Purpose: Bleomycin is an antibiotic medication that inhibits the synthesis of DNA, RNA, and proteins and is now used in a variety of medical conditions including vascular anomalies. The aim of this study was to evaluate the clinical efficacy of transmucosal intralesional injection of bleomycin in the management of tongue lymphatic malformations. Method: A single institutional case series was presented on patients with recalcitrant lymphatic malformations of the tongue who were treated with bleomycin. Age at the time of injection, gender, number of treatments, amount of bleomycin injected per session, post-injection complications, pre- and post-injection symptoms, and anatomic extent of the lymphatic malformation were all recorded and analyzed. Results: Five patients received transmucosal bleomycin and were followed over a 10-month period. The patients included 4 females and 1 male, aged from 3.25 to 36 years (average 13.52 years). Four patients had one treatment while 1 required two treatments. A total of 1 to 6 units were injected per session. Overall reduction in size of the lymphatic malformation and improvement in all symptoms were observed in the patients by day 14. Average follow-up was 9 to 12 months. Conclusion: Intralesional injection of bleomycin is an effective treatment modality in patients with lymphatic malformations of the tongue.
Vascular malformations manifest as either high-flow lesions (arteriovenous malformations and fistulae) or low- flow lesions (venous, lymphatic, capillary, or mixed malformations) [
Currently in non-oral cavity LMs, direct puncture sclerotherapy is used both as an adjunct and as an alternative to surgery [
Bleomycin, an antibiotic with cytotoxic antitumor properties via the inhibition of DNA, RNA, and protein synthesis, has been used in a variety of medical conditions including in a role as a sclerosant. It is favored by some clinicians because of its clinical efficacy combined with a low incidence of significant postoperative edema [
A case series of 5 patients with lymphatic malformations of the oral tongue treated with transmucosal bleomycin sclerotherapy between June 2013 and March 2014 is presented. The target lesions were identified preoperatively with computed tomography (CT) and magnetic resonance imaging (MRI). The following inclusion criteria were met by all of the patients: presence of an extensive lymphatic malformation involving the majority (>75%) of the anterior tongue; prior treatment consisting of partial CO2 laser ablations; recalcitrant disease with chronic hemorrhagic vesicles, malodor, pain, and swelling; and pre- and post-operative photographs for assessment and comparison. The outcome measures were overall tongue size, number of vesicles, presence of leakage from the vesicles and interval time between treatments.
If and when these patients developed lymphangitis or acute inflammation involving the malformation, treatment consisted of high dose corticosteroids and antibiotics. We recorded the age at the time of the injection, gender, number of treatments, amount of bleomycin injected per session (0.5 mg/kg was the maximum dose per session), postinjection complications, pre-/post-injection symptoms and anatomic extent of the LM.
All procedures were performed in the operating room under general anesthesia. A Denhardt mouth gag was used to provide adequate exposure along with either a towel clamp on the distal tongue or a Weider retractor to hold the tongue to one side. A 1-cc syringe with a 25-gauge needle was used. The total amount of bleomycin available per session was 0.5 mg per kilogram with a maximum of 15 mg per session. The needle was advanced across the region of the malformation and filled the malformation with the sclerosant in a retrograde fashion while gradually withdrawing the needle.
The five patients were followed for a period of 9 to 12 months (mean of 10.8) and consisted of four females and one male with ages ranging from 3.25 to 36 years (average 13.52 years). Four of the patients required only one treatment while one required a total of two. A total of 1 to 6 units were injected per session, depending on the patient’s weight (
All of the patients developed early reactive swelling; however, no airway interventions were necessary. Due to this finding, the injections were limited to the anterior 1/2 - 2/3 of the tongue. In 2 patients, oral corticosteroids were prescribed after 3 - 4 days as the pain from the swelling was affecting their oral intake. At the two- week follow-up appointment, the swelling was noted to be completely resolved and the overall size of the
Patient (age in years, gender) | Location of LM | # of treatments | Bleomycin amount (units) |
---|---|---|---|
36F | Anterior tongue, floor of mouth | 1 | 6.0 |
3M | Anterior tongue, floor of mouth | 1 | 1.8 |
7M | Anterior tongue | 1 | 1.7 |
9F | Anterior tongue | 2 | 6.0 |
10F | Anterior tongue | 1 | 1.0 |
tongue was reduced. At the end of the follow-up, the patients reported an overall reduction in tongue size, decreased number of vesicles and increased length of interval time between treatments. The patients also reported an improvement in their quality of life given the effectiveness regarding improvement in speech and reduction/ elimination of hemorrhage, malodor, pain, and swelling.
The treatment for extensive lymphatic malformations of the tongue involves any combination of sclerotherapy, laser therapy, and surgery. Unfortunately, there is no conclusive evidence demonstrating which sclerosant is the best. So far in the literature and with our experience, Bleomycin is the ideal sclerosant for airway lesions because of its effectiveness along with its minimal postoperative swelling [
The other sclerotherapy agents such as STS, doxycycline, ethanol and OK-432 have shown varying degrees of effectiveness with significant risk factors. For example, ethanol, though inexpensive and very effective, is associated with nerve injury, skin necrosis and catastrophic systemic effects such as cardiopulmonary collapse. OK-432, an agent once described as being the most widely used sclerosant for LMs, reported a regression of disease in 96% of patients. Its side effects include swelling, erythema, pain and a low-grade fever for up to 5 days post-injection [
Bleomycin was first introduced as a sclerosant in 1977 by Yura et al. It is an antibiotic with cytotoxic antitumoral properties [
The more common side effect is hyperpigmentation, which is reported to occur in 8% - 38% of patients. This finding does not seem to be dose dependent as it has been reported to occur with doses as low as 5 mg. The mechanism of action is unknown; however, histologic studies have shown that bleomycin reduces the epidermal turnover resulting in a prolonged contact between melanocytes and keratinocytes [
Although our case series has only 5 patients, bleomycin has shown promising results in the oral tongue. Once the cohort of patients is increased and the results can be collected on an objective scale, a direct comparison can be made of the different (
extremely effective in treating laryngeal LMs and this new application in the tongue will likely be equally successful.
Intralesional injection of bleomycin is an effective modality of treatment for patients with lymphatic malformations of the tongue. Bleomycin is shown to be an effective sclerosant with a low risk profile. All of the patients in this series were extremely satisfied with the results and no complications or side effects of bleomycin were reported.
None.
Eric W. Cerrati,Teresa M. O,David Binetter,Yelena Bernstein,Milton Waner, (2015) Transmucosal Bleomycin for Tongue Lymphatic Malformations. International Journal of Otolaryngology and Head & Neck Surgery,04,81-85. doi: 10.4236/ijohns.2015.42015