Open Journal of Stomatology, 2013, 3, 359-364 OJST
http://dx.doi.org/10.4236/ojst.2013.37061 Published Online October 2013 (http://www.scirp.org/journal/ojst/)
Intralesional pingyangmycin injection sclerotherapy for
oral ranulas*
Zhifang Chen1#, Jiawei Zheng2#, Shanyong Zhang2#
1Department of Oral and Maxillofacial Surgery, Hefei Stomatological Hospital, Clinical School of Anhui Medical University, Hefei,
China
2Department of Oral and Maxillofacial Surgery, Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University
School of Medicine, Shanghai, China
Received 12 March 2013; revised 12 April 2013; accepted 15 May 2013
Copyright © 2013 Zhifang Chen et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Objective: To investigate the efficiency of pingyang-
mycin (PYM) intralesional injection for the treatment
of ranulas in clinical practice. Methods: PYM con-
centrations were 2.0 mg/ml (8 mg PYM powder + 1
ml normal saline + 2 ml 2% lidocaine + 1 ml dexa-
methasone). The mixed PYM solution was intrale-
sional injected into ranulas after drawing out isomet-
ric cyst fluid in 3 patients. Results: The ranulas of 3
patients showed total disappearance after the sclero-
therapy, and no recurrence was found after 6 months
to 3 years’ follow-up. Compared to surgical therapy,
the PYM sclerotherapy was advocated by clinicians
for its advantages of less injury, no scar, less suffering,
etc. Conclusions: PYM is an effective sclerosing agent
for ranulas. Intracystic injection of PYM may be an
optimal method for the treatment of ranulas.
Keywords: Ranula; Pingyangmycin; Sclerotherapy
1. INTRODUCTION
Ranulas are mucoceles that develop as a consequence of
mucous extravasation, which typically present in the
floor of mouth from the sublingual gland. Plunging
ranulas are mucous extravasation pseudocyst herniating
through the mylohyoid muscle. The treatments of ranulas
mainly include surgical excision of the ranulas and no-
surgical sclerotherapy. Surgical management of ranulas
is still the first-choice therapy. However, due to the sur-
gical complications, the latter has been advocated by
clinicians for its advantages of less injury, no scar, less
suffering, etc.
Pingyangmycin (PYM), the single component of bleo-
mycin A5, is an anticancer agent that is refined from
Streptomyces pingyangensis and shows a strong damage
function to vascular endothelial cells. PYM has been
used as a conventio nal sclerosing agent for hemang ioma,
vascular malformations and lymphatic malformations [1].
PYM also can be used to treat cysts as a sclerosing agent
[2]. Recently, it has been reported that PYM is also a
relatively effective sclerosing agent for ranulas [3]. Ac-
cording to a series of data obtained about the safety and
efficacy of direct puncture injection with PYM in treat-
ing superficial cysts, we have used this method to treat
ranula since the early days of October 2010. In our study,
we attempt to describe our experience and to ev aluate th e
efficacy of intralesional injection with PYM for the
treatment of ranulas.
2. MATERIALS AND METHODS
2.1. Patients and Evaluation
3 clinical cases related to 14 - 22 years old female pa-
tients (mean 18.3 years old) were included in our study.
All patients’ chief complaints were the swelling in the
floor of mouth, and suffered from 3 - 35 months. No
correlative treatment was performed before accepting
PYM sclerotherapy (Figure 1). They underwent sclero-
therapy with the direct intralesional injection of PYM
between 20th October 2010 and 5th March 2013. The
protocol was approved and written informed consent was
obtained from them before the procedures. All patients
were treated on an outpatient basis.
Initial evaluation of the patients was composed of
physical examination, recordings of case history, photo-
graph findings. All patients, treated with local submu-
cous intralesional injection of PYM, didn’t undergo acute *Funding: Hefei City Science and Technology Bureau (No. 2010-070)
#Corresponding author.

Z. F. Chen et al. / Open Journal of Stomatology 3 (2013) 359-364 360
Figure 1. The patient had suffered from a ranula for 35
months, and taken no correlative treatment before ac-
cepting treatme nt.
pain and aggrav ated swelling any more.
2.2. Procedure
For the safety sake, the patient received relevant exami-
nations before accepting sclerotherapy, including blood
routine, hepatic and renal function, and chest radiography.
