International Journal of Oral & Maxillofacial Pathology.

2012;3(1):28-33 ISSN 2231 – 2250

Available online at http://www.journalgateway.com or www.ijomp.org

Case Report

The Use of Cryosurgery in Treatment of the Gingival Leukoplakia: Report of a Case Series
Adriana Spinola Ribeiro, Mauro Henrique Nogueira Guimarães de Abreu, Tarcília Aparecida da Silva,
Ricardo Alves Mesquita

Abstract
Background: Oral leukoplakia is preferentially treated by conventional surgery, but other
treatments may also be considered. Conventional surgery cannot be used for high-risk surgical
patients, have high-time of work and for large or multiples lesions is necessary two or more
excisions with high-risk to prove scar. On the other hand, cryosurgery did not present these
disadvantages. Aims & Objectives: To report of a case series of gingival leukoplakia treated with
cryosurgery. Materials and Methods: Incisional biopsy was performed. The procedure was
performed with Cry-Ac® using the spray technique for two consecutive freeze cycles of 10
seconds, under local anesthesia. The performance of the cryosurgery was evaluated according
to: 1) postoperative pain, 2) edema, 3) bleeding, 4) secondary infection, 5) clinical healing, 6) loss
tissue, 7) scarring, and 8) recurrence of the lesion. Results: The mean age of patients was 57.6
years and there were more women (5 patients). The microscopic evaluation demonstrated
hyperkeratosis in 3 cases, hyperkeratosis with mild epithelial dysplasia in 2 cases and
hyperkeratosis with moderate epithelial dysplasia in 1 case. No bleeding, no loss of tissue, no
scarring, and no infection could be observed following the treatment. Also, pain was not noticed
by patients. Three patients reported discrete edema within 24 hours after treatment. All treated
gingival sites were clinically healing of leukoplakia and recurrence was not observed.
Conclusions: In this light, when leukoplakia involves the gingiva, cryosurgery should be
considered the treatment of choice. In addition, cryosurgery can potentially be used in the
treatment of other gingival conditions.

Keywords: Cryosurgery;Surgical Procedures;Operative Ablation Techniques;Gingiva;

Leukoplakia;Disease Management;Freeze;Hyperkeratosis.

Adriana Spinola Ribeiro, Mauro Henrique Nogueira Guimarães de Abreu, Tarcília Aparecida da Silva,
Ricardo Alves Mesquita. The Use of Cryosurgery in Treatment of the Gingival Leukoplakia: Report of a Case
Series. International Journal of Oral & Maxillofacial Pathology; 2012:3(1):28-33. ©International Journal of
Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All
Rights Reserved.

Received on: 05/12/2011 Accepted on: 05/03/2012

Introduction with high-risk to prove a loss of tissue and

2
Oral leukoplakia (OL) is a potentially scar. Cryosurgery is a therapeutic method
malignant disorder described as “a characterized by simple application,
predominant white lesion of the oral mucosa effectiveness, and with a low incidence of
12
which cannot be defined as any other known secondary infection and bleeding. The
1
lesion”. The concept of OL should technique of cryosurgery stresses rapid
acknowledge white lesions, excluding any cooling, slow thawing, and the repetition of
other lesions or known disorders which do the freezing process to maximize tissue
13
not present a potential malignant risk, such destruction. It can be used for high-risk
as candidiasis, lupus erythematosus, oral surgical patients, such as patients with a
hairy leukoplakia, frictional keratosis, pacemaker, the elderly, and those with a
2,3
nicotinic stomatitis, and leukoedema. The coagulopathies. Furthermore, it would be the
treatment of OL is usually performed by first choice in the cases of multiple and large
surgery. The surgical treatment may be lesions, areas of difficult surgical access,
2
done through conventional surgery , and locations where aesthetics is
5 12
electrocautery, laser ablation , or important. Cryosurgery is also considered
6-11
cryosurgery. However, recurrence has a simple and efficient therapeutic
2-11 8,10,11,14,15
been reported in a rate variable. management of OL. Since tissue is
not removed in cryosurgery, it thus
Conventional surgery cannot be used for represents a suitable treatment for areas,
high-risk surgical patients; there is a high- such as the gingiva, where aesthetics is an
time of the work and for large or multiple important factor. Gingival melanin
lesions is necessary two or more excisions pigmentation treated with cryosurgery has

