FP1230 : Intralesional Bleomicin in the Treatment of Orbital Lymphangioma

Dr. Trivedi Nitin Vinaykant, T02244

 

Introduction:

Although benign and representing only 1 to 3 percent of all orbital masses, Orbital and periorbitallymphangiomas are an obstinate bunch: These hamartomatous, unencapsulated tumors intertwine with surrounding normal tissue, increase in size with infections, and create proteinaceous or blood-filled cysts that can bleed spontaneously—despite the absence of an identifiable blood supply.

Abstract

A prospective study of 15 patients with orbital lymphangioma ,diagnosed clinically and radiologically,is presented. Age of patient varied from 2 to 45 years. Treatment of patients was a combination of intralesional injection Bleomycin(in all patients )with surgical excision in some were the cyst was anteriorly situated . Dose of drug was 0.5 mg /Kg body weight, not exceeding 10 units at  a time.A 24 g needle was passed into the orbital cyst and fluid was aspirated. Keeping needle in same position, drug was injected into the cyst. Follow up after 6 months,4 patients had total regression clinically and on B scan .Seven patients had partial regression and injection was repeated.In 2 patients as mass was anteriorly situated, surgical excision with injection of dye in posterior lesions was done. In  2 patients there were residualasymptomatic cysts in posterior part and so patients were kept under observation. No significant side effects were observed.

Aim:

The study was conducted to find out the clinical effect of InjectionBleomicin on clinically diagnosed orbital lymphangiomas.

Material :

This is a prospective non randomized clinical study carried out in Nagri  Eye Hospital, Ahmedabad between  January 2015 and April 2016. Patients having complaints indicating lymphangioma were investigated radiologically with B scan ultrasonography, CT scan and MRI. If diagnosed as lymphangioma ,patients were  included in the study . Clinical features were proptosis ,bluish conjunctival mass, subconjunctival  hemorrhage with proptosis or dilated blood vessels,or rarelyhemolacryma. There was a history of upper respiratory tract in 5 patients. Four patients gave a history of sudden increase in the amount of proptosis with URI.One patient gave a past history of being operated by a neurosurgeon for swelling on the forehead 5 years back.  On systemic examination, a two year old child showed a brownish vascular tuft on the hard  palate in the mouth.

Age of the patient varied from 2 year to 45 years and all were reported to have developed it in five years of life . There were 8 females and 7 males. It was unilateral in all cases. None had a positive family history.

Method:

Two treatment modalities were employed in the study. If the mass was anteriorly situated and well localized, the surgical excision was done with injection of Bleomycin in the microcysts .If the lesion was big and posteriorly situated , an attempt was made to expose the anterior extent of the lesion which on examination  under microscopeappeared as bluish pearly lobules. A 24 gauge needle with5 cc empty syringe was inserted in the mass towards center and posterior pole. With a suction of the syringe ,fluid was aspirated, which was dark brown in all cases, sometimes fresh blood was aspirated along with it. This led to collapse of the macrocyst and the proptosis reduced. A gentle pressure was maintained and with needle in place the syringe was detached. Another syringe containing bleomicin solution was attached and the solution was injected into thecyst. Amount of fluid injected   was either equivalent to the amount of fluid aspirated or according to pre injection dose calculated. Constant firm pressure was maintained and pad was applied to prevent upthrust. Eye was bandaged with moderate pressure.

Injection Bleomycin is available in avial . A fresh drug is prepared. It is diluted in 5 cc saline. Dose of drug was 0.5 mg /Kg body weight, not exceeding 10 units at  a time.

Observation:

Patients were followed up on the firstpost-operative day to examine the  status of proptosis, chemosis,, visual acuity and fundus to see the condition of optic disc . Next follow ups were done after 15, 30 45 and 60 days. Late follow up was at the end of one year. On follow up after 6 months, 4 patients had total regression clinically and on B scan .  Seven patients had partial regression and injection was repeated. In 2 patients as mass was anteriorly situated, surgical excision with injection of dye in posterior lesions was done with total regression.In  2 patients there were residual asymptomatic microcysts in posterior part and so patients were kept under observation. No significant side effects were observed.

Disiscussion:

 Lymphangiomas are rare vascular hemartoma of lymphatic channels.

