SMGr up Research Article

SM Journal of Intralesional Bleomycin Injection in

Pediatric Surgery Pediatric Lymphangioma, Is it the Magic
Solution?
Mohamed Fathy* and Alaa A Elsayed
Pediatric surgery unit, Minia University, Egypt

Article Information Abstract

Received date: Sep 20, 2018 Background: Intralesional injection of sclerosing agents has gained popularity in the last years as a first line
Accepted date: Oct 01, 2018 of treatment of lymphangioma to avoid serious surgical complications.

Published date: Oct 04, 2018 Objective: In this study we have evaluated the efficacy and safety of intralesional bleomycin injection in
different cases of lymphangioma.
*Corresponding author
Patients and Methods: This prospective study was carried out in pediatric surgery unit, Minia university
Mohamed Fathy, Pediatric surgery unit, hospital from June 2013 to February 2018 on 34 patients. Most of our patients presented by a swelling.
Diagnosis was done by clinical examination of the swelling. The site of the swelling was detected. Superficial
Minia University, Egypt, ultrasonography was done for all patients. CT and MRI were asked for some cases. Pre and after treatment
Tel: 01006350884; photograph after written consent from parents were taken. The dose of bleomycin is estimated as 0.5 mg per kg
Email: [email protected] body weight of bleomycin aqueous solution (1.5 mg l ml water). The dose not exceeded 10 mg at a time. The
numbers of injection for each case were recorded. Also complications related to the procedure were recorded.
Distributed under Creative Commons Results: In our study the neck was the most common site of lymphangioma 22 cases (64.7%) followed by
CC-BY 4.0 face and axilla 4 cases (11.8%) in each site.

Keywords Lymphangioma; Bleomycin; 16 cases (47.1%) needed 2 trials of intralesional bleomycin injections, 6 cases (17.6%) needed only one
trial,4 cases (11.8%) needed 3 trials, 4 cases (11.8%) needed 4 trials, 2 cases (5.9%) needed 5 trials and another
Sclerosing Agents 2 cases (5.9%) needed 6 trials of intralesional bleomycin injections. Excellent response of lymphangioma to
intralesional bleomycin injection by complete regression occurred in 12 cases (35.3%), good response by more
than 50% regression in the size of the swelling occurred in 18 cases (52.9%),while poor response by less than
50% regression in the size of the swelling occurred only in 4 cases (11.8%).

Out of 34 cases of lymphangioma 16 cases (47.1%) had no serious complications in the form of fever,
intralesional bleeding, local infection and skin discoloration. We hadn’t reported any cases of recurrence.

Conclusion: Intralesional bleomycin injection is an effective and safe modality of treatment of lymphangioma
with non considerable complications.

Introduction
Lymphangioma is a congenital disorder that arises from malformed lymphatic system [1]. They
are considered to be aberrations of lymphatic channels that consist of cysts filled with chyle and
lined with endothelium [2]. They may occur in all body regions but are most commonly seen in
neck (75%), axilla (20%), and inguinal areas (2%) [3]. About, 60% of lymphangioma presents since
birth, 80% appears within the first two years of life or may present later on any time [1]. It has a
variable incidence that ranges between 1 in 1000 and 16000 live births [4]. According to the size
of the lymphatic cavities incorporated, Lymphangiomas can be classified as microcystic (capillary
lymphangiomas), macrocystic (cavernous lymphangiomas) and cystic hygromas [5]. Cystic hygroma
usually forms in loose areolar tissue, whereas capillary and cavernous types of lymphangiomas tend
to present in muscle [4]. The most prominent manifestation of all lymphangiomas is the presence of
a mass. This may be small and unnoticed at birth and present later with an upper respiratory tract
disorder or incidental trauma at the site of the mass [6]. Surgery is the main modality of treatment
for head and neck lymphangioma. However, it carries complications that may reach 12-33% and
recurrence 15-53% [7].
Surgical resection for complete excision in many cases is impossible, this is due to the nature
of the lesion, which has a tendency to infiltrate tissue planes and encircle neurovascular structures.
Tumor recurrences and nerve injuries are most common complications for surgery [8].
To avoid the morbidity associated with surgical resection, intralesional injection of sclerosing
agents like boiling water, 50% dextrose, hypertonic saline, or absolute alcohol has been used. With
the use of agents like Bleomycin, acetic acid, OK-432, Doxycycline, many centers are using them as
first line of therapy with good results [9].