No contraindicating was found in the ex amination results.
The PYM solution in these cases was prepared before the
procedure. The mixed liquor with 2.0 mg/ml concen-
trations was configured as follows: 8 mg of PYM powder
(Laibotong Pharmaceutical Co. LTD, Harbin, China) was
dissolved in the mixed liquor which was composed of
1ml normal saline, 2 ml 2% lidocaine and 1ml dexa-
methasone [2]. The dosage of PYM varied from 0.05 to
0.2 mg/kg of body weight according previous literatures
experience [1].
Half an hour before the procedure, local anesthetic
was performed after sterilization of the oral region. A
1.5-inch (3.8-cm) 25-gauge fine-needle was used for the
puncture. 1ml 2% lidocaine was directly injected into the
critical normal site of the lesion. The normal location for
submucous was determined by the needle route.
After the point of the needle found intralesionally,
Partial cyst fluid was drawn out before sclerosing agent
had been injected (Figure 2, 3). The liquid volume aspi-
rated was about half of the cyst. Otherwise, it is difficulty
to puncture again. The sclerosing agent was injected
slowly to ensure that PYM was confined solely to the
lesions. Finally the injection was stopped when the lesion
was filled sufficiently (Figure 4, 5). The volume of scle-
rosing agent injected was estimated by the initial volume
of cyst fluid drew out. Care was taken not to go too far
medially and to avoid puncturing out of the cystic wall.
The puncture site was gently compressed for 5 - 10 min-
utes with a bandage. Patients were observed during the
procedure the time lasted least 4 hours for the detection
Figure 2. After the point of the needle found intra-
lesionally, Partial cyst fluid was drawn out before scle-
rosing agent had been injected.
Figure 3. The cyst fluid drawn out show saffron yellow,
glutinous liquid after 4 years.
of early complication after the procedure (Figure 6).
Systemic corticosteroids (dexamethasone, 10 mg/d for 3
days) were administered to manage postoperative oral
swelling. Nonstero idal antiinfla mmatory agents were used
for the pain relief when necessary.
2.3. Definitions and Follow-Up
The effectiveness of sclerotherapy was assessed on the
basis of the follow-up clinical findings and the photo-
graph findings of follow-up (Figure 7). The treatment of
the patient, who has not presented oral regional recur-
rence after the procedure followed-up more than 6
months, is considered to be effective.
3. RESULTS
3.1. Efficacy Outcomes
Technically, the intralesional PYM injection of sclero-
therapy was successful after more than 6 months fol-
lowed-up. The volume of PYM solution injected was 2.0
- 3.0 ml (mean, dose of PYM 4.9 mg), PYM was well

Z. F. Chen et al. / Open Journal of Stomatology 3 (2013) 359-364 361
Figure 4. Pingyangmycin was well impregnated in the
lesions, The volume of PYM injected was 3.0 ml (total
dose of PYM 6.0 mg)
Figure 5. To prevent the cyst liquid mixed residual
Pingyangmyein outflow from ruptured cyst, puncture
local was pressured for 10 minutes after Pingyang-
myein injection
impregnated in the lesions (Figures 4 and 5). Outflow of
cyst liquid with residual PYM from ruptured cyst was
spitted out. The patient expressed some clinical symptoms
such as: local light swelling within 1 week after the pro-
cedure, light pain after the cyst rupturing and pain dis-
appearance within 4 - 8 days (mean, 5.3 days). At the
same time, the articulation and swallowing function in-
disposed because of the swelling cyst displaced and in-
terfered the tongue. The procedure was beneficial for the
patient with diffuse lesions (Figure 7). The results were
reported in the Table 1.
3.2. Safety Outcomes
Local swelling and pain in the floor of mouth disappeared
after the administration of anti-inflammatory agents and
oral care. Others complications, such as acute oral in-
flammation, infection, hemorrhage, mucous necrosis,
oral scar, symptomatic embolism of sclerosing agent into
submaxillary gland duct, blood routine, hepatic and renal
Figure 6. Patients have been observed during the
procedure and been for at least 4 hours after the pro-
cedure for detection of early complications. Local swell-
ing and pain in the floor of mouth were light. Others
complications, such as acute oral inflammation, hemor-
rhage, and symptomatic embolism of sclerosing agent
into submaxillary gland duct were not observed.