They are hemodynamically isolated from the vascular system and are most commonly found in head and neck region.They consist of enlarged, non–encapsulated channels lined with a single layer of endotheliumThe lesion is a hemartoma- abnormal growth of endothelial lined channels interspersed with normal tissue

Histopathologic studyoflymphangioma shows infiltrative endothelium like channels, with a sparse cellular network and lymphocytes.Lymphatic follicles are also seen in the walls of the tumor.Red blood cells not are present unless secondary hemorrhage has occurred.Orbital imagingis essential to help make correct diagnosis and alsoto determine the extent of the lesion .Superficial lesions can be identified clinically but deep lesions can be diagnosed only with the use of radiology.USGis the first line of investigation and should be performed in all the patients.In capillary hemangiomas – USG shows high amplitude, closely packed echoesfrom vessel walls adjacent to blood filled spaces.Lymphangiomashave a similar USG pattern, however, with very wide separations of echoes due to larger fluid lakes. CTScanplays a very important role in diagnosisas well as for depiction of extent of the disease due to its multiplaner reformation capabilityand high spatial resolution.CT findings correlate well with surgical and histological findings.MRI on T1 signal shows blood as hyperintense but rest of the lesion will behypointense.On T2 signal lesiongives hyperintense signals. In Flow Void Phenomenon tumor vessels can be delineated without the use of contrast agents

Treatment optionsfor lymphangiomacan be broadly categorized  into:

Observation

Surgical excision

Non-surgical interventions

Surgery can be carried out for well localized small lesions or as a part of debulking.Non surgical therapy is in the form  ofsclersoing agents like ethyl alcohol, Na             tetradecylsulphate, ethanolamine oleate,  OK-432, Doxycycline and Bleomycin.Cryotherapy,radiotherapy or CO2 laser are useful in selected cases

Injection of bleomicinintralesionally is a new modality which is found to be useful in lymphangioma.Its mechanism of action is:

1. Cytotoxicity mediated by DNA cleavage at the level of linker DNA between nucleosomes
2. apoptosis is induced in rapidly growing immature cells including those of vascular malformations
3. Specific Sclerosing effecton vascular endothelium cells

Bleomycin  is a cytotoxic antitumor antibiotic. It can be administered intralesionally by transcutaneous injections and effective as a modulator of vascular anomalies. It provides “Non-surgical” and “Scarless” treatment. It is predictable and significant response rates are observed in vascular malformations including microcystic lymphatic malformations.

15 (15 mg) units of bleomycin powder is available in a vial. The solution is

reconstituted with 15 ml of 0.9% normal saline yielding a 1unit/ml concentration

A 24 Gauge needle attached with a 5cc syringe is used to administer the dose

Dose of bleomycin in one sessionis 0.5 – 1 unit /Kg notexceeding  10 mg at a time.

Its side effects are minimal with a big safety margin. A rare complication is pulmonary fibrosis which is dose dependent .Erythema, edema, pain at the site of the injection is some of the minor complication which can be easily treated.

Local skin necrosis and eschar formation at the site of injection are also rare.

Limitation of study:

1. Shorter follow up.
2. No controlled study with other drugs. Small number of patients. Not all cases diagnosed on histopathology.

Conclusion :Intralesionalbleomicin is one of the  effective noninvasive methods for the treatment of orbital lymphangiomas. It is safe without major complications.

 References:

1. AnnieStuart,ContributingWriterNovel Approaches to Orbital Lymphangioma ,Eye Net Magazine Interviewing Kenneth V. Cahill, MD, Jill A. Foster, MD, and Mary O’Hara, MD,2014.
2. Caroline Godding et al; IntralesionalBleomycin: A Potential Treatment for Refractory Orbital Lymphangiomas; OphthalPlastReconstrSurg, Vol. 30, No. 3, 2014
3. Jason L Acevedo; Non-surgical therapies for lymphangiomas: a systemic review;Otolaryngology–Head and Neck Surgery (2008) 138, 418-424
4.  4.IntralesionalBleomycin in Lymphangioma: An Effective and  Safe  non Operative Modality of  Treatment; V Kumar, P Kumar, A Pandey, D K Gupta, R C Shukla, S P Sharma, and

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