OPEN ACCESS How to cite this article Fathy M and Elsayed AA. Intralesional Bleomycin Injection in
Pediatric Lymphangioma, Is it the Magic Solution? SM J Pediatr Surg. 2018; 4(4): 1074.
ISSN: 2573-3419
SMGr up Copyright  Fathy M

Figure 1: Before bleomycin injection. Figure 3: Complete disappearance of the mass after 2 trials of injection.

In this study we have evaluated the efficacy and safety of Most of our patients presented by a swelling, Diagnosis was done
intralesional bleomycin injection in different cases of lymphangioma. by clinical examination of the swelling that was cystic in nature,
partially compressible and translucent. The site of the swelling was
Patients and Methods detected. Superficial ultrasonography was done for all patients. CT
This prospective study was carried out in pediatric surgery unit, and MRI were asked for some cases. We classified lymphangioma
Minia university hospital from June 2013 to February 2018 on 34 into microcystic (less than 1 cm), macrocystic (more than 1 cm) and
patients. mixed (containing both cysts) as suggested by Ortega et al [10]. Pre
and after treatment photograph after written consent from parents
Department ethical Committee approval was taken before the
were taken (Figures 1-7).
beginning of the study. The parents were informed about the study
and any possible complications and a written consent was taken from Procedure
them.
The dose of bleomycin is estimated as 0.5 mg per kg body weight
Exclusion criteria included age more than 18 years, mediastinal of bleomycin aqueous solution (1.5 mg l ml water) the dose not
and retroperitoneal lymphangioma due to difficult access, recurrent exceeded 10 mg at a time.
cases and cases with history of previous injection of any sclerosing
agent.

Figure 2: After one trial of injection. Figure 4: Before bleomycin injection.

Citation: Fathy M and Elsayed AA. Intralesional Bleomycin Injection in Pediatric

Lymphangioma, Is it the Magic Solution? SM J Pediatr Surg. 2018; 4(4): 1074.
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SMGr up Copyright  Fathy M

Figure 5: Complete disappearance of the mass after one trial of injection.

In operative room the site of lymphangioma was sterilized. The

fluid of lymphangioma was aspirated by 10 ml disposable syringe
then with the same needle while still in the cyst; the bleomycin that
was prepared according to weight was injected. In lymphangioma
with multiple cysts the calculated dose was divided by the number of Figure 7: MRI of neck lymphangioma.
cysts then after aspiration of each cyst the divided dose was injected.
Compression was applied for 5 minutes after completion of injection
classified by clinical examination and ultrasonography into Excellent
to prevent hematoma formation. Paracetamol was prescribed for
with complete regression, Good with regression >50% and Poor with
fever if occurred. Re-evaluation of the patients was done every
regression <50% [3].
3 weeks and re aspiration and injection was done if the size of the
cyst was 1 cm or more. Intralesional injection of bleomycin was The collected data were coded, tabulated, and statistically
stopped when the cyst disappeared clinically or by ultrasonography, analyzed using SPSS program (Statistical Package for Social Sciences)
become stationary in size even after 3 or 4 injections or the cyst software version 25. Descriptive statistics were done for parametric
failed to respond to injection. The numbers of injection for each quantitative data by mean, standard deviation and minimum&
case were recorded. Also complications related to the procedure maximum of the range, while they were done for categorical data
were recorded. Patients were followed for 6 months after the last by number and percentage. Analyses were done for qualitative
injection. The response to intralesional injection of bleomycin was data using Fisher exact test .The level of significance was taken at
(P value < 0.05).
Results
This prospective study was carried out in pediatric surgery unit,
Minia university hospital from June 2013 to February 2018 on 34
patients. The age of our patients ranged from 3 to 48 months. Among
them we had 20 (58.8%) males and 14 (42.2%) females (Table 1). In
our study the neck was the most common site of lymphangioma 22
cases (64.7%) followed by face and axilla 4 cases (11.8%) in each site.
While lymphangioma presented in anterior abdominal wall and back
in 2 cases (5.8%) for each site of them. Macrocystic lymphangioma
found in 14 cases (41.2%), mixed type in 16 cases (47.1%) while
microcystic type of lymphangioma only found in 4 cases (11.8%).16
cases (47.1%) needed 2 trials of intralesional bleomycin injections, 6
cases (17.6%) needed only one trial,4 cases (11.8%) needed 3 trials,
4 cases (11.8%) needed 4 trials, 2 cases (5.9%) needed 5 trials and
another 2 cases (5.9%) needed 6 trials of intralesional bleomycin
injections (Table 2). Excellent response of lymphangioma to
intralesional bleomycin injection by complete regression occurred in
12 cases (35.3%), good response by more than 50% regression in the
size of the swelling occurred in 18 cases (52.9%), while poor response
by less than 50% regression in the size of the swelling occurred only in
4 cases (11.8%) (Table 3). About the type of lymphangioma we had 14
Figure 6: MRI of neck lymphangioma.
cases of macrocystic type 12 (85.7%) of them had excellent response