©2012 International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights Reserved
29 Ribeiro AS. et al
demonstrated excellent results without
16-18
aesthetic defects. In the management of
gingival leukoplakia (GL), only the study of
7
Al-Drouby (1983) presented two of three
cases that disappeared completely with
cryosurgery. Increasing aesthetic demands
in dentistry have created a need to maintain
and restore the different parts of the
18
gingiva. Treatment of GL must be
appropriate in order to avoid unexpected
defects. So, in the current study it is
presented and discussed a series of six
cases of GL treated by cryosurgery.
Materials and Methods
The protocol of this study was approved by
the Ethics Committee of the Federal
University of Minas Gerais (Number 36/08).
Six patients with GL were included in the
study. The clinical diagnosis criteria for GL
4
were in accordance with Neville and Day
(2002). Age, gender, smoker status,
location, size, and microscopic evaluation of
GL were recorded. Incisional biopsy of the
GL was performed in all patients before the
treatment with cryosurgery. No patient
presented diseases that did not indicate the
treatment with cryosurgery.
Cryosurgery technique: Following local
anesthesia, the treatment was performed by
a direct application of liquid nitrogen with a
®
spray technique using a CryAc apparatus
(Brymill Cryogenics Systems, Ellington, CT,
USA). Each lesion was exposed directly to
two consecutive freeze-thaw cycles of 10
seconds each, beginning at the center of the
lesion and moving outward toward the
borders until the entire lesion was white.
After the ice ball produced during freezing
had completely thawed, the next freezing
was performed. Thawing occurred
spontaneously after 30-60 seconds.
GL larger than 10mm received two or more
sections of treatment. Additional cryosurgical
sections were performed one month later.
The performance of the cryosurgery was
evaluated according to: 1) postoperative
pain, 2) edema, 3) bleeding, 4) secondary
infection, 5) clinical healing, 6) tissue loss, 7)
scarring, and 8) recurrence of the lesion.
Patients were examined at 1, 2, and 4
weeks, and 3 and 6 months after of the
cryosurgery. Patients were subsequently
recalled every 6 months.
Postoperative measures and analysis:
The pain assessment was based on
19
Caraceni et al. (2002). The patients were
ISSN 2231 - 2250
asked, in terms that could be easily
understood, if the pain they felt was 1) no
pain; 2) mild pain; 3) moderate pain; 4)
severe pain; or 5) unbearable pain. The
patients were also asked whether or not an
edema and bleeding was present.
Secondary infection was investigated
objectively by clinical examination for the
presence or absence of local exudation and
by measure of the fever. These parameters
were evaluated one week after cryosurgical
technique had been applied.
Clinical healing was determined when the
leukoplakia could no longer be seen in the
primary location. Objective clinical
examination also verified whether or not a
tissue loss or scarring was present. These
parameters were evaluated every 6 months
after of the cryosurgery.
Post-cryosurgical care: All patients
underwent special oral hygiene care,
especially as regards to hot, hard, and
acidifying foods, during the post-cryosurgical
period. Patients were instructed not to ingest
any form of analgesic during the post-
cryosurgical period, except in case of the
unbearable pain.
Results
Clinical and microscopic findings of six
patients with GL treated with cryosurgery are
summarized in Table 1. The mean age of
patients was 57.6 years and 5 patients were
women. The clinical features of GL were
asymptomatic, homogenous white plaques
with a uniform, flat, thin surface containing
many fine cracks or fissures (Figures 1A,
1C, 1E, 1G, 1I, 1K). The microscopic
evaluation demonstrated hyperkeratosis in 3
cases, hyperkeratosis with mild epithelial
dysplasia in 2 cases and hyperkeratosis with
moderate epithelial dysplasia in 1 case. After
3-5 days of cryosurgery, a superficial
necrotic tissue could be observed in the
treated area. The necrotic tissue separated
spontaneously after 1-2 weeks, leaving a
fully epithelialized surface and healed tissue.
Total clinical healing of GL was observed in
all patients. Three patients reported discrete
edema within 24 hours after treatment. No
patient complained of pain after the
treatment. No bleeding, no loss of tissue, no
scarring, and no infection in the gingival
sites treated could be observed (Figures 1B,
1D, 1F, 1H, 1J, and 1L). At the 24-month
follow-up visit, no recurrence was noted in
any of the patients.
ISSN 2231 – 2250 Cryosurgery in Treatment of the Leukoplakia..... 30