Figure 7. Local bump was disappeared after Pingyang-
myein injection 2 weeks.
function, and pulmonary fibrosis, and so on, were not
observed during the follow-up periods.
4. DISCUSSION
Ranulas is a kind of pseudocyst that has been developing
as a result of mucous extravasation from the sublingual
gland which can be originated from obstruction of ex-
cretory ducts or extravasation and subsequent accumula-
tion of saliva caus ed by trauma [4]. It is classified into 3
clinical types according to the sites of primary swelling:
oral ranula, plunging ranula, and mixed ranula. Oral
ranula often presents as fluctuation, soft mass with light
blue colour which locates between the mucosa and mus-
cles in the floor of mouth and may displace the tongue
and interfere with oral fun ction when the cyst extends.
A variety of therapeutic modalities hav e been reported
to manage ranulas in the past literatures, mainly includ-
ing surgical resection of the lesion and/or sublingual

Z. F. Chen et al. / Open Journal of Stomatology 3 (2013) 359-364 362
Table 1. The results of PYM sclerotherapy.
Patient No. Age (y)/Sex Location Aspiration (cc)Injection (cc)Duration of Follow- up ( mo) Result
1 22/F Left sublingual 3.0 3.0 35 total disappearance
2 19/F Right sublingual 2.4 2.4 13 total disappearance
3 14/F Left sublingual 2.0 2.0 6 total disappearance
gland, marsupialization and sclerotherapy using sodium
morrhuate [5-7], OK-432 [8,9], ethanol [10], trichlo-
roacetic acid [11], etc. Surgical resection of the lesion
and/or sublingual gland is the mainstay treatment of
ranulas. However, the effect is still controversial, due to
the various kinds of complications such as recurrence,
tongue hypesthesia, bleeding/hematoma, postoperative
infection, Wharton’s duct injury, etc. In addition, surgi-
cal therapy might be difficult for infant an d child patien ts
with ranulas under local anesthesia. Marsupialization is
not approved of adoption because of its high recurrence
rate. To avoid the complications associated with the sur-
gical procedures, nonsurgical sclerotherapy, reported to
have the advantages of minimal scaring, little morbidity,
and few complications, has been better to treat oral and
plunging ranulas, compared with surgical procedures.
According to the literatures, there are several kinds of
sclerosing agents that are used clinically. For example,
OK-432, a lyophilized mixture of low-virulence group A
Streptococcus pyogens with penicillin G potassium, has
been applied to the treatment of patients with lymphatic
malformations due to its cytotoxic action against endo-
thelial cells and the fibrotic changes related to cytokine
action in the lymphatic malformations [12]. Ogita et al.
first reported intracystic injection of OK-432 for cystic
hygroma in 1987 [12]. Henceforth, the effectivences and
safety of intralesional injection of OK-432 for lymphan-
gioma has been reported repeatedly [13,14]. Recently, it
was reported that OK-432 could also be used in ranulas
by increasing absorption and decreasing saliva produc-
tion, resulting in the collapse and adhesion of the pseu-
docyst [11-15]. However, patients often suffered from a
lot of troubles because of its high incidence of recurrence
and repeated intralesional injection. Rhoa et al. reported
OK-432 sclerotherapy of plunging ranula in 21 patients,
only 7 patients (33.3%) showed total shrinke and resolu-
tion, and the overall recurrence rate after each injection
was 47% (16 of 34 injections in 21 patients) [8].
Pingyangmycin (PYM) has been successfully used in
intralesional injection treatment of cystic hydromas and
haemangiomas, based specifically on a high sclerosing
effect on vascular endothelium [2]. It is a kind of bleo-
mycin A5 isolated from many components of bleomycin
made in China which can affect G2 and S phases of fast
dividing cells and causes breakage of single-stranded
DNA via preventing DNA repair by inhibiting DNA li-
gase. Intralesional injection of PYM brings the drug into
direct contact with the endoth elial linin g and destroys th e
endothelial cells, resulting in sclerosteno sis of the lumen,
and has been proved to be an effective, inexpensive, and
safe method for venous malformations of oral and max-
illofacial region [16,17]. Yang et al. [3] hypothesize that
PYM may cause damage of the cystic wall of the ranulas,
resulting in local fibrosis which subsequently eliminate
the cyst of ranulas and yield excellent treatment effects.