Citation: Fathy M and Elsayed AA. Intralesional Bleomycin Injection in Pediatric

Lymphangioma, Is it the Magic Solution? SM J Pediatr Surg. 2018; 4(4): 1074.
Page 3/5
SMGr up Copyright  Fathy M

Table 1: Age and sex distribution. to intra lesional bleomycin injections, while 2 cases (14.3%) had good
Descriptive statistics (n=34) response. 4 cases had microcystic type of lymphangioma and all of
them (100%) had poor response to intralesional bleomycin injection.
Range (3-48)
Age 16 cases had mixed type of lymphangioma and all of them (100%) had
Mean ± SD 14.7±11.8 good response to bleomycin injection with significant p-value (Table
Male 20(58.8%) 4).
Sex
Female 14(42.2%) Out of 34 cases of lymphangioma 16 cases (47.1%) had no serious
complications in the form of fever, intralesional bleeding, local
Table 2: Site, size and type of lymhangioma and total no of injection. infection and skin discoloration. Fever occurred in 10 cases (29.4%)
Descriptive statistics and responded to oral paracetamol, local infection occurred in 6 cases
(n=34) (17.6%) and managed by systemic and local antibiotics, intralesional
Neck
22(64.7%) bleeding occurred in 4 cases (11.8%), while skin discoloration
Face
Axilla
4(11.8%) occurred also in 4 cases (11.8%) (Table 5). we hadn’t reported any
Site of the lesion
Anterior abdominal
4(11.8%) cases of recurrence.
2(5.9%)
Discussion
wall
2(5.9%)
Back
Micro-cystic 4(11.8%)
Type of lymphangioma Mixed 16(47.1%)
There are many hypotheses trying to explain Lymphangioma
Macro-cystic 14(41.2%) development. It may occur when the lymphtic system fails to connect
Size
Range (3-9) with or fails to separate from venous system. Abnormal budding
Mean ± SD 6.3±1.4 of lymphatic system from its cardinal vein may be the cause of
1 6(17.6%)
lymphangioma. Also lymphangioma may occur in response to acquired
2 16(47.1%)
Total number of 3 4(11.8%) factors like trauma, inflammations, infections, and obstructions [10].
injections 4 4(11.8%) Complete surgical excision remains the main option in dealing with
5 2(5.9%) lymphangioma by many surgeons. However, incomplete surgical
6 2(5.9%)
excision usually associated with high incidence of recurrence that
Table 3: Response to intralesional bleomycin injection. appears in a short time after operation, but it may appears later on
after years [11]. Complications of surgical excision include nerve
Descriptive statistics injury and injury of adjacent vital structures especially in neck site
(n=34) of lymphangioma. The nature of the lesion that has a tendency to
Poor 4(11.8%) infiltrate tissue planes and encircle neurovascular structures may
Response Good 18(52.9%) render complete surgical excision making it impossible. Intralesional
Excellent 12(35.3%) injection of sclerosing agents has gained popularity in the last years
as a first line of treatment of lymphangioma to avoid serious surgical
Table 4: Response of different types of lymphangioma to intralesional bleomycin complications. sclerosing agents include boiling water, ethanol,
injection.
dextrose 50% and recently bleomycin and O.K 432. Bleomycin is a
Type of lymphangioma cytotoxic glycoprotein antibiotic that is isolated from some strains of
Streptomyces verticillus, discovered by Umezawa as antitumor agent
P value
Micro-cystic
Mixed (n=16)
Macro-cystic in 1966 [12]. OK432 is a strain of Streptococcus pyogenes with low
(n=4) (n=14)
virulence that is cultured with penicillin-G. However it is expensive
Response and not widely available [13]. The major problem of bleomycin is
Poor 4(100%) 0(0%) 0(0%)
<0.001*
pulmonary toxicity. This risk is dose dependent that may be associated
Good 0(0%) 16(100%) 2(14.3%) with a total dose more than 400 IU. or a single dose more than 30 mg/
Excellent 0(0%) 0(0%) 12(85.7%)
m2 of body surface area [8]. And the mentioned dose should be given
Table 5: Complications of intralesional bleomycin injection. intra-venously that is not the route in our study. The dose we used
was 0.5 mg per kg. That is the same dose used in the study of kumar
Descriptive statistics (n=17) et al [3]. In the study done by Niramis R et al the dose of bleomycin
ranged from 0.3 to 0.6 mg/kg [14], while in some studies the dose
Complications
No 18(52.9%) was higher as that in the study of Baskin D et al that ranged from
Yes 16(47.1%)
1-3 mg/kg [15]. In our study the response of lymphangioma to local
Skin discoloration
No 30(88.2%) bleomycin injection was satisfactory (excellent and good response)
Yes 4(11.8%)
in 88.2% of cases as we have excellent response in 35.3% of cases and
Fever
No 24(70.6%) good response in 52.9% of cases. kumar V et al noted satisfactory
Yes 10(29.4%)
results in 95% of cases (Excellent in 20% and good in 74.2) [3]. In the
Local infection
No 28(82.4%) study done by Baskin et al good activity of bleomycin noted in 95%
Yes 6(17.6%)
of cases [15]. The sum of good and excellent response to intralesional
Intralesional bleeding
No 30(88.2%) bleomycin injection in head and neck lymphangioma in the study
Yes 4(11.8%)
of Deepak R et al reached 13 from 15 patients [13]. Pradyumna Pan