Discussion
OL has an annual malignant transformation
20,21
rate of 0.1% to 17.0%. The degree of
dysplasia is regarded as the most important
indicator of potential progression. OL
presenting low to moderate malignant risk
may either be completely removed or not,
and the decision should consider factors
such as gender, location, size and, in the
case of smokers, the patient’s dedication to
2 10
quitting smoking. OL’s located on the floor
of the mouth, soft palate, and tongue are
considered lesions of high-risk for malignant
transformation, while, in other areas, such
as the gingiva, these are considered to
4
represent a low risk of malignancy. Prior
reports have described a predominance in
the buccal mucosa and the lower alveolar
22-24
mucosa as the main locations of OL.
However, other studies have defended that
25-28
the gingiva is the most frequent location.
The frequent involvement of the gingival
area has mostly been described in studies
carried out in the USA, with OL occurring in
22,24
23.7% to 41.8% of these cases.
Therefore, the GL is a frequent condition in
clinical practices and its appropriate
management is necessary. The present
study includes a series of six cases of GL
which were successfully treated with
cryosurgery. The choice of treatment of GL
with cryosurgery was justified due to 1) the
29
aesthetic factor; 2) the degree of dysplasia ;
29,30 29,30
3) no smoking ; and 4) gender.
OL is commonly treated by conventional
surgery, electrocautery, cryosurgery, or laser
2,4,5,7
ablasion. Conventional surgery is more
frequently used, but may cause scars and a
loss of tissue and there is a high time of
work in relation to the cryosurgery.
Moreover, recurrence has been reported in
23,30
10% to 35% of the cases. Results of
treatment with cryosurgery have been
varied. A 32% recurrence rate of OL cases
treated by cryosurgery has been reported
when considering follow-up periods of 3 to
46 months . Other investigators have
obtained recurrence rates of 0% in 3
15 8
months and 6 months and 3% in 12
6
months. However, in other studies, the
recurrence rates from treatment with
cryosurgery have proven to be variable
7,9,11,30
within a period of up to five years. No
recurrence of GL in the cases studied herein
could be observed within an 24-month
follow-up period.
Our results demonstrate that 100% of the
GL cases treated with cryosurgery
presented a total clinical healing. Healed
gingival tissue could be observed with a
normal clinical appearance without
leukoplakia. Loss of tissue, postoperative
pain, hemorrhage, infection, or scarring did
not occur in any of the cases. The present
study results are in accordance with the
majority of the studies reviewed concerning
the treatment of OL with cryosurgery in
6-11,30
locations other than the oral mucosa.
Furthermore, the uneventful healing in the
present study was corroborated by previous
results in which cryosurgery was used to
7,30
treat GL.

Patients Age Gender Smoking ygoashtapstsiH Size Location

(Figures) status (mm)
1 45 Female No Hyperkeratosis 18 Vestibular attached gingiva
(Fig 1A, 1B) with mild epithelial extending to vestibular oral
dysplasia mucosa close to tooth 12
2 69 Male No Hyperkeratosis 25 Vestibular attached gingiva
(Fig 1C, close to teeth 4 to the 7
1D)
3 45 Female Yes Hyperkeratosis 12 Ridge alveolar edentate of
(Fig 1E, 1F) tooth 30
4 73 Female No Hyperkeratosis 8 Lingual attached gingiva
(Fig 1G, close to teeth 22, 26 and 27
1H)
5 59 Female No Hyperkeratosis 15 Vestibular marginal gingiva
(Fig 1I, 1J) with mild epithelial extending to attached gingiva
dysplasia and oral mucosa between
teeth 3 and 5
6 55 Female No Hyperkeratosis 5 Vestibular gingiva papilla
(Fig 1K, 1L) with moderate between teeth 14 and 15
epithelial dysplasia

Table 1: Clinical and microscopic findings of six patients with gingival leukoplakia treated with
cryosurgery.
31 Ribeiro AS. et al ISSN 2231 - 2250

Figure 1: Clinical aspects of gingival Clinically normal gingiva after the treatment
leukoplakia (1A, 1C, 1E, 1G, 1I, 1K). with cryosurgery (1B, 1D, 1F, 1H, 1J, 1L).
ISSN 2231 – 2250
Cryosurgery, an effective method of tissue
destruction by freezing, has become a firmly
established surgical technique in both
medical and dental practices. Physical and
chemical changes induced by freezing lead
to cell destruction and tissue death. While
most vital tissues freeze at approximately
2°C, ultralow temperatures (below 20°C)
30
result in total cell death. A cryogenic agent,
whether applied directly or indirectly, will
cause a selective necrosis of the tissue,
whose extension depends on the type of
29
lesion and the area to be treated. Liquid
nitrogen is the cryogen of choice for oral
surgery, due to its easy access and
30
coldness (-196ºC). The effectiveness of
cryosurgical treatment is based on the
formation of extracellular and intracellular ice
crystals. A rapid build-up of toxic electrolyte
concentrations, an alteration in pH, protein
denaturation, and the disruption of cell
membranes subsequently occur. The
vascular status of the cryo-lesion is also
regarded as the factor responsible for the
completion of cell destruction in the frozen
30
area. The cryodose of 10 seconds, which
was found to be in accordance with previous
30
studies, was selected. This dose was high
enough to remove a superficial layer of
gingiva containing the diseased tissue with
minimal damage to the underlying
connective tissue.
Cryosurgery is useful for superficial,
irregular, and multiple lesions, as well as for
those of difficult surgical access.
30
Particularly in the treatment of large,
multifocal lesions or areas of difficult surgical
access, cryosurgery represents a sound
alternative to surgical excision, given that
the destruction of the pathologically changed
tissue is possible and subsequently allows
the mucosa to return to a normal clinical
appearance with no formation of scars. In
addition, when patients have a history of
medical problems, present a high-risk for
surgery, or are elderly, as observed in the
patients of this study, cryosurgery becomes
a treatment of choice.
30
The absolute
contraindications to cryosurgery include
systemic diseases, such as: cold urticaria,
cryoglobulinemia, cryofibrinogenemia,
coagulopathy, Raynaud’s disease, vascular
peripheral diseases, and uncontrolled
30
diabetes. The patients of the current study
did not present any of these conditions.
Conclusion
In conclusion, the results presented herein
suggest that cryosurgery should be
Cryosurgery in Treatment of the Leukoplakia..... 32
considered the treatment of choice when OL
involves gingiva and can potentially be used
in the treatment of other gingival conditions.
Also, this is a preliminary study and for
comparison of the treatment methods, future
studies of the randomized clinical trials are
necessary.
Author Affiliations
1. Adriana Spinola Ribeiro, Graduate Student,
Department of Oral Surgery and Pathology. 2.
Mauro Henrique Nogueira Guimarães de Abreu,
Professor, Department of Social and Preventive
Dentistry, 3. Tarcília Aparecida da Silva,
Professor, 4. Ricardo Alves Mesquita, Professor,
Department of Oral Surgery and Pathology,
School of Dentistry, Universidade Federal de
Minas Gerais, Belo Horizonte-MG, Brazil.
Acknowledgement
We would like to thank the staff members of the
Oral Surgery and Pathology department for their
support & cooperation.
References
1. van der Waal I, Axéll T. Oral leukoplakia:
A proposal for uniform reporting. Oral
Oncol 2002;38:521-6.
2. van der Waal I, Schepman KP, van der
Meij EH, Smeele LE. Oral leukoplakia: a
clinicopathological review. Oral Oncol
1997;33:91-101.
3. Warnakulasuriya S, Johnson WN, van
der Waal I. Nomenclature and
classification of potentially malignant
disorders of the oral mucosa. J Oral
Pathol Med 2007;36:575-80.
4. Neville BW, Day TA. Oral Cancer and
Precancerous lesions. CA Cancer J Clin
2002;52:195-215.
5. Ishii J, Fujita K, Komori T. Laser
treatment for oral leukoplakia. Oral
Oncol 2003;39:759-69.
6. Vercellino V, Magnani G, Goia F,
Gandolfo S. La nostra esperienza clínica
con la criochirurgia delle lesioni orali di
interesse odontostomatologico. Minerva
Stomatol 1980;29:253-8.
7. Al-Drouby HAL. Oral leukoplakia and
Cryotherapy. Br Dent J 1983;15:124-5.
8. Gongloff RK, Gage AA. Cryosurgical
treatment of oral lesions: report of
cases. JADA 1983;106:47-51.
9. Barrellier P, Louis MY, Babin E.
Utilization de la cryothérapie en
pathologie buccale. Rev Stomatol Chir
Maxillofac 1992;93:345-8.
10. Yeh CJ. Simple cryosurgical treatment
for oral lesions. Int J Oral Maxillofac
Surg 2000;29:212-6.
11. Yu CH, Chen HM, Chang CC, Hung HY,
Hsiao CK, Chiang CP. Cotton-swab
33 Ribeiro AS. et al
cryotherapy for oral leukoplakia. Head
Neck 2009;31:983–8.
12. Ameerally PJ, Colver GB. Cutaneous
cryotherapy in maxillofacial surgery. J
Oral Maxillofac Surg 2007;65:1785-92.
13. Farah CS, Savage NW. Cryotherapy for
treatment of oral lesions. Austr Dent J
2006;51:2-5.
14. Malmström M, Leikomaa H. Experiences
with cryotherapy in the treatment of oral
lesions. Proc Finn Dent Soc
1980;76:117-23.
15. Tal H, Cohen MA, Lemmer J. Clinical
and histological changes following
cryotherapy in a case of widespread oral
leukoplakia. Int J Oral Surg 1982;11:64-
8.
16. Tal H, Landsberg J, Kozlovsky A.
Cryosurgical depigmentation of the
gingiva. J Clin Periodontol 1987;14:614-
7.
17. Yeh CJ. Cryosurgical treatment of
melanin-pigmented gingiva. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod
1998;86:660-3.
18. Yeh CJ. Treatment of verrucous
hyperplasia and verrucous carcinoma by
shave excision and simple cryosurgery.
Int J Oral Maxillofac Surg 2003;32:280–
3.
19. Caraceni A, Cherny N, Fainsinger R,
Kaasa S, Poulain P, Radbruch L, et al.
Pain measurement tools and methods in
clinical research in palliative care:
recommendations of an expert working
group of the European Association of
Palliative Care. J Pain Symp Manage
2002;23:239–55.
20. Saito T, Sugiura C, Hirai A, Notani K,
Totsuka Y, Shindoh M, et al.
Development of squamous cell
carcinoma from pre-existent oral
leukoplakia: with respect to treatment
modality. Int J Oral Maxillofac Surg
2001;30:49-53.
21. Lodi G, Porter S. Management of
potentially malignant disorders: evidence
and critique. J Oral Pathol Med
2008;37:63-9.
Source of Support: Nil, Conflict of Interest: None Declared.
ISSN 2231 - 2250
22. Waldron CA, Shafer WG. Leukoplakia
revisited: A clinicopathologic study of
3256 oral leukoplakias. Cancer
1975;36:1386-92.
23. Silverman S, Gorsky M, Lozada F. Oral
leukoplakia and malignant
transformation. A follow-up study of 257
patients. Cancer 1984;53:563-8.
24. Bouquot JE, Gorlin RJ. Leukoplakia,
lichen planus, and other oral keratoses
in 23,616 white Americans over the age
of 35 years. Oral Surg Oral Med Oral
Pathol 1986;61:373-81.
25. Saito T, Sugiura C, Hirai A, Totsuka Y,
Shindoh M, Kohgo T, et al. High
malignant transformation rate of wide
spread multiple oral leukoplakias. Oral
Dis 1999;5:15-9.
26. Ishii J, Fujita K, Komori T. Clinical
assessment of laser monotherapy for
squamous cell carcinoma of the mobile
tongue. J Clin Laser Med Surg
2002;20:57-61.
27. Scheifele C, Reichart PA, Dietrich T.
Low prevalence of oral leukoplakia in
representative sample of the US
population. Oral Oncol 2003;39:619-25.
28. van der Waal I. Potentially malignant
disorders of the oral and oropharyngeal
mucosa; terminology, classification and
present concepts of management. Oral
Oncol 2009;45:317-23.
29. Napier SS, Speight PM. Natural history
of potentially malignant oral lesions and
conditions: an overview of the literature.
J Oral Pathol Med 2008;37:1-10.
30. Kuflik EG. Cryosurgery updated. J Am
Acad Dermatol 1994;31:925-46.
Corresponding Author
Dr.Ricardo Alves Mesquita,
Universidade Federal de Minas Gerais
Faculdade de Odontologia,
Departamento de Clínica,
Patologia e Cirurgia Odontológicas
Av.: Antônio Carlos, 6627, Sala 3202-D
Pampulha, 31.270-901,
Belo Horizonte, MG – Brasil.
Voice: +55 31 34092499 or +55 31
34092479
Fax: +55 31 34092430
E-mail: ramesquita@ufmg.br