The cystic wall of oral ranula is similar to the endothe-
lial lining in that it is also very th in. The effectiveness of
PYM for treating the cystic hydromas and haemangio-
mas might also be effective for treating ranulas. Zhao et
al. [18] attempted PYM scleroyherapy in 785 cases of
sublingual cyst, 756 patients were cured completely, oth-
ers had significant improvement, and concluded that it is
a safe and effective therapy for sublingual cyst, and can
be used as a treatment of choice in some selected cases.
The similarity conclusion was obtained by other Chin ese
resarchers. PYM expressed more significant effective
compared with OK-432. Similarly, in our study, the cyst
showed total disappearance after PYM sclerotherapy
about 2 weeks (Figure 7) in 3 patients with ranulas. The
reason for the different cure time in our study may be
related to a different concentration of PYM in cyst, as the
different volume injected of PYM solution and the dif-
ferent residual cystic fluid.
Zhou et al. [19] believe, to achieve the desired effect,
that concentration is more important than dose per treat-
ment. However, most authors didn’t report the concen-
tration they used and the dose varied greatly [17,18]. The
most serious potential complication of using PYM is
pulmonary fibrosis in cancer therapy. The risk of this
toxicity is felt mini mal when, as suggested by Sung et al.
[20] that the dose per treatment be kept under 1 mg/kg
per session and no more frequently than an interval of a
week, with the total dose limited to 5 mg/kg. We believe
that the use of minimum per kg dose as described in the
literature is not mandatory for the sclerosing effect of
PYM to occur, and that the maximum dose and concen-
tration are important for efficiency and safety.
Higher PYM concentrations 2.0 mg/ml (8 mg PYM
powder + 1ml normal saline + 2 ml 2% lidocaine + 1 ml
dexamethasone) was adopted in our study. Although
most of ranulas described as “mucous extravasation cysts
[21]” without epithelial lining, should have a higher rate
of response to intralesional PYM injectio n in theory, Par-
tial residuary and secretory cyst fluid should dilute the

Z. F. Chen et al. / Open Journal of Stomatology 3 (2013) 359-364 363
concentrations of PYM. We achieved the desired clinic
effect in fact. The addition and peroral of dexamethasone
is to prevent fever, pain and swelling post injection. We
believe that this modality is more rational and further
clinical trials are required for validation.
The advantage of PYM intralesional injection for oral
ranulas less trauma, low recurrence rate, and it is simple
and practicable. While surgery of ranula is not just only
selectable treatment which is a more complicated proce-
dure with the sequela of leaving some residual lesion and
the chance of recurrence. Other complications of surgery
include temporary or permanent paraesthesia in the dis-
tribution of the lingual nerve, transient or permanent
marginal mandibular nerve palsy, wound infection, and
stitch granuloma. Wh at’s more, PYM is a potential better
sclerosing agent than others reported, such as OK-432,
Iodine tinctune, Trichloroacetic acid (TDA), sodium
morrhuate, etc. The mechanism of PYM sclerotherapy is
that PYM can affect cell division directly via preventing
DNA, which leads to apoptosis. We speculated that the
cystic wall cell might be necrotic and ruptured after the
injection of PYM solution. All 3 patients were cured af-
ter only one injection and showed no recurrence fol-
lowed-up for 6 - 35 months. Finally, the advantage of
PYM sclerotherapy is that the complications are mini-
mal, as seen in the Zhao’s paper [18]. In our study, minor
discomforts, such as light swelling at the injection site,
light pain in rupture site, were seen within the first week
after the injection and diappeared after 2 weeks. There
were no more complications found in our study probably
because the number of the collected patients was insuffi-
cient.
6. CONCLUSION
Our results suggest that PYM scleroyherap y of ranulas is
a safe and significantly effective therapy, which may be
used as a primary or first-choice treatment of ranulas.
Further studies may be desired to focus on the ranula
animal models to investigate the effects and side effects
of this method as well as its exact mechanisms. Our
prospect is to find a safe and convenient concentration
that is less suffering to patients with ranulas in the fu-
ture.
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