Citation: Fathy M and Elsayed AA. Intralesional Bleomycin Injection in Pediatric

Lymphangioma, Is it the Magic Solution? SM J Pediatr Surg. 2018; 4(4): 1074.
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SMGr up Copyright  Fathy M

in his study noted 86% satisfactory response [16]. Rozman et al in 3. Kumar V, Kumar P, Pandey A, Gupta DK, Shukla RC, Sharma S P, et
their study reported excellent response in 63% and good response in al. Intralesional Bleomycin in Lymphangioma: An Effective and Safe Non-
Operative Modality of Treatment. J Cutan Aesthet Surg. 2012; 5: 133-136.
21% patients [8]. In this study non serious complications occurred
in 16 patients (47.1%) and included intralesional bleeding in 4 cases 4. Filston HC. Hemangiomas, cystic hygromas, and teratomas of head and
(11.8%), fever in 10 cases (29.4%), local infection in 6 patients (17.6) neck. Semin Pediatr Surg. 1994; 3: 147-159.

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them developed fever, transient increase in size of cysts occurred in 6. Grasso DL, Pelizzo1 G, Zocconi E, Schleef J. Lymphangiomas of the head
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Pan noted side effects in 9 from 36 patients that included fever in 3 surgical management of cystic lymphangioma. Indian J Otolaryngol Head
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Citation: Fathy M and Elsayed AA. Intralesional Bleomycin Injection in Pediatric

Lymphangioma, Is it the Magic Solution? SM J Pediatr Surg. 2018; 4(4): 1074.
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