and frequently does not achieve complete tumor excision, resulting in higher rates of recurrence, complications, and persistent symptomatic disease.^2,3

For that reason, and due to the absence of sclerosing action outside the walls of the lymphangioma, OK-432 has become the first-line therapy for lymphangioma. Surgery is reserved for cases that require rapid improvement of the patient¹⁴ or when OK-432-induced sclerosis of the lesion is ineffective. According to Luzzatto et al.⁶ OK-432 can be considered ineffective when 3 injections spaced by 12-week intervals are administered without improvement, although up to 7 injections in same lymphangioma are given in some series.^4,5

 

 

Correspondence:
Ekaitz Valle Rodríguez
Servicio de Cirugía Oral y Maxilofacial.
Hospital Virgen del Arrixaca
Ctra. Cartagena s/n (El Palmar), Murcia, España.
Email: ekaitzvalle@hotmail.com

Recibido: 01.02.07
Aceptado: 17.09.07

 

 

